CN1314880A - Novel method for preparing optically active alpha-aminonitriles - Google Patents
Novel method for preparing optically active alpha-aminonitriles Download PDFInfo
- Publication number
- CN1314880A CN1314880A CN00801171A CN00801171A CN1314880A CN 1314880 A CN1314880 A CN 1314880A CN 00801171 A CN00801171 A CN 00801171A CN 00801171 A CN00801171 A CN 00801171A CN 1314880 A CN1314880 A CN 1314880A
- Authority
- CN
- China
- Prior art keywords
- group
- alkyl
- contain
- chemical formula
- metal
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000000034 method Methods 0.000 title claims abstract description 70
- 238000005669 hydrocyanation reaction Methods 0.000 claims abstract description 33
- 239000000126 substance Substances 0.000 claims description 71
- 125000004432 carbon atom Chemical group C* 0.000 claims description 69
- PPTXVXKCQZKFBN-UHFFFAOYSA-N (S)-(-)-1,1'-Bi-2-naphthol Chemical compound C1=CC=C2C(C3=C4C=CC=CC4=CC=C3O)=C(O)C=CC2=C1 PPTXVXKCQZKFBN-UHFFFAOYSA-N 0.000 claims description 57
- 229910052799 carbon Inorganic materials 0.000 claims description 53
- 229910052751 metal Inorganic materials 0.000 claims description 50
- 239000002184 metal Substances 0.000 claims description 50
- 125000000217 alkyl group Chemical group 0.000 claims description 42
- -1 methylenedioxyphenyl Chemical group 0.000 claims description 35
- 239000002585 base Substances 0.000 claims description 34
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 28
- 125000003545 alkoxy group Chemical group 0.000 claims description 27
- 239000010936 titanium Substances 0.000 claims description 24
- 230000006698 induction Effects 0.000 claims description 22
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 20
- 239000000203 mixture Substances 0.000 claims description 19
- 125000004414 alkyl thio group Chemical group 0.000 claims description 18
- 238000006243 chemical reaction Methods 0.000 claims description 17
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 17
- 239000000460 chlorine Substances 0.000 claims description 16
- 125000001188 haloalkyl group Chemical group 0.000 claims description 16
- 239000002905 metal composite material Substances 0.000 claims description 15
- LELOWRISYMNNSU-UHFFFAOYSA-N hydrogen cyanide Chemical group N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 claims description 14
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 13
- 229910052801 chlorine Inorganic materials 0.000 claims description 13
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 claims description 13
- 239000003153 chemical reaction reagent Substances 0.000 claims description 12
- 229910052719 titanium Inorganic materials 0.000 claims description 11
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 10
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 claims description 10
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 10
- 125000000304 alkynyl group Chemical group 0.000 claims description 10
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 10
- 125000005843 halogen group Chemical group 0.000 claims description 10
- 125000001624 naphthyl group Chemical group 0.000 claims description 10
- 229910052760 oxygen Inorganic materials 0.000 claims description 10
- 239000001301 oxygen Substances 0.000 claims description 10
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 9
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 9
- 239000004411 aluminium Substances 0.000 claims description 9
- 229910052782 aluminium Inorganic materials 0.000 claims description 9
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 9
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 9
- 229910052794 bromium Inorganic materials 0.000 claims description 9
- JMANVNJQNLATNU-UHFFFAOYSA-N oxalonitrile Chemical compound N#CC#N JMANVNJQNLATNU-UHFFFAOYSA-N 0.000 claims description 9
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 claims description 8
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 8
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 8
- 125000003342 alkenyl group Chemical group 0.000 claims description 8
- 125000006350 alkyl thio alkyl group Chemical group 0.000 claims description 8
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 8
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 8
- 150000001875 compounds Chemical class 0.000 claims description 8
- 229910052731 fluorine Inorganic materials 0.000 claims description 8
- 239000011737 fluorine Substances 0.000 claims description 8
- QCWXUUIWCKQGHC-UHFFFAOYSA-N Zirconium Chemical compound [Zr] QCWXUUIWCKQGHC-UHFFFAOYSA-N 0.000 claims description 7
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 7
- 125000003118 aryl group Chemical group 0.000 claims description 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 7
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 7
- 125000001424 substituent group Chemical group 0.000 claims description 7
- 229910052726 zirconium Inorganic materials 0.000 claims description 7
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims description 6
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims description 6
- 239000005864 Sulphur Substances 0.000 claims description 6
- 125000002252 acyl group Chemical group 0.000 claims description 6
- 150000002500 ions Chemical class 0.000 claims description 6
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 6
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 claims description 6
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 claims description 5
- 229910052742 iron Inorganic materials 0.000 claims description 5
- 230000000737 periodic effect Effects 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- 229910052706 scandium Inorganic materials 0.000 claims description 5
- WGLLSSPDPJPLOR-UHFFFAOYSA-N 2,3-dimethylbut-2-ene Chemical group CC(C)=C(C)C WGLLSSPDPJPLOR-UHFFFAOYSA-N 0.000 claims description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 4
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Divinylene sulfide Natural products C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 4
- GYHNNYVSQQEPJS-UHFFFAOYSA-N Gallium Chemical compound [Ga] GYHNNYVSQQEPJS-UHFFFAOYSA-N 0.000 claims description 4
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 4
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 claims description 4
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 claims description 4
- 229910052769 Ytterbium Inorganic materials 0.000 claims description 4
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 4
- 150000001336 alkenes Chemical class 0.000 claims description 4
- 125000005108 alkenylthio group Chemical group 0.000 claims description 4
- 125000005133 alkynyloxy group Chemical group 0.000 claims description 4
- 125000005336 allyloxy group Chemical group 0.000 claims description 4
- 125000005160 aryl oxy alkyl group Chemical group 0.000 claims description 4
- 229910052728 basic metal Inorganic materials 0.000 claims description 4
- 150000003818 basic metals Chemical class 0.000 claims description 4
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 4
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 4
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 239000010949 copper Substances 0.000 claims description 4
- 229910052802 copper Inorganic materials 0.000 claims description 4
- 125000000058 cyclopentadienyl group Chemical group C1(=CC=CC1)* 0.000 claims description 4
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 claims description 4
- ZSWFCLXCOIISFI-UHFFFAOYSA-N endo-cyclopentadiene Natural products C1C=CC=C1 ZSWFCLXCOIISFI-UHFFFAOYSA-N 0.000 claims description 4
- 238000011066 ex-situ storage Methods 0.000 claims description 4
- 125000002541 furyl group Chemical group 0.000 claims description 4
- 229910052733 gallium Inorganic materials 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 238000011065 in-situ storage Methods 0.000 claims description 4
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 4
- 125000005956 isoquinolyl group Chemical group 0.000 claims description 4
- 229910052749 magnesium Inorganic materials 0.000 claims description 4
- 239000011777 magnesium Substances 0.000 claims description 4
- 150000002825 nitriles Chemical class 0.000 claims description 4
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 125000005493 quinolyl group Chemical group 0.000 claims description 4
- SIXSYDAISGFNSX-UHFFFAOYSA-N scandium atom Chemical compound [Sc] SIXSYDAISGFNSX-UHFFFAOYSA-N 0.000 claims description 4
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- 229930192474 thiophene Natural products 0.000 claims description 4
- NAWDYIZEMPQZHO-UHFFFAOYSA-N ytterbium Chemical compound [Yb] NAWDYIZEMPQZHO-UHFFFAOYSA-N 0.000 claims description 4
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 3
- 229910016570 AlCu Inorganic materials 0.000 claims description 3
- 229910017073 AlLi Inorganic materials 0.000 claims description 3
- 125000004429 atom Chemical group 0.000 claims description 3
- 125000001891 dimethoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- 239000011630 iodine Substances 0.000 claims description 3
- 229910052740 iodine Inorganic materials 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- AHLBNYSZXLDEJQ-FWEHEUNISA-N orlistat Chemical compound CCCCCCCCCCC[C@H](OC(=O)[C@H](CC(C)C)NC=O)C[C@@H]1OC(=O)[C@H]1CCCCCC AHLBNYSZXLDEJQ-FWEHEUNISA-N 0.000 claims description 3
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 3
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims description 3
- 125000005554 pyridyloxy group Chemical group 0.000 claims description 3
- 125000005270 trialkylamine group Chemical group 0.000 claims description 3
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- VGMKUVCDINAAFC-UHFFFAOYSA-N 1-methoxy-2-(2-methoxyphenyl)benzene Chemical group COC1=CC=CC=C1C1=CC=CC=C1OC VGMKUVCDINAAFC-UHFFFAOYSA-N 0.000 claims description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 2
- CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 claims description 2
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 claims description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 2
- 125000005118 N-alkylcarbamoyl group Chemical group 0.000 claims description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims description 2
- 229920001774 Perfluoroether Polymers 0.000 claims description 2
- WNYFTWLTSLCQLO-UHFFFAOYSA-N [As].N1=CC=CC=C1 Chemical compound [As].N1=CC=CC=C1 WNYFTWLTSLCQLO-UHFFFAOYSA-N 0.000 claims description 2
- 150000001257 actinium Chemical class 0.000 claims description 2
- 229910052783 alkali metal Inorganic materials 0.000 claims description 2
- 150000004703 alkoxides Chemical class 0.000 claims description 2
- 125000005256 alkoxyacyl group Chemical group 0.000 claims description 2
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 2
- 125000004691 alkyl thio carbonyl group Chemical group 0.000 claims description 2
- 150000001412 amines Chemical class 0.000 claims description 2
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 2
- 150000004982 aromatic amines Chemical class 0.000 claims description 2
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 2
- DBTXVEOHOJDNRW-UHFFFAOYSA-N benzenethiol 1,1'-biphenyl Chemical compound C1(=CC=CC=C1)S.C1(=CC=CC=C1)C1=CC=CC=C1 DBTXVEOHOJDNRW-UHFFFAOYSA-N 0.000 claims description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 2
- 239000004305 biphenyl Substances 0.000 claims description 2
- 235000010290 biphenyl Nutrition 0.000 claims description 2
- 125000002837 carbocyclic group Chemical group 0.000 claims description 2
