CN101437827A - Process for producing optically active chromene oxide compound - Google Patents
Process for producing optically active chromene oxide compound Download PDFInfo
- Publication number
- CN101437827A CN101437827A CNA2007800165479A CN200780016547A CN101437827A CN 101437827 A CN101437827 A CN 101437827A CN A2007800165479 A CNA2007800165479 A CN A2007800165479A CN 200780016547 A CN200780016547 A CN 200780016547A CN 101437827 A CN101437827 A CN 101437827A
- Authority
- CN
- China
- Prior art keywords
- formula
- carbonyl
- alkyl
- amino
- halogen atom
- Prior art date
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- Granted
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 189
- QZHPTGXQGDFGEN-UHFFFAOYSA-N chromene Chemical compound C1=CC=C2C=C[CH]OC2=C1 QZHPTGXQGDFGEN-UHFFFAOYSA-N 0.000 title claims abstract description 82
- 238000000034 method Methods 0.000 title claims abstract description 78
- -1 benzopyran compound Chemical class 0.000 claims abstract description 1222
- 239000010936 titanium Substances 0.000 claims abstract description 102
- 229910052719 titanium Inorganic materials 0.000 claims abstract description 95
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 claims abstract description 89
- 125000005843 halogen group Chemical group 0.000 claims description 340
- 239000001301 oxygen Substances 0.000 claims description 197
- 229910052760 oxygen Inorganic materials 0.000 claims description 197
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 161
- 238000006243 chemical reaction Methods 0.000 claims description 142
- 125000000217 alkyl group Chemical class 0.000 claims description 133
- 125000004390 alkyl sulfonyl group Chemical class 0.000 claims description 126
- 125000003545 alkoxy group Chemical class 0.000 claims description 116
- 230000003287 optical effect Effects 0.000 claims description 116
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 113
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 109
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 107
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 97
- 229910052757 nitrogen Inorganic materials 0.000 claims description 92
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 91
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 88
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 83
- 238000004519 manufacturing process Methods 0.000 claims description 69
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical class C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims description 66
- 125000003118 aryl group Chemical class 0.000 claims description 59
- 239000002904 solvent Substances 0.000 claims description 58
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 55
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 54
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 54
- 125000004391 aryl sulfonyl group Chemical class 0.000 claims description 50
- NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 claims description 46
- 125000001072 heteroaryl group Chemical class 0.000 claims description 46
- 238000006735 epoxidation reaction Methods 0.000 claims description 37
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 34
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 28
- 150000008371 chromenes Chemical class 0.000 claims description 28
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 27
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical group O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 claims description 27
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 25
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 24
- 125000004429 atom Chemical group 0.000 claims description 24
- 125000003830 C1- C4 alkylcarbonylamino group Chemical group 0.000 claims description 23
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 23
- 125000005974 C6-C14 arylcarbonyl group Chemical group 0.000 claims description 22
- 125000005129 aryl carbonyl group Chemical class 0.000 claims description 22
- 229910052801 chlorine Inorganic materials 0.000 claims description 22
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 22
- 125000004448 alkyl carbonyl group Chemical class 0.000 claims description 21
- 125000005223 heteroarylcarbonyl group Chemical group 0.000 claims description 20
- 125000001246 bromo group Chemical group Br* 0.000 claims description 19
- 238000009833 condensation Methods 0.000 claims description 18
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 15
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 15
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 14
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 13
- 125000005422 alkyl sulfonamido group Chemical class 0.000 claims description 12
- 125000004657 aryl sulfonyl amino group Chemical class 0.000 claims description 12
- 125000005143 heteroarylsulfonyl group Chemical class 0.000 claims description 12
- 239000000203 mixture Substances 0.000 claims description 12
- CFHIDWOYWUOIHU-UHFFFAOYSA-N oxomethyl Chemical compound O=[CH] CFHIDWOYWUOIHU-UHFFFAOYSA-N 0.000 claims description 12
- AQLJVWUFPCUVLO-UHFFFAOYSA-N urea hydrogen peroxide Chemical compound OO.NC(N)=O AQLJVWUFPCUVLO-UHFFFAOYSA-N 0.000 claims description 12
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 11
- 239000005864 Sulphur Substances 0.000 claims description 10
- SMDGVPQREIZILS-UHFFFAOYSA-N $l^{1}-oxidanylmethylbenzene Chemical compound [O]CC1=CC=CC=C1 SMDGVPQREIZILS-UHFFFAOYSA-N 0.000 claims description 9
- 125000005100 aryl amino carbonyl group Chemical class 0.000 claims description 8
- 229910052799 carbon Inorganic materials 0.000 claims description 8
- 229910052738 indium Inorganic materials 0.000 claims description 8
- FRIBMENBGGCKPD-UHFFFAOYSA-N 3-(2,3-dimethoxyphenyl)prop-2-enal Chemical compound COC1=CC=CC(C=CC=O)=C1OC FRIBMENBGGCKPD-UHFFFAOYSA-N 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical class 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 125000005241 heteroarylamino group Chemical class 0.000 claims description 6
- 125000005309 thioalkoxy group Chemical class 0.000 claims description 6
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims description 5
- 150000002148 esters Chemical class 0.000 claims description 5
- 150000002170 ethers Chemical class 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- JYJVVHFRSFVEJM-UHFFFAOYSA-N iodosobenzene Chemical compound O=IC1=CC=CC=C1 JYJVVHFRSFVEJM-UHFFFAOYSA-N 0.000 claims description 5
- 150000002825 nitriles Chemical class 0.000 claims description 5
- 238000010992 reflux Methods 0.000 claims description 5
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 5
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 4
- 125000003282 alkyl amino group Chemical class 0.000 claims description 4
- 125000003368 amide group Chemical group 0.000 claims description 4
- 230000005494 condensation Effects 0.000 claims description 4
- 125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 claims description 4
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 4
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 claims description 4
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 claims description 3
- LFTLOKWAGJYHHR-UHFFFAOYSA-N N-methylmorpholine N-oxide Chemical compound CN1(=O)CCOCC1 LFTLOKWAGJYHHR-UHFFFAOYSA-N 0.000 claims description 3
- COGNCXJCCDGTDV-UHFFFAOYSA-N [O].N1C=CC=CC=C1 Chemical compound [O].N1C=CC=CC=C1 COGNCXJCCDGTDV-UHFFFAOYSA-N 0.000 claims description 3
- 125000001769 aryl amino group Chemical class 0.000 claims description 3
- LSXWFXONGKSEMY-UHFFFAOYSA-N di-tert-butyl peroxide Chemical compound CC(C)(C)OOC(C)(C)C LSXWFXONGKSEMY-UHFFFAOYSA-N 0.000 claims description 3
- LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 claims description 3
- CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical compound CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 claims description 3
- JVJQPDTXIALXOG-UHFFFAOYSA-N nitryl fluoride Chemical group [O-][N+](F)=O JVJQPDTXIALXOG-UHFFFAOYSA-N 0.000 claims description 2
- 150000002466 imines Chemical class 0.000 claims 1
- 239000000126 substance Substances 0.000 abstract description 5
- 239000003054 catalyst Substances 0.000 abstract description 2
- 206010003119 arrhythmia Diseases 0.000 abstract 1
- 230000006793 arrhythmia Effects 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 150
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 111
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 81
- 239000000243 solution Substances 0.000 description 80
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 53
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 52
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 50
- 238000003756 stirring Methods 0.000 description 48
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 46
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 42
- XPDWGBQVDMORPB-UHFFFAOYSA-N Fluoroform Chemical compound FC(F)F XPDWGBQVDMORPB-UHFFFAOYSA-N 0.000 description 39
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 33
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 32
- 230000035484 reaction time Effects 0.000 description 32
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 30
- DOLVFFGLNYMIPV-UHFFFAOYSA-N 2,4-ditert-butyl-6-[3-[(3,5-ditert-butyl-2-hydroxyphenyl)methylideneamino]propyliminomethyl]phenol Chemical compound CC(C)(C)C1=CC(C(C)(C)C)=CC(C=NCCCN=CC=2C(=C(C=C(C=2)C(C)(C)C)C(C)(C)C)O)=C1O DOLVFFGLNYMIPV-UHFFFAOYSA-N 0.000 description 29
- 239000012074 organic phase Substances 0.000 description 29
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 28
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 27
- 238000004458 analytical method Methods 0.000 description 26
- 230000014759 maintenance of location Effects 0.000 description 26
- 239000011159 matrix material Substances 0.000 description 26
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 24
- 230000009466 transformation Effects 0.000 description 24
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 23
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 23
- 239000000872 buffer Substances 0.000 description 23
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N dimethylmethane Natural products CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 23
- 229910052731 fluorine Inorganic materials 0.000 description 22
- 125000001153 fluoro group Chemical group F* 0.000 description 22
- NNPPMTNAJDCUHE-UHFFFAOYSA-N trimethylmethane Natural products CC(C)C NNPPMTNAJDCUHE-UHFFFAOYSA-N 0.000 description 22
- 239000003205 fragrance Substances 0.000 description 20
- 239000001294 propane Substances 0.000 description 20
- 230000002194 synthesizing effect Effects 0.000 description 18
- 239000001273 butane Substances 0.000 description 17
- 239000003960 organic solvent Substances 0.000 description 17
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 16
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 238000005160 1H NMR spectroscopy Methods 0.000 description 14
- 238000004440 column chromatography Methods 0.000 description 14
- 239000012153 distilled water Substances 0.000 description 14
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 13
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- 238000004128 high performance liquid chromatography Methods 0.000 description 12
- 229910052740 iodine Inorganic materials 0.000 description 12
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 12
- 238000005070 sampling Methods 0.000 description 12
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 11
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 11
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
- 238000000605 extraction Methods 0.000 description 10
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 10
- ZCRZCMUDOWDGOB-UHFFFAOYSA-N ethanesulfonimidic acid Chemical compound CCS(N)(=O)=O ZCRZCMUDOWDGOB-UHFFFAOYSA-N 0.000 description 9
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 9
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 9
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 9
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 9
- 239000000843 powder Substances 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 8
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 8
- VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 description 8
- BUUUKZRZHRJEAP-UHFFFAOYSA-N CCCC([O])CC Chemical compound CCCC([O])CC BUUUKZRZHRJEAP-UHFFFAOYSA-N 0.000 description 7
- RUOUWAAGKLKLAI-UHFFFAOYSA-N CCCCC(C)[O] Chemical compound CCCCC(C)[O] RUOUWAAGKLKLAI-UHFFFAOYSA-N 0.000 description 7
- GPYKQOCYDCMGOA-UHFFFAOYSA-N CCCCCC[O] Chemical compound CCCCCC[O] GPYKQOCYDCMGOA-UHFFFAOYSA-N 0.000 description 7
- 150000001562 benzopyrans Chemical class 0.000 description 7
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 7
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 7
- 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 description 7
- VEUMBMHMMCOFAG-UHFFFAOYSA-N 2,3-dihydrooxadiazole Chemical compound N1NC=CO1 VEUMBMHMMCOFAG-UHFFFAOYSA-N 0.000 description 6
- GTEZSHJBMRWRIG-UHFFFAOYSA-N 2-amino-3-[4-(naphthalene-2-carbonyloxy)phenyl]propanoic acid Chemical group C1=CC(CC(N)C(O)=O)=CC=C1OC(=O)C1=CC=C(C=CC=C2)C2=C1 GTEZSHJBMRWRIG-UHFFFAOYSA-N 0.000 description 6
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 6
- UOCJDOLVGGIYIQ-PBFPGSCMSA-N cefatrizine Chemical group S([C@@H]1[C@@H](C(N1C=1C(O)=O)=O)NC(=O)[C@H](N)C=2C=CC(O)=CC=2)CC=1CSC=1C=NNN=1 UOCJDOLVGGIYIQ-PBFPGSCMSA-N 0.000 description 6
- 125000006260 ethylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])C([H])([H])[H] 0.000 description 6
- 125000004672 ethylcarbonyl group Chemical group [H]C([H])([H])C([H])([H])C(*)=O 0.000 description 6
- QWTDNUCVQCZILF-UHFFFAOYSA-N iso-pentane Natural products CCC(C)C QWTDNUCVQCZILF-UHFFFAOYSA-N 0.000 description 6
- 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 description 6
- 125000004674 methylcarbonyl group Chemical group CC(=O)* 0.000 description 6
- 125000002950 monocyclic group Chemical group 0.000 description 6
- CRSOQBOWXPBRES-UHFFFAOYSA-N neopentane Chemical compound CC(C)(C)C CRSOQBOWXPBRES-UHFFFAOYSA-N 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- MNCMBBIFTVWHIP-UHFFFAOYSA-N 1-anthracen-9-yl-2,2,2-trifluoroethanone Chemical group C1=CC=C2C(C(=O)C(F)(F)F)=C(C=CC=C3)C3=CC2=C1 MNCMBBIFTVWHIP-UHFFFAOYSA-N 0.000 description 5
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 5
- 125000002078 anthracen-1-yl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C([*])=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 description 5
- 125000000748 anthracen-2-yl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C([H])=C([*])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 description 5
- 239000008346 aqueous phase Substances 0.000 description 5
- 239000007810 chemical reaction solvent Substances 0.000 description 5
- 229910052748 manganese Inorganic materials 0.000 description 5
- 239000011572 manganese Substances 0.000 description 5
- KHUXNRRPPZOJPT-UHFFFAOYSA-N phenoxy radical Chemical compound O=C1C=C[CH]C=C1 KHUXNRRPPZOJPT-UHFFFAOYSA-N 0.000 description 5
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium(II) oxide Chemical compound [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 5
- VEUMANXWQDHAJV-UHFFFAOYSA-N 2-[2-[(2-hydroxyphenyl)methylideneamino]ethyliminomethyl]phenol Chemical group OC1=CC=CC=C1C=NCCN=CC1=CC=CC=C1O VEUMANXWQDHAJV-UHFFFAOYSA-N 0.000 description 4
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 4
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 4
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 4
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 4
- FTMNEOFXEYHPCT-UHFFFAOYSA-N O=C1C=CC=C2[CH]C=CC=C12 Chemical compound O=C1C=CC=C2[CH]C=CC=C12 FTMNEOFXEYHPCT-UHFFFAOYSA-N 0.000 description 4
- AQPOTPPWSGMEED-UHFFFAOYSA-N O=C1[CH]c2ccccc2C=C1 Chemical compound O=C1[CH]c2ccccc2C=C1 AQPOTPPWSGMEED-UHFFFAOYSA-N 0.000 description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 125000000623 heterocyclic group Chemical group 0.000 description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 4
- LZOZLBFZGFLFBV-UHFFFAOYSA-N sulfene Chemical compound C=S(=O)=O LZOZLBFZGFLFBV-UHFFFAOYSA-N 0.000 description 4
- SBXDENYROQKXBE-UHFFFAOYSA-N 2-phenylbenzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1C1=CC=CC=C1 SBXDENYROQKXBE-UHFFFAOYSA-N 0.000 description 3
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 125000006251 butylcarbonyl group Chemical group 0.000 description 3
- 150000001721 carbon Chemical group 0.000 description 3
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 3
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 3
- PYLWMHQQBFSUBP-UHFFFAOYSA-N monofluorobenzene Chemical compound FC1=CC=CC=C1 PYLWMHQQBFSUBP-UHFFFAOYSA-N 0.000 description 3
- 125000006606 n-butoxy group Chemical group 0.000 description 3
- 239000007800 oxidant agent Substances 0.000 description 3
- 239000012279 sodium borohydride Substances 0.000 description 3
- 229910000033 sodium borohydride Inorganic materials 0.000 description 3
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 3
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 3
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 2
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 2
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 2
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 2
- KDDQRKBRJSGMQE-UHFFFAOYSA-N 4-thiazolyl Chemical group [C]1=CSC=N1 KDDQRKBRJSGMQE-UHFFFAOYSA-N 0.000 description 2
- CWDWFSXUQODZGW-UHFFFAOYSA-N 5-thiazolyl Chemical group [C]1=CN=CS1 CWDWFSXUQODZGW-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 150000001336 alkenes Chemical class 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- 125000006309 butyl amino group Chemical group 0.000 description 2
- KVNRLNFWIYMESJ-UHFFFAOYSA-N butyronitrile Chemical compound CCCC#N KVNRLNFWIYMESJ-UHFFFAOYSA-N 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 2
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 2
- 239000012046 mixed solvent Substances 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- SJGALSBBFTYSBA-UHFFFAOYSA-N oxaziridine Chemical compound C1NO1 SJGALSBBFTYSBA-UHFFFAOYSA-N 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 2
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 2
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 description 2
- 125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 238000006722 reduction reaction Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 238000001308 synthesis method Methods 0.000 description 2
- 125000003698 tetramethyl group Chemical group [H]C([H])([H])* 0.000 description 2
- JMXKSZRRTHPKDL-UHFFFAOYSA-N titanium ethoxide Chemical compound [Ti+4].CC[O-].CC[O-].CC[O-].CC[O-] JMXKSZRRTHPKDL-UHFFFAOYSA-N 0.000 description 2
- 238000003809 water extraction Methods 0.000 description 2
- WYRSGXAIHNMKOL-UHFFFAOYSA-N $l^{1}-sulfanylethane Chemical compound CC[S] WYRSGXAIHNMKOL-UHFFFAOYSA-N 0.000 description 1
- QSLPNSWXUQHVLP-UHFFFAOYSA-N $l^{1}-sulfanylmethane Chemical compound [S]C QSLPNSWXUQHVLP-UHFFFAOYSA-N 0.000 description 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 1
- ZFEZIAPMHMZNRS-UHFFFAOYSA-N 2-$l^{1}-sulfanyl-2-methylpropane Chemical compound CC(C)(C)[S] ZFEZIAPMHMZNRS-UHFFFAOYSA-N 0.000 description 1
- MUAMNDBPYAHPCU-UHFFFAOYSA-N CCC(C)[S] Chemical compound CCC(C)[S] MUAMNDBPYAHPCU-UHFFFAOYSA-N 0.000 description 1
- UWDRZGFZOORDQV-UHFFFAOYSA-N CCCCCC[S] Chemical compound CCCCCC[S] UWDRZGFZOORDQV-UHFFFAOYSA-N 0.000 description 1
- WAUHABGEEBVFTF-UHFFFAOYSA-N CCCC[S] Chemical compound CCCC[S] WAUHABGEEBVFTF-UHFFFAOYSA-N 0.000 description 1
- 239000004593 Epoxy Substances 0.000 description 1
- 229910010082 LiAlH Inorganic materials 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000003288 anthiarrhythmic effect Effects 0.000 description 1
- MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 description 1
- 239000003416 antiarrhythmic agent Substances 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 125000004230 chromenyl group Chemical group O1C(C=CC2=CC=CC=C12)* 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- QNLOWBMKUIXCOW-UHFFFAOYSA-N indol-2-one Chemical compound C1=CC=CC2=NC(=O)C=C21 QNLOWBMKUIXCOW-UHFFFAOYSA-N 0.000 description 1
- 150000002475 indoles Chemical class 0.000 description 1
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 125000004095 oxindolyl group Chemical class N1(C(CC2=CC=CC=C12)=O)* 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000011218 segmentation Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003609 titanium compounds Chemical class 0.000 description 1
- UBZYKBZMAMTNKW-UHFFFAOYSA-J titanium tetrabromide Chemical compound Br[Ti](Br)(Br)Br UBZYKBZMAMTNKW-UHFFFAOYSA-J 0.000 description 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 1
Landscapes
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
To provide an efficient process for producing an optically active chromene oxide compound which is an important intermediate for a benzopyran compound effective in the treatment of arrhythmia. [MEANS FOR SOLVING PROBLEMS] The process for producing an optically active chromene oxide compound comprises using an optically active titanium complex represented by, e.g., the formula (1) or (2) as a catalyst to asymmetrically oxidize an optically active chromene compound with high enantioselectivity in high chemical yield.
Description
Technical field
The present invention relates to the efficient manufacture method of conduct to the optically active chromene oxide compound of the important intermediate of the effective benzopyran compounds of ARR treatment.
Background technology
Open as benzopyran compounds and manufacture method thereof that anti-arrhythmic is useful.That is, benzopyran compounds is after the optical activity manganese complex being carried out asymmetric Epoxidation formation optically active chromene oxide compound with chromene compounds, makes epoxy addition with amine compound, makes (with reference to patent documentation 1).
By making chromene compounds carry out the method that asymmetric Epoxidation is made optically active chromene oxide compound, be disclosed (with reference to patent documentation 2, patent documentation 3, patent documentation 4, patent documentation 5 and patent documentation 6) with the optical activity manganese complex.In above-mentioned patent documentation, put down in writing,, used the optical activity manganese complex,, used the Production Example of the optically active chromene oxide compound of iodosobenzene, clorox or 30% aquae hydrogenii dioxidi as co-oxidants as catalyzer.
In the asymmetric oxidation reaction that utilizes the optical activity manganese complex to carry out, except co-oxidants, also need to be called as the additive of the 4-phenylpyridine-N-oxide compound etc. of a part, expectation utilization is not used the manufacture method of the optically active chromene oxide compound that other method of a part carries out.
Put down in writing on the other hand, by using asymmetrical optical activity manganese complex, even the usage quantity of 0.01～0.2 mole of %, also can make the method (with reference to patent documentation 7) of optically active chromene oxide compound with high chemical yield and optical yield, in the document, only put down in writing and used the example of iodosobenzene as co-oxidants, so and then in industrial favourable efficient manufacture method.
Reported in the optical activity titanium complex, two-μ-oxygen titanium Salalen complex compound, with aquae hydrogenii dioxidi as oxygenant, do not have in the asymmetric epoxidation reaction of heteroatomic various simple alkene, react with the high antimer selectivity.But, about heteroatomic olefin(e) compound and chromene compounds are arranged, not report example (non-patent literature 8).
Patent documentation 1: the spy opens the 2001-151767 communique
Patent documentation 2: the spy opens flat 05-301878 communique
Patent documentation 3: the spy opens flat 07-285983 communique
Patent documentation 4: the spy opens flat 08-245668 communique
Patent documentation 5:WO2005/090357A1
Patent documentation 6:WO2005/080368A2
Patent documentation 7: the spy opens flat 11-335384 communique
Non-patent literature 8:K.Matsumoto, Y.Sawada, B.Saito, K.Sakai, T.Katsuki, Angew.Chem.Int.Ed. (2005), 44,4935-4939.
Summary of the invention
The invention provides the manufacture method of conduct to the optically active chromene oxide compound of the important intermediate of the effective benzopyran compounds of ARR treatment.
Present inventors further investigate the manufacture method of the optically active chromene oxide compound of the important intermediate of the effective benzopyran compounds of ARR treatment conduct, found that, by utilizing the optical activity titanium complex as catalyzer, can the high antimer selectivity and high chemical yield make optically active chromene oxide compound, thereby finished the present invention.
In the present invention, as the 1st scheme, be formula (14), formula (15), the manufacture method of the optically active chromene oxide compound shown in formula (16) or the formula (17), it is characterized in that, use formula (1), formula (1 '), formula (2), formula (2 '), formula (3), formula (3 '), optical activity titanium complex shown in any one of formula (4) and formula (4 ') is as catalyzer, with formula (10), formula (11), chromene compounds shown in formula (12) or the formula (13) is in solvent, carry out asymmetric Epoxidation with oxygenant
(the R in formula (1), formula (1 '), formula (2), formula (2 '), formula (3), formula (3 '), formula (4) and the formula (4 ')
1Expression hydrogen atom, halogen atom, C
1-4Alkyl, C
1-4Alkoxyl group, C
6-12Aryloxy or C
6-22(this aryl can be by C for aryl
1-4Alkyl (this alkyl can be replaced arbitrarily by halogen atom), C
1-7Alkoxyl group or benzyl oxygen base replace arbitrarily, are optical activity or non-optical activity),
R
2Expression hydrogen atom, halogen atom, C
1-4Alkyl, C
1-4Alkoxyl group, C
6-12Aryloxy or C
6-18Aryl,
R
3Expression C
1-4Alkyl, C
6-18Aryl, perhaps, at 2 R
3Form under the situation of ring expression C together
3-5The group of divalence,
R
4Represent hydrogen atom, halogen atom, C respectively independently
1-4Alkyl, C
1-4Alkoxyl group, nitro or cyano group,
M represents TiJ
1J
2(at TiJ
1J
2In, Ti represents titanium atom, J
1And J
2Represent halogen atom, C respectively independently
1-4Alkoxyl group, perhaps J
1With J
2Represent Sauerstoffatom together, perhaps J
1With J
2Form ring together, expression is as the formula (5) of the group of divalence
(about the part-structure O-E-O in the formula, wherein, O represents Sauerstoffatom, in formula (1), as O-E-O, is represented by following formula (6); In formula (1 '),, represent by following formula (6 ') as O-E-O; In formula (2),, represent by following formula (7) as O-E-O; In formula (2 '),, represent by following formula (7 ') as O-E-O; In formula (3),, represent by following formula (8) as O-E-O; In formula (3 '),, represent by following formula (8 ') as O-E-O; In formula (4),, represent by following formula (9) as O-E-O; In formula (4 '), as O-E-O, by following formula (9 ') expression,
B represents 1～10 integer, R
1, R
2, R
3And R
4Same as described above));
(the R in the formula (10)
5, R
6, R
7And R
8Represent hydrogen atom, cyano group, nitro, halogen atom, C respectively independently
1-4(this alkyl can be by halogen atom, hydroxyl, cyano group, nitro, C for alkyl
1-4Alkoxyl group, C
1-4Alkyl-carbonyl oxygen base, C
1-4Alkyl-carbonyl-amino, C
1-4Any replacement of alkoxy carbonyl (this alkoxyl group, alkyl-carbonyl oxygen base, alkyl-carbonyl-amino and alkoxy carbonyl can be replaced arbitrarily by halogen atom)), C
1-4(this alkoxyl group can be by halogen atom, hydroxyl, cyano group, nitro, C for alkoxyl group
1-4Alkoxyl group, C
1-4Alkyl-carbonyl oxygen base, C
1-4Alkyl-carbonyl-amino, C
1-4Any replacement of alkoxy carbonyl (this alkoxyl group, alkyl-carbonyl oxygen base, alkyl-carbonyl-amino and alkoxy carbonyl can be replaced arbitrarily by halogen atom)), C
1-4(this alkyl-carbonyl-amino can be by halogen atom, C for alkyl-carbonyl-amino
6-10Aryl (this C
6-10Aryl can be by halogen atom, hydroxyl, cyano group, nitro, C
1-4Alkyl or C
1-4Alkoxyl group replaces arbitrarily) replace arbitrarily), C
1-4Alkyl-carbonyl (N-C
1-4Alkyl) amino (this alkyl-carbonyl (N-alkyl) amino can be replaced arbitrarily by halogen atom), C
1-4Alkoxy carbonyl (this alkoxy carbonyl can be replaced arbitrarily by halogen atom), C
6-10(this aryl-amino-carbonyl can be by halogen atom, C for aryl-amino-carbonyl
1-4Alkyl, C
1-4Alkoxyl group, cyano group or nitro replace), C
6-10Aryl carbonyl (N-C
1-4It is alkyl) amino that (this aryl carbonyl (N-alkyl) amino can be by halogen atom, C
1-4Alkyl, C
1-4Alkoxyl group, cyano group or nitro replace), benzyloxycarbonyl group amino, formyl radical, formamyl, C
1-4Alkyl sulphonyl, C
6-10(this alkyl sulphonyl and aryl sulfonyl can be by halogen atom, C for aryl sulfonyl
1-4Alkyl, C
1-4Alkoxyl group, cyano group or nitro replace), sulfamyl, C
1-4Alkylsulfonamido, C
6-10(this alkylsulfonamido and aryl-sulfonyl amino can be by halogen atom, C for aryl-sulfonyl amino
1-4Alkyl, C
1-4Alkoxyl group, cyano group or nitro replace), two (C
1-4Alkyl sulfonyl) (alkyl sulfonyl of this pair (alkyl sulfonyl) imido grpup can be by halogen atom, C for imido grpup
1-4Alkyl, C
1-4Alkoxyl group, cyano group or nitro replace), two (C
6-10Arylsulfonyl) (arylsulfonyl of this pair (arylsulfonyl) imido grpup can be by halogen atom, C for imido grpup
1-4Alkyl, C
1-4Alkoxyl group, cyano group or nitro replace), [N, N '-(C
1-4Alkyl sulfonyl) (C
6-10Arylsulfonyl)] (alkyl sulfonyl and the arylsulfonyl that are somebody's turn to do [N, N '-(alkyl sulfonyl) (arylsulfonyl)] imido grpup can be by halogen atom, C for imido grpup
1-4Alkyl, C
1-4Alkoxyl group, cyano group or nitro replace);
R in the formula (10)
9And R
10Represent hydrogen atom, C respectively independently
1-6(this alkyl can be by halogen atom, C for alkyl
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom) or hydroxyl replace arbitrarily), C
6-14(this aryl can be by halogen atom, hydroxyl, nitro, cyano group, C for aryl
1-6(this alkyl can be by halogen atom, C for alkyl
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom) or hydroxyl replace arbitrarily) or C
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom) replaces arbitrarily);
R in formula (11) and the formula (12)
9And R
10Represent hydrogen atom, C respectively independently
1-6(this alkyl can be by halogen atom, C for alkyl
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom) or hydroxyl replace arbitrarily) or C
6-14(this aryl can be by halogen atom, hydroxyl, nitro, cyano group, C for aryl
1-6(this alkyl can be by halogen atom, C for alkyl
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom) or hydroxyl replace arbitrarily) or C
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom) replaces arbitrarily);
Part ring structure A in formula (11) and the formula (12) is 5,6 or 7 Yuans part-structures that ring is represented that partly form condensed ring with phenyl ring, and wherein, these 5,6 or 7 Yuans rings can be by h R
11(R
11Be halogen atom, hydroxyl, C
1-6(this alkyl can be by halogen atom, hydroxyl, cyano group, amino, nitro, C for alkyl
1-4Alkoxyl group, C
1-4Alkyl-carbonyl oxygen base, C
1-4Alkyl-carbonyl-amino or C
1-4Any replacement of alkoxy carbonyl (this alkoxyl group, alkyl-carbonyl oxygen base, alkyl-carbonyl-amino and alkoxy carbonyl can be replaced arbitrarily by halogen atom)), C
1-6(this alkoxyl group can be by halogen atom, hydroxyl, cyano group, amino, nitro, C for alkoxyl group
1-4Alkoxyl group, C
1-4Alkyl-carbonyl oxygen base, C
1-4Alkyl-carbonyl-amino or C
1-4Any replacement of alkoxy carbonyl (this alkoxyl group, alkyl-carbonyl oxygen base, alkyl-carbonyl-amino and alkoxy carbonyl can be replaced arbitrarily by halogen atom)), nitro, cyano group, formyl radical, formamido-, formamyl, sulfo group, sulfoamino-, sulfamyl, alkylsulfonyl, amino, carboxyl, C
1-6Alkylamino, two C
1-6Alkylamino, C
1-6Alkyl-carbonyl-amino, C
1-6Alkylsulfonamido, C
6-14Aryl-sulfonyl amino, C
1-6Alkyl amino-carbonyl, two C
1-6Alkyl amino-carbonyl, C
1-6Alkyl-carbonyl, C
1-6Alkoxy carbonyl, C
1-6Alkyl sulphonyl, C
6-14Aryl sulfonyl or C
6-14Aryl carbonyl (this alkylamino, dialkyl amido, alkyl-carbonyl-amino, alkylsulfonamido, aryl-sulfonyl amino, alkyl amino-carbonyl, dialkyl amino carbonyl, alkyl-carbonyl, alkoxy carbonyl, alkyl sulphonyl, aryl sulfonyl and aryl carbonyl can be replaced arbitrarily by halogen atom); h is 1～6 integer; be under 2～6 the situation at h, R
11Can be the same or different) replace arbitrarily, constituting atom as ring, can contain 1～3 Sauerstoffatom, nitrogen-atoms or sulphur atom alone or in combination, the number of intra-annular unsaturated link(age), the unsaturated link(age) that comprises the phenyl ring of condensation, be 1,2 or 3, the carbon atom that constitutes ring can be carbonyl or thiocarbonyl
X in the formula (13) represents NR
20(R
20Expression hydrogen atom or C
1-4Alkyl),
Y in the formula (13) represents Direct Bonding, SO or SO
2,
Z in the formula (13) represents C
1-4(this alkyl can (this phenyl can be by C by 1～5 halogen atom or phenyl for alkyl
1-4Alkyl replaces arbitrarily) replace arbitrarily) or phenyl (this phenyl can be by C
1-4Alkyl replaces arbitrarily),
W in the formula (13) represents hydrogen atom, hydroxyl, C
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom), halogen atom, C
1-4Alkyl or C
1-6Alkylsulfonamido (this alkyl and alkylsulfonamido can be replaced arbitrarily by halogen atom),
R in the formula (13)
9And R
10Represent hydrogen atom, C respectively independently
1-6(this alkyl can be by halogen atom, C for alkyl
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom) or hydroxyl replace arbitrarily) or C
6-14(this aryl can be by halogen atom, hydroxyl, nitro, cyano group, C for aryl
1-6(this alkyl can be by halogen atom, C for alkyl
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom) or hydroxyl replace arbitrarily) or C
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom) replaces arbitrarily)),
(R in the formula
5, R
6, R
7, R
8, R
9, R
10, A, W, X, Y and Z be same as described above, the absolute configuration of * institute marked carbon atoms is (R) or (S));
As the 2nd scheme, it is manufacture method according to the described optically active chromene oxide compound of the 1st scheme, it is characterized in that, use the optical activity titanium complex shown in any one of above-mentioned formula (1), formula (1 '), formula (2), formula (2 '), formula (3), formula (3 '), formula (4) and formula (4 ') as catalyzer, with the chromene compounds shown in the above-mentioned formula (10) in solvent, carry out asymmetric Epoxidation with oxygenant
R in the above-mentioned formula (10)
5And R
6Represent hydrogen atom, cyano group, nitro, halogen atom, C respectively independently
1-4(this alkyl can be by halogen atom, hydroxyl, cyano group, nitro, C for alkyl
1-4Alkoxyl group, C
1-4Alkyl-carbonyl oxygen base, C
1-4Alkyl-carbonyl-amino, C
1-4Any replacement of alkoxy carbonyl (this alkoxyl group, alkyl-carbonyl oxygen base, alkyl-carbonyl-amino and alkoxy carbonyl can be replaced arbitrarily by halogen atom)), C
1-4(this alkoxyl group can be by halogen atom, hydroxyl, cyano group, nitro, C for alkoxyl group
1-4Alkoxyl group, C
1-4Alkyl-carbonyl oxygen base, C
1-4Alkyl-carbonyl-amino, C
1-4Any replacement of alkoxy carbonyl (this alkoxyl group, alkyl-carbonyl oxygen base, alkyl-carbonyl-amino and alkoxy carbonyl can be replaced arbitrarily by halogen atom)), C
1-4Alkyl-carbonyl-amino (this alkyl-carbonyl-amino can be replaced arbitrarily by halogen atom), C
1-4Alkyl-carbonyl (N-C
1-4Alkyl) amino (this alkyl-carbonyl (N-alkyl) amino can be replaced arbitrarily by halogen atom) C
6-10Aryl carbonyl (N-C
1-4It is alkyl) amino that (this aryl carbonyl (N-alkyl) amino can be by halogen atom, C
1-4Alkyl, C
1-4Alkoxyl group, cyano group or nitro replace), formamyl, two (C
1-4Alkyl sulfonyl) (alkyl sulfonyl of this pair (alkyl sulfonyl) imido grpup can be by halogen atom, C for imido grpup
1-4Alkyl, C
1-4Alkoxyl group, cyano group or nitro replace), two (C
6-10Arylsulfonyl) (arylsulfonyl of this pair (arylsulfonyl) imido grpup can be by halogen atom, C for imido grpup
1-4Alkyl, C
1-4Alkoxyl group, cyano group or nitro replace) or [N, N '-(C
1-4Alkyl sulfonyl) (C
6-10Arylsulfonyl)] (alkyl sulfonyl and the arylsulfonyl that are somebody's turn to do [N, N '-(alkyl sulfonyl) (arylsulfonyl)] imido grpup can be by halogen atom, C for imido grpup
1-4Alkyl, C
1-4Alkoxyl group, cyano group or nitro replace),
R in the formula (10)
7Expression hydrogen atom, cyano group, nitro, two (C
1-4Alkyl sulfonyl) (alkyl sulfonyl of this pair (alkyl sulfonyl) imido grpup can be by halogen atom, C for imido grpup
1-4Alkyl, C
1-4Alkoxyl group, cyano group or nitro replace), two (C
6-10Arylsulfonyl) (arylsulfonyl of this pair (arylsulfonyl) imido grpup can be by halogen atom, C for imido grpup
1-4Alkyl, C
1-4Alkoxyl group, cyano group or nitro replace) or [N, N '-(C
1-4Alkyl sulfonyl) (C
6-10Arylsulfonyl)] (alkyl sulfonyl and the arylsulfonyl that are somebody's turn to do [N, N '-(alkyl sulfonyl) (arylsulfonyl)] imido grpup can be by halogen atom, C for imido grpup
1-4Alkyl, C
1-4Alkoxyl group, cyano group or nitro replace),
R in the formula (10)
8Expression hydrogen atom, nitro or C
1-4Alkyl (this alkyl can be replaced arbitrarily by halogen atom),
R in the formula (10)
9And R
10Expression C
1-6Alkyl (this alkyl can be replaced arbitrarily by halogen atom);
As the 3rd scheme, be manufacture method according to the described optically active chromene oxide compound of the 2nd scheme, the R in the above-mentioned formula (10)
5And R
6Represent hydrogen atom, nitro, fluorine atom, methoxyl group, methyl carbonylamino or methyl carbonyl (N-ethyl) amino respectively independently, the R in the formula (10)
7Expression hydrogen atom, nitro or two (C
1-4Alkyl sulfonyl) imido grpup, the R in the formula (10)
8Expression hydrogen atom, nitro or trifluoromethyl, the R in the formula (10)
9And R
10The expression methyl;
As the 4th scheme, it is manufacture method according to the described optically active chromene oxide compound of the 1st scheme, it is characterized in that, use the optical activity titanium complex shown in any one of above-mentioned formula (1), formula (1 '), formula (2), formula (2 '), formula (3), formula (3 '), formula (4) and formula (4 ') as catalyzer, with the chromene compounds shown in above-mentioned formula (11) or the formula (12) in solvent, carry out asymmetric Epoxidation with oxygenant
The part ring structure of A in above-mentioned formula (11) or the formula (12) is by formula (a), formula (b), formula (c), formula (d), formula (e), formula (f), formula (g), formula (h), formula (i), formula (j), formula (k), formula (l), formula (m), formula (n), formula (o), formula (p), formula (q), formula (r), formula (s), formula (t), formula (u), formula (v), formula (w), formula (x), formula (y), formula (z), formula (aa), formula (ab), formula (ac), formula (ad), formula (ae), formula (af), any one expression of formula (ag) and formula (ah)
(above-mentioned formula (a), formula (b), formula (e), formula (f), formula (g), formula (h), formula (i), formula (j), formula (k), formula (l), formula (m), formula (n), formula (p), formula (q), formula (v), the R in formula (w), formula (x), formula (ab), formula (ae), formula (af) and the formula (ag)
12And R
13Represent hydrogen atom, C respectively independently
1-6(this alkyl can be by halogen atom, C for alkyl
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom), amino, hydroxyl, C
6-14Aryl, C
2-9(this aryl and heteroaryl can be by q R for heteroaryl
18(R
18Expression and R
11Identical implication, q represents 1～3 integer, is under 2 or 3 the situation at q, R
18Can be the same or different) replace arbitrarily), C
1-6Alkyl amino-carbonyl, two C
1-6Alkyl amino-carbonyl, C
1-6Alkyl-carbonyl oxygen base, C
1-6Alkyl-carbonyl (this alkyl-carbonyl oxygen base and alkyl-carbonyl can be replaced arbitrarily by halogen atom), C
1-6Alkyl-carbonyl-amino, C
3-8Naphthene base carbonyl, C
1-6Alkoxy carbonyl, C
1-6Alkyl sulphonyl (this naphthene base carbonyl, alkoxy carbonyl and alkyl sulphonyl can be replaced arbitrarily by halogen atom), carboxyl, C
6-14Aryl carbonyl (this aryl carbonyl can be replaced arbitrarily by halogen atom) or C
2-9The heteroaryl carbonyl replaces arbitrarily), C
6-14Aryl, C
2-9(this aryl and heteroaryl can be by q R for heteroaryl
18(R
18Expression and R
11Identical implication, q represents 1～3 integer, is under 2 or 3 the situation at q, R
18Can be the same or different) replace arbitrarily), C
1-6Alkyl amino-carbonyl, two C
1-6Alkyl amino-carbonyl, C
1-6Alkyl-carbonyl, C
3-8Naphthene base carbonyl, C
1-6Alkoxy carbonyl, C
1-6Alkyl sulphonyl, C
6-14Aryl sulfonyl, C
2-9(this aryl sulfonyl and heteroarylsulfonyl can be by q R for heteroarylsulfonyl
18(R
18Expression and R
11Identical implication, q represents 1～3 integer, is under 2 or 3 the situation at q, R
18Can be the same or different) replace arbitrarily), carboxyl, C
6-14Aryl carbonyl or C
2-9(this aryl carbonyl and heteroaryl carbonyl can be by q R for the heteroaryl carbonyl
18(R
18Expression and R
11Identical implication, q represents 1～3 integer, is under 2 or 3 the situation at q, R
18Can be the same or different) replace arbitrarily),
Above-mentioned formula (a), formula (b), formula (c), formula (d), formula (f), formula (g), formula (h), formula (j), formula (k), formula (m), formula (n), formula (o), formula (p), formula (q), formula (r), formula (s), formula (t), formula (u), formula (v), the R in formula (w), formula (y), formula (z), formula (aa), formula (ab), formula (ac), formula (ad), formula (ae) and the formula (af)
14, R
15, R
16And R
17Represent hydrogen atom, halogen atom, C respectively independently
1-6(this alkyl can be by halogen atom, C for alkyl
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom), amino, hydroxyl, C
6-14Aryl, C
2-9(this aryl and heteroaryl can be by r R for heteroaryl
19(R
19Expression and R
11Identical implication, r represents the implication identical with q) replace arbitrarily), C
1-6Alkyl amino-carbonyl, two C
1-6Alkyl amino-carbonyl, C
1-6Alkyl-carbonyl oxygen base, C
1-6Alkyl-carbonyl (this alkyl-carbonyl oxygen base and alkyl-carbonyl can be replaced arbitrarily by halogen atom), C
1-6Alkyl-carbonyl-amino, C
3-8Naphthene base carbonyl, C
1-6Alkoxy carbonyl, C
1-6Alkyl sulphonyl (this naphthene base carbonyl, alkoxy carbonyl and alkyl sulphonyl can be replaced arbitrarily by halogen atom), carboxyl, C
6-14Aryl carbonyl (this aryl carbonyl can be replaced arbitrarily by halogen atom) or C
2-9The heteroaryl carbonyl replaces arbitrarily), C
3-8(this cycloalkyl can be by halogen atom, C for cycloalkyl
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom), amino or hydroxyl replace arbitrarily), C
1-6(this alkoxyl group can be by halogen atom, C for alkoxyl group
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom), carboxyl, amino, hydroxyl, C
6-14Aryl or C
2-9(this aryl and heteroaryl can be by r R for heteroaryl
19(R
19Expression and R
11Identical implication, r represents the implication identical with q) replace arbitrarily) replace arbitrarily), C
1-6(this thio alkoxy can be by halogen atom, C for thio alkoxy
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom), carboxyl, hydroxyl, C
6-14Aryl or C
2-9(this aryl and heteroaryl can be by r R for heteroaryl
19(R
19Expression and R
11Identical implication, r represents the implication identical with q) replace arbitrarily) replace arbitrarily), hydroxyl, C
6-14Aryl, C
2-9(this aryl and heteroaryl can be by r R for heteroaryl
19(R
19Expression and R
11Identical implication, r represents the implication identical with q) replace arbitrarily), C
1-6Alkyl-carbonyl oxygen base, nitro, cyano group, formyl radical, formamido-, amino, sulfo group, C
1-6Alkylamino, two C
1-6Alkylamino, C
6-14Arylamino, C
2-9(this arylamino and heteroaryl amino can be by r R for heteroaryl amino
19(R
19Expression and R
11Identical implication, r represents the implication identical with q) replace arbitrarily), C
1-6Alkyl-carbonyl-amino, C
1-6Alkylsulfonamido, formamyl, C
1-6Alkyl amino-carbonyl, two C
1-6Alkyl amino-carbonyl, C
1-6Alkyl-carbonyl, C
6-14Aryl carbonyl, C
2-9(this aryl carbonyl and heteroaryl carbonyl can be by r R for the heteroaryl carbonyl
19(R
19Expression and R
11Identical implication, r represents the implication identical with q) replace arbitrarily), C
1-6Alkoxy carbonyl, sulfamyl, C
1-6Alkyl sulphonyl, C
6-14Aryl sulfonyl, C
2-9(this aryl sulfonyl and heteroarylsulfonyl can be by r R for heteroarylsulfonyl
19(R
19Expression and R
11Identical implication, r represents the implication identical with q) replace arbitrarily), carboxyl or C
2-9(this heterocyclic radical can be by halogen atom, C for heterocyclic radical
1-6(this alkyl can be by halogen atom, C for alkyl
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom), amino, carboxyl or hydroxyl replace arbitrarily), C
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom), C
6-14Aryl, C
2-9(this aryl and heteroaryl can be by r R for heteroaryl
19(R
19Expression and R
11Identical implication, r represents the implication identical with q) replace arbitrarily), hydroxyl, nitro, cyano group, formyl radical, formamido-, amino, C
1-6Alkylamino, two C
1-6Alkylamino, C
1-6Alkyl-carbonyl-amino, C
1-6Alkylsulfonamido, formamyl, C
1-6Alkyl amino-carbonyl, two C
1-6Alkyl amino-carbonyl, C
1-6Alkyl-carbonyl, C
1-6Alkoxy carbonyl, sulfamyl, C
1-6Alkyl sulphonyl, carboxyl or C
6-14Aryl carbonyl replaces arbitrarily),
(v), the Q in formula (w), formula (ab), formula (ac) and the formula (ad) represents O (Sauerstoffatom), S (sulphur atom), SO (sulfinyl) or SO for above-mentioned formula (c), formula (d), formula (p), formula (q), formula
2(alkylsulfonyl));
As the 5th scheme, be manufacture method according to the described optically active chromene oxide compound of the 4th scheme, the R in above-mentioned formula (11) or the formula (12)
9And R
10It is methyl;
As the 6th scheme, it is manufacture method according to the 4th scheme or the described optically active chromene oxide compound of the 5th scheme, A in above-mentioned formula (11) or the formula (12) is by following formula (a), formula (b), formula (i), formula (k), formula (o), formula (p), formula (s), formula (v), formula (y), formula (ae), formula (ag) or formula (ah) expression
(in the formula, R
12, R
13, R
14, R
15And R
16Identical with the record in the 4th scheme);
As the 7th scheme, it is manufacture method according to the described optically active chromene oxide compound of the 6th scheme, A in above-mentioned formula (11) or the formula (12) represents above-mentioned formula (a), formula (b), formula (i), formula (k), formula (o), formula (p), formula (s), formula (v), formula (y), formula (ae), formula (ag) or formula (ah)
Formula (a), formula (b), formula (i), formula (k), formula (p), formula (v), the R in formula (ae) and the formula (ag)
12And R
13Represent hydrogen atom, C respectively independently
1-6(this alkyl can be by halogen atom, C for alkyl
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom), amino or hydroxyl replace arbitrarily), formula (a), formula (b), formula (k), formula (o), formula (p), formula (s), formula (v), the R in formula (y) and the formula (ae)
14, R
15And R
16Represent hydrogen atom, halogen atom or C respectively independently
1-6(this alkyl can be by halogen atom, C for alkyl
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom), amino, hydroxyl, C
1-6Alkyl amino-carbonyl, two C
1-6Alkyl amino-carbonyl, C
1-6Alkyl-carbonyl oxygen base, C
1-6Alkyl-carbonyl (this alkyl-carbonyl oxygen base and alkyl-carbonyl can be replaced arbitrarily by halogen atom), C
1-6Alkyl-carbonyl-amino, C
3-8Naphthene base carbonyl or C
1-6Alkoxy carbonyl replaces arbitrarily), Q represents O (Sauerstoffatom);
As the 8th scheme, it is manufacture method according to the described optically active chromene oxide compound of the 7th scheme, A expression (a) in above-mentioned formula (11) or the formula (12), formula (b), formula (i), formula (k), formula (o), formula (p), formula (s), formula (v), formula (y), formula (ae), formula (ag) or formula (ah), formula (a), formula (b), formula (i), formula (k), formula (p), formula (v), the R in formula (ae) and the formula (ag)
12And R
13Represent hydrogen atom, methyl respectively independently, formula (a), formula (b), formula (k), formula (o), formula (p), formula (s), formula (v), the R in formula (y) and the formula (ae)
14, R
15And R
16Represent hydrogen atom, halogen atom or C respectively independently
1-6(this alkyl can be by halogen atom, C for alkyl
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom), amino, hydroxyl, C
1-6Alkyl amino-carbonyl, two C
1-6Alkyl amino-carbonyl, C
1-6Alkyl-carbonyl oxygen base, C
1-6Alkyl-carbonyl (this alkyl-carbonyl oxygen base and alkyl-carbonyl can be replaced arbitrarily by halogen atom), C
1-6Alkyl-carbonyl-amino, C
3-8Naphthene base carbonyl or C
1-6Alkoxy carbonyl replaces arbitrarily), Q represents O (Sauerstoffatom);
As the 9th scheme, it is manufacture method according to the described optically active chromene oxide compound of the 1st scheme, it is characterized in that, use the optical activity titanium complex shown in any one of above-mentioned formula (1), formula (1 '), formula (2), formula (2 '), formula (3), formula (3 '), formula (4) and formula (4 ') as catalyzer, with the chromene compounds shown in the above-mentioned formula (13) in solvent, carry out asymmetric Epoxidation with oxygenant, the R in the above-mentioned formula (13)
9And R
10All represent methyl;
As the 10th scheme, be manufacture method according to the described optically active chromene oxide compound of the 9th scheme, the W in the above-mentioned formula (13) represents hydrogen atom, hydroxyl, methoxyl group, chlorine atom, bromine atoms, methyl, ethyl or methylsulfonyl amido;
As the 11st scheme, be that the Y in the above-mentioned formula (13) represents SO according to the manufacture method of the 9th scheme or the described optically active chromene oxide compound of the 10th scheme
2(alkylsulfonyl), Z are represented the C1-4 alkyl;
As the 12nd scheme, be manufacture method according to the described optically active chromene oxide compound of the 10th scheme, the Y in the above-mentioned formula (13) represents Direct Bonding, Z represents C
1-4Alkyl;
As the 13rd scheme, be manufacture method according to the described optically active chromene oxide compound of the 1st scheme, the R in above-mentioned formula (1), formula (1 '), formula (2), formula (2 '), formula (3), formula (3 '), formula (4) and the formula (4 ')
1Expression C
6-22(this aryl can be by C for aryl
1-4Alkyl (this alkyl can be replaced arbitrarily by halogen atom) C
1-7Alkoxyl group or benzyl oxygen base replace arbitrarily, are optical activity or non-optical activity),
R
2Expression hydrogen atom, halogen atom, C
1-4Alkyl, C
1-4Alkoxyl group, C
6-12Aryloxy or C
6-18Aryl,
R
3Expression C
1-4Alkyl, C
6-18Aryl, perhaps, at 2 R
3Form under the situation of ring expression C together
3-5The group of divalence,
R
4Represent hydrogen atom, halogen atom, C respectively independently
1-4Alkyl, C
1-4Alkoxyl group, nitro or cyano group,
M represents TiJ
1J
2(at TiJ
1J
2In, Ti represents titanium atom, J
1And J
2Represent halogen atom, C respectively independently
1-4Alkoxyl group, J
1With J
2Represent Sauerstoffatom together, perhaps, J
1With J
2Form ring together, (about the part-structure O-E-O in the formula, wherein, O is a Sauerstoffatom, in formula (1), as O-E-O, is represented by above-mentioned formula (6) as the above-mentioned formula (5) of the group of divalence in expression; In formula (1 '),, represent by above-mentioned formula (6 ') as O-E-O; In formula (2),, represent by above-mentioned formula (7) as O-E-O; In formula (2 '),, represent by above-mentioned formula (7 ') as O-E-O; In formula (3),, represent by above-mentioned formula (8) as O-E-O; In formula (3 '),, represent by above-mentioned formula (8 ') as O-E-O; In formula (4),, represent by above-mentioned formula (9) as O-E-O; In formula (4 '), as O-E-O, by above-mentioned formula (9 ') expression, b is 1～10 integer, R
1, R
2, R
3And R
4Same as described above));
As the 14th scheme, be manufacture method according to the described optically active chromene oxide compound of the 13rd scheme, the R in above-mentioned formula (1), formula (1 '), formula (2), formula (2 '), formula (3), formula (3 '), formula (4) and the formula (4 ')
1(this phenyl can be by C for the expression phenyl
1-4Alkyl (this alkyl can be replaced arbitrarily by halogen atom), benzyl oxygen base or C
1-7Alkoxyl group replaces arbitrarily) or naphthyl (this naphthyl can be by C
1-4Alkyl (this alkyl can be replaced arbitrarily by halogen atom), C
1-7Alkoxyl group or phenyl replace arbitrarily),
R
2The expression hydrogen atom,
R
3Represent 2 R
3Form the C of ring together
3-5The group of divalence,
R
4The expression hydrogen atom,
M represents TiJ
1J
2(at TiJ
1J
2In, Ti represents titanium atom, J
1And J
2Represent halogen atom, C respectively independently
1-4Alkoxyl group, perhaps, J
1With J
2Represent Sauerstoffatom together, perhaps, J
1With J
2Form ring together, (about the part-structure O-E-O in the formula, wherein, O is a Sauerstoffatom, in formula (1), as O-E-O, is represented by above-mentioned formula (6) as the above-mentioned formula (5) of the group of divalence in expression; In formula (1 '),, represent by above-mentioned formula (6 ') as O-E-O; In formula (2),, represent by above-mentioned formula (7) as O-E-O; In formula (2 '),, represent by above-mentioned formula (7 ') as O-E-O; In formula (3),, represent by above-mentioned formula (8) as O-E-O; In formula (3 '),, represent by above-mentioned formula (8 ') as O-E-O; In formula (4),, represent by above-mentioned formula (9) as O-E-O; In formula (4 '), as O-E-O, by above-mentioned formula (9 ') expression, b is 1～10 integer, R
1, R
2, R
3And R
4Same as described above));
As the 15th scheme, it is manufacture method according to each described optically active chromene oxide compound of the 1st scheme～the 14th scheme, the usage quantity of optical activity titanium complex is 0.001～100 mole of % with respect to the chromene compounds shown in formula (10), formula (11), formula (12) or the formula (13);
As the 16th scheme, it is manufacture method according to each described optically active chromene oxide compound of the 1st scheme～the 14th scheme, the solvent that uses in the asymmetric epoxidation reaction is halogen series solvent, aromatic hydrocarbons series solvent, ester series solvent, ether series solvent, nitrile series solvent, pure series solvent, the mixture of perhaps above-mentioned solvent;
As the 17th scheme, be the manufacture method according to each described optically active chromene oxide compound of the 1st scheme～the 14th scheme, the oxygenant that uses in the asymmetric epoxidation reaction is the mixture of iodosobenzene, clorox, metachloroperbenzoic acid, Oxone (E.I.Du Pont Company's registered trademark), aquae hydrogenii dioxidi, urea-hydrogen peroxide adduct (UHP), azepine oxygen triatomic ring (oxaziridine), N-methylmorpholine oxide compound (NMO), tertbutyl peroxide (TBHP), cumene hydroperoxide (CHP) or these oxygenants;
As the 18th scheme, be manufacture method according to the described optically active chromene oxide compound of the 17th scheme, the oxygenant that uses in the asymmetric epoxidation reaction is the mixture of aquae hydrogenii dioxidi, urea-hydrogen peroxide adduct (UHP) or these oxygenants;
As the 19th scheme, be manufacture method according to the described optically active chromene oxide compound of the 18th scheme, the oxygenant that uses in the asymmetric epoxidation reaction is an aquae hydrogenii dioxidi, concentration is 1～100 quality %;
As the 20th scheme, it is manufacture method according to each described optically active chromene oxide compound of the 1st scheme～the 14th scheme, the usage quantity of the oxygenant that uses in the asymmetric epoxidation reaction is 1～10 equivalent with respect to the chromene compounds shown in above-mentioned formula (10), formula (11), formula (12) or the formula (13);
As the 21st scheme, be manufacture method according to the described optically active chromene oxide compound of the 20th scheme, the addition means of the oxygenant that uses in the asymmetric epoxidation reaction is portion-wise addition or adds continuously;
As the 22nd scheme, be manufacture method according to the described optically active chromene oxide compound of the 21st scheme, the addition means of the oxygenant that uses in the asymmetric epoxidation reaction is continuous interpolation, its interpolation speed per hour is 0.01～40000 equivalent;
As the 23rd scheme, be manufacture method according to the described optically active chromene oxide compound of the 21st scheme, the addition means of the oxygenant that uses in the asymmetric epoxidation reaction is a portion-wise addition, number of times is in 2～100 scope in batches;
As the 24th scheme, be manufacture method according to each described optically active chromene oxide compound of the 1st scheme～the 23rd scheme, the temperature of reaction of asymmetric epoxidation reaction is the reflux temperature of 0 ℃～employed solvent;
As the 26th scheme, be manufacture method according to each described optically active chromene oxide compound of the 1st scheme～the 24th scheme, the scope of the pressure in the reaction system of asymmetric epoxidation reaction is 10kPa～1100kPa.
According to the present invention, can make the optically active chromene oxide compound of conduct efficiently to the important intermediate of the effective benzopyran compounds of ARR treatment.
Embodiment
" n " just representing in this specification sheets, and " i " expression is different, and " s " represents secondary, and " t " represents uncle, and " c " representative ring, " o " are represented adjacent, and between " m " expression, it is right that " p " represents.
Below, the present invention is described in detail.In the present invention, the titanium complex that uses as chromene compounds being carried out the catalyzer of asymmetric Epoxidation with oxygenant, with following formula (1), formula (1 '), formula (2), formula (2 '), formula (3), formula (3 '), formula (4) and formula (4 ') expression,
(the R in formula (1), formula (1 '), formula (2), formula (2 '), formula (3), formula (3 '), formula (4) and the formula (4 ')
1Expression hydrogen atom, halogen atom, C
1-4Alkyl, C
1-4Alkoxyl group, C
6-12Aryloxy or C
6-22(this aryl can be by C for aryl
1-4Alkyl (this alkyl can be replaced arbitrarily by halogen atom), C
1-7Alkoxyl group or benzyl oxygen base replace arbitrarily, are optical activity or non-optical activity), R
2Expression hydrogen atom, halogen atom, C
1-4Alkyl, C
1-4Alkoxyl group, C
6-12Aryloxy or C
6-18Aryl, R
3Expression C
1-4Alkyl, C
6-18Aryl, perhaps, at 2 R
3Form under the situation of ring expression C together
3-5The group of divalence, R
4Represent hydrogen atom, halogen atom, C respectively independently
1-4Alkyl, C
1-4Alkoxyl group, nitro or cyano group, M represents TiJ
1J
2(at TiJ
1J
2In, Ti represents titanium atom, J
1And J
2Represent halogen atom, C respectively independently
1-4Alkoxyl group, perhaps, J
1With J
2Represent Sauerstoffatom together, perhaps J
1With J
2Form ring together, expression is as the formula (5) of the group of divalence
(about the part-structure O-E-O in the formula, wherein O represents Sauerstoffatom, in formula (1), as O-E-O, is represented by following formula (6); In formula (1 '),, represent by following formula (6 ') as O-E-O; In formula (2),, represent by following formula (7) as O-E-O; In formula (2 '),, represent by following formula (7 ') as O-E-O; In formula (3),, represent by following formula (8) as O-E-O; In formula (3 '),, represent by following formula (8 ') as O-E-O; In formula (4),, represent by following formula (9) as O-E-O; In formula (4 '), as O-E-O, by following formula (9 ') expression,
B is 1～10 integer, R
1, R
2, R
3And R
4Same as described above))).
Below, each substituting group in above-mentioned formula (1), formula (1 '), formula (2), formula (2 '), formula (3), formula (3 '), formula (4) and the formula (4 ') is described.
R in above-mentioned formula (1), formula (1 '), formula (2), formula (2 '), formula (3), formula (3 '), formula (4) and the formula (4 ')
1Expression hydrogen atom, halogen atom, C
1-4Alkyl, C
1-4Alkoxyl group, C
6-12Aryloxy or C
6-22(this aryl can be by C for aryl
1-4Alkyl (this alkyl can be replaced arbitrarily by halogen atom), C
1-7Alkoxyl group or benzyl oxygen base replace arbitrarily, are optical activity or non-optical activity).
Below, to the R in formula (1), formula (1 '), formula (2), formula (2 '), formula (3), formula (3 '), formula (4) and the formula (4 ')
1Carry out specific description.
As this halogen atom, can list fluorine atom, chlorine atom, bromine atoms and iodine atom,
As this C
1-4Alkyl can list methyl, ethyl, n-propyl group, i-propyl group, n-butyl, i-butyl, s-butyl and t-butyl etc.,
As this C
1-4Alkoxyl group can list methoxyl group, oxyethyl group, n-propoxy-, i-propoxy-, c-propoxy-, n-butoxy, i-butoxy, s-butoxy, t-butoxy and c-butoxy etc.,
As this C
6-12Aryloxy can list phenyl oxygen base, 1-naphthyl oxygen base, 2-naphthyl oxygen base, 2-xenyl oxygen base, 3-xenyl oxygen base and 4-xenyl oxygen base etc.,
As this C
6-22(this aryl can be by C for aryl
1-4Alkyl (this alkyl can be replaced arbitrarily by halogen atom), C
1-7Alkoxyl group, or benzyl oxygen base replaces arbitrarily, be optical activity or non-optical activity), can list phenyl, the 2-aminomethyl phenyl, the 2-trifluoromethyl, the 4-aminomethyl phenyl, the 2-ethylphenyl, 2-pentafluoroethyl group phenyl, 3, the 5-3,5-dimethylphenyl, the 2-p-methoxy-phenyl, the 3-p-methoxy-phenyl, the 4-p-methoxy-phenyl, the 2-ethoxyl phenenyl, 2-i-propoxy-phenyl, 2-benzyl oxygen base phenyl, 3, the 5-Dimethoxyphenyl, the 1-naphthyl, the 2-naphthyl, the 2-xenyl, the 3-xenyl, the 4-xenyl, 2-methyl isophthalic acid-naphthyl, 2-phenyl-1-naphthyl, 2-methoxyl group-1-naphthyl, 2-[3, the 5-3,5-dimethylphenyl]-the 1-naphthyl, the 2-[4-aminomethyl phenyl]-the 1-naphthyl, 2-(o-xenyl)-1-naphthyl, 2-(m-xenyl)-1-naphthyl and 2-(p-xenyl)-1-naphthyl etc.In addition, above-mentioned C
6-22Aryl can be optical activity, also can be non-optical activity.
R in above-mentioned formula (1), formula (1 '), formula (2), formula (2 '), formula (3), formula (3 '), formula (4) and the formula (4 ')
1Be preferably hydrogen atom, fluorine atom, the chlorine atom, bromine atoms, the iodine atom, methyl, ethyl, the n-propyl group, the i-propyl group, the n-butyl, the i-butyl, the s-butyl, the tertiary butyl, methoxyl group, oxyethyl group, the n-propoxy-, the i-propoxy-, the c-propoxy-, the n-butoxy, the i-butoxy, the s-butoxy, the t-butoxy, the c-butoxy, phenyl oxygen base, 1-naphthyl oxygen base, 2-naphthyl oxygen base, phenyl, the 2-aminomethyl phenyl, the 2-trifluoromethyl, the 4-aminomethyl phenyl, the 2-ethylphenyl, 3, the 5-3,5-dimethylphenyl, the 2-p-methoxy-phenyl, the 3-p-methoxy-phenyl, the 4-p-methoxy-phenyl, the 2-ethoxyl phenenyl, 2-i-propoxy-phenyl, 2-benzyl oxygen base phenyl, 3, the 5-Dimethoxyphenyl, the 1-naphthyl, the 2-naphthyl, the 2-xenyl, the 3-xenyl, the 4-xenyl, 2-phenyl-1-naphthyl, 2-methoxyl group-1-naphthyl, 2-(m-xenyl)-1-naphthyl, 2-(p-xenyl)-1-naphthyl, wherein, R
1More preferably phenyl, 2-aminomethyl phenyl, 2-trifluoromethyl, 2-ethylphenyl, 2-p-methoxy-phenyl, 2-benzyl oxygen base phenyl, 1-naphthyl, 2-naphthyl, 2-xenyl, 2-phenyl-1-naphthyl, 2-methoxyl group-1-naphthyl, 2-(m-xenyl)-1-naphthyl, 2-(p-xenyl)-1-naphthyl (this 2-phenyl-1-naphthyl, 2-methoxyl group-1-naphthyl, 2-(m-xenyl)-1-naphthyl or 2-(p-xenyl)-1-naphthyl are optical activity or non-optical activity), wherein, as R
1, more preferably phenyl, 2-aminomethyl phenyl, 2-trifluoromethyl, 2-p-methoxy-phenyl, 2-benzyl oxygen base phenyl, 2-phenyl-1-naphthyl.
R in above-mentioned formula (1), formula (1 '), formula (2), formula (2 '), formula (3), formula (3 '), formula (4) and the formula (4 ')
2Expression hydrogen atom, halogen atom, C
1-4Alkyl, C
1-4Alkoxyl group, C
6-12Aryloxy or C
6-18Aryl.
To the R in above-mentioned formula (1), formula (1 '), formula (2), formula (2 '), formula (3), formula (3 '), formula (4) and the formula (4 ')
2Be specifically described.
As this halogen atom, can list fluorine atom, chlorine atom, bromine atoms and iodine atom,
As this C
1-4Alkyl can list methyl, ethyl, n-propyl group, i-propyl group, n-butyl, i-butyl, s-butyl and the tertiary butyl etc.,
As this C
1-4Alkoxyl group can list methoxyl group, oxyethyl group, n-propoxy-, i-propoxy-, c-propoxy-, n-butoxy, i-butoxy, s-butoxy, t-butoxy and c-butoxy etc.,
As this C
6-12Aryloxy can list phenyl oxygen base, 1-naphthyl oxygen base, 2-naphthyl oxygen base, 2-xenyl oxygen base, 3-xenyl oxygen base and 4-xenyl oxygen base etc.,
As this C
6-18Aryl, can list phenyl, 3,5-3,5-dimethylphenyl, 4-aminomethyl phenyl, 1-naphthyl, 2-naphthyl, 2-xenyl, 2-phenyl-1-naphthyl, 2-methyl isophthalic acid-naphthyl, 2-[3,5-3,5-dimethylphenyl]-1-naphthyl, 2-[4-aminomethyl phenyl]-1-naphthyl and 2-methoxyl group-1-naphthyl etc.
R in above-mentioned formula (1), formula (1 '), formula (2), formula (2 '), formula (3), formula (3 '), formula (4) and the formula (4 ')
2Be preferably hydrogen atom, fluorine atom, the chlorine atom, bromine atoms, the iodine atom, methyl, ethyl, the n-propyl group, the i-propyl group, the n-butyl, the tertiary butyl, methoxyl group, phenyl oxygen base, 1-naphthyl oxygen base, 2-naphthyl oxygen base, phenyl, 3, the 5-3,5-dimethylphenyl, the 4-aminomethyl phenyl, 3, the 5-Dimethoxyphenyl, the 4-p-methoxy-phenyl, the 1-naphthyl, the 2-naphthyl, the 2-xenyl, the 3-xenyl, the 4-xenyl, 2-methoxyl group-1-naphthyl, wherein, R2 is hydrogen atom more preferably, fluorine atom, the chlorine atom, bromine atoms, the iodine atom, methyl, ethyl, the n-propyl group, the i-propyl group, the n-butyl, the tertiary butyl, methoxyl group, phenyl oxygen base, phenyl, the 1-naphthyl, the 2-naphthyl, the 2-xenyl, wherein, R
2Hydrogen atom more preferably.
R in above-mentioned formula (1), formula (1 '), formula (2), formula (2 '), formula (3), formula (3 '), formula (4) and the formula (4 ')
3, expression C
1-4Alkyl, C
6-18Aryl is perhaps at 2 R
3Form under the situation of ring expression C together
3-5The group of divalence.
To the R in above-mentioned formula (1), formula (1 '), formula (2), formula (2 '), formula (3), formula (3 '), formula (4) and the formula (4 ')
3Be specifically described.
As this C
1-4Alkyl can list methyl, ethyl, n-propyl group, i-propyl group, n-butyl, i-butyl, s-butyl and the tertiary butyl etc.,
As this C
6-18Aryl, can list phenyl, 3,5-3,5-dimethylphenyl, 2,4,6-trimethylphenyl, 4-aminomethyl phenyl, 1-naphthyl, 2-xenyl, 2-phenyl-1-naphthyl, 2-methyl isophthalic acid-naphthyl, 2-[3, the 5-3,5-dimethylphenyl]-1-naphthyl, 2-[4-aminomethyl phenyl]-1-naphthyl and 2-methoxyl group-1-naphthyl etc.
At 2 R
3Forming under the situation of ring together, is C
3-5The group of divalence, can list trimethylene and tetramethylene etc.
R in above-mentioned formula (1), formula (1 '), formula (2), formula (2 '), formula (3), formula (3 '), formula (4) and the formula (4 ')
3Be preferably phenyl, 3,5-3,5-dimethylphenyl, 2,4,6-trimethylphenyl, 4-aminomethyl phenyl, 2 R
3The tetramethylene of bonding, wherein, R
32 R more preferably
3The tetramethylene of mutual bonding.
R in above-mentioned formula (1), formula (1 '), formula (2), formula (2 '), formula (3), formula (3 '), formula (4) and the formula (4 ')
4Expression hydrogen atom, halogen atom, C
1-4Alkyl, C
1-4Alkoxyl group, nitro or cyano group.
To the R in above-mentioned formula (1), formula (1 '), formula (2), formula (2 '), formula (3), formula (3 '), formula (4) and the formula (4 ')
4Be specifically described.
As this halogen radical, can list fluorine atom, chlorine atom, bromine atoms and iodine atom,
As this C
1-4Alkyl can list methyl, ethyl, n-propyl group, i-propyl group, n-butyl, i-butyl, s-butyl and the tertiary butyl etc.,
As this C
1-4Alkoxyl group can list methoxyl group, oxyethyl group, n-propoxy-, i-propoxy-, n-butoxy, i-butoxy, s-butoxy and t-butoxy etc.
R in above-mentioned formula (1), formula (1 '), formula (2), formula (2 '), formula (3), formula (3 '), formula (4) and the formula (4 ')
4Be preferably hydrogen atom, fluorine atom, chlorine atom, bromine atoms, methyl, ethyl, n-propyl group, i-propyl group, n-butyl, i-butyl, s-butyl, the tertiary butyl, methoxyl group, oxyethyl group, n-propoxy-, i-propoxy-, n-butoxy, i-butoxy, s-butoxy, t-butoxy, wherein, as R
4, more preferably hydrogen atom.
M in above-mentioned formula (1), formula (1 '), formula (2), formula (2 '), formula (3), formula (3 '), formula (4) and the formula (4 ') represents TiJ
1J
2(at TiJ
1J
2In, Ti represents titanium atom, J
1And J
2Represent halogen atom, C respectively independently
1-4Alkoxyl group, perhaps J
1With J
2Represent Sauerstoffatom together, perhaps J
1With J
2Form ring together, expression is as the formula (5) of the group of divalence
(about the part-structure O-E-O in the formula, wherein O is a Sauerstoffatom, in formula (1), as O-E-O, with following formula (6) expression, in formula (1 '), as O-E-O, with following formula (6 ') expression, in formula (2), as O-E-O, with following formula (7) expression, in formula (2 '), as O-E-O, with following formula (7 ') expression, in formula (3), as O-E-O, with following formula (8) expression, in formula (3 '), as O-E-O, with following formula (8 ') expression, in formula (4), as O-E-O, with following formula (9) expression, in formula (4 '), as O-E-O, represent with following formula (9 ')
B is 1～10 integer, R
1, R
2, R
3And R
4Same as described above)).
In addition, at J
1With J
2Represent together under the situation of Sauerstoffatom that formula (1), formula (1 '), formula (2), formula (2 '), formula (3), formula (3 '), formula (4) and formula (4 ') as all structures of molecule, become the oxygen titanium complex of monokaryon, at J
1With J
2Form together under ring, the situation of expression as the formula (5) of the group of divalence, formula (1), formula (1 '), formula (2), formula (2 '), formula (3), formula (3 '), formula (4) and formula (4 '), as all structures of molecule, become μ-oxygen titanium (b+1) nuclear complex compound as polynuclear complex.
In addition, in formula (1), formula (1 '), formula (2), formula (2 '), formula (3), formula (3 '), formula (4) and formula (4 ') is under the situation of above-mentioned oxygen titanium complex or μ-oxygen titanium (b+1) nuclear complex compound, and optical activity titanium complex of the present invention can be that these oxygen titanium complexs or b are the mixture that any one state μ-oxygen titanium (b+1) down of 1～10 is examined complex compound.
As preferred J
1And J
2, can list J
1With J
2Represent Sauerstoffatom together, or J
1With J
2Form ring together, expression is as the situation of the formula (5) of the group of divalence, and in these cases, the optical activity titanium complex is respectively the oxygen titanium complex or μ-oxygen titanium (b+1) the nuclear complex compound (b is 1～10 integer) of monokaryon.
And then, about optical activity titanium complex of the present invention, the type that is divided into the titanium Salan complex compound shown in optical activity titanium Salalen complex compound shown in above-mentioned formula (1), formula (1 '), formula (3) and the formula (3 ') or formula (2), formula (2 '), formula (4) and the formula (4 '), below, the combination and all structures of molecule of preferred substituted described.
Optical activity titanium Salalen complex compound shown in above-mentioned formula (1), formula (1 '), formula (3) and the formula (3 ') is used J
1With J
2Form above-mentioned formula (5) expression as the group of divalence of ring together, in formula (5), b is preferably 1.In this case, formula (1), formula (1 '), formula (3) and formula (3 ') as all structures of molecule, become the μ shown in following formula (18) and (18 ')-oxygen titanium two nuclear complex compounds.
(in the formula, O-NH-N-O in formula (1), is following formula (19); In formula (1 '), it is formula (19 '); In formula (2), be formula (20); In formula (2 '), be formula (20 '),
(R here,
1, R
2, R
3And R
4Same as described above), the complex compound of formula (18 ') is the enantiomer of the complex compound of formula (18).)
Particularly preferred substituent combination and all structures of molecule in the above-mentioned optical activity titanium Salalen complex compound are described.Particularly preferred optical activity titanium Salalen complex compound is represented with formula (18) and formula (18 '), part-structure O-NH-N-O in this formula is following formula (21), (21 '), (22) or formula (22 ') expression (aRS Δ, the aRS Δ)-two-μ-oxygen titanium two nuclear complex compounds and (aSR Λ, aSR Λ)-two-μ-oxygen titanium two nuclear complex compounds.
As the particularly preferred substituent combination in the optical activity titanium Salan complex compound shown in above-mentioned formula (2), formula (2 '), formula (4) and the formula (4 '), can list the oxygen titanium complex or μ-oxygen titanium (b+1) the amount body (b is 1～10 integer) of the monokaryon shown in following formula (23), (23 '), (24) or the formula (24 ')
(M in the formula represents TiJ
1J
2, J
1With J
2Represent Sauerstoffatom together, perhaps form ring together, expression is as the above-mentioned formula (5) of the group of divalence, and in formula (5), b is 1～10 integer, and part-structure O-E-O is respectively by following formula (25), (25 '), (26) or formula (26 ') expression).
Then, the manufacture method to the optical activity titanium complex of formula (1), formula (1 '), formula (2), formula (2 '), formula (3), formula (3 '), formula (4) and formula (4 ') expression describes.
About as the Salan part shown in formula (29), formula (29 '), formula (31) or the formula (31 ') of the part of the titanium Salan complex compound shown in formula (2), formula (2 '), formula (4) and the formula (4 '), can be respectively by the Salen compound shown in following formula (28), formula (28 '), formula (30) or the formula (30 ') being gone back original the manufacturing.
As reductive agent, can list sodium borohydride (NaBH
4), cyaniding sodium borohydride (NaBH
3CN) and lithium aluminum hydride (LiAlH
4) etc., preferred sodium borohydride (NaBH
4).
Optical activity titanium Salan complex compound shown in formula (2), formula (2 '), formula (4) and the formula (4 '), can be by Salan part and titanium alkoxide, titanium tetrachloride or titanium tetrabromide with correspondence, in the organic solvent of methylene dichloride etc. after the reaction, water or water-containing solvent are (in organic solvent, in quality %, the mixed solvent that contains 0.1～100% water, organic solvent as using can list THF, methyl alcohol and i-propyl alcohol etc.) handle and make.The usage quantity of water with respect to the equivalent of above-mentioned Salan part, is preferably 1～1000 mole scope, more preferably 1～10 mole scope.
In addition, in reaction system, also can generate above-mentioned optical activity titanium Salan complex compound,, not separate, and carry out the asymmetric epoxidation reaction of chromene compounds as catalyzer.At this moment, aquae hydrogenii dioxidi can be added, also water can be added as oxygenant.
As titanium compound, preferred titanium alkoxide as this titanium alkoxide, can list tetramethyl alcohol titanium, titanium tetraethoxide, four n-propyl alcohol titaniums, titanium tetraisopropylate, four propyl carbinol titaniums and four trimethyl carbinol titaniums etc., wherein, and more preferably titanium tetraisopropylate [Ti (Oi-Pr)
4].The usage quantity of titanium alkoxide is with respect to above-mentioned Salan ligand 1 mole, preferred 1～2 mole scope.
Optical activity titanium Salalen complex compound shown in formula (1), formula (1 '), formula (3) and the formula (3 ') can according to non-patent literature 8 (Angew.Chem.Int.Ed. (2005), 44,4935-4939.) Ji Zai method is made.Promptly, make corresponding Salen part and titanium alcohol reactant salt, by Meerwein-Ponndrof-Verley (MPV) reduction reaction, make the side reduction of 2 imido base keies of Salen part, form titanium complex simultaneously, after reaction finishes, water or water-containing solvent are (in organic solvent, in quality %, contain the mixed solvent of 0.1～100% water, the organic solvent as using can list THF, methyl alcohol and i-propyl alcohol etc.) handle and make.
In addition, in reaction system, can also generate above-mentioned optical activity titanium Salalen complex compound,, not separate, and carry out the asymmetric epoxidation reaction of chromene compounds as catalyzer.
In addition,, can list tetramethyl alcohol titanium, titanium tetraethoxide, four n-propyl alcohol titaniums, titanium tetraisopropylate, four propyl carbinol titaniums and titanium four trimethyl carbinol titaniums etc. as this titanium alkoxide, wherein, preferred titanium tetraisopropylate [Ti (Oi-Pr)
4].The usage quantity of titanium alkoxide, with respect to 1 mole of above-mentioned Salen part, preferred 1～2 mole scope.In addition, the usage quantity of water with respect to the equivalent of above-mentioned Salen part, is preferably 1～1000 mole scope, more preferably 1～10 mole scope.
Reaction solvent when making the optical activity titanium complex is the organic solvent of non-protic, the organic solvent of protic or the mixture of these solvents.Organic solvent as non-proton property, can list halogen series solvent, aromatic hydrocarbons series solvent, ester series solvent, ether series solvent or nitrile series solvent etc., specifically, can list methylene dichloride, chloroform, 1,2-ethylene dichloride, chlorobenzene, toluene, acetate ethyl ester, tetrahydrofuran (THF), ether, butyronitrile, propionitrile, acetonitrile etc.As the organic solvent of protic, can list pure series solvent, specifically, can list ethanol, i-propyl alcohol or t-butanols etc.
Preferred reaction solvent is the methylene dichloride, 1 as the organic solvent of non-proton property, 2-ethylene dichloride, chlorobenzene, toluene, acetate ethyl ester.
In manufacture method of the present invention, by use formula (1), formula (1 '), formula (2), formula (2 '), formula (3), formula (3 '), formula (4) and the represented optical activity titanium complex of formula (4 '), chromene compounds as starting raw material is carried out asymmetric Epoxidation, can make a side of the enantiomer of chromene oxide compound with high selectivity.Specifically, by the either party of complex compound shown in the use formula (1) or the complex compound shown in the formula (1 '), a side that can optionally make two enantiomers of optically active chromene oxide compound.By any one of complex compound shown in the use formula (2) or the complex compound shown in the formula (2 '), a side that can optionally make two enantiomers of optically active chromene oxide compound.By any one of complex compound shown in the use formula (3) or the complex compound shown in the formula (3 '), a side that can optionally make two enantiomers of optically active chromene oxide compound.By complex compound shown in the use formula (4) or the complex compound shown in the formula (4 ') any one, can optionally make two enantiomers of optically active chromene oxide compound.