- 125000001651 cyanato group Chemical group [*]OC#N 0.000 claims description 2
- 125000006575 electron-withdrawing group Chemical group 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 229910052732 germanium Inorganic materials 0.000 claims description 2
- GNPVGFCGXDBREM-UHFFFAOYSA-N germanium atom Chemical compound [Ge] GNPVGFCGXDBREM-UHFFFAOYSA-N 0.000 claims description 2
- 125000005252 haloacyl group Chemical group 0.000 claims description 2
- 125000004993 haloalkoxycarbonyl group Chemical group 0.000 claims description 2
- 125000004693 haloalkylthiocarbonyl group Chemical group 0.000 claims description 2
- 125000000623 heterocyclic group Chemical group 0.000 claims description 2
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 229910000037 hydrogen sulfide Inorganic materials 0.000 claims description 2
- 229910052747 lanthanoid Inorganic materials 0.000 claims description 2
- 150000002602 lanthanoids Chemical class 0.000 claims description 2
- 239000003446 ligand Substances 0.000 claims description 2
- 229910052744 lithium Inorganic materials 0.000 claims description 2
- HZVOZRGWRWCICA-UHFFFAOYSA-N methanediyl Chemical compound [CH2] HZVOZRGWRWCICA-UHFFFAOYSA-N 0.000 claims description 2
- 125000002757 morpholinyl group Chemical group 0.000 claims description 2
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 2
- 125000004193 piperazinyl group Chemical group 0.000 claims description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 2
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
- 238000006884 silylation reaction Methods 0.000 claims description 2
- XTQHKBHJIVJGKJ-UHFFFAOYSA-N sulfur monoxide Chemical group S=O XTQHKBHJIVJGKJ-UHFFFAOYSA-N 0.000 claims description 2
- 125000002769 thiazolinyl group Chemical group 0.000 claims description 2
- 150000007944 thiolates Chemical class 0.000 claims description 2
- 229910052723 transition metal Inorganic materials 0.000 claims description 2
- OWVIRVJQDVCGQX-VSGBNLITSA-N [(4r,5r)-5-[hydroxy(diphenyl)methyl]-2,2-dimethyl-1,3-dioxolan-4-yl]-diphenylmethanol Chemical compound C=1C=CC=CC=1C(O)([C@H]1[C@@H](OC(O1)(C)C)C(O)(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 OWVIRVJQDVCGQX-VSGBNLITSA-N 0.000 claims 3
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 1
- 239000003054 catalyst Substances 0.000 abstract description 16
- 150000002894 organic compounds Chemical class 0.000 abstract description 4
- 238000003786 synthesis reaction Methods 0.000 abstract description 4
- 239000003795 chemical substances by application Substances 0.000 abstract description 3
- 230000015572 biosynthetic process Effects 0.000 abstract 1
- 150000004696 coordination complex Chemical class 0.000 abstract 1
- 230000001939 inductive effect Effects 0.000 abstract 1
- 239000000543 intermediate Substances 0.000 abstract 1
- 150000004658 ketimines Chemical class 0.000 abstract 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 78
- 239000000243 solution Substances 0.000 description 33
- 150000001721 carbon Chemical group 0.000 description 25
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 24
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 16
- 150000002466 imines Chemical class 0.000 description 14
- 239000011541 reaction mixture Substances 0.000 description 11
- 150000001408 amides Chemical class 0.000 description 9
- LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 8
- 238000002156 mixing Methods 0.000 description 7
- 125000005219 aminonitrile group Chemical group 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 238000006460 hydrolysis reaction Methods 0.000 description 5
- 238000002955 isolation Methods 0.000 description 5
- 239000002253 acid Substances 0.000 description 4
- 239000012429 reaction media Substances 0.000 description 4
- 230000035484 reaction time Effects 0.000 description 4
- 230000009466 transformation Effects 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 238000002407 reforming Methods 0.000 description 3
- 238000010189 synthetic method Methods 0.000 description 3
- 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 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical class NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 150000004705 aldimines Chemical class 0.000 description 2
- 125000003282 alkyl amino group Chemical group 0.000 description 2
- 238000007327 hydrogenolysis reaction Methods 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 239000007791 liquid phase Substances 0.000 description 2
- 229910021645 metal ion Inorganic materials 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000000935 solvent evaporation Methods 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- KFZJOPXLHUIAKE-UHFFFAOYSA-N 2-(benzylamino)-2-phenylpropanamide Chemical compound C=1C=CC=CC=1C(C)(C(N)=O)NCC1=CC=CC=C1 KFZJOPXLHUIAKE-UHFFFAOYSA-N 0.000 description 1
- HLFDNKVYUJIQJD-UHFFFAOYSA-N 2-(benzylamino)-2-phenylpropanenitrile Chemical compound C=1C=CC=CC=1C(C)(C#N)NCC1=CC=CC=C1 HLFDNKVYUJIQJD-UHFFFAOYSA-N 0.000 description 1
- HGKUPDZBTAQFGJ-UHFFFAOYSA-N 2-amino-2-phenylpropanamide Chemical compound NC(=O)C(N)(C)C1=CC=CC=C1 HGKUPDZBTAQFGJ-UHFFFAOYSA-N 0.000 description 1
- MWFMGBPGAXYFAR-UHFFFAOYSA-N 2-hydroxy-2-methylpropanenitrile Chemical compound CC(C)(O)C#N MWFMGBPGAXYFAR-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 229910017489 Cu I Inorganic materials 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- QLDHWVVRQCGZLE-UHFFFAOYSA-N acetyl cyanide Chemical compound CC(=O)C#N QLDHWVVRQCGZLE-UHFFFAOYSA-N 0.000 description 1
- 150000001264 acyl cyanides Chemical class 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 150000003797 alkaloid derivatives Chemical class 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- 125000005263 alkylenediamine group Chemical group 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- PLQYMJTWHLJUIL-UHFFFAOYSA-N copper;toluene Chemical compound [Cu].CC1=CC=CC=C1 PLQYMJTWHLJUIL-UHFFFAOYSA-N 0.000 description 1
- 238000006264 debenzylation reaction Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 125000005265 dialkylamine group Chemical group 0.000 description 1
- 150000004985 diamines Chemical class 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 229940031815 mycocide Drugs 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000012797 qualification Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 229910052721 tungsten Inorganic materials 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/16—Preparation of optical isomers
- C07C231/18—Preparation of optical isomers by stereospecific synthesis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
- C07C255/24—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the same saturated acyclic carbon skeleton
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/22—Organic complexes
- B01J31/2204—Organic complexes the ligands containing oxygen or sulfur as complexing atoms
- B01J31/2208—Oxygen, e.g. acetylacetonates
- B01J31/2226—Anionic ligands, i.e. the overall ligand carries at least one formal negative charge
- B01J31/223—At least two oxygen atoms present in one at least bidentate or bridging ligand
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/22—Organic complexes
- B01J31/2204—Organic complexes the ligands containing oxygen or sulfur as complexing atoms
- B01J31/226—Sulfur, e.g. thiocarbamates
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/30—Preparation of optical isomers
- C07C227/32—Preparation of optical isomers by stereospecific synthesis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/08—Preparation of carboxylic acid nitriles by addition of hydrogen cyanide or salts thereof to unsaturated compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/10—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings
- C07D317/14—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D317/18—Radicals substituted by singly bound oxygen or sulfur atoms
- C07D317/20—Free hydroxyl or mercaptan
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
- B01J2231/30—Addition reactions at carbon centres, i.e. to either C-C or C-X multiple bonds
- B01J2231/32—Addition reactions to C=C or C-C triple bonds
- B01J2231/322—Hydrocyanation
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/02—Compositional aspects of complexes used, e.g. polynuclearity
- B01J2531/0213—Complexes without C-metal linkages
- B01J2531/0216—Bi- or polynuclear complexes, i.e. comprising two or more metal coordination centres, without metal-metal bonds, e.g. Cp(Lx)Zr-imidazole-Zr(Lx)Cp
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/30—Complexes comprising metals of Group III (IIIA or IIIB) as the central metal
- B01J2531/31—Aluminium
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/30—Complexes comprising metals of Group III (IIIA or IIIB) as the central metal
- B01J2531/32—Gallium
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/30—Complexes comprising metals of Group III (IIIA or IIIB) as the central metal
- B01J2531/35—Scandium
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/30—Complexes comprising metals of Group III (IIIA or IIIB) as the central metal
- B01J2531/38—Lanthanides other than lanthanum
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/40—Complexes comprising metals of Group IV (IVA or IVB) as the central metal
- B01J2531/46—Titanium
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/40—Complexes comprising metals of Group IV (IVA or IVB) as the central metal
- B01J2531/48—Zirconium
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/40—Complexes comprising metals of Group IV (IVA or IVB) as the central metal
- B01J2531/49—Hafnium
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/80—Complexes comprising metals of Group VIII as the central metal
- B01J2531/84—Metals of the iron group
- B01J2531/842—Iron
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Health & Medical Sciences (AREA)
- Toxicology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Catalysts (AREA)
Abstract
The invention concerns a novel method for preparing optically active alpha -aminonitriles of formula (I) by enantioselective hydrocyanation using a hydrocyanation agent, in the presence of a chiral or chirality inducing metal complex acting as catalyst, of ketimines of formula (II) wherein the radicals R1 and R2 and T are such as defined in the description. The invention also concerns the use of alpha -aminonitriles of formula (I) as synthesis intermediates of optically active organic compounds.
Description
Invention field
The present invention relates to a kind ofly prepare the novel method of optically active alpha-aminonitriles, and the optically active alpha-aminonitriles that is made by this method is as the application of intermediate in synthetic opticity organic compound by the enantio-selectivity hydrocyanation of imines.
Prior art
As everyone knows, in the organic synthesis field, the imines hydrocyanation can make alpha-aminonitriles.And can obtaining a-amino acid, the alpha-aminonitriles hydrolysis also knows.
At present, most a-amino acids comprise asymmetric center.No matter be direct use, still as the synthetic more intermediate of complex organic compound, the non-racemic form that obtains these a-amino acids (and corresponding alpha-aminonitriles precursor) is normally very important.
A lot of methods that prepare optically-active a-amino acid or alpha-aminonitriles are arranged in the literature, these methods mainly are based on following method: carry out the fractionation of racemic mixture with liquid phase chromatography, or split for example also undocumented french patent application 98/06339 with alkaloid or enzymatic method.
These method for splitting have those shortcomings of existing method, are difficult to industrialization and quite expensive.Its reason is that the method for using is very expensive, and splits principle itself and be actually and separate, and obtains two enantiomorphs, and conceivable usually just one of enantiomorph.
Industrial method-the term " industrial method " of preparation optically-active a-amino acid or alpha-aminonitriles is meant any preparation method-needs enantio-selectivity synthesis method except that prepared in laboratory, promptly only produce required enantiomorph, and the very high synthetic method of this enantiomeric purity.
The method that the imines hydrocyanation prepares alpha-aminonitriles is known.And up to now, the stereoselectivity hydrocyanation method of imines reacts particularly including stoichiometric non-enantiomer selectivity, and this reaction realizes by introduce the chiral induction agent on nitrogen.The example that produces chirality with catalyzer seldom.In this case, catalyzer is alkaline, and itself is the derivative of a-amino acid.The example of making catalyzer with Salen-aluminium mixture is disclosed in J.Am.Chem.Soc. (1998), 120,4901-4902.
People's such as H.Ishitani research (Angew.Chem.Int.Ed., 37 (22), (1998) 3186-8), have introduced the use zirconium-containing catalyst, the enantio-selectivity synthetic method of the alpha-aminonitriles that is begun by aldimine.Yet these researchs only limit to the hydrocyanation of aldimine, this method can not obtain with amino and carbon that carboxyl links to each other on be with two substituent a-amino acids.
One object of the present invention is to propose a kind ofly to prepare the method for optically active alpha-aminonitriles by the enantio-selectivity hydrocyanation of imines, can obtain the optically-active a-amino acid thus, and not have above-mentioned shortcoming.
One object of the present invention be to propose a kind of imines that passes through, or the enantio-selectivity hydrocyanation of preferred ketoimine prepares the method for optically active alpha-aminonitriles.
Another object of the present invention is to propose a kind of method for preparing optically active alpha-aminonitriles by imines, particularly ketoimine.
Another object of the present invention is to propose a kind of method that imines, particularly ketoimine prepare optically active alpha-aminonitriles of passing through, and is all very high by the enantiomeric purity and the productive rate of this method gained.
It is existing that oneself finds that according to method of the present invention, all these purposes can realize partly or entirely that this method is described below.
The invention summary
The present invention includes and a kind ofly prepare the novel method of optically active alpha-aminonitriles, it is characterized in that, ketoimine is contacted with hydrocyanation reagent in the presence of as the metal composite of catalyzer by the enantio-selectivity hydrocyanation of ketoimine.This catalyzer can be the monometallic type, and promptly every mol catalyst only contains a metal ion, or bimetal type, and promptly every mol catalyst contains two metal ions.
This method can make optically active alpha-aminonitriles, and its hydrolysis can obtain the optically-active a-amino acid, alpha-amino group ester and alpha-amino group acid amides.In other place of this specification sheets, except particularly pointing out, term " a-amino acid " not only comprises acid, also comprises ester and amide derivatives that these are sour.
Thus obtained optically-active a-amino acid can be used as the preparation chiral material synthetic intermediate, these chiral materials the treatment or agriculture aspect particularly useful.For example, disclosed in patent EP-A-0 629 616, these optically-active a-amino acids can be used as the intermediate of some mycocides of preparation such as 2-tetrahydroglyoxaline-5 ketone and 2-tetrahydroglyoxaline-5-thioketones.
Detailed Description Of The Invention the present invention relates to a kind of novel method for preparing the optically active alpha-aminonitriles of chemical formula I:
This method is in the presence of the metal composite as catalyzer, uses hydrocyanation reagent that the ketoimine of chemical formula II is carried out the enantio-selectivity hydrocyanation:
In the chemical formula I of representing alpha-aminonitriles and ketoimine respectively and (II): R
1And R
2Be different, and be selected from:
-on straight or branched, contain the alkyl or the haloalkyl of 1～6 carbon atom;
-on straight or branched, contain the alkoxyalkyl of 2～6 carbon atoms, alkyl-thio-alkyl, alkyl sulphur substituted alkyl, alkyl monosubstituted amino alkyl, alkenyl or alkynyl;
-on straight or branched, contain the dialkyl aminoalkyl or the cycloalkyl of 3～7 carbon atoms;
-aryl, i.e. phenyl, naphthyl, thienyl, furyl, pyridyl, benzothienyl, benzofuryl, quinolyl, isoquinolyl or methylenedioxyphenyl base, the perhaps aryl that is replaced by 1～3 group that is selected from R6; With
-aralkyl, aryloxyalkyl group, fragrant alkylthio, fragrant sulphur substituted alkyl, the definition of term " aryl " and " alkyl " is as above;
Or selectively
-R
1And R
2Can form carbocyclic ring or the heterocycle that contains 5～7 atoms with the carbon that they connected, all right and phenyl of these rings perhaps contains 1～3 and is selected from R
6Substituent phenyl condense; R
6The group of representative is selected from:
-halogen atom;
-contain the alkyl of 1～6 carbon atom, haloalkyl, alkoxyl group, halogenated alkoxy, alkylthio, halogenated alkylthio or alkane sulfo group;
-contain the cycloalkyl of 3～6 carbon atoms, halogenated cycloalkyl, alkene oxygen base, alkynyloxy group, alkenylthio group or alkynes sulfenyl;
-nitro or cyano group;
-contained the alkyl or the acyl group of 1～6 carbon atom, or contain single arbitrarily the replacement or disubstituted amino of carbalkoxy of 2～6 carbon atoms; With
-phenyl, phenoxy group or pyridyloxy, these groups can be selected from R by 1～3
7Identical or different group replace; R
7The group of representative is selected from:
-be selected from fluorine, chlorine, the halogen atom of bromine and iodine;
-contain the alkyl of the linearity or the branching of 1～6 carbon atom;
-contain the alkoxyl group or the alkylthio of the linearity or the branching of 1～6 carbon atom;
-contain the halogenated alkoxy or the halogenated alkylthio of the linearity or the branching of 1～6 carbon atom;
-itrile group; With
-nitro; Represent leavings group with T, be selected from:
-contain the alkyl of the linearity or the branching of 1～6 carbon atom; With
-aryl, as phenyl or naphthyl, or aralkyl, as benzyl, styroyl or hydrocinnamyl, these groups can be substituted.
According to a kind of optimal way of the present invention, the ketoimine of chemical formula II is such:
-R
1Represent aryl, can be by 1～3 R as defined above
6Group replaces;
-R
2Represent the alkyl or the haloalkyl that contain 1～6 carbon atom on the straight or branched, and
-T represents alkyl, the preferred tertiary alkyl, and as the tertiary butyl or 1,1,2,2-tetramethyl ethyl, or phenyl, preferably by electron-withdrawing group replaced, or benzyl, two or trityl, 4-methoxy-benzyl or 2,4-methoxy-benzyl.
According to the most preferred a kind of mode of the present invention, the ketoimine of chemical formula II is such:
-R
1Represent phenyl, can be by a R as defined above
6Base replaces;
-R
2Represent alkyl, be selected from methyl, ethyl, the propyl group of linearity or branching, the butyl of linearity or branching, the hexyl of the amyl group of linearity or branching and linearity or branching; And
-T represents alkyl, phenyl or benzyl, and these groups can be substituted.
T represents benzyl.
Asterisk (*) expression amino-nitrile in the chemistry formula I on the asymmetric carbon is opticity, and promptly amino-nitrile comes down to S or R configuration.
Method of the present invention can obtain substantial optically active alpha-aminonitriles." substantial optically active alpha-aminonitriles ", the specific rotation value that is meant amino-nitrile is not in fact 0, promptly one of enantiomorph R or S are to exist with much bigger amount than another enantiomorph S or R.The enantiomeric excess that " much bigger amount " is meant described enantiomorph is greater than 30%, more preferably greater than 50%.
" enantiomeric excess " this statement is meant the extra proportion of required enantiomorph with respect to unwanted enantiomorph.This ratio is calculated by one of following equation:
Wherein:
-%e.e. (S) represents the enantiomeric excess of isomer S,
-%e.e. (R) represents the enantiomeric excess of isomer R,
-[S] represent isomer S concentration and
-[R] represents the concentration of isomer R.
The inventive method is characterised in that, uses hydrocyanation reagent that the ketoimine of chemical formula II is as defined above carried out hydrocyanation.Hydrocyanation reagent is to discharge cryanide ion CN
-Organic compound.These organic compound are known to the synthetic expert of machine, and they are, for example prussic acid; tributyl cyaniding tin, acyl cyanide is as pyruvonitrile; trimethyl silicane cyanogen, basic metal or alkaline-earth metal prussiate, metal cyanides; as zinc cyanide, cyanalcohol, particularly acetone cyanohydrin; prussic acid; tributyl cyaniding tin and silylation cyanalcohol, for example trialkyl silica base cyanogen alkane.According to a kind of optimal way of the present invention, cryanide ion is with prussic acid, and tributyl cyaniding tin or trimethyl silicane cyanogen form provide, and being more preferably with prussic acid or trimethyl silicane cyanogen form provides.
Very surprisingly, people find, by adding the method for metal catalyst, can carry out the enantio-selectivity hydrocyanation to ketoimine, catalyst system therefor itself be chirality or the chiral induction agent.Term " chiral catalyst " is meant a kind of compound, and it contains at least one chiral atom and/or at least one chiral centre, and/or at least one chirality plane, and/or at least one chiral axis.Term " chiral induction catalyzer " is meant a kind of compound, itself is achirality, but because it is substituent sterically hindered, can induce the generation chirality in reaction product.