Then, the manufacture method to optically active chromene oxide compound of the present invention describes.Be to make following formula (14), formula (15), the method of the optically active chromene oxide compound shown in formula (16) or the formula (17), wherein, by with formula (10), formula (11), chromene compounds shown in formula (12) or the formula (13) and formula (1), formula (1 '), formula (2), formula (2 '), formula (3), formula (3 '), optical activity titanium complex shown in any one of formula (4) and formula (4 '), under nitrogen atmosphere or in atmosphere, be dissolved in the organic solvent, in this reaction soln, add oxygenant, stir, carry out asymmetric epoxidation reaction
(the R in the formula (10)
5, R
6, R
7And R
8Represent hydrogen atom, cyano group, nitro, halogen atom, C respectively independently
1-4(this alkyl can be by halogen atom, hydroxyl, cyano group, nitro, C for alkyl
1-4Alkoxyl group, C
1-4Alkyl-carbonyl oxygen base, C
1-4Alkyl-carbonyl-amino, C
1-4Any replacement of alkoxy carbonyl (this alkoxyl group, alkyl-carbonyl oxygen base, alkyl-carbonyl-amino and alkoxy carbonyl can be replaced arbitrarily by halogen atom)), C
1-4(this alkoxyl group can be by halogen atom, hydroxyl, cyano group, nitro, C for alkoxyl group
1-4Alkoxyl group, C
1-4Alkyl-carbonyl oxygen base, C
1-4Alkyl-carbonyl-amino, C
1-4Any replacement of alkoxy carbonyl (this alkoxyl group, alkyl-carbonyl oxygen base, alkyl-carbonyl-amino and alkoxy carbonyl can be replaced arbitrarily by halogen atom)), C
1-4(this alkyl-carbonyl-amino can (this phenyl can be by halogen atom, hydroxyl, cyano group, nitro, C by halogen atom, phenyl for alkyl-carbonyl-amino
1-4Alkyl or C
1-4Alkoxyl group replaces arbitrarily) replace arbitrarily), C
1-4Alkyl-carbonyl (N-C
1-4Alkyl) amino (this alkyl-carbonyl (N-alkyl) amino can be replaced arbitrarily by halogen atom), C
1-4Alkoxy carbonyl (this alkoxy carbonyl can be replaced arbitrarily by halogen atom), C
6-10(this aryl-amino-carbonyl can be by halogen atom, C for aryl-amino-carbonyl
1-4Alkyl, C
1-4Alkoxyl group, cyano group or nitro replace), C
6-10Aryl carbonyl (N-C
1-4It is alkyl) amino that (this aryl carbonyl (N-alkyl) amino can be by halogen atom, C
1-4Alkyl, C
1-4Alkoxyl group, cyano group or nitro replace), benzyloxycarbonyl group amino, formyl radical, formamyl, C
1-4Alkyl sulphonyl, C
6-10(this alkyl sulphonyl and aryl sulfonyl can be by halogen atom, C for aryl sulfonyl
1-4Alkyl, C
1-4Alkoxyl group, cyano group or nitro replace), sulfamyl, C
1-4Alkylsulfonamido, C
6-10(this alkylsulfonamido and aryl-sulfonyl amino can be by halogen atom, C for aryl-sulfonyl amino
1-4Alkyl, C
1-4Alkoxyl group, cyano group or nitro replace), two (C
1-4Alkyl sulfonyl) (alkyl sulfonyl of this pair (alkyl sulfonyl) imido grpup can be by halogen atom, C for imido grpup
1-4Alkyl, C
1-4Alkoxyl group, cyano group or nitro replace), two (C
6-10Arylsulfonyl) (arylsulfonyl of this pair (arylsulfonyl) imido grpup can be by halogen atom, C for imido grpup
1-4Alkyl, C
1-4Alkoxyl group, cyano group or nitro replace), [N, N '-(C
1-4Alkyl sulfonyl) (C
6-10Arylsulfonyl)] (alkyl sulfonyl and the arylsulfonyl that are somebody's turn to do [N, N '-(alkyl sulfonyl) (arylsulfonyl)] imido grpup can be by halogen atom, C for imido grpup
1-4Alkyl, C
1-4Alkoxyl group, cyano group or nitro replace),
R in the formula (10)
9And R
10Represent hydrogen atom, C respectively independently
1-6(this alkyl can be by halogen atom, C for alkyl
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom) or hydroxyl replace arbitrarily), C
6-14(this aryl can be by halogen atom, hydroxyl, nitro, cyano group, C for aryl
1-6(this alkyl can be by halogen atom, C for alkyl
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom) or hydroxyl replace arbitrarily) or C
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom) replaces arbitrarily),
R in formula (11) and the formula (12)
9And R
10Represent hydrogen atom, C respectively independently
1-6(this alkyl can be by halogen atom, C for alkyl
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom) or hydroxyl replace arbitrarily) or C
6-14(this aryl can be by halogen atom, hydroxyl, nitro, cyano group, C for aryl
1-6(this alkyl can be by halogen atom, C for alkyl
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom) or hydroxyl replace arbitrarily) or C
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom) replaces arbitrarily),
Part ring structure A in formula (11) and the formula (12) represents partly to form the represented part-structure of 5,6 or 7 Yuans of condensed ring rings with phenyl ring, and (wherein, these 5,6 or 7 Yuans rings can be by h R
11Replace (wherein, R arbitrarily
11Be halogen atom, hydroxyl, C
1-6(this alkyl can be by halogen atom, hydroxyl, cyano group, amino, nitro, C for alkyl
1-4Alkoxyl group, C
1-4Alkyl-carbonyl oxygen base, C
1-4Alkyl-carbonyl-amino, C
1-4Any replacement of alkoxy carbonyl (this alkoxyl group, alkyl-carbonyl oxygen base, alkyl-carbonyl-amino and alkoxy carbonyl can be replaced arbitrarily by halogen atom)), C
1-6(this alkoxyl group can be by halogen atom, hydroxyl, cyano group, amino, nitro, C for alkoxyl group
1-4Alkoxyl group, C
1-4Alkyl-carbonyl oxygen base, C
1-4Alkyl-carbonyl-amino, C
1-4Any replacement of alkoxy carbonyl (this alkoxyl group, alkyl-carbonyl oxygen base, alkyl-carbonyl-amino and alkoxy carbonyl can be replaced arbitrarily by halogen atom)), nitro, cyano group, formyl radical, formamido-, formamyl, sulfo group, sulfoamino-, sulfamyl, alkylsulfonyl, amino, carboxyl, C
1-6Alkylamino, two C
1-6Alkylamino, C
1-6Alkyl-carbonyl-amino, C
1-6Alkylsulfonamido, C
6-14Aryl-sulfonyl amino, C
1-6Alkyl amino-carbonyl, two C
1-6Alkyl amino-carbonyl, C
1-6Alkyl-carbonyl, C
1-6Alkoxy carbonyl, C
1-6Alkyl sulphonyl, C
6-14Aryl sulfonyl or C
6-14Aryl carbonyl (this alkylamino, dialkyl amido, alkyl-carbonyl-amino, alkylsulfonamido, aryl-sulfonyl amino, alkyl amino-carbonyl, dialkyl amino carbonyl, alkyl-carbonyl, alkoxy carbonyl, alkyl sulphonyl, aryl sulfonyl and aryl carbonyl can be replaced arbitrarily by halogen atom); h is 1～6 integer; be under 2～6 the situation at h, R
11Can be the same or different, the constituting atom as ring can contain 1～3 Sauerstoffatom, nitrogen-atoms or sulphur atom alone or in combination, the number of intra-annular unsaturated link(age) comprises the unsaturated link(age) of the phenyl ring of condensation, is 1,2 or 3, the carbon atom that constitutes ring can be carbonyl or thiocarbonyl)
X in the formula (13) represents NR
20(R
20Expression hydrogen atom or C
1-4Alkyl), the Y in the formula (13) represents Direct Bonding, SO or SO
2, the Z in the formula (13) represents C
1-4(this alkyl can (this phenyl can be by C by 1～5 halogen atom or phenyl for alkyl
1-4Alkyl replaces arbitrarily) replace arbitrarily) or phenyl (this phenyl can be by C
1-4Alkyl replaces arbitrarily), the W in the formula (13) represents hydrogen atom, hydroxyl, C
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom), halogen atom, C
1-4Alkyl or C
1-6Alkylsulfonamido (this alkyl and alkylsulfonamido can be replaced arbitrarily by halogen atom),
R in the formula (13)
9And R
10Represent hydrogen atom, C respectively independently
1-6(this alkyl can be by halogen atom, C for alkyl
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom) or hydroxyl replace arbitrarily) or C
6-14(this aryl can be by halogen atom, hydroxyl, nitro, cyano group, C for aryl
1-6(this alkyl can be by halogen atom, C for alkyl
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom) or hydroxyl replace arbitrarily) or C
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom) replaces arbitrarily)),
(R in the formula
5, R
6, R
7, R
8, R
9, R
10, A, W, X, Y and Z be same as described above, the absolute configuration of * marked carbon atoms is (R) or (S)).
In addition, can make by the method shown in the following reaction formula 1.
Reaction formula 1
Reaction formula 1 (R in the formula
5, R
6, R
7, R
8, R
9, R
10, A, W, X, Y and Z be same as described above.* the absolute configuration of marked carbon atoms is (R) or (S)), be by in solvent, chromene compounds with formula (10), formula (11), formula (12) or formula (13), handle with oxygenant and optical activity titanium complex, by the optically active chromene oxide shown in formula (10) the manufacturing formula (14), by the optically active chromene oxide shown in formula (11) the manufacturing formula (15), by the optically active chromene oxide shown in formula (12) the manufacturing formula (16) or by the method for the optically active chromene oxide compound shown in formula (13) the manufacturing formula (17).
Chromene compounds as shown in above-mentioned formula (10), formula (11), formula (12) or the formula (13) of starting raw material of the present invention can use the general synthesis method of following chromene ring to synthesize.In addition, synthetic about the condensed ring in formula (11), the formula (12), can by will various heterocyclic synthetic methods shown below and chromene cyclization established law appropriate combination make and be used for realization.
The general synthesis method of zero chromene ring
Can be according to known method (J.M.Evans, et al., J.Med.Chem.1984,27,1127., J.Med.Chem.1986,29,2194., J.T.North, et al., J.Org.Chem.1995,60,3397., the spy opens clear 56-57785 communique, spy and opens clear 56-57786 communique, spy and open that clear 58-188880 communique, spy are opened flat 2-141 communique, the spy opens the method for records such as flat 10-87650 communique and the flat 11-209366 communique of Te Kai) come synthetic.
Zero indoles, oxindoles (oxoindole)
Can be according to known method (T.Sakamoto, et al., Heterocycles,, 24,31. in 1986
M.Belley, et al., Synthesis, calendar year 2001,222.
A.D.Cross, et al., J.Chem.Soc.,, the method for record such as 2714. grades in 1961) synthetic.
Zero imidazolone
Can come synthetic according to known method (J.Kitteringham, et.al., Synthetic Commun.,, the method for 30,1937. records in 2000).
Zero quinoline
Can be according to known method (S.Imor, et al., Synthetic Commun.,, 26,2197. in 1996
Y.Kitahara, et al., Tetrahedron,, 53,6001. in 1997
A.G.Osborne, et al., J.Chem.Soc.Perkin Trans.1993,1,181.
R.T.Shuman, et al., J.Org.Chem., nineteen ninety, 55,738.
T.Sakamoto, et al., Chem.Pharm.Bull.,, 29,2485. in 1981
Y.Tsuji, et al., J.Org.Chem.,, 52,1673. in 1987
Z.Song, et al., J.Heterocyclic Chem.,, the method for record such as 30,17. grades in 1993) synthesize.
Zero quinolinone
Can be according to known method (M.R.Sabol, et al., Synthetic Commun.,, 30,427. in 2000
Z-Y.Yang, et al., Tetrahedron Lett.,, 40,4505. in 1999
H-B Sun, et al., Synthesis,, 1249. in 1997
A.Guiotto, et al., J.Heterocyclic Chem.,, 26,917. in 1989
K.Konno, et al., Heterocycles,, 24,2169. in 1986
E.Fernandez, et al., Synthesis, nineteen ninety-five, the method for record such as 1362. grades) synthesize.
Zero benzothiazole, triazole,
Can be according to known method (N.B.Ambati, et al., Synthetic Commun.,, 27,1487. in 1997
D.E.Burton, et al., J.Chem.Soc (C)., nineteen sixty-eight, the method for record such as 1268. grades) synthesize.
Zero quinoxaline, quinazolone
Can be according to known method (J.H.Liu, et al., J.Org.Chem.,, 65,3395. in 2000
J.J.Li, et al., Tetrahedron Lett.,, 40,4507. in 1999
Y.Ahmed, et al., Bull.Chem.Soc.Jpn.,, the method for record such as 60,1145. grades in 1987) synthesize.
Zero benzoxazinone
Can be according to known method (G.H.Jones, et al., J.Med.Chem.,, 30,295. in 1987
J.L.Wright, et al., J.Med.Chem.,, 43,3408. in 2000
M.Kluge, et al., J.Heterocyclic Chem., nineteen ninety-five, the method for record such as 32,395. grades) synthesize.
Zero following formula (35), the compound shown in (36) can obtain by making compound (33) and compound (34) reaction.(reference Y.Tsuji, et al., J.Org.Chem.,, 52,1673. in 1987)
Zero following formula (35), the compound shown in (36) also can obtain by compound (33) and compound (37) are reacted in the presence of acid catalyst.(reference Y.Kitahara, et al., Tetrahedron 1997,53,6001., Z.Song, et al., J.Heterocyclic Chem.,, 30,17. in 1993)
Chromene compounds shown in the zero following formula (40) can be synthetic by compound (38), via being the compound (39) of amine with the platinum C catalyst with nitroreduction, then, carries out methylsulfonylization and obtain.
Each substituting group to the chromene compounds shown in above-mentioned formula (10), formula (11), formula (12) or the formula (13) is specifically described.
Below, each substituting group of above-mentioned formula (10) is described.R in the formula (10)
5, R
6, R
7And R
8Represent hydrogen atom, cyano group, nitro, halogen atom, C respectively independently
1-4(this alkyl can be by halogen atom, hydroxyl, cyano group, nitro, C for alkyl
1-4Alkoxyl group, C
1-4Alkyl-carbonyl oxygen base, C
1-4Alkyl-carbonyl-amino, C
1-4Any replacement of alkoxy carbonyl (this alkoxyl group, alkyl-carbonyl oxygen base, alkyl-carbonyl-amino and alkoxy carbonyl can be replaced arbitrarily by halogen atom)), C
1-4(this alkoxyl group can be by halogen atom, hydroxyl, cyano group, nitro, C for alkoxyl group
1-4Alkoxyl group, C
1-4Alkyl-carbonyl oxygen base, C
1-4Alkyl-carbonyl-amino, C
1-4Any replacement of alkoxy carbonyl (this alkoxyl group, alkyl-carbonyl oxygen base, alkyl-carbonyl-amino and alkoxy carbonyl can be replaced arbitrarily by halogen atom)), C
1-4(this alkyl-carbonyl-amino can be by halogen atom, C for alkyl-carbonyl-amino
6-10Aryl (this C
6-10Aryl can be by halogen atom, hydroxyl, cyano group, nitro, C
1-4Alkyl or C
1-4Alkoxyl group replaces arbitrarily) replace arbitrarily), [C
1-4Alkyl-carbonyl (N-C
1-4Alkyl) amino (this alkyl-carbonyl (N-alkyl) amino can be replaced arbitrarily by halogen atom), C
1-4Alkoxy carbonyl (this alkoxy carbonyl can be replaced arbitrarily by halogen atom), C
6-10(this aryl-amino-carbonyl can be by halogen atom, C for aryl-amino-carbonyl
1-4Alkyl, C
1-4Alkoxyl group, cyano group or nitro replace arbitrarily), C
6-10Aryl carbonyl (N-C
1-4It is alkyl) amino that (this aryl carbonyl (N-alkyl) amino can be by halogen atom, C
1-4Alkyl, C
1-4Alkoxyl group, cyano group or nitro replace arbitrarily), benzyloxycarbonyl group amino, formyl radical, formamyl, C
1-4Alkyl sulphonyl (this alkyl sulphonyl can be replaced arbitrarily by halogen atom), C
6-10(this aryl sulfonyl can be by halogen atom, C for aryl sulfonyl
1-4Alkyl, C
1-4Alkoxyl group, cyano group or nitro replace arbitrarily), sulfamyl, C
1-4Alkylsulfonamido, C
6-10(this alkylsulfonamido and this aryl-sulfonyl amino can be by halogen atom, C for aryl-sulfonyl amino
1-4Alkyl, C
1-4Alkoxyl group, cyano group or nitro replace arbitrarily), two (C
1-4Alkyl sulfonyl) (alkyl sulfonyl of this pair (alkyl sulfonyl) imido grpup can be by halogen atom, C for imido grpup
1-4Alkyl, C
1-4Alkoxyl group, cyano group or nitro replace arbitrarily), two (C
6-10Arylsulfonyl) (arylsulfonyl of this pair (arylsulfonyl) imido grpup can be by halogen atom, C for imido grpup
1-4Alkyl, C
1-4Alkoxyl group, cyano group or nitro replace arbitrarily), [N, N '-(C
1-4Alkyl sulfonyl) (C
6-10Arylsulfonyl)] (arylsulfonyl and the alkyl sulfonyl that are somebody's turn to do [N, N '-(alkyl sulfonyl) (arylsulfonyl)] imido grpup can be by halogen atom, C for imido grpup
1-4Alkyl, C
1-4Alkoxyl group, cyano group, nitro replace arbitrarily).
Below, to the R in the formula (10)
5, R
6, R
7And R
8Each substituting group be specifically described.
As this halogen atom, can list fluorine atom, chlorine atom, bromine atoms and iodine atom, as this C
1-4Alkyl can list methyl, trifluoromethyl, trichloromethyl, ethyl, n-propyl group, i-propyl group, c-propyl group, n-butyl, i-butyl, s-butyl, the tertiary butyl and c-butyl etc., as this C
1-4Alkoxyl group can list methoxyl group, trifluoromethoxy, trichlorine methoxyl group, oxyethyl group, n-propoxy-, i-propoxy-, c-propoxy-, n-butoxy, i-butoxy, s-butoxy, t-butoxy and c-butoxy etc., as this C
1-4Alkyl-carbonyl-amino, can list, methyl carbonylamino, trifluoromethyl carbonylamino, trichloromethyl carbonylamino, ethyl carbonylamino, n-propyl group carbonylamino, i-propyl group carbonylamino, c-propyl group carbonylamino, n-butyl carbonylamino, i-butyl carbonylamino, s-butyl carbonylamino, tertiary butyl carbonylamino, c-butyl carbonylamino, p-anisole ylmethyl carbonylamino, p-nitrophenyl methyl carbonylamino and p-p-methoxy-phenyl ethyl carbonylamino etc. are as this C
1-4Alkyl-carbonyl (N-C
1-4Alkyl) amino, can list methyl carbonyl (N-methyl) amino, trifluoromethyl carbonyl (N-methyl) amino, methyl carbonyl (N-ethyl) amino, trifluoromethyl carbonyl (N-ethyl) amino, ethyl carbonyl (N-ethyl) amino, n-propyl group carbonyl (N-ethyl) amino, i-propyl group carbonyl (N-ethyl) amino, c-propyl group carbonyl (N-ethyl) amino, n-butyl carbonyl (N-ethyl) amino, i-butyl carbonyl (N-ethyl) amino, s-butyl carbonyl (N-ethyl) amino, tertiary butyl carbonyl (N-ethyl) amino and c-butyl carbonyl (N-ethyl) amino etc. are as this C
1-4Alkoxy carbonyl, can list methoxycarbonyl, trifluoromethoxy carbonyl, ethoxy carbonyl, n-propoxycarbonyl, i-propoxycarbonyl, c-propoxycarbonyl, n-butoxy carbonyl, i-butoxy carbonyl, s-butoxy carbonyl, t-butoxy carbonyl and c-butoxy carbonyl etc., as this C
6-10Aryl-amino-carbonyl can list phenylcarbonyl group amino, 1-naphthyl carbonyl amino and 2-naphthyl carbonyl amino etc., as this C
6-10Aryl carbonyl (N-C
1-4Alkyl) amino can list phenylcarbonyl group (N-methyl) amino, phenylcarbonyl group (N-ethyl) amino, 1-naphthyl carbonyl (N-ethyl) amino and 2-naphthyl carbonyl (N-ethyl) amino etc., as this C
1-4Alkyl sulphonyl; can list methane sulfonyl, trifluoromethane sulfonyl group, ethane alkylsulfonyl, n-propane alkylsulfonyl, i-propane alkylsulfonyl, c-propane alkylsulfonyl, n-butane alkylsulfonyl, i-butane alkylsulfonyl, s-butane alkylsulfonyl, t-butane alkylsulfonyl and c-butane alkylsulfonyl etc., as this C
6-10Aryl sulfonyl can list benzenesulfonyl, p-fluorobenzene alkylsulfonyl, p-tosyl group, 1-naphthalene sulfonyl base and 2-naphthalene sulfonyl base etc., as this C
1-4Alkylsulfonamido, can list methylsulfonyl amido, fluoroform sulfoamido, ethane sulphonamide base, n-propane sulfoamido, i-propane sulfoamido, c-propane sulfoamido, n-butane sulfoamido, i-butane sulfoamido, s-butane sulfoamido, t-butane sulfoamido and c-butane sulfoamido etc., as this C
6-10Aryl-sulfonyl amino can list benzene sulfonamido, p-fluorobenzene sulfoamido, p-tolylsulfonyl amido, 1-naphthalene sulfonyl amido and 2-naphthalene sulfonyl amido etc., as this pair (C
1-4Alkyl sulfonyl) imido grpup, can list two (sulfonyl methane) imido grpups, two (trifluoromethane sulphonyl) imido grpup, two (ethane sulphonyl) imido grpup, two (n-propane sulphonyl) imido grpup, two (i-propane sulphonyl) imido grpup, two (c-propane sulphonyl) imido grpup, two (n-butane sulphonyl) imido grpup, two (i-butane sulphonyl) imido grpup, two (s-butane sulphonyl) imido grpup, two (t-butane sulphonyl) imido grpup and two (c-butane sulphonyl) imido grpups etc., as this pair (C
6-10Arylsulfonyl) imido grpup can list two (benzene sulfonyl) imido grpups, two (p-fluorobenzene sulphonyl) imido grpup, two (p-tolylsulfonyl) imido grpup, two (1-naphthalene sulfonyl) imido grpup and two (2-naphthalene sulfonyl) imido grpups etc., as this [N, N '-(C
1-4Alkyl sulfonyl) (C
6-10Arylsulfonyl)] imido grpup, can list [N, N '-(methane) (benzene)] imido grpup, [N, N '-(trifluoromethane) (benzene)] imido grpup, [N, N '-(trifluoromethane) (p-fluorobenzene)] imido grpup, [N, N '-(ethane) (benzene)] imido grpup, [N, N '-(methane) (p-toluene)] imido grpup, [N, N '-(trifluoromethane) (p-toluene)] imido grpup, [N, N '-(ethane) (p-toluene)] imido grpup, [N, N '-(methane) (1-naphthalene)] imido grpup, [N, N '-(trifluoromethane) (1-naphthalene)] imido grpup, [N, N '-(ethane) (1-naphthalene)] imido grpup, [N, N '-(methane) (2-naphthalene)] imido grpup, [N, N '-(trifluoromethane) (2-naphthalene)] imido grpup and [N, N '-(ethane) (2-naphthalene)] imido grpup etc.
R in the formula (10)
5And R
6Independent respectively; preferred hydrogen atom; cyano group; nitro; fluorine atom; the chlorine atom; bromine atoms; the iodine atom; methyl; trifluoromethyl; ethyl; the n-propyl group; the i-propyl group; the c-propyl group; the n-butyl; the i-butyl; the s-butyl; the tertiary butyl; the c-butyl; methoxyl group; trifluoromethoxy; oxyethyl group; the n-propoxy-; the i-propoxy-; the c-propoxy-; the n-butoxy; the i-butoxy; the s-butoxy; the t-butoxy; the c-butoxy; the methyl carbonylamino; the trifluoromethyl carbonylamino; the ethyl carbonylamino; n-propyl group carbonylamino; i-propyl group carbonylamino; c-propyl group carbonylamino; n-butyl carbonylamino; i-butyl carbonylamino; s-butyl carbonylamino; tertiary butyl carbonylamino; c-butyl carbonylamino; methyl carbonyl (N-methyl) amino; trifluoromethyl carbonyl (N-methyl) amino; methyl carbonyl (N-ethyl) amino; trifluoromethyl carbonyl (N-ethyl) amino; ethyl carbonyl (N-ethyl) amino; n-propyl group carbonyl (N-ethyl) amino; i-propyl group carbonyl (N-ethyl) amino; c-propyl group carbonyl (N-ethyl) amino; n-butyl carbonyl (N-ethyl) amino; i-butyl carbonyl (N-ethyl) amino; s-butyl carbonyl (N-ethyl) amino; tertiary butyl carbonyl (N-ethyl) amino; c-butyl carbonyl (N-ethyl) amino; methoxycarbonyl; the trifluoromethoxy carbonyl; ethoxy carbonyl; the n-propoxycarbonyl; the i-propoxycarbonyl; phenylcarbonyl group amino; 1-naphthyl carbonyl amino; 2-naphthyl carbonyl amino; phenylcarbonyl group (N-methyl) amino; phenylcarbonyl group (N-ethyl) amino; 1-naphthyl carbonyl (N-ethyl) amino; 2-naphthyl carbonyl (N-ethyl) amino; benzyloxycarbonyl group amino; formyl radical; formamyl; the methylsulfonyl amido; the fluoroform sulfoamido; the ethane sulphonamide base; n-propane sulfoamido; i-propane sulfoamido; c-propane sulfoamido; n-butane sulfoamido; i-butane sulfoamido; s-butane sulfoamido; t-butane sulfoamido; c-butane sulfoamido; two (sulfonyl methane) imido grpup; two (trifluoromethane sulphonyl) imido grpup; two (ethane sulphonyl) imido grpup; two (n-propane sulphonyl) imido grpup; two (i-propane sulphonyl) imido grpup; two (c-propane sulphonyl) imido grpup; two (n-butane sulphonyl) imido grpup; two (i-butane sulphonyl) imido grpup; two (s-butane sulphonyl) imido grpup; two (t-butane sulphonyl) imido grpup; two (c-butane sulphonyl) imido grpup; two (benzene sulfonyl) imido grpup; two (p-tolylsulfonyl) imido grpup; two (1-naphthalene sulfonyl) imido grpup; two (2-naphthalene sulfonyl) imido grpup; [N; N '-(methane) (benzene)] imido grpup; [N; N '-(trifluoromethane) (benzene)] imido grpup; [N; N '-(ethane) (benzene)] imido grpup; [N; N '-(methane) (p-toluene)] imido grpup; [N; N '-(trifluoromethane) (p-toluene)] imido grpup; [N; N '-(ethane) (p-toluene)] imido grpup; [N; N '-(methane) (1-naphthalene)] imido grpup; [N; N '-(trifluoromethane) (1-naphthalene)] imido grpup; [N; N '-(ethane) (1-naphthalene)] imido grpup; [N; N '-(methane) (2-naphthalene)] imido grpup; [N; N '-(trifluoromethane) (2-naphthalene)] imido grpup; [N; N '-(ethane) (2-naphthalene)] imido grpup; hydrogen atom more preferably; nitro; fluorine atom; the chlorine atom; methoxyl group; the methyl carbonylamino; methyl carbonyl (N-ethyl) amino; two (trifluoromethane sulphonyl) imido grpup; [N; N '-(trifluoromethane) (benzene)] imido grpup; [N, N '-(trifluoromethane) (p-toluene)] imido grpup.
R in the formula (10)
7Preferred hydrogen atom, cyano group, nitro, the methylsulfonyl amido, the fluoroform sulfoamido, the ethane sulphonamide base, n-propane sulfoamido, i-propane sulfoamido, c-propane sulfoamido, n-butane sulfoamido, i-butane sulfoamido, s-butane sulfoamido, t-butane sulfoamido, c-butane sulfoamido, two (sulfonyl methane) imido grpup, two (trifluoromethane sulphonyl) imido grpup, two (ethane sulphonyl) imido grpup, two (n-propane sulphonyl) imido grpup, two (i-propane sulphonyl) imido grpup, two (c-propane sulphonyl) imido grpup, two (n-butane sulphonyl) imido grpup, two (i-butane sulphonyl) imido grpup, two (s-butane sulphonyl) imido grpup, two (t-butane sulphonyl) imido grpup, two (c-butane sulphonyl) imido grpup, two (benzene sulfonyl) imido grpup, two (p-tolylsulfonyl) imido grpup, two (1-naphthalene sulfonyl) imido grpup, two (2-naphthalene sulfonyl) imido grpup, [N, N '-(methane) (benzene)] imido grpup, [N, N '-(trifluoromethane) (benzene)] imido grpup, [N, N '-(trifluoromethane) (p-fluorobenzene)] imido grpup, [N, N '-(ethane) (benzene)] imido grpup, [N, N '-(methane) (p-toluene)] imido grpup, [N, N '-(trifluoromethane) (p-toluene)] imido grpup, [N, N '-(ethane) (p-toluene)] imido grpup, [N, N '-(methane) (1-naphthalene)] imido grpup, [N, N '-(trifluoromethane) (1-naphthalene)] imido grpup, [N, N '-(ethane) (1-naphthalene)] imido grpup, [N, N '-(methane) (2-naphthalene)] imido grpup, [N, N '-(trifluoromethane) (2-naphthalene)] imido grpup, [N, N '-(ethane) (2-naphthalene)] imido grpup, more preferably hydrogen atom, nitro, two (sulfonyl methane) imido grpup, two (trifluoromethane sulphonyl) imido grpup, [N, N '-(trifluoromethane) (benzene)] imido grpup, [N, N '-(trifluoromethane) (p-toluene)] imido grpup.
R in the formula (10)
8Preferred hydrogen atom, fluorine atom, chlorine atom, cyano group, nitro, methyl, trifluoromethyl, ethyl, n-propyl group, i-propyl group, c-propyl group, n-butyl, i-butyl, s-butyl, the tertiary butyl, c-butyl, more preferably hydrogen atom, fluorine atom, nitro, methyl, trifluoromethyl.
R in the formula (10)
9And R
10Represent hydrogen atom, C respectively independently
1-6(this alkyl can be by halogen atom, C for alkyl
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom) or hydroxyl replace arbitrarily) or C
6-14(this aryl can be by halogen atom, hydroxyl, nitro, cyano group, C for aryl
1-6(this alkyl can be by halogen atom, C for alkyl
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom) or hydroxyl replace arbitrarily) or C
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom) replaces arbitrarily).
To the R in the formula (10)
9And R
10Each substituting group be specifically described.As this C
1-6Alkyl, can list methyl, trifluoromethyl, ethyl, n-propyl group, i-propyl group, n-butyl, i-butyl, s-butyl, the tertiary butyl, 1-amyl group, 2-amyl group, 3-amyl group, i-amyl group, neo-pentyl, 2,2-dimethyl propyl, 1-hexyl, 2-hexyl, 3-hexyl, 1-methyl-n-amyl group, 1,1,2-trimethylammonium-n-propyl group, 1,2,2-trimethylammonium-n-propyl group and 3,3-dimethyl-n-butyl etc. are as this C
6-14Aryl can list phenyl, o-xenyl, m-xenyl, p-xenyl, 1-naphthyl, 2-naphthyl, 1-anthryl, 2-anthryl, 9-anthryl, 1-phenanthryl, 2-phenanthryl, 3-phenanthryl, 4-phenanthryl and 9-phenanthryl etc.
As the R in the formula (10)
9And R
10, be preferably hydrogen atom, methyl, trifluoromethyl, ethyl, phenyl, more preferably methyl.
Each substituting group in formula (11) and the formula (12) is described.
R in formula (11) and the formula (12)
9And R
10Represent hydrogen atom, C respectively independently
1-6(this alkyl can be by halogen atom, C for alkyl
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom) or hydroxyl replace arbitrarily) or C
6-14(this aryl can be by halogen atom, hydroxyl, nitro, cyano group, C for aryl
1-6(this alkyl can be by halogen atom, C for alkyl
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom) or hydroxyl replace arbitrarily) or C
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom) replaces arbitrarily).
To the R in formula (11) and the formula (12)
9And R
10Each substituting group be specifically described.
As this C
1-6Alkyl, can list methyl, trifluoromethyl, ethyl, n-propyl group, i-propyl group, n-butyl, i-butyl, s-butyl, the tertiary butyl, 1-amyl group, 2-amyl group, 3-amyl group, i-amyl group, neo-pentyl, 2,2-dimethyl propyl, 1-hexyl, 2-hexyl, 3-hexyl, 1-methyl-n-amyl group, 1,1,2-trimethylammonium-n-propyl group, 1,2,2-trimethylammonium-n-propyl group and 3,3-dimethyl-n-butyl etc.
As this C
6-14Aryl can list phenyl, o-xenyl, m-xenyl, p-xenyl, 1-naphthyl, 2-naphthyl, 1-anthryl, 2-anthryl, 9-anthryl, 1-phenanthryl, 2-phenanthryl, 3-phenanthryl, 4-phenanthryl and 9-phenanthryl etc.
R in formula (11) and the formula (12)
9And R
10Be preferably hydrogen atom, methyl, trifluoromethyl, ethyl, phenyl, more preferably methyl.
Part ring structure A in formula (11) and the formula (12) is described.Part ring structure A represents partly to form the part-structure shown in 5,6 or 7 Yuans rings of condensed ring with phenyl ring, and (wherein, these 5,6 or 7 Yuans rings can be by h R
11Replace (wherein, R arbitrarily
11Be halogen atom, hydroxyl, C
1-6(this alkyl can be by halogen atom, hydroxyl, cyano group, amino, nitro, C for alkyl
1-4Alkoxyl group, C
1-4Alkyl-carbonyl oxygen base, C
1-4Alkyl-carbonyl-amino, C
1-4Any replacement of alkoxy carbonyl (this alkoxyl group, alkyl-carbonyl oxygen base, alkyl-carbonyl-amino and alkoxy carbonyl can be replaced arbitrarily by halogen atom)), C
1-6(this alkoxyl group can be by halogen atom, hydroxyl, cyano group, amino, nitro, C for alkoxyl group
1-4Alkoxyl group, C
1-4Alkyl-carbonyl oxygen base, C
1-4Alkyl-carbonyl-amino, C
1-4Any replacement of alkoxy carbonyl (this alkoxyl group, alkyl-carbonyl oxygen base, alkyl-carbonyl-amino and alkoxy carbonyl can be replaced arbitrarily by halogen atom)), nitro, cyano group, formyl radical, formamido-, formamyl, sulfo group, sulfoamino-, sulfamyl, alkylsulfonyl, amino, carboxyl, C
1-6Alkylamino, two C
1-6Alkylamino, C
1-6Alkyl-carbonyl-amino, C
1-6Alkylsulfonamido, C
6-14Aryl-sulfonyl amino, C
1-6Alkyl amino-carbonyl, two C
1-6Alkyl amino-carbonyl, C
1-6Alkyl-carbonyl, C
1-6Alkoxy carbonyl, C
1-6Alkyl sulphonyl, C
6-14Aryl sulfonyl or C
6-14Aryl carbonyl (this alkylamino, dialkyl amido, alkyl-carbonyl-amino, alkylsulfonamido, aryl-sulfonyl amino, alkyl amino-carbonyl, dialkyl amino carbonyl, alkyl-carbonyl, alkoxy carbonyl, alkyl sulphonyl, aryl sulfonyl and aryl carbonyl can be replaced arbitrarily by halogen atom); h is 1～6 integer; be under 2～6 the situation at h, R
11Can be the same or different), the constituting atom as ring can contain 1～3 Sauerstoffatom, nitrogen-atoms or sulphur atom alone or in combination, the number of intra-annular unsaturated link(age), the unsaturated link(age) that comprises the phenyl ring of condensation is 1,2 or 3, and the carbon atom that constitutes ring can be carbonyl or thiocarbonyl).
To above-mentioned R
11Be specifically described.
As this halogen atom, can list fluorine atom, chlorine atom, bromine atoms and iodine atom,
As this C
1-6Alkyl, can list methyl, trifluoromethyl, ethyl, the n-propyl group, the i-propyl group, the n-butyl, the i-butyl, the s-butyl, the tertiary butyl, the 1-amyl group, the 2-amyl group, the 3-amyl group, the i-amyl group, neo-pentyl, 2, the 2-dimethyl propyl, the 1-hexyl, the 2-hexyl, the 3-hexyl, 1-methyl-n-amyl group, 1,1,2-trimethylammonium-n-propyl group, 1,2,2-trimethylammonium-n-propyl group, 3,3-dimethyl-n-butyl, methyl ketonic oxygen ylmethyl, ethyl ketonic oxygen ylmethyl, methyl ketonic oxygen base ethyl, ethyl ketonic oxygen base ethyl, methyl carbonylamino methyl, trifluoromethyl carbonylamino methyl, ethyl carbonylamino methyl, methyl carbonylamino ethyl, ethyl carbonylamino ethyl, the methoxycarbonyl methyl, trifluoromethoxy carbonyl methyl, the ethoxy carbonyl methyl, methoxycarbonyl ethyl and ethoxy carbonyl ethyl etc.
As this C
1-6Alkoxyl group, can list methoxyl group, trifluoromethoxy, oxyethyl group, the n-propoxy-, the i-propoxy-, the n-butoxy, the i-butoxy, the s-butoxy, the t-butoxy, 1-amyl group oxygen base, 2-amyl group oxygen base, 3-amyl group oxygen base, i-amyl group oxygen base, neo-pentyl oxygen base, 2,2-dimethyl propoxy-, 1-hexyl oxygen base, 2-hexyl oxygen base, 3-hexyl oxygen base, 1-methyl-n-amyl group oxygen base, 1,1,2-trimethylammonium-n-propoxy-, 1,2,2-trimethylammonium-n-propoxy-, 3,3-dimethyl-n-butoxy, methyl ketonic oxygen ylmethoxy, ethyl ketonic oxygen ylmethoxy, methyl ketonic oxygen base oxethyl, ethyl ketonic oxygen base oxethyl, methyl carbonylamino methoxyl group, trifluoromethyl carbonylamino methoxyl group, ethyl carbonylamino methoxyl group, methyl carbonylamino oxyethyl group, ethyl carbonylamino oxyethyl group, the methoxycarbonyl methoxyl group, trifluoromethoxy carbonyl methoxyl group, ethoxycarbonyl methoxy, methoxycarbonyl oxyethyl group and ethoxy carbonyl oxyethyl group etc.
As this C
1-6Alkylamino, can list methylamino, trifluoromethyl amino, ethylamino, n-propyl group amino, i-propyl group amino, c-propyl group amino, n-butyl amino, i-butyl amino, s-butyl amino, tertiary butyl amino, c-butyl amino, 1-amyl group amino, 2-amyl group amino, 3-amyl group amino, i-amyl group amino, neo-pentyl amino, t-amyl group amino, c-amyl group amino, 1-hexyl amino, 2-hexyl amino, 3-hexyl amino, c-hexyl amino, 1-methyl-n-amyl group amino, 1,1,2-trimethylammonium-n-propyl group amino, 1,2,2-trimethylammonium-n-propyl group amino and 3,3-dimethyl-n-butyl amino etc.
As this two C
1-6Alkylamino, can list dimethylamino, two-(trifluoromethyl) amino, diethylamino, two-n-propyl group amino, two-i-propyl group amino, two-c-propyl group amino, two-n-butyl amino, two-i-butyl amino, two-s-butyl amino, two-tertiary butyl amino, two-c-butyl amino, two-1-amyl group amino, two-2-amyl group amino, two-3-amyl group amino, two-i-amyl group amino, two-neo-pentyl amino, two-t-amyl group amino, two-c-amyl group amino, two-1-hexyl amino, two-2-hexyl amino, two-3-hexyl amino, two-c-hexyl amino, two-(1-methyl-n-amyl group) amino, two-(1,1,2-trimethylammonium-n-propyl group) amino, two-(1,2,2-trimethylammonium-n-propyl group) amino, two-(3,3-dimethyl-n-butyl) amino, methyl (ethyl) amino, methyl (n-propyl group) amino, methyl (i-propyl group) amino, methyl (c-propyl group) amino, methyl (n-butyl) amino, methyl (i-butyl) amino, methyl (s-butyl) amino, methyl (tertiary butyl) amino, methyl (c-butyl) amino, ethyl (n-propyl group) amino, ethyl (i-propyl group) amino, ethyl (c-propyl group) amino, ethyl (n-butyl) amino, ethyl (i-butyl) amino, ethyl (s-butyl) amino, ethyl (tertiary butyl) amino, ethyl (c-butyl) amino, n-propyl group (i-propyl group) amino, n-propyl group (c-propyl group) amino, n-propyl group (n-butyl) amino, n-propyl group (i-butyl) amino, n-propyl group (s-butyl) amino, n-propyl group (t-butyl) amino, n-propyl group (c-butyl) amino, i-propyl group (c-propyl group) amino, i-propyl group (n-butyl) amino, i-propyl group (i-butyl) amino, i-propyl group (s-butyl) amino, i-propyl group (t-butyl) amino, i-propyl group (c-butyl) amino, c-propyl group (n-butyl) amino, c-propyl group (i-butyl) amino, c-propyl group (s-butyl) amino, c-propyl group (tertiary butyl) amino, c-propyl group (c-butyl) amino, n-butyl (i-butyl) amino, n-butyl (s-butyl) amino, n-butyl (t-butyl) amino, n-butyl (c-butyl) amino, i-butyl (s-butyl) amino, i-butyl (t-butyl) amino, i-butyl (c-butyl) amino, s-butyl (t-butyl) amino, s-butyl (c-butyl) amino and the tertiary butyl (c-butyl) amino etc.
As this C
1-6Alkyl-carbonyl-amino, can list the methyl carbonylamino, the trifluoromethyl carbonylamino, the ethyl carbonylamino, n-propyl group carbonylamino, i-propyl group carbonylamino, n-butyl carbonylamino, i-butyl carbonylamino, s-butyl carbonylamino, tertiary butyl carbonylamino, 1-amyl group carbonylamino, 2-amyl group carbonylamino, 3-amyl group carbonylamino, i-amyl group carbonylamino, the neo-pentyl carbonylamino, t-amyl group carbonylamino, 1-hexyl carbonylamino, 2-hexyl carbonylamino and 3-hexyl carbonylamino etc.
As this C
1-6Alkylsulfonamido, can list the methylsulfonyl amido, the fluoroform sulfoamido, the ethane sulphonamide base, n-propane sulfoamido, i-propane sulfoamido, n-butane sulfoamido, i-butane sulfoamido, s-butane sulfoamido, t-butane sulfoamido, 1-pentane sulfoamido, 2-pentane sulfoamido, 3-pentane sulfoamido, i-pentane sulfoamido, the neopentane sulfoamido, t-pentane sulfoamido, 1-hexane sulfoamido, 2-hexane sulfoamido and 3-hexane sulfoamido etc.
As this C
6-14Aryl-sulfonyl amino, can list benzene sulfonamido, p-tolylsulfonyl amido, o-biphenyl sulfonamide base, m-biphenyl sulfonamide base, p-biphenyl sulfonamide base, 1-naphthalene sulfonyl amido, 2-naphthalene sulfonyl amido, 1-anthracene sulfoamido, 2-anthracene sulfoamido, 9-anthracene sulfoamido, the luxuriant and rich with fragrance sulfoamido of 1-, the luxuriant and rich with fragrance sulfoamido of 2-, the luxuriant and rich with fragrance sulfoamido of 3-, the luxuriant and rich with fragrance sulfoamido of 4-and the luxuriant and rich with fragrance sulfoamido of 9-etc.
As this C
1-6Alkyl amino-carbonyl, can list the methylamino carbonyl, the trifluoromethyl aminocarboxyl, the ethylamino carbonyl, n-propyl group aminocarboxyl, i-propyl group aminocarboxyl, n-butyl aminocarboxyl, i-butyl aminocarboxyl, s-butyl aminocarboxyl, tertiary butyl aminocarboxyl, 1-amyl group aminocarboxyl, 2-amyl group aminocarboxyl, 3-amyl group aminocarboxyl, i-amyl group aminocarboxyl, the neo-pentyl aminocarboxyl, t-amyl group aminocarboxyl, 1-hexyl aminocarboxyl, 2-hexyl aminocarboxyl and 3-hexyl aminocarboxyl etc.