Used chirality or chiral induction metal catalyst in the inventive method can be the monometallic type of chemical formula (Ml), or the bimetal type of chemical formula (M2): L
1 N1Metal
1L
2 N2L
1 N1Metal
1Metal
2L
2 N2(M1) (M2)
In above-mentioned chemical formula:
-metal " Metal
1" and metal " Metal
2" can be identical, also can be different, and be selected from alkali metal cation, alkaline earth metal cation, transition-metal cation, i.e. the positively charged ion of the 1st to the 8th subgroup element in the periodic table of elements comprises the positively charged ion of the 8th family's element in group of the lanthanides and actinium series and the periodic table of elements;
-ligand L
1And L
2Can be identical, also can be different, and be selected from halogen, be fluorine, chlorine, bromine or iodine, the alkoxyl group that contains the linearity or the branching of 1～6 carbon atom on straight or branched contains the perfluoro alkoxy of the linearity or the branching of 1～6 carbon atom on straight or branched, contain the ether of 2～10 carbon atoms on straight or branched, prussiate, cyclopentadienyl or metallocenyl, particularly ferrocenyl, amine, alkylamine for example, dialkylamine, trialkylamine and tetraalkyl alkylene diamines, and cyclammonium, aromatic amine, pyridine for example, phosphine, alkoxide and thiolate, all these groups can be with substituting group and as following chemical formula (ⅰ), compound (ⅱ) and (ⅲ):
Wherein:
* X is selected from Sauerstoffatom, and sulphur atom contains the linearity or the branching of 1～6 carbon atom
Alkoxyl group, and contain the linearity or the branching allyloxy of 2～6 carbon atoms;
* R is selected from linearity or the branched-alkyl that contains 1～6 carbon atom, phenyl, trifluoro
Methyl, naphthyl is selected from fluorine, chlorine, the halogen atom of bromine and iodine, nitro, contain 1～
The linearity of 6 carbon atoms or branched alkoxy, and contain 2～6 carbon atoms
Linearity or branching allyl group or allyloxy;
* R
8And R
9Can be identical, also can be different, be selected from the linearity that contains 1～6 carbon atom
Or branched-alkyl, phenyl and naphthyl, each of these groups all can be by one
Or a plurality of bases of R as defined above replace; And
* Z represents 0,1 or 2, should be understood that when Z equals 2, as defined above
Two R bases can be identical, also can be different; And
N1 and n2 can be identical, also can be different, and represent 0 or integer, make when the monometallic mixture, n1+n2's and be definitely greater than 0, and be less than or equal to Metal
1Valency, or when the bimetal mixture, equal Metal
1And Metal
2The valency sum.
In the definition of above-mentioned monometallic (M1) and bimetal (M2) chirality or chiral induction mixture:
The the 1st to the 8th subgroup and the 8th family's element are meant the art technology people in the periodictable
Known to the member, and publish in as " physics and chemical handbook ", CRC publishes
Society, 55 editions (1974-1975), the 1b in the periodic table of elements of B-3 page or leaf～8b row
With the element in the 8th row;
When on behalf of oxygen and Z, equal 0 as X, the part of chemical formula (ⅰ) was 2,2 '-biphenyl
Phenol, the part of chemical formula (ⅱ) is dinaphthol (BINOL), chemical formula (ⅲ) joins
The decorum is called TADDOL.The particularly preferred a kind of TADDOL of the inventive method is it
Middle R
8Represent methylidene, R
9Represent the part of the chemical formula (ⅲ) of phenyl.
In preferred chirality of the inventive method or the chiral induction single-metal reforming catalyst, the mixture of preferred chemical formula (M1) can be individually or is contained one or more following feature: L in combination
1Be BINOL or TADDOL; Metal
1Be aluminium
III, zirconium
IVOr titanium
TVL
2Be halogen, alkoxyl group, cyclopentadienyl, prussiate, chemistry as defined above
The part of the part of formula (ⅰ) or chemical formula (ⅱ), ether, dimethoxy second
Alkane, trialkylamine, Tetramethyl Ethylene Diamine, arsenic pyridine or phosphuret-(t)ed hydrogen; With n1+n2's be strict greater than 0 and be less than or equal to Metal
1The integer of valence state.
In preferred chirality of the inventive method or the chiral induction single-metal reforming catalyst, the mixture of preferred chemical formula (M2) can be individually or is contained one or more following feature: L in combination
1Be the part of chemical formula (ⅰ) or the part of chemical formula (ⅱ); Metal
1Be aluminium
III, scandium
III, iron
III, ytterbium
III, germanium
III, gallium
III, zirconium
IIIOr titanium
IIIMetal
2Be basic metal, magnesium or copper; L
2Be the part of chemical formula (ⅰ) or the part of chemical formula (ⅱ); And n1+n2's and be strict greater than 0 and be less than or equal to Metal
1With Metal
2Valency
Attitude and integer.
Most preferably, in chirality of in this patent, using or the chiral induction single-metal reforming catalyst: L
1Be TADDOL; Metal
1It is zirconium
IVOr titanium
IVL
2Be chlorine, isopropoxy, cyclopentadienyl, prussiate, BINOL maybe can be with replacement
2 of base, 2 '-xenol; And n1 equals 1, and n2 equals 2; Or selectively, L
1Be BINOL; Metal
1Be aluminium
III, or titanium
IVL
2Be chlorine, isopropoxy, prussiate, BINOL or can be, 3 ', 5 and/or 5 ' 3
On be with substituent 2,2 '-xenol; With can be with substituent 2,2 '-biphenyl thiophenol,
3,3 '-dithio-2,2 '-dinaphthalene, 2,2 '-dimethoxy-biphenyl, 3,3 '-diformazan
Oxygen base-2,2 '-dinaphthalene, 2,2 '-two allyloxy biphenyl, ether, dimethoxy second
Alkane, Tetramethyl Ethylene Diamine or pyridine; And n1 equals 1, and n2 equals 3.
Most preferably, in chirality of in this patent, using or the chiral induction bimetallic catalyst: L
1Be BINOL or 3,3 '-dithio-2,2 '-dinaphthalene; Metal
1Be aluminium
III, scandium
III, iron
III, ytterbium
III, gallium
III, or titanium
IVMetal
2Be lithium, magnesium or copper; L
2Be BINOL, 3,3 '-dithio-2,2 '-dinaphthalene, or 2,2 '-xenol, its
Can be 3, go up the band substituting group for 3 ', 5 and/or 5 '; And n1+n2's and be strict greater than 0 and be less than or equal to Metal
1With Metal
2Valency
Attitude and integer.
According to method of the present invention, the indefiniteness example of spendable chirality of the hydrocyanation of ketoimine or chiral induction catalyzer comprises Ti (TADDOL) Cl
2, Ti (BINOL) (OiPr)
2, Ti (BINOL) (OiPr)
2(xenol H
2), Ti (BINOL) is (OiPr)
2Tetramethyl Ethylene Diamine, Al (BINOL)
2Li, AlLi (BINOL) (3,5,3 ', 5 '-four-tertiary butyl-2,2 '-xenol), AlH (BINOL)
2, AlCu (BINOL)
2, AlMgBr (BINOL)
2,, FeLi (BINOL)
2, TiLi (BINOL)
2, GeLi (BINOL)
2, YLi (BINOL)
2And ScLi (BINOL)
2
Can be used for chirality of the present invention or chiral induction metal catalyst can be with ex situ method preparation, promptly prepares with its oneself synthetic method, and it is contacted with ketoimine; Selectively, metal catalyst can prepare with in-situ method, promptly need not separate before the hydrocyanation reaction of participating in ketoimine of the present invention.
A kind of mode according to the inventive method, adopt the hydrocyanation reaction of the ketoimine of chirality as defined above or chiral induction metal catalyst, can in any solvent that is suitable for this reactive mode, carry out, for example in the mixture of organic solvent or organic solvent, carry out.Term " organic solvent " preferably is meant aprotic solvent, hydro carbons for example, and preferred hexanaphthene, benzene, toluene or dimethylbenzene, ether, t-butyl methyl ether, Di Iso Propyl Ether or tetrahydrofuran (THF), and/or halogenated solvent, chlorinated solvent for example is as methylene dichloride.
The inventive method is preferably carried out in toluene or methylene dichloride.
The hydrocyanation reaction of ketoimine normally carries out at low temperatures, for example-110 ℃～30 ℃, is preferably-80 ℃～20 ℃, more preferably-60 ℃～0 ℃, and for example-40 ℃～-20 ℃.Clearly, the said temperature scope provides in non-limiting mode.Temperature of reaction depends on used solvent in the type, hydrocyanation reagent of ketoimine and the reaction, and the organic synthesis expert understands suitable selective reaction temperature.
Similarly, the reaction times is relevant with solvent with used ketoimine kind, hydrocyanation reagent, catalyzer.Reaction times will be depended on the reaction degree of carrying out, available ordinary method detection reaction degree well known by persons skilled in the art, for example thin layer, liquid phase or gas-chromatography etc., NMR, mass spectrum or infrared spectra etc.Reaction times is generally 10 minutes～and two days, be preferably 10 minutes～24 hours, more preferably 20 minutes～7 hours.The embodiment of this specification sheets back will provide the order of magnitude in reaction times for the organic synthesis expert.
The preparation method of the alpha-aminonitriles of chemical formula I as defined above comprises the steps: a) according to known in fact, and be disclosed in as Angew.Chem.Int.Ed., 37 (22), (1998), the method among the 3186-8, in suitable solvent, for example toluene or methylene dichloride, at room temperature, reaction several minutes～several hours, for example 10 minutes～1 hour, ex situ or in-situ preparing metal composite; B) add hydrocyanation reagent; C) ketoimine of the chemical formula II of adding.
At last, after reaction finishes, according to the ordinary skill in the art, for example neutralize, washing, recrystallization, distillation, drying etc. are isolated the optically active alpha-aminonitriles of required chemical formula I from reaction medium.Under operational condition well known to those skilled in the art, can be simultaneously or implement in these separation methods one or multinomial in succession, those skilled in the art will know that reagent and reaction conditions how to select to be fit to every kind of situation.
In the above in the reaction scheme of Xiang Shuing, step b) and c) can carry out at the same time or separately, step c) also can be before step b).
The optically active alpha-aminonitriles of the chemical formula I that obtains like this, by removing the leavings group T in chemical as defined above formula I or the chemical formula II, and nitrile is hydrolyzed to the acid of chemical formula (AA), ester (AE) or acid amides (AD), be easy to change into the a-amino acid of the chemical formula (AA) of opticity, the alpha-amino group acid amides of the alpha-amino group ester of chemical formula (AE) or chemical formula (AD) for example changes into the opticity a-amino acid of chemical formula (AA):
R wherein
1And R
7Definition as above in the face of the qualification of chemical formula I or (II),
The step that removes of leavings group T is well known to those skilled in the art, and comprises the step that those can be understood or obtain in document, U.S. chemical abstract (CA), patent and Computer Database.When T represents alkyl, be easy to be removed, for example in acidic medium.
When T represented the phenyl that replaces arbitrarily, it was easy to be removed, for example in alkaline medium.
At last, when T represents benzyl, two-or trityl group, 4-methoxy-benzyl or 2, during the 4-methoxy-benzyl, it is easy to be removed, for example under oxidizing condition.
For example, when leavings group T is the N-benzyl, can under nitrogen atmosphere, in acidic medium, under the palladium carbon catalyst effect, remove in 20 ℃ of hydrogenolysis.
Itrile group is converted into acid, and behind ester or the amide functional group, the reaction that removes of carrying out leavings group T also is favourable.
Itrile group is converted into acid, and the reaction of ester or amide functional group is well known to those skilled in the art, and comprises the step that those can be understood or obtain in document, CA, patent and Computer Database.
These reactions are disclosed in for example J.Am.Chem.Soc., and 78, (1956) are in 5416.
The optically-active a-amino acid of chemical formula (AA) as defined above, its best application is as synthetic intermediate, is used for preparing especially at treatment or the useful chiral material of agricultural.
For example, disclosed among the patent EP-A-0 629 616, the optically-active a-amino acid of chemical formula (AA) is used to prepare some mycocide as intermediate, as chemical formula (A) 2-tetrahydroglyoxaline-5 ketone and 2-tetrahydroglyoxaline-5-thioketones:
R wherein
1And R
2As defined above in the face of the definition of the a-amino acid of chemical formula (1), and
W represention oxygen atom or sulphur atom or S=O group;
M represention oxygen atom or sulphur atom or methylene radical, but methylene radical halo;
P equals 0 or 1 integer;
R
3Representative:
-when P equal 0 or (M) p be CH
2When base, be hydrogen atom or can halogenated C
1-C
2Alkyl,
-when (M) p represention oxygen atom or sulphur atom, for can halogenated C
1-C
2Alkyl;
R
4Representative:
-hydrogen atom, or
-contain the alkyl of 1～6 carbon atom, or
-contain the alkoxyalkyl of 2～6 carbon atoms, alkylthio alkyl, haloalkyl, Qing Wanji, the thiocyano alkyl, alkenyl or alkynyl, or
-contain the dialkyl aminoalkyl of 3～6 carbon atoms, alkoxycarbonyl alkyl or N-alkyl-carbamoyl alkyl, or
-contain the N of 4～8 carbon atoms, N-dialkyl amido formyl radical alkyl, or
-aryl comprises phenyl, naphthyl, and thienyl, furyl, pyridyl, pyrimidyl, pyridazinyl, pyrazinyl, benzothienyl, benzofuryl, quinolyl, isoquinolyl or methylenedioxyphenyl, these groups can be selected from R by 1-3
6Group replace, or
-aralkyl, aryloxyalkyl group, fragrant sulfane base or fragrant sulphur substituted alkyl, the definition of term " aryl " and " alkyl " is as above;
R
5Representative:
-hydrogen or contain the alkyl of 1～6 carbon atom, haloalkyl, alkane sulfo group or haloalkane sulfo group, or
-contain the alkoxyalkyl of 2～6 carbon atoms, the alkane alkylthio, acyl group, thiazolinyl, alkynyl, the halo acyl group, carbalkoxy, the haloalkoxy carbonyl, alcoxyl alkane sulfo group or cyano group alkane sulfo group, or
-contain the alkoxyl group carbalkoxy of 3～6 carbon atoms, alkane sulfo-carbalkoxy or cyano group carbalkoxy, or
-formyl radical or contain the cycloalkyl of 3～6 carbon atoms, alkoxy acyl, alkane sulfo-acyl group, cyanato, alkene carbonyl or alkynes carbonyl, or
-contain the naphthene base carbonyl of 4～8 carbon atoms, or
-phenyl, aromatic alkyl carbonyl, particularly phenylacetyl and hydrocinnamoyl, aromatic carbonyl particularly can be selected from R by 1～3
6The benzoyl that replaces of group, the thiophene carbonyl, the furans carbonyl, the pyridine carbonyl, benzyloxycarbonyl, chaff oxygen base carbonyl, tetrahydrochysene chaff oxygen base carbonyl, the thiophene methoxycarbonyl, the pyridine methoxycarbonyl, carbobenzoxy or benzene thiocarbonyl, phenyl itself can be selected from R by 1～3
6Group replace alkyl thiocarbonyl, haloalkyl thio carbonyl, alkoxyalkyl thiocarbonyl, the Qing Wanji thiocarbonyl, benzyl thiocarbonyl, furfurylthio carbonyl, tetrahydrofurfuryl thiocarbonyl, the thenyl thiocarbonyl, picolyl thiocarbonyl or fragrant sulfo group, or
-can be replaced or disubstituted formamyl by the following groups list:
-contain the alkyl or the haloalkyl of 1～6 carbon atom,
-contain the cycloalkyl of 3～6 carbon atoms, alkenyl or alkynyl,
-contain the alkoxyalkyl of 2～6 carbon atoms, alkyl-thio-alkyl or Qing Wanji, or
-can be by 1～3 R
6The phenyl that base replaces;
-can be replaced or disubstituted sulfamyl by the following groups list:
-contain the alkyl or the haloalkyl of 1～6 carbon atom,
-contain the cycloalkyl of 3～6 carbon atoms, alkenyl or alkynyl,
-contain the alkoxyalkyl of 2～6 carbon atoms, alkyl-thio-alkyl or Qing Wanji,
Or
-can be by 1～3 R
6The phenyl that base replaces;
-contain the alkylthio alkane sulfo group of 3～8 carbon atoms or contain the ring of 3～7 carbon atoms
The alkyl sulfo group;
-R
4And R
5Connect together, also can constitute pyrrolidone-base with the nitrogen-atoms that they connected, the alkyl that piperidino-(1-position only), morpholinyl or piperazinyl, these groups can be contained 1～3 carbon atom replaces.
R
6Representative:
-halogen atom, or
-contain the alkyl of 1～6 carbon atom, haloalkyl, alkoxyl group, halogenated alkoxy, alkylthio, halogenated alkylthio or alkane sulfo group, or
-contain the cycloalkyl of 3～6 carbon atoms, halogenated cycloalkyl, alkene oxygen base, alkynyloxy group, alkenylthio group or alkynes sulfenyl, or
-nitro or cyano group, or
-can be contained the alkyl or the acyl group of 1～6 carbon atom, or contain the replacement of carbalkoxy list or the disubstituted amino of 2～6 carbon atoms, or
-phenyl, phenoxy group or pyridyloxy, these groups can be selected from R by 1～3
7Identical or different group replace,
R
7Representative:
-be selected from fluorine, chlorine, the halogen atom of bromine and iodine, or
-contain the alkyl of 1～6 carbon atom, or
-contain the alkoxyl group or the alkylthio of 1～6 carbon atom, or
-contain the halogenated alkoxy or the halogenated alkylthio of 1～6 carbon atom, or
-itrile group or nitro.
The preparation method of the compound of chemical formula (A) can represent with figure below:
Radicals R among the figure
1, R
2, R
3, R
4, R
5, M, the definition of P and W as above, R
10Representation hydroxy contains the alkoxyl group of 1～6 carbon atom, benzyloxy, amino, alkylamino or dialkyl amido, or contain the alkylamino of 1～6 carbon atom, and the Y representative group of leaving away, as be selected from chlorine, the halogen atom of bromine and iodine, or sulfate radical, alkyl sulphur oxygen base or aryl sulphur oxygen base.
In last figure:
-step (1) relates to method of the present invention, and illustrates hereinafter;
-step (2)～(5) are disclosed among the patent WO 98/03490, and its content is combined in herein as a reference;
-step (6) is disclosed among the EP-A-0 629 616, and its content is combined in herein as a reference.
By the ketoimine of the chemical formula II intermediate through chemical formula I, the entire method of the compound of synthetic chemistry formula (A) is new, and comprises within the scope of the invention.
The following examples will help to be illustrated more clearly in and to be familiar with the purpose and the advantage of the inventive method, but limit its scope anything but.Ex situ prepares the general EXAMPLE Example 1:M of metal composite
3+Li (BINOL)
2(M=Fe, Ti, Ge, Y, Sc):
At 0 ℃, will
nBuLi (0.4ml, the hexane solution of 1.5M) joins BINOL, and (29mg is in diethyl ether solution 0.1mmol).Behind the room temperature reaction 0.5h, add MCl
3THF (0.5mmol) (4ml) solution, this mixture refluxes a night.Behind the reaction medium cool to room temperature, add toluene (15ml), and solvent evaporation is fallen.Add toluene once more, and once more solvent evaporation is fallen, to obtain the extremely low catalyzer of polar solvent content.Add 5ml toluene, catalyzer is standby.Use hydrocyanation EXAMPLE Example 2:Ti (TADDOL) Cl of the metal composite of in-situ method preparation
2:
In methylene dichloride, use equimolar TiCl
4And Ti (OiPr)
4Mixture is prepared TiCl
2(OiPr)
2Solution.(1ml 0.1M) joins 4S, and (47mg is in methylene dichloride 0.1mmol) (1ml) solution for 5S-TADDOL with this solution.This reaction mixture at room temperature reacted 1 hour.This reaction mixture is cooled to-40 ℃ in bath, add N-benzyl-methyl-benzene imines (210mg 1mmol), obtains the solution of darkorange, add then TMSCN (0.26ml, 2mmol).-40 ℃ are reacted after 6 hours, with saturated Na down
2CO
3Solution is hydrolyzed.After isolation of purified program commonly used, imines is 60% to the transformation efficiency of amino-nitrile, and enantiomeric excess is 24% (detecting under Chiralcel AD state with the solid-liquid chromatogram).Embodiment 3:Ti (BINOL) (OiPr)
2
Tetraisopropoxy titanium (0.5ml, 0.1M toluene solution) is joined BINOL, and (14mg, in toluene 0.05mmol) (4.5ml) solution, reaction mixture at room temperature stirred 20 minutes.Solution is cooled to-20 ℃, add successively subsequently TMSCN (0.13ml) and N-benzyl-methyl-benzene imines (105mg, 0.5mmol).After 1 hour, use NaHCO-20 ℃ of reactions
3Hydrolysis.Transformation efficiency is 80%, and enantiomeric excess is 20%.Embodiment 4:Ti (BINOL) (OiPr)
2(xenol H
2):
Tetraisopropoxy titanium (0.5ml, 0.1M toluene solution) is joined BINOL, and (14mg, in toluene 0.05mmol) (4.5ml) solution, reaction mixture at room temperature stirred 20 minutes.Add 3,3 ', 5 then, 5 '-tetra-tert xenol (0.05mmol), solution becomes redness.At once solution is cooled to-20 ℃, add successively subsequently TMSCN (0.13ml) and N-benzyl-methyl-benzene imines (105mg, 0.5mmol).React after 1 hour, use NaHCO
3Hydrolysis.After isolation of purified program commonly used, transformation efficiency is 87%, and enantiomeric excess is 48%.Embodiment 5:Ti (BINOL) (OiPr)
2TMEDA
n
Tetraisopropoxy titanium (0.5ml, 0.1M toluene solution) is joined BINOL, and (14mg, in toluene 0.05mmol) (4.5ml) solution, reaction mixture at room temperature stirred 20 minutes.Add tetramethyl-ethylene base diamines (0.1mmol) then.At once solution is cooled to-20 ℃, add successively subsequently TMSCN (O.13ml) and N-benzyl-methyl-benzene imines (105mg, 0.5mmol).React after 1 hour, use NaHCO
3Hydrolysis.After isolation of purified program commonly used, transformation efficiency is 80%, and enantiomeric excess is 56%.Embodiment 6:Al (BINOL)
2Li:
At 0 ℃ with nBuLi (0.5ml, the toluene/hexane mixing solutions of 0.1M) and Et
3Al (0.5ml, the toluene/hexane mixing solutions of 0.1M) joins BINOL, and (29mg is in toluene 0.1mmol) (4ml) solution.Reaction mixture is stirred 0.5h, be cooled to-20 ℃ then, add trimethyl silicane cyanogen (0.13ml) and N-benzyl-methyl-benzene imines (0.5mmol) subsequently successively.