As this two C
1-6Alkyl amino-carbonyl, can list the dimethylamino carbonyl, two (trifluoromethyl) aminocarboxyl, the diethylamino carbonyl, two-n-propyl group aminocarboxyl, two-i-propyl group aminocarboxyl, two-c-propyl group aminocarboxyl, two-n-butyl aminocarboxyl, two-i-butyl aminocarboxyl, two-s-butyl aminocarboxyl, two-tertiary butyl aminocarboxyl, two-c-butyl aminocarboxyl, two-1-amyl group aminocarboxyl, two-2-amyl group aminocarboxyl, two-3-amyl group aminocarboxyl, two-i-amyl group aminocarboxyl, two-neo-pentyl aminocarboxyl, two-t-amyl group aminocarboxyl, two-c-amyl group aminocarboxyl, two-1-hexyl aminocarboxyl, two-2-hexyl aminocarboxyl, two-3-hexyl aminocarboxyl, two-c-hexyl aminocarboxyl, two-(1-methyl-n-amyl group) aminocarboxyls, two-(1,1,2-trimethylammonium-n-propyl group) aminocarboxyl, two-(1,2,2-trimethylammonium-n-propyl group) aminocarboxyl, two-(3,3-dimethyl-n-butyl) aminocarboxyl, methyl (ethyl) aminocarboxyl, trifluoromethyl (ethyl) aminocarboxyl, methyl (n-propyl group) aminocarboxyl, methyl (i-propyl group) aminocarboxyl, methyl (c-propyl group) aminocarboxyl, methyl (n-butyl) aminocarboxyl, methyl (i-butyl) aminocarboxyl, methyl (s-butyl) aminocarboxyl, methyl (t-butyl) aminocarboxyl, methyl (c-butyl) aminocarboxyl, ethyl (n-propyl group) aminocarboxyl, ethyl (i-propyl group) aminocarboxyl, ethyl (c-propyl group) aminocarboxyl, ethyl (n-butyl) aminocarboxyl, ethyl (i-butyl) aminocarboxyl, ethyl (s-butyl) aminocarboxyl, ethyl (t-butyl) aminocarboxyl, ethyl (c-butyl) aminocarboxyl, n-propyl group (i-propyl group) aminocarboxyl, n-propyl group (c-propyl group) aminocarboxyl, n-propyl group (n-butyl) aminocarboxyl, n-propyl group (i-butyl) aminocarboxyl, n-propyl group (s-butyl) aminocarboxyl, n-propyl group (t-butyl) aminocarboxyl, n-propyl group (c-butyl) aminocarboxyl, i-propyl group (c-propyl group) aminocarboxyl, i-propyl group (n-butyl) aminocarboxyl, i-propyl group (i-butyl) aminocarboxyl, i-propyl group (s-butyl) aminocarboxyl, i-propyl group (t-butyl) aminocarboxyl, i-propyl group (c-butyl) aminocarboxyl, c-propyl group (n-butyl) aminocarboxyl, c-propyl group (i-butyl) aminocarboxyl, c-propyl group (s-butyl) aminocarboxyl, c-propyl group (t-butyl) aminocarboxyl, c-propyl group (c-butyl) aminocarboxyl, n-butyl (i-butyl) aminocarboxyl, n-butyl (s-butyl) aminocarboxyl, n-butyl (t-butyl) aminocarboxyl, n-butyl (c-butyl) aminocarboxyl, i-butyl (s-butyl) aminocarboxyl, i-butyl (t-butyl) aminocarboxyl, i-butyl (c-butyl) aminocarboxyl, s-butyl (t-butyl) aminocarboxyl, s-butyl (c-butyl) aminocarboxyl and the tertiary butyl (c-butyl) aminocarboxyl etc.
As this C
1-6Alkyl-carbonyl, can list methyl carbonyl, trifluoromethyl carbonyl, ethyl carbonyl, n-propyl group carbonyl, i-propyl group carbonyl, n-butyl carbonyl, i-butyl carbonyl, s-butyl carbonyl, tertiary butyl carbonyl, 1-amyl group carbonyl, 2-amyl group carbonyl, 3-amyl group carbonyl, i-amyl group carbonyl, neo-pentyl carbonyl, t-amyl group carbonyl, 1-hexyl carbonyl, 2-hexyl carbonyl and 3-hexyl carbonyl etc.
As this C
1-6Alkoxy carbonyl, can list methoxycarbonyl, trifluoromethoxy carbonyl, ethoxy carbonyl, n-propoxycarbonyl, i-propoxycarbonyl, n-butoxy carbonyl, i-butoxy carbonyl, s-butoxy carbonyl, t-butoxy carbonyl, 1-amyl group oxygen base carbonyl, 2-amyl group oxygen base carbonyl, 3-amyl group oxygen base carbonyl, i-amyl group oxygen base carbonyl, neo-pentyl oxygen base carbonyl, t-amyl group oxygen base carbonyl, 1-hexyl oxygen base carbonyl, 2-hexyl oxygen base carbonyl and 3-hexyl oxygen base carbonyl etc.
As this C
1-6Alkyl sulphonyl can list methane sulfonyl, trifluoromethane sulfonyl group, ethane alkylsulfonyl, n-propane alkylsulfonyl and n-butane alkylsulfonyl etc.,
As this C
6-14Aryl sulfonyl; can list benzenesulfonyl, p-fluorobenzene alkylsulfonyl, p-tosyl group, o-biphenyl sulfonyl, m-biphenyl sulfonyl, p-biphenyl sulfonyl, 1-naphthalene sulfonyl base, 2-naphthalene sulfonyl base, 1-anthracene alkylsulfonyl, 2-anthracene alkylsulfonyl, 9-anthracene alkylsulfonyl, the luxuriant and rich with fragrance alkylsulfonyl of 1-, the luxuriant and rich with fragrance alkylsulfonyl of 2-, the luxuriant and rich with fragrance alkylsulfonyl of 3-, the luxuriant and rich with fragrance alkylsulfonyl of 4-and the luxuriant and rich with fragrance alkylsulfonyl of 9-etc.
As this C6-14 aryl carbonyl, can list phenylcarbonyl group, p-fluorophenyl carbonyl, o-xenyl carbonyl, m-xenyl carbonyl, p-xenyl carbonyl, 1-naphthyl carbonyl, 2-naphthyl carbonyl, 1-anthryl carbonyl, 2-anthryl carbonyl, 9-anthryl carbonyl, 1-phenanthryl carbonyl, 2-phenanthryl carbonyl, 3-phenanthryl carbonyl, 4-phenanthryl carbonyl and 9-phenanthryl carbonyl etc.
About above-mentioned R
11, preferred atom and substituting group are specifically described.
R
11Be preferably fluorine atom; the chlorine atom; bromine atoms; methyl; trifluoromethyl; ethyl; the n-propyl group; the i-propyl group; the n-butyl; the n-amyl group; the i-amyl group; 3; 3-dimethyl-n-butyl; methyl ketonic oxygen ylmethyl; ethyl ketonic oxygen ylmethyl; methyl ketonic oxygen base ethyl; ethyl ketonic oxygen base ethyl; methyl carbonylamino methyl; trifluoromethyl carbonylamino methyl; ethyl carbonylamino methyl; methyl carbonylamino ethyl; ethyl carbonylamino ethyl; the methoxycarbonyl methyl; trifluoromethoxy carbonyl methyl; the ethoxy carbonyl methyl; the methoxycarbonyl ethyl; the ethoxy carbonyl ethyl; methoxyl group; trifluoromethoxy; oxyethyl group; the n-propoxy-; the i-propoxy-; 3,3-dimethyl-n-butoxy; methyl ketonic oxygen ylmethoxy; ethyl ketonic oxygen ylmethoxy; methyl ketonic oxygen base oxethyl; ethyl ketonic oxygen base oxethyl; methyl carbonylamino methoxyl group; trifluoromethyl carbonylamino methoxyl group; ethyl carbonylamino methoxyl group; methyl carbonylamino oxyethyl group; ethyl carbonylamino oxyethyl group; the methoxycarbonyl methoxyl group; trifluoromethoxy carbonyl methoxyl group; ethoxycarbonyl methoxy; the methoxycarbonyl oxyethyl group; the ethoxy carbonyl oxyethyl group; methylamino; trifluoromethyl amino; ethylamino; n-propyl group amino; i-propyl group amino; n-butyl amino; dimethylamino; two-(trifluoromethyl) amino; diethylamino; two-n-propyl group amino; two-i-propyl group amino; two-n-butyl amino; the methyl carbonylamino; the trifluoromethyl carbonylamino; the ethyl carbonylamino; n-propyl group carbonylamino; i-propyl group carbonylamino; n-butyl carbonylamino; the methylsulfonyl amido; the fluoroform sulfoamido; the ethane sulphonamide base; n-propane sulfoamido; i-propane sulfoamido; n-butane sulfoamido; benzene sulfonamido; p-tolylsulfonyl amido; the methylamino carbonyl; the trifluoromethyl aminocarboxyl; the ethylamino carbonyl; n-propyl group aminocarboxyl; i-propyl group aminocarboxyl; n-butyl aminocarboxyl; the dimethylamino carbonyl; two (trifluoromethyl) aminocarboxyl; the diethylamino carbonyl; two-n-propyl group aminocarboxyl; two-i-propyl group aminocarboxyl; two-c-propyl group aminocarboxyl; two-n-butyl aminocarboxyl; methyl (ethyl) aminocarboxyl; trifluoromethyl (ethyl) aminocarboxyl; the methyl carbonyl; the trifluoromethyl carbonyl; the ethyl carbonyl; n-propyl group carbonyl; i-propyl group carbonyl; n-butyl carbonyl; methoxycarbonyl; the trifluoromethoxy carbonyl; ethoxy carbonyl; the n-propoxycarbonyl; the i-propoxycarbonyl; the n-butoxy carbonyl; the i-butoxy carbonyl; the s-butoxy carbonyl; the t-butoxy carbonyl; methane sulfonyl; trifluoromethane sulfonyl group; the ethane alkylsulfonyl; benzenesulfonyl; the o-biphenyl sulfonyl; the m-biphenyl sulfonyl; the p-biphenyl sulfonyl; 1-naphthalene sulfonyl base; 2-naphthalene sulfonyl base; phenylcarbonyl group; o-xenyl carbonyl; m-xenyl carbonyl; p-xenyl carbonyl; the 1-naphthyl carbonyl; the 2-naphthyl carbonyl; hydroxyl; nitro; cyano group; formyl radical; formamido-; formamyl; sulfoamino-; sulfamyl; amino; carboxyl.
To the part ring structure A in above-mentioned formula (11) and the formula (12) by following formula (a), formula (b), formula (c), formula (d), formula (e), formula (f), formula (g), formula (h), formula (i), formula (j), formula (k), formula (l), formula (m), formula (n), formula (o), formula (p), formula (q), formula (r), formula (s), formula (t), formula (u), formula (v), formula (w), formula (x), formula (y), formula (z), formula (aa), formula (ab), formula (ac), formula (ad), formula (ae), formula (af), formula (ag) and formula (ah)
Above-mentioned formula (a) under the situation of expression, formula (b), formula (c), formula (d), formula (e), formula (f), formula (g), formula (h), formula (i), formula (j), formula (k), formula (l), formula (m), formula (n), formula (o), formula (p), formula (q), formula (r), formula (s), formula (t), formula (u), formula (v), formula (w), formula (x), formula (y), formula (z), formula (aa), formula (ab), formula (ac), formula (ad), formula (ae), formula (af), R in formula (ag) and the formula (ah)
12, R
13, R
14, R
15, R
16And R
17Each substituting group describe.
At first, to above-mentioned formula (a), formula (b), formula (e), formula (f), formula (g), formula (h), formula (i), formula (j), formula (k), formula (l), formula (m), formula (n), formula (p), formula (q), formula (v), the R in formula (w), formula (x), formula (ab), formula (ae), formula (af) and the formula (ag)
12And R
13Describe.
Formula (a), formula (b), formula (e), formula (f), formula (g), formula (h), formula (i), formula (j), formula (k), formula (l), formula (m), formula (n), formula (p), formula (q), formula (v), the R in formula (w), formula (x), formula (ab), formula (ae), formula (af) and the formula (ag)
12And R
13Represent hydrogen atom, C respectively independently
1-6(this alkyl can be by halogen atom, C for alkyl
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom), amino, hydroxyl, C
6-14Aryl, C
2-9(this aryl and heteroaryl can be by q R for heteroaryl
18(R
18Expression and R
11Identical implication, q represents 1～3 integer, is under 2 or 3 the situation at q, R
18Can be the same or different) replace arbitrarily), C
1-6Alkyl amino-carbonyl, two C
1-6Alkyl amino-carbonyl, C
1-6Alkyl-carbonyl oxygen base, C
1-6Alkyl-carbonyl (this alkyl-carbonyl oxygen base and alkyl-carbonyl can be replaced arbitrarily by halogen atom), C
1-6Alkyl-carbonyl-amino, C
3-8Naphthene base carbonyl, C
1-6Alkoxy carbonyl, C
1-6Alkyl sulphonyl (this naphthene base carbonyl, alkoxy carbonyl and alkyl sulphonyl can be replaced arbitrarily by halogen atom), carboxyl, C
6-14Aryl carbonyl (this aryl carbonyl can be replaced arbitrarily by halogen atom) or C
2-9The heteroaryl carbonyl replaces arbitrarily), C
6-14Aryl, C
2-9(this aryl and heteroaryl can be by q R for heteroaryl
18(R
18Expression and R
11Identical implication, q represents 1～3 integer, is under 2 or 3 the situation at q, R
18Can be the same or different) replace arbitrarily), C
1-6Alkyl amino-carbonyl, two C
1-6Alkyl amino-carbonyl, C
1-6Alkyl-carbonyl, C
3-8Naphthene base carbonyl, C
1-6Alkoxy carbonyl, C
1-6Alkyl sulphonyl, C
6-14Aryl sulfonyl, C
2-9(this aryl sulfonyl and heteroarylsulfonyl can be by q R for heteroarylsulfonyl
18(R
18Expression and R
11Identical implication, q represents 1～3 integer, is under 2 or 3 the situation at q, R
18Can be the same or different) replace arbitrarily), carboxyl, C
6-14Aryl carbonyl or C
2-9(this aryl carbonyl and heteroaryl carbonyl can be by q R for the heteroaryl carbonyl
18(R
18Expression and R
11Identical implication, q represents 1～3 integer, is under 2 or 3 the situation at q, R
18Can be the same or different) replace arbitrarily).To above-mentioned formula (a), formula (b), formula (e), formula (f), formula (g), formula (h), formula (i), formula (j), formula (k), formula (l), formula (m), formula (n), formula (p), formula (q), formula (v), the R in formula (w), formula (x), formula (ab), formula (ae), formula (af) and the formula (ag)
12And R
13Each substituting group be specifically described.
As this C
1-6Alkyl, can list methyl, trifluoromethyl, ethyl, the n-propyl group, the i-propyl group, the n-butyl, the i-butyl, the s-butyl, the tertiary butyl, the n-amyl group, the 2-amyl group, the 3-amyl group, the i-amyl group, neo-pentyl, 2, the 2-dimethyl propyl, the n-hexyl, the 2-hexyl, the 3-hexyl, 1-methyl-n-amyl group, 1,1,2-trimethylammonium-n-propyl group, 1,2,2-trimethylammonium-n-propyl group, 3,3-dimethyl-n-butyl, methyl ketonic oxygen ylmethyl, ethyl ketonic oxygen ylmethyl, methyl ketonic oxygen base ethyl, ethyl ketonic oxygen base ethyl, methyl carbonylamino methyl, trifluoromethyl carbonylamino methyl, ethyl carbonylamino methyl, methyl carbonylamino ethyl, ethyl carbonylamino ethyl, the methoxycarbonyl methyl, the ethoxy carbonyl methyl, methoxycarbonyl ethyl and ethoxy carbonyl ethyl etc.
As this C
6-14Aryl can list phenyl, o-xenyl, m-xenyl, p-xenyl, 1-naphthyl, 2-naphthyl, 1-anthryl, 2-anthryl, 9-anthryl, 1-phenanthryl, 2-phenanthryl, 3-phenanthryl, 4-phenanthryl and 9-phenanthryl etc.
As this C
2-9Heteroaryl comprises the C of 5～7 Yuans rings that can contain 1～3 Sauerstoffatom, nitrogen-atoms, sulphur atom alone or in combination
2-6Monocyclic type heteroaromatic base and constituting atom number are 8～10 C
5-9Condensation two ring type heterocyclic radicals.
C as these 5～7 Yuans rings
2-6The monocyclic type heteroaromatic base, can list the 2-thienyl, the 3-thienyl, the 2-furyl, the 3-furyl, the 2-pyranyl, the 3-pyranyl, the 4-pyranyl, the 1-pyrryl, the 2-pyrryl, the 3-pyrryl, the 1-imidazolyl, the 2-imidazolyl, the 4-imidazolyl, the 1-pyrazolyl, the 3-pyrazolyl, the 4-pyrazolyl, the 2-thiazolyl, the 4-thiazolyl, the 5-thiazolyl, the 3-isothiazolyl, the 4-isothiazolyl, the 5-isothiazolyl, the 2-oxazolyl, the 4-oxazolyl, the 5-oxazolyl, the 3-isoxazolyl, the 4-isoxazolyl, the 5-isoxazolyl, the 2-pyridyl, the 3-pyridyl, the 4-pyridyl, the 2-pyrazinyl, the 2-pyrimidyl, the 4-pyrimidyl, the 5-pyrimidyl, the 3-pyridazinyl, the 4-pyridazinyl, 2-1,3,4-oxadiazole base, 2-1,3, the 4-thiadiazolyl group, 3-1,2,4-oxadiazole base, 5-1,2,4-oxadiazole base, 3-1,2, the 4-thiadiazolyl group, 5-1,2, the 4-thiadiazolyl group, 3-1,2,5-oxadiazole base and 3-1,2,5-thiadiazolyl groups etc. are this C of 8～10 as the constituting atom number
5-9Condensation two ring type heterocyclic radicals, can list the 2-benzofuryl, the 3-benzofuryl, the 4-benzofuryl, the 5-benzofuryl, the 6-benzofuryl, the 7-benzofuryl, the 1-isobenzofuran-base, the 4-isobenzofuran-base, the 5-isobenzofuran-base, the 2-benzothienyl, the 3-benzothienyl, the 4-benzothienyl, the 5-benzothienyl, the 6-benzothienyl, the 7-benzothienyl, the 1-isobenzo-thienyl, the 4-isobenzo-thienyl, the 5-isobenzo-thienyl, 2-chromenyl (chromenyl), the 3-chromenyl, the 4-chromenyl, the 5-chromenyl, the 6-chromenyl, the 7-chromenyl, the 8-chromenyl, 1-indolizine base (Indolizinyl), 2-indolizine base, 3-indolizine base, 5-indolizine base, 6-indolizine base, 7-indolizine base, 8-indolizine base, the 1-pseudoindoyl, the 2-pseudoindoyl, the 4-pseudoindoyl, the 5-pseudoindoyl, the 1-indyl, the 2-indyl, the 3-indyl, the 4-indyl, the 5-indyl, the 6-indyl, the 7-indyl, the 1-indazolyl, the 2-indazolyl, the 3-indazolyl, the 4-indazolyl, the 5-indazolyl, the 6-indazolyl, the 7-indazolyl, the 1-purine radicals, the 2-purine radicals, the 3-purine radicals, the 6-purine radicals, the 7-purine radicals, the 8-purine radicals, the 2-quinolyl, the 3-quinolyl, the 4-quinolyl, the 5-quinolyl, the 6-quinolyl, the 7-quinolyl, the 8-quinolyl, the 1-isoquinolyl, the 3-isoquinolyl, the 4-isoquinolyl, the 5-isoquinolyl, the 6-isoquinolyl, the 7-isoquinolyl, the 8-isoquinolyl, the 1-phthalazinyl, the 5-phthalazinyl, the 6-phthalazinyl, 1-2, the 7-naphthyridinyl, 3-2, the 7-naphthyridinyl, 4-2, the 7-naphthyridinyl, 1-2, the 6-naphthyridinyl, 3-2, the 6-naphthyridinyl, 4-2, the 6-naphthyridinyl, 2-1, the 8-naphthyridinyl, 3-1, the 8-naphthyridinyl, 4-1, the 8-naphthyridinyl, 2-1, the 7-naphthyridinyl, 3-1, the 7-naphthyridinyl, 4-1, the 7-naphthyridinyl, 5-1, the 7-naphthyridinyl, 6-1, the 7-naphthyridinyl, 8-1, the 7-naphthyridinyl, 2-1, the 6-naphthyridinyl, 3-1, the 6-naphthyridinyl, 4-1, the 6-naphthyridinyl, 5-1, the 6-naphthyridinyl, 7-1, the 6-naphthyridinyl, 8-1, the 6-naphthyridinyl, 2-1, the 5-naphthyridinyl, 3-1, the 5-naphthyridinyl, 4-1, the 5-naphthyridinyl, 6-1, the 5-naphthyridinyl, 7-1, the 5-naphthyridinyl, 8-1, the 5-naphthyridinyl, the 2-quinoxalinyl, the 5-quinoxalinyl, the 6-quinoxalinyl, the 2-quinazolyl, the 4-quinazolyl, the 5-quinazolyl, the 6-quinazolyl, the 7-quinazolyl, the 8-quinazolyl, 3-cinnolines base, 4-cinnolines base, 5-cinnolines base, 6-cinnolines base, 7-cinnolines base, 8-cinnolines base, the 2-pteridine radicals, the 4-pteridine radicals, 6-pteridine radicals and 7-pteridine radicals etc.
As this C
1-6Alkyl amino-carbonyl, can list methylamino carbonyl, ethylamino carbonyl, n-propyl group aminocarboxyl, i-propyl group aminocarboxyl, n-butyl aminocarboxyl, i-butyl aminocarboxyl, s-butyl aminocarboxyl, tertiary butyl aminocarboxyl, 1-amyl group aminocarboxyl, 2-amyl group aminocarboxyl, 3-amyl group aminocarboxyl, i-amyl group aminocarboxyl, neo-pentyl aminocarboxyl, t-amyl group aminocarboxyl, 1-hexyl aminocarboxyl, 2-hexyl aminocarboxyl and 3-hexyl aminocarboxyl etc.
As this two C
1-6Alkyl amino-carbonyl, can list the dimethylamino carbonyl, the diethylamino carbonyl, two-n-propyl group aminocarboxyl, two-i-propyl group aminocarboxyl, two-c-propyl group aminocarboxyl, two-n-butyl aminocarboxyl, two-i-butyl aminocarboxyl, two-s-butyl aminocarboxyl, two-tertiary butyl aminocarboxyl, two-c-butyl aminocarboxyl, two-1-amyl group aminocarboxyl, two-2-amyl group aminocarboxyl, two-3-amyl group aminocarboxyl, two-i-amyl group aminocarboxyl, two-neo-pentyl aminocarboxyl, two-t-amyl group aminocarboxyl, two-c-amyl group aminocarboxyl, two-1-hexyl aminocarboxyl, two-2-hexyl aminocarboxyl, two-3-hexyl aminocarboxyl, two-c-hexyl aminocarboxyl, two-(1-methyl-n-amyl group) aminocarboxyls, two-(1,1,2-trimethylammonium-n-propyl group) aminocarboxyl, two-(1,2,2-trimethylammonium-n-propyl group) aminocarboxyl, two-(3,3-dimethyl-n-butyl) aminocarboxyl, methyl (ethyl) aminocarboxyl, methyl (n-propyl group) aminocarboxyl, methyl (i-propyl group) aminocarboxyl, methyl (c-propyl group) aminocarboxyl, methyl (n-butyl) aminocarboxyl, methyl (i-butyl) aminocarboxyl, methyl (s-butyl) aminocarboxyl, methyl (t-butyl) aminocarboxyl, methyl (c-butyl) aminocarboxyl, ethyl (n-propyl group) aminocarboxyl, ethyl (i-propyl group) aminocarboxyl, ethyl (c-propyl group) aminocarboxyl, ethyl (n-butyl) aminocarboxyl, ethyl (i-butyl) aminocarboxyl, ethyl (s-butyl) aminocarboxyl, ethyl (t-butyl) aminocarboxyl, ethyl (c-butyl) aminocarboxyl, n-propyl group (i-propyl group) aminocarboxyl, n-propyl group (c-propyl group) aminocarboxyl, n-propyl group (n-butyl) aminocarboxyl, n-propyl group (i-butyl) aminocarboxyl, n-propyl group (s-butyl) aminocarboxyl, n-propyl group (t-butyl) aminocarboxyl, n-propyl group (c-butyl) aminocarboxyl, i-propyl group (c-propyl group) aminocarboxyl, i-propyl group (n-butyl) aminocarboxyl, i-propyl group (i-butyl) aminocarboxyl, i-propyl group (s-butyl) aminocarboxyl, i-propyl group (t-butyl) aminocarboxyl, i-propyl group (c-butyl) aminocarboxyl, c-propyl group (n-butyl) aminocarboxyl, c-propyl group (i-butyl) aminocarboxyl, c-propyl group (s-butyl) aminocarboxyl, c-propyl group (t-butyl) aminocarboxyl, c-propyl group (c-butyl) aminocarboxyl, n-butyl (i-butyl) aminocarboxyl, n-butyl (s-butyl) aminocarboxyl, n-butyl (t-butyl) aminocarboxyl, n-butyl (c-butyl) aminocarboxyl, i-butyl (s-butyl) aminocarboxyl, i-butyl (t-butyl) aminocarboxyl, i-butyl (c-butyl) aminocarboxyl, s-butyl (t-butyl) aminocarboxyl, s-butyl (c-butyl) aminocarboxyl and the tertiary butyl (c-butyl) aminocarboxyl etc.
As this C
1-6Alkyl-carbonyl, can list methyl carbonyl, ethyl carbonyl, n-propyl group carbonyl, i-propyl group carbonyl, n-butyl carbonyl, i-butyl carbonyl, s-butyl carbonyl, tertiary butyl carbonyl, 1-amyl group carbonyl, 2-amyl group carbonyl, 3-amyl group carbonyl, i-amyl group carbonyl, neo-pentyl carbonyl, t-amyl group carbonyl, 1-hexyl carbonyl, 2-hexyl carbonyl and 3-hexyl carbonyl
As this C
3-8Naphthene base carbonyl, can list c-propyl group carbonyl, c-butyl carbonyl, 1-methyl-c-propyl group carbonyl, 2-methyl-c-propyl group carbonyl, c-amyl group carbonyl, 1-methyl-c-butyl carbonyl, 2-methyl-c-butyl carbonyl, 3-methyl-c-butyl carbonyl, 1,2-dimethyl-c-propyl group carbonyl, 2,3-dimethyl-c-propyl group carbonyl, 1-ethyl-c-propyl group carbonyl, 2-ethyl-c-propyl group carbonyl, c-hexyl carbonyl, c-heptyl carbonyl, c-octyl group carbonyl, 1-methyl-c-hexyl carbonyl, 2-methyl-c-hexyl carbonyl, 3-methyl-c-hexyl carbonyl, 1,2-dimethyl-c-hexyl carbonyl, 2,3-dimethyl-c-propyl group carbonyl, 1-ethyl-c-propyl group carbonyl, 1-methyl-c-amyl group carbonyl, 2-methyl-c-amyl group carbonyl, 3-methyl-c-amyl group carbonyl, 1-ethyl-c-butyl carbonyl, 2-ethyl-c-butyl carbonyl, 3-ethyl-c-butyl carbonyl, 1,2-dimethyl-c-butyl carbonyl, 1,3-dimethyl-c-butyl carbonyl, 2,2-dimethyl-c-butyl carbonyl, 2,3-dimethyl-c-butyl carbonyl, 2,4-dimethyl-c-butyl carbonyl, 3,3-dimethyl-c-butyl carbonyl, 1-n-propyl group-c-propyl group carbonyl, 2-n-propyl group-c-propyl group carbonyl, 1-i-propyl group-c-propyl group carbonyl, 2-i-propyl group-c-propyl group carbonyl, 1,2,2-trimethylammonium-c-propyl group carbonyl, 1,2,3-trimethylammonium-c-propyl group carbonyl, 2,2,3-trimethylammonium-c-propyl group carbonyl, 1-ethyl-2-methyl-c-propyl group carbonyl, 2-ethyl-1-methyl-c-propyl group carbonyl, 2-ethyl-2-methyl-c-propyl group carbonyl and 2-ethyl-3-methyl-c-propyl group carbonyl etc.
As this C
1-6Alkoxy carbonyl, can list methoxycarbonyl, ethoxy carbonyl, n-propoxycarbonyl, i-propoxycarbonyl, n-butoxy carbonyl, i-butoxy carbonyl, s-butoxy carbonyl, t-butoxy carbonyl, 1-amyl group oxygen base carbonyl, 2-amyl group oxygen base carbonyl, 3-amyl group oxygen base carbonyl, i-amyl group oxygen base carbonyl, neo-pentyl oxygen base carbonyl, t-amyl group oxygen base carbonyl, 1-hexyl oxygen base carbonyl, 2-hexyl oxygen base carbonyl and 3-hexyl oxygen base carbonyl etc.
As this C
1-6Alkyl sulphonyl can list methane sulfonyl, trifluoromethane sulfonyl group and ethane alkylsulfonyl,
As this C
6-14Aryl sulfonyl can list benzenesulfonyl, o-biphenyl sulfonyl, m-biphenyl sulfonyl, p-biphenyl sulfonyl, 1-naphthalene sulfonyl base, 2-naphthalene sulfonyl base, 1-anthracene alkylsulfonyl, 2-anthracene alkylsulfonyl, 9-anthracene alkylsulfonyl, the luxuriant and rich with fragrance alkylsulfonyl of 1-, the luxuriant and rich with fragrance alkylsulfonyl of 2-, the luxuriant and rich with fragrance alkylsulfonyl of 3-, the luxuriant and rich with fragrance alkylsulfonyl of 4-and the luxuriant and rich with fragrance alkylsulfonyl of 9-etc.
As this C
2-9Heteroarylsulfonyl comprises the C of 5～7 Yuans rings that can contain 1～3 Sauerstoffatom, nitrogen-atoms, sulphur atom alone or in combination
2-6Monocyclic type heteroaromatic alkylsulfonyl and constituting atom number are 8～10 C
5-9Condensation two ring type heterocycle alkylsulfonyls.
C as these 5～7 Yuans rings
2-6The monocyclic type heteroaromatic alkylsulfonyl; can list 2-thienyl sulphonyl base; 3-thienyl sulphonyl base; 2-furyl alkylsulfonyl; 3-furyl alkylsulfonyl; 2-pyranyl alkylsulfonyl; 3-pyranyl alkylsulfonyl; 4-pyranyl alkylsulfonyl; 1-pyrryl alkylsulfonyl; 2-pyrryl alkylsulfonyl; 3-pyrryl alkylsulfonyl; 1-imidazolyl alkylsulfonyl; 2-imidazolyl alkylsulfonyl; 4-imidazolyl alkylsulfonyl; 1-pyrazolyl alkylsulfonyl; 3-pyrazolyl alkylsulfonyl; 4-pyrazolyl alkylsulfonyl; 2-thiazolyl alkylsulfonyl; 4-thiazolyl alkylsulfonyl; 5-thiazolyl alkylsulfonyl; 3-isothiazolyl alkylsulfonyl; 4-isothiazolyl alkylsulfonyl; 5-isothiazolyl alkylsulfonyl; 2-oxazolyl alkylsulfonyl; 4-oxazolyl alkylsulfonyl; 5-oxazolyl alkylsulfonyl; 3-isoxazolyl alkylsulfonyl; 4-isoxazolyl alkylsulfonyl; 5-isoxazolyl alkylsulfonyl; the 2-pyridyl sulfonyl; the 3-pyridyl sulfonyl; the 4-pyridyl sulfonyl; 2-pyrazinyl alkylsulfonyl; 2-pyrimidyl alkylsulfonyl; 4-pyrimidyl alkylsulfonyl; 5-pyrimidyl alkylsulfonyl; 3-pyridazinyl alkylsulfonyl; 4-pyridazinyl alkylsulfonyl; 2-1; 3; 4-oxadiazole base alkylsulfonyl; 2-1; 3; 4-thiadiazolyl group alkylsulfonyl; 3-1; 2; 4-oxadiazole base alkylsulfonyl; 5-1; 2; 4-oxadiazole base alkylsulfonyl; 3-1; 2; 4-thiadiazolyl group alkylsulfonyl; 5-1; 2; 4-thiadiazolyl group alkylsulfonyl; 3-1; 2; 5-oxadiazole base alkylsulfonyl and 3-1; 2,5-thiadiazolyl group alkylsulfonyl etc.
As the constituting atom number this C of 8～10
5-9Condensation two ring type heterocycle alkylsulfonyls; can list 2-benzofuryl alkylsulfonyl; 3-benzofuryl alkylsulfonyl; 4-benzofuryl alkylsulfonyl; 5-benzofuryl alkylsulfonyl; 6-benzofuryl alkylsulfonyl; 7-benzofuryl alkylsulfonyl; 1-isobenzofuran-base alkylsulfonyl; 4-isobenzofuran-base alkylsulfonyl; 5-isobenzofuran-base alkylsulfonyl; 2-benzothienyl alkylsulfonyl; 3-benzothienyl alkylsulfonyl; 4-benzothienyl alkylsulfonyl; 5-benzothienyl alkylsulfonyl; 6-benzothienyl alkylsulfonyl; 7-benzothienyl alkylsulfonyl; 1-isobenzo-thienyl alkylsulfonyl; 4-isobenzo-thienyl alkylsulfonyl; 5-isobenzo-thienyl alkylsulfonyl; 2-chromenyl alkylsulfonyl; 3-chromenyl alkylsulfonyl; 4-chromenyl alkylsulfonyl; 5-chromenyl alkylsulfonyl; 6-chromenyl alkylsulfonyl; 7-chromenyl alkylsulfonyl; 8-chromenyl alkylsulfonyl; 1-indolizine base alkylsulfonyl; 2-indolizine base alkylsulfonyl; 3-indolizine base alkylsulfonyl; 5-indolizine base alkylsulfonyl; 6-indolizine base alkylsulfonyl; 7-indolizine base alkylsulfonyl; 8-indolizine base alkylsulfonyl; 1-pseudoindoyl alkylsulfonyl; 2-pseudoindoyl alkylsulfonyl; 4-pseudoindoyl alkylsulfonyl; 5-pseudoindoyl alkylsulfonyl; 1-indyl alkylsulfonyl; 2-indyl alkylsulfonyl; 3-indyl alkylsulfonyl; 4-indyl alkylsulfonyl; 5-indyl alkylsulfonyl; 6-indyl alkylsulfonyl; 7-indyl alkylsulfonyl; 1-indazolyl alkylsulfonyl; 2-indazolyl alkylsulfonyl; 3-indazolyl alkylsulfonyl; 4-indazolyl alkylsulfonyl; 5-indazolyl alkylsulfonyl; 6-indazolyl alkylsulfonyl; 7-indazolyl alkylsulfonyl; 1-purine radicals alkylsulfonyl; 2-purine radicals alkylsulfonyl; 3-purine radicals alkylsulfonyl; 6-purine radicals alkylsulfonyl; 7-purine radicals alkylsulfonyl; 8-purine radicals alkylsulfonyl; 2-quinolyl alkylsulfonyl; 3-quinolyl alkylsulfonyl; 4-quinolyl alkylsulfonyl; 5-quinolyl alkylsulfonyl; 6-quinolyl alkylsulfonyl; 7-quinolyl alkylsulfonyl; 8-quinolyl alkylsulfonyl; 1-isoquinolyl alkylsulfonyl; 3-isoquinolyl alkylsulfonyl; 4-isoquinolyl alkylsulfonyl; 5-isoquinolyl alkylsulfonyl; 6-isoquinolyl alkylsulfonyl; 7-isoquinolyl alkylsulfonyl; 8-isoquinolyl alkylsulfonyl; 1-phthalazinyl alkylsulfonyl; 5-phthalazinyl alkylsulfonyl; 6-phthalazinyl alkylsulfonyl; 1-2; 7-naphthyridinyl alkylsulfonyl; 3-2; 7-naphthyridinyl alkylsulfonyl; 4-2; 7-naphthyridinyl alkylsulfonyl; 1-2; 6-naphthyridinyl alkylsulfonyl; 3-2; 6-naphthyridinyl alkylsulfonyl; 4-2; 6-naphthyridinyl alkylsulfonyl; 2-1; 8-naphthyridinyl alkylsulfonyl; 3-1; 8-naphthyridinyl alkylsulfonyl; 4-1; 8-naphthyridinyl alkylsulfonyl; 2-1; 7-naphthyridinyl alkylsulfonyl; 3-1; 7-naphthyridinyl alkylsulfonyl; 4-1; 7-naphthyridinyl alkylsulfonyl; 5-1; 7-naphthyridinyl alkylsulfonyl; 6-1; 7-naphthyridinyl alkylsulfonyl; 8-1; 7-naphthyridinyl alkylsulfonyl; 2-1; 6-naphthyridinyl alkylsulfonyl; 3-1; 6-naphthyridinyl alkylsulfonyl; 4-1; 6-naphthyridinyl alkylsulfonyl; 5-1; 6-naphthyridinyl alkylsulfonyl; 7-1; 6-naphthyridinyl alkylsulfonyl; 8-1; 6-naphthyridinyl alkylsulfonyl; 2-1; 5-naphthyridinyl alkylsulfonyl; 3-1; 5-naphthyridinyl alkylsulfonyl; 4-1; 5-naphthyridinyl alkylsulfonyl; 6-1; 5-naphthyridinyl alkylsulfonyl; 7-1; 5-naphthyridinyl alkylsulfonyl; 8-1,5-naphthyridinyl alkylsulfonyl; 2-quinoxalinyl alkylsulfonyl; 5-quinoxalinyl alkylsulfonyl; 6-quinoxalinyl alkylsulfonyl; 2-quinazolyl alkylsulfonyl; 4-quinazolyl alkylsulfonyl; 5-quinazolyl alkylsulfonyl; 6-quinazolyl alkylsulfonyl; 7-quinazolyl alkylsulfonyl; 8-quinazolyl alkylsulfonyl; 3-cinnolines base alkylsulfonyl; 4-cinnolines base alkylsulfonyl; 5-cinnolines base alkylsulfonyl; 6-cinnolines base alkylsulfonyl; 7-cinnolines base alkylsulfonyl; 8-cinnolines base alkylsulfonyl; 2-pteridine radicals alkylsulfonyl; 4-pteridine radicals alkylsulfonyl; 6-pteridine radicals alkylsulfonyl and 7-pteridine radicals alkylsulfonyl etc.
As this C
6-14Aryl carbonyl can list phenylcarbonyl group, o-xenyl carbonyl, m-xenyl carbonyl, p-xenyl carbonyl, 1-naphthyl carbonyl, 2-naphthyl carbonyl, 1-anthryl carbonyl, 2-anthryl carbonyl, 9-anthryl carbonyl, 1-phenanthryl carbonyl, 2-phenanthryl carbonyl, 3-phenanthryl carbonyl, 4-phenanthryl carbonyl and 9-phenanthryl carbonyl etc.
As this C
2-9The heteroaryl carbonyl comprises the C of 5～7 Yuans rings that can contain 1～3 Sauerstoffatom, nitrogen-atoms, sulphur atom alone or in combination
2-6Monocyclic type heteroaromatic carbonyl and constituting atom number are 8～10 C
5-9Condensation two ring type heterocycle carbonyls.
C as these 5～7 Yuans rings
2-6The monocyclic type heteroaromatic carbonyl, can list the 2-thienyl carbonyl, the 3-thienyl carbonyl, the 2-furyl carbonyl, the 3-furyl carbonyl, 2-pyranyl carbonyl, 3-pyranyl carbonyl, 4-pyranyl carbonyl, 1-pyrryl carbonyl, 2-pyrryl carbonyl, 3-pyrryl carbonyl, 1-imidazolyl carbonyl, 2-imidazolyl carbonyl, 4-imidazolyl carbonyl, 1-pyrazolyl carbonyl, 3-pyrazolyl carbonyl, 4-pyrazolyl carbonyl, 2-thiazolyl carbonyl, 4-thiazolyl carbonyl, 5-thiazolyl carbonyl, 3-isothiazolyl carbonyl, 4-isothiazolyl carbonyl, 5-isothiazolyl carbonyl, 2-oxazolyl carbonyl, 4-oxazolyl carbonyl, 5-oxazolyl carbonyl, 3-isoxazolyl carbonyl, 4-isoxazolyl carbonyl, 5-isoxazolyl carbonyl, 2-pyridyl carbonyl, 3-pyridyl carbonyl, 4-pyridyl carbonyl, 2-pyrazinyl carbonyl, 2-pyrimidyl carbonyl, 4-pyrimidyl carbonyl, 5-pyrimidyl carbonyl, 3-pyridazinyl carbonyl, 4-pyridazinyl carbonyl, 2-1,3,4-oxadiazole base carbonyl, 2-1,3,4-thiadiazolyl group carbonyl, 3-1,2,4-oxadiazole base carbonyl, 5-1,2,4-oxadiazole base carbonyl, 3-1,2,4-thiadiazolyl group carbonyl, 5-1,2,4-thiadiazolyl group carbonyl, 3-1,2,5-oxadiazole base carbonyl and 3-1,2,5-thiadiazolyl group carbonyl etc.
As the constituting atom number this C of 8～10
5-9Condensation two ring type heterocycle carbonyls, can list 2-benzofuryl carbonyl, 3-benzofuryl carbonyl, 4-benzofuryl carbonyl, 5-benzofuryl carbonyl, 6-benzofuryl carbonyl, 7-benzofuryl carbonyl, 1-isobenzofuran-base carbonyl, 4-isobenzofuran-base carbonyl, 5-isobenzofuran-base carbonyl, 2-benzothienyl carbonyl, 3-benzothienyl carbonyl, 4-benzothienyl carbonyl, 5-benzothienyl carbonyl, 6-benzothienyl carbonyl, 7-benzothienyl carbonyl, 1-isobenzo-thienyl carbonyl, 4-isobenzo-thienyl carbonyl, 5-isobenzo-thienyl carbonyl, 2-chromenyl carbonyl, 3-chromenyl carbonyl, 4-chromenyl carbonyl, 5-chromenyl carbonyl, 6-chromenyl carbonyl, 7-chromenyl carbonyl, 8-chromenyl carbonyl, 1-indolizine base carbonyl, 2-indolizine base carbonyl, 3-indolizine base carbonyl, 5-indolizine base carbonyl, 6-indolizine base carbonyl, 7-indolizine base carbonyl, 8-indolizine base carbonyl, 1-pseudoindoyl carbonyl, 2-pseudoindoyl carbonyl, 4-pseudoindoyl carbonyl, 5-pseudoindoyl carbonyl, the 1-indole carbonyl, the 2-indole carbonyl, the 3-indole carbonyl, the 4-indole carbonyl, the 5-indole carbonyl, the 6-indole carbonyl, the 7-indole carbonyl, 1-indazolyl carbonyl, 2-indazolyl carbonyl, 3-indazolyl carbonyl, 4-indazolyl carbonyl, 5-indazolyl carbonyl, 6-indazolyl carbonyl, 7-indazolyl carbonyl, 1-purine radicals carbonyl, 2-purine radicals carbonyl, 3-purine radicals carbonyl, 6-purine radicals carbonyl, 7-purine radicals carbonyl, 8-purine radicals carbonyl, the 2-quinolyl carbonyl, the 3-quinolyl carbonyl, the 4-quinolyl carbonyl, the 5-quinolyl carbonyl, the 6-quinolyl carbonyl, the 7-quinolyl carbonyl, the 8-quinolyl carbonyl, 1-isoquinolyl carbonyl, 3-isoquinolyl carbonyl, 4-isoquinolyl carbonyl, 5-isoquinolyl carbonyl, 6-isoquinolyl carbonyl, 7-isoquinolyl carbonyl, 8-isoquinolyl carbonyl, 1-phthalazinyl carbonyl, 5-phthalazinyl carbonyl, 6-phthalazinyl carbonyl, 1-2,7-naphthyridinyl carbonyl, 3-2,7-naphthyridinyl carbonyl, 4-2,7-naphthyridinyl carbonyl, 1-2,6-naphthyridinyl carbonyl, 3-2,6-naphthyridinyl carbonyl, 4-2,6-naphthyridinyl carbonyl, 2-1,8-naphthyridinyl carbonyl, 3-1,8-naphthyridinyl carbonyl, 4-1,8-naphthyridinyl carbonyl, 2-1,7-naphthyridinyl carbonyl, 3-1,7-naphthyridinyl carbonyl, 4-1,7-naphthyridinyl carbonyl, 5-1,7-naphthyridinyl carbonyl, 6-1,7-naphthyridinyl carbonyl, 8-1,7-naphthyridinyl carbonyl, 2-1,6-naphthyridinyl carbonyl, 3-1,6-naphthyridinyl carbonyl, 4-1,6-naphthyridinyl carbonyl, 5-1,6-naphthyridinyl carbonyl, 7-1,6-naphthyridinyl carbonyl, 8-1,6-naphthyridinyl carbonyl, 2-1,5-naphthyridinyl carbonyl, 3-1,5-naphthyridinyl carbonyl, 4-1,5-naphthyridinyl carbonyl, 6-1,5-naphthyridinyl carbonyl, 7-1,5-naphthyridinyl carbonyl, 8-1,5-naphthyridinyl carbonyl, 2-quinoxalinyl carbonyl, 5-quinoxalinyl carbonyl, 6-quinoxalinyl carbonyl, 2-quinazolyl carbonyl, 4-quinazolyl carbonyl, 5-quinazolyl carbonyl, 6-quinazolyl carbonyl, 7-quinazolyl carbonyl, 8-quinazolyl carbonyl, 3-cinnolines base carbonyl, 4-cinnolines base carbonyl, 5-cinnolines base carbonyl, 6-cinnolines base carbonyl, 7-cinnolines base carbonyl, 8-cinnolines base carbonyl, 2-pteridine radicals carbonyl, 4-pteridine radicals carbonyl, 6-pteridine radicals carbonyl and 7-pteridine radicals carbonyl etc.
Formula (a), formula (b), formula (e), formula (f), formula (g), formula (h), formula (i), formula (j), formula (k), formula (l), formula (m), formula (n), formula (p), formula (q), formula (v), the R in formula (w), formula (x), formula (ab), formula (ae), formula (af) and the formula (ag)
12And R
13, be preferably hydrogen atom; methyl; ethyl; the n-propyl group; the i-propyl group; the n-butyl; the n-amyl group; the i-amyl group; methyl ketonic oxygen ylmethyl; ethyl ketonic oxygen ylmethyl; methyl ketonic oxygen base ethyl; ethyl ketonic oxygen base ethyl; methyl carbonylamino methyl; ethyl carbonylamino ethyl; methyl carbonylamino ethyl; ethyl carbonylamino ethyl; the methoxycarbonyl methyl; the ethoxy carbonyl methyl; the methoxycarbonyl ethyl; the ethoxy carbonyl ethyl; phenyl; the o-xenyl; the m-xenyl; the p-xenyl; the 1-naphthyl; the 2-naphthyl; the 2-pyridyl; the 3-pyridyl; the 4-pyridyl; the methylamino carbonyl; the ethylamino carbonyl; n-propyl group aminocarboxyl; i-propyl group aminocarboxyl; n-butyl aminocarboxyl; the dimethylamino carbonyl; the diethylamino carbonyl; two-n-propyl group aminocarboxyl; two-i-propyl group aminocarboxyl; two-c-propyl group aminocarboxyl; two-n-butyl aminocarboxyl; the methyl carbonyl; the ethyl carbonyl; n-propyl group carbonyl; i-propyl group carbonyl; n-butyl carbonyl; c-amyl group carbonyl; c-hexyl carbonyl; methoxycarbonyl; ethoxy carbonyl; the n-propoxycarbonyl; the i-propoxycarbonyl; the n-butoxy carbonyl; the i-butoxy carbonyl; the s-butoxy carbonyl; the t-butoxy carbonyl; methane sulfonyl; trifluoromethane sulfonyl group; benzenesulfonyl; the o-biphenyl sulfonyl; the m-biphenyl sulfonyl; the p-biphenyl sulfonyl; 1-naphthalene sulfonyl base; 2-naphthalene sulfonyl base; the 2-pyridyl sulfonyl; the 3-pyridyl sulfonyl; the 4-pyridyl sulfonyl; phenylcarbonyl group; o-xenyl carbonyl; m-xenyl carbonyl; p-xenyl carbonyl; the 1-naphthyl carbonyl; the 2-naphthyl carbonyl; 2-pyridyl carbonyl; 3-pyridyl carbonyl; 4-pyridyl carbonyl.More preferably hydrogen atom, methyl.
Then, to above-mentioned formula (a), formula (b), formula (c), formula (d), formula (f), formula (g), formula (h), formula (j), formula (k), formula (m), formula (n), formula (o), formula (p), formula (q), formula (r), formula (s), formula (t), formula (u), formula (v), the R in formula (w), formula (y), formula (z), formula (aa), formula (ab), formula (ac), formula (ad), formula (ae) and the formula (af)
14, R
15, R
16And R
17Describe.Formula (a), formula (b), formula (c), formula (d), formula (f), formula (g), formula (h), formula (j), formula (k), formula (m), formula (n), formula (o), formula (p), formula (q), formula (r), formula (s), formula (t), formula (u), formula (v), the R in formula (w), formula (y), formula (z), formula (aa), formula (ab), formula (ac), formula (ad), formula (ae) and the formula (af)
14, R
15, R
16And R
17Represent hydrogen atom, halogen atom, C respectively independently
1-6(this alkyl can be by halogen atom, C for alkyl
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom), amino, hydroxyl, C
6-14Aryl, C
2-9(this aryl and heteroaryl can be by R for heteroaryl
19(R
19Expression and R
11Identical implication, r represents the implication identical with q) replace arbitrarily), C
1-6Alkyl amino-carbonyl, two C
1-6Alkyl amino-carbonyl, C
1-6Alkyl-carbonyl oxygen base, C
1-6Alkyl-carbonyl (this alkyl-carbonyl oxygen base and alkyl-carbonyl can be replaced arbitrarily by halogen atom), C
1-6Alkyl-carbonyl-amino, C
3-8Naphthene base carbonyl, C
1-6Alkoxy carbonyl, C
1-6Alkyl sulphonyl (this naphthene base carbonyl, alkoxy carbonyl and alkyl sulphonyl can be replaced arbitrarily by halogen atom), carboxyl, C
6-14Aryl carbonyl (this aryl carbonyl can be replaced arbitrarily by halogen atom) or C
2-9The heteroaryl carbonyl replaces arbitrarily), C
3-8(this cycloalkyl can be by halogen atom, C for cycloalkyl
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom), amino or hydroxyl replace arbitrarily), C
1-6(this alkoxyl group can be by halogen atom, C for alkoxyl group
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom), carboxyl, amino, hydroxyl, C
6-14Aryl or C
2-9(this aryl and heteroaryl can be by R for heteroaryl
19(R
19Expression and R
11Identical implication, r represents the implication identical with q) replace arbitrarily) replace arbitrarily), C
1-6(this thio alkoxy can be by halogen atom, C for thio alkoxy
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom), carboxyl, hydroxyl, C
6-14Aryl or C
2-9(this aryl and heteroaryl can be by R for heteroaryl
19(R
19Expression and R
11Identical implication, r represents the implication identical with q) replace arbitrarily) replace arbitrarily), hydroxyl, C
6-14Aryl, C
2-9(this aryl and heteroaryl can be by R for heteroaryl
19(R
19Expression and R
11Identical implication, r represents the implication identical with q) replace arbitrarily), C
1-6Alkyl-carbonyl oxygen base, nitro, cyano group, formyl radical, formamido-, amino, sulfo group, C
1-6Alkylamino, two C
1-6Alkylamino, C
6-14Arylamino, C
2-9(this arylamino and heteroaryl amino can be by R for heteroaryl amino
19(R
19Expression and R
11Identical implication, r represents the implication identical with q) replace arbitrarily), C
1-6Alkyl-carbonyl-amino, C
1-6Alkylsulfonamido, formamyl, C
1-6Alkyl amino-carbonyl, two C
1-6Alkyl amino-carbonyl, C
1-6Alkyl-carbonyl, C
6-14Aryl carbonyl, C
2-9(this aryl carbonyl and heteroaryl carbonyl can be by R for the heteroaryl carbonyl
19(R
19Expression and R
11Identical implication, r represents the implication identical with q) replace arbitrarily), C
1-6Alkoxy carbonyl, sulfamyl, C
1-6Alkyl sulphonyl, C
6-14Aryl sulfonyl, C
2-9(this aryl sulfonyl and heteroarylsulfonyl can be by R for heteroarylsulfonyl
19(R
19Expression and R
11Identical implication, r represents the implication identical with q) replace arbitrarily), carboxyl or C
2-9(this heterocyclic radical can be by halogen atom, C for heterocyclic radical
1-6(this alkyl can be by halogen atom, C for alkyl
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom), amino, carboxyl or hydroxyl replace arbitrarily), C
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom), C
6-14Aryl, C
2-9(this aryl and heteroaryl can be by R for heteroaryl
19(R
19Expression and R
11Identical implication, r represents the implication identical with q) replace arbitrarily), hydroxyl, nitro, cyano group, formyl radical, formamido-, amino, C
1-6Alkylamino, two C
1-6Alkylamino, C
1-6Alkyl-carbonyl-amino, C
1-6Alkylsulfonamido, formamyl, C
1-6Alkyl amino-carbonyl, two C
1-6Alkyl amino-carbonyl, C
1-6Alkyl-carbonyl, C
1-6Alkoxy carbonyl, sulfamyl, C
1-6Alkyl sulphonyl, carboxyl or C
6-14Aryl carbonyl replaces arbitrarily).
To formula (a), formula (b), formula (c), formula (d), formula (f), formula (g), formula (h), formula (j), formula (k), formula (m), formula (n), formula (o), formula (p), formula (q), formula (r), formula (s), formula (t), formula (u), formula (v), the R in formula (w), formula (y), formula (z), formula (aa), formula (ab), formula (ac), formula (ad), formula (ae) and the formula (af)
14, R
15, R
16And R
17Each atom and each substituting group be specifically described.As this halogen atom, can list fluorine atom, chlorine atom, bromine atoms and iodine atom, as this C
1-6Alkyl, can list methyl, ethyl, the n-propyl group, the i-propyl group, the n-butyl, the i-butyl, the s-butyl, the tertiary butyl, the n-amyl group, the 2-amyl group, the 3-amyl group, the i-amyl group, neo-pentyl, 2, the 2-dimethyl propyl, the n-hexyl, the 2-hexyl, the 3-hexyl, 1-methyl-n-amyl group, 1,1,2-trimethylammonium-n-propyl group, 1,2,2-trimethylammonium-n-propyl group and 3,3-dimethyl-n-butyl, methyl ketonic oxygen ylmethyl, ethyl ketonic oxygen ylmethyl, methyl ketonic oxygen base ethyl, ethyl ketonic oxygen base ethyl, methyl carbonylamino methyl, ethyl carbonylamino methyl, methyl carbonylamino ethyl, ethyl carbonylamino ethyl, the methoxycarbonyl methyl, the ethoxy carbonyl methyl, methoxycarbonyl ethyl and ethoxy carbonyl ethyl etc.
As C
3-8Cycloalkyl, can list the c-propyl group, the c-butyl, 1-methyl-c-propyl group, 2-methyl-c-propyl group, the c-amyl group, 1-methyl-c-butyl, 2-methyl-c-butyl, 3-methyl-c-butyl, 1,2-dimethyl-c-propyl group, 2,3-dimethyl-c-propyl group, 1-ethyl-c-propyl group, 2-ethyl-c-propyl group, the c-hexyl, the c-heptyl, the c-octyl group, 1-methyl-c-hexyl, 2-methyl-c-hexyl, 3-methyl-c-hexyl, 1,2-dimethyl-c-hexyl, 2,3-dimethyl-c-propyl group, 1-ethyl-c-propyl group, 1-methyl-c-amyl group, 2-methyl-c-amyl group, 3-methyl-c-amyl group, 1-ethyl-c-butyl, 2-ethyl-c-butyl, 3-ethyl-c-butyl, 1,2-dimethyl-c-butyl, 1,3-dimethyl-c-butyl, 2,2-dimethyl-c-butyl, 2,3-dimethyl-c-butyl, 2,4-dimethyl-c-butyl, 3,3-dimethyl-c-butyl, 1-n-propyl group-c-propyl group, 2-n-propyl group-c-propyl group, 1-i-propyl group-c-propyl group, 2-i-propyl group-c-propyl group, 1,2,2-trimethylammonium-c-propyl group, 1,2,3-trimethylammonium-c-propyl group, 2,2,3-trimethylammonium-c-propyl group, 1-ethyl-2-methyl-c-propyl group, 2-ethyl-1-methyl-c-propyl group, 2-ethyl-2-methyl-c-propyl group and 2-ethyl-3-methyl-c-propyl group etc.
As this C
1-6Alkoxyl group, can list methoxyl group, oxyethyl group, n-propoxy-, i-propoxy-, n-butoxy, i-butoxy, s-butoxy, t-butoxy, 1-amyl group oxygen base, 2-amyl group oxygen base, 3-amyl group oxygen base, i-amyl group oxygen base, neo-pentyl oxygen base, 2,2-dimethyl propoxy-, 1-hexyl oxygen base, 2-hexyl oxygen base, 3-hexyl oxygen base, 1-methyl-n-amyl group oxygen base, 1,1,2-trimethylammonium-n-propoxy-, 1,2,2-trimethylammonium-n-propoxy-and 3,3-dimethyl-n-butoxy etc.
As C
1-6Thio alkoxy, can list methyl sulphur, ethyl sulphur, n-propylthio, i-propylthio, c-propylthio, n-butyl sulphur, i-butyl sulphur, s-butyl sulphur, t-butyl sulphur, n-amyl group sulphur, i-amyl group sulphur, neo-pentyl sulphur, t-amyl group sulphur, n-hexyl sulphur and c-hexyl sulphur etc.
As this C
6-14Aryl can list phenyl, o-xenyl, m-xenyl, p-xenyl, 1-naphthyl, 2-naphthyl, 1-anthryl, 2-anthryl, 9-anthryl, 1-phenanthryl, 2-phenanthryl, 3-phenanthryl, 4-phenanthryl and 9-phenanthryl etc.
As this C
2-9Heteroaryl comprises the C of 5～7 Yuans rings that can contain 1～3 Sauerstoffatom, nitrogen-atoms, sulphur atom alone or in combination
2-6Monocyclic type heteroaromatic base and constituting atom number are 8～10 C
5-9Condensation two ring type heterocyclic radicals.
C as these 5～7 Yuans rings
2-6The monocyclic type heteroaromatic base, can list the 2-thienyl, the 3-thienyl, the 2-furyl, the 3-furyl, the 2-pyranyl, the 3-pyranyl, the 4-pyranyl, the 1-pyrryl, the 2-pyrryl, the 3-pyrryl, the 1-imidazolyl, the 2-imidazolyl, the 4-imidazolyl, the 1-pyrazolyl, the 3-pyrazolyl, the 4-pyrazolyl, the 2-thiazolyl, the 4-thiazolyl, the 5-thiazolyl, the 3-isothiazolyl, the 4-isothiazolyl, the 5-isothiazolyl, the 2-oxazolyl, the 4-oxazolyl, the 5-oxazolyl, the 3-isoxazolyl, the 4-isoxazolyl, the 5-isoxazolyl, the 2-pyridyl, the 3-pyridyl, the 4-pyridyl, the 2-pyrazinyl, the 2-pyrimidyl, the 4-pyrimidyl, the 5-pyrimidyl, the 3-pyridazinyl, the 4-pyridazinyl, 2-1,3,4-oxadiazole base, 2-1,3, the 4-thiadiazolyl group, 3-1,2,4-oxadiazole base, 5-1,2,4-oxadiazole base, 3-1,2, the 4-thiadiazolyl group, 5-1,2, the 4-thiadiazolyl group, 3-1,2,5-oxadiazole base and 3-1,2,5-thiadiazolyl group etc.
As the constituting atom number this C of 8～10
5-9Condensation two ring type heterocyclic radicals, can list the 2-benzofuryl, the 3-benzofuryl, the 4-benzofuryl, the 5-benzofuryl, the 6-benzofuryl, the 7-benzofuryl, the 1-isobenzofuran-base, the 4-isobenzofuran-base, the 5-isobenzofuran-base, the 2-benzothienyl, the 3-benzothienyl, the 4-benzothienyl, the 5-benzothienyl, the 6-benzothienyl, the 7-benzothienyl, the 1-isobenzo-thienyl, the 4-isobenzo-thienyl, the 5-isobenzo-thienyl, the 2-chromenyl, the 3-chromenyl, the 4-chromenyl, the 5-chromenyl, the 6-chromenyl, the 7-chromenyl, the 8-chromenyl, 1-indolizine base, 2-indolizine base, 3-indolizine base, 5-indolizine base, 6-indolizine base, 7-indolizine base, 8-indolizine base, the 1-pseudoindoyl, the 2-pseudoindoyl, the 4-pseudoindoyl, the 5-pseudoindoyl, the 1-indyl, the 2-indyl, the 3-indyl, the 4-indyl, the 5-indyl, the 6-indyl, the 7-indyl, the 1-indazolyl, the 2-indazolyl, the 3-indazolyl, the 4-indazolyl, the 5-indazolyl, the 6-indazolyl, the 7-indazolyl, the 1-purine radicals, the 2-purine radicals, the 3-purine radicals, the 6-purine radicals, the 7-purine radicals, the 8-purine radicals, the 2-quinolyl, the 3-quinolyl, the 4-quinolyl, the 5-quinolyl, the 6-quinolyl, the 7-quinolyl, the 8-quinolyl, the 1-isoquinolyl, the 3-isoquinolyl, the 4-isoquinolyl, the 5-isoquinolyl, the 6-isoquinolyl, the 7-isoquinolyl, the 8-isoquinolyl, the 1-phthalazinyl, the 5-phthalazinyl, the 6-phthalazinyl, 1-2, the 7-naphthyridinyl, 3-2, the 7-naphthyridinyl, 4-2, the 7-naphthyridinyl, 1-2, the 6-naphthyridinyl, 3-2, the 6-naphthyridinyl, 4-2, the 6-naphthyridinyl, 2-1, the 8-naphthyridinyl, 3-1, the 8-naphthyridinyl, 4-1, the 8-naphthyridinyl, 2-1, the 7-naphthyridinyl, 3-1, the 7-naphthyridinyl, 4-1, the 7-naphthyridinyl, 5-1, the 7-naphthyridinyl, 6-1, the 7-naphthyridinyl, 8-1, the 7-naphthyridinyl, 2-1, the 6-naphthyridinyl, 3-1, the 6-naphthyridinyl, 4-1, the 6-naphthyridinyl, 5-1, the 6-naphthyridinyl, 7-1, the 6-naphthyridinyl, 8-1, the 6-naphthyridinyl, 2-1, the 5-naphthyridinyl, 3-1, the 5-naphthyridinyl, 4-1, the 5-naphthyridinyl, 6-1, the 5-naphthyridinyl, 7-1, the 5-naphthyridinyl, 8-1, the 5-naphthyridinyl, the 2-quinoxalinyl, the 5-quinoxalinyl, the 6-quinoxalinyl, the 2-quinazolyl, the 4-quinazolyl, the 5-quinazolyl, the 6-quinazolyl, the 7-quinazolyl, the 8-quinazolyl, 3-cinnolines base, 4-cinnolines base, 5-cinnolines base, 6-cinnolines base, 7-cinnolines base, 8-cinnolines base, the 2-pteridine radicals, the 4-pteridine radicals, 6-pteridine radicals and 7-pteridine radicals etc.
As this C
1-6The alkyl-carbonyl oxygen base, can list methyl ketonic oxygen base, ethyl ketonic oxygen base, n-propyl group ketonic oxygen base, i-propyl group ketonic oxygen base, n-butyl ketonic oxygen base, i-butyl ketonic oxygen base, s-butyl ketonic oxygen base, tertiary butyl ketonic oxygen base, 1-amyl group ketonic oxygen base, 2-amyl group ketonic oxygen base, 3-amyl group ketonic oxygen base, i-amyl group ketonic oxygen base, neo-pentyl ketonic oxygen base, t-amyl group ketonic oxygen base, 1-hexyl ketonic oxygen base, 2-hexyl ketonic oxygen base, 3-hexyl ketonic oxygen base, 1-methyl-n-amyl group ketonic oxygen base, 1,1,2-trimethylammonium-n-propyl group ketonic oxygen base, 1,2,2-trimethylammonium-n-propyl group ketonic oxygen base and 3,3-dimethyl-n-butyl ketonic oxygen base etc.
As this C
1-6Alkylamino, can list methylamino, ethylamino, n-propyl group amino, i-propyl group amino, c-propyl group amino, n-butyl amino, i-butyl amino, s-butyl amino, tertiary butyl amino, c-butyl amino, 1-amyl group amino, 2-amyl group amino, 3-amyl group amino, i-amyl group amino, neo-pentyl amino, t-amyl group amino, c-amyl group amino, 1-hexyl amino, 2-hexyl amino, 3-hexyl amino, c-hexyl amino, 1-methyl-n-amyl group amino, 1,1,2-trimethylammonium-n-propyl group amino, 1,2,2-trimethylammonium-n-propyl group amino and 3,3-dimethyl-n-butyl amino etc.
As this two C
1-6Alkylamino, can list dimethylamino, diethylamino, two-n-propyl group amino, two-i-propyl group amino, two-c-propyl group amino, two-n-butyl amino, two-i-butyl amino, two-s-butyl amino, two-tertiary butyl amino, two-c-butyl amino, two-1-amyl group amino, two-2-amyl group amino, two-3-amyl group amino, two-i-amyl group amino, two-neo-pentyl amino, two-t-amyl group amino, two-c-amyl group amino, two-1-hexyl amino, two-2-hexyl amino, two-3-hexyl amino, two-c-hexyl amino, two-(1-methyl-n-amyl group) amino, two-(1,1,2-trimethylammonium-n-propyl group) amino, two-(1,2,2-trimethylammonium-n-propyl group) amino, two-(3,3-dimethyl-n-butyl) amino, methyl (ethyl) amino, methyl (n-propyl group) amino, methyl (i-propyl group) amino, methyl (c-propyl group) amino, methyl (n-butyl) amino, methyl (i-butyl) amino, methyl (s-butyl) amino, methyl (t-butyl) amino, methyl (c-butyl) amino, ethyl (n-propyl group) amino, ethyl (i-propyl group) amino, ethyl (c-propyl group) amino, ethyl (n-butyl) amino, ethyl (i-butyl) amino, ethyl (s-butyl) amino, ethyl (t-butyl) amino, ethyl (c-butyl) amino, n-propyl group (i-propyl group) amino, n-propyl group (c-propyl group) amino, n-propyl group (n-butyl) amino, n-propyl group (i-butyl) amino, n-propyl group (s-butyl) amino, n-propyl group (t-butyl) amino, n-propyl group (c-butyl) amino, i-propyl group (c-propyl group) amino, i-propyl group (n-butyl) amino, i-propyl group (i-butyl) amino, i-propyl group (s-butyl) amino, i-propyl group (t-butyl) amino, i-propyl group (c-butyl) amino, c-propyl group (n-butyl) amino, c-propyl group (i-butyl) amino, c-propyl group (s-butyl) amino, c-propyl group (t-butyl) amino, c-propyl group (c-butyl) amino, n-butyl (i-butyl) amino, n-butyl (s-butyl) amino, n-butyl (t-butyl) amino, n-butyl (c-butyl) amino, i-butyl (s-butyl) amino, i-butyl (t-butyl) amino, i-butyl (c-butyl) amino, s-butyl (t-butyl) amino, s-butyl (c-butyl) amino and the tertiary butyl (c-butyl) amino etc.
As this C
6-14Arylamino, can list phenyl amino, o-xenyl amino, m-xenyl amino, p-xenyl amino, 1-naphthyl amino, 2-naphthyl amino, 1-anthryl amino, 2-anthryl amino, 9-anthryl amino, 1-phenanthryl amino, 2-phenanthryl amino, 3-phenanthryl amino, 4-phenanthryl amino and 9-phenanthryl amino
As this C
2-9Heteroaryl amino comprises the C of 5～7 Yuans rings that can contain 1～3 Sauerstoffatom, nitrogen-atoms, sulphur atom alone or in combination
2-6Monocyclic type heteroaromatic amino and constituting atom number are 8～10 C
5-9Condensation two ring type heterocyclic amino group.
This C as 5～7 Yuans rings
2-6Monocyclic type heteroaromatic amino, can list 2-thienyl amino, 3-thienyl amino, 2-furyl amino, 3-furyl amino, 2-pyranyl amino, 3-pyranyl amino, 4-pyranyl amino, 1-pyrryl amino, 2-pyrryl amino, 3-pyrryl amino, 1-imidazolyl amino, 2-imidazolyl amino, 4-imidazolyl amino, 1-pyrazolyl amino, 3-pyrazolyl amino, 4-pyrazolyl amino, 2-thiazolyl amino, 4-thiazolyl amino, 5-thiazolyl amino, 3-isothiazolyl amino, 4-isothiazolyl amino, 5-isothiazolyl amino, 2-oxazolyl amino, 4-oxazolyl amino, 5-oxazolyl amino, 3-isoxazolyl amino, 4-isoxazolyl amino, 5-isoxazolyl amino, the 2-pyridinylamino, the 3-pyridinylamino, the 4-pyridinylamino, 2-pyrazinyl amino, the 2-pyrimidinyl-amino, the 4-pyrimidinyl-amino, the 5-pyrimidinyl-amino, 3-pyridazinyl amino, 4-pyridazinyl amino, 2-1,3,4-oxadiazole base amino, 2-1,3,4-thiadiazolyl group amino, 3-1,2,4-oxadiazole base amino, 5-1,2,4-oxadiazole base amino, 3-1,2,4-thiadiazolyl group amino, 5-1,2,4-thiadiazolyl group amino, 3-1,2,5-oxadiazole base amino and 3-1,2,5-thiadiazolyl group amino etc.
As the constituting atom number this C of 8～10
5-9Condensation two ring type heterocyclic amino group, can list 2-benzofuryl amino, 3-benzofuryl amino, 4-benzofuryl amino, 5-benzofuryl amino, 6-benzofuryl amino, 7-benzofuryl amino, 1-isobenzofuran-base amino, 4-isobenzofuran-base amino, 5-isobenzofuran-base amino, 2-benzothienyl amino, 3-benzothienyl amino, 4-benzothienyl amino, 5-benzothienyl amino, 6-benzothienyl amino, 7-benzothienyl amino, 1-isobenzo-thienyl amino, 4-isobenzo-thienyl amino, 5-isobenzo-thienyl amino, 2-chromenyl amino, 3-chromenyl amino, 4-chromenyl amino, 5-chromenyl amino, 6-chromenyl amino, 7-chromenyl amino, 8-chromenyl amino, 1-indolizine base amino, 2-indolizine base amino, 3-indolizine base amino, 5-indolizine base amino, 6-indolizine base amino, 7-indolizine base amino, 8-indolizine base amino, 1-pseudoindoyl amino, 2-pseudoindoyl amino, 4-pseudoindoyl amino, 5-pseudoindoyl amino, 1-indyl amino, 2-indyl amino, 3-indyl amino, 4-indyl amino, 5-indyl amino, 6-indyl amino, 7-indyl amino, 1-indazolyl amino, 2-indazolyl amino, 3-indazolyl amino, 4-indazolyl amino, 5-indazolyl amino, 6-indazolyl amino, 7-indazolyl amino, 1-purine radicals amino, 2-purine radicals amino, 3-purine radicals amino, 6-purine radicals amino, 7-purine radicals amino, 8-purine radicals amino, 2-quinolyl amino, 3-quinolyl amino, 4-quinolyl amino, 5-quinolyl amino, 6-quinolyl amino, 7-quinolyl amino, 8-quinolyl amino, 1-isoquinolyl amino, 3-isoquinolyl amino, 4-isoquinolyl amino, 5-isoquinolyl amino, 6-isoquinolyl amino, 7-isoquinolyl amino, 8-isoquinolyl amino, 1-phthalazinyl amino, 5-phthalazinyl amino, 6-phthalazinyl amino, 1-2,7-naphthyridinyl amino, 3-2,7-naphthyridinyl amino, 4-2,7-naphthyridinyl amino, 1-2,6-naphthyridinyl amino, 3-2,6-naphthyridinyl amino, 4-2,6-naphthyridinyl amino, 2-1,8-naphthyridinyl amino, 3-1,8-naphthyridinyl amino, 4-1,8-naphthyridinyl amino, 2-1,7-naphthyridinyl amino, 3-1,7-naphthyridinyl amino, 4-1,7-naphthyridinyl amino, 5-1,7-naphthyridinyl amino, 6-1,7-naphthyridinyl amino, 8-1,7-naphthyridinyl amino, 2-1,6-naphthyridinyl amino, 3-1,6-naphthyridinyl amino, 4-1,6-naphthyridinyl amino, 5-1,6-naphthyridinyl amino, 7-1,6-naphthyridinyl amino, 8-1,6-naphthyridinyl amino, 2-1,5-naphthyridinyl amino, 3-1,5-naphthyridinyl amino, 4-1,5-naphthyridinyl amino, 6-1,5-naphthyridinyl amino, 7-1,5-naphthyridinyl amino, 8-1,5-naphthyridinyl amino, 2-quinoxalinyl amino, 5-quinoxalinyl amino, 6-quinoxalinyl amino, 2-quinazolyl amino, 4-quinazolyl amino, 5-quinazolyl amino, 6-quinazolyl amino, 7-quinazolyl amino, 8-quinazolyl amino, 3-cinnolines base amino, 4-cinnolines base amino, 5-cinnolines base amino, 6-cinnolines base amino, 7-cinnolines base amino, 8-cinnolines base amino, 2-pteridine radicals amino, 4-pteridine radicals amino, 6-pteridine radicals amino and 7-pteridine radicals amino etc.
As this C
1-6Alkyl-carbonyl-amino, can list methyl carbonylamino, ethyl carbonylamino, n-propyl group carbonylamino, i-propyl group carbonylamino, n-butyl carbonylamino, i-butyl carbonylamino, s-butyl carbonylamino, tertiary butyl carbonylamino, 1-amyl group carbonylamino, 2-amyl group carbonylamino, 3-amyl group carbonylamino, i-amyl group carbonylamino, neo-pentyl carbonylamino, t-amyl group carbonylamino, 1-hexyl carbonylamino, 2-hexyl carbonylamino and 3-hexyl carbonylamino etc.
As this C
1-6Alkylsulfonamido, can list methylsulfonyl amido, ethane sulphonamide base, n-propane sulfoamido, i-propane sulfoamido, n-butane sulfoamido, i-butane sulfoamido, s-butane sulfoamido, t-butane sulfoamido, 1-pentane sulfoamido, 2-pentane sulfoamido, 3-pentane sulfoamido, i-pentane sulfoamido, neopentane sulfoamido, t-pentane sulfoamido, 1-hexane sulfoamido, 2-hexane sulfoamido and 3-hexane sulfoamido etc.
As this C
1-6Alkyl amino-carbonyl, can list methylamino carbonyl, ethylamino carbonyl, n-propyl group aminocarboxyl, i-propyl group aminocarboxyl, n-butyl aminocarboxyl, i-butyl aminocarboxyl, s-butyl aminocarboxyl, tertiary butyl aminocarboxyl, 1-amyl group aminocarboxyl, 2-amyl group aminocarboxyl, 3-amyl group aminocarboxyl, i-amyl group aminocarboxyl, neo-pentyl aminocarboxyl, t-amyl group aminocarboxyl, 1-hexyl aminocarboxyl, 2-hexyl aminocarboxyl and 3-hexyl aminocarboxyl etc.
As this two C
1-6Alkyl amino-carbonyl, can list the dimethylamino carbonyl, the diethylamino carbonyl, two-n-propyl group aminocarboxyl, two-i-propyl group aminocarboxyl, two-c-propyl group aminocarboxyl, two-n-butyl aminocarboxyl, two-i-butyl aminocarboxyl, two-s-butyl aminocarboxyl, two-tertiary butyl aminocarboxyl, two-c-butyl aminocarboxyl, two-1-amyl group aminocarboxyl, two-2-amyl group aminocarboxyl, two-3-amyl group aminocarboxyl, two-i-amyl group aminocarboxyl, two-neo-pentyl aminocarboxyl, two-t-amyl group aminocarboxyl, two-c-amyl group aminocarboxyl, two-1-hexyl aminocarboxyl, two-2-hexyl aminocarboxyl, two-3-hexyl aminocarboxyl, two-c-hexyl aminocarboxyl, two-(1-methyl-n-amyl group) aminocarboxyls, two-(1,1,2-trimethylammonium-n-propyl group) aminocarboxyl, two-(1,2,2-trimethylammonium-n-propyl group) aminocarboxyl, two-(3,3-dimethyl-n-butyl) aminocarboxyl, methyl (ethyl) aminocarboxyl, methyl (n-propyl group) aminocarboxyl, methyl (i-propyl group) aminocarboxyl, methyl (c-propyl group) aminocarboxyl, methyl (n-butyl) aminocarboxyl, methyl (i-butyl) aminocarboxyl, methyl (s-butyl) aminocarboxyl, methyl (t-butyl) aminocarboxyl, methyl (c-butyl) aminocarboxyl, ethyl (n-propyl group) aminocarboxyl, ethyl (i-propyl group) aminocarboxyl, ethyl (c-propyl group) aminocarboxyl, ethyl (n-butyl) aminocarboxyl, ethyl (i-butyl) aminocarboxyl, ethyl (s-butyl) aminocarboxyl, ethyl (t-butyl) aminocarboxyl, ethyl (c-butyl) aminocarboxyl, n-propyl group (i-propyl group) aminocarboxyl, n-propyl group (c-propyl group) aminocarboxyl, n-propyl group (n-butyl) aminocarboxyl, n-propyl group (i-butyl) aminocarboxyl, n-propyl group (s-butyl) aminocarboxyl, n-propyl group (t-butyl) aminocarboxyl, n-propyl group (c-butyl) aminocarboxyl, i-propyl group (c-propyl group) aminocarboxyl, i-propyl group (n-butyl) aminocarboxyl, i-propyl group (i-butyl) aminocarboxyl, i-propyl group (s-butyl) aminocarboxyl, i-propyl group (t-butyl) aminocarboxyl, i-propyl group (c-butyl) aminocarboxyl, c-propyl group (n-butyl) aminocarboxyl, c-propyl group (i-butyl) aminocarboxyl, c-propyl group (s-butyl) aminocarboxyl, c-propyl group (t-butyl) aminocarboxyl, c-propyl group (c-butyl) aminocarboxyl, n-butyl (i-butyl) aminocarboxyl, n-butyl (s-butyl) aminocarboxyl, n-butyl (t-butyl) aminocarboxyl, n-butyl (c-butyl) aminocarboxyl, i-butyl (s-butyl) aminocarboxyl, i-butyl (t-butyl) aminocarboxyl, i-butyl (c-butyl) aminocarboxyl, s-butyl (t-butyl) aminocarboxyl, s-butyl (c-butyl) aminocarboxyl and the tertiary butyl (c-butyl) aminocarboxyl etc.
As this C
1-6Alkyl-carbonyl, can list methyl carbonyl, ethyl carbonyl, n-propyl group carbonyl, i-propyl group carbonyl, n-butyl carbonyl, i-butyl carbonyl, s-butyl carbonyl, tertiary butyl carbonyl, 1-amyl group carbonyl, 2-amyl group carbonyl, 3-amyl group carbonyl, i-amyl group carbonyl, neo-pentyl carbonyl, t-amyl group carbonyl, 1-hexyl carbonyl, 2-hexyl carbonyl and 3-hexyl carbonyl etc.
As this C
6-14Aryl carbonyl can list phenylcarbonyl group, o-xenyl carbonyl, m-xenyl carbonyl, p-xenyl carbonyl, 1-naphthyl carbonyl, 2-naphthyl carbonyl, 1-anthryl carbonyl, 2-anthryl carbonyl, 9-anthryl carbonyl, 1-phenanthryl carbonyl, 2-phenanthryl carbonyl, 3-phenanthryl carbonyl, 4-phenanthryl carbonyl and 9-phenanthryl carbonyl etc.
As this C
2-9The heteroaryl carbonyl comprises the C of 5～7 Yuans rings that can contain 1～3 Sauerstoffatom, nitrogen-atoms, sulphur atom alone or in combination
2-6Monocyclic type heteroaromatic carbonyl and constituting atom number are 8～10 C
5-9Condensation two ring type heterocycle carbonyls.
This C as 5～7 Yuans rings
2-6The monocyclic type heteroaromatic carbonyl, can list the 2-thienyl carbonyl, the 3-thienyl carbonyl, the 2-furyl carbonyl, the 3-furyl carbonyl, 2-pyranyl carbonyl, 3-pyranyl carbonyl, 4-pyranyl carbonyl, 1-pyrryl carbonyl, 2-pyrryl carbonyl, 3-pyrryl carbonyl, 1-imidazolyl carbonyl, 2-imidazolyl carbonyl, 4-imidazolyl carbonyl, 1-pyrazolyl carbonyl, 3-pyrazolyl carbonyl, 4-pyrazolyl carbonyl, 2-thiazolyl carbonyl, 4-thiazolyl carbonyl, 5-thiazolyl carbonyl, 3-isothiazolyl carbonyl, 4-isothiazolyl carbonyl, 5-isothiazolyl carbonyl, 2-oxazolyl carbonyl, 4-oxazolyl carbonyl, 5-oxazolyl carbonyl, 3-isoxazolyl carbonyl, 4-isoxazolyl carbonyl, 5-isoxazolyl carbonyl, 2-pyridyl carbonyl, 3-pyridyl carbonyl, 4-pyridyl carbonyl, 2-pyrazinyl carbonyl, 2-pyrimidyl carbonyl, 4-pyrimidyl carbonyl, 5-pyrimidyl carbonyl, 3-pyridazinyl carbonyl, 4-pyridazinyl carbonyl, 2-1,3,4-oxadiazole base carbonyl, 2-1,3,4-thiadiazolyl group carbonyl, 3-1,2,4-oxadiazole base carbonyl, 5-1,2,4-oxadiazole base carbonyl, 3-1,2,4-thiadiazolyl group carbonyl, 5-1,2,4-thiadiazolyl group carbonyl, 3-1,2,5-oxadiazole base carbonyl and 3-1,2,5-thiadiazolyl group carbonyl etc.
As the constituting atom number this C of 8～10
5-9Condensation two ring type heterocycle carbonyls, can list 2-benzofuryl carbonyl, 3-benzofuryl carbonyl, 4-benzofuryl carbonyl, 5-benzofuryl carbonyl, 6-benzofuryl carbonyl, 7-benzofuryl carbonyl, 1-isobenzofuran-base carbonyl, 4-isobenzofuran-base carbonyl, 5-isobenzofuran-base carbonyl, 2-benzothienyl carbonyl, 3-benzothienyl carbonyl, 4-benzothienyl carbonyl, 5-benzothienyl carbonyl, 6-benzothienyl carbonyl, 7-benzothienyl carbonyl, 1-isobenzo-thienyl carbonyl, 4-isobenzo-thienyl carbonyl, 5-isobenzo-thienyl carbonyl, 2-chromenyl carbonyl, 3-chromenyl carbonyl, 4-chromenyl carbonyl, 5-chromenyl carbonyl, 6-chromenyl carbonyl, 7-chromenyl carbonyl, 8-chromenyl carbonyl, 1-indolizine base carbonyl, 2-indolizine base carbonyl, 3-indolizine base carbonyl, 5-indolizine base carbonyl, 6-indolizine base carbonyl, 7-indolizine base carbonyl, 8-indolizine base carbonyl, 1-pseudoindoyl carbonyl, 2-pseudoindoyl carbonyl, 4-pseudoindoyl carbonyl, 5-pseudoindoyl carbonyl, the 1-indole carbonyl, the 2-indole carbonyl, the 3-indole carbonyl, the 4-indole carbonyl, the 5-indole carbonyl, the 6-indole carbonyl, the 7-indole carbonyl, 1-indazolyl carbonyl, 2-indazolyl carbonyl, 3-indazolyl carbonyl, 4-indazolyl carbonyl, 5-indazolyl carbonyl, 6-indazolyl carbonyl, 7-indazolyl carbonyl, 1-purine radicals carbonyl, 2-purine radicals carbonyl, 3-purine radicals carbonyl, 6-purine radicals carbonyl, 7-purine radicals carbonyl, 8-purine radicals carbonyl, the 2-quinolyl carbonyl, the 3-quinolyl carbonyl, the 4-quinolyl carbonyl, the 5-quinolyl carbonyl, the 6-quinolyl carbonyl, the 7-quinolyl carbonyl, the 8-quinolyl carbonyl, 1-isoquinolyl carbonyl, 3-isoquinolyl carbonyl, 4-isoquinolyl carbonyl, 5-isoquinolyl carbonyl, 6-isoquinolyl carbonyl, 7-isoquinolyl carbonyl, 8-isoquinolyl carbonyl, 1-phthalazinyl carbonyl, 5-phthalazinyl carbonyl, 6-phthalazinyl carbonyl, 1-2,7-naphthyridinyl carbonyl, 3-2,7-naphthyridinyl carbonyl, 4-2,7-naphthyridinyl carbonyl, 1-2,6-naphthyridinyl carbonyl, 3-2,6-naphthyridinyl carbonyl, 4-2,6-naphthyridinyl carbonyl, 2-1,8-naphthyridinyl carbonyl, 3-1,8-naphthyridinyl carbonyl, 4-1,8-naphthyridinyl carbonyl, 2-1,7-naphthyridinyl carbonyl, 3-1,7-naphthyridinyl carbonyl, 4-1,7-naphthyridinyl carbonyl, 5-1,7-naphthyridinyl carbonyl, 6-1,7-naphthyridinyl carbonyl, 8-1,7-naphthyridinyl carbonyl, 2-1,6-naphthyridinyl carbonyl, 3-1,6-naphthyridinyl carbonyl, 4-1,6-naphthyridinyl carbonyl, 5-1,6-naphthyridinyl carbonyl, 7-1,6-naphthyridinyl carbonyl, 8-1,6-naphthyridinyl carbonyl, 2-1,5-naphthyridinyl carbonyl, 3-1,5-naphthyridinyl carbonyl, 4-1,5-naphthyridinyl carbonyl, 6-1,5-naphthyridinyl carbonyl, 7-1,5-naphthyridinyl carbonyl, 8-1,5-naphthyridinyl carbonyl, 2-quinoxalinyl carbonyl, 5-quinoxalinyl carbonyl, 6-quinoxalinyl carbonyl, 2-quinazolyl carbonyl, 4-quinazolyl carbonyl, 5-quinazolyl carbonyl, 6-quinazolyl carbonyl, 7-quinazolyl carbonyl, 8-quinazolyl carbonyl, 3-cinnolines base carbonyl, 4-cinnolines base carbonyl, 5-cinnolines base carbonyl, 6-cinnolines base carbonyl, 7-cinnolines base carbonyl, 8-cinnolines base carbonyl, 2-pteridine radicals carbonyl, 4-pteridine radicals carbonyl, 6-pteridine radicals carbonyl and 7-pteridine radicals carbonyl etc.
As this C
1-6Alkoxy carbonyl, can list methoxycarbonyl, ethoxy carbonyl, n-propoxycarbonyl, i-propoxycarbonyl, n-butoxy carbonyl, i-butoxy carbonyl, s-butoxy carbonyl, t-butoxy carbonyl, 1-amyl group oxygen base carbonyl, 2-amyl group oxygen base carbonyl, 3-amyl group oxygen base carbonyl, i-amyl group oxygen base carbonyl, neo-pentyl oxygen base carbonyl, t-amyl group oxygen base carbonyl, 1-hexyl oxygen base carbonyl, 2-hexyl oxygen base carbonyl and 3-hexyl oxygen base carbonyl etc.
As this C
1-6Alkyl sulphonyl can list methane sulfonyl, trifluoromethane sulfonyl group and ethane alkylsulfonyl.As this C
6-14Aryl sulfonyl can list benzenesulfonyl, o-biphenyl sulfonyl, m-biphenyl sulfonyl, p-biphenyl sulfonyl, 1-naphthalene sulfonyl base, 2-naphthalene sulfonyl base, 1-anthracene alkylsulfonyl, 2-anthracene alkylsulfonyl, 9-anthracene alkylsulfonyl, the luxuriant and rich with fragrance alkylsulfonyl of 1-, the luxuriant and rich with fragrance alkylsulfonyl of 2-, the luxuriant and rich with fragrance alkylsulfonyl of 3-, the luxuriant and rich with fragrance alkylsulfonyl of 4-and the luxuriant and rich with fragrance alkylsulfonyl of 9-etc.
As this C
2-9Heteroarylsulfonyl comprises the C of 5～7 Yuans rings that can contain 1～3 Sauerstoffatom, nitrogen-atoms, sulphur atom alone or in combination
2-6Monocyclic type heteroaromatic alkylsulfonyl and constituting atom number are 8～10 C
5-9Condensation two ring type heterocycle alkylsulfonyls.
This C as 5～7 Yuans rings
2-6The monocyclic type heteroaromatic alkylsulfonyl; can list 2-thienyl sulphonyl base; 3-thienyl sulphonyl base; 2-furyl alkylsulfonyl; 3-furyl alkylsulfonyl; 2-pyranyl alkylsulfonyl; 3-pyranyl alkylsulfonyl; 4-pyranyl alkylsulfonyl; 1-pyrryl alkylsulfonyl; 2-pyrryl alkylsulfonyl; 3-pyrryl alkylsulfonyl; 1-imidazolyl alkylsulfonyl; 2-imidazolyl alkylsulfonyl; 4-imidazolyl alkylsulfonyl; 1-pyrazolyl alkylsulfonyl; 3-pyrazolyl alkylsulfonyl; 4-pyrazolyl alkylsulfonyl; 2-thiazolyl alkylsulfonyl; 4-thiazolyl alkylsulfonyl; 5-thiazolyl alkylsulfonyl; 3-isothiazolyl alkylsulfonyl; 4-isothiazolyl alkylsulfonyl; 5-isothiazolyl alkylsulfonyl; 2-oxazolyl alkylsulfonyl; 4-oxazolyl alkylsulfonyl; 5-oxazolyl alkylsulfonyl; 3-isoxazolyl alkylsulfonyl; 4-isoxazolyl alkylsulfonyl; 5-isoxazolyl alkylsulfonyl; the 2-pyridyl sulfonyl; the 3-pyridyl sulfonyl; the 4-pyridyl sulfonyl; 2-pyrazinyl alkylsulfonyl; 2-pyrimidyl alkylsulfonyl; 4-pyrimidyl alkylsulfonyl; 5-pyrimidyl alkylsulfonyl; 3-pyridazinyl alkylsulfonyl; 4-pyridazinyl alkylsulfonyl; 2-1; 3; 4-oxadiazole base alkylsulfonyl; 2-1; 3; 4-thiadiazolyl group alkylsulfonyl; 3-1; 2; 4-oxadiazole base alkylsulfonyl; 5-1; 2; 4-oxadiazole base alkylsulfonyl; 3-1; 2; 4-thiadiazolyl group alkylsulfonyl; 5-1; 2; 4-thiadiazolyl group alkylsulfonyl; 3-1; 2; 5-oxadiazole base alkylsulfonyl and 3-1; 2,5-thiadiazolyl group alkylsulfonyl etc.
As the constituting atom number this C of 8～10
5-9Condensation two ring type heterocycle alkylsulfonyls; can list 2-benzofuryl alkylsulfonyl; 3-benzofuryl alkylsulfonyl; 4-benzofuryl alkylsulfonyl; 5-benzofuryl alkylsulfonyl; 6-benzofuryl alkylsulfonyl; 7-benzofuryl alkylsulfonyl; 1-isobenzofuran-base alkylsulfonyl; 4-isobenzofuran-base alkylsulfonyl; 5-isobenzofuran-base alkylsulfonyl; 2-benzothienyl alkylsulfonyl; 3-benzothienyl alkylsulfonyl; 4-benzothienyl alkylsulfonyl; 5-benzothienyl alkylsulfonyl; 6-benzothienyl alkylsulfonyl; 7-benzothienyl alkylsulfonyl; 1-isobenzo-thienyl alkylsulfonyl; 4-isobenzo-thienyl alkylsulfonyl; 5-isobenzo-thienyl alkylsulfonyl; 2-chromenyl alkylsulfonyl; 3-chromenyl alkylsulfonyl; 4-chromenyl alkylsulfonyl; 5-chromenyl alkylsulfonyl; 6-chromenyl alkylsulfonyl; 7-chromenyl alkylsulfonyl; 8-chromenyl alkylsulfonyl; 1-indolizine base alkylsulfonyl; 2-indolizine base alkylsulfonyl; 3-indolizine base alkylsulfonyl; 5-indolizine base alkylsulfonyl; 6-indolizine base alkylsulfonyl; 7-indolizine base alkylsulfonyl; 8-indolizine base alkylsulfonyl; 1-pseudoindoyl alkylsulfonyl; 2-pseudoindoyl alkylsulfonyl; 4-pseudoindoyl alkylsulfonyl; 5-pseudoindoyl alkylsulfonyl; 1-indyl alkylsulfonyl; 2-indyl alkylsulfonyl; 3-indyl alkylsulfonyl; 4-indyl alkylsulfonyl; 5-indyl alkylsulfonyl; 6-indyl alkylsulfonyl; 7-indyl alkylsulfonyl; 1-indazolyl alkylsulfonyl; 2-indazolyl alkylsulfonyl; 3-indazolyl alkylsulfonyl; 4-indazolyl alkylsulfonyl; 5-indazolyl alkylsulfonyl; 6-indazolyl alkylsulfonyl; 7-indazolyl alkylsulfonyl; 1-purine radicals alkylsulfonyl; 2-purine radicals alkylsulfonyl; 3-purine radicals alkylsulfonyl; 6-purine radicals alkylsulfonyl; 7-purine radicals alkylsulfonyl; 8-purine radicals alkylsulfonyl; 2-quinolyl alkylsulfonyl; 3-quinolyl alkylsulfonyl; 4-quinolyl alkylsulfonyl; 5-quinolyl alkylsulfonyl; 6-quinolyl alkylsulfonyl; 7-quinolyl alkylsulfonyl; 8-quinolyl alkylsulfonyl; 1-isoquinolyl alkylsulfonyl; 3-isoquinolyl alkylsulfonyl; 4-isoquinolyl alkylsulfonyl; 5-isoquinolyl alkylsulfonyl; 6-isoquinolyl alkylsulfonyl; 7-isoquinolyl alkylsulfonyl; 8-isoquinolyl alkylsulfonyl; 1-phthalazinyl alkylsulfonyl; 5-phthalazinyl alkylsulfonyl; 6-phthalazinyl alkylsulfonyl; 1-2; 7-naphthyridinyl alkylsulfonyl; 3-2; 7-naphthyridinyl alkylsulfonyl; 4-2; 7-naphthyridinyl alkylsulfonyl; 1-2; 6-naphthyridinyl alkylsulfonyl; 3-2; 6-naphthyridinyl alkylsulfonyl; 4-2; 6-naphthyridinyl alkylsulfonyl; 2-1; 8-naphthyridinyl alkylsulfonyl; 3-1; 8-naphthyridinyl alkylsulfonyl; 4-1; 8-naphthyridinyl alkylsulfonyl; 2-1; 7-naphthyridinyl alkylsulfonyl; 3-1; 7-naphthyridinyl alkylsulfonyl; 4-1; 7-naphthyridinyl alkylsulfonyl; 5-1; 7-naphthyridinyl alkylsulfonyl; 6-1; 7-naphthyridinyl alkylsulfonyl; 8-1; 7-naphthyridinyl alkylsulfonyl; 2-1; 6-naphthyridinyl alkylsulfonyl; 3-1; 6-naphthyridinyl alkylsulfonyl; 4-1; 6-naphthyridinyl alkylsulfonyl; 5-1; 6-naphthyridinyl alkylsulfonyl; 7-1; 6-naphthyridinyl alkylsulfonyl; 8-1; 6-naphthyridinyl alkylsulfonyl; 2-1; 5-naphthyridinyl alkylsulfonyl; 3-1; 5-naphthyridinyl alkylsulfonyl; 4-1; 5-naphthyridinyl alkylsulfonyl; 6-1; 5-naphthyridinyl alkylsulfonyl; 7-1; 5-naphthyridinyl alkylsulfonyl; 8-1,5-naphthyridinyl alkylsulfonyl; 2-quinoxalinyl alkylsulfonyl; 5-quinoxalinyl alkylsulfonyl; 6-quinoxalinyl alkylsulfonyl; 2-quinazolyl alkylsulfonyl; 4-quinazolyl alkylsulfonyl; 5-quinazolyl alkylsulfonyl; 6-quinazolyl alkylsulfonyl; 7-quinazolyl alkylsulfonyl; 8-quinazolyl alkylsulfonyl; 3-cinnolines base alkylsulfonyl; 4-cinnolines base alkylsulfonyl; 5-cinnolines base alkylsulfonyl; 6-cinnolines base alkylsulfonyl; 7-cinnolines base alkylsulfonyl; 8-cinnolines base alkylsulfonyl; 2-pteridine radicals alkylsulfonyl; 4-pteridine radicals alkylsulfonyl; 6-pteridine radicals alkylsulfonyl and 7-pteridine radicals alkylsulfonyl etc.
As this C
2-9Heterocyclic radical can list the atom of freely selecting and the monocycle of 2～9 carbon atoms and the heterocyclic radical of the ring two ring property that contract that contain more than 1 from nitrogen-atoms, Sauerstoffatom and sulphur atom, specifically, can list following radicals etc.
With
Put down in writing in each ring structure in the following formula-(expression bonding), can be taken at the position arbitrarily that can replace on the chemical structure, do not represent specific replacement position.
Formula (a), formula (b), formula (c), formula (d), formula (f), formula (g), formula (h), formula (j), formula (k), formula (m), formula (n), formula (o), formula (p), formula (q), formula (r), formula (s), formula (t), formula (u), formula (v), the R in formula (w), formula (y), formula (z), formula (aa), formula (ab), formula (ac), formula (ad), formula (ae) and the formula (af)
14, R
15, R
16And R
17Independent respectively; preferred hydrogen atom; fluorine atom; the chlorine atom; bromine atoms; methyl; ethyl; the n-propyl group; the i-propyl group; the n-butyl; the n-amyl group; the i-amyl group; 3,3-dimethyl-n-butyl; methyl ketonic oxygen ylmethyl; ethyl ketonic oxygen ylmethyl; methyl ketonic oxygen base ethyl; ethyl ketonic oxygen base ethyl; methyl carbonylamino methyl; ethyl carbonylamino methyl; methyl carbonylamino ethyl; ethyl carbonylamino ethyl; the methoxycarbonyl methyl; the ethoxy carbonyl methyl; the methoxycarbonyl ethyl; the ethoxy carbonyl ethyl; the c-propyl group; the c-amyl group; c-hexyl methoxyl group; oxyethyl group; the n-propoxy-; the i-propoxy-; the methyl sulfenyl; the ethyl sulfenyl; phenyl; the o-xenyl; the m-xenyl; the p-xenyl; the 1-naphthyl; the 2-naphthyl; the 2-pyridyl; the 3-pyridyl; the 4-pyridyl; methyl ketonic oxygen base; ethyl ketonic oxygen base; n-propyl group ketonic oxygen base; i-propyl group ketonic oxygen base; n-butyl ketonic oxygen base; tertiary butyl ketonic oxygen base; methylamino; ethylamino; n-propyl group amino; i-propyl group amino; n-butyl amino; dimethylamino; diethylamino; two-n-propyl group amino; two-i-propyl group amino; two-n-butyl amino; phenyl amino; o-xenyl amino; m-xenyl amino; p-xenyl amino; 1-naphthyl amino; 2-naphthyl amino; the 2-pyridinylamino; the 3-pyridinylamino; the 4-pyridinylamino; the methyl carbonylamino; the ethyl carbonylamino; n-propyl group carbonylamino; i-propyl group carbonylamino; n-butyl carbonylamino; the methylsulfonyl amido; the ethane sulphonamide base; n-propane sulfoamido; i-propane sulfoamido; n-butane sulfoamido; the methylamino carbonyl; the ethylamino carbonyl; n-propyl group aminocarboxyl; i-propyl group aminocarboxyl; n-butyl aminocarboxyl; the dimethylamino carbonyl; the diethylamino carbonyl; two-n-propyl group aminocarboxyl; two-i-propyl group aminocarboxyl; two-c-propyl group aminocarboxyl; two-n-butyl aminocarboxyl; the methyl carbonyl; the ethyl carbonyl; n-propyl group carbonyl; i-propyl group carbonyl; n-butyl carbonyl; phenylcarbonyl group; o-xenyl carbonyl; m-xenyl carbonyl; p-xenyl carbonyl; the 1-naphthyl carbonyl; the 2-naphthyl carbonyl; 2-pyridyl carbonyl; 3-pyridyl carbonyl; 4-pyridyl carbonyl; methoxycarbonyl; ethoxy carbonyl; the n-propoxycarbonyl; the i-propoxycarbonyl; the n-butoxy carbonyl; the i-butoxy carbonyl; the s-butoxy carbonyl; the t-butoxy carbonyl; methane sulfonyl; trifluoromethane sulfonyl group; benzenesulfonyl; the o-biphenyl sulfonyl; the m-biphenyl sulfonyl; the p-biphenyl sulfonyl; 1-naphthalene sulfonyl base; 2-naphthalene sulfonyl base; the 2-pyridyl sulfonyl; the 3-pyridyl sulfonyl; the 4-pyridyl sulfonyl; amino; cyano group; formamyl; carboxyl;
Put down in writing in each ring structure in the following formula-(expression bonding), can be taken at the position arbitrarily that can replace on the chemical structure, do not represent specific replacement position.
Above-mentioned formula (c), formula (d), formula (p), formula (q), formula (v), the Q in formula (w), formula (ab), formula (ac) and the formula (ad), expression O (Sauerstoffatom), S (sulphur atom), SO (sulfinyl) or SO
2(alkylsulfonyl).(v), Q is preferably O (Sauerstoffatom) in formula (w), formula (ab), formula (ac) and the formula (ad) for formula (c), formula (d), formula (p), formula (q), formula.
Below, be formula (a), formula (b), formula (i), formula (k), formula (o), formula (p), formula (s), formula (v), the formula (a) under the situation of formula (y), formula (ae), formula (ag) or formula (ah), formula (b), formula (i), formula (k), formula (o), formula (p), formula (s), formula (v), the R in formula (y), formula (ae), formula (ag) or the formula (ah) to the part ring structure A in above-mentioned formula (11) or the formula (12)
12, R
13, R
14, R
15And R
16Describe.
Part ring structure to the A in above-mentioned formula (11) or the formula (12) is formula (a), formula (b), formula (i), formula (k), formula (o), formula (p), formula (s), formula (v), the formula (a) under the situation of formula (y), formula (ae), formula (ag) or formula (ah), formula (b), formula (i), formula (k), formula (p), formula (v), the R in formula (ae) and the formula (ag)
12And R
13Describe.
Formula (a), formula (b), formula (i), formula (k), formula (p), formula (v), the R in formula (ae) and the formula (ag)
12And R
13Represent hydrogen atom, C respectively independently
1-6(this alkyl can be by halogen atom, C for alkyl
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom), amino or hydroxyl replace arbitrarily).
To formula (a), formula (b), formula (i), formula (k), formula (p), formula (v), the R in formula (ae) and the formula (ag)
12And R
13Each substituting group be specifically described.
As this C
1-6Alkyl, can list methyl, trifluoromethyl, methoxymethyl, ethyl, n-propyl group, i-propyl group, n-butyl, i-butyl, s-butyl, the tertiary butyl, n-amyl group, 2-amyl group, 3-amyl group, i-amyl group, neo-pentyl, 2,2-dimethyl propyl, n-hexyl, 2-hexyl, 3-hexyl, 1-methyl-n-amyl group, 1,1,2-trimethylammonium-n-propyl group, 1,2,2-trimethylammonium-n-propyl group and 3,3-dimethyl-n-butyl etc.
Formula (a), formula (b), formula (i), formula (k), formula (p), formula (v), the R in formula (ae) and the formula (ag)
12And R
13Independent respectively, be preferably hydrogen atom, methyl, trifluoromethyl, methoxymethyl, ethyl, n-propyl group, i-propyl group, n-butyl, n-amyl group, i-amyl group, amino, hydroxyl, more preferably hydrogen atom, methyl.
Part ring structure to the A in above-mentioned formula (11) or the formula (12) is formula (a), formula (b), formula (i), formula (k), formula (o), formula (p), formula (s), formula (v), the formula (a) under the situation of formula (y), formula (ae), formula (ag) or formula (ah), formula (b), formula (k), formula (o), formula (p), formula (s), formula (v), the R in formula (y) and the formula (ae)
14, R
15And R
16Describe.Formula (a), formula (b), formula (k), formula (o), formula (p), formula (s), formula (v), the R in formula (y) and the formula (ae)
14, R
15And R
16Represent hydrogen atom, halogen atom or C respectively independently
1-6(this alkyl can be by halogen atom, C for alkyl
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom), amino, hydroxyl, C
1-6Alkyl amino-carbonyl, two C
1-6Alkyl amino-carbonyl, C
1-6Alkyl-carbonyl oxygen base, C
1-6Alkyl-carbonyl (this alkyl-carbonyl oxygen base and alkyl-carbonyl can be replaced arbitrarily by halogen atom), C
1-6Alkyl-carbonyl-amino, C
3-8Naphthene base carbonyl or C
1-6Alkoxy carbonyl replaces arbitrarily).
To formula (a), formula (b), formula (k), formula (o), formula (p), formula (s), formula (v), the R in formula (y) and the formula (ae)
14, R
15And R
16Each atom and each substituting group be specifically described.As this halogen atom, can list fluorine atom, chlorine atom, bromine atoms and iodine atom,
As this C
1-6Alkyl, can list methyl, trifluoromethyl, ethyl, the n-propyl group, the i-propyl group, the n-butyl, the i-butyl, the s-butyl, the tertiary butyl, the n-amyl group, the 2-amyl group, the 3-amyl group, the i-amyl group, neo-pentyl, 2, the 2-dimethyl propyl, the n-hexyl, the 2-hexyl, the 3-hexyl, 1-methyl-n-amyl group, 1,1,2-trimethylammonium-n-propyl group, 1,2,2-trimethylammonium-n-propyl group and 3,3-dimethyl-n-butyl, methyl ketonic oxygen ylmethyl, ethyl ketonic oxygen ylmethyl, methyl ketonic oxygen base ethyl, ethyl ketonic oxygen base ethyl, methyl carbonylamino methyl, ethyl carbonylamino methyl, methyl carbonylamino ethyl, ethyl carbonylamino ethyl, the methoxycarbonyl methyl, the ethoxy carbonyl methyl, the methoxycarbonyl ethyl, trifluoromethoxy carbonyl methyl and ethoxy carbonyl ethyl etc.As this C
1-6Alkyl-carbonyl-amino, can list the methyl carbonylamino, the trifluoromethyl carbonylamino, the ethyl carbonylamino, n-propyl group carbonylamino, i-propyl group carbonylamino, n-butyl carbonylamino, i-butyl carbonylamino, s-butyl carbonylamino, t-butyl carbonylamino, 1-amyl group carbonylamino, 2-amyl group carbonylamino, 3-amyl group carbonylamino, i-amyl group carbonylamino, the neo-pentyl carbonylamino, t-amyl group carbonylamino, 1-hexyl carbonylamino, 2-hexyl carbonylamino and 3-hexyl carbonylamino etc.
As this C
3-8Naphthene base carbonyl, can list c-propyl group carbonyl, c-butyl carbonyl, 1-methyl-c-propyl group carbonyl, 2-methyl-c-propyl group carbonyl, c-amyl group carbonyl, 1-methyl-c-butyl carbonyl, 2-methyl-c-butyl carbonyl, 3-methyl-c-butyl carbonyl, 1,2-dimethyl-c-propyl group carbonyl, 2,3-dimethyl-c-propyl group carbonyl, 1-ethyl-c-propyl group carbonyl, 2-ethyl-c-propyl group carbonyl, c-hexyl carbonyl, c-heptyl carbonyl, c-octyl group carbonyl, 1-methyl-c-hexyl carbonyl, 2-methyl-c-hexyl carbonyl, 3-methyl-c-hexyl carbonyl, 1,2-dimethyl-c-hexyl carbonyl, 2,3-dimethyl-c-propyl group carbonyl, 1-ethyl-c-propyl group carbonyl, 1-methyl-c-amyl group carbonyl, 2-methyl-c-amyl group carbonyl, 3-methyl-c-amyl group carbonyl, 1-ethyl-c-butyl carbonyl, 2-ethyl-c-butyl carbonyl, 3-ethyl-c-butyl carbonyl, 1,2-dimethyl-c-butyl carbonyl, 1,3-dimethyl-c-butyl carbonyl, 2,2-dimethyl-c-butyl carbonyl, 2,3-dimethyl-c-butyl carbonyl, 2,4-dimethyl-c-butyl carbonyl, 3,3-dimethyl-c-butyl carbonyl, 1-n-propyl group-c-propyl group carbonyl, 2-n-propyl group-c-propyl group carbonyl, 1-i-propyl group-c-propyl group carbonyl, 2-i-propyl group-c-propyl group carbonyl, 1,2,2-trimethylammonium-c-propyl group carbonyl, 1,2,3-trimethylammonium-c-propyl group carbonyl, 2,2,3-trimethylammonium-c-propyl group carbonyl, 1-ethyl-2-methyl-c-propyl group carbonyl, 2-ethyl-1-methyl-c-propyl group carbonyl, 2-ethyl-2-methyl-c-propyl group carbonyl and 2-ethyl-3-methyl-c-propyl group carbonyl etc.
As this C
1-6Alkoxy carbonyl can list methoxycarbonyl, ethoxy carbonyl, n-propoxycarbonyl, i-propoxycarbonyl, n-butoxy carbonyl, i-butoxy carbonyl, s-butoxy carbonyl, t-butoxy carbonyl, 1-amyl group oxygen base carbonyl, 2-amyl group oxygen base carbonyl, 3-amyl group oxygen base carbonyl, i-amyl group oxygen base carbonyl, neo-pentyl oxygen base carbonyl, t-amyl group oxygen base carbonyl, 1-hexyl oxygen base carbonyl, 2-hexyl oxygen base carbonyl and 3-hexyl oxygen base carbonyl etc.
Formula (a), formula (b), formula (k), formula (o), formula (p), formula (s), formula (v), the R in formula (y) and the formula (ae)
14, R
15And R
16Independent respectively, preferred hydrogen atom, fluorine atom, the chlorine atom, bromine atoms, methyl, trifluoromethyl, ethyl, the n-propyl group, the i-propyl group, the n-butyl, the n-amyl group, the i-amyl group, methyl ketonic oxygen ylmethyl, ethyl ketonic oxygen ylmethyl, methyl ketonic oxygen base ethyl, ethyl ketonic oxygen base ethyl, methyl carbonylamino methyl, ethyl carbonylamino ethyl, methyl carbonylamino ethyl, ethyl carbonylamino ethyl, the methoxycarbonyl methyl, the ethoxy carbonyl methyl, the methoxycarbonyl ethyl, trifluoromethoxy carbonyl methyl, ethoxy carbonyl ethyl, more preferably hydrogen atom, fluorine atom, the chlorine atom, methyl, trifluoromethyl, ethyl, the n-propyl group, the i-propyl group, methyl ketonic oxygen ylmethyl, ethyl ketonic oxygen ylmethyl, methyl carbonylamino ethyl, ethyl carbonylamino ethyl, the methoxycarbonyl methyl, trifluoromethoxy carbonyl methyl.
The part ring structure of A in above-mentioned formula (11) or the formula (12) is that (v), (Q v) means O (Sauerstoffatom), S (sulphur atom), SO (sulfinyl) or SO for above-mentioned formula (p) or formula for above-mentioned formula (p) and formula
2(alkylsulfonyl).(Q v) is preferably O (Sauerstoffatom) for formula (p) or formula.
To the R in the above-mentioned formula (13)
9, R
10, W, X, Y and Z describe.
R in the formula (13)
9And R
10Represent hydrogen atom, C respectively independently
1-6(this alkyl can be by halogen atom, C for alkyl
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom) or hydroxyl replace arbitrarily), C
6-14(this aryl can be by halogen atom, hydroxyl, nitro, cyano group, C for aryl
1-6(this alkyl can be by halogen atom, C for alkyl
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom) or hydroxyl replace arbitrarily), C
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom) replaces arbitrarily).
To the R in the formula (13)
9And R
10Each substituting group be specifically described.
As this C
1-6Alkyl, can list methyl, trifluoromethyl, methoxymethyl, ethyl, n-propyl group, i-propyl group, n-butyl, i-butyl, s-butyl, the tertiary butyl, 1-amyl group, 2-amyl group, 3-amyl group, i-amyl group, neo-pentyl, 2,2-dimethyl propyl, 1-hexyl, 2-hexyl, 3-hexyl, 1-methyl-n-amyl group, 1,1,2-trimethylammonium-n-propyl group, 1,2,2-trimethylammonium-n-propyl group and 3,3-dimethyl-n-butyl etc.
As this C
6-14Aryl can list phenyl, o-xenyl, m-xenyl, p-xenyl, 1-naphthyl, 2-naphthyl, 1-anthryl, 2-anthryl, 9-anthryl, 1-phenanthryl, 2-phenanthryl, 3-phenanthryl, 4-phenanthryl and 9-phenanthryl etc.
R in the formula (13)
9And R
10Preferable methyl, trifluoromethyl, ethyl, more preferably methyl.
W in the formula (13) represents hydrogen atom, hydroxyl, C
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom), halogen atom, C
1-4Alkyl or C
1-6Alkylsulfonamido (this alkyl and alkylsulfonamido can be replaced arbitrarily by halogen atom).
Each atom and each substituting group to the W in the formula (13) are specifically described.
As this C
1-6Alkoxyl group, can list methoxyl group, oxyethyl group, n-propoxy-, i-propoxy-, n-butoxy, i-butoxy, s-butoxy, t-butoxy, 1-amyl group oxygen base, 2-amyl group oxygen base, 3-amyl group oxygen base, i-amyl group oxygen base, neo-pentyl oxygen base, 2,2-dimethyl propoxy-, 1-hexyl oxygen base, 2-hexyl oxygen base, 3-hexyl oxygen base, 1-methyl-n-amyl group oxygen base, 1,1,2-trimethylammonium-n-propoxy-, 1,2,2-trimethylammonium-n-propoxy-and 3,3-dimethyl-n-butoxy etc.
As this halogen atom, can list fluorine atom, chlorine atom, bromine atoms and iodine atom,
As this C
1-4Alkyl can list methyl, trifluoromethyl, ethyl, n-propyl group, i-propyl group, n-butyl, i-butyl, s-butyl and the tertiary butyl etc.,
As this C
1-6Alkylsulfonamido can list methylsulfonyl amido, fluoroform sulfoamido, ethane sulphonamide base, n-propane sulfoamido, i-propane sulfoamido, n-butane sulfoamido, i-butane sulfoamido, s-butane sulfoamido, t-butane sulfoamido, 1-pentane sulfoamido, 2-pentane sulfoamido, 3-pentane sulfoamido, i-pentane sulfoamido, neopentane sulfoamido, t-pentane sulfoamido, 1-hexane sulfoamido, 2-hexane sulfoamido and 3-hexane sulfoamido etc.
W in the formula (13) is preferably hydrogen atom, hydroxyl, fluorine atom, chlorine atom, bromine atoms, methyl, trifluoromethyl, ethyl, methoxyl group, oxyethyl group, n-propoxy-, i-propoxy-, methylsulfonyl amido, fluoroform sulfoamido, ethane sulphonamide base, n-propane sulfoamido, i-propane sulfoamido, n-butane sulfoamido, more preferably hydrogen atom, hydroxyl, fluorine atom, methyl, trifluoromethyl, ethyl, methoxyl group, methylsulfonyl amido, fluoroform sulfoamido.
X in the formula (13) represents NR
20, N represents nitrogen-atoms,
R
20Expression hydrogen atom or C
1-4Alkyl.
To the R among the X of formula (13)
20Each substituting group be specifically described.
As this C
1-4Alkyl can list methyl, ethyl, n-propyl group, i-propyl group, n-butyl, i-butyl, s-butyl and the tertiary butyl etc.
R among the X of formula (13)
20Be preferably hydrogen atom, methyl, ethyl.
Y in the formula (13) is Direct Bonding, SO (sulfinyl) or SO
2(alkylsulfonyl) is preferably Direct Bonding and SO
2
Z in the formula (13) represents C
1-4Alkyl (this C
1-4Alkyl can (this phenyl can be by C by 1～5 halogen atom or phenyl
1-4Alkyl replaces arbitrarily) replace arbitrarily) or phenyl (this phenyl can be by C
1-4Alkyl replaces arbitrarily).
Each substituting group to the Z in the formula (13) is specifically described.
As this C
1-4Alkyl can list methyl, trifluoromethyl, ethyl, n-propyl group, i-propyl group, n-butyl, i-butyl, s-butyl and the tertiary butyl etc.
Z in the formula (13) is preferably methyl, trifluoromethyl, ethyl, n-propyl group, i-propyl group, phenyl.
When using the optical activity titanium complex shown in any one of above-mentioned formula (1), formula (1 '), formula (2), formula (2 '), formula (3), formula (3 '), formula (4) and formula (4 ') as catalyzer, the usage quantity of this optical activity titanium complex, with respect to the chromene compounds shown in formula (10), formula (11), formula (12) or the formula (13), in the scope of 0.001～100 mole of %, preferably in the scope of 0.01～20 mole of %, more preferably in the scope of 0.3～5 mole of %.
When using the optical activity titanium complex shown in any one of above-mentioned formula (1), formula (1 '), formula (2), formula (2 '), formula (3), formula (3 '), formula (4) and formula (4 ') as catalyzer, the solvent that uses in the asymmetric epoxidation reaction, organic solvent as non-proton property, be halogen series solvent, aromatic hydrocarbons series solvent, ester series solvent, ether series solvent or nitrile series solvent, as the organic solvent of protic, be pure series solvent.As the halogen series solvent, can list methylene dichloride, chloroform, 1,2-ethylene dichloride, chlorobenzene etc. as the aromatic hydrocarbons series solvent, can list benzene, toluene etc., as the ester series solvent, acetate ethyl ester etc. can be listed,, tetrahydrofuran (THF), ether etc. can be listed as the ether series solvent, as the nitrile series solvent, can list butyronitrile, propionitrile, acetonitrile etc.As pure series solvent, can list methyl alcohol, ethanol, i-propyl alcohol etc., and then can also list the mixture of above-mentioned solvent.In addition, when using the aqueous solution (aquae hydrogenii dioxidi) of hydrogen peroxide in this reaction, by mixing with the organic solvent that is not dissolved in water, organic phase is also separated with water sometimes, but the 2 such solvents that are mutually also can be used as reaction solvent of the present invention.Preferred solvent is the methylene dichloride, 1 as the organic solvent of non-proton property, the mixture of 2-ethylene dichloride, chlorobenzene, toluene, acetate ethyl ester or these solvents.
As manufacturing operation, as long as add chromene compounds, optical activity titanium complex, oxygenant in organic solvent, reaction is just carried out.As the interpolation order, preferably in the solution that contains organic solvent, chromene compounds, optical activity titanium complex, add oxygenant.
As the concrete example of the oxygenant that uses in the reaction, can list the mixture of iodosobenzene, clorox, metachloroperbenzoic acid, Oxone (E.I.Du Pont Company's registered trademark), aquae hydrogenii dioxidi, urea-hydrogen peroxide adduct (UHP), azepine oxygen triatomic ring (oxaziridine), N-methylmorpholine oxide compound (NMO), tertbutyl peroxide (TBHP), cumene hydroperoxide (CHP) and these oxygenants.Wherein, the mixture of preferred aquae hydrogenii dioxidi, urea-hydrogen peroxide adduct (UHP) and these oxygenants.Oxygenant is the concentration under the situation of aquae hydrogenii dioxidi, can list the scope of 1～100% (weight %), is preferably the scope of 5～60% (weight %).
As the usage quantity of the oxygenant that uses in the reaction, the chromene compounds with respect to shown in formula (10), formula (11), formula (12) or the formula (13) can list 1～10 normal scope, preferred 1～3 normal scope.
As the addition means of oxygenant, except adding in the lump, can also list portion-wise addition and interpolation continuously.
Under the situation of adding continuously, interpolation speed is the scope that sharply do not rise of the interior temperature in reaction solvent system preferably, specifically, and preferred 0.01～40000 normal scope per hour, more preferably 0.05～0.3 normal scope per hour.In addition, portion-wise addition is the method that the oxygenant that will use divides p (p for integer) arbitrarily interpolation.Five equilibrium can be in batches, also non-five equilibrium, the scope of p preferred 2～100 can be.
Temperature of reaction can list-78 ℃～solvent refluxing temperature, the scope of perhaps employed solvent melting temperature～solvent refluxing temperature, preferred-20～50 ℃ scope, more preferably 0～35 ℃ scope.
Pressure in the reaction system can list the scope of 10kPa～1100kPa, preferred 15kPa～200kPa.By pressurization, react under the high temperature of solvent refluxing temperature that can be when being higher than normal pressure.
In the process of reacting, can append the optical activity titanium complex of interpolation as catalyzer, shorten the reaction times.In addition, can append the interpolation oxygenant, shorten the reaction times.
After reaction finishes, carry out distillation procedure, silica gel column chromatography, separatory extracting operation, recrystallization operation or combination aforesaid operations, carry out separation and purification, obtain the active chromene oxide compound of objective optics.
The optical purity of the optically active chromene oxide compound that is obtained can be passed through optical activity efficient liquid phase chromatographic analysis, optical activity gas chromatographic analysis or angle-of-rotation measuring etc., analyzes.
Be described in detail below by embodiment, but the invention is not restricted to this.
In addition, in the optically active chromene oxide compound among the embodiment, also there is the compound of the absolute configuration of not distinguishing asymmetric carbon.About these compounds, asymmetric carbon among the figure and the absolute configuration souvenir in the compound name have asterisk (*), and the record of presentation graphs and compound name is the absolute configuration souvenir of supposition.
(B) and (C) synthetic of optical activity titanium Salalen complex compound (A)
The optical activity titanium Salalen complex compound (A) that uses among the embodiment (B) and (C), according to non-patent literature 8 (Angew.Chem.Int.Ed. (2005), 44,4935-4939.) Ji Zai method manufacturing.
Following such acquisition of optical activity titanium Salan complex compound (D) shown in the following formula.
Salan part (42 ')
In the methylene dichloride reaction solvent of Salan part (42 '), under nitrogen atmosphere,,, add 1.1 moles titanium tetraisopropylate [Ti (Oi-Pr) with respect to 1 mole of Salan part (42 ') at 25～28 ℃
4], stirred 5 hours, add water at 25～28 ℃ then, stirring reaction solution is 12 hours then.Then, heat up in a steamer the dereaction solvent, it is biological to obtain thick one-tenth, and it is carried out the recrystallization operation with methylene dichloride, obtains optical activity titanium complex (D).
The yellowish white solid
MS(CSI)＝1082，2163
Optical activity titanium Salan complex compound (E) and (F) also obtains with manufacture method same as described above.
Embodiment 1
(3S, 4S)-6-ethanamide-3,4-epoxy-3,4-dihydro-2,2-dimethyl-7-nitro-2H-1-chromene (compound (I)) synthetic
At 28 ℃, in the dichloromethane solution (3mL) of optical activity titanium Salalen complex compound (B) (38mg, 0.021mmol) (is 1.0 moles of % with respect to matrix), add 6-ethanamide-2,2-dimethyl-7-nitro-2H-1-chromene (0.54g, 2.1mmol).Stirring reaction solution on one side, on one side with 10 hours 28 ℃ of interpolation 7.5% aquae hydrogenii dioxidis (1.4g, 3.1mmol).With interpolation time opening of 7.5% aquae hydrogenii dioxidi as the reaction time opening, the reaction beginning after 14 hours 28 ℃ add 7.5% aquae hydrogenii dioxidis (0.1g, 0.2mmol), and then 28 ℃ continue to stir 19 hours that calculate from the reaction time opening till.After reaction finishes, in reaction solution, add methylene dichloride (6mL) and distilled water (6mL), with the organic phase separatory, and then will be from the organic phase merging of water extraction with methylene dichloride (6mL), with column chromatography spissated thick resultant is made with extra care, obtain the compound (I) (0.49g, yield 86% is more than the optical purity 99.9%ee) of yellow powder shape.
Analysis condition: chromatographic column name CHIRALPAK OJ-RH, elutriant acetonitrile/methanol/0.01M sodium chloride aqueous solution=1/3/5 (v/v/v), flow 1.5mL/min, 40 ℃ of column temperatures, the resultant of this reaction of retention time: 15.9 minutes (3S, 4S), enantiomer: (3R 4R), measured wavelength 242nm. in 11.7 minutes
1H-NMR(CDCl
3)δ；1.27(s，3H)，1.59(s，3H)，2.28(s，3H)，3.55(d，J＝4.1Hz，1H)，3.97(d，J＝4.1Hz，1H)，7.64(s，1H)，8.79(s，1H)，10.10(br，1H)
Embodiment 2
(3R, 4R)-6-ethanamide-3,4-epoxy-3,4-dihydro-2,2-dimethyl-7-nitro-2H-1-chromene (compound (II)) synthetic
30 ℃ to optical activity titanium Salan complex compound (E) (25.6mg, 0.021mmol) (with respect to matrix, be 1.0 moles of %) dichloromethane solution (3mL) in add 6-ethanamide-2,2-dimethyl-7-nitro-2H-1-chromene (537.4mg, 2.1mmol).Stirring reaction solution on one side, on one side with 1 second 30 ℃ of interpolation 30% aquae hydrogenii dioxidis (302.7mg, 2.7mmol).Then, continue to stir 7 hours at 30 ℃.After reaction finishes, methylene dichloride and distilled water are added in the reaction solution, organic phase is carried out separatory, and then will merge with the organic phase of methylene dichloride from the water extraction, make with extra care with column chromatography concentrating the thick resultant that obtains, obtain yellow powder shape compound (II) (0.53g, yield 93% is more than the optical purity 99.9%ee).Analysis condition: chromatographic column name CHIRALPAK OJ-RH, elutriant acetonitrile/methanol/0.01M sodium chloride aqueous solution=1/3/5 (v/v/v), flow 1.5mL/min, 40 ℃ of column temperatures, the resultant of this reaction of retention time: 13.4 minutes (3R, 4R), enantiomer: (3S 4S), measured wavelength 242nm. in 17.5 minutes
1H-NMR(CDCl
3)δ；1.27(s，3H)，1.59(s，3H)，2.28(s，3H)，3.55(d，J＝4.2Hz，1H)，3.97(d，J＝4.5Hz，1H)，7.63(s，1H)，8.79(s，1H)，10.09(br，1H)
Embodiment 3
(3S, 4S)-3,4-epoxy-3,4-dihydro-2,2-dimethyl-6-nitro-2H-1-chromene (compound (III)) synthetic
25 ℃ to optical activity titanium Salalen complex compound (B) (73mg 0.041mmol) adds 2 in the dichloromethane solution (8mL) of (with respect to matrix, being 2.0 moles of %), 2-dimethyl-6-nitro-2H-1-chromene (0.41g, 2.0mmol).Stirring reaction solution on one side, on one side with 2 seconds 25 ℃ of interpolation 30% aquae hydrogenii dioxidis (0.24g, 2.1mmol).The interpolation time opening of 30% aquae hydrogenii dioxidi is as the reaction time opening, the time opening begin to calculate from reaction 25 ℃ of stirrings 27 hours.Reaction finishes the back, adds methylene dichloride (6mL) and distilled water (6mL) in reaction solution, organic phase is carried out separatory, and then will merge from the organic phase that water extracts with methylene dichloride (6ml), spissated thick resultant is made with extra care with column chromatography, obtain white yellow powder shape compound (III) (0.43g, yield 97% is more than the optical purity 99.9%ee).Analysis condition: chromatographic column name CHIRALCEL OD-H, elutriant n-hexane/i-propyl alcohol=9/1 (v/v), flow 1.0mL/min, 40 ℃ of column temperatures, the resultant of this reaction of retention time: 9.6 minutes (3S, 4S), enantiomer: 8.4 minutes (3R, 4R), measure wavelength 300nm.
1H-NMR(CDCl
3)δ；1.33(s，3H)，1.63(s，3H)，3.57(d，J＝4.4Hz，1H)，4.00(d，J＝4.4Hz，1H)，6.89(d，J＝9.1Hz，1H)，8.15(dd，J＝9.1，2.8Hz，1H)，8.31(d，J＝2.8Hz，1H)
Embodiment 4
(3S, 4S)-3,4-epoxy-3,4-dihydro-2,2-dimethyl-6-nitro-2H-1-chromene (compound (III)) synthetic
(4.9mg 0.0080mmol) adds titanium tetraisopropylate [Ti (Oi-Pr) in the dichloromethane solution (0.3mL) of (with respect to matrix, being 4.0 moles of %) to the Salan part shown in the formula (43 ') at 20 ℃
4] (2.3mg, 0.0080mmol).After 1 hour, in above-mentioned solution, add 2 20 ℃ of stirrings, and 2-dimethyl-6-nitro-2H-1-chromene (41mg, 0.20mmol).With 30% aquae hydrogenii dioxidi (0.034g 0.30mmol) is divided into 3 five equilibriums, on one side stirring reaction solution, make the 1st time 20 ℃ of interpolations on one side, make and after 30 minutes, add for the 2nd time, make and after 1 hour, add for the 3rd time.With interpolation time of the 1st time 30% aquae hydrogenii dioxidi as the reaction time opening, after calculate from the reaction time opening 20 ℃ of stirrings 24 hours, with the reaction solution sampling, with HPLC analytical reaction transformation efficiency.Transformation efficiency to compound (III) is more than 99%, and optical purity is 99%ee.
Analysis condition: chromatographic column name CHIRALPAKAD-RH carries out 3 and connects dress, elutriant: acetonitrile/20mM (pH8) phosphoric acid buffer=6/4 (v/v), flow: 1.0mL/min, 40 ℃ of column temperatures, the resultant of this reaction of retention time: 15.8 minutes (3S, 4S), enantiomer: 12.6 minutes (3R, 4R), measure wavelength: 330nm.
Embodiment 5
(3R, 4R)-3,4-epoxy-3,4-dihydro-2,2-dimethyl-6-nitro-2H-1-chromene (compound (IV)) synthetic
To optical activity titanium Salan complex compound (E) (48mg 0.040mmol) in the dichloromethane solution (6mL) of (with respect to matrix, being 2.0 moles of %), adds 2 at 20 ℃, 2-dimethyl-6-nitro-2H-1-chromene (0.41g, 2.0mmol).With 30% aquae hydrogenii dioxidi (0.24g 2.1mmol) is divided into 3 five equilibriums, on one side stirring reaction solution, make the 1st time 20 ℃ of interpolations on one side, make and after 30 minutes, add for the 2nd time, make and after 1 hour, add for the 3rd time.The interpolation time of the 1st time 30% aquae hydrogenii dioxidi is as the reaction time opening, after calculate from the reaction time opening 20 ℃ of stirrings 24 hours, in reaction solution, add methylene dichloride (5mL) and distilled water (5mL), organic phase is carried out separatory, and then will merge from the organic phase that 2 extractions of aqueous phase obtain with methylene dichloride (5mL, 3mL), spissated thick resultant is made with extra care with column chromatography, obtain white yellow powder shape compound (IV) (0.41g, yield 94% is more than the optical purity 99.9%ee).Analysis condition: chromatographic column name CHIRALPAK AD-RH carries out 3 and connects dress, elutriant: acetonitrile/20mM (pH8) phosphoric acid buffer=6/4 (v/v), flow: 1.0mL/min, 40 ℃ of column temperatures, the resultant of this reaction of retention time: 12.6 minutes (3R, 4R), enantiomer: 15.8 minutes (3S, 4S), measure wavelength: 330nm.
1H-NMR(CDCl
3)δ；1.33(s，3H)，1.62(s，3H)，3.58(d，J＝4.4Hz，1H)，4.00(d，J＝4.4Hz，1H)，6.89(d，J＝8.6Hz，1H)，8.14(dd，J＝8.6，3.0Hz，1H)，8.30(d，J＝3.0Hz，1H)
Embodiment 6
(3R, 4R)-3,4-epoxy-3,4-dihydro-2,2-dimethyl-6-nitro-2H-1-chromene (compound (IV)) synthetic
In the dichloromethane solution (8mL) of optical activity titanium Salalen complex compound (A) (73mg, 0.041mmol) (, being 2.0 moles of %) with respect to matrix, add 2 at 25 ℃, 2-dimethyl-6-nitro-2H-1-chromene (0.41g, 2.0mmol).Stirring reaction solution on one side, on one side with 2 seconds 25 ℃ of interpolation 30% aquae hydrogenii dioxidis (0.24g, 2.1mmol).Continue to stir at 25 ℃ then, with interpolation time opening of 30% aquae hydrogenii dioxidi as the reaction time opening, the reaction beginning is after 8 hours, with the reaction solution sampling, with HPLC analytical reaction transformation efficiency.Transformation efficiency to compound (IV) is more than 99%, and optical purity is 96%ee.
Analysis condition: chromatographic column name CHIRALPAK AD-RH, elutriant: acetonitrile/20mM (pH8) phosphoric acid buffer=6/4 (v/v), flow: 1.0mL/min, 40 ℃ of column temperatures, the resultant of this reaction of retention time: 5.2 minutes (3R, 4R), enantiomer: (3S 4S), measured wavelength: 330nm. in 6.1 minutes
Embodiment 7
(3S
*, 4S
*)-3,4-epoxy-3,4-dihydro-2,2-dimethyl-7-nitro-6-methoxyl group-2H-1-chromene is (in the compound (V)
*Synthesizing expression relative configuration)
Perhaps
To optical activity titanium Salalen complex compound (B) (71mg, 0.040mmol) (with respect to matrix, be 2.0 moles of %) dichloromethane solution (8mL) in, add 2 at 25 ℃, and 2-dimethyl-7-nitro-6-methoxyl group-2H-1-chromene (0.47g, 2.0mmol).Stirring reaction solution on one side, on one side with 2 seconds 25 ℃ of interpolation 30% aquae hydrogenii dioxidis (0.24g, 2.1mmol).With interpolation time opening of 30% aquae hydrogenii dioxidi as the reaction time opening, reaction beginning back continues to stir 19 hours at 25 ℃.Reaction finishes the back, adds methylene dichloride (3mL) and distilled water (3mL) in reaction solution, organic phase is carried out separatory, and then will merge from the organic phase that the aqueous phase extraction obtains with methylene dichloride (3mL), spissated thick resultant is made with extra care with column chromatography, obtain yellow oily compound (V) (0.50g, yield 99% is more than the optical purity 99.9%ee).Analysis condition: chromatographic column name CHIRALPAK AD-RH carries out 3 and connects dress, elutriant: acetonitrile/20mM (pH8) phosphoric acid buffer=6/4 (v/v), flow: 0.8mL/min, 40 ℃ of column temperatures, the resultant of this reaction of retention time: 12.1 minutes, enantiomer: 11.3 minutes, measure wavelength: 225nm.
1H-NMR(CDCl
3)δ；1.26(s，3H)，1.59(s，3H)，3.53(d，J＝4.4Hz，1H)，3.90(d，J＝4.4Hz，1H)，3.95(s，3H)，7.08(s，1H)，7.33(s，1H)
Embodiment 8
(3S
*, 4S
*)-3,4-epoxy-3,4-dihydro-2,2-dimethyl-7-nitro-6-methoxyl group-2H-1-chromene is (in the compound (V)
*Synthesizing expression relative configuration)
(14mg 0.020mmol) in the dichloromethane solution (0.9mL) of (with respect to matrix, being 4.0 moles of %), adds titanium tetraisopropylate [Ti (Oi-Pr) at 20 ℃ to the Salan part shown in the formula (41 ')
4] (5.7mg, 0.020mmol).After 1 hour, add 2 20 ℃ of stirrings, and 2-dimethyl-7-nitro-6-methoxyl group-2H-1-chromene (0.118g, 0.50mmol).With 30% aquae hydrogenii dioxidi (0.085g 0.75mmol) is divided into 3 five equilibriums, on one side stirring reaction solution, carry out the 1st time at 20 ℃ on one side and add, make and after 30 minutes, add for the 2nd time, make and after 1 hour, add for the 3rd time.With interpolation time of the 1st time 30% aquae hydrogenii dioxidi as the reaction time opening, reaction beginning back 20 ℃ stir 24 hours after, with the reaction solution sampling, with HPLC analytical reaction transformation efficiency.Transformation efficiency to compound (V) is more than 99%, and optical purity is 99%ee.Analysis condition: chromatographic column name CHIRALPAK AD-RH carries out 3 and connects dress, elutriant: acetonitrile/20mM (pH8) phosphoric acid buffer=6/4 (v/v), flow: 0.5mL/min, 40 ℃ of column temperatures, the resultant of this reaction of retention time: 18.3 minutes, enantiomer: 17.5 minutes, measure wavelength: 225nm.
Embodiment 9
(3R
*, 4R
*)-3,4-epoxy-3,4-dihydro-2,2-dimethyl-7-nitro-6-methoxyl group-2H-1-chromene (compound (V ') in
*Synthesizing expression relative configuration)
To optical activity titanium Salan complex compound (E) (48mg, 0.040mmol) in the dichloromethane solution (7mL) of (, being 2.0 moles of %), add 2 at 25 ℃ with respect to matrix, 2-dimethyl-7-nitro-6-methoxyl group-2H-1-chromene (0.47g, 2.0mmol).With 30% aquae hydrogenii dioxidi (0.24g 2.1mmol) is divided into 3 five equilibriums, on one side stirring reaction solution, carry out the 1st time at 20 ℃ on one side and add, make and after 30 minutes, add for the 2nd time, make and after 1 hour, add for the 3rd time.The interpolation time of the 1st time 30% aquae hydrogenii dioxidi is as the reaction time opening, reaction beginning back 20 ℃ stir 24 hours after, methylene dichloride (5mL) and distilled water (5mL) are added in the reaction solution, organic phase is carried out separatory, and then will merge from the organic phase that 2 extractions of water obtain with methylene dichloride (5mL, 3mL), spissated thick resultant is made with extra care with column chromatography, and acquisition yellow oily compound (V ') (0.48g, yield 96% is more than the optical purity 99.9%ee).
Analysis condition: chromatographic column name CHIRALPAKAD-RH carries out 3 and connects dress, elutriant: acetonitrile/20mM (pH8) phosphoric acid buffer=6/4 (v/v), flow: 0.5mL/min, 40 ℃ of column temperatures, the resultant of this reaction of retention time: 17.5 minutes, enantiomer: 18.3 minutes, measure wavelength: 225nm.
1H-NMR(CDCl
3)δ；1.26(s，3H)，1.58(s，3H)，3.54(d，J＝4.5Hz，1H)，3.91(d，J＝4.5Hz，1H)，3.95(s，3H)，7.09(s，1H)，7.32(s，1H)
Embodiment 10
(3R
*, 4R
*)-3,4-epoxy-3,4-dihydro-2,2-dimethyl-7-nitro-6-methoxyl group-2H-1-chromene (compound (V ') in
*Synthesizing expression relative configuration)
To optical activity titanium Salalen complex compound (A) (71mg, 0.040mmol) in the dichloromethane solution (8mL) of (, being 2.0 moles of %), add 2 at 25 ℃ with respect to matrix, 2-dimethyl-7-nitro-6-methoxyl group-2H-1-chromene (0.47g, 2.0mmol).Stirring reaction solution on one side, on one side with 2 seconds 25 ℃ of interpolation 30% aquae hydrogenii dioxidis (0.24g, 2.1mmol).With interpolation time opening of 30% aquae hydrogenii dioxidi as the reaction time opening, the reaction beginning is after 18 hours, with the reaction solution sampling, with HPLC analytical reaction transformation efficiency.Transformation efficiency to compound (V ') is more than 99%, and optical purity is 99%ee.
Analysis condition: chromatographic column name CHIRALPAK AD-RH carries out 3 and connects dress, elutriant: acetonitrile/20mM (pH8) phosphoric acid buffer=6/4 (v/v), flow: 0.8mL/min, 40 ℃ of column temperatures, the resultant of this reaction of retention time: 11.3 minutes, enantiomer: 12.1 minutes, measure wavelength: 225nm.
Embodiment 11
(3S
*, 4S
*)-3,4-epoxy-3,4-dihydro-2,2-dimethyl-7-nitro-2H-1-chromene is (in the compound (VI)
*Synthesizing expression relative configuration)
Perhaps
To optical activity titanium Salalen complex compound (B) (36mg 0.020mmol) in the dichloromethane solution (4mL) of (with respect to matrix, being 2.0 moles of %), adds 2 at 25 ℃, 2-dimethyl-7-nitro-2H-1-chromene (0.21g, 1.0mmol).Stirring reaction solution on one side, on one side with add for 2 seconds 30% aquae hydrogenii dioxidi (0.12g, 1.1mmol).With interpolation time opening of 30% aquae hydrogenii dioxidi as the reaction time opening, stirred 27 hours at 25 ℃ reaction beginning back.After reaction finishes, methylene dichloride (2mL) and distilled water (2mL) are added in the reaction solution, organic phase is carried out separatory, and then will merge from the organic phase that the aqueous phase extraction obtains with methylene dichloride (2mL), spissated thick resultant is made with extra care with column chromatography, obtain yellow powder shape compound (VI) (0.43g, yield 99%, optical purity 99.4%ee).
Analysis condition: chromatographic column name CHIRALPAK AD-RH, elutriant: acetonitrile/20mM (pH8) phosphoric acid buffer=6/4 (v/v), flow: 1.0mL/min, 40 ℃ of column temperatures, the resultant of this reaction of retention time: 9.2 minutes, enantiomer: 4.9 minutes, measure wavelength: 220nm.
1H-NMR(CDCl
3)δ；1.29(s，3H)，1.62(s，3H)，3.58(d，J＝4.4Hz，1H)，3.97(d，J＝4.4Hz，1H)，7.50(d，J＝8.3Hz，1H)，7.67(dd，J＝8.3，2.2Hz，1H)，7.80(d，J＝2.2Hz，1H)
Embodiment 12
(3S
*, 4S
*)-3,4-epoxy-3,4-dihydro-2,2-dimethyl-7-nitro-2H-1-chromene is (in the compound (VI)
*Synthesizing expression relative configuration)
To optical activity titanium Salan complex compound (F) (48mg 0.040mmol) in the dichloromethane solution (6mL) of (with respect to matrix, being 2.0 moles of %), adds 2 at 25 ℃, 2-dimethyl-7-nitro-2H-1-chromene (0.41g, 2.0mmol).With 30% aquae hydrogenii dioxidi (0.25g 2.2mmol) is divided into 3 five equilibriums, on one side stirring reaction solution, carry out the 1st time at 20 ℃ on one side and add, make and after 30 minutes, add for the 2nd time, make and after 1 hour, add for the 3rd time.With interpolation time of the 1st time 30% aquae hydrogenii dioxidi as the reaction time opening, stirred 24 hours at 20 ℃ reaction beginning back.Reaction finishes the back, methylene dichloride (5mL) and distilled water (5mL) is added in the reaction solution, organic phase is carried out separatory, and then will merge from the organic phase that 2 extractions of water obtain with methylene dichloride (5mL, 3mL), spissated thick resultant is made with extra care with column chromatography, obtain yellow crystal compound (VI) (0.44g, yield 98%, optical purity 99.9%ee).
Analysis condition: chromatographic column name CHIRALPAKAD-RH carries out 3 and connects dress, elutriant: acetonitrile/20mM (pH8) phosphoric acid buffer=6/4 (v/v), flow: 1.0mL/min, 40 ℃ of column temperatures, the resultant of this reaction of retention time: 25.2 minutes, enantiomer: 13.9 minutes, measure wavelength: 220nm.
1H-NMR(CDCl
3)δ；1.29(s，3H)，1.61(s，3H)，3.60(d，J＝4.5Hz，1H)，3.99(d，J＝4.5Hz，1H)，7.52(d，J＝8.3Hz，1H)，7.62(d，J＝2.1Hz，1H)，7.70(dd，J＝8.3，2.1Hz，1H)
Embodiment 13
(3R
*, 4R
*)-3,4-epoxy-3,4-dihydro-2,2-dimethyl-7-nitro-2H-1-chromene (compound (VI ') in
*Synthesizing expression relative configuration)
To optical activity titanium Salalen complex compound (A) (36mg 0.020mmol) in the dichloromethane solution (4mL) of (with respect to matrix, being 2.0 moles of %), adds 2 at 25 ℃, 2-dimethyl-7-nitro-2H-1-chromene (0.21g, 1.0mmol).Stirring reaction solution on one side, on one side with 2 seconds 25 ℃ of interpolation 30% aquae hydrogenii dioxidis (0.12g, 1.1mmol).Continue to stir at 25 ℃ then, with interpolation time opening of 30% aquae hydrogenii dioxidi as the reaction time opening, the reaction beginning after 24 hours with the reaction solution sampling, with HPLC analytical reaction transformation efficiency.Transformation efficiency to compound (VI ') is more than 99%, and optical purity is 99%ee.
Analysis condition: chromatographic column name CHIRALPAK AD-RH, elutriant: acetonitrile/20mM (pH8) phosphoric acid buffer=6/4 (v/v), flow: 1.0mL/min, 40 ℃ of column temperatures, the resultant of this reaction of retention time: 4.9 minutes, enantiomer: 9.2 minutes, measure wavelength: 220nm.
Embodiment 14
(3R
*, 4R
*)-3,4-epoxy-3,4-dihydro-2,2-dimethyl-7-nitro-2H-1-chromene (compound (VI ') in
*Synthesizing expression relative configuration)
To optical activity titanium Salan complex compound (E) (24mg 0.020mmol) in the dichloromethane solution (3mL) of (with respect to matrix, being 2.0 moles of %), adds 2 at 20 ℃, 2-dimethyl-7-nitro-2H-1-chromene (0.205g, 1.0mmol).With 30% aquae hydrogenii dioxidi (0.12g 1.1mmol) is divided into 3 five equilibriums, on one side stirring reaction solution, carry out the 1st time at 20 ℃ on one side and add, make and after 30 minutes, add for the 2nd time, make and after 1 hour, add for the 3rd time.The interpolation time of the 1st time 30% aquae hydrogenii dioxidi, the reaction beginning 20 ℃ of stirrings, then with the reaction solution sampling, was used HPLC analytical reaction transformation efficiency after 24 hours as the reaction time opening.Transformation efficiency to compound (VI ') is more than 99%, and optical purity is 99%ee.
Analysis condition: chromatographic column name CHIRALPAK AD-RH carries out 3 and connects dress, elutriant: acetonitrile/20mM (pH8) phosphoric acid buffer=6/4 (v/v), flow: 1.0mL/min, 40 ℃ of column temperatures, the resultant of this reaction of retention time: 13.9 minutes, enantiomer: 25.2 minutes, measure wavelength: 220nm.
Embodiment 15
(3S
*, 4S
*)-3,4-epoxy-6-fluoro-3,4-dihydro-2,2-dimethyl-8-nitro-2H-1-chromene is (in the compound (VII)
*Synthesizing expression relative configuration)
Perhaps
To optical activity titanium Salalen complex compound (B) (37mg 0.021mmol) in the dichloromethane solution (4mL) of (with respect to matrix, being 2.0 moles of %), adds 6-fluoro-2 at 25 ℃, 2-dimethyl-8-nitro-2H-1-chromene (0.23g, 1.0mmol).Stirring reaction solution on one side, on one side with 2 seconds 25 ℃ of interpolation 30% aquae hydrogenii dioxidis (0.12g, 1.1mmol).With interpolation time opening of 30% aquae hydrogenii dioxidi as the reaction time opening, stirred 29 hours at 25 ℃ reaction beginning back.Reaction finishes the back, methylene dichloride (2mL) and distilled water (2mL) is added in the reaction solution, organic phase is carried out separatory, and then will merge from the organic phase that the aqueous phase extraction obtains with methylene dichloride (2mL), spissated thick resultant is made with extra care with column chromatography, obtain yellow powder shape compound (VII) (0.23g, yield 94% is more than the optical purity 99.9%ee).Analysis condition: chromatographic column name CHIRALPAK AD-RH carries out 3 and connects dress, elutriant: acetonitrile/20mM (pH8) phosphoric acid buffer=6/4 (v/v), flow: 0.5mL/min, 40 ℃ of column temperatures, the resultant of this reaction of retention time: 17.4 minutes, enantiomer: 18.1 minutes, measure wavelength: 220nm.
1H-NMR(CDCl
3)δ；1.33(s，3H)，1.64(s，3H)，3.57(d，J＝4.4Hz，1H)，3.94(d，J＝4.4Hz，1H)，7.35(dd，J＝4.4，7.1Hz，1H)，7.56(dd，J＝4.4，7.9Hz，1H)
Embodiment 16
(3S
*, 4S
*)-3,4-epoxy-6-fluoro-2,2-dimethyl-8-nitro-2H-1-chromene is (in the compound (VII)
*Synthesizing expression relative configuration)
To the Salan part shown in the formula (44 ') (43mg, 0.080mmol) in the dichloromethane solution (1.7mL) of (, being 4.0 moles of %) with respect to matrix, 25 ℃ add titanium tetraisopropylates [Ti (Oi-Pr) 4] (11mg, 0.040mmol).After 1 hour, add 6-fluoro-2 20 ℃ of stirrings, and 2-dimethyl-8-nitro-2H-1-chromene (0.446g, 2.0mmol).With 30% aquae hydrogenii dioxidi (0.25g 2.2mmol) is divided into 3 five equilibriums, on one side stirring reaction solution, carry out the 1st time at 20 ℃ on one side and add, make and after 30 minutes, add for the 2nd time, make and after 1 hour, add for the 3rd time.With interpolation time of the 1st time 30% aquae hydrogenii dioxidi as the reaction time opening, stirred 40 hours at 20 ℃ reaction beginning back.After reaction finishes, methylene dichloride (5mL) and distilled water (5mL) are added in the reaction solution, organic phase is carried out separatory, and then will merge from the organic phase that 2 extractions of water obtain with methylene dichloride (5mL, 3mL), spissated thick resultant is made with extra care with column chromatography, obtain yellow oily compound (VII) (optical purity is more than the 99.9%ee for 0.43g, yield 90%).
Analysis condition: chromatographic column name CHIRALPAK AD-RH carries out 3 and connects dress, elutriant: acetonitrile/20mM (pH8) phosphoric acid buffer=6/4 (v/v), flow: 0.5mL/min, 40 ℃ of column temperatures, the resultant of this reaction of retention time: 16.8 minutes, enantiomer: 17.3 minutes, measure wavelength: 220nm.
1H-NMR(CDCl
3)δ；1.33(s，3H)，1.63(s，3H)，3.60(d，J＝4.5Hz，1H)，3.98(d，J＝4.5Hz，1H)，7.38(dd，J＝3.0，7.4Hz，1H)，7.54(dd，J＝3.0，7.4Hz，1H)
Embodiment 17
(3R
*, 4R
*)-3,4-epoxy-6-fluoro-3,4-dihydro-2,2-dimethyl-8-nitro-2H-1-chromene (compound (VII ') in
*Synthesizing expression relative configuration)
To optical activity titanium Salalen complex compound (A) (37mg 0.021mmol) in the dichloromethane solution (4mL) of (with respect to matrix, being 2.0 moles of %), adds 6-fluoro-2 at 25 ℃, 2-dimethyl-8-nitro-2H-1-chromene (0.23g, 1.0mmol).On one side stirring reaction solution used for 2 seconds on one side, 25 ℃ of interpolation 30% aquae hydrogenii dioxidis (0.12g, 1.1mmol).With interpolation time opening of 30% aquae hydrogenii dioxidi as the reaction time opening, the reaction beginning is after 3 hours, with the reaction solution sampling, with HPLC analytical reaction transformation efficiency.Transformation efficiency to compound (VII ') is 76%, and optical purity is 99%ee.
Analysis condition: chromatographic column name CHIRALPAK AD-RH carries out 3 and connects dress, elutriant: acetonitrile/20mM (pH8) phosphoric acid buffer=6/4 (v/v), flow: 0.5mL/min, 40 ℃ of column temperatures, the resultant of this reaction of retention time: 18.1 minutes, enantiomer: 17.4 minutes, measure wavelength: 220nm.
Embodiment 18
(3R
*, 4R
*)-3,4-epoxy-6-fluoro-3,4-dihydro-2,2-dimethyl-8-nitro-2H-1-chromene (compound (VII ') in
*Synthesizing expression relative configuration)
To optical activity titanium Salan complex compound (E) (24mg 0.020mmol) in the dichloromethane solution (3mL) of (with respect to matrix, being 2.0 moles of %), adds 6-fluoro-2 at 20 ℃, 2-dimethyl-8-nitro-2H-1-chromene (0.23g, 1.0mmol).With 30% aquae hydrogenii dioxidi (0.12g 1.1mmol) is divided into 3 five equilibriums, on one side stirring reaction solution, carry out the 1st time at 20 ℃ on one side and add, make and after 30 minutes, add for the 2nd time, make and after 1 hour, add for the 3rd time.With interpolation time of the 1st time 30% aquae hydrogenii dioxidi as the reaction time opening, 20 ℃ stir 24 hours after, with the reaction solution sampling, with HPLC analytical reaction transformation efficiency.Transformation efficiency to compound (VII ') is 96%, and optical purity is more than the 99%ee.
Analysis condition: chromatographic column name CHIRALPAK AD-RH carries out 3 and connects dress, elutriant: acetonitrile/20mM (pH8) phosphoric acid buffer=6/4 (v/v), flow: 0.5mL/min, 40 ℃ of column temperatures, the resultant of this reaction of retention time: 17.3 minutes, enantiomer: 16.8 minutes, measure wavelength: 220nm.
Embodiment 19
(3R
*, 4R
*)-(3,4-epoxy-2,2,9-trimethylammonium-3,4-dihydro-2H-pyrans be [2,3-g] quinoline-7-yl also)-the methyl acetic acid ester (compound (VIII ') in
*Synthesizing expression relative configuration)
Perhaps
In the dichloromethane solution (3mL) of optical activity titanium Salalen complex compound (A) (71mg, 0.040mmol) (, being 1.9 moles of %), add (2 at 28 ℃ with respect to matrix, 2,9-trimethylammonium-2H-pyrans is [2,3-g] quinoline-7-yl also)-the methyl acetic acid ester (0.61g, 2.1mmol).Stirring reaction solution on one side, on one side with 10 hours 28 ℃ of interpolation 7.5% aquae hydrogenii dioxidis (1.4g, 3.1mmol).With interpolation time opening of 7.5% aquae hydrogenii dioxidi as the reaction time opening, the reaction beginning after 12 hours 28 ℃ append add 7.5% aquae hydrogenii dioxidi (0.1g, 0.2mmol).Continued to stir 14 hours that calculate from the reaction time opening at 28 ℃ then.Reaction finishes the back, adds methylene dichloride (6mL) and distilled water (6mL) in reaction solution, organic phase is carried out separatory, and then will merge from the organic phase that water extracts with methylene dichloride (6ml), spissated thick resultant is made with extra care with column chromatography, acquisition yellow oily compound (VIII ') (0.65g, yield 99% is more than the optical purity 99.9%ee).
Analysis condition: chromatographic column name CHIRALPAK AD-RH, elutriant: acetonitrile/20mM (pH8) phosphoric acid buffer=6/4 (v/v), flow: 1.0mL/min, 40 ℃ of column temperatures, the resultant of this reaction of retention time: 3.9 minutes, enantiomer: 9.3 minutes, measure wavelength: 254nm.
1H-NMR(CDCl
3)δ；1.30(s，3H)，1.65(s，3H)，2.19(s，3H)，2.62(d，J＝0.8Hz，3H)，3.61(d，J＝4.4Hz，1H)，4.15(d，J＝4.4Hz，1H)，5.30(s，2H)，7.26(s，1H)，7.32(s，1H)，8.10(s，1H)
Embodiment 20
(3R
*, 4R
*)-(3,4-epoxy-2,2,9-trimethylammonium-3,4-dihydro-2H-pyrans be [2,3-g] quinoline-7-yl also)-methyl acetic acid ester (compound (VIII)) synthetic
To optical activity titanium Salan complex compound (D) (6.2mg, 0.006mmol) (with respect to matrix, be 5.0 moles of %) dichloromethane solution (1.2mL) in, add (2 at 28 ℃, 2,9-trimethylammonium-2H-pyrans is [2,3-g] quinoline-7-yl also)-methyl acetic acid ester (34.2mg, 0.12mmol), Yi Bian stir this reaction soln, on one side with 1 second 28 ℃ of interpolation 30% aquae hydrogenii dioxidis (8.5mg, 0.075mmol).With interpolation time opening of 30% aquae hydrogenii dioxidi as the reaction time opening, the reaction beginning is after 20 minutes, with 1 second 28 ℃ of interpolation 30% aquae hydrogenii dioxidis (8.5mg, 0.075mmol).Then, continue to stir, with the reaction solution sampling, use HPLC analytical reaction transformation efficiency after 3 hours at 28 ℃.Transformation efficiency to compound (VIII) is 80%, and optical purity is 99%ee.
Analysis condition: chromatographic column name CHIRALPAK AD-RH, elutriant: acetonitrile/20mM (pH8) phosphoric acid buffer=6/4 (v/v), flow: 1.0mL/min, 40 ℃ of column temperatures, the resultant of this reaction of retention time: 10.2 minutes, enantiomer: 4.1 minutes, measure wavelength: 254nm.
Embodiment 21
(3R
*, 4R
*)-(3,4-epoxy-2,2,9-trimethylammonium-3,4-dihydro-2H-pyrans be [2,3-g] quinoline-7-yl also)-the methyl acetic acid ester (compound (VIII ') in
*Synthesizing expression relative configuration)
(48mg is 0.040mmol) in the dichloromethane solution (4mL) of (with respect to matrix, being 2.0 moles of %) to optical activity titanium Salan complex compound (E), 20 ℃ of interpolations (2,2,9-trimethylammonium-2H-pyrans also [2,3-g] quinoline-7-yl)-the methyl acetic acid ester (0.595g, 2.0mmol).With 30% aquae hydrogenii dioxidi (0.34g 3.0mmol) is divided into 3 five equilibriums, on one side stirring reaction solution, carry out the 1st time at 20 ℃ on one side and add, make and after 30 minutes, add for the 2nd time, make and after 1 hour, add for the 3rd time.The interpolation time of the 1st time 30% aquae hydrogenii dioxidi continued to stir 24 hours that calculate from the reaction time opening at 20 ℃ as the reaction time opening then.Reaction finishes the back, methylene dichloride (5mL) and distilled water (5mL) is added in reaction solution, organic phase is carried out separatory, and then will merge from the organic phase that 2 extractions of water obtain with methylene dichloride (5mL, 3mL), spissated thick resultant is made with extra care with column chromatography, acquisition yellow powder shape compound (VIII ') (0.61g, yield 97%, optical purity 99.3%ee).
Analysis condition: chromatographic column name CHIRALPAK AD-RH carries out 3 and connects dress, elutriant: acetonitrile/20mM (pH8) phosphoric acid buffer=6/4 (v/v), flow: 1.0mL/min, 40 ℃ of column temperatures, the resultant of this reaction of retention time: 11.2 minutes, enantiomer: 26.6 minutes, measure wavelength: 320nm.
1H-NMR(CDCl
3)δ；1.30(s，3H)，1.65(s，3H)，2.19(s，d，J＝1.9Hz，3H)，2.60(s，3H)，3.60(dd，J＝4.5Hz，1.9Hz，1H)，4.14(d，J＝4.5Hz，1H)，5.30(s，2H)，7.25(s，1H)，7.31(s，1H)，8.10(s，1H)
Embodiment 22
(3S
*, 4S
*)-7-chloro-3,4-epoxy-2,2,9-trimethylammonium-3,4-dihydro-2H-pyrans be [2,3-g] quinoline (in the compound (IX) also
*Synthesizing expression relative configuration)
Perhaps
In the dichloromethane solution (2mL) of optical activity titanium Salan complex compound (F) (120mg, 0.10mmol) (, being 10 moles of %) with respect to matrix, add 7-chloro-2,2 at 20 ℃, 9-trimethylammonium-2H-pyrans also [2,3-g] quinoline (0.26g, 1.0mmol).With 30% aquae hydrogenii dioxidi (0.17g 1.5mmol) is divided into 3 five equilibriums, on one side stirring reaction solution, carry out the 1st time at 20 ℃ on one side and add, make and after 30 minutes, add for the 2nd time, make and after 1 hour, add for the 3rd time.With interpolation time of the 1st time 30% aquae hydrogenii dioxidi as the reaction time opening, reaction beginning back continues to stir 26 hours at 20 ℃.Reaction finishes the back, methylene dichloride (5mL) and distilled water (5mL) is added in the reaction solution, organic phase is carried out separatory, and then will merge from the organic phase that 2 extractions of aqueous phase obtain with methylene dichloride (5mL, 3mL), spissated thick resultant is made with extra care with column chromatography, obtain pale yellow powder compound (IX) (0.21g, yield 77% is more than the optical purity 99.9%ee).
Analysis condition: chromatographic column name CHIRALPAK AD-RH carries out 3 and connects dress, elutriant: acetonitrile/20mM (pH8) phosphoric acid buffer=6/4 (v/v), flow: 1.0mL/min, 40 ℃ of column temperatures, the resultant of this reaction of retention time: 42.1 minutes, enantiomer: 21.7 minutes, measure wavelength: 220nm.
1H-NMR(CDCl
3)δ；1.30(s，3H)，1.64(s，3H)，2.56(s，3H)，3.61(d，J＝4.2Hz，1H)，4.13(d，J＝4.2Hz，1H)，7.15(s，1H)，7.27(s，1H)，8.00(s，1H)
Embodiment 23
(3R
*, 4R
*)-7-chloro-3,4-epoxy-2,2,9-trimethylammonium-3,4-dihydro-2H-pyrans are also in [2,3-g] quinoline (compound (IX ')
*Synthesizing expression relative configuration)
(27mg 0.050mmol) in the dichloromethane solution (0.5mL) of (with respect to matrix, being 10 moles of %), adds titanium tetraisopropylate [Ti (Oi-Pr) at 20 ℃ to the Salan part shown in the formula (44)
4] (2.8mg, 0.010mmol).20 ℃ stir 1 hour after, add 7-chloro-2,2,9-trimethylammonium-2H-pyrans also [2,3-g] quinoline (0.130g, 0.50mmol) and methylene dichloride (1mL).With 30% aquae hydrogenii dioxidi (0.085g 0.75mmol) is divided into 3 five equilibriums, on one side stirring reaction solution, carry out the 1st time at 20 ℃ on one side and add, make and after 30 minutes, add for the 2nd time, make and after 1 hour, add for the 3rd time.The interpolation time of the 1st time 30% aquae hydrogenii dioxidi, stirred 45 hours at 20 ℃ reaction beginning back as the reaction time opening, then with the reaction solution sampling, with HPLC analytical reaction transformation efficiency.Transformation efficiency to compound (IX ') is more than 99%, and optical purity is 99%ee.
Analysis condition: chromatographic column name CHIRALPAK AD-RH carries out 3 and connects dress, elutriant: acetonitrile/20mM (pH8) phosphoric acid buffer=6/4 (v/v), flow: 1.0mL/min, 40 ℃ of column temperatures, the resultant of this reaction of retention time: 21.7 minutes, enantiomer: 42.1 minutes, measure wavelength: 220nm.
Embodiment 24
(3S
*, 4S
*)-3,4-epoxy-3,4-dihydro-2,2-dimethyl-7-bismethane sulfonamido-6-methoxyl group-2H-1-chromene is (in the compound (X)
*Synthesizing expression relative configuration)
Perhaps
To optical activity titanium Salan complex compound (F) (12mg, 0.010mmol) (with respect to matrix, be 2.0 moles of %) dichloromethane solution (1mL) in, add 2 at 20 ℃, and 2-dimethyl-7-bismethane sulfonamido-6-methoxyl group-2H-1-chromene (0.18g, 0.50mmol).With 30% aquae hydrogenii dioxidi (0.085g 0.75mmol) is divided into 3 five equilibriums, on one side stirring reaction solution, carry out the 1st time at 20 ℃ on one side and add, make and after 30 minutes, add for the 2nd time, make and after 1 hour, add for the 3rd time.With interpolation time of the 1st time 30% aquae hydrogenii dioxidi as the reaction time opening, stirred 30 hours at 20 ℃ reaction beginning back, then methylene dichloride (2mL) and distilled water (2mL) are added in the reaction solution, organic phase is carried out separatory, and then will merge from the organic phase that 2 extractions of water obtain with methylene dichloride (2mL, 1mL), spissated thick resultant is made with extra care with column chromatography, obtain white powder compound (X) (0.18g, yield 97.5%, optical purity 99%).
Analysis condition: chromatographic column name CHIRALPAK AD-RH carries out 3 and connects dress, elutriant: acetonitrile/20mM (pH8) phosphoric acid buffer=3/7 (v/v), flow: 1.0mL/min, 40 ℃ of column temperatures, the resultant of this reaction of retention time: 19.8 minutes, enantiomer: 18.6 minutes, measure wavelength: 320nm.
1H-NMR(CDCl
3)δ；1.26(s，3H)，1.55(s，3H)，3.35(s，3H)，3.42(s，3H)，3.49(d，J＝4.5Hz，1H)，3.88(s，3H)，3.88(d，J＝4.5Hz，1H)，6.77(s，1H)，7.00(s，1H)
Embodiment 25
(3R
*, 4R
*)-3,4-epoxy-3,4-dihydro-2,2-dimethyl-7-bismethane sulfonamido-6-methoxyl group-2H-1-chromene (compound (X ') in
*Synthesizing expression relative configuration)
To optical activity titanium Salan complex compound (E) (12mg, 0.010mmol) (with respect to matrix, be 2.0 moles of %) dichloromethane solution (1mL) in, add 2 at 20 ℃, and 2-dimethyl-7-bismethane sulfonamido-6-methoxyl group-2H-1-chromene (72mg, 0.20mmol).With 30% aquae hydrogenii dioxidi (0.034g 0.30mmol) is divided into 3 five equilibriums, on one side stirring reaction solution, carry out the 1st time at 20 ℃ on one side and add, make and after 30 minutes, add for the 2nd time, make and after 1 hour, add for the 3rd time.With interpolation time of the 1st time 30% aquae hydrogenii dioxidi as the reaction time opening, stirred 48 hours at 20 ℃ reaction beginning back, then with the reaction solution sampling, with HPLC analytical reaction transformation efficiency.Transformation efficiency to compound (X ') is 99%, and optical purity is 99%ee.
Analysis condition: chromatographic column name CHIRALPAK AD-RH carries out 3 and connects dress, elutriant: acetonitrile/20mM (pH8) phosphoric acid buffer=3/7 (v/v), flow: 1.0mL/min, 40 ℃ of column temperatures, the resultant of this reaction of retention time: 18.5 minutes, enantiomer: 20.0 minutes, measure wavelength: 320nm.
Embodiment 26
(3S
*, 4S
*)-3,4-epoxy-3,4-dihydro-2,2-dimethyl-7-bismethane sulfonamido-6-methoxyl group-2H-1-chromene (compound (X) in * represent relative configuration) synthetic
To optical activity titanium Salalen complex compound (C) (16mg, 0.010mmol) (with respect to matrix, be 2.0 moles of %) dichloromethane solution (0.5mL) in, add 2 at 20 ℃, and 2-dimethyl-7-bismethane sulfonamido-6-methoxyl group-2H-1-chromene (72mg, 0.20mmol).With 30% aquae hydrogenii dioxidi (0.034g 0.30mmol) is divided into 3 five equilibriums, on one side stirring reaction solution, carry out the 1st time at 20 ℃ on one side and add, make and after 30 minutes, add for the 2nd time, make and after 1 hour, add for the 3rd time.The interpolation time of the 1st time 30% aquae hydrogenii dioxidi, stirred 24 hours at 20 ℃ reaction beginning back as the reaction time opening, then with the reaction solution sampling, with HPLC analytical reaction transformation efficiency.Transformation efficiency to compound (X) is 83%, and optical purity is 99%ee.Analysis condition: chromatographic column name CHIRALPAKAD-RH carries out 3 and connects dress, elutriant: acetonitrile/20mM (pH8) phosphoric acid buffer=3/7 (v/v), flow: 1.0mL/min, 40 ℃ of column temperatures, the resultant of this reaction of retention time: 19.8 minutes, enantiomer: 18.6 minutes, measure wavelength: 320nm.
The industry utilizability
According to the present invention, can not use for the lock out operation that object is carried out optical segmentation, with High yield more than 90% obtains to have the optically active chromene oxygen of the above high-optical-purity of 99%ee The compound compound, can be fully with the weight of the effective benzopyran compounds of ARR treatment of opposing Want intermediate. Therefore, the present invention industrial be useful.
Claims (25)
1. the manufacture method of the optically active chromene oxide compound shown in formula (14), formula (15), formula (16) or the formula (17), it is characterized in that, optical activity titanium complex shown in any one of use formula (1), formula (1 '), formula (2), formula (2 '), formula (3), formula (3 '), formula (4) and formula (4 ') is as catalyzer, with the chromene compounds shown in formula (10), formula (11), formula (12) or the formula (13) in solvent, carry out asymmetric Epoxidation with oxygenant
(the R in formula (1), formula (1 '), formula (2), formula (2 '), formula (3), formula (3 '), formula (4) and the formula (4 ')
1Expression hydrogen atom, halogen atom, C
1-4Alkyl, C
1-4Alkoxyl group, C
6-12Aryloxy or C
6-22(this aryl can be by C for aryl
1-4Alkyl (this alkyl can be replaced arbitrarily by halogen atom), C
1-7Alkoxyl group or benzyl oxygen base replace arbitrarily, are optical activity or non-optical activity),
R
2Expression hydrogen atom, halogen atom, C
1-4Alkyl, C
1-4Alkoxyl group, C
6-12Aryloxy or C
6-18Aryl,
R
3Expression C
1-4Alkyl, C
6-18Aryl, perhaps, at 2 R
3Form under the situation of ring expression C together
3-5The group of divalence,
R
4Represent hydrogen atom, halogen atom, C respectively independently
1-4Alkyl, C
1-4Alkoxyl group, nitro or cyano group,
M represents TiJ
1J
2(at TiJ
1J
2In, Ti represents titanium atom, J
1And J
2Represent halogen atom, C respectively independently
1-4Alkoxyl group, perhaps J
1With J
2Represent Sauerstoffatom together, perhaps J
1With J
2Form ring together, expression is as the formula (5) of the group of divalence
(about the part-structure O-E-O in the formula, wherein, O represents Sauerstoffatom, in formula (1), as O-E-O, is represented by following formula (6); In formula (1 '),, represent by following formula (6 ') as O-E-O; In formula (2),, represent by following formula (7) as O-E-O; In formula (2 '),, represent by following formula (7 ') as O-E-O; In formula (3),, represent by following formula (8) as O-E-O; In formula (3 '),, represent by following formula (8 ') as O-E-O; In formula (4),, represent by following formula (9) as O-E-O; In formula (4 '), as O-E-O, by following formula (9 ') expression,
B represents 1～10 integer, R
1, R
2, R
3Same as described above with R4));
(the R in the formula (10)
5, R
6, R
7And R
8Represent hydrogen atom, cyano group, nitro, halogen atom, C respectively independently
1-4(this alkyl can be by halogen atom, hydroxyl, cyano group, nitro, C for alkyl
1-4Alkoxyl group, C
1-4Alkyl-carbonyl oxygen base, C
1-4Alkyl-carbonyl-amino, C
1-4Any replacement of alkoxy carbonyl (this alkoxyl group, alkyl-carbonyl oxygen base, alkyl-carbonyl-amino and alkoxy carbonyl can be replaced arbitrarily by halogen atom)), C
1-4(this alkoxyl group can be by halogen atom, hydroxyl, cyano group, nitro, C for alkoxyl group
1-4Alkoxyl group, C
1-4Alkyl-carbonyl oxygen base, C
1-4Alkyl-carbonyl-amino, C
1-4Any replacement of alkoxy carbonyl (this alkoxyl group, alkyl-carbonyl oxygen base, alkyl-carbonyl-amino and alkoxy carbonyl can be replaced arbitrarily by halogen atom)), C
1-4(this alkyl-carbonyl-amino can be by halogen atom, C for alkyl-carbonyl-amino
6-10Aryl (this C
6-10Aryl can be by halogen atom, hydroxyl, cyano group, nitro, C
1-4Alkyl or C
1-4Alkoxyl group replaces arbitrarily) replace arbitrarily), C
1-4Alkyl-carbonyl (N-C
1-4Alkyl) amino (this alkyl-carbonyl (N-alkyl) amino can be replaced arbitrarily by halogen atom), C
1-4Alkoxy carbonyl (this alkoxy carbonyl can be replaced arbitrarily by halogen atom), C
6-10(this aryl-amino-carbonyl can be by halogen atom, C for aryl-amino-carbonyl
1-4Alkyl, C
1-4Alkoxyl group, cyano group or nitro replace), C
6-10Aryl carbonyl (N-C
1-4It is alkyl) amino that (this aryl carbonyl (N-alkyl) amino can be by halogen atom, C
1-4Alkyl, C
1-4Alkoxyl group, cyano group or nitro replace), benzyloxycarbonyl group amino, formyl radical, formamyl, C
1-4Alkyl sulphonyl, C
6-10(this alkyl sulphonyl and aryl sulfonyl can be by halogen atom, C for aryl sulfonyl
1-4Alkyl, C
1-4Alkoxyl group, cyano group or nitro replace), sulfamyl, C
1-4Alkylsulfonamido, C
6-10(this alkylsulfonamido and aryl-sulfonyl amino can be by halogen atom, C for aryl-sulfonyl amino
1-4Alkyl, C
1-4Alkoxyl group, cyano group or nitro replace), two (C
1-4Alkyl sulfonyl) (alkyl sulfonyl of this pair (alkyl sulfonyl) imido grpup can be by halogen atom, C for imido grpup
1-4Alkyl, C
1-4Alkoxyl group, cyano group or nitro replace), two (C
6-10Arylsulfonyl) (arylsulfonyl of this pair (arylsulfonyl) imido grpup can be by halogen atom, C for imido grpup
1-4Alkyl, C
1-4Alkoxyl group, cyano group or nitro replace), [N, N '-(C
1-4Alkyl sulfonyl) (C
6-10Arylsulfonyl)] (alkyl sulfonyl and the arylsulfonyl that are somebody's turn to do [N, N '-(alkyl sulfonyl) (arylsulfonyl)] imido grpup can be by halogen atom, C for imido grpup
1-4Alkyl, C
1-4Alkoxyl group, cyano group or nitro replace);
R in the formula (10)
9And R
10Represent hydrogen atom, C respectively independently
1-6(this alkyl can be by halogen atom, C for alkyl
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom) or hydroxyl replace arbitrarily), C
6-14(this aryl can be by halogen atom, hydroxyl, nitro, cyano group, C for aryl
1-6(this alkyl can be by halogen atom, C for alkyl
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom) or hydroxyl replace arbitrarily) or C
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom) replaces arbitrarily);
R in formula (11) and the formula (12)
9And R
10Represent hydrogen atom, C respectively independently
1-6(this alkyl can be by halogen atom, C for alkyl
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom) or hydroxyl replace arbitrarily) or C
6-14(this aryl can be by halogen atom, hydroxyl, nitro, cyano group, C for aryl
1-6(this alkyl can be by halogen atom, C for alkyl
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom) or hydroxyl replace arbitrarily) or C
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom) replaces arbitrarily);
Part ring structure A in formula (11) and the formula (12) is 5,6 or 7 Yuans part-structures that ring is represented that partly form condensed ring with phenyl ring, and wherein, these 5,6 or 7 Yuans rings can be by h R
11Replace (wherein, R arbitrarily
11Be halogen atom, hydroxyl, C
1-6(this alkyl can be by halogen atom, hydroxyl, cyano group, amino, nitro, C for alkyl
1-4Alkoxyl group, C
1-4Alkyl-carbonyl oxygen base, C
1- 4Alkyl-carbonyl-amino or C
1-4Any replacement of alkoxy carbonyl (this alkoxyl group, alkyl-carbonyl oxygen base, alkyl-carbonyl-amino and alkoxy carbonyl can be replaced arbitrarily by halogen atom)), C
1-6(this alkoxyl group can be by halogen atom, hydroxyl, cyano group, amino, nitro, C for alkoxyl group
1-4Alkoxyl group, C
1-4Alkyl-carbonyl oxygen base, C
1-4Alkyl-carbonyl-amino or C
1-4Any replacement of alkoxy carbonyl (this alkoxyl group, alkyl-carbonyl oxygen base, alkyl-carbonyl-amino and alkoxy carbonyl can be replaced arbitrarily by halogen atom)), nitro, cyano group, formyl radical, formamido-, formamyl, sulfo group, sulfoamino-, sulfamyl, alkylsulfonyl, amino, carboxyl, C
1-6Alkylamino, two C
1-6Alkylamino, C
1 -6Alkyl-carbonyl-amino, C
1-6Alkylsulfonamido, C
6-14Aryl-sulfonyl amino, C
1-6Alkyl amino-carbonyl, two C
1-6Alkyl amino-carbonyl, C
1-6Alkyl-carbonyl, C
1-6Alkoxy carbonyl, C
1-6Alkyl sulphonyl, C
6-14Aryl sulfonyl or C
6-14Aryl carbonyl (this alkylamino, dialkyl amido, alkyl-carbonyl-amino, alkylsulfonamido, aryl-sulfonyl amino, alkyl amino-carbonyl, dialkyl amino carbonyl, alkyl-carbonyl, alkoxy carbonyl, alkyl sulphonyl, aryl sulfonyl and aryl carbonyl can be replaced arbitrarily by halogen atom); h is 1～6 integer; be under 2～6 the situation at h, R
11Can be the same or different), the constituting atom as ring can contain 1～3 Sauerstoffatom, nitrogen-atoms or sulphur atom alone or in combination, the number of intra-annular unsaturated link(age) comprises the unsaturated link(age) of the phenyl ring of condensation, is 1,2 or 3, the carbon atom that constitutes ring can be carbonyl or thiocarbonyl
X in the formula (13) represents NR
20(R
20Expression hydrogen atom or C
1-4Alkyl),
Y in the formula (13) represents Direct Bonding, SO or SO
2,
Z in the formula (13) represents C
1-4(this alkyl can (this phenyl can be by C by 1～5 halogen atom or phenyl for alkyl
1-4Alkyl replaces arbitrarily) replace arbitrarily) or phenyl (this phenyl can be by C
1 -4Alkyl replaces arbitrarily),
W in the formula (13) represents hydrogen atom, hydroxyl, C
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom), halogen atom, C
1-4Alkyl or C
1-6Alkylsulfonamido (this alkyl and alkylsulfonamido can be replaced arbitrarily by halogen atom),
R in the formula (13)
9And R
10Represent hydrogen atom, C respectively independently
1-6(this alkyl can be by halogen atom, C for alkyl
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom) or hydroxyl replace arbitrarily) or C
6-14(this aryl can be by halogen atom, hydroxyl, nitro, cyano group, C for aryl
1-6(this alkyl can be by halogen atom, C for alkyl
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom) or hydroxyl replace arbitrarily) or C
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom) replaces arbitrarily)),
(R in the formula
5, R
6, R
7, R
8, R
9, R
10, A, W, X, Y and Z be same as described above, the absolute configuration of the carbon atom that * is represented is (R) or (S)).
2. the manufacture method of optically active chromene oxide compound according to claim 1, it is characterized in that, use the optical activity titanium complex shown in any one of above-mentioned formula (1), formula (1 '), formula (2), formula (2 '), formula (3), formula (3 '), formula (4) and formula (4 ') as catalyzer, with the chromene compounds shown in the above-mentioned formula (10) in solvent, carry out asymmetric Epoxidation with oxygenant
R in the above-mentioned formula (10)
5And R
6Represent hydrogen atom, cyano group, nitro, halogen atom, C respectively independently
1-4(this alkyl can be by halogen atom, hydroxyl, cyano group, nitro, C for alkyl
1-4Alkoxyl group, C
1-4Alkyl-carbonyl oxygen base, C
1-4Alkyl-carbonyl-amino, C
1-4Any replacement of alkoxy carbonyl (this alkoxyl group, alkyl-carbonyl oxygen base, alkyl-carbonyl-amino and alkoxy carbonyl can be replaced arbitrarily by halogen atom)), C
1-4(this alkoxyl group can be by halogen atom, hydroxyl, cyano group, nitro, C for alkoxyl group
1-4Alkoxyl group, C
1-4Alkyl-carbonyl oxygen base, C
1-4Alkyl-carbonyl-amino, C
1-4Any replacement of alkoxy carbonyl (this alkoxyl group, alkyl-carbonyl oxygen base, alkyl-carbonyl-amino and alkoxy carbonyl can be replaced arbitrarily by halogen atom)), C
1-4Alkyl-carbonyl-amino (this alkyl-carbonyl-amino can be replaced arbitrarily by halogen atom), C
1-4Alkyl-carbonyl (N-C
1-4Alkyl) amino (this alkyl-carbonyl (N-alkyl) amino can be replaced arbitrarily by halogen atom) C
6-10Aryl carbonyl (N-C
1-4It is alkyl) amino that (this aryl carbonyl (N-alkyl) amino can be by halogen atom, C
1-4Alkyl, C
1-4Alkoxyl group, cyano group or nitro replace), formamyl, two (C
1-4Alkyl sulfonyl) (alkyl sulfonyl of this pair (alkyl sulfonyl) imido grpup can be by halogen atom, C for imido grpup
1-4Alkyl, C
1-4Alkoxyl group, cyano group or nitro replace), two (C
6-10Arylsulfonyl) (arylsulfonyl of this pair (arylsulfonyl) imido grpup can be by halogen atom, C for imido grpup
1-4Alkyl, C
1-4Alkoxyl group, cyano group or nitro replace) or [N, N '-(C
1-4Alkyl sulfonyl) (C
6-10Arylsulfonyl)] (alkyl sulfonyl and the arylsulfonyl that are somebody's turn to do [N, N '-(alkyl sulfonyl) (arylsulfonyl)] imido grpup can be by halogen atom, C for imido grpup
1-4Alkyl, C
1-4Alkoxyl group, cyano group or nitro replace),
R in the formula (10)
7Expression hydrogen atom, cyano group, nitro, two (C
1-4Alkyl sulfonyl) (alkyl sulfonyl of this pair (alkyl sulfonyl) imido grpup can be by halogen atom, C for imido grpup
1-4Alkyl, C
1 -4Alkoxyl group, cyano group or nitro replace), two (C
6-10Arylsulfonyl) (arylsulfonyl of this pair (arylsulfonyl) imido grpup can be by halogen atom, C for imido grpup
1-4Alkyl, C
1-4Alkoxyl group, cyano group or nitro replace) or [N, N '-(C
1-4Alkyl sulfonyl) (C
6-10Arylsulfonyl)] (alkyl sulfonyl and the arylsulfonyl that are somebody's turn to do [N, N '-(alkyl sulfonyl) (arylsulfonyl)] imido grpup can be by halogen atom, C for imido grpup
1-4Alkyl, C
1-4Alkoxyl group, cyano group or nitro replace),
R in the formula (10)
8Expression hydrogen atom, nitro or C
1-4Alkyl (this alkyl can be replaced arbitrarily by halogen atom),
R in the formula (10)
9And R
10Expression C
1-6Alkyl (this alkyl can be replaced arbitrarily by halogen atom).
3. the manufacture method of optically active chromene oxide compound according to claim 2, the R in the above-mentioned formula (10)
5And R
6Represent hydrogen atom, nitro, fluorine atom, methoxyl group, methyl carbonylamino or methyl carbonyl (N-ethyl) amino respectively independently, the R in the formula (10)
7Expression hydrogen atom, nitro or [two (C
1-4Alkyl sulfonyl) imines] base, the R in the formula (10)
8Expression hydrogen atom, nitro or trifluoromethyl, the R in the formula (10)
9And R
10The expression methyl.
4. the manufacture method of optically active chromene oxide compound according to claim 1, it is characterized in that, use the optical activity titanium complex shown in any one of above-mentioned formula (1), formula (1 '), formula (2), formula (2 '), formula (3), formula (3 '), formula (4) and formula (4 ') as catalyzer, with the chromene compounds shown in above-mentioned formula (11) or the formula (12) in solvent, carry out asymmetric Epoxidation with oxygenant
The part ring structure of A in above-mentioned formula (11) or the formula (12) is by formula (a), formula (b), formula (c), formula (d), formula (e), formula (f), formula (g), formula (h), formula (i), formula (j), formula (k), formula (l), formula (m), formula (n), formula (o), formula (p), formula (q), formula (r), formula (s), formula (t), formula (u), formula (v), formula (w), formula (x), formula (y), formula (z), formula (aa), formula (ab), formula (ac), formula (ad), formula (ae), formula (af), any one expression of formula (ag) and formula (ah)
(above-mentioned formula (a), formula (b), formula (e), formula (f), formula (g), formula (h), formula (i), formula (j), formula (k), formula (l), formula (m), formula (n), formula (p), formula (q), formula (v), the R in formula (w), formula (x), formula (ab), formula (ae), formula (af) and the formula (ag)
12And R
13Represent hydrogen atom, C respectively independently
1-6(this alkyl can be by halogen atom, C for alkyl
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom), amino, hydroxyl, C
6-14Aryl, C
2-9(this aryl and heteroaryl can be by q R for heteroaryl
18(R
18Expression and R
11Identical implication, q represents 1～3 integer, is under 2 or 3 the situation at q, R
18Can be the same or different) replace arbitrarily), C
1-6Alkyl amino-carbonyl, two C
1-6Alkyl amino-carbonyl, C
1-6Alkyl-carbonyl oxygen base, C
1-6Alkyl-carbonyl (this alkyl-carbonyl oxygen base and alkyl-carbonyl can be replaced arbitrarily by halogen atom), C
1-6Alkyl-carbonyl-amino, C
3-8Naphthene base carbonyl, C
1-6Alkoxy carbonyl, C
1-6Alkyl sulphonyl (this naphthene base carbonyl, alkoxy carbonyl and alkyl sulphonyl can be replaced arbitrarily by halogen atom), carboxyl, C
6-14Aryl carbonyl (this aryl carbonyl can be replaced arbitrarily by halogen atom) or C
2-9The heteroaryl carbonyl replaces arbitrarily), C
6-14Aryl, C
2-9(this aryl and heteroaryl can be by q R for heteroaryl
18(R
18Expression and R
11Identical implication, q represents 1～3 integer, is under 2 or 3 the situation at q, R
18Can be the same or different) replace arbitrarily), C
1-6Alkyl amino-carbonyl, two C
1-6Alkyl amino-carbonyl, C
1-6Alkyl-carbonyl, C
3-8Naphthene base carbonyl, C
1-6Alkoxy carbonyl, C
1-6Alkyl sulphonyl, C
6-14Aryl sulfonyl, C
2- 9(this aryl sulfonyl and heteroarylsulfonyl can be by q R for heteroarylsulfonyl
18(R
18Expression and R
11Identical implication, q represents 1～3 integer, is under 2 or 3 the situation at q, R
18Can be the same or different) replace arbitrarily), carboxyl, C
6-14Aryl carbonyl or C
2-9(this aryl carbonyl and heteroaryl carbonyl can be by q R for the heteroaryl carbonyl
18(R
18Expression and R
11Identical implication, q represents 1～3 integer, is under 2 or 3 the situation at q, R
18Can be the same or different) replace arbitrarily),
Above-mentioned formula (a), formula (b), formula (c), formula (d), formula (f), formula (g), formula (h), formula (j), formula (k), formula (m), formula (n), formula (o), formula (p), formula (q), formula (r), formula (s), formula (t), formula (u), formula (v), the R in formula (w), formula (y), formula (z), formula (aa), formula (ab), formula (ac), formula (ad), formula (ae) and the formula (af)
14, R
15, R
16And R
17Represent hydrogen atom, halogen atom, C respectively independently
1-6(this alkyl can be by halogen atom, C for alkyl
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom), amino, hydroxyl, C
6-14Aryl, C
2-9(this aryl and heteroaryl can be by r R for heteroaryl
19(R
19Expression and R
11Identical implication, r represents the implication identical with q) replace arbitrarily), C
1-6Alkyl amino-carbonyl, two C
1-6Alkyl amino-carbonyl, C
1-6Alkyl-carbonyl oxygen base, C
1-6Alkyl-carbonyl (this alkyl-carbonyl oxygen base and alkyl-carbonyl can be replaced arbitrarily by halogen atom), C
1-6Alkyl-carbonyl-amino, C
3-8Naphthene base carbonyl, C
1-6Alkoxy carbonyl, C
1-6Alkyl sulphonyl (this naphthene base carbonyl, alkoxy carbonyl and alkyl sulphonyl can be replaced arbitrarily by halogen atom), carboxyl, C
6-14Aryl carbonyl (this aryl carbonyl can be replaced arbitrarily by halogen atom) or C
2-9The heteroaryl carbonyl replaces arbitrarily), C
3-8(this cycloalkyl can be by halogen atom, C for cycloalkyl
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom), amino or hydroxyl replace arbitrarily), C
1-6(this alkoxyl group can be by halogen atom, C for alkoxyl group
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom), carboxyl, amino, hydroxyl, C
6-14Aryl or C
2-9(this aryl and heteroaryl can be by r R for heteroaryl
19(R
19Expression and R
11Identical implication, r represents the implication identical with q) replace arbitrarily) replace arbitrarily), C
1-6(this thio alkoxy can be by halogen atom, C for thio alkoxy
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom), carboxyl, hydroxyl, C
6-14Aryl or C
2- 9(this aryl and heteroaryl can be by r R for heteroaryl
19(R
19Expression and R
11Identical implication, r represents the implication identical with q) replace arbitrarily) replace arbitrarily), hydroxyl, C
6-14Aryl, C
2-9(this aryl and heteroaryl can be by r R for heteroaryl
19(R
19Expression and R
11Identical implication, r represents the implication identical with q) replace arbitrarily), C
1-6Alkyl-carbonyl oxygen base, nitro, cyano group, formyl radical, formamido-, amino, sulfo group, C
1-6Alkylamino, two C
1-6Alkylamino, C
6-14Arylamino, C
2-9(this arylamino and heteroaryl amino can be by r R for heteroaryl amino
19(R
19Expression and R
11Identical implication, r represents the implication identical with q) replace arbitrarily), C
1-6Alkyl-carbonyl-amino, C
1-6Alkylsulfonamido, formamyl, C
1-6Alkyl amino-carbonyl, two C
1-6Alkyl amino-carbonyl, C
1-6Alkyl-carbonyl, C
6-14Aryl carbonyl, C
2-9(this aryl carbonyl and heteroaryl carbonyl can be by r R for the heteroaryl carbonyl
19(R
19Expression and R
11Identical implication, r represents the implication identical with q) replace arbitrarily), C
1-6Alkoxy carbonyl, sulfamyl, C
1-6Alkyl sulphonyl, C
6-14Aryl sulfonyl, C
2-9(this aryl sulfonyl and heteroarylsulfonyl can be by r R for heteroarylsulfonyl
19(R
19Expression and R
11Identical implication, r represents the implication identical with q) replace arbitrarily), carboxyl or C
2-9(this heterocyclic radical can be by halogen atom, C for heterocyclic radical
1-6(this alkyl can be by halogen atom, C for alkyl
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom), amino, carboxyl or hydroxyl replace arbitrarily), C
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom), C
6-14Aryl, C
2-9(this aryl and heteroaryl can be by r R for heteroaryl
19(R
19Expression and R
11Identical implication, r represents the implication identical with q) replace arbitrarily), hydroxyl, nitro, cyano group, formyl radical, formamido-, amino, C
1-6Alkylamino, two C
1-6Alkylamino, C
1-6Alkyl-carbonyl-amino, C
1-6Alkylsulfonamido, formamyl, C
1-6Alkyl amino-carbonyl, two C
1-6Alkyl amino-carbonyl, C
1-6Alkyl-carbonyl, C
1-6Alkoxy carbonyl, sulfamyl, C
1-6Alkyl sulphonyl, carboxyl or C
6-14Aryl carbonyl replaces arbitrarily),
(v), the Q in formula (w), formula (ab), formula (ac) and the formula (ad) represents O (Sauerstoffatom), S (sulphur atom), SO (sulfinyl) or SO for above-mentioned formula (c), formula (d), formula (p), formula (q), formula
2(alkylsulfonyl)).
5. the manufacture method of optically active chromene oxide compound according to claim 4, the R in above-mentioned formula (11) or the formula (12)
9And R
10It is methyl.
6. according to the manufacture method of claim 4 or 5 described optically active chromene oxide compounds, A in above-mentioned formula (11) or the formula (12) is by following formula (a), formula (b), formula (i), formula (k), formula (o), formula (p), formula (s), formula (v), formula (y), formula (ae), formula (ag) or formula (ah) expression
(in the formula, R
12, R
13, R
14, R
15And R
16Identical with the record in the claim 4).
7. the manufacture method of optically active chromene oxide compound according to claim 6, A in above-mentioned formula (11) or the formula (12) represents above-mentioned formula (a), formula (b), formula (i), formula (k), formula (o), formula (p), formula (s), formula (v), formula (y), formula (ae), formula (ag) or formula (ah)
Formula (a), formula (b), formula (i), formula (k), formula (p), formula (v), the R in formula (ae) and the formula (ag)
12And R
13Represent hydrogen atom, C respectively independently
1-6(this alkyl can be by halogen atom, C for alkyl
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom), amino or hydroxyl replace arbitrarily), formula (a), formula (b), formula (k), formula (o), formula (p), formula (s), formula (v), the R in formula (y) and the formula (ae)
14, R
15And R
16Represent hydrogen atom, halogen atom or C respectively independently
1-6(this alkyl can be by halogen atom, C for alkyl
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom), amino, hydroxyl, C
1-6Alkyl amino-carbonyl, two C
1-6Alkyl amino-carbonyl, C
1-6Alkyl-carbonyl oxygen base, C
1-6Alkyl-carbonyl (this alkyl-carbonyl oxygen base and alkyl-carbonyl can be replaced arbitrarily by halogen atom), C
1-6Alkyl-carbonyl-amino, C
3-8Naphthene base carbonyl or C
1-6Alkoxy carbonyl replaces arbitrarily), Q represents O (Sauerstoffatom).
8. the manufacture method of optically active chromene oxide compound according to claim 7, A expression (a) in above-mentioned formula (11) or the formula (12), formula (b), formula (i), formula (k), formula (o), formula (p), formula (s), formula (v), formula (y), formula (ae), formula (ag) or formula (ah), formula (a), formula (b), formula (i), formula (k), formula (p), formula (v), the R in formula (ae) and the formula (ag)
12And R
13Represent hydrogen atom, methyl respectively independently, formula (a), formula (b), formula (k), formula (o), formula (p), formula (s), formula (v), the R in formula (y) and the formula (ae)
14, R
15And R
16Represent hydrogen atom, halogen atom or C respectively independently
1-6(this alkyl can be by halogen atom, C for alkyl
1-6Alkoxyl group (this alkoxyl group can be replaced arbitrarily by halogen atom), amino, hydroxyl, C
1-6Alkyl amino-carbonyl, two C
1-6Alkyl amino-carbonyl, C
1-6Alkyl-carbonyl oxygen base, C
1-6Alkyl-carbonyl (this alkyl-carbonyl oxygen base and alkyl-carbonyl can be replaced arbitrarily by halogen atom), C
1-6Alkyl-carbonyl-amino, C
3-8Naphthene base carbonyl or C
1-6Alkoxy carbonyl replaces arbitrarily), Q represents O (Sauerstoffatom).
9. the manufacture method of optically active chromene oxide compound according to claim 1, it is characterized in that, use the optical activity titanium complex shown in any one of above-mentioned formula (1), formula (1 '), formula (2), formula (2 '), formula (3), formula (3 '), formula (4) and formula (4 ') as catalyzer, with the chromene compounds shown in the above-mentioned formula (13) in solvent, carry out asymmetric Epoxidation with oxygenant, the R in the above-mentioned formula (13)
9And R
10All represent methyl.
10. the manufacture method of optically active chromene oxide compound according to claim 9, the W in the above-mentioned formula (13) represents hydrogen atom, hydroxyl, methoxyl group, chlorine atom, bromine atoms, methyl, ethyl or methylsulfonyl amido.
11. according to the manufacture method of claim 9 or 10 described optically active chromene oxide compounds, the Y in the above-mentioned formula (13) represents SO
2(alkylsulfonyl), Z represents C
1-4Alkyl.
12. the manufacture method of optically active chromene oxide compound according to claim 10, the Y in the above-mentioned formula (13) represents Direct Bonding, and Z represents C
1-4Alkyl.
13. the manufacture method of optically active chromene oxide compound according to claim 1, the R in above-mentioned formula (1), formula (1 '), formula (2), formula (2 '), formula (3), formula (3 '), formula (4) and the formula (4 ')
1Expression C
6-22(this aryl can be by C for aryl
1-4Alkyl (this alkyl can be replaced arbitrarily by halogen atom) C
1-7Alkoxyl group or benzyl oxygen base replace arbitrarily, are optical activity or non-optical activity),
R
2Expression hydrogen atom, halogen atom, C
1-4Alkyl, C
1-4Alkoxyl group, C
6-12Aryloxy or C
6-18Aryl,
R
3Expression C
1-4Alkyl, C
6-18Aryl, perhaps, at 2 R
3Form under the situation of ring expression C together
3-5The group of divalence,
R
4Represent hydrogen atom, halogen atom, C respectively independently
1-4Alkyl, C
1-4Alkoxyl group, nitro or cyano group,
M represents TiJ
1J
2(at TiJ
1J
2In, Ti represents titanium atom, J
1And J
2Represent halogen atom, C respectively independently
1-4Alkoxyl group, J
1With J
2Represent Sauerstoffatom together, perhaps, J
1With J
2Form ring together, (about the part-structure O-E-O in the formula, wherein, O is a Sauerstoffatom, in formula (1), as O-E-O, is represented by above-mentioned formula (6) as the above-mentioned formula (5) of the group of divalence in expression; In formula (1 '),, represent by above-mentioned formula (6 ') as O-E-O; In formula (2),, represent by above-mentioned formula (7) as O-E-O; In formula (2 '),, represent by above-mentioned formula (7 ') as O-E-O; In formula (3),, represent by above-mentioned formula (8) as O-E-O; In formula (3 '),, represent by above-mentioned formula (8 ') as O-E-O; In formula (4),, represent by above-mentioned formula (9) as O-E-O; In formula (4 '), as O-E-O, by above-mentioned formula (9 ') expression, b is 1～10 integer, R
1, R
2, R
3And R
4Same as described above)).
14. the manufacture method of optically active chromene oxide compound according to claim 13, the R in above-mentioned formula (1), formula (1 '), formula (2), formula (2 '), formula (3), formula (3 '), formula (4) and the formula (4 ')
1(this phenyl can be by C for the expression phenyl
1-4Alkyl (this alkyl can be replaced arbitrarily by halogen atom), benzyl oxygen base or C
1-7Alkoxyl group replaces arbitrarily) or naphthyl (this naphthyl can be by C
1-4Alkyl (this alkyl can be replaced arbitrarily by halogen atom), C
1-7Alkoxyl group or phenyl replace arbitrarily),
R
2The expression hydrogen atom,
R
3Represent 2 R
3Form the C of ring together
3-5The group of divalence,
R
4The expression hydrogen atom,
M represents TiJ
1J
2(at TiJ
1J
2In, Ti represents titanium atom, J
1And J
2Represent halogen atom, C respectively independently
1-4Alkoxyl group, perhaps, J
1With J
2Represent Sauerstoffatom together, perhaps, J
1With J
2Form ring together, (about the part-structure O-E-O in the formula, wherein, O is a Sauerstoffatom, in formula (1), as O-E-O, is represented by above-mentioned formula (6) as the above-mentioned formula (5) of the group of divalence in expression; In formula (1 '),, represent by above-mentioned formula (6 ') as O-E-O; In formula (2),, represent by above-mentioned formula (7) as O-E-O; In formula (2 '),, represent by above-mentioned formula (7 ') as O-E-O; In formula (3),, represent by above-mentioned formula (8) as O-E-O; In formula (3 '),, represent by above-mentioned formula (8 ') as O-E-O; In formula (4),, represent by above-mentioned formula (9) as O-E-O; In formula (4 '), as O-E-O, by above-mentioned formula (9 ') expression, b is 1～10 integer, R
1, R
2, R
3And R
4Same as described above)).
15. manufacture method according to each described optically active chromene oxide compound of claim 1～14, the usage quantity of optical activity titanium complex is 0.001～100 mole of % with respect to the chromene compounds shown in formula (10), formula (11), formula (12) or the formula (13).
16. manufacture method according to each described optically active chromene oxide compound of claim 1～14, the solvent that uses in the asymmetric epoxidation reaction is halogen series solvent, aromatic hydrocarbons series solvent, ester series solvent, ether series solvent, nitrile series solvent, pure series solvent, the mixture of perhaps above-mentioned solvent.
17. according to the manufacture method of each described optically active chromene oxide compound of claim 1～14, the oxygenant that uses in the asymmetric epoxidation reaction is the mixture of iodosobenzene, clorox, metachloroperbenzoic acid, Oxone (E.I.Du Pont Company's registered trademark), aquae hydrogenii dioxidi, urea-hydrogen peroxide adduct (UHP), azepine oxygen triatomic ring, N-methylmorpholine oxide compound (NMO), tertbutyl peroxide (TBHP), cumene hydroperoxide (CHP) or these oxygenants.
18. the manufacture method of optically active chromene oxide compound according to claim 17, the oxygenant that uses in the asymmetric epoxidation reaction are the mixtures of aquae hydrogenii dioxidi, urea-hydrogen peroxide adduct (UHP) or these oxygenants.
19. the manufacture method of optically active chromene oxide compound according to claim 18, the oxygenant that uses in the asymmetric epoxidation reaction is an aquae hydrogenii dioxidi, and concentration is 1～100 quality %.
20. manufacture method according to each described optically active chromene oxide compound of claim 1～14, the usage quantity of the oxygenant that uses in the asymmetric epoxidation reaction is 1～10 equivalent with respect to the chromene compounds shown in above-mentioned formula (10), formula (11), formula (12) or the formula (13).
21. the manufacture method of optically active chromene oxide compound according to claim 20, the addition means of the oxygenant that uses in the asymmetric epoxidation reaction are portion-wise addition or add continuously.
22. the manufacture method of optically active chromene oxide compound according to claim 21, the addition means of the oxygenant that uses in the asymmetric epoxidation reaction are continuous interpolations, its interpolation speed per hour is 0.01～40000 equivalent.
23. the manufacture method of optically active chromene oxide compound according to claim 21, the addition means of the oxygenant that uses in the asymmetric epoxidation reaction is a portion-wise addition, and number of times is in 2～100 scope in batches.
24. according to the manufacture method of each described optically active chromene oxide compound of claim 1～23, the temperature of reaction of asymmetric epoxidation reaction is the reflux temperature of 0 ℃～employed solvent.
25. according to the manufacture method of each described optically active chromene oxide compound of claim 1～24, the scope of the pressure in the reaction system of asymmetric epoxidation reaction is 10kPa～1100kPa.
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2006066818 | 2006-03-10 | ||
| JP066818/2006 | 2006-03-10 | ||
| JP2006084285 | 2006-03-24 | ||
| JP084285/2006 | 2006-03-24 | ||
| PCT/JP2007/054730 WO2007105658A1 (en) | 2006-03-10 | 2007-03-09 | Process for producing optically active chromene oxide compound |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101437827A true CN101437827A (en) | 2009-05-20 |
| CN101437827B CN101437827B (en) | 2012-08-29 |
Family
ID=40711600
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2007800165479A Expired - Fee Related CN101437827B (en) | 2006-03-10 | 2007-03-09 | Process for producing optically active chromene oxide compound |
Country Status (3)
| Country | Link |
|---|---|
| CN (1) | CN101437827B (en) |
| UA (1) | UA94449C2 (en) |
| ZA (1) | ZA200808177B (en) |
Cited By (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103068831A (en) * | 2010-06-18 | 2013-04-24 | 雷蒙特亚特特拉维夫大学有限公司 | Salalen ligands and organometallic complexes |
| US8937137B2 (en) | 2013-03-13 | 2015-01-20 | Exxonmobil Chemical Patents Inc. | Diphenylamine salan catalyst |
| US8952114B2 (en) | 2012-08-03 | 2015-02-10 | Exxonmobil Chemical Patents Inc. | Halogenated catalysts comprising Salan ligands |
| US8957172B2 (en) | 2012-08-03 | 2015-02-17 | Exxonmobil Chemical Patents Inc. | Nonsymmetric catalysts comprising salan ligands |
| US8957171B2 (en) | 2012-08-03 | 2015-02-17 | Exxonmobil Chemical Patents Inc. | Catalysts comprising salan ligands |
| US9045568B2 (en) | 2012-08-03 | 2015-06-02 | Exxonmobil Chemical Patents Inc. | Vinyl terminated polyethylene with long chain branching |
| US9120879B2 (en) | 2012-11-02 | 2015-09-01 | Exxonmobil Chemical Patents Inc. | Supported Salan catalysts |
| US9150676B2 (en) | 2013-06-20 | 2015-10-06 | Exxonmobil Chemical Patents Inc. | Thio-salalen catalyst |
| US9193813B2 (en) | 2014-03-31 | 2015-11-24 | Exxonmobil Chemical Patents Inc. | Phenylene-bridged salalen catalysts |
| US9200099B2 (en) | 2013-06-20 | 2015-12-01 | Exxonmobil Chemical Patents Inc. | Salenol catalyst |
| US9200100B2 (en) | 2013-06-20 | 2015-12-01 | Exxonmobil Chemical Patents Inc. | Long-bridged salen catalyst |
| US9290589B2 (en) | 2013-12-13 | 2016-03-22 | Exxonmobil Chemical Patents Inc. | Cyclopentadienyl-substituted salan catalysts |
| US9365661B2 (en) | 2012-08-03 | 2016-06-14 | Exxonmobil Chemical Patents Inc. | Polyalphaolefins prepared using modified salan catalyst compounds |
| US9382349B2 (en) | 2012-08-03 | 2016-07-05 | Exxonmobil Chemical Patents Inc. | Polyalphaolefins prepared using modified Salan catalyst compounds |
| US10696641B2 (en) | 2015-04-27 | 2020-06-30 | Univation Technologies, Llc | Bis(aminophenylphenol) ligands and transition metal catalysts prepared therefrom |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5352814A (en) * | 1991-08-30 | 1994-10-04 | Nissan Chemical Industries, Ltd. | Asymmetric epoxidation reaction |
| GB0018973D0 (en) * | 2000-08-02 | 2000-09-20 | King S College London | Synthesis of chiral cyanohydrins |
| GB0103857D0 (en) * | 2001-02-16 | 2001-04-04 | Avecia Ltd | Preparation of chloromandelic acid |
-
2007
- 2007-03-09 CN CN2007800165479A patent/CN101437827B/en not_active Expired - Fee Related
- 2007-03-09 ZA ZA200808177A patent/ZA200808177B/en unknown
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Cited By (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103068831A (en) * | 2010-06-18 | 2013-04-24 | 雷蒙特亚特特拉维夫大学有限公司 | Salalen ligands and organometallic complexes |
| CN103068831B (en) * | 2010-06-18 | 2016-08-03 | 雷蒙特亚特特拉维夫大学有限公司 | Salalen part and metal-organic complex |
| US9365661B2 (en) | 2012-08-03 | 2016-06-14 | Exxonmobil Chemical Patents Inc. | Polyalphaolefins prepared using modified salan catalyst compounds |
| US8952114B2 (en) | 2012-08-03 | 2015-02-10 | Exxonmobil Chemical Patents Inc. | Halogenated catalysts comprising Salan ligands |
| US8957171B2 (en) | 2012-08-03 | 2015-02-17 | Exxonmobil Chemical Patents Inc. | Catalysts comprising salan ligands |
| US9045568B2 (en) | 2012-08-03 | 2015-06-02 | Exxonmobil Chemical Patents Inc. | Vinyl terminated polyethylene with long chain branching |
| US8957172B2 (en) | 2012-08-03 | 2015-02-17 | Exxonmobil Chemical Patents Inc. | Nonsymmetric catalysts comprising salan ligands |
| US9464148B2 (en) | 2012-08-03 | 2016-10-11 | Exxonmobil Chemical Patents Inc. | Vinyl terminated polyethylene with long chain branching |
| US9382349B2 (en) | 2012-08-03 | 2016-07-05 | Exxonmobil Chemical Patents Inc. | Polyalphaolefins prepared using modified Salan catalyst compounds |
| US9120879B2 (en) | 2012-11-02 | 2015-09-01 | Exxonmobil Chemical Patents Inc. | Supported Salan catalysts |
| US9556287B2 (en) | 2012-11-02 | 2017-01-31 | Exxonmobil Chemical Patents Inc. | Vinyl terminated macromonomers |
| US8937137B2 (en) | 2013-03-13 | 2015-01-20 | Exxonmobil Chemical Patents Inc. | Diphenylamine salan catalyst |
| US9200100B2 (en) | 2013-06-20 | 2015-12-01 | Exxonmobil Chemical Patents Inc. | Long-bridged salen catalyst |
| US9200099B2 (en) | 2013-06-20 | 2015-12-01 | Exxonmobil Chemical Patents Inc. | Salenol catalyst |
| US9150676B2 (en) | 2013-06-20 | 2015-10-06 | Exxonmobil Chemical Patents Inc. | Thio-salalen catalyst |
| US9290589B2 (en) | 2013-12-13 | 2016-03-22 | Exxonmobil Chemical Patents Inc. | Cyclopentadienyl-substituted salan catalysts |
| US9193813B2 (en) | 2014-03-31 | 2015-11-24 | Exxonmobil Chemical Patents Inc. | Phenylene-bridged salalen catalysts |
| US10696641B2 (en) | 2015-04-27 | 2020-06-30 | Univation Technologies, Llc | Bis(aminophenylphenol) ligands and transition metal catalysts prepared therefrom |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101437827B (en) | 2012-08-29 |
| ZA200808177B (en) | 2009-12-30 |
| UA94449C2 (en) | 2011-05-10 |
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