When replacing TMSCN with HCN, the catalyzer for preparing in toluene can rise to suitable temperature.Imines joined in the reaction mixture before HCN.Embodiment 7:AlLi (BINOL) (3,5,3 ', 5 '-tetra-tert-2,2 '-xenol):
At 0 ℃ with nBuLi (0.5ml, the toluene/hexane mixing solutions of 0.1M) and Et
3Al (0.5ml, the toluene/hexane mixing solutions of 0.1M), join BINOL (14mg, 0.05mmol) and 3,5,3 ', 5 '-tetra-tert-2, (18mg is in toluene 0.05mmol) (4ml) solution for 2 '-xenol.Reaction mixture is stirred 0.5h, be cooled to-20 ℃ then.Add TMSCN (0.13ml) and imines (0.5mmol) then successively.Embodiment 8:AlH (BINOL)
2:
At 0 ℃, with Et
3Al (0.5ml, the toluene/hexane mixing solutions of 0.1M) joins BINOL, and (29mg is in toluene 0.1mmol) (4.5ml) solution.Reaction mixture is stirred 0.5h, and is cooled to-20 ℃.Add TMSCN (0.13ml) and imines (0.5mmol) then successively.Embodiment 9:AlCu (BINOL)
2:
At 0 ℃, with Et
3Al (0.5ml, the toluene/hexane mixing solutions of 0.1M) and (Cu
I) (this solution contains Synthetic 2 for 0.33ml, the toluene solution of 0.15M, and 4, the dioxane in the 6-Three methyl Benzene copper process) (29mg is in toluene 0.1mmol) (4ml) solution to join BINOL.Reaction mixture is stirred 0.5h, and is cooled to-20 ℃.Add TMSCN (0.13ml) and imines (0.5mmol) then successively.Embodiment 10:AlMgBr (BINOL)
2:
At 0 ℃, with Et
3Al (0.5ml, the toluene/hexane mixing solutions of 0.1M) and MeMgBr (0.016ml, the diethyl ether solution of 3M) join BINOL, and (29mg is in toluene 0.1mmol) (4.5 ml) solution.Reaction mixture is stirred 0.5h, be cooled to-20 ℃ subsequently.Add TMSCN (0.13ml) and imines (0.5mmol) then successively.Nitrile is converted into the EXAMPLE Example 11 of acid amides: the hydration of amino-nitrile
At 0 ℃, with amino-nitrile (1-benzylamino-1-cyanoethyl benzene; 4.0mmol) mix with 1.8g sulfuric acid (95%).With mixture at 90 ℃ of constant temperature 1.5h.After the cooling, reaction medium is used the 20ml washed with dichloromethane 3 times again with the dilution of 3ml water.After adding the 0.5g solid sodium hydroxide, with dichloromethane extraction amino amides (2-benzylamino-2-Phenylpropionamide).After isolation of purified program commonly used, productive rate is 43%.Remove the hydrogenolysis of the EXAMPLE Example 12:N-benzyl amino amides of leavings group
(0.35mmol) is dissolved in the 5ml methyl alcohol with amino amides.Add 0.2ml acetate, add 52mg catalyzer (10% load on palladium hydroxide on the gac) then.Reaction medium stirs 18h in 20 ℃ under 1 atmospheric hydrogen atmosphere.Through isolation of purified commonly used with after purifying, obtain debenzylation acid amides (2-amino-2-Phenylpropionamide), productive rate is 95%.
Claims (20)
1. method for preparing the optically active alpha-aminonitriles of chemical formula I:
This method is in the presence of chirality or chiral induction metal composite as catalyzer, uses hydrocyanation reagent that the ketoimine of chemical formula II is carried out hydrocyanation:
In the chemical formula I of representing alpha-aminonitriles and ketoimine respectively and (II): R
1And R
2Be different, and be selected from:
-on straight or branched, contain the alkyl or the haloalkyl of 1～6 carbon atom;
-on straight or branched, contain the alkoxyalkyl of 2～6 carbon atoms, alkyl-thio-alkyl, alkyl sulphur substituted alkyl, alkyl monosubstituted amino alkyl, alkenyl or alkynyl;
-on straight or branched, contain the dialkyl aminoalkyl or the cycloalkyl of 3～7 carbon atoms;
-aryl, i.e. phenyl, naphthyl, thienyl, furyl, pyridyl, benzothienyl, benzofuryl, quinolyl, isoquinolyl or methylenedioxyphenyl base, these groups can randomly be selected from R by 1～3
6Group replace; With
-aralkyl, aryloxyalkyl group, fragrant alkylthio, fragrant sulphur substituted alkyl, the definition of term " aryl " and " alkyl " is as above;
Or selectively
-R
1And R
2Can form carbocyclic ring or the heterocycle that contains 5～7 atoms with the carbon that they connected, all right and phenyl of these rings perhaps has 1～3 and is selected from R
6The phenyl of substituent optional replacement condense; R
6The group of representative is selected from:
-halogen atom;
-contain the alkyl of 1～6 carbon atom, haloalkyl, alkoxyl group, halogenated alkoxy, alkylthio, halogenated alkylthio or alkane sulfo group;
-contain the cycloalkyl of 3～6 carbon atoms, halogenated cycloalkyl, alkene oxygen base, alkynyloxy group, alkenylthio group or alkynes sulfenyl;
-nitro or cyano group;
-can be contained the alkyl or the acyl group of 1～6 carbon atom, or the carbalkoxy that contains 2～6 carbon atoms randomly singly replaces or disubstituted amino; With
-phenyl, phenoxy group or pyridyloxy, these groups can randomly be selected from R by 1～3
7Identical or different group replace; R
7The group of representative is selected from:
-be selected from fluorine, chlorine, the halogen atom of bromine and iodine;
-contain the alkyl of the linearity or the branching of 1～6 carbon atom;
-contain the alkoxyl group or the alkylthio of the linearity or the branching of 1～6 carbon atom;
-contain the halogenated alkoxy or the halogenated alkylthio of the linearity or the branching of 1～6 carbon atom;
-itrile group; With
-nitro; Represent leavings group with T, be selected from:
-contain the alkyl of the linearity or the branching of 1～6 carbon atom; With
-aryl, as phenyl or naphthyl, or aralkyl, as benzyl, styroyl or hydrocinnamyl, these groups can be optionally substituted.
2. according to the method for claim 1, it is characterized in that the ketoimine of chemical formula II is such:
-R
1Represent aryl, can be by 1～3 R as defined above
6Group is optional to be replaced;
-R
2Represent the alkyl or the haloalkyl that contain 1～6 carbon atom on the straight or branched, and
-T represents alkyl, the preferred tertiary alkyl, and as the tertiary butyl or 1,1,2,2-tetramethyl ethyl, or phenyl are preferably replaced by electron-withdrawing group, or benzyl, and two or trityl, 4-methoxy-benzyl or 2,4-methoxy-benzyl.
3. according to the method for aforementioned arbitrary claim, it is characterized in that the ketoimine of chemical formula II is such:
-R
1Represent phenyl, can be by a R as defined above
6Base is optional to be replaced;
-R
2Represent alkyl, be selected from methyl, ethyl, the propyl group of linearity or branching, the butyl of linearity or branching, the hexyl of the amyl group of linearity or branching and linearity or branching; And
-T represents alkyl, phenyl or benzyl, and these groups can be optionally substituted.
4. according to the method for aforementioned arbitrary claim, it is characterized in that leavings group T is a benzyl.
5. according to the method for aforementioned arbitrary claim, it is characterized in that it comprises the steps:
A) ex situ or in-situ preparing chirality or chiral induction metal composite;
B) add hydrocyanation reagent;
C) ketoimine of the chemical formula II of adding; Step b) and c) can carry out at the same time or separately, step c) also can be before step b).
6. according to the method for aforementioned arbitrary claim, it is characterized in that reaction is carried out at low temperatures, for example-110 ℃～30 ℃, be preferably-80 ℃～20 ℃, more preferably-60 ℃～0 ℃.
7. according to the method for one of claim 1～6, it is characterized in that hydrocyanation reagent is selected from prussic acid, tributyl cyaniding tin, trimethyl silicane cyanogen, basic metal or alkaline-earth metal prussiate, metal cyanides, cyanalcohol and silylation cyanalcohol.
8. according to the method for claim 7, it is characterized in that hydrocyanation reagent is selected from prussic acid, tributyl cyaniding tin or trimethyl silicane cyanogen.
9. according to the method for one of claim 1～6, it is characterized in that chirality or chiral induction metal composite can be the monometallic types of chemical formula (M1), or the bimetal type of chemical formula (M2):
L
1 n1Metal
1L
2 n2 L
1 n1Metal
1Metal
2L
2 n2
(M1) (M2)
At chemical formula (M1) with (M2):
-metal " Metal
1" and metal " Metal
2" can be identical, also can be different, and be selected from alkali metal cation, alkaline earth metal cation, transition-metal cation, i.e. the positively charged ion of the 1st to the 8th subgroup element in the periodic table of elements comprises the positively charged ion of the 8th family's element in group of the lanthanides and actinium series and the periodic table of elements;
-ligand L
1And L
2Can be identical, also can be different, and be selected from halogen, i.e. fluorine, chlorine, bromine or iodine contains the alkoxyl group of the linearity or the branching of 1～6 carbon atom on straight or branched, contain the perfluoro alkoxy of the linearity or the branching of 1～6 carbon atom on straight or branched, the ether that on straight or branched, contains 2～10 carbon atoms, prussiate, cyclopentadienyl or metallocenyl, particularly ferrocenyl, amine, cyclammonium, aromatic amine, phosphine, alkoxide and thiolate, all these groups can be chosen area substituting group and following chemical formula (ⅰ) wantonly, compound (ⅱ) and (ⅲ):
Wherein:
* X is selected from Sauerstoffatom, and sulphur atom contains the linearity or the branching of 1～6 carbon atom
Alkoxyl group, and contain the linearity or the branching allyloxy of 2～6 carbon atoms;
* R is selected from linearity or the branched-alkyl that contains 1～6 carbon atom, phenyl, trifluoro
Methyl, naphthyl is selected from fluorine, chlorine, the halogen atom of bromine and iodine, nitro, contain 1～
The linearity of 6 carbon atoms or branched alkoxy, and contain 2～6 carbon atoms
Linearity or branching allyl group or allyloxy;
* R
8And R
9Can be identical, also can be different, be selected from the linearity that contains 1～6 carbon atom
Or branched-alkyl, phenyl and naphthyl, each of these groups all can be by one
Or a plurality of bases of R as defined above replace; And
* Z represents 0,1 or 2, should be understood that when Z equals 2, as defined above
Two R bases can be identical, also can be different; And
N1 and n2 can be identical, also can be different, and represent 0 or integer, make when the monometallic mixture, n1+n2's and be definitely greater than 0, and be less than or equal to Metal
1Valency, or when the bimetal mixture, equal Metal
1And Metal
2The valency sum.
10. according to the method for claim 9, wherein, chirality or chiral induction metal composite are the monometallic mixture of chemical formula (M1), can be individually or contain one or more following feature: L in combination
1Be BINOL or TADDOL; Metal
1Be aluminium
III, zirconium
IVOr titanium
IVL
2Be halogen, alkoxyl group, cyclopentadienyl, prussiate is as fixed in the claim 9
The part of the chemical formula (ⅰ) of justice or the part of molecular formula (ⅱ), ether, dimethoxy second
Alkane, trialkylamine, Tetramethyl Ethylene Diamine, arsenic pyridine or phosphine; With n1+n2's be strict greater than 0 and be less than or equal to Metal
1The integer of valence state.
11. according to the method for one of claim 9 and 10, wherein, chirality or chiral induction metal composite are the monometallic mixture of chemical formula (M1), wherein: L
1Be TADDOL; Metal
1It is zirconium
IVOr titanium
IVL
2Be chlorine, isopropoxy, cyclopentadienyl, prussiate, BINOL, or with or without substituent 2,2 '-xenol; And n1 equals 1, and n2 equals 2;
12. according to the method for one of claim 9～11, wherein, chirality or chiral induction metal composite are the monometallic mixture of chemical formula (M1), wherein: L
1Be BINOL; Metal
1Be aluminium
III, or titanium
IVL
2Be chlorine, isopropoxy, prussiate, BINOL or can be 3, be with substituently 2 on 3 ', 5 and/or 5 ', 2 '-xenol can be with substituent 2,2 '-biphenyl thiophenol, 3,3 '-dithio-2,2 '-dinaphthalene, 2,2 '-dimethoxy-biphenyl, 3,3 '-dimethoxy-2,2 '-dinaphthalene, 2,2 '-two allyloxy biphenyl, ether, glycol dimethyl ether, Tetramethyl Ethylene Diamine or pyridine; And n1 equals 1, and n2 equals 3.
13. according to the method for claim 9, wherein, chirality or chiral induction metal composite are the bimetal mixture of chemical formula (M2), can be individually or contain one or more following feature: L in combination
1Be the part of chemical formula (ⅰ) or the part of chemical formula (ⅱ); Metal
1Be aluminium
III, scandium
III, iron
III, ytterbium
III, germanium
III, gallium
III, zirconium
IIIOr titanium
IIIMetal
2Be basic metal, magnesium or copper; L
2Be the part of chemical formula (ⅰ) or the part of chemical formula (ⅱ); And n1+n2's and be strict greater than 0 and be less than or equal to Metal
1With Metal
2Valence state and integer.
14. according to the method for one of claim 9 and 13, wherein, chirality or chiral induction metal composite are the bimetal mixture of chemical formula (M2), wherein: L
1Be BINOL or 3,3 '-dithio-2,2 '-dinaphthalene; Metal
1Be aluminium
III, scandium
III, iron
III, ytterbium
III, gallium
III, or titanium
IVMetal
2Be lithium, magnesium or copper; L
2Be BINOL, 3,3 '-dithio-2,2 '-dinaphthalene, or 2,2 '-xenol, its
Can be 3, go up with or without substituting group for 3 ', 5 and/or 5 '; And n1+n2's and be strict greater than 0 and be less than or equal to Metal
1With Metal
2Valence state and integer.
15. according to claim 9, any one method in 10,11,12,13 and 14, wherein, chirality or chiral induction metal composite are selected from Ti (TADDOL) Cl
2, Ti (BINOL) (OiPr)
2, Ti (BINOL) (OiPr)
2(xenol H
2), Ti (BINOL) is (OiPr)
2Tetramethyl Ethylene Diamine, Al (BINOL)
2Li, AlLi (BINOL) (3,5,3 ', 5 '-four-tertiary butyl-2,2 '-xenol), AlH (BINOL)
2, AlCu (BINOL)
2, AlMgBr (BINOL)
2, FeLi (BINOL)
2, TiLi (BINOL)
2, GeLi (BINOL)
2, YLi (BINOL)
2And ScLi (BINOL
)2.
16. chirality in one of claim 9～16 or the application of chiral induction metal composite in the hydrocyanation of the ketoimine of the chemical formula II of one of claim 1～8.
17. the optically active alpha-aminonitriles of the chemical formula I that obtains according to the method for one of claim 1～15.
18. prepare chemical formula (AA) according to following reaction stream formula, the method for compound (AD) and (AE):
Wherein, R
1, R
2With the definition in one of the definition of T group such as claim 1～4, and this flow process is characterised in that, step (1) is the method according to one of claim 1～15, the ketoimine hydrocyanation of chemical formula II is changed into the process of the optically active alpha-aminonitriles of chemical formula I.
19. the chemical formula (AA) that obtains according to the method for last claim, (AD) and compound (AE).
20. prepare the method for chemical formula (A) according to following reacting flow chart:
Wherein, R
1, R
2With the definition in one of the definition of T group such as claim 1～4, and
W represention oxygen atom or sulphur atom or S=O group;
M represention oxygen atom or sulphur atom or methylene radical, but methylene radical halo or do not have halo;
P equals 0 or 1 integer;
R
3Representative:
-when P equal 0 or (M) p be CH
2When base is for hydrogen atom or halo or there is not halogenated C
1-C
2Alkyl,
-when (M) p represention oxygen atom or sulphur atom, for halo or there is not halogenated C
1-C
2Alkyl;
R
4Representative:
-hydrogen atom, or
-contain the alkyl of 1～6 carbon atom, or
-contain the alkoxyalkyl of 2～6 carbon atoms, alkylthio alkyl, haloalkyl, Qing Wanji, the thiocyanogen alkyl, alkenyl or alkynyl, or
-contain the dialkyl aminoalkyl of 3～6 carbon atoms, alkoxycarbonyl alkyl or N-alkyl-carbamoyl alkyl, or
-contain the N of 4～8 carbon atoms, N-dialkyl amido formyl radical alkyl, or
-aryl comprises phenyl, naphthyl, and thienyl, furyl, pyridyl, pyrimidyl, pyridazinyl, pyrazinyl, benzothienyl, benzofuryl, quinolyl, isoquinolyl or methylenedioxyphenyl, these groups can be selected from R by 1-3
6Group randomly replace, or
-aralkyl, aryloxyalkyl group, fragrant sulfane base or fragrant sulphur substituted alkyl, the definition of term " aryl " and " alkyl " is as above;
R
5Representative:
-hydrogen or contain the alkyl of 1～6 carbon atom, haloalkyl, alkane sulfo group or haloalkane sulfo group, or
-contain the alkoxyalkyl of 2～6 carbon atoms, the alkane alkylthio, acyl group, thiazolinyl, alkynyl, the halo acyl group, carbalkoxy, the haloalkoxy carbonyl, alcoxyl alkane sulfo group or cyano group alkane sulfo group, or
-contain the alkoxyl group carbalkoxy of 3～6 carbon atoms, alkane sulfo-carbalkoxy or cyano group carbalkoxy, or
-formyl radical or contain the cycloalkyl of 3～6 carbon atoms, alkoxy acyl, alkane sulfo-acyl group, cyanato, alkene carbonyl or alkynes carbonyl, or
-contain the naphthene base carbonyl of 4～8 carbon atoms, or
-phenyl, aromatic alkyl carbonyl, particularly phenylacetyl and hydrocinnamoyl, aromatic carbonyl particularly can be selected from R by 1～3
6The optional benzoyl that replaces of group, the thiophene carbonyl, the furans carbonyl, the pyridine carbonyl, benzyloxycarbonyl, chaff oxygen base carbonyl, tetrahydrochysene chaff oxygen base carbonyl, the thiophene methoxycarbonyl, the pyridine methoxycarbonyl, carbobenzoxy or benzene thiocarbonyl, phenyl itself can be selected from R by 1～3
6Group optional replace alkyl thiocarbonyl, haloalkyl thio carbonyl, alkoxyalkyl thiocarbonyl, the Qing Wanji thiocarbonyl, benzyl thiocarbonyl, furfurylthio carbonyl, tetrahydrofurfuryl thiocarbonyl, the thenyl thiocarbonyl, picolyl thiocarbonyl or fragrant sulfo group, or
-can be replaced or disubstituted formamyl by the optional list of following groups:
-contain the alkyl or the haloalkyl of 1～6 carbon atom,
-contain the cycloalkyl of 3～6 carbon atoms, alkenyl or alkynyl,
-contain the alkoxyalkyl of 2～6 carbon atoms, alkyl-thio-alkyl or Qing Wanji, or
-can be by 1～3 R
6The optional phenyl that replaces of base;
-can be replaced or disubstituted sulfamyl by the optional list of following groups:
-contain the alkyl or the haloalkyl of 1～6 carbon atom,
-contain the cycloalkyl of 3～6 carbon atoms, alkenyl or alkynyl,
-contain the alkoxyalkyl of 2～6 carbon atoms, alkyl-thio-alkyl or Qing Wanji,
Or
-can be by 1～3 R
6The optional phenyl that replaces of base;
-contain the alkylthio alkane sulfo group of 3～8 carbon atoms or contain 3～7 carbon atoms
The cycloalkyl sulfo group;
-R
4And R
5Connect together, can constitute pyrrolidone-base with the nitrogen-atoms that they connected, piperidino-(1-position only), morpholinyl or piperazinyl, these groups can be contained optional replacement of alkyl of 1～3 carbon atom;
R
6Representative:
-halogen atom, or
-contain the alkyl of 1～6 carbon atom, haloalkyl, alkoxyl group, halogenated alkoxy, alkylthio, halogenated alkylthio or alkane sulfo group, or
-contain the cycloalkyl of 3～6 carbon atoms, halogenated cycloalkyl, alkene oxygen base, alkynyloxy group, alkenylthio group or alkynes sulfenyl, or
-nitro or cyano group, or
-can be contained the alkyl or the acyl group of 1～6 carbon atom, or contain optional single the replacement or disubstituted amino of carbalkoxy of 2～6 carbon atoms, or
-phenyl, phenoxy group or arsenic pyridine oxygen base, these groups can be selected from R by 1～3
7Optional replacement of identical or different group;
R
7Representative:
-be selected from fluorine, chlorine, the halogen atom of bromine and iodine, or
-contain the alkyl of 1～6 carbon atom, or
-contain the alkoxyl group or the alkylthio of 1～6 carbon atom, or
-contain the halogenated alkoxy or the halogenated alkylthio of 1～6 carbon atom, or
-itrile group or nitro;
This flow process is characterised in that step (1) is the method according to one of claim 1～15, the ketoimine hydrocyanation of chemical formula II is changed into the process of the optically active alpha-aminonitriles of chemical formula I.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR9907512A FR2794743A1 (en) | 1999-06-09 | 1999-06-09 | NOVEL PROCESS FOR THE PREPARATION OF OPTICALLY ACTIVE ALPHA-AMINONITRILES |
| FR99/07512 | 1999-06-09 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1314880A true CN1314880A (en) | 2001-09-26 |
Family
ID=9546766
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN00801171A Pending CN1314880A (en) | 1999-06-09 | 2000-06-09 | Novel method for preparing optically active alpha-aminonitriles |
Country Status (11)
| Country | Link |
|---|---|
| EP (1) | EP1102744A1 (en) |
| JP (1) | JP2003501411A (en) |
| KR (1) | KR20010072385A (en) |
| CN (1) | CN1314880A (en) |
| AU (1) | AU5540900A (en) |
| BR (1) | BR0006829A (en) |
| FR (1) | FR2794743A1 (en) |
| HU (1) | HUP0103428A2 (en) |
| PL (1) | PL345995A1 (en) |
| TR (1) | TR200100435T1 (en) |
| WO (1) | WO2000075104A1 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103342652A (en) * | 2013-07-24 | 2013-10-09 | 重庆紫光化工股份有限公司 | Preparation method for N,N-dimethylamino acetate |
| CN103962180A (en) * | 2013-08-06 | 2014-08-06 | 汕头大学 | Salen coordination polymer catalyst for preparing alpha-aminonitrile and preparation method of catalyst |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2398569B (en) * | 2003-02-19 | 2006-12-27 | Merck Patent Gmbh | Chiral compounds comprising Group IV element with two 1,1'-binaphth-2,2'-diyl-containing or related substituents |
| US20100179343A1 (en) * | 2007-03-29 | 2010-07-15 | Agency For Science, Technology And Research | Method of producing an optically active cyanohydrin derivative |
| WO2009041919A1 (en) * | 2007-09-28 | 2009-04-02 | Agency For Science, Technology And Research | Titanium compound and process for asymmetric cyanation of imines |
| US8580991B2 (en) * | 2008-12-17 | 2013-11-12 | Takasago International Corporation | Aluminium complexes and use thereof as a catalyst in intramolecular ring closure reactions |
| JP5501701B2 (en) * | 2009-09-09 | 2014-05-28 | 三井化学株式会社 | Method for asymmetric cyanation of imine |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2706456B1 (en) * | 1993-06-18 | 1996-06-28 | Rhone Poulenc Agrochimie | Optically active derivatives of 2-imidazoline-5-ones and 2-imidazoline-5-thiones fungicides. |
| FR2751327A1 (en) * | 1996-07-22 | 1998-01-23 | Rhone Poulenc Agrochimie | INTERMEDIATES FOR THE PREPARATION OF 2-IMIDAZOLINE-5-ONES |
-
1999
- 1999-06-09 FR FR9907512A patent/FR2794743A1/en not_active Withdrawn
-
2000
- 2000-06-09 JP JP2001501585A patent/JP2003501411A/en not_active Withdrawn
- 2000-06-09 HU HU0103428A patent/HUP0103428A2/en unknown
- 2000-06-09 WO PCT/FR2000/001597 patent/WO2000075104A1/en not_active Application Discontinuation
- 2000-06-09 PL PL00345995A patent/PL345995A1/en unknown
- 2000-06-09 BR BR0006829-2A patent/BR0006829A/en not_active IP Right Cessation
- 2000-06-09 TR TR2001/00435T patent/TR200100435T1/en unknown
- 2000-06-09 EP EP00940478A patent/EP1102744A1/en not_active Withdrawn
- 2000-06-09 AU AU55409/00A patent/AU5540900A/en not_active Abandoned
- 2000-06-09 CN CN00801171A patent/CN1314880A/en active Pending
- 2000-06-09 KR KR1020017001744A patent/KR20010072385A/en not_active Application Discontinuation
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103342652A (en) * | 2013-07-24 | 2013-10-09 | 重庆紫光化工股份有限公司 | Preparation method for N,N-dimethylamino acetate |
| CN103962180A (en) * | 2013-08-06 | 2014-08-06 | 汕头大学 | Salen coordination polymer catalyst for preparing alpha-aminonitrile and preparation method of catalyst |
| CN103962180B (en) * | 2013-08-06 | 2016-02-17 | 汕头大学 | For the preparation of the Salen coordination polymer Catalysts and its preparation method of alpha-aminonitriles |
Also Published As
| Publication number | Publication date |
|---|---|
| HUP0103428A2 (en) | 2002-01-28 |
| TR200100435T1 (en) | 2001-08-21 |
| EP1102744A1 (en) | 2001-05-30 |
| WO2000075104A1 (en) | 2000-12-14 |
| JP2003501411A (en) | 2003-01-14 |
| FR2794743A1 (en) | 2000-12-15 |
| KR20010072385A (en) | 2001-07-31 |
| BR0006829A (en) | 2001-10-30 |
| PL345995A1 (en) | 2002-01-14 |
| AU5540900A (en) | 2000-12-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1293942C (en) | Latalyst system containing Ni(O) for hydrocyanation | |
| CN1212294C (en) | Improved separating method | |
| CN1649861A (en) | Kinetics resolution method | |
| CN1106396A (en) | Intermediates useful in the production of aromatic amino-alcohol derivatives having anti-diabetic an21443/o1besity properties | |
| CN1674989A (en) | Method for making nitrile compounds from ethylenically unsaturated compounds | |
| CN1914167A (en) | Method for the separation of pentenenitrile isomers | |
| CN1875027A (en) | Use of azeotropically dried nickel(ii) halogenides | |
| CN101068782A (en) | Process for the synthesis of 4-(3-sulfonylphenyl)-piperidines | |
| CN1675172A (en) | Process for making nitrile compounds from ethylenically unsaturated compounds | |
| CN1767895A (en) | System suitable for the hydrocyanation of olefinically unsaturated compounds. | |
| CN1874845A (en) | Method for producing of nickel(0)/phosphorus ligand complexes | |
| CN1314880A (en) | Novel method for preparing optically active alpha-aminonitriles | |
| CN1898255A (en) | Process for the preparation of pyridine derivatives | |
| CN101054355A (en) | Compound of optically pure disulfenamides and application thereof | |
| CN1668599A (en) | Process for preparing quinolone antibiotic intermediates | |
| CN1216039A (en) | Process to prepare taxol | |
| CN1163472C (en) | Novel method for preparing chiral amino acids | |
| CN1199729A (en) | Process to chloroketones using oxazolines | |
| CN1874974A (en) | Diastereoselective method of preparing olefins by means of the Horner-Wadsworth-Emmons reaction using a particular phosphonate which improves diastereoselectivity at all temperatures including at ambi | |
| CN1160350C (en) | Method for preparing asymmetric lactone | |
| CN1174103C (en) | Process for preparing chiral substituted arylepoxyethane compounds and its biol by selective splitting of Aspergillus niger | |
| CN1103761C (en) | Process for producing 1 -substituted -hydantoins | |
| CN1524835A (en) | Method for processing asymmetric hydroxylamination and dihydroxylation reaction by use of supported bi-cinchoni alkaloid ligand | |
| CN1295217C (en) | New asymmetric process for the preparation of diarylmethylpiperazines derivatives and novel asymmetric diarylmetylamines as intermediates | |
| CN1784378A (en) | Method for the synthesis of 4-hydroxyisoleucine and the derivatives thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| C10 | Entry into substantive examination | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |