CN1036649C - 制备α-不饱和胺或其盐的方法 - Google Patents
制备α-不饱和胺或其盐的方法 Download PDFInfo
- Publication number
- CN1036649C CN1036649C CN93114206A CN93114206A CN1036649C CN 1036649 C CN1036649 C CN 1036649C CN 93114206 A CN93114206 A CN 93114206A CN 93114206 A CN93114206 A CN 93114206A CN 1036649 C CN1036649 C CN 1036649C
- Authority
- CN
- China
- Prior art keywords
- methyl
- nmr
- compound
- picolyl
- cdcl
- 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.)
- Expired - Lifetime
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- 150000001412 amines Chemical class 0.000 title claims abstract description 87
- 238000004519 manufacturing process Methods 0.000 title description 8
- 150000003839 salts Chemical class 0.000 claims abstract description 57
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 27
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 18
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 16
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 11
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 11
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 9
- 150000001875 compounds Chemical class 0.000 claims description 379
- -1 sulphonyl thiocarbamoyl Chemical group 0.000 claims description 222
- 238000000034 method Methods 0.000 claims description 72
- 229910052760 oxygen Inorganic materials 0.000 claims description 24
- 239000001301 oxygen Substances 0.000 claims description 23
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 23
- 229910052736 halogen Inorganic materials 0.000 claims description 21
- 150000002367 halogens Chemical class 0.000 claims description 20
- 239000001257 hydrogen Substances 0.000 claims description 20
- 229910052739 hydrogen Inorganic materials 0.000 claims description 20
- 125000004076 pyridyl group Chemical group 0.000 claims description 14
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 11
- 239000000376 reactant Substances 0.000 claims description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 125000000335 thiazolyl group Chemical group 0.000 claims description 7
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 5
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 125000005493 quinolyl group Chemical group 0.000 claims description 3
- 229910052728 basic metal Chemical group 0.000 claims description 2
- 150000003818 basic metals Chemical group 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims 1
- 125000005103 alkyl silyl group Chemical group 0.000 claims 1
- 125000006350 alkyl thio alkyl group Chemical group 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 abstract description 25
- 125000000623 heterocyclic group Chemical group 0.000 abstract description 8
- 125000000753 cycloalkyl group Chemical group 0.000 abstract description 7
- 239000003905 agrochemical Substances 0.000 abstract description 6
- 230000000749 insecticidal effect Effects 0.000 abstract description 6
- 230000003129 miticidal effect Effects 0.000 abstract 1
- 125000004430 oxygen atom Chemical group O* 0.000 abstract 1
- 238000005481 NMR spectroscopy Methods 0.000 description 331
- 239000000203 mixture Substances 0.000 description 176
- 238000006243 chemical reaction Methods 0.000 description 139
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 123
- 239000013078 crystal Substances 0.000 description 110
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 97
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 82
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 81
- IXAGRXJIXIPQDR-UHFFFAOYSA-N 2-nitroethenamine Chemical group NC=C[N+]([O-])=O IXAGRXJIXIPQDR-UHFFFAOYSA-N 0.000 description 74
- 239000002585 base Substances 0.000 description 73
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 71
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 65
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 64
- NESLOYMMIUOLMU-UHFFFAOYSA-N 1-n'-methyl-2-nitroethene-1,1-diamine Chemical group CNC(N)=C[N+]([O-])=O NESLOYMMIUOLMU-UHFFFAOYSA-N 0.000 description 54
- 239000000243 solution Substances 0.000 description 54
- 238000003756 stirring Methods 0.000 description 50
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 46
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 45
- 238000001035 drying Methods 0.000 description 44
- 238000010898 silica gel chromatography Methods 0.000 description 43
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 43
- 239000000460 chlorine Substances 0.000 description 41
- 239000011541 reaction mixture Substances 0.000 description 41
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 39
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 38
- 239000000047 product Substances 0.000 description 38
- 239000012043 crude product Substances 0.000 description 37
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 37
- 239000002904 solvent Substances 0.000 description 36
- 238000010992 reflux Methods 0.000 description 35
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 34
- LGDSHSYDSCRFAB-UHFFFAOYSA-N Methyl isothiocyanate Chemical compound CN=C=S LGDSHSYDSCRFAB-UHFFFAOYSA-N 0.000 description 34
- 238000001816 cooling Methods 0.000 description 32
- 239000000284 extract Substances 0.000 description 29
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 27
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
- 239000003513 alkali Substances 0.000 description 25
- 238000010025 steaming Methods 0.000 description 25
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 24
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 24
- 239000003921 oil Substances 0.000 description 24
- AJEQAGLDUXLZQG-UHFFFAOYSA-N 1-n',1-n'-dimethyl-2-nitroethene-1,1-diamine Chemical group CN(C)C(N)=C[N+]([O-])=O AJEQAGLDUXLZQG-UHFFFAOYSA-N 0.000 description 23
- 239000007864 aqueous solution Substances 0.000 description 23
- 238000000605 extraction Methods 0.000 description 22
- 239000007788 liquid Substances 0.000 description 21
- 238000010790 dilution Methods 0.000 description 19
- 239000012895 dilution Substances 0.000 description 19
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
- 238000005406 washing Methods 0.000 description 18
- XALCOJXGWJXWBL-UHFFFAOYSA-N 1-(6-chloropyridin-3-yl)-n-methylmethanamine Chemical compound CNCC1=CC=C(Cl)N=C1 XALCOJXGWJXWBL-UHFFFAOYSA-N 0.000 description 17
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 17
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
- 239000000706 filtrate Substances 0.000 description 16
- 239000000843 powder Substances 0.000 description 16
- 229910000104 sodium hydride Inorganic materials 0.000 description 16
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
- 239000003153 chemical reaction reagent Substances 0.000 description 15
- 235000008504 concentrate Nutrition 0.000 description 15
- 239000012141 concentrate Substances 0.000 description 15
- 239000000126 substance Substances 0.000 description 15
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 14
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 13
- 125000000217 alkyl group Chemical group 0.000 description 13
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 13
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 13
- 239000011780 sodium chloride Substances 0.000 description 13
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
- 229910052801 chlorine Inorganic materials 0.000 description 12
- 230000008030 elimination Effects 0.000 description 12
- 238000003379 elimination reaction Methods 0.000 description 12
- 239000000741 silica gel Substances 0.000 description 12
- 229910002027 silica gel Inorganic materials 0.000 description 12
- 229960001866 silicon dioxide Drugs 0.000 description 12
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 11
- 229940073608 benzyl chloride Drugs 0.000 description 11
- 239000006227 byproduct Substances 0.000 description 11
- 238000004440 column chromatography Methods 0.000 description 11
- 238000010438 heat treatment Methods 0.000 description 11
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 11
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 10
- 241001556089 Nilaparvata lugens Species 0.000 description 10
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 10
- 239000000642 acaricide Substances 0.000 description 10
- 238000002425 crystallisation Methods 0.000 description 10
- 230000008025 crystallization Effects 0.000 description 10
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 10
- 230000035484 reaction time Effects 0.000 description 10
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 10
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- 239000002253 acid Substances 0.000 description 9
- 150000001721 carbon Chemical group 0.000 description 9
- 238000001953 recrystallisation Methods 0.000 description 9
- 239000012312 sodium hydride Substances 0.000 description 9
- 235000011121 sodium hydroxide Nutrition 0.000 description 9
- XPARFBOWIYMLMY-UHFFFAOYSA-N (6-chloropyridin-3-yl)methanamine Chemical compound NCC1=CC=C(Cl)N=C1 XPARFBOWIYMLMY-UHFFFAOYSA-N 0.000 description 8
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 8
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 8
- 125000003368 amide group Chemical group 0.000 description 8
- 150000001408 amides Chemical class 0.000 description 8
- 235000011114 ammonium hydroxide Nutrition 0.000 description 8
- 229910052794 bromium Inorganic materials 0.000 description 8
- 125000006575 electron-withdrawing group Chemical group 0.000 description 8
- 150000002170 ethers Chemical class 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
- FMKGJQHNYMWDFJ-CVEARBPZSA-N 2-[[4-(2,2-difluoropropoxy)pyrimidin-5-yl]methylamino]-4-[[(1R,4S)-4-hydroxy-3,3-dimethylcyclohexyl]amino]pyrimidine-5-carbonitrile Chemical compound FC(COC1=NC=NC=C1CNC1=NC=C(C(=N1)N[C@H]1CC([C@H](CC1)O)(C)C)C#N)(C)F FMKGJQHNYMWDFJ-CVEARBPZSA-N 0.000 description 7
- IYHHRZBKXXKDDY-UHFFFAOYSA-N BI-605906 Chemical compound N=1C=2SC(C(N)=O)=C(N)C=2C(C(F)(F)CC)=CC=1N1CCC(S(C)(=O)=O)CC1 IYHHRZBKXXKDDY-UHFFFAOYSA-N 0.000 description 7
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 7
- 241000238631 Hexapoda Species 0.000 description 7
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 7
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 7
- 240000007594 Oryza sativa Species 0.000 description 7
- 235000007164 Oryza sativa Nutrition 0.000 description 7
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 7
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 7
- 239000012230 colorless oil Substances 0.000 description 7
- 229910052731 fluorine Inorganic materials 0.000 description 7
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 7
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 7
- 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 description 7
- CFHIDWOYWUOIHU-UHFFFAOYSA-N oxomethyl Chemical compound O=[CH] CFHIDWOYWUOIHU-UHFFFAOYSA-N 0.000 description 7
- 235000009566 rice Nutrition 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 6
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 6
- LFRYVKXHKZPNED-UHFFFAOYSA-N 6-chloro-n-methylpyridin-3-amine Chemical compound CNC1=CC=C(Cl)N=C1 LFRYVKXHKZPNED-UHFFFAOYSA-N 0.000 description 6
- QAJYCQZQLVENRZ-UHFFFAOYSA-N 6-chloropyridin-3-amine Chemical compound NC1=CC=C(Cl)N=C1 QAJYCQZQLVENRZ-UHFFFAOYSA-N 0.000 description 6
- 241000196324 Embryophyta Species 0.000 description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
- 229910052783 alkali metal Inorganic materials 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 6
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 6
- 239000011737 fluorine Substances 0.000 description 6
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 6
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 6
- 239000005457 ice water Substances 0.000 description 6
- LFGREXWGYUGZLY-UHFFFAOYSA-N phosphoryl Chemical group [P]=O LFGREXWGYUGZLY-UHFFFAOYSA-N 0.000 description 6
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 6
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 6
- 229920006395 saturated elastomer Polymers 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 238000004809 thin layer chromatography Methods 0.000 description 6
- 239000004563 wettable powder Substances 0.000 description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 5
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 5
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 5
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 5
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 5
- 239000005864 Sulphur Substances 0.000 description 5
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 5
- 125000004423 acyloxy group Chemical group 0.000 description 5
- 150000001298 alcohols Chemical class 0.000 description 5
- 125000003118 aryl group Chemical group 0.000 description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 5
- 125000000392 cycloalkenyl group Chemical group 0.000 description 5
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 5
- 238000004821 distillation Methods 0.000 description 5
- 239000003480 eluent Substances 0.000 description 5
- 229910052500 inorganic mineral Inorganic materials 0.000 description 5
- 235000010755 mineral Nutrition 0.000 description 5
- 239000011707 mineral Substances 0.000 description 5
- 238000006386 neutralization reaction Methods 0.000 description 5
- 229950007908 piconol Drugs 0.000 description 5
- 238000001556 precipitation Methods 0.000 description 5
- HDOUGSFASVGDCS-UHFFFAOYSA-N pyridin-3-ylmethanamine Chemical compound NCC1=CC=CN=C1 HDOUGSFASVGDCS-UHFFFAOYSA-N 0.000 description 5
- 150000003222 pyridines Chemical class 0.000 description 5
- 229910052708 sodium Inorganic materials 0.000 description 5
- UAOUIVVJBYDFKD-XKCDOFEDSA-N (1R,9R,10S,11R,12R,15S,18S,21R)-10,11,21-trihydroxy-8,8-dimethyl-14-methylidene-4-(prop-2-enylamino)-20-oxa-5-thia-3-azahexacyclo[9.7.2.112,15.01,9.02,6.012,18]henicosa-2(6),3-dien-13-one Chemical compound C([C@@H]1[C@@H](O)[C@@]23C(C1=C)=O)C[C@H]2[C@]12C(N=C(NCC=C)S4)=C4CC(C)(C)[C@H]1[C@H](O)[C@]3(O)OC2 UAOUIVVJBYDFKD-XKCDOFEDSA-N 0.000 description 4
- WIHIUTUAHOZVLE-UHFFFAOYSA-N 1,3-diethoxypropan-2-ol Chemical compound CCOCC(O)COCC WIHIUTUAHOZVLE-UHFFFAOYSA-N 0.000 description 4
- DWEOHDUCDDTHLZ-UHFFFAOYSA-N 1-(6-bromopyridin-3-yl)-n-methylmethanamine Chemical compound CNCC1=CC=C(Br)N=C1 DWEOHDUCDDTHLZ-UHFFFAOYSA-N 0.000 description 4
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 4
- KQPKSECAKXTEMS-UHFFFAOYSA-N 6-chloro-n-ethylpyridin-3-amine Chemical compound CCNC1=CC=C(Cl)N=C1 KQPKSECAKXTEMS-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 4
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
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- CEAJFNBWKBTRQE-UHFFFAOYSA-N methanamine;methanol Chemical compound NC.OC CEAJFNBWKBTRQE-UHFFFAOYSA-N 0.000 description 1
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- JHZWMBRFGLKQSH-UHFFFAOYSA-N methyl $l^{1}-oxidanylformate Chemical compound COC([O])=O JHZWMBRFGLKQSH-UHFFFAOYSA-N 0.000 description 1
- VYPPZXZHYDSBSJ-UHFFFAOYSA-N methyl 6-methylpyridine-3-carboxylate Chemical class COC(=O)C1=CC=C(C)N=C1 VYPPZXZHYDSBSJ-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- NRKLCRZZQIJMAF-UHFFFAOYSA-N methyl n-(6-chloropyridin-3-yl)-n'-ethyl-n-methylcarbamimidothioate Chemical compound CCN=C(SC)N(C)C1=CC=C(Cl)N=C1 NRKLCRZZQIJMAF-UHFFFAOYSA-N 0.000 description 1
- KBXNOAQLDBAVEW-UHFFFAOYSA-N methyl n-(6-chloropyridin-3-yl)-n'-methyl-n-propylcarbamimidothioate Chemical compound CCCN(C(SC)=NC)C1=CC=C(Cl)N=C1 KBXNOAQLDBAVEW-UHFFFAOYSA-N 0.000 description 1
- QYROKLQMYFSNCQ-UHFFFAOYSA-N methyl n-(6-chloropyridin-3-yl)-n,n'-diethylcarbamimidothioate Chemical compound CCN=C(SC)N(CC)C1=CC=C(Cl)N=C1 QYROKLQMYFSNCQ-UHFFFAOYSA-N 0.000 description 1
- ISWYLQPJHOENML-UHFFFAOYSA-N methyl n-(6-chloropyridin-3-yl)-n-methyl-n'-propylcarbamimidothioate Chemical compound CCCN=C(SC)N(C)C1=CC=C(Cl)N=C1 ISWYLQPJHOENML-UHFFFAOYSA-N 0.000 description 1
- XKDNDALTJFUQHM-UHFFFAOYSA-N methyl n-[(2,6-dimethylpyridin-4-yl)methyl]-n,n'-dimethylcarbamimidothioate Chemical compound CSC(=NC)N(C)CC1=CC(C)=NC(C)=C1 XKDNDALTJFUQHM-UHFFFAOYSA-N 0.000 description 1
- DRZYNGXDFRIGEB-UHFFFAOYSA-N methyl n-[(2-chloropyridin-3-yl)methyl]-n,n'-dimethylcarbamimidothioate Chemical compound CSC(=NC)N(C)CC1=CC=CN=C1Cl DRZYNGXDFRIGEB-UHFFFAOYSA-N 0.000 description 1
- IKUTWFJSAOPJQT-UHFFFAOYSA-N methyl n-[(5-bromopyridin-3-yl)methyl]-n,n'-dimethylcarbamimidothioate Chemical compound CSC(=NC)N(C)CC1=CN=CC(Br)=C1 IKUTWFJSAOPJQT-UHFFFAOYSA-N 0.000 description 1
- ISNVBUSHZBDYMG-UHFFFAOYSA-N methyl n-[(6-bromopyridin-3-yl)methyl]-n'-methylcarbamimidothioate Chemical compound CSC(=NC)NCC1=CC=C(Br)N=C1 ISNVBUSHZBDYMG-UHFFFAOYSA-N 0.000 description 1
- AINJLUUAWHFLCB-UHFFFAOYSA-N methyl n-[(6-bromopyridin-3-yl)methyl]-n,n'-dimethylcarbamimidothioate Chemical compound CSC(=NC)N(C)CC1=CC=C(Br)N=C1 AINJLUUAWHFLCB-UHFFFAOYSA-N 0.000 description 1
- HWVHJNNXTHKITQ-UHFFFAOYSA-N methyl n-[(6-bromopyridin-3-yl)methyl]-n-ethyl-n'-methylcarbamimidothioate Chemical compound CSC(=NC)N(CC)CC1=CC=C(Br)N=C1 HWVHJNNXTHKITQ-UHFFFAOYSA-N 0.000 description 1
- AIYUZRWYQVBRJM-UHFFFAOYSA-N methyl n-[(6-chloropyridin-3-yl)methyl]-n'-ethyl-n-methylcarbamimidothioate Chemical compound CCN=C(SC)N(C)CC1=CC=C(Cl)N=C1 AIYUZRWYQVBRJM-UHFFFAOYSA-N 0.000 description 1
- NYNMJPBNLBLEDZ-UHFFFAOYSA-N methyl n-[(6-chloropyridin-3-yl)methyl]-n'-methyl-n-propylcarbamimidothioate Chemical compound CCCN(C(SC)=NC)CC1=CC=C(Cl)N=C1 NYNMJPBNLBLEDZ-UHFFFAOYSA-N 0.000 description 1
- LYZCUEOHQMXCKL-UHFFFAOYSA-N methyl n-[(6-chloropyridin-3-yl)methyl]-n,n'-dimethylcarbamimidothioate Chemical compound CSC(=NC)N(C)CC1=CC=C(Cl)N=C1 LYZCUEOHQMXCKL-UHFFFAOYSA-N 0.000 description 1
- ACCWCZRJVRRLQM-UHFFFAOYSA-N methyl n-[(6-chloropyridin-3-yl)methyl]-n-ethyl-n'-methylcarbamimidothioate Chemical compound CSC(=NC)N(CC)CC1=CC=C(Cl)N=C1 ACCWCZRJVRRLQM-UHFFFAOYSA-N 0.000 description 1
- GHOPSGFVEQQDQQ-UHFFFAOYSA-N methyl n-[(6-fluoropyridin-3-yl)methyl]-n,n'-dimethylcarbamimidothioate Chemical compound CSC(=NC)N(C)CC1=CC=C(F)N=C1 GHOPSGFVEQQDQQ-UHFFFAOYSA-N 0.000 description 1
- XGCJHCCMFJMBKO-UHFFFAOYSA-N methyl n-butyl-n-(6-chloropyridin-3-yl)-n'-methylcarbamimidothioate Chemical compound CCCCN(C(SC)=NC)C1=CC=C(Cl)N=C1 XGCJHCCMFJMBKO-UHFFFAOYSA-N 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- XGEGHDBEHXKFPX-NJFSPNSNSA-N methylurea Chemical compound [14CH3]NC(N)=O XGEGHDBEHXKFPX-NJFSPNSNSA-N 0.000 description 1
- 239000010445 mica Substances 0.000 description 1
- 229910052618 mica group Inorganic materials 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- DOTMOQHOJINYBL-UHFFFAOYSA-N molecular nitrogen;molecular oxygen Chemical compound N#N.O=O DOTMOQHOJINYBL-UHFFFAOYSA-N 0.000 description 1
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 1
- NBVXSUQYWXRMNV-UHFFFAOYSA-N monofluoromethane Natural products FC NBVXSUQYWXRMNV-UHFFFAOYSA-N 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- LVDLXEFCWOMUGO-UHFFFAOYSA-N n,6-dimethylpyridin-3-amine Chemical compound CNC1=CC=C(C)N=C1 LVDLXEFCWOMUGO-UHFFFAOYSA-N 0.000 description 1
- YUKCGCYZOBXEBG-UHFFFAOYSA-N n,6-dimethylpyridin-3-amine;oxalic acid Chemical compound OC(=O)C(O)=O.CNC1=CC=C(C)N=C1 YUKCGCYZOBXEBG-UHFFFAOYSA-N 0.000 description 1
- CZFNISFYDPIDNM-UHFFFAOYSA-N n,n-dimethylformamide;oxolane Chemical compound CN(C)C=O.C1CCOC1 CZFNISFYDPIDNM-UHFFFAOYSA-N 0.000 description 1
- UIJQDAKXWHOPIB-UHFFFAOYSA-N n-(sulfanylidenemethylidene)methanesulfonamide Chemical compound CS(=O)(=O)N=C=S UIJQDAKXWHOPIB-UHFFFAOYSA-N 0.000 description 1
- BFLXSKZTPUZOCG-UHFFFAOYSA-N n-[(6-bromopyridin-3-yl)methyl]ethanamine Chemical compound CCNCC1=CC=C(Br)N=C1 BFLXSKZTPUZOCG-UHFFFAOYSA-N 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- YGBMCLDVRUGXOV-UHFFFAOYSA-N n-[6-[6-chloro-5-[(4-fluorophenyl)sulfonylamino]pyridin-3-yl]-1,3-benzothiazol-2-yl]acetamide Chemical compound C1=C2SC(NC(=O)C)=NC2=CC=C1C(C=1)=CN=C(Cl)C=1NS(=O)(=O)C1=CC=C(F)C=C1 YGBMCLDVRUGXOV-UHFFFAOYSA-N 0.000 description 1
- JLSBBCYKZLAADL-UHFFFAOYSA-N n-benzylmethanimine Chemical compound C=NCC1=CC=CC=C1 JLSBBCYKZLAADL-UHFFFAOYSA-N 0.000 description 1
- BLMSDGDROBLBIR-UHFFFAOYSA-N n-ethyl-2-pyridin-3-ylethanamine Chemical compound CCNCCC1=CC=CN=C1 BLMSDGDROBLBIR-UHFFFAOYSA-N 0.000 description 1
- QEUIXVGKTZABLL-UHFFFAOYSA-N n-methoxy-1-pyridin-3-ylmethanamine Chemical compound CONCC1=CC=CN=C1 QEUIXVGKTZABLL-UHFFFAOYSA-N 0.000 description 1
- DBGFNLVRAFYZBI-UHFFFAOYSA-N n-methylpyridin-3-amine Chemical compound CNC1=CC=CN=C1 DBGFNLVRAFYZBI-UHFFFAOYSA-N 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000005186 naphthyloxy group Chemical group C1(=CC=CC2=CC=CC=C12)O* 0.000 description 1
- IOMMMLWIABWRKL-WUTDNEBXSA-N nazartinib Chemical compound C1N(C(=O)/C=C/CN(C)C)CCCC[C@H]1N1C2=C(Cl)C=CC=C2N=C1NC(=O)C1=CC=NC(C)=C1 IOMMMLWIABWRKL-WUTDNEBXSA-N 0.000 description 1
- 230000001069 nematicidal effect Effects 0.000 description 1
- 239000005645 nematicide Substances 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 125000001196 nonadecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229940060184 oil ingredients Drugs 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000003883 ointment base Substances 0.000 description 1
- PIDFDZJZLOTZTM-KHVQSSSXSA-N ombitasvir Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C(=O)NC1=CC=C([C@H]2N([C@@H](CC2)C=2C=CC(NC(=O)[C@H]3N(CCC3)C(=O)[C@@H](NC(=O)OC)C(C)C)=CC=2)C=2C=CC(=CC=2)C(C)(C)C)C=C1 PIDFDZJZLOTZTM-KHVQSSSXSA-N 0.000 description 1
- 125000005461 organic phosphorous group Chemical group 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
- 125000000913 palmityl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 125000002958 pentadecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
- 229940100684 pentylamine Drugs 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 125000004934 phenanthridinyl group Chemical group C1(=CC=CC2=NC=C3C=CC=CC3=C12)* 0.000 description 1
- 125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 description 1
- 125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 0.000 description 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
- 239000005648 plant growth regulator Substances 0.000 description 1
- 239000003375 plant hormone Substances 0.000 description 1
- 230000007096 poisonous effect Effects 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- UKPBXIFLSVLDPA-UHFFFAOYSA-N propylhydrazine Chemical compound CCCNN UKPBXIFLSVLDPA-UHFFFAOYSA-N 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 239000002728 pyrethroid Substances 0.000 description 1
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 description 1
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical group OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 1
- QJZUKDFHGGYHMC-UHFFFAOYSA-N pyridine-3-carbaldehyde Chemical compound O=CC1=CC=CN=C1 QJZUKDFHGGYHMC-UHFFFAOYSA-N 0.000 description 1
- BGUWFUQJCDRPTL-UHFFFAOYSA-N pyridine-4-carbaldehyde Chemical compound O=CC1=CC=NC=C1 BGUWFUQJCDRPTL-UHFFFAOYSA-N 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 229910052903 pyrophyllite Inorganic materials 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- RYGIHSLRMNXWCN-UHFFFAOYSA-N quinoline-3-carbaldehyde Chemical compound C1=CC=CC2=CC(C=O)=CN=C21 RYGIHSLRMNXWCN-UHFFFAOYSA-N 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- GGWBHVILAJZWKJ-KJEVSKRMSA-N ranitidine hydrochloride Chemical compound [H+].[Cl-].[O-][N+](=O)\C=C(/NC)NCCSCC1=CC=C(CN(C)C)O1 GGWBHVILAJZWKJ-KJEVSKRMSA-N 0.000 description 1
- 239000005871 repellent Substances 0.000 description 1
- 230000002940 repellent Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 238000006884 silylation reaction Methods 0.000 description 1
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
- 239000000779 smoke Substances 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- 229910001388 sodium aluminate Inorganic materials 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- UIICPZFWHBJNIG-UHFFFAOYSA-N sodium;2-methoxyethanolate Chemical compound [Na+].COCC[O-] UIICPZFWHBJNIG-UHFFFAOYSA-N 0.000 description 1
- BXBUVIPNRGDTNE-UHFFFAOYSA-N sodium;hydrobromide Chemical compound [Na].Br BXBUVIPNRGDTNE-UHFFFAOYSA-N 0.000 description 1
- 239000002689 soil Substances 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 239000010421 standard material Substances 0.000 description 1
- 125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 229960002317 succinimide Drugs 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 238000006277 sulfonation reaction Methods 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical compound OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 1
- 239000012747 synergistic agent Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 238000001220 thermal lens spectroscopy Methods 0.000 description 1
- 125000002769 thiazolinyl group Chemical group 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- 125000002889 tridecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229960004418 trolamine Drugs 0.000 description 1
- 125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229940099259 vaseline Drugs 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000003871 white petrolatum Substances 0.000 description 1
- 229940102001 zinc bromide Drugs 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
- C07D213/40—Acylated substituent nitrogen atom
-
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Abstract
本发明是关于式I化合物及其盐中的新化合物及其制法;这些化合物在农业上有杀虫/杀螨作用。式I中X1、X2中一个是吸电基团,另一个是H或吸电基团;R1为通过N相连的基团;R2为H或通过C、N或O相连的基团;n为0,1或2;A为杂环或环烃基。这些化合物的制法例如有使式II化合物与Y-W2反应等等,其中当W1为基团(1)时,W2为R1,而当W1为R1时,W2为基团(1)。
Description
本发明涉及具有杀虫/杀螨活性的农业化学应用的α-不饱和胺,其生产方法及其应用。
在α-不饱和胺中,如(i)西咪替丁(叙述于如Jouralof Medicinal Chemistry 24 913,1981中),(ii)雷尼替丁(叙述于如AgentsActions 11,160,1981中)和(iii)法莫替丁(叙述于如Journal of MedicinalChemistry 27,849,1984)这样的化合物作为组胺H2受体拮抗药是已知的。
作为农业杀虫/杀螨剂,有机磷或氨基甲酸酯类农药对温血动物是高毒性的。对于有毒害虫,特别是对这些农药有抗性的“ Hemiptera”类害虫,长久以来需要改进对这些抗性害虫有杀虫活性的农药。
从上述组胺H2受体拮抗药得到启发,本发明者合成了各种各样的α-不饱和胺并研究了它们的活性。结果,意外地发现,在侧链上没有亚烷基或仅有短链亚烷基的本发明化合物具有农业上有用的杀虫/杀螨活性。
基于以上发现,发明者进行了进-步的研究并完成了本发明。
本发明涉及:
(1)通式为〔I°〕的新的α-不饱和胺或其盐,通式中X1和X2之中一个是吸电子基团,另一个是氢或吸电子基团;R1是经氮原子连接的基团;R2是氢或经碳,氮或氧连接的基团;n是整数0,1或2;A°是杂环基,条件是当R2是氢时,R1是通式如下的基团:,其中R3a是氢,C1-4烷基,C7-9芳烷或C1-4酰基,R4a是氢,C1-4烷基,C1-4烷氧基-C1-4烷基,(二-C1-4烷基氨基)-C1-4烷基,三-C1-4烷基甲硅烷基-C1-4烷基,C2-4链烯基,或吡啶基-C1-2烷基或噻唑基-C1-2烷基,其中吡啶基或噻唑基可任意取代有卤素,或者R3a和R4a与邻近连接的氮原子一起组成吡咯烷基,A°是可以任意取代有卤素,C1-4烷基,C1-4烷硫基或C1-4烷氧基的吡啶基、吡嗪基或噻唑基,
(2)一种含有通式〔I〕的α-不饱和胺或其盐的杀虫剂/农药组合物及其生产方法:通式中X1和X2之中的一个是吸电子基团,另一个是氢或吸电子基团;R1是经氮原子连接的基团;-R2是氢或经碳、氮或氧原子连接的基团;N是整数0,1或2;A是杂环基或环烃基,条件是当R1是β-N-吡咯烷代乙氨基和R2是氢原子时,A是如下基团:其中Hal是卤原子(如Cl、Br、F等)。
就上面通式〔I°〕和〔I〕而言,X1和X2之中的一个是吸电子基团,另一个是氢或吸电子基团。吸电子基团X1,X2包括氰基,硝基,C1-4烷氧基-羰基(如甲氧基羰基,乙氧基羰基等),羟基羰基,C6-10芳氧基-羰基(如苯氧基羰基等),杂环氧基羰基,其中杂环部分如下所述例如吡啶氧羰基,噻吩氧羰基等,可取代有卤素的C1-4烷磺酰基(如甲磺酰基,三氟甲磺酰基,乙磺酰基等),氰基磺酰基,二-C1-4烷氧基磷酰基(如二乙氧基磷酰基等〕,可取代有卤素的C1-4酰基(例如C1-4烷基酰基如乙酰基,三氯乙酰基。三氟乙酰基等),C1-4烷磺酰基硫代氨甲酰基(如甲磺酰基硫代氨甲酰基等),氨甲酰基等等。X1和X2之中的一个可以是卤素如氟,氯,溴或碘;X1和X2可以与邻接的碳原子连在一起形成环,例如 的较好例子是C2NCH。
就上面通式〔I°〕和〔I〕而言,R′可以是经碳,氧或硫原子连接的基团,但最好是经氮原子连接的基团。例如,可以是通式为的基团。在上面通式中R3例如是氢原子,烷基(例如C1-6烷基如甲基,乙基,正丙基,异丙基,正-丁基,异-丁基,正-己基等〕,C6-10芳基(例如苯基等〕,C7-9芳烷基(例如苯烷基如苄基等),下述杂环基(例如吡啶基等),C1-4酰基(例如,甲酰基,乙酰基,丙酰基等),C6-10芳基羰基(例如苯甲酰基等),烷氧羰基(例如,C1-4烷氧羰基如甲氧羰基,乙氧羰基等),C6-10芳氧羰基(例如,苯氧羰基等),杂环氧羰基(例如是喃呋基)其中的杂环如下述,C6-10芳磺酰基(例如,苯磺酰基等),烷磺酰基(例如,C1-4烷磺酰基如甲磺酰基等),二烷氧磷酰基(例如,二-C1-4烷氧磷酰基如二乙氧磷酰基等),烷氧基(例如,C1-4烷氧烷如甲氧基,乙氧基等),羰基,氨基,二烷基氨基(例如二-C1-4烷基氨基如二甲氨基,二乙氨基等),酰胺基(例如,C1-4酰胺基如甲酰胺基,乙酰胺基,丙酰胺基等),烷氧羰基氨基(例如C1-4烷氧羰基氨基,如甲氧基氨基等),烷磺酰胺基(例如,C1-4烷基磺酰基如甲磺酰胺基等),二-烷氧磷酰胺基((例如,二-C1-4烷氧基磷酰胺基如二乙氧基磷酰胺基等),C7-9芳烷氧基(例如,苄氧基等),烷氧羰基烷基(例如,C1-4烷氧羰基-C1-4烷基如甲氧羰基甲基等)或类似基团。R4是例如氢原子或烷基(例如,C1-4烷基如甲基,乙基等),环烷基(例如,C3-6环烷基如环己基等),链烯基(例如,C2-4烯基如乙烯基,烯丙基等),环烯基(例如,C3-6环烯基如环己烯基等)或炔基(例如,C2-4炔基如乙炔基等),以上基团可任意取代有1-3个取代基(例如,羟基,C1-4烷氧基如甲氧基,卤素如氟,二-C1-4烷氨基如二甲氨基,C1-4烷硫基如异丙硫基和正丙硫基,C1-3酰胺基如乙酰胺基,C1-4烷磺酰胺基如甲磺酰胺基,三-C1-4烷基甲硅烷基如三甲基硅烷基,吡啶基或噻唑基,而这些基团又可任意取代有卤素等)。此外,R3和R4可以与邻接的氮原子组成如下的5-或6-元环氨基,例如:
通过氮原子连接的R1基团包括可以任意取代的氨基(例如,取代基是上面R3和R4中定义的任何烷基、芳基,芳烷基,杂环基,酰基,烷氧羰基,芳氧羰基,杂环氧羰基,芳磺酰基,烷磺酰基,二烷氧磷酰基,环烷基,链烯基,环烯基和炔基)例如二取代氨基如二-C1-6烷氨基,N-C1-6烷基-N-甲酰胺基等,单取代氨基如单-C1-6烷氨基等,和未取代的氨基,可任意取代的肼基(例如,取代基是上面R3中定义的任何烷基,酰基,烷氧羰基,烷磺酰基,二烷氧磷酰基和其它基团)或可任意取代的羟氨基(例如可由上面R3中定义的任何烷基,芳烷基和其它基团所取代)。
R2是氢原子或经碳、氮或氧原子连接的基团。经碳原子连接的基团R2包括C1-4酰基(如甲酰基,乙酰基,丙酰基等),烷基(如甲基,乙基,正丙基,异丙基,正-丁基,异-丁基,仲-丁基等C1-4烷基),链烯基(如乙烯基,烯丙基等C2-4烯基),环烷基(如环戊基,环己基等C3-6环烷基),C6-10芳基(如苯基、萘基等),C7-9芳烷基(例如苯烷基如苄基等〕和如下所述的在其碳原子上有一自由键的杂环基(如3-或4-吡啶基等)。这些基团的每一个又可取代有1-3个取代基(例如,甲硫基、乙硫基等C1-4烷硫基,甲氧基,乙氧基等C1-4烷氧基,甲氨基、二甲氨基等单-或双-C1-4烷氨基,甲氧羰基、乙氧羰基等C1-4烷氧羰基,甲磺酰基,乙磺酰基等C1-4烷磺酰基,氟、氯、溴、碘等卤素,包括链烷酰基如乙酰基等C1-4酰基,苯甲酰基,苯磺酰基,吡啶基等)。经氮原子连接的基团R2包括在R1中定义的那些基团。经氧原子连接的基团R2包括烷氧基(如甲氧基、乙氧基等C1-4烷氧基),环烷氧基(如环己氧基等C3-6环烷氧基),链烯氧基(如乙烯氧基、烯丙氧基等C2-4烯氧基),环烯氧基(如环己烯氧基等C3-6环烯氧基),炔氧基(如乙炔氧基等),C6-10芳氧基(如苯氧基等),杂环氧基(如噻吩氧基等),其中杂环部分如下述,和羟基。这些基团的每一个可有1-3个取代基(如氟、氯、溴、苯基等)。经碳、氮或氧连接的R2最好是可任意取代有C1-4烷硫基、C1-4烷氧基、单-或双-烷氨基、C1-4烷氧羰基、C1-4烷磺酰基、乙酰基、苯甲酰基、苯磺酰基、吡啶基等的甲酰基和烷基(特别是甲基、乙基等C1-4烷基),可任意取代的氨基(例如R1中定义的基团之一取代的氨基)和可由例如上述的C1-4烷基、C3-6环烷基、C2-4链烯基、C3-6环烯基、C2-4炔基、C6-10芳基和杂环基任意取代的羟基(尤其是C1-4烷氧基如甲氧基等)。n是0,1或2。因此,在通式(I°]和[I]中-CnH2n-代表单键,-CH2-,-CH2CH2-,或,最好是单键或-CH2-。取代基A°和A代表如下面所述的杂环基(例如3-吡啶基,6-氯-3-吡啶基,6-甲氧基-3-吡啶基,6-甲基-3-吡啶基,3-喹啉基等),较好是可任意取代有1-3个选自下述(i),(iv),(viii),(xvii),(xLvi),(xLviii)等的基团或如下面所述的环烷基(例如环丙基,环己基,苯基,对-氯苯基等)的杂环基,最好是任意取代有1-2个选自下述(xvii)的基团的杂环基。A°或A代表的杂环基更好是任意取代的吡啶基或噻唑基,例如3-吡啶基,6-氯-3-吡啶基,6-溴-3-吡啶基,2-氯-5-噻唑基等。环烃基A更好是卤代苯基如对-氯苯基等。
X1,X2,R1,R2,R3,R4,A°和A定义中的烷基,环烷基,烯基,环烯基,炔基,芳基,芳烷基,杂环基和环烃基可以采用下述基团,并且这些基团的每一个可以有1-5个例如下文(i)至(Lii)中列出的取代基。
烷基含1-20个碳原子为好,更好是含1-8个碳原子。这个烷基可以是直链的或支链的。烷基的具体例子包括甲基,乙基,丙基,异-丙基,丁基,异-丁基,仲-丁基,叔-丁基,戊基,己基,庚基,辛基,壬基,2-乙基己基,癸基,十一烷基,十二烷基,十三烷基,十四烷基,十五烷基,十六烷基,十八烷基,十九烷基,二十烷基等。
环烷基最好含3-6个碳原子,例如环丙基,环丁基,环戊基,环己基等。
链烯基最好含2-6个碳原子,例如乙烯基,烯丙基,异丙烯基,甲代烯丙基,1,1-二甲代烯丙基,2-丁烯基,3-丁烯基,2-戊烯基,4-戊烯基,5-己烯基等。
环烯基最好含3-6个碳原子,例如1-环丙烯基,2-环丙烯基,1-环丁烯基,2-环丁烯基,1-环戊烯基,2-环戊烯基,3-环戊烯基,1-环己烯基,2-环己烯基,3-环己烯基,1,3-环己二烯-1-基,1,4-环己二烯-1-基,1,3-环戊二烯-1-基,2,4-环戊二烯-1-基等。
炔基最好含2-6个碳原子,例如乙炔基,丙炔基,2-丁炔-1-基,3-丁炔-1-基,3-丁炔-2-基,1-戊炔-3-基,3-戊炔-1-基,4-戊炔-2-基,3-己炔-1-基等。
芳基例如是苯基或萘基。
芳烷基例如是苄基,苯乙基,萘甲基等。
杂环基包括含1-5个杂原子(例如氧、硫或氮)的5-8元环或其稠环,例如2-或3-噻吩基,2-或3-呋喃基,2-或3-吡咯基,2-,3-,或4-吡啶基,2-,4-或5-噁唑基,2-,4-或5-噻唑基,3-,4-或5-吡唑基,2-,4-或5-咪唑基,3-,4-或5-异噁唑基,3-,4-或5-异噻唑基,3-或5-(1,2,4-噁二唑基),1,3,4-噁二唑基,3-或5-(1,2,4-噻二唑基),1,3,4-噻二唑基,4-或5-(1,2,3-噻二唑基),1,2,5-噻二唑基,1,2,3-三唑基,1,2,4-三唑基,1H-或2H-四唑基,N-氧-2-,3-或4-吡啶基, 2-,4-或5-嘧啶基,N-氧-2-,4-或5-嘧啶基,3-或4-哒嗪基,吡嗪基,N-氧-3-或4-哒嗪基,苯并喃呋基,苯并噻唑基,苯并噁唑基,三嗪基,氧代三嗪基,四唑并〔1,5-b〕哒嗪基,三唑并〔4,5-b〕哒嗪基,氧代咪唑基(oxojmjdazjnyl),二氧代三嗪基吡咯烷基,哌啶基,吡喃基,噻喃基,1,4-噁嗪基,吗啉基,1,4-噻嗪基,1,3-噻嗪基,哌嗪基,苯并咪唑基,喹啉基,异喹啉基,噌啉基,2,3-二氮杂萘基,喹唑啉基,喹喔啉基,中氮茚基,喹嗪基,1,8-二氮杂萘基,嘌呤基,蝴啶基,二苯并呋喃基,咔唑基,吖啶基,菲啶基,吩嗪基,吩噻嗪基,吩噁嗪基等。
环烃基包括例如环丙基、环丁基、环戊基、环己基等C3-6环烷基,1-环丙烯基、2-环丁烯基、1-环己烯基、2-环己烯基,1,3-环己二烯-1-基等C3-6环烯基和苯基、萘基等C6-10芳基。
使用了如下基团:
(i)甲基、乙基、丙基、异-丙基、丁基、异-丁基、仲-丁基、叔-丁基等C1-4烷基;
(ii)环丙基、环丁基、环戊基、环己基等C3-6环烷基;
(iii)苯基、萘基等C6-10芳基;
(iv)甲氧基、乙氧基、丙氧基、异-丙氧基、丁氧基、叔-丁氧基等C1-4烷氧基;
(v)环丙氧基、环戊氧基、环己氧基等C3-6环烷氧基;
(vi)苯氧基、萘氧基等C6-10芳氧基;
(vii)苄氧基、2-苯乙氧基、1-苯乙氧基等C7-12芳氧基;
(viii)甲硫基、乙硫基、丙硫基、丁硫基等C1-4烷硫基;
(ix)环丙硫基、环戊硫基、环己硫基等C3-6环烷硫基;
(x)苯硫基、萘硫基等C6-10芳硫基;
(xi)苄硫基、2-苯乙硫基、1-苯乙硫基等C7-12芳烷硫基;
(xii)甲氨基、乙氨基、丙氨基、异-丙氨基、丁氨基、异-丁氨基、叔-丁氨基等单C1-4烷氨基;
(xiii)二甲氨基、二乙氨基、二丙氨基、二丁氨基、N-甲基-N-乙基氨基、N-甲基-N-丙基氨基、N-甲基-N-丁基氨基等二-C1-4烷氨基;
(xiv)环丙氨基、环戊氨基、环己氨基等C3-6环烷氨基;
(xv)苯氨基等C6-10芳氨基;
(xvi)苄氨基、2-苯乙氨基、1-苯乙氨基等C7-12芳烷氨基;
(xvii)氟、氯、溴和碘等卤素;
(xviii)甲氧羰基、丙氧羰基、异-丙氧羰基、丁氧羰基、叔-丁氧羰基、异-丁氧羰基等C1-4烷氨羰基;
(xix)苯氧羰基等C6-10芳氧羰基;
(xx)环丙氧羰基、环戊氧羰基,环己氧羰基等C3-6环烷氧羰基;
(xxi)苄氧羰基、1-苯乙氧羰基、2-苯乙氧羰基等C7-12芳烷氧羰基;
(xxii)甲酰基、乙酰基、丙酰基、丁酰基、新戊酰基等C1-5链烷酰基;
(xxiii)甲酰氧基、乙酰氧基、丁酰氧基、新戊酰氧基、戊酰氧基、己酰氧基、庚酰氧基辛酰氧基、壬酰氧基、癸酰氧基、十一酰氧基、十二酰氧基、十三酰氧基、十四酰氧基、十五酰氧基等C1-15烷酰氧基;
(xxiv)可任意取代的氨基甲酰基,例如氨基甲酰基、N-甲基氨基甲酰基、N,N-二甲基氨基甲酰基、N-乙基氨基甲酰基、N,N-二乙基氨基甲酰基、N-苯基氨基甲酰基、吡咯烷代氨基甲酰基、哌啶代氨基甲酰基、哌嗪代氨基甲酰基,吗啉代氨基甲酰基、N-苄基氨基甲酰基等;
(xxv)N-甲基氨基甲酰氧基、N,N-二甲基氨基甲酰氧基、N-乙基氨基甲酰氧基、N-苄基氨基甲酰氧基、N,N-二苄基氨基甲酰氧基、N-苯基氨基甲酰氧基等取代的氨基甲酰氧基;
(xxvi)甲酰胺基、乙酰胺基、丙酰胺基、丁酰胺基等C1-4烷酰胺基;
(xxvii)苯甲酰胺基等C6-10芳基羰胺基;
(xxviii)甲氧羰胺基、乙氧羰胺基、丁氧羰胺基、叔-丁氧羰胺基等C1-4烷氧羰胺基;
(xxix)苄氧羰胺基、4-甲氧苄氧胺基、4-硝基苄氧羰胺基、4-氯苄氧羰胺基等C7-12芳烷氧羰胺基;
(xxx)甲磺酰胺基、乙磺酰胺基、丁磺酰胺基、苯磺酰胺基、甲苯磺酰胺基、萘磺酰胺基、三氟甲磺酰胺基、2-氯乙磺酰胺基、2,2,2-三氟乙磺酰胺基等取代的磺酰胺基;
(xxxi)吡咯烷基、吡咯基、吡唑基、咪唑基、呋喃基、噻吩基、噁唑基、异噁唑基、异噻唑基、噻唑基、哌啶基、吡啶基、哌嗪基、嘧啶基、吡喃基、四氢吡喃基、四氢呋喃基、吲哚基、喹啉基、1,3,4-噁二唑基、噻吩并〔2,3-d〕吡啶基、1,2,3-噻二唑基,1,3,4-噻二唑基、1, 2,3-三唑基、1,2,4-三唑基、1,3,4-三唑基、四唑基、4,5-二氢-1,3-二噁唑基、四唑并〔1,5-b 〕哒嗪基、苯并噻唑基、苯并噁唑基、苯并咪唑基、苯并噻吩基等含1-5个杂原子(氮氧和/或硫)的杂环基;
(xxxii)杂环硫基,杂环氧基,杂环氨基和杂环羰氨基以及将将(xxxi)的任一种杂环基与S、O、N或羰氨基相连而得到的基团;
(xxxiii)二甲基硫膦氨基、二乙基硫膦氨基等二-C1-4烷基硫膦氨基;
(xxxiv)甲氧亚氨基、乙氧亚氨基、2-氟乙氧亚氨基、羧甲氧亚氨基、1-羧基-1-甲基乙氧亚氨基、2,2,2-三氯乙氧羰甲氧亚氨基、1-(2,2,2-三氯乙氧羰基)-1-甲基乙氧亚氨基、(2-氨基噻唑-4-基)甲氧亚氨基、(1H-咪唑-4-基)甲氧亚氨基等烷氧亚氨基;
(xxxv)甲磺酰氧基、乙磺酰氧基、丁磺酰氧基等C1-4烷磺酰氧基;
(xxxvi)苯磺酰氧基、甲苯磺酰氧基等C6-10芳磺酰氧基;
(xxxvii)二苯基硫膦氨基等二-C6-10芳基硫膦氨基;
(xxxviii)硫代氨基甲酰硫基、N-甲基硫代氨基甲酰硫基、N,N-二甲基硫代氨基甲酰硫基、N-乙基硫代氨基甲酰硫基、N-苄基硫代氨基甲酰硫基、N,N-二苄基硫代氨基甲酰硫基、N-苯基硫代氨基甲酰硫基等可任意取代的硫代氨基甲酰硫基;
(xxxix)三甲基甲硅烷氧基、叔-丁基二甲基甲硅烷氧基、叔-丁基二苯基甲硅烷氧基、二甲基苯基甲硅烷氧基等甲硅烷氧基;
(XL)三甲基甲硅烷基、叔-丁基二甲基甲硅烷基、叔-丁基二苯基甲硅烷基、二甲基苯基甲硅烷基等甲硅烷基;
(XLi)甲亚磺酰基、乙亚磺酰基、丙亚磺酰基、丁亚磺酰基等C1-4烷基亚磺酰基;
(XLii)苯亚磺酰基、萘亚磺酰基等C6-10芳基亚磺酰基;
(XLiii)甲磺酰基、乙磺酰基、丁磺酰基等C1-4烷磺酰基;
(XLiv)苯磺酰基、甲苯磺酰基等C6-10芳磺酰基;
(XLV)甲氧羰氧基、乙氧羰氧基、叔-丁氧羰氧基等C1-4烷氧羰氧基;
(XLVi)三氟甲基、1,1,2,2-四氟乙基、二氟甲基、一氟甲基、三氯甲基、二氯甲基、一氯甲基等卤代-C1-4烷基;
(XLVii)卤代-C1-4烷氧基,卤代-C1-4烷硫基,卤代-C1-4烷亚磺酰基和卤代-C1-4烷磺酰基以及任何卤代-C1-4烷基(XLVi)连接到氧、硫、亚磺酰基和磺酰基部分上衍生的基团;
(XLViii)氰基,硝基,羟基,羧基,磺基和膦酰基;
(XLiX)甲氧磺酰基、乙氧磺酰基、丁氧磺酰基等C1-4烷氧磺酰基;
(L)苯氧磺酰基、甲苯氧磺酰基等C6-10芳基氧磺酰基;
(Li)苄氧磺酰基、2-苯乙氧磺酰基、1-苯乙氧磺酰基等C7-12芳烷基氧磺酰基;
(Lii)二甲氧磷酰基、二乙氧磷酰基、二丁氧磷酰基等二-C1-4烷氧磷酰基。通式〔I°〕和〔I〕的不饱和胺或其盐的更佳例子包括:通式〔Ia〕的α-不饱和胺或其盐,通式中R1a是单-C1-6烷氨基,N-C1-6烷基-N-甲酰胺基或氨基;R2a是C1-4烷基或C1-4烷氧基;Aa是氯代吡啶基;
通式〔Id 〕的α-不饱和胺或其盐,通式中R1,R2,X1,X2和A°的定义同上。
以R1a或R1b代表的上述通式〔Ia〕,〔Ib〕和〔Ic〕中的单-C1-6烷氨基包括-单-甲氨基、单-乙氨基、单-正丙氨基、单-异丙氨基、单-正丁氨基、单-异丁氨基、甲-正己氨基等,并且最好是甲-甲氨基、单-乙氨基等甲-C1-4烷氨基。R1a或R1b代表的N-C1-6烷基-N-甲酰胺基包括N-甲基-N-甲酰胺基、N-乙基-N-甲酰胺基、N-正丙基-N-甲酰胺基、N-异丙基-N-甲酰胺基、N-正丁基-N-甲酰胺基、N-正己基-N-甲酰胺基等,并且最好是N-甲基-N-甲酰胺基、N-乙基-N-甲酰胺基等N-C1-4烷基-N-甲酰胺基。R1c代表的二-C1-6烷氨基包括二甲氨基、N-乙基-N-甲基氨基、二乙氨基、二-正丙氨基、二-异丙氨基、二-正丁氨基、二-异丁氨基、二-正戊氨基、二-异戊氨基、二-正己氨基等,并且最好是二甲氨基、N-乙基-N-甲基氨基和二乙氨基。R2a和R2c代表的C1-4烷基包括在上面R2中所定义的烷基,并且最好是甲基、乙基等。R2a代表的C1-4烷氧基包括在上面R2中所定义的烷氧基,并且最好是甲氧基、乙氧基等。Aa或Ab代表的氯代吡啶基包括2-氯-3-吡啶基、4-氯-3-吡啶基、3-氯-3-吡啶基、6-氯-3-吡啶基、3-氯-4-吡啶基等,并且最好是6-氯-3-吡啶基等。Ab代表的吡啶基包括3-吡啶基、4-吡啶基等,并且最好是3-吡啶基。典型的通式为〔I°〕和〔I〕的α-不饱和胺或其盐包括:通式〔Ie〕的α-不饱和胺或其盐:通式中X2a是氢、C1-4烷氧羰基或C1-4烷磺酰基硫代氨基甲酰基;R2c是氢、C1-3酰基、C1-4烷基、单-或二-C1-4烷氧基-C1-4烷基、C7-9芳烷基、单-或二-C1-4烷氨基或C1-4烷氧基;Ac是3-或4-吡啶基、吡嗪基或4-或5-噻唑基,这些杂环还可任意取代有卤素、C1-4烷基或C1-4烷氧基;和R3a、R4a和n的定义同上;
通式〔If〕的α-不饱和胺或其盐:通式中X2a是氢、C1-4烷氧羰基或C1-4烷磺酰基硫代氨基甲酰基;R1d是氨基、单-或二-C1-4烷氨基、N-C1-4烷基-N-C1-3酰胺基、C7-9芳烷氨基、卤代噻唑基-C1-2烷氨基或C1-4烷氧基-C1-2烷氨基;R2c是氢、C1-3酰基、C1-4烷基、单-或二-C1-4烷氧基-C1-4烷基、C7-9芳烷基、单-或二-C1-4烷氨基或C1-4烷氧基;n是整数0、1或2;Ad是3-或4-吡啶基、吡嗪基或5-噻唑基,这些杂环基还可任意取代有卤素、C1-4烷基或C1-4烷氧基;
通式〔Ig〕的α-不饱和胺或其盐:通式中X2b是氢或C1-2烷磺酰基硫代氨基甲酰基;R1e是氨基,单-或双-烷氨基或N-C1-2烷基-N-甲酰氨基;R2d是氢、C1-2烷基或C1-3酰基;和Ae是如下的基团:其中Hal是卤素;
通式〔Ih〕的α-不饱和胺或其盐:通式中X2c是氢或甲磺酰基硫代氨基甲酰基;R1f是氨基、甲氨基、二甲氨基或N-甲基-N-甲酰胺基;R2d是氢、甲酰基或C1-2烷基;Ae是如下的基团:其中Hal是卤素;
通式〔Ii〕的α-不饱和胺或其盐:通式中R1e是氨基、单-或二-C1-2烷基或N-C1-2烷基-N-甲酰胺基;R2e是C1-2烷基或甲酰基;Hal是卤素。
在上面通式〔Ie〕-〔Ii〕中X2a、X2b和X2c代表的基团;R1d、R1e和R1f代表的基团;R2c、R2d和R2e代表的基团,和Ac、Ad和Ae代表的基团为上面X2,R1,R2、A0和A中所述的基团。
化合物〔I〕或其盐可通过类似的已知方法制得,此外也可以用下述方法来制备,例如:
方法4)通式X1、X2、R1、R2、Hal、n和A的定义,
方法5)通式中X1、X2、R1、R2、Hal、n和A的意义同上。
方法6)通式中R1、R2、n、A和R5的定义同上;X3是吸电子基团。
方法7)烷基化,酰化,烷氧羰化,磺化或磷酰化通式中X1、X2、R1、R2、n和A的定义同上;R6是经含至少一个氢原子的氮原子连接的基团。
在方法1)-7)中,化合物〔III〕,〔IV〕,〔V〕,〔VI〕,〔IX〕,〔IX′〕,〔IX″〕,〔X〕,〔XIV〕,〔XVI〕,〔XVII〕,〔XVIII〕,〔XIX〕,〔I-5〕〔I-6〕等可以以盐的形式使用〔例如,下面化合物〔I〕中所述的盐)。
按照上述方法1),通式〔II〕的化合物与通式〔III〕的氨基化合物或其盐反应,得到通式〔IV〕的化合物,然后,通式〔IV〕化合物再与通式〔V〕的氨基化合物或其盐反应,或者通式〔II〕的化合物与通式〔V〕的化合物反应,得到通式〔VI〕的化合物,通式〔VI〕化合物再与通式〔III〕化合物反应,最后得到化合物〔I〕。在实施方法1)时,反应〔II〕→〔IV〕,〔IV〕→〔I〕,〔II〕→〔VI〕,和〔VI〕→〔I〕分别地可以在合适的溶剂中进行。只要不与反应剂试剂或反应产物相互作用生成付产物,对溶剂没有限制,但所用溶剂最好能溶解反应剂和试剂。这样的溶剂的例子有:甲醇、乙醇、丙醇、丁醇等醇类,苯、甲苯、二甲苯等芳烃类,乙醚、二丙醚、二丁醚、四氢呋喃、二噁烷等醚类,乙腈、丙腈等腈类,二甲基甲酰胺、二甲基乙酰胺等酰胺类,二甲基亚砜等亚砜类,四氢噻吩砜等砜类,六甲基磷酰胺等磷酰胺类,以及这些溶剂的各种混合物及其与水的混合物。尽管上述每一反应一般都在常压下进行,但如日本未审查专利申请公开62-138478(1987)所述,可在减压下进行此反应以除去付产物——低沸点硫醇并因此抑制付反应。在使用低沸点溶剂情况下,最好在加压下进行。上述每一反应的反应温度可以是30-150℃,最好是50-150℃。反应时间,一般是5分钟至48分钟,这取决于反应温度、反应剂、试剂和溶剂。在反应〔II〕→〔IV〕和反应〔II〕→〔VI〕中试剂〔III〕和〔V〕的用量相对于(II)而言分别可为1-1.2摩尔当量。进一步过量使用〔III〕和〔V〕应当避免,以防止生成付产物二氨基化合物。由于在浓反应混合物中,反应〔II〕→〔IV〕和反应〔II〕→〔VI〕有时会产生付产物二氨基化合物,因此,应避免这样的反应条件。在反应〔IV〕→〔I〕和反应〔VI〕→〔I〕中试剂〔V〕和〔III〕的用量通常为1~1.5摩尔当量,并且与在反应〔II〕→〔IV〕和反应〔II〕→〔VI〕不同,应用较大过量的〔V〕或〔II〕也不至于引起付产物的形成。为了促进该反应或抑制付反应,可以允许伴有碱的存在。为此,可以使用有机碱如三乙胺、N-甲基吗啉、吡啶、1,8-二氮杂双环〔5,4,0〕-7-十一碳烯,1,5-二氮杂双环〔4,3,0〕-5-烯等,以及无机碱如碳酸钾、碳酸氢钾、碳酸钠、碳酸氢钠、碳酸锂、碳酸氢锂等。所用试剂〔III〕或〔V〕的碱金属盐可以是钠盐、锂盐、钾盐等。化合物〔IV〕或〔VI〕可通过常规方法分离和提纯,例如浓缩、减压浓缩、调节PH值、再分配、溶剂提取、蒸馏、结晶、重结晶、色谱法等并用于下一步反应。也可以将含有〔IV〕或〔VI〕的反应混合物直接用作下一步反应的起始反应剂。
方法1)的通式为〔II〕的起始化合物可通过Chem.Ber.100,591(1967),Acta.Chem.Scand.22,1107(1968),Synthesis 1986,967,Chem.Ber.95,2861(1962),Tetraheron 30,2413(1974),Synt-hesis 1984,797和其它文献所述的方法或类似方法合成。化合物〔III〕可通过Academic出版社出版的“Ora-gnic Functional Group Prepara-tions”第一卷,第十三章(1968)和第三卷,第十章(1972)和其它文献所述方法或类似方法合成;化合物〔V〕可通过1970年出版的“Survey of OrganicSynthesis,Wiley-Interscience”第八章和其它文献所述方法及类似方法合成。
上述方法2)包括(1)通式〔III〕的氨基化合物(Y=H)或其碱金属盐(如钠或钾盐)与通式〔VII〕的异硫氟酸酯反应,生成通式〔VIII〕的硫脲,然后,该硫脲再与通式为R5I的化合物(如碘甲烷等)反应,生成通式为〔IX〕的异硫脲,该异硫脲再与通式〔X〕的活泼亚甲基化合物反应,(2)通式〔III〕的氨基化合物(Y=H)或其碱金属盐与通式〔VII′〕的异硫氰酸酯反应,所得硫脲〔VIII′〕再与通式为R6I的化合物(如碘甲烷等)反应生成异硫脲〔IX′〕,该异硫脲进一步与活性亚甲基化合物〔X〕反应,或(3)通式〔V〕的氨基化合物(Y=H)或其碱金属盐与异硫氰酸酯〔VII″〕反应,所得硫脲〔VIII′〕再与通式为R5I的化合物(如碘甲烷等)反应,所得的异硫脲〔IX″〕进一步与活泼亚甲基化合物反应,得到所要的化合物〔I〕。
方法2)中的反应〔III〕Y=H→〔VIII〕,〔III〕Y=H→〔〔VIII′〕和〔V〕Y=H→〔VIII″〕及反应〔VIII〕→〔IX〕,〔VIII′〕→〔IX′〕和〔VIII″〕→〔IX″〕中每一个都可通过文献中所述的已知方法或类似的方法进行。所说的文献如Shin JikkenKagaku Koza(实验化学新系列)Vol.14,IIIMaruzen(1978)第7和21章;OrganicFunctional Group Preparations,Vol.2,Academic Press(1971)第6和7章及其第二版(1986)等。
反应〔III〕Y=H→〔VIII〕,〔III〕Y=H→〔VIII′〕和〔V〕〔V〕Y=H→〔VIII″〕中每一反应都可在适宜的溶剂中进行。对这样的溶剂没有限制,不过它不能与反应剂或试剂相互作用,而且最好选择能溶解反应剂和试剂的溶剂。这样的溶剂例如可以是苯、甲苯、二甲苯等芳烃类;戊烷、己烷、庚烷、石油醚,粗汽油、石油苯等脂肪烃类;乙醚、二丙醚、乙丁醚、四氢呋喃、二氧杂环己烷等醚类;二甲基甲酰胺、二甲基乙酰胺等酰胺类;二甲基亚砜等亚砜类;六甲基磷酰胺等磷酰胺类;氯仿、二氯甲烷、四氯化碳,1,2-二氯乙烷等卤代烃类;以及其各种混合物。反应温度约为-30°-200℃,最好是0°-150℃。反应时间随反应温度、反应剂、试剂、反应体系的浓度和溶剂等条件而变,一般是1分钟至24小时。
在各反应中所需化合物〔VII〕、〔VII′〕和〔VII″〕的量相对于〔III〕Y=H,〔III〕Y=H和〔V〕Y=H可以是0.5-2摩尔当量,最好是0.8-1.2摩尔当量。所得化合物〔VIII〕,〔VIII′〕和〔VIII″〕每一个都可以不经分离或用已知方法从反应混合物中分离后而用于进行下一步反应。
反应〔VIII〕→〔IX〕,〔VIII′〕→〔IX′〕和〔VIII″〕→〔IX″〕中每一反应也可在溶剂中进行。除了对于反应〔III〕Y=H→〔VIII〕,〔III〕Y=H→〔VIII′〕和〔V〕Y=H→〔VIII″〕所举出的溶剂外,也可以用甲醇、乙醇、丙醇、丁醇等醇类;丙酮、甲乙酮等酮类;乙酸甲酯、乙酸乙酯、乙酸丁酯、甲酸甲酯、甲酸乙酯、丙酸乙酯等酯类。试剂碘甲烷可用作溶剂。为了促进反应并减少付产物,允许反应体系中存在碱或允许反应前或反应后使碱作用于反应体系,在一些情况下这样做可得到更有利的结果。为上述目的可使用的碱有氢化钠,金属钠,乙醇钠、甲醇钠、叔-丁醇钠等醇化物,三乙胺、二异丙基乙基胺、吡啶、N,N-二甲基苯胺等有机碱,和碳酸钾等无机碱。碱对〔VIII〕,〔VIII′〕或〔VIII″〕的比例最好为0.8-1.2摩尔当量。反应体系中无碱时,〔IX〕,〔IX′〕或〔IX″〕以氢碘酸盐形式存在,于是,必须中和此氢碘酸盐以得到〔IX〕,〔IX′〕或〔〔IX″〕。为此目的所用的碱最好是水溶性的无机碱,例如碳酸钠、碳酸氢钠、碳酸氢钾、碳酸钾、氢氧化钠、氢氧化钾等。反应温度是0-100℃,最好是20-80℃。反应时间一般为0.1-24小时。所需碘甲烷对〔VIII〕,〔VIII′〕或〔VIII″〕的比例不小于1摩尔当量,并可作为溶剂较大量地使用。所得〔IX〕,〔IX′〕或〔IX″〕可以在用于下一步反应之前以常规方法分离,也可将反应产物混合物作为下步反应的起始物质直接使用。
反应〔IX〕→〔I-1〕,〔IX′〕→〔I-2〕和〔IX″〕→〔I-3〕中每一反应可按照Tetrahedron 37,1453(1981),Indian Journal ofChemistry 15B,297(1977)和其它文献所述方法进行。可以用过量活性亚甲基化合物〔X〕作溶剂或在不同溶剂中进行该反应。所说的溶剂可以是苯、甲苯、二甲苯等芳烃类,二甲基甲酰胺、二甲基乙酰胺、二甲基亚砜、四氢噻吩砜、六甲基磷酰胺等非质子极性溶剂,和四氢呋喃、二氧杂环己烷等醚类。特别在使用非质子极性溶剂、反应在减压下进行并且从反应体系中排出付产物甲硫醇的情况下,可以抑制付产物的形成并改进反应产率。反应也可在催化剂存在下进行。这样的催化剂可以是氯化锌、溴化锌、碘化锌、氯化铜等。反应温度是30-200℃,最好是50-150℃。反应时间一般是0.1-48小时。活性亚甲基化合物〔X〕对〔IX〕,〔IX′〕或〔IX″〕的比例是1-5摩尔当量。〔X〕是低沸化合物时,可以以溶剂量使用。
化合物〔VII〕、〔VII′〕和〔VII″〕可通过Academic出版社1968年出版的“Organic FunctionalGroup Preparations”卷1第12章和其它文献叙述的方法或类似的方法合成,而化合物〔X〕可以通过GeorgThieme 1973年出版的Suttgert的“Form-ation of C-C Bonds”卷1和其它文献中所述的方法合成。
上述方法3)包括使化合物〔XI〕或〔XII〕与通式〔III〕的氨基化合物或其盐(如钠或钾那样的碱金属盐)反应,所得产物再与通式〔V〕的氨基化合物或其盐(如碱金属盐)反应;或者使化合物〔XI〕或〔XII〕与通式〔V〕的氨基化合物或其盐反应,然后使所得产物与通式〔III〕的氨基化合物或其盐反应,得到要求的化合物〔I〕。
方法3)中的反应可以与方法1)同样的方式进行并可采用方法1)中所述的反应条件。不过,因为化合物〔XI〕和〔XII〕一般比化合物〔II〕更活泼,反应最好在比方法1)稍温和的条件下进行。
化合物〔XI〕和〔XII〕可以通过Chemical Abst-racts44,1011f,Journal of Org-anic Chemistry 25,1312(1960)和其它文献所述的方法或类似的方法制备。
上述方法4)包括使通式〔XIII〕的酰胺或通式〔XV〕的酰胺与卤化剂反应,得到通式〔XIV〕或〔XVI〕的卤化物,该卤化物再与通式〔V〕的氨基化合物或其盐或者通式〔III〕的氨基化合物或其盐反应,得到所要的化合物〔I〕。
反应〔XIII〕→〔XIV〕和〔XV〕→〔XVI〕最好在溶剂中进行。所说的溶剂可以是二氯甲烷、氯仿、四氯化碳、1,2-二氯乙烷等卤代烃类,乙醚、四氢呋喃、二氧杂环己烷等醚类,乙腈、丙腈等腈类,等等。该反应最好在无水条件下进行。卤化剂例如可以是五氯化磷、磷酰氯、三氯化磷、亚硫酰氯、草酰氯或类似物。卤化剂对〔XIII〕或〔XV〕的比是1-10摩尔当量,最好是1-5摩尔当量。为了捕集付产物氯化氢,反应体系中最好有碱存在,这样的碱可以是各种有机碱例如吡啶,三乙胺,二异丙基乙基胺,N-甲基吗啉,N,N-二甲基苯胺,N,N-二乙胺等。反应温度是-80-100℃,最好是-50-50℃。反应时间一般是0.1-24小时,这取决于反应剂,碱、溶剂、反应浓度和反应温度。产物〔XIV〕和〔XVI〕可以在用于下一步反应之前用已知方法分离并提纯,将反应产物混合物直接用于下一步反应。
反应〔XIV 〕→〔I〕和〔XVI〕→〔I〕可以在对于反应〔XIII〕→〔XIV〕和〔XV〕→〔XVI〕所提到的类似的溶剂中进行,最好在无水条件下进行。〔V〕或其盐和〔III〕或其盐分别对〔XIV〕和〔XVI〕的比例是1-10摩尔当量,最好是1-5摩尔当量。为了捕集付产物氯化氢,〔V〕或其盐或者〔III〕或其盐可以过量使用,最好有不同的碱存在。所说的碱可以是对于反应〔XIII〕→〔XIV〕和〔XV〕→〔XVI〕中所提到的任何碱。反应温度是-80-100℃,最好是-50-50℃。反应时间一般是0.1-24小时。起始化合物〔XIII〕和〔XV〕可通过GeorgThieme 1973年出版的Stuttgart的“For-mation of C-C Bonds”第1卷所述的方法和日本化学会出版的“Shin Jikken Kagaku Koza”(实验化学新系列)卷14,11(1977)第5和7章和其它文献所述的方法或类似的方法合成。
方法5)包括使通式〔XVII〕化合物与通式〔XVIII〕的卤化物反应,得到所要的化合物〔I〕。
方法5)的反应最好在适宜的溶剂中进行。所说的溶剂可以用二甲基甲酰胺、二甲基乙酰胺等酰胺类,二甲基亚砜等亚砜类,四氢噻吩砜等砜类,六甲基磷酰胺等磷酰胺类,四氢呋喃、二氧杂环己烷、1,2-二甲氧基乙烷、二乙二醇二甲醚等醚类,等等。也可使用这些溶剂的混合物。反应最好在碱存在下进行。所说的碱可以是氢化钠,氢化钾,氢化锂,氢化钙,正丁基锂,二异丙基氨化锂,氨化钠等。反应前,最好将化合物〔XVII〕转化为该碱的盐。该碱对〔XVII〕的比最好是1-1.5摩尔当量。反应最好在无水条件下进行并可在氮气或氩气氛下进行。〔XVIII〕对〔XVII〕的比是1-2摩尔当量,最好是1-1.5摩尔当量。反应温度是-70°-150℃,最好是-50-100℃。反应时间一般是0.1-48小时。
化合物〔XVII〕可以容易地制备,例如用通式R2NH2的化合物(R2的定义同上述)代替方法1)-4)中的化合物〔III〕。化合物〔XVIII〕可通过1968年Academic出版社出版的““Organic Functional Group Pre-parations”卷1,第6章和其它文献所述方法或类似方法合成。
上述方法6)包括使属于化合物〔I〕类别的通式为〔XIX〕的化合物发生水解反应,接着脱羧,得到属于化合物〔I〕类别的通式为〔I-4〕的化合物。
上述水解反应可以在已知技术中酯水解的条件下进行。
所用溶剂(包括溶剂混合物)例如是水,醇类(如甲醇、乙醇、丙醇、丁醇、二乙二醇、2-甲氧基乙醇等),酮类(如丙酮等),醚类(如四氢呋喃、二氧杂环己烷、二甲氧基乙烷等),酰胺类(如二甲基甲酰胺、二甲基乙酰胺、六甲基磷酰胺等),亚砜类(如二甲基亚砜等),砜类(如四氢噻吩砜等)和羧酸类(如甲酸、乙酸等)。该水解反应可使用酸(例如盐酸、氢溴酸、硫酸等无机酸,对-甲苯磺酸等有机酸,强酸性离子交换树脂等)或碱(例如氢氧化钠、氢氧化钾、碳酸钾、碳酸氢钠、氢氧化钡、氢氧化钙、甲氧基钠、氨等)进行,但最好使用碱。碱对〔XIX〕的比约为1-10摩尔当量,最好为约1.2-4摩尔当量。反应温度是约-20-200℃,最好是约-5°-120℃反应时间是约0.1-48小时,最好是约00.1-24小时。在许多情况下,脱羧反应与该水解反应同时进行,通常不需要专门的脱羧步骤。如果需要,此反应可通过在水解溶剂中加热进行。反应温度一般是约0-200℃,最好是30-150℃,反应时间是0.1-48小时,最好是0.1-24小时。
上述方法7)包括将通式为〔I-5〕的化合物或通式为〔I-6〕的化合物烷基化、酰化、烷氧羰基化、磺酰化或磷酰化为化合物〔I〕。
就烷基化反应而言,在〔I-5〕或〔I-6〕中的氨基用例如氯代烷、溴代烷、碘代烷、硫酸二烷基酯等烷基化剂烷基化。在许多情况下,烷基化剂对起始化合物的比为约1-3当量。该烷基化反应可以在对于方法5)所述的同样条件下进行。
酰化、磺酰化、磷酰化和烷氧羰基化反应都可以用已知方法或类似的方法进行。
酰化反应使用的酰化剂可以是例如含R1或R2基团的酰卤或酸酐。磺酰化反应使用的磺酰化剂可以是例如含R1或R2基团的磺酰卤或磺酸酐。烷氧基羰基化反应使用的烷氧基羰基化剂可以是例如含R1或R2基团的烷氧基羰基卤或碳酸酯。在上述卤化剂中涉及的卤素优选溴和氯。每一种试剂对起始化合物的比至少是1摩尔当量,最好是约1-5摩尔当量。在上述酰化反应中用作酰化剂的酸酐可以过量使用。这些反应在能溶解化合物〔I-5〕或〔I-6〕和各种试剂的溶剂中进行,这样的溶剂的较好例子有二氯甲烷、氯仿、二氯乙烷、四氢呋喃、二氧杂环己烷、N,N-二甲基甲酰胺、N,N-二甲基乙酰胺、二甲基亚砜、六甲基磷酸三酰胺、吡啶等。反应温度为约-50-150℃;反应时间为约0.1-48小时。当该反应在附随的胺(例如三乙胺、二甲氨基吡啶、吡啶、N,N-二甲基苯胺、N,N-二乙基苯胺等),氢化钠,氢化钾,氨基化钠,正-丁基锂,二异丙基氨化锂等存在下进行时,反应可加速,副反应可被抑制,从而使产率增加。
这样得到的目的化合物〔I〕或其盐可以通过常规方法例如浓缩,减压浓缩,蒸馏,分馏,调节PH值,再分配,溶剂提取,结晶,重结晶,色谱法等分离和提纯。
应用常规方法可将以游离化合物形式得到的化合物〔I〕转化为盐,亦可将获得的盐转化为游离化合物〔I〕。
在其X1,X2,R1,R2和/或A位置会有例如羧基,磺基和/或膦酰基等酸性基团的化合物〔I〕可以与碱生成盐。为此目的使用的碱有例如钠、钾、锂、钙、镁、氨等无机碱和例如吡啶、可力丁、三乙胺、三乙醇胺等有机碱。在其X1,X2,R1,R2和/或A位置含有例如氨基、取代氨基和/或其它碱性基团的化合物〔I〕可以与酸形成盐。与酸形成的盐的例子有盐酸盐、氢溴酸盐、氢碘酸盐、硝酸盐、硫酸盐、磷酸盐、乙酸盐、苯甲酸盐、马来酸盐、富马酸盐、琥珀酸盐、酒石酸盐、柠檬酸盐、草酸盐、乙醛酸盐、天冬氨酸盐、甲磺酸盐、甲二磺酸盐、1,2-二乙磺酸盐、苯磺酸盐等。
化合物〔I〕可以形成内盐,这种内盐也在本发明的范围内。
化合物〔I〕及其立体异构体和互变异构体〔例如化合物〔I〕为下式化合物时,(其中各符号的定义同前),其互变异构体:(其中的各符号的定义同前)也在化合物〔I〕的范围之内〕可单独或以混合物形成用作杀虫/杀螨剂。
本发明的化合物〔I〕及其盐可有效地防治家庭害虫和动物或植物寄生昆虫和螨,当直接施用于宿主动物和植物时,可产生接触毒物样的强杀虫效果。本发明化合物最显著的特点是具有很强的杀虫作用,甚至在本发明化合物经植物的根、叶、茎等被吸收并在害虫吸食或咬食植物时而与害虫接触后也是如此。这一性质非常有利于防治吸/咬的昆虫和蜱。另外,本发明的化合物对植物和鱼毒性很小,所以,作为农用化学品具有安全实用的特点。
化合物〔I〕及其盐和含有化合物〔I〕及其盐的组合物对防治下列害虫特别有效:半翅目如甘蓝菜蝽、稻里蝽、豆缘蝽、梨冠网蝽、灰稻虱、稻褐飞虱、黑尾叶蝉、矢尖盾蚧、大豆蚜、萝卜蚜、甘蓝蚜、棉蚜、白背稻虱、稻绿蝽、温室粉虱、桃蚜、康氏粉蚧、苹果蚜、绿蝽、温带臭虫、木虱等;鳞翅目如灰翅夜蛾、小菜蛾、菜粉蝶、二化螟、黑纹金斑蛾、Halicov-erpa assulta、粘虫、甘蓝夜蛾、棉褐带卷蛾、棉卷叶螟、稻纵卷叶螟、马铃薯麦蛾等;Cleoptera目如马铃薯瓢虫、黄守瓜、曲条跳甲、稻负泥虫、稻鳞象甲等;双翅目如家蝇、尖音库蚊淡色亚种、三角虻、葱蝇、种蝇等;直翅目如飞蝗、非洲蝼蛄等;蠊目如德国小蠊、烟色大蠊等;叶螨如棉叶螨、红叶螨、神泽叶螨、柑桔全爪螨、苹果全爪螨、刺锈螨等和nem-atodes目如稻白端滑刃线虫等等。
本发明的化合物〔I〕或其盐用作杀虫/杀螨剂时,可制成任何可能和需要的农用化学品应用剂型。例如,通过溶解或分散一种或多种通式〔I〕的化合物或其盐于适合的液体载体或赋形剂中或掺和于或使其吸收于适合的固体载体中,可制成乳油、油剂、可湿性粉剂、粉剂、颗粒剂、片剂、气雾剂、油膏等。如果必要,这样的组合物可另外添加乳化剂、悬浮剂、铺展剂、粘着剂、渗透剂、湿润剂、增稠剂、稳定剂等,并且这些剂型的任何一种都可以按已知方法制造。
在本发明的这种杀虫/杀螨组合物中有效成分(化合物〔I〕或其盐)的浓度取决于预定的施用方式。一般来说,例如对于乳油和可湿性粉剂适合的浓度约为10-90%(重量),对于油剂和粉剂约为0.1-10%(重量),对于粒剂约为1-20%(重量)。不过可以根据预定的施用方式调节浓度。在乳油或可湿性粉剂情形下,在喷洒前用水或其它液体稀释至适宜的浓度(例如稀释100-100,000倍)。
液体载体(溶剂)包括:水,醇类(例如甲醇、乙醇、正-丙醇、异丙醇、乙二醇等),酮类(例如丙酮、甲乙酮等),醚类(例如二氧杂环己烷、四氢呋喃、乙二醇单甲醚、二乙二醇单甲醚、丙二醇单甲醚等),脂肪烃类(例如煤油、燃料油、机油等),芳香烃类(例如苯、甲苯、二甲苯、溶剂石脑油、甲基苯等),卤代烃类(例如二氯甲烷、氯仿、四氯化碳等),酰胺类(例如二甲基甲酰胺、二甲基乙酰胺等),醚类(例如乙酸乙酯、乙酸丁酯、脂肪酸甘油酯等),腈类(例如乙腈、丙腈等)等等。这些溶剂之一种或它们的两种或多种的混合物可用作载体。
固体载体包括植物粉末(例如豆粉、烟草粉、小麦粉、木屑等),无机粉末(例如高岭土、膨润土、酸性白土等粘土,滑石粉,叶蜡石粉等滑石粉和硅藻土、云母粉等硅酸盐),氧化铝,硫黄粉,活性炭等。这些粉末可单独或混合使用。
可应用的软膏基质包括聚乙二醇,果胶,高级脂肪酸多元醇酯(如单硬脂酸甘油酯等),纤维素衍生物(如甲基纤维素等),藻酸钠,膨润土,高级醇,多元醇(如甘油),凡士林,白矿脂,液体石蜡,猪脂,植物油,羊毛脂,无水羊毛脂,氢化油,树脂等或其混合物或与下述任何表面活性剂的混合物。
可根据需要使用并用作上述乳化剂,铺展剂/粘着剂,渗透剂,分散剂等的表面活性剂包括皂类和非离子或阴离子型表面活性剂例如聚氧乙烯烷基芳基醚类(如Daiichi Kogyo Seiy-aku有限公司(日本)制造的Noigen,E.A.142和Toho化学公司(日本)制造的Nonal),烷基硫酸盐类(如Kao公司制造的Emal 10,Emal 40),烷基磺酸盐类(如Daiichi Kogyo Seiyaku有限公司制造的Neogen,Neogen T;Kao公司制造的Neopellex),聚乙二醇醚类(如Sanyo化学工业有限公司制造的Nonipol 85),Nonipzl100,Nonipol 160)和多元醇酯类(如Kao公司制造的Tween 20,Tween 80)。
本发明的化合物可以与其它杀虫剂(拟除虫菊酯杀虫剂、有机磷杀虫剂、氨基甲酸酯杀虫剂、天然杀虫剂等),杀螨剂,杀线虫剂,除草剂,植物激素,植物生长调节剂,杀菌剂(铜杀菌剂、有机氯杀菌剂、有机硫杀菌剂、酚类杀菌剂等),增效剂、引诱剂,拒斥剂,生色剂,肥料等联使用。
本发明的杀虫/杀螨剂毒性低、安全,是优良的农用化学品,本发明的杀虫/杀螨剂可以以与常规杀虫剂和杀螨剂同样的方法应用,并产生超过现有杀虫剂和杀螨剂的效果。例如,本发明的杀虫/杀螨剂可以通过苗床处理,茎/叶喷洒或撤粉,直接施用于害虫,稻田水处理,土壤处理等方法来防治害虫。一般来说,有效成分(化合物〔I〕或其盐)的用量是每公顷0.3g-3,000g,50g-1,000g更好。当本发明的杀虫/杀螨剂以可湿性粉剂提供时,可以稀释后再用,这样,最后有效成分的浓度在0.1-1,000ppm范围内,最好是10-500ppm。
本发明的化合物〔I〕具有优良的杀虫/杀螨活性,通过以下实施例可以银好地说明。
试验实施例1对稻褐飞虱的杀虫效果
将按下面实施例112以同样方法制备的本发明化合物的乳油用水稀释成500ppm的浓度,并按每纸盆10ml的比例喷洒于2叶期稻苗的茎和叶上。试管中放入水,再将处理过的稻苗放到试管中。然后,在每只试管中放入10只稻褐飞虱,并盖上铝帽。将这些试管保持于25℃的培育箱中,7天后记录死虫数。按下式计算死亡率(%),结果示于表1中。
表1
对稻褐飞虱的防除效果
本发明化合物的编号 | 7天后的死亡率(%) |
347121417181920242526282931323334 | 100100100100100100100100100100100100100100100100100100 |
表1(续)
本发明化合物的编号 | 7天后的死亡率(%) |
3537384041424344454647495051525556575859 | 100100100100100100100100100100100100100100100100100100100100 |
表1(续)
本发明化合物的编号 | 7天后的死亡率(%) |
6061626465676870717273757677787980848586 | 100100100100100100100100100100100100100100100100100100100100 |
表1(续)
本发明化合物的编号 | 7天后的死亡率(%) |
8889909192939596979899100101102103104105106107108 | 100100100100100100100100100100100100100100100100100100100100 |
表1(续)
本发明化合物的编号 | 7天后的死亡率(%) |
109110111112113114和115的混合物(7∶3)116117118119和120的混合物(90∶10)119和120的混合物(40∶60)121122123和124的混合物(70∶30) | 100100100100100100100100100100100100100100 |
表1(续)
本发明化合物的编号 | 7天后的死亡率(%) |
124125126127128129130131 | 100100100100100100100100 |
由表1易见,本发明的化合物〔I〕对稻褐飞虱具有优良的杀虫活性。
下面的参考例和制备实例是要进一步阐明本发明,但不构成对本发明范围的限制。
在参考例和实施例中所述柱色谱方法中,洗脱是在薄层色谱(TLC)监测下进行。在TLC监测中,用Merck Kie-selgel 60 F254(产品5715)作TLC板,用柱色谱洗脱剂作展开剂,以UV检测器为检测手段。色谱柱中装填的硅胶是Merck Kieselgel 60(70-230筛目,产品7734)。NMR数据指使用四甲基硅烷作内标物质或外标物质,在Varian EM390(90MHE)光谱仪(另有说明的除外)中测得的1H-NMR谱数据。标有400MHz的NMR数据是用J EOL CX-400(400MHz)光谱仪测出的。所有δ值的单位都是ppm。在应用溶剂混合物作展开剂和洗脱剂的情形下,各溶剂的比在括号中给出。
在对比实例和实例中使用的缩写以及英文的含义如下:Me:甲基;npr:正-丙基;ipr:异丙基;Ee:乙基;Ac:乙酰基;S:单峰;br:宽峰;d:双峰;t:三重峰;q:四重峰;m:多重峰;dd:双重双峰;tt:三重三峰;ddt:双三重峰;td:三重双峰;ddd:双双重双峰;S+S:两个单峰;sextet:六重峰;J:耦合常数;Hz:赫兹;DMSO-d6:二甲基-d6亚砜;%:重量%;m.p:熔点;b.p:沸点;quinoline:喹啉;Nujol:石蜡;benzene:苯;pyridime:吡啶;thiazole:噻唑;decompn:分解;compourd:化合物;each:各个;neat:纯态。
对比实例1
N-甲基-N-3-吡啶甲胺
搅拌下将甲胺(1.36g,0.175mol)的40%水溶液滴加到用冰-水冷却的25ml 20%的NaOH水溶液中,历时5分钟,接着在10分钟内再滴加8.2g(0.05mol)3-吡啶甲基氯盐酸化物的水溶液(10ml)。在室温下再将混合物搅拌2小时,然后用二氯甲烷提取(100ml×3)。用MgSO4干燥提取液,并蒸馏除去溶剂。残余物经真空蒸馏后得到2.6g黄色油状的标题化合物。
b.p.:66℃/2mmHg
NMR(CDCl3)δ:1.48(s,NH),2.45(s,NMe),3.76(s,CH2N)
对比实例2
N-(6-氯-3-吡啶甲基)苯邻二甲酰亚胺
在20ml EtOH中将9.4g(6.4×10-2mol)苯邻二甲酰亚胺和4.2g KOH搅拌30分钟,接着加入100mlDMF(二甲基甲酰胺)和5.2g(2.5×10-2mol)6-氯-3-吡啶甲基氯。在60℃搅拌混合物1小时,减压蒸除EtOH和DMF,用硅胶柱对残余物进行色谱分离并用二氯甲烷洗脱。经过上述步骤得到6.7g无色针晶状的标题化合物。
m.p.:142-143℃
NMR(CDCl3)δ:4.85(s,2H),7.28(d,J=8.9Hz,1
H),7.6-8.0(m,5H),8.51(d,J=2.8Hz,1H)
对比实例3
6-氯-3-吡啶-甲胺
将水合肼(1.7ml)加入6.5g(2.4×10-2mol)N-(6-氯-3-吡啶-甲基)苯邻二甲酰亚胺于100mlEtOH中的回流溶液中,并将混合物再回流1小时。加入20ml水后,减压蒸除乙醇。往残留物中加入浓盐酸(25ml),并将混合物回流1小时。冷却后,用NaOH中和反应混合物,并用NaCl饱和水层,再用Et2O提取。用Na2SO4干燥提取液,蒸除溶剂,得到2.4g黄色油状的标题化合物。
NMR(CDCl3)δ:1.4-2.0(br,2H),3.89(s,2H),
7.27(d,J=8.9Hz,1H),7.67(dd,J=8.9&
2.7Hz,1H),8.32(d,J=2.7Hz,1H)
对比实例4
1-甲硫基-1-哌啶子基-2-硝基乙烯
加热下将1.7g(0.01mol)1,1-双(甲硫基)-2-硝基乙烯溶于20ml EtOH,回流下将溶于10mlEtOH的0.9g(0.01mol)哌啶分三批隔30分钟加入到所得溶液中。回流2小时后,蒸除溶剂,用硅胶柱色谱对残余物进行色谱分离,用ACOEt-甲苯(2∶3)洗脱。经过上述步骤,得到0.8g黄色棱晶状的标题化合物。
m.p.:65-67℃
NMR(CDCl3)δ:2.45s),6.68(s)
IR(Nujol):1650,1530,1380cm-1
对比实例5
按与对比实例4相同的方法使1,1-双(甲硫基)-2-硝基乙烯与各种胺反应,得到下列化合物:
(1)1-甲氨基-1-甲硫基-2-硝基乙烯(黄色鳞片状)
m.p.:111-112℃
NMR(CDCl3)δ:2.45(s),3.15(d),6.62(s),10.5
(br s)IR(Nujol):3200,1575,1345cm-1(2)1-(2,2-二甲基-1-肼基)-1-甲硫基-2-硝
基乙烯(浅黄色棱晶状)
m.p.:139-140℃
NMR(CDCl3)δ:2.26(s),2.65(s),6.40(s),10.46
(brs)
IR(Nujol):3130,1535,1340cm-1
对比实例6
N-(6-氯-3-吡啶甲基)-N-甲胺 (1) 将0.8g(5.7×10-3mol)6-氯吡啶-3-
醛和10g Na2SO4加入30ml甲苯中,在搅拌混
合时,在30分钟内滴加40%的甲胺(1.4g,1.1
×10-2mol)的水溶液,接着加入10g MgSO4。
混合物在室温下放置过液,然后过滤。浓缩滤液,得到0.6g
(60%产率)晶状的N-(6-氯-3-吡啶 亚甲基)甲
胺。
NMR(CDCl3)δ:3.52(d,3H),7.35(d,J=8.8Hz,
1H),8.04(dd,J=8.8&2.7Hz,1H),
8.2-8.4(m,1H),8.59(d,J=2.7Hz,1H)(2) 将步骤(1)获得的N-(6-氯-3-吡啶亚甲基)甲胺溶于
10ml MeOH中,在0℃搅拌下,小批量加入0.07g
(1.9×10-3mol)氢硼化钠。30分钟后,蒸
除MeOH,用5ml水稀释残留物,再用ACOEt
(10ml×3)提取残留物,用MgSO4干燥提取液,
然后浓缩,得到0.43g(产率为71%)黄色油状的标
题化合物。
NMR(CDCl3)δ:1.90(s,1H),2.44(s,3H),3.74
(s,2H),7.28(d,J=8.2Hz,1H).7.67(dd,
J=8.2&2.8Hz,1H),8.31(d,J=2.8Hz,1H)
对比实例7
按与对比实例6(1)相同的方法使吡啶-3-醛或喹啉-3-醛与各种胺或1,1-二甲基肼反应,得到下列化合物。
(1) N-(3-吡啶 亚甲基)乙胺(浅黄色油状)
NMR(CDCl3)δ:1.30(t),3.66(q),8.31(s)
(2) N-(3-吡啶亚甲基)-2-二甲氧乙胺(黄色油状)
NMR(CDCl3)δ:3.43(s),3.83(d),4.71(t),8.35
(s)
(3) N-(3-吡啶亚甲基-2-甲氧乙胺(浅黄色油状)
NMR(CDCl3)δ:3.39(s),3.76(m),8.36(s)
(4) N-(3-喹啉亚甲基)甲胺(黄色油状)
NMR(CDCl3)δ:3.53&3.54(each s,=NMe),7.1-8.5
(m,6H,quinoline-H6),9.28&9.30(each s,
CH=N)
IR(neat):1690,1645,1615,1490,785,750cm-1
(5) 1,1-二甲基-2-(3-吡啶亚甲基)肼(无色油状)
b.p.:110℃/2mmHg
NMR(CDCl3)δ:3.00(s,NMe 2),7.15(s,CH=N)
IR(neat):1580,1550,1465,1415,1040,710cm-1
(6) N-(3-吡啶亚甲基)-正丁胺(浅黄色油状)
NMR(CDCl3)δ:0.95(t),1.75(m),3.62(t),7.33
(dd),8.12(dt),8.31(s,CH=N),8.62(dd),
8.86(d)
(7) N-(3-吡啶亚甲基)-正丁胺(浅黄色油状)
NMR(CDCl3)δ:0.94(t),1.20-1.90(m),3.65(t),
7.33(dd),8.12(dt),8.31(s,CH=N),8.62
(dd),8.86(d)
(8) N-(3-吡啶亚甲基-苄胺(浅黄色油状)
NMR(CDCl3)δ:4.84(s,CH2),7.33(s,C6H5),7.33
(dd),8.15(dt),8.40(br s,CH=N),8.65
(dd),8.88(d)
对比实例8
按与对比实例6(2)相同的方法使对比实例7(1)-(4)和(6)-(8)的化合物分别反应,得到下列化合物。
(1) N-乙基-N-(3-吡啶甲基)胺(浅黄色油状) b.p.:60℃/0.7mmHgNMR(CDCl3)δ:1.13(t),1.45(br s),3.70(q),
3.82(s)(2) N-(2-二甲氧乙基)-N-(3-吡啶甲基)胺(黄色
油状)
NMR(CDCl3)δ:1.73(br s),2.75(d),3.36(s),
3.82(br s),4.46(t)(3) N-(2-甲氧乙基)-N-(3-吡啶甲基)胺(无色油
状)
b.p.:90℃/0.7mmHg
NMR(CDCl3)δ:1.86(br s), 2.82(t),3.36(s),
3.53(t),3.83(s)(4) N-甲基-N-(3-喹啉基甲基)胺(黄色油状)
NMR(CDCl3)δ:2.24(s,NMe),3.09(br,NH),3.86
(s,NCH2),7.3-8.2(m,5H,quinoline-H5),
8.83(d,J=2Hz,1H,quinoline-H1)(5) N-(正丙基)-N-(3-吡啶甲基)胺(黄色油状)
b.p.:85℃/1.5mmHg
NMR(CDCl3)δ:0.90(t),1.30-1.76(m),1.64
(br s,NH),2.60(t),3.80(s),7.23(dd),
7.67(dt),8.43-8.63(m)
(6) N-(正丁基)-N-(3-吡啶甲基)胺(浅黄色油状)
b.p.:83℃/1mmHg
NMR(CDCl3)δ:0.78-1.06(m),1.1-1.75(m),1.45
(br s,NH),2.63(t),3.80(s),7.24(dd),
7.69(dt),8.46-9.63(m,2H)
(7) N-苄基-N-(3-吡啶甲基)胺(无色油状)
b.p.:125℃/0.5mmHg
NMR(CDCl3)δ:1.83(br s,NH),3.77(s,4H),
7.26(dd),7.32(br s,C6H5),7.66(dt),
8.43-8.60(m,2H)
对比实例9
1,1-二甲基-2-(3-吡啶甲基)肼
将4.6g氢化铝锂悬浮于100ml无水乙醚中,搅拌下在氮气气氛中滴加12.0g 1,1-二甲基-2-(3-吡啶亚甲基)肼于50ml无水乙醚中的溶液。将混合物回流5小时,然后冷却至5℃,搅拌下相继滴加5ml水、5ml 20%NaOH水溶液和15ml水。滤去不溶的物质,浓缩滤液。用硅胶柱色谱法(洗脱液:氯仿/乙醇二10/1)提纯残余物。减压蒸馏得到的油状物,得到2.5g黄色油状的标题化合物。
b.p:100-115℃/1mmHg
NMR(CDCl3)δ:2.47(s,NMe2),2.81(br s,NH),
3.93(s,CH2N)
对比实例10
2,6-二氯-3-吡啶甲胺
(1) 将3.9g(0.021mol)苯邻二甲酰亚胺钾悬浮于40ml DMF中,接着加入3.9g(0.02mol)2,6-二氯-3-吡啶甲基氯,在60-70℃搅拌混合物2小时。减压蒸除DMF,用50ml水稀释残留物,再用CHCl3提取(50ml×3)。用MgSO4干燥提取液并浓缩,过滤收集产生的沉淀,用乙醚洗涤,干燥,得到3.8g白色棱晶状的N-2,6-二氯-3-吡啶甲基)苯邻二甲酰亚胺。
m.p.:189-190℃
NMR(CDCl3)δ:4.95(s,2H),7.22(d,J=8.5Hz),
7.65(d,J=8.5Hz),7.66-8.0(m,4H)
(2) 在50ml EtOH和20ml DMF的混合液中加热溶解3.1g(0.01mol)N-(2,6-二氯-3-吡啶甲基)苯邻二甲酰亚胺,接着在回流条件下加入0.75g(0.015mol)水合肼。回流1小时后,蒸除EtOH和DMF。往残余物中加入10ml浓盐酸和5ml水,并将混合物回流30分钟。滤去产生的晶体,用NaHCO3中和滤液,用CH2Cl2提取(30ml×3)。用MgSO4干燥提取液,蒸除溶剂,得到1.45g黄色油状的标题化合物。
NMR(CDCl3)δ:1.55(s,2H),3.96(s,2H),7.27
(d,J=8.5Hz),7.82(d,J=8.5Hz)
对比实例11
N-(2,6-二氯-3-吡啶甲基-N-甲胺
在50ml乙腈中溶解7.8g.(0.1mol)40%的甲胺水溶液,在搅拌和冰冷却下,在5分钟内滴加3.9g(0.02mol)2,6-二氯-3-吡啶甲基氯于10ml乙腈中的溶液。滴加完毕,在室温下搅拌混合物2小时,然后浓缩。用乙醚提取残余物(30ml×3),用MgSO4干燥。最后,蒸除溶剂,得到浅黄色油状的标题化合物。
NMR(CDCl3)δ:1.46(s,NH),2.46(s,3H),3.82
(s,2H),7.26(d,J=8.5Hz),7.75(d,J=8.5
Hz)
对比实例12
1-〔N-(2,6-二氯-3-吡啶甲基)N-甲基〕氨基-1-甲硫基-2-硝基乙烯
除了用N-(2,6-二氯-3-吡啶甲基)-N-甲胺代替哌啶外,重复对比实例4的反应,得到黄色棱晶状的标题化合物。
m.p.:111-112℃
NMR(CDCl3)δ:2.46(s,3H),3.12(s,3H),4.84
(s,2H),6.79(s,1H),7.35(d,J=8.5Hz),
7.66(d,J=8.5Hz)
对比实例13
按与对比实例4相同的方法,使1,1-双(甲硫基)-2-硝基乙烯与各种胺反应,得到下列化合物。
(1) 1-二甲氨基-1-甲硫基-2-硝基乙烯(黄色油状)
NMR(CDCl3)δ:2.46(s,3H),3.21(s,6H),6.69
(s,1H)
(2) 1-(N-乙基-N-甲基)氨基-1-甲硫基-2-硝基乙
烯(黄色油状)
NMR(CDCl3)δ:1.27(t,J=6.5Hz,3H),2.48
(s,3H),3.13(s,3H),3.64(q,J=6.5Hz,2
H),6.73(s,1H)
(3) 1-(4-氯苄基)氨基-1-甲硫基-2-硝基乙烯(浅黄
色结晶)
m.p.:121-123℃
NMR(CDCl3)δ:2.43(s,Me),4.60(d,J=6Hz,
CH2),6.59(s,=CHNO2),7.23&7.36(each d,
J=9Hz,each 2H,benzene-H4),10.71(br,NH)
对比实例14
N-甲基-N-〔2-(3-吡啶)乙基〕胺
(1) 在100ml CHCl3中溶解6.39g(0.052mol)2-(3-吡啶)乙醇,接着在室温和搅拌下滴加15.6ml亚硫酰氯。然后搅拌混合物1.5小时,再蒸除溶剂。加入乙醚后,过滤收集晶体,并干燥。得到9.13g白色晶状2-(3-吡啶基)乙基氯盐酸化物。
m.p.:157-158℃
NMR(DMSO-d6)δ:3.33(t,J=7Hz,CH2Cl),4.02(t,
J=7Hz,
CH 2-pyridine),8.10(dd,J=6&8Hz),
8.64(m),8.90(d,J=6Hz),9.00(d,J=2Hz),
11.5(br)
(2)搅拌下往32.6g 40%甲胺水溶液中小批量加入7.48g(0.042mol)2-(3-吡啶基)乙基氯盐酸化物。将混合物移入不锈钢反应柱中,在外部温度为80℃下加热4小时。冷却后,在冰冷却和搅拌下加入3.36g NaOH,用NaCl饱和此混合物,并用CH2Cl2提取。用MgSO4干燥提取液,蒸除CH2Cl2,得到6.32g黄色油状的标题化合物,为粗产品。
NMR(CDCl3)δ:1.58(s,NH),2.44(s,NMe),2.82
(m,CH2CH2),7.21(dd,J=5&8Hz,1 H),7.55
(m,1H),8.47(m,2H)
对比实例15
按与对比实例6(1)相同的方法使吡啶-4-醛和吡啶-2-醛分别与甲胺反应,得到下列化合物。
(1) N-(4-吡啶亚甲基)甲胺(黄色油状)
NMR(CDCl3)δ:3.52(d,J=2Hz,MeN),7.53(m,2
H,pyridyl-H2),8.20(m,CH=N),8.65(m,2H,
pyridyl-H2)
IR(neat):1645,1590,1410,995,810cm-1
(2) N-(2-吡啶亚甲基)甲胺(黄色油状)
NMR(CDCl3)δ:3.54(d,J=2Hz,MeN),7.30(m,1
H,pyridine-H1),7.71(m,1H,pyridine-H1),
7.97(m,1H,pyridine-H1),8.40(m,CH=N),
8.31(d,J=5Hz,1H,pyridine-H1)
IR(neat):1650,1585,1645,1430,990,770cm-1
对比实例16
按与对比实例6(2)相同的方法使对比实例15(1)和(2)的化合物分别反应,得到下列化合物。
(1) N-甲基-N-(4-吡啶甲基)胺(棕黄色油状)
NMR(CDCl3)δ:1.86(br s,NH),2.44(s,Me),3.76
(s,CH2),7.30(m,2H,pyridine-H2),8.53
(m,2H,pyridine-H2)
IR(neat):3260,1600,1440,1410,790cm-1
(2) N-甲基-N-(2-吡啶甲基)胺(橙色油状)
NMR(CDCl3)δ:2.48(s,Me),3.87(s,CH2),
7.0-7.4(m,2H,pyridine-H2),7.64(t,J=8
Hz,1H,pyridine-H1),8.56(d,J=4Hz,
pyridine-H1)
IR(neat):1590,1570,1470,1430,755cm-1
对比实例17
N-(6-氯-3-吡啶甲基)-N-乙胺
使用6-氯-3-吡啶甲基氯和70%的乙胺水溶液,按对比实例11的方法进行反应,得到棕色油状的标题化合物。
NMR(CDCl3)δ:1.11(t,J=7Hz,CH2CH3),1.43(s,
NH),2.68(q,J=7Hz,CH2CH3),3.79(s,
CH 2-pyridine),7.28(d,J=8Hz,1H),7.71
(dd,J=2&8Hz,1H),8.33(d,J=2Hz,1H)
IR(neat):1595,1565,1460(sh),1450,1380,1100
cm-1
对比实例18
O-甲基-N-(3-吡啶甲基)羟基胺
将6.6g(0.04mol)3-吡啶甲基氯盐酸化物悬浮在200ml乙腈中,接着加入10g(0.12mol)O-甲基羟基胺盐酸盐和16.2g(0.16mol)三乙胺。在50℃搅拌混合物15小时,滤去不溶物质,浓缩滤液。用硅胶柱色谱法分离残余物,用EtOH-CHCl3(1∶10)作洗脱液。得到1.0g黄色油状标题化合物。NMR(CDCl2)δ:3.47(s,3H),4.05(s,2H), 5.73
(br,NH),7.27(dd,J=8&5Hz,1H),7.73
(dt,J=8&2Hz,1H),8.50-8.70(m,2H)IR(neat):3200,1580,1425,710cm-1
对比实例19
异硫氰酸(2-甲氧基)乙酯
在70ml水中溶解4.6g(0.11mol)NaOH,然后剧烈搅拌下加入6.4ml(0.11mol)二硫化碳,逐步滴加8.0g(0.11摩尔)2-甲氧基乙胺。在70℃搅拌混合物2小时,然后在室温下滴加8.2ml(0.11mol)氯甲酸甲酯。在50℃下搅拌混合物1小时。将油状物与水层分开,用乙醚提取油状物并用MgSO4干燥。蒸除乙醚,减压蒸馏残余物,得到无色油状的标题化合物。
b.p:77-80℃/22mmHg
NMR(CDCl3)δ:3.41(s,3H),3.4-3.8(m,4H)
IR(neat):2080,1720,1340cm-1
对比实例20
6-氯-3-吡啶甲基氯和6-氯-3-吡啶甲基氯盐酸化物
(1) 在70ml MeOH中悬浮12.0g(0.086mol)6-羟基烟酸,接着加入4ml浓硫酸。将混合物回流10小时。冷却后,蒸除MeOH,用饱和碳酸氢钠水溶液调节残余物的PH值至约8。过滤收集沉淀,用水漂洗(二次),干燥,得到10.5g浅黄色晶状的6-羟基烟酸甲酯。该产物是吡啶酮结构。
NMR(DMSO-d6)δ:3.77(s,3H),6.38(d,J=10Hz,
1H),7.80(dd,J=10&3Hz,1H),8.05(d,
J=3Hz,1H),11(br)
(2) 在100ml乙腈中溶解4.0g(0.026mol)6-羟基烟酸甲酯,接着加入0.9ml三乙胺。回流混合物,在15分钟内搅拌下滴加3.7ml磷酰氯。再回流混合物3小时。冷却后,蒸除乙腈,用20ml水稀释残余物,用饱和碳酸氢钠水溶液调节PH至8左右。过滤收集生成的晶体,用水漂洗,干燥,得到3.6g浅黄色针晶状6-氯烟酸甲酯。
m.p.:87-88℃
MNR(CDCl3)δ:3.97(s,3H),7.44(d,J=8Hz,1
H),8.27(dd,J=8&2Hz,1H).9.02(d,J=2
Hz,1H)IR(Nujol):1715,1585,1440,1290,1280,1125
cm-1
(3) 搅拌回流下,在1小时内将8.0ml MeOH加入到3.0g(0.0175mol)6-氯烟酸甲酯、2.0g氢硼化钠和60ml THF的混合物中。滴加完毕,再回流混合物30分钟,冷却后蒸除溶剂。用30ml水稀释残余物,用NaCl使之饱和,用CH2Cl2(20ml×3)提取。用MgSO4干燥CH2Cl2层,然后蒸除CH2Cl2得到2.3g黄色油状的6-氯-3-吡啶甲醇。在室温下放置,该产物全部结晶出。NMR(CDCl3)δ:2.89(br,1H),4.69(s,2H),7.28
(d,J=9Hz,1H),7.69(dd,J=9&3Hz,1H),
8.28(d,J=3Hz,1H)
(4) 在500ml CHCl3中溶解47.3g(0.33mol)6-氯-3-吡啶甲醇,接着在室温和搅拌下滴加亚硫酰氯。滴加完毕,再搅拌混合物1.5小时,然后放置过夜。减压蒸除CHCl3,收集残余的结晶体和油状物。用乙醚稀释残余物,过滤收集,干燥,得到45.2g 6-氯-3-吡啶甲基氯盐酸化物,为白色晶体。
NMR(DMSO-d6)δ:4.82(s,2H),7.51(d,J=8Hz,1
H),7.97(dd,J=8&2Hz,1H),8.50(d,J=2
Hz,1H)
将分离出上述大量结晶体后残余物的母液浓缩,使不溶性残余物溶于EtOH,用甲苯稀释,浓缩。重复上述步骤共3次,得到9.04g 6-氯-3-吡啶甲基氯,为油状粗产品。
(5) 将15.0g(0.076mol)6-氯-3-吡啶甲基氯盐酸化物悬浮于50ml水中,用饱和碳酸氢钠水溶液调节悬浮液的PH值至约8。用乙醚(100ml×3)提取得到的混合物,用MgSO4干燥,然后减压蒸除乙醚,得到结晶状残余物。加入己烷后,过滤收集晶体,用己烷洗涤,干燥,得到11.0g白色棱晶状的6-氯-3-吡啶甲基氯。
m.p.:39-40℃
NMR(CDCl3)δ:4.56(s,2H),7.35(d,J=8Hz,1
H),7.73(dd,J=8&2Hz,1H),8.40(d,J=2
Hz,1H)IR(Nujol):1585,1445,1280,1135,1105,820,740
cm-1
对比实例21
N-甲基-N-(2-吡嗪基)甲胺
(1) 在300ml CCl4中溶解9.4g(0.1mol)2-甲基吡嗪,接着加入13.4g N-氯琥珀酰亚胺和0.5g过氧化苯甲酰。回流混合物24小时。冷却后,滤去不溶性物质,浓缩滤液,得到11.0g 2-氯甲基吡嗪,为油状物。
NMR(CDCl3)δ:4.73(s,2H),8.36-8.70(m,2H),
8.80(s,1H)
(2) 用2-氯甲基吡嗪代替2,6-二氯-3-吡啶甲基氯,按对比实例11的方法进行反应,得到油状的标题化合物。NMR(CDCl3)δ:2.50(s,3H),2.63(br,1H),3.93
(s,2H),8.45-8.60(m,2H),8.63(s,1H)
对比实例22
1-〔N-(6-氯-3-吡啶甲基)-N-正丙基〕氨基-1-甲硫基-2-硝基乙烯
(1) 在15ml乙腈中溶解6.05g(0.0373mol)6-氯-3-吡啶甲基氯,在冰-水冷却和搅拌下,将所得溶液滴加到10.97g正丙胺于50ml乙腈的溶液中。滴加完毕,在室温下搅拌混合物1小时。在外部温度为50℃下再搅拌1小时。蒸除乙腈,用碳酸氢钠水溶液稀释残余物,用CH2Cl2(100ml×3)提取。用MgSO4干燥提取液,蒸除CH2Cl2,得到6.94g棕黄色油状的N-(6-氯-3-吡啶甲基)-N-正丙胺。
NMR(CDCl3)δ:0.90(t,J=7Hz,CH2CH3),1.32(s,
NH),1.52(sextet,J=7Hz,CH2CH3),2.59(t,
J=7Hz,NCH2CH2),3.79(s,C
H 2-pyridine),
7.29(d,J=8Hz,1H),7.71(dd,J=8&2Hz,
1H),8.35(d,J=2Hz,1H)
(2) 在回流温度下将4.47g 1,1-双(二甲硫基)-2-硝基乙烯溶于100ml EtOH中。然后在搅拌和回流条件下滴加3.50g(0.0190mol)N-6-氯-3-吡啶甲基-N-正丙胺于15ml EtOH的溶液,再将混合物回流12.5小时。反应混合物在室温下放置过夜并滤去产生的结晶。浓缩滤液,用EtOH-CHCl3(1∶20)作洗脱液,用硅胶(250g)柱色谱法分离残余物,得到2.98g黄色粘油状的标题化合物。
NMR(CDCl3)δ:0.90(t,J=7Hz,CH2CH3),1.68
(sextet,J=7Hz,CH2CH3),2.46(s,MeS),3.42
(t,J=7Hz,NCH2CH2),4.70(s,CH2-pyridine),
6.80(s,=CHNO2),7.36(d,J=8Hz,1H),7.61
(dd,J=8&2Hz,1H),8.29(d,J=2Hz,1H)
对比实例23
1-〔N-(6-氯-3-吡啶甲基)-N-异丙氨基-1-甲硫基-2-硝基乙烯
用异丙胺代替正丙胺,按对比实例22的步骤(1)和(2)进行反应,分别得到下列化合物。
(I)N-(6-氯-3-吡啶甲基)-N-异丙胺(油状)
NMR(CDCl3)δ:1.07(d,J=6Hz,
Me2CH),1.21
(br s,NH),2.84(septet,J=6Hz,C
HMe2),
3.77(s,CH2),7.28(d,J=8z,1H),7.71
(dd,J=8&2Hz,1H),8.35(d,J=2Hz,1H)
(2)标题化合物(粘油状)
NMR(CDCl3)δ:1.35(d,J=7Hz,CH
Me 2),2.38(s,
MeS),4.64(s,CH2),6.57(s,=CHNO2)
对比实例24
2-氯-5-甲氨基吡啶
往5.0g(0.039mol)5-氨基-2-氯吡啶中加入40ml原甲酸乙酯,回流混合物5小时。减压浓缩反应混合物,将残余物溶于50ml EtOH中。加入1.8g氢溴酸钠后,在70-80℃搅拌混合物3小时。浓缩反应混合物,加入50ml冰水和5ml浓盐酸后,用NaHCO3调节混合物的pH值至7~8,用AcOEt提取(50ml×3)。汇集AcOEt层,用水洗涤,用MgSO4干燥。蒸除AcOEt,往结晶的残余物中加入己烷,过滤收集晶体,用己烷洗涤,干燥,得到5.1g白色晶状的标题化合物。
m.p.:70℃
NMR(CDCl3)δ:2.85(br d,J=4.5Hz,3H),3.3-4.3
(m,1H),6.87(dd,J=8.0&3.0Hz,1H),
7.11(d,J=8.7Hz,1H),7.78(d,J=3.3Hz,1
H)
对比实例25
N-(2,6-二甲基-4-吡啶甲基)-N-甲胺
(1) 在77ml CHCl3中溶解7.00g(0.0511mol)(2,6-二甲基-4-吡啶基)甲醇,在室温搅拌下,滴加15.3ml亚硫酰氯。滴加完毕,搅拌混合物3小时,浓缩。用碳酸氢钠水溶液稀释残余物,用AcOEt提取(100ml×3)。用MgSO4干燥提取液,蒸除AcOEt,得到6.37g油状的(2,6-二甲基-4-吡啶)甲基氯。
NMR(CDCl3)δ:2.53(s,Mex2),4.45(s,CH2),
6.98(s,pyridine-H2)
(2) 用(2,6-二甲基-4-吡啶基)甲基氯化替2,6-二氯-3-吡啶甲基氯,按对比实例11的方法进行反应,得到油状的标题化合物。
NMR(CDCl3):2.44(s,NMe),2.50(s,pyridine-
Mex2),3.68(s,CH2),6.94(s,pyridine-H2)
对比实例26
N-(2-氯-3-吡啶甲基)-N-甲胺
(1) 往10.24g(0.065mol)2-氯烟酸中加入20ml 1,2-二氯乙烷和9.5ml亚硫酰氯。回流混合物1小时,浓缩反应混合物,待到11.9g橙色油状的2-氯烟酰氯。在室温下放置时,该产物完全固化。
NMR(CDCl3)δ:7.54(dd,J=8&5Hz,1H),8.48
(dd,J=8&1Hz,1H),8.65(dd,J=5&1Hz,
1H)
(2) 在100ml冷水中溶解8.98g氢硼化钠,在冰冷却和搅拌下,小批量加入11.7g(0.0665mol)2-氯烟酰氯,在相同的温度下再搅拌混合物30分钟,然后用Et2O(100ml×3)提取。用MgSO4干燥提取液,蒸除Et2O,得到8.75g浅黄色油状的(2-氯-3-吡啶)甲醇。在室温下放置时,该产物完全固化。
NMR(CDCl3)δ:4.53(br,OH),4.77(s,CH2),7.30
(m,1H),7.97(m,1H),8.25(m,1H)
(3) 用(2-氯-3-吡啶基)甲醇代替(2,6-二甲基-4-吡啶)甲醇,按对比实例25(1)的方法进行反应,得到(2-氯-3-吡啶基)甲基氯,为黄色油状物。
NMR(CDCl3)δ:4.71(s,CH2),7.31(dd,J=8&5
Hz,1H),7.88(dd,J=8&2Hz,1H),8.33
(dd,J=5&2Hz,1H)
(4) 用(2-氯-3-吡啶基)甲基氯代替2,6-二氯-3-吡啶甲基氯,得到黄色油状的标题化合物。
NMR(CDCl3)δ:1.95(s,NH),2.47(s,Me),3.84
(s,CH2),7.26(dd,J=8&5Hz,1H),7.80
(dd,J=8&2Hz,1H),8.30(dd,J=5&2Hz,
1H)
对比实例27
2-甲基-5-甲氨基吡啶草酸酯
往5.0g(0.04mol)5-氨基-2-甲基吡啶中加入40ml原甲酸乙酯,回流混合物1小时。减压浓缩反应混合物,将残余物溶于50ml EtOH中,接着加入2.1g氢硼化钠。搅拌下回流混合物2.5小时。浓缩反应混合物,往残余物中加入50ml冰水和8ml浓盐酸。用NaHCO3调节混合物至pH等于7,用AcOEt(50ml,30ml×2)提取。合并AcOEt层,用氯化钠水溶液洗涤,用MgSO4干燥。蒸除AcOEt,用Et2O稀释残余物,滤去不溶性物质。往滤液中加入草酸于EtOH中的溶液(约10%),过滤收集得到的晶体,用EtOH洗涤,干燥,得到4.3g浅黄色晶状的标题化合物。
m.p.:118.5-119.5℃
NMR(DMSO-d6)δ:2.43(3H,s),2.73(3H,s),
7.1-7.5(2H,m),7.8-8.0(1H,m),8.2-9.0
(m)
对比实例28
N-(5-溴-3-吡啶甲基)-N-甲胺
除了用5-溴烟酸代替2-氯烟酸外,重复对比实例26的步骤(1)、(2)、(3)和(4),各步骤分别获得下列化合物。
(1) 5-溴烟酰氯(白色晶状)
NMR(CDCl3)δ:8.54(m,1H),8.99(d,J=1Hz,1
H),9.25(d,J=1Hz,1H)
(2) (5-溴-3-吡啶甲醇(橙色油状的粗产物)
NMR(CDCl3)δ:4.39(brs,OH),4.73(s,CH2),
7.90(m,1H),8.47(d,J=1Hz,1H),8.55
(d,J=2Hz,1H)
(3) (5-溴-3-吡啶)甲基氯(油状粗产物)
NMR(CDCl3)δ:4.57(s,CH2),7.92(m,1H),8.56
(d,J=1Hz,1H),8.65(d,J=1Hz,1H)
(4) 标题化合物(油状粗产物)
NMR(CDCl3)δ:2.44(s,Me),3.76(s,CH2),
7.89(m,1H),8.48(d,J=1Hz,1H),8.57
(d,J=1Hz,1H)
对比实例29
N-(2-甲硫基-3-吡啶甲基)-N-甲胺
除了用2-甲硫基烟酸代替2-氯烟酸外,重复对比实例26的步骤(1)、(2)、(3)和(4),各步分别获得下列化合物。
(1) 2-甲硫基烟酰氯(白色-浅黄色晶状)
NMR(CDCl3)δ:2.56(s,MeS),7.17(dd,J=5&8
Hz,1H),8.52(dd,J=8&2Hz,1H),8.67
(dd,J=5&2Hz,1H)
(2) (2-甲硫基-3-吡啶基)甲醇(浅黄色油状,放置时完全结晶)
NMR(CDCl3)δ:2.56(s,MeS),3.46(br s,OH),
4.62(s,CH2),6.99(dd,J=5&8Hz,1H),
7.62(dd,J=8&1Hz,1H),8.33(dd,J=5&8
Hz,1H)
(3) (2-甲硫基-3-吡啶基)甲基氯(浅黄色油状物)
NMR(CDCl3)δ:2.61(s,MeS),4.60(s,CH2),
6.99(dd,J=5&8Hz,1H),7.58(dd,J=8&2
Hz,1H),8.43(dd,J=5&2Hz,1H)
(4) 标题化合物(黄色油状)
NMR(CDCl3)δ:1.50(s,NH),2.44(s,MeN),2.57
(s,MeS),3.73(s,CH2),6.97(dd,J=5&8
Hz,1H),7.51(dd,J=8&1Hz,1H),8.37
(dd,J=5&1Hz,1H)
对比实例30
N-甲基-N-(4-噻唑基)甲胺
除了用4-甲基噻唑代替2-甲基吡嗪外,重复对比实例21(1)的反应步骤,得到4-氯甲基噻唑,为油状粗产物。
NMR(CDCl3)δ:4.72(s,CH2Cl),7.37(m,1H),
8.78(d,J=2Hz,1H)
除了用4-氯甲基噻唑粗产物代替2,6-二氯-3-吡啶甲基氯,反应在室温下进行1小时和在50℃再进行2小时外,重复对比实例11的反应步骤,得到标题化合物,为油状粗产物。
NMR(CDCl3)δ:2.43(s,MeN),3.89(s,CH2),
7.17(m,1H),8.74(d,J=2Hz,1H)
对比实例31
2-氯-5-乙氨基吡啶
将10g(0.078mol)5-氨基-2-氯吡啶和50ml原乙酸乙酯的混合物回流2小时。减压浓缩反应混合物,将残余物溶于60ml无水THF中。在连续搅拌下将所得溶液在15分钟内滴加到7.0g氢硼化锂于100ml无水THF中的悬浮液中。滴加完毕,搅拌下回流混合物27小时,冷却后,蒸除溶剂,往残余物中加入100ml冰-水和35ml浓盐酸,在67℃加热混合物一段时间。冷却后,用碳酸氢钠调节反应混合物的pH值至7,用AcOEt提取(50ml×3)。合并AcOEt层,用氯化钠水溶液洗涤,用MgSO4干燥。蒸除AcOEt,过滤收集残留的结晶体,用己烷洗涤,干燥。得到9.2g标题化合物,为带有浅黄色的绿色晶体。
m.p.:65-66℃
NMR(CDCl3)δ:1.25(3H,t,J=7.4Hz),2.9-3.4(2
H,m),3.4-4.1(1H,m,NH),6.86(1H,dd,
J=9.0&3.0Hz),7.09(1H,d,J=7.8Hz),
7.77(1H,d,J=2.7Hz)
对比实例32
2-氯-5-正丙氨基吡啶
(1) 往6.4g(0.05mol)5-氨基-2-氯吡啶中加入25g原丙酸三乙酯,回流混合物3小时。然后使用真空泵,在70℃的外部温度下,减压浓缩反应混合物,得到10.5g黄色油状的N-(6-氯-3-吡啶基-O-乙基丙酰亚胺。
NMR(CDCl3)δ:1.07(t,J=8Hz,3H),1.33(t,J=7
Hz,3H),2.16(q,J=8Hz,2H),4.22(q,J=7
Hz,2H),7.06(dd,J=8&3Hz,1H),7.25
(d,J=8Hz,1H),7.87(d,J=3Hz,1H)
(2) 往二氢-双(2-甲氧乙氧)铝酸钠于甲苯中的70%溶液,在室温和搅拌下,滴加8.5g(0.04mol)N-(6-氯-3-吡啶)-O-乙基丙酰亚胺于20ml甲苯中的溶液,历时5分钟。在室温下搅拌混合物1小时,在50℃下再搅拌2小时,然后在冰冷却下在5分钟内滴加50ml水。在50℃搅拌混合物15分钟。分离出甲苯层,用MgSO4干燥,浓缩,用己烷丙酮(2∶1)作洗脱液,对残余物进行硅胶标色谱分离,得到5.9g黄色油状的标题化合物。
NMR(CDCl3)δ:0.99(t,J=7Hz,3H),1.65(m,2
H),3.07(dt,J=7&6Hz,2H),3.83(br,1
H),6.86(dd,J=8&3Hz,1H),7.10(d,J=8
Hz,1H),7.77(d,J=3Hz,1H)
对比实例33
2-氯-5-正丁氨基吡啶
除了用原丁酸三甲酯代替原丙酸三乙酯外,重复对比实例32的步骤(1)和(2),各步分别获得下列化合物。
(1) N-(6-氯-3-吡啶基)-O-甲基丁酰亚胺(黄色油状)
NMR(CDCl3)δ:0.85(t,J=7Hz,3H),1.33-1.80
(m,2H),2.16(t,J=7Hz,2H),3.80(s,3
H),7.06(dd,J=8&3Hz,1H),7.27(d,J=8
Hz,1H),7.88(d,J=3Hz,1H)
(2) 标题化合物(黄色晶体状)
m.p.:46-48℃
NMR(CDCl3)δ:0.93(t,J=7Hz,3H),1.16-1.83
(m,4H),3.08(dt,J=7&6Hz,2H),3.78
(br,1H),6.84(dd,J=8&3Hz,1H),7.08
(d,J=8Hz,1H),7.75(d,J=3Hz,1H)
对比实例34
3-甲氨基-5-三氟甲基吡啶
除了用3-氨基-5-三氟甲基吡啶代替5-氨基-2-氯吡啶,重复对比实例24的反应步骤,获得白色晶状的标题化合物。
m.p.:69-70℃
NMR(CDCl3):2.89(3H,d,J=5.1Hz),3.8-4.5(1H,
m,NH),6.9-7.1(1H,m),8.1-8.3(2H,m)
对比实例35
N-甲基-N-(6-甲基-3-吡啶甲基)胺
(1) 除了用6-甲基烟酸甲酯代替6-氯烟酸甲酯外,重复对比实例20(3)的反应步骤,得到6-甲基-3-吡啶甲醇,为黄色油状的粗产物。
NMR(CDCl3)δ:2.49(s,Me),4.66(s,CH2),
4.93(br,OH),7.14(d,J=8Hz,1H),7.63
(dd,J=8&2Hz,1H),8.36(d,J=2Hz,1H)
(2) 除了用6-甲基-3-吡啶甲醇粗产物代替(2,6-二甲基-4-吡啶)甲醇外,重复对比实例25(1)的反应步骤,得到(6-甲基-3-吡啶基)甲基氯,为油状粗产物。
NMR(CDCl3)δ:2.54(s,Me),4.55(s,CH2),7.16
(d,J=8Hz,1H),7.62(dd,J=8&2Hz,1H),
8.49(dd,J=2Hz,1H)
(3) 用冰冷却16.6g 40%MeNH2水溶液和52mlCH3CN的混合物,在连续搅拌下,滴加6.08g(0.043mol纯产物)粗的(6-甲基-3-吡啶基)甲基氯。滴加完毕,在室温下搅拌混合物1.5小时,然后立即蒸除溶剂。用CH2Cl2提取固体残余物,用MgSO4干燥CH2Cl2层。蒸除CH2Cl2,用70ml Et2O稀释残余物,滤去不溶性物质,最后浓缩滤液,得到4.60g标题化合物,为油状粗产物。
NMR(CDCl3)δ:2.43(s,MeN),2.53(s,pyridine-Me),
3.71(s,CH2),7.13(d,J=8Hz,1H),7.57
(dd,J=8&2Hz,1H),8.40(d,J=2Hz,1H)
对比实施例36
N-(6-氟-3-吡啶基甲基)-N-甲胺
(1)将7.2g(0.0648mol)2-氟-5-甲基吡啶,12.0g N-溴琥珀酰亚胺,0.5g过氧化苯甲酰和200mlCCl4的混合物回流2小时。冷却后,滤去沉淀,用水洗涤滤液,干燥。最终蒸除CCl4,得到12.68g(6-氟-3-吡啶基)甲基溴,为浅黄色油状粗产物。
NMR(CDCl3)δ:4.47(2H,s,CH2),6.96(1H,dd,
J=8.4&2.7Hz),7.86(1H,ddd,J=8.4,2.4&
8.4Hz),8.29(1H,d,J=2.4Hz)
(2) 在不断搅拌下,将3.0g(6-氟-3-吡啶基)甲基溴粗品滴加到2.5g 40%甲胺水溶液和30ml CH3CN的混合物中,在室温下放置混合物过夜,减压浓缩。用AcOEt提取残余物,用MgSO4干燥提取液,浓缩。得到1.35g标题化合物,为橙色油状粗产物。
NMR(CDCl3)δ:2.53(3H,s,Me),3.94(2H,s,
CH2)5.40(1H,s,NH)
对比实例37
N-(6-溴-3-吡啶甲基)-N-甲胺
(1) 除了用2-溴-5-甲基吡啶代替2-氨-5-甲基吡啶外,重复对比实例36(1)的反应步骤,得到(6-溴-3-吡啶基)甲基溴,为黄色油状粗产物。
NMR(CDCl3)δ:4.42(2H,s),7.48(1H,d,J=8.4
Hz),7.61(1H,dd,J=8.4&2.7Hz),8.40(1
H,d,J=2.7Hz)
(2) 搅拌下将8.0g(6-溴-3-吡啶基)甲基溴粗产物加入到12.3g 40%甲胺水溶液和40ml CH3CN的混合物中,在室温下再搅拌混合物30分钟。浓缩由此获得的反应混合物,用甲苯稀释残余物。用共沸蒸馏法蒸除水。然后用Et2O提取可溶性馏份。用MgSO4干燥Et2O层,浓缩,得到4.4g黄色油状的标题化合物。
NMR(CDCl3)δ:2.48(3H,s),2.73(1H,s),3.80
(2H,s),7.45(1H,d,J=8.4Hz),7.63(1H,
dd,J=8.4&2.7Hz),8.36(1H,d,J=2.7Hz)
对比实例38
N-(6-溴-3-吡啶甲基)-N-甲胺
除了用70%乙胺水溶液代替40%甲胺水溶液外,重复对比实例37(2)的反应步骤,得到标题化合物,为油状粗产物。
NMR(CDCl3)δ:1.11(3H,t,J=8.1Hz),2.16(1H,
br s),2.68(2H,q,J=8.1Hz),3.78(2H,
s),7.45(1H,d,J=8.4Hz),7.58(1H,dd,
J=8.4&2.7Hz),8.33(1H,d,J=2.7Hz)
对比实例39
N-(2-氯-5-噻唑基甲基)-N-甲胺
除了用2-氯-5-氯甲基噻唑粗品代替2,6-二氯-3-吡啶甲基氯,用CH2Cl2作提取剂外,重复对比实例11的反应步骤,得到标题化合物,为油状粗产物。
NMR(CDCl3)δ:2.45(s,MeN),3.89(s,CH2),7.37
(s,thiazole-H)
对比实例40
N-(2-氯-5-噻唑基甲基)-N-乙胺
除了用2-氯-5-氯甲基噻唑粗产物代替6-氯-3-吡啶甲基氯,用CH2Cl2作为提取剂外,重复对比实例17的反应步骤,得到标题化合物,为油状粗产物。
NMR(CDCl3)δ:1.10(t,J=7Hz,CH2CH3),2.69(q,
J=7Hz,CH2CH3),3.93(s,CH2N),7.36(s,
thiazole-H)
对比实例41
2-氯-5-噻唑基甲胺
(1) 除了用2-氯-5-氯甲基噻唑粗品代替2,6-二氯-3-吡啶甲基氯外,重复对比实例10(1)的反应步骤,得到N-(2-氯-5-噻唑基甲基)-苯邻二甲酰亚胺,为浅黄色晶体。
m.p.:108-109℃
NMR(CDCl3)δ:4.97(2H,s),7.60(1H,s),
7.6-8.1(m,4H)
(2) 除了用N-(2-氯-5-噻唑甲基)-苯邻二甲酰亚胺代替N-(6-氯-3-吡啶甲基)苯邻二甲酰亚胺外,重复对比实例3的反应步骤,得到黄色油状的标题化合物。
NMR(CDCl3)δ:1.68(2H,brs),4.04(2H,s),
7.38(1H,s)
对比实例42
2-甲氧基-5-甲氨基吡啶
除了用5-氨基-2-甲氧基吡啶代替5-氨基-2-氯吡啶外,重复对比实例24的反应步骤,得到黄色油状的标题化合物。
NMR(CDCl3)δ:2.81(3H,s),3.1-3.8(1H,m),
3.87(3H,s),6.64(1H,d,J=9.0Hz),6.98
(1H,dd,J=8.7&3.2Hz),7.59(1H,d,
J=2.4Hz)
对比实例43
6-溴-3-吡啶甲胺
(1) 除了用6-溴-3-吡啶甲基溴代替2,6-二氯-3-吡啶甲基氯外,重复对比实例10(1)的反应步骤,得到白色晶状的N-(6-溴-3-吡啶甲基)苯邻二甲酰亚胺。
m.p.:130-131℃
NMR(CDCl3)δ:4.83(s,2H),7.44(d,J=8Hz,1H),7.6-8.0
(m,5H),8.49(d,J=2Hz,1H)
(2) 除了用N-(6-溴-3-吡啶甲基)苯邻二甲酰亚胺代替N-(6-氯-3-吡啶甲基)苯邻二甲酰亚胺外,重复对比实例3的反应步骤,得到浅黄色晶状的标题化合物。m.p.:57-58℃NMR(CDCl3)δ:1.46(br s,2H),3.86(s,2H),7.42(d,
J=8Hz,1H),7.58(dd,J=8&2Hz,1H),8.32(d,J=2Hz,1H)
对比实例44
N-(6-氯-3-吡啶甲基)-N-(2,2,2-三氟乙基)胺
在15ml水中溶解12.55g 2,2,2-三氟乙胺盐酸盐,在冰-水冷却和搅拌下接着加入68ml CH3CN1再加入9.35gEt3N,最后加入3.00g(0.0185mol)6-氯-3-吡啶甲基氯。在室温下搅拌混合物1小时,在50℃下搅拌1小时,再在70℃下搅拌90分钟。蒸除CH3CH,往残余物中加入NaHCO3,然后用CH2Cl2(100ml×3)提取。用MgSO4干燥提取液,蒸除CH2Cl2。往残余物中加入100mlEt2O,滤去产生的不溶性物质。浓缩滤液,得到3.85g黄色油状的标题化合物。NMR(CDCl3)δ:1.81(br,NH),3.21(q,J=9Hz,CF3CH2),
3.92(s,pyridine-CH2),7.30(d,J=8Hz,1H),7.71(dd,
J=8&2Hz,1H),8.32(d,J=2Hz,1H)
实例1
1-甲硫基-1-(3-吡啶甲基)氨基-2-硝基乙烯(化合物(1-1)和1,1-双(3-吡啶甲基)-氨基-2-硝基乙烯(化合物1-2)
在100ml EtOH中加热溶解5.0g(0.03mol)1,1-双(甲硫基)-2-硝基乙烯,然后在回流下,以20至30分钟间隔时间分3次滴加3.2g(0.03mol)3-吡啶甲胺于30ml EtOH中的溶液。再回流混合物2小时,蒸除EtOH,用CHCl3-MeOH(5∶1)作洗脱液,对残余物进行硅胶柱色谱分离,分别得到4.0g和0.5g标题化合物(1-1和1-2),均为白色粉末。
Compound 1-1
m.p.:129-130℃
Compound 1-2
m.p.:141-143℃
NMR(DMSO-d6)δ:4.55(d),6.52(s),10.26(br s)
IR(Nujol):3150,1575,1390cm-1
实例2
1-甲硫基-1-(N-甲基-N-3-吡啶甲基)氨基-2-硝基乙烯(化合物2)
除了用N-甲基-N-吡啶甲胺代替3-吡啶甲胺外,重复实例1的步骤,得到标题化合物,为浅黄色粘油状物。
NMR(CDCl3)δ:2.50(s),3.06(s),4.81(s),6.81
(s)
实例3
1-甲氨基-1-(3-吡啶甲基)氨基-2-硝基乙烯(化合物3)
在50ml EtOH中加热溶解2.3g(0.01摩尔)1-甲硫基-1-(3-吡啶甲基-2-硝基乙烯,然后在回流下滴加1.2g(0.015mol)40%甲胺水溶液于10mlEtOH的溶液。再回流混合物2小时,然后浓缩。过滤收集晶体,用乙腈重结晶,得到1.6g白色棱晶状的标题化合物。
m.p.:159-160℃
NMR(DMSO-d6)δ:2.86(br s),4.49(d),6.46(s)
实例4
按与实例3相同的方法使1-甲硫基-1-(3-吡啶甲基)氨基-2-硝基乙烯与各种胺(或铵)反应,用重结晶法或硅胶柱色谱法提纯产物,得到下列化合物4-22。
(1) 1-乙氨基-1-(3-吡啶甲基)氨基-2-硝基乙烯(化合物4)
m.p.:161-162℃
(2) 1-异丙氨基-1-(3-吡啶甲基)氨基-2-硝基乙烯(化合物5)
m.p.:148-150℃
NMR(CDCl3)δ:4.46(d),6.52(s),7.28(br s),
10.1(br s)
(3) 1-正丁氨基-1-(3-吡啶甲基)氨基-2-硝基乙烯(化合物6)
m.p.:110-112℃
(4) 1-烯丙氨基-1-(3-吡啶甲基)氨基-2-硝基乙烯(化合物7)
m.p.:114-115℃
(5) 1-正戊氨基-1-(3-吡啶甲基-2-硝基乙烯(化合物8)
m.p.:97-98℃
(6) 1-苯胺基-1-(3-吡啶甲基)氨基-2-硝基乙烯(化合物9)
m.p.:217-218℃
(7) 1-氨基-1-(3-吡啶甲基)氨基-2-硝基乙烯(化合物10)
m.p.:177-178℃(decompn.)
(8) 1-(2-正丙硫基乙基)氨基-1-(3-吡啶甲基)氨基-2-硝基乙烯(化合物11)(白色棱晶状)
m.p.:93-94℃
NMR(CDCl3)δ:4.48(d),6.23(br s),6.63(s),
10.5(br s)
(9) 1-(2-二甲氨基乙基)氨基-1-(3-吡啶甲基)-氨基-2-硝基乙烯(化合物12)(白色棱晶状)
m.p.:110-111℃
NMR(CDCl3)δ:2.02(s),4.30(m),6.60(s),10.3
(br s)
(10) 1-(2-羟基乙基)氨基-1-(3-吡啶甲基)氨基-2-硝基乙烯(化合物13)
m.p.161-163℃
(11) 1-(2-甲氧基乙基)氨基-1-(3-吡啶甲基)氨基-2-硝基乙烯基(化合物14)
m.p.:108-109℃
(12) 1-(2,2-二甲氧基乙基)氨基-1-(3-吡啶甲基)-氨基-2-硝基乙烯(化合物15)(白色棱晶状)
m.p.:96-98℃
NMR(CDCl3)δ:6.55(s),6.85(br s),10.3(br s)
(13) 1-(3-吡啶甲基)氨基-1-(2,2,2-三氟乙基)-氨基-2-硝基乙烯(化合物16)
m.p.:164-165℃
NMR(DMSO-d6)δ:4.09(m),6.58(s)
(14) 1-(3-吡啶甲基)氨基-1-(三甲基硅甲基)-氨基-2-硝基乙烯(化合物17)
m.p.:156-157℃
NMR(CDCl3)δ:0.10(s),2.67(d),4.32(d),6.37
(s),7.12(br s),10.1(br s)
(15) 1-肼基-1-(3-吡啶甲基)氨基-2-硝基乙烯(化合物18)
m.p.:176-177℃(decompn.)
(16) 1-二甲氨基-1-(3-吡啶甲基)氨基-2-硝基乙烯(化合物19)
m.p.:68-70℃
NMR(CDCl3)δ:2.93(s),4.48(d),6.52(s),9.77
(br s)
(17) 1-(3-吡啶甲基)氨基-1-吡咯烷基-2-硝基乙烯(化合物20)(浅黄色粉末)
m.p.:103-105℃
NMR(CDCl3)δ:4.61(d),6.63(s),10.42(br s)
(18) 1-(4-甲基哌嗪代)-1-(3-吡啶甲基)氨基-2-硝基乙烯(化合物21)
NMR(CDCl3)δ:2.32(s),2.46(t),3.25(t),4.53
(d),6.50(s),9.73(br s)
(19) 1-(吗啉代基)-1-(3-吡啶甲基)氨基-2-硝基乙烯(化合物22)
m.p.:102-103℃
实例5
1-哌啶代基-1-(3-吡啶甲基)氨基-2-硝基乙烯(化合物23)
在20ml EtOH中溶解0.8g(0.004mol)1-甲硫基-1-哌啶代基-2-硝基乙烯,接着加入0.4g(0.004mol)3-吡啶基甲胺。回流混合物2小时。蒸除乙醇,用硅胶柱色谱法对残余物提纯,得到0.3g标题化合物,为浅黄色粉末。
m.p.:106-108℃
实例6
1-(2,2-二甲基-1-肼基)-1-(3-吡啶甲基)氨基-2-硝基乙烯(化合物24)
使用1-(2,2-二甲基-1-肼基)-1-甲硫基-2-硝基乙烯,重复实例5的步骤,得到白色棱晶状的标题化合物。
m.p.:158-159℃
NMR(CDCl3)δ:2.63(s),4.36(d),6.45(s),6.85
(br s),10.36(br s)
实例7
1-氨基-1-(N-甲基-N-3-吡啶甲基氨基-2-硝基乙烯(化合物25)
在50ml MeOH中溶解7.2g(0.03mol)1-甲硫基-1-(N-甲基-N-3-吡啶甲基)氨基-2-硝基乙烯,接着加入10ml 25%氨水。回流混合物2小时,然后蒸除溶剂。用CHCl3-MeOH(5∶1)作洗脱剂,用硅胶标色谱对残余物进行分离,得到1.5g白色棱晶状标题化合物。
m.p.:158-159℃
NMR(DMSO-d6)δ:3.06(s),4.66(s),6.63(s),
8.93(br s)
实例8
1-甲氨基-1-(N-甲基-N-3-吡啶甲基)氨基-2-硝基乙烯(化合物26)
(1)在30ml甲苯中溶解2.5g(0.02mol)N-甲基-N-3-吡啶甲胺,接着加入1.5g(0.02mol)异硫氰酸甲酯,在室温下搅拌混合物过夜。最后,蒸除溶剂,得到3.8gN-甲基-N′-甲基-N′-3-吡啶甲硫脲,为黄色粘油状物。用HeOH-CHCl3(1∶10)作洗脱液,采用硅胶柱色谱法提纯该油状产物,得到晶体。
m.p.:86-87℃NMR(CDCl3)δ:3.06(s),3.17(d),5.22(s),6.16
(br s),7.28(dd.J=8&5Hz,1H),7.74(m.1H),8.54(m.2H)
(2) 在30ml MeOH中溶解3.8g(0.02mol)步骤1获得的N-甲基-N ′-甲基-N′-3-吡啶甲硫脲,接着加入2.8g(0.02mol)甲基碘,回流混合物4小时。蒸除溶剂,用10ml饱和碳酸氢钠水溶液稀释,用ACOEt提取(50ml×3)。用MgSO4干燥提取液,蒸除溶剂,得到1.0gS-甲基-N-甲基-N′-甲基-N′-(3-吡啶甲基)异硫脲,为黄色油状的粗产物。NMR(CDCl3)δ:2.33(s),2.83(s),3.26(s),4.56
(s),7.25(dd,J=8&5Hz,1H),7.60(m,1H),8.55(m,2H)
(3) 将5ml硝基甲烷加入1.0g(0.048ol)步骤(2)获得的S-甲基-N-甲基-N′-(3-吡啶甲基)异硫脲,在90℃搅拌混合物15小时。蒸除硝基甲烷,用CHCl3-MeOH(5∶1)作洗脱液,用硅胶柱色谱法对残余物进行提纯,得到0.3g黄色粘油状的标题化合物。将该产物冷却至5℃,用乙酸乙酶洗涤得到的结晶体,干燥。该产物的熔点为86-87℃。NMR(CDCl3)δ:2.83(s),3.07(d),4.43(s),6.53
(s),7.35(dd,J=8&5Hz,1H),7.61(m,1H),8.60(m,1H),
9.73(br s)
实例9
1-(6-氯-3-吡啶甲基)氨基-1-甲硫基-2-硝基乙烯(化合物27)
往100ml EtOH中加2.4g(1.5×10-2mol)1,1-双(甲硫基)-2-硝基乙烯和1.4g(9.8×10-3mol)6-氯-3-吡啶甲胺,回流混合物2小时。蒸除EtOH,用CH2Cl2作洗脱液,对残余物进行硅胶柱色谱分离,得到1.2g浅黄色固体状的标题化合物NMR(DMSO-d6)δ:2.48(s,3H),4.71(d,J=6.7Hz,
2H),6.66(brs,1H),7.50(d,J=8.8Hz,1
H),7.84(dd,J=8.8&2.8Hz,1H),8.41(d,
J=2.8Hz,1H),10.0-11.0(br,1H)
实例10
1-(6-氯-3-吡啶甲基)氨基-1-甲氨基-2-硝基乙烯(化合物28)
在100ml EtOH中溶解1.2g(4.6×10-3mol)1-(6-氯-3-吡啶甲基)氨基-1-甲硫基-2-硝基乙烯,回流下在1小时内滴加0.84g 40%含水甲胺于30ml EtOH中的溶液,冷却后,减压浓缩反应混合物至约50ml,过滤收集产生的结晶体,干燥,得到0.6g浅黄色针晶状的标题化合物。
m.p.:181-183℃
NMR(DMSO-d6)δ:2.6-3.1(m,3H),4.47(d,J=6.3
Hz,2H),6.45(s,1H),7.48(d,J=8.8Hz,1
H),7.81(dd,J=8.8&2.7Hz),8.39(d,J=2.7
Hz,1H),9.5-10.4(br,1H)
实例11
1-〔N-(6-氯-3-吡啶甲基)-N-甲基〕氨基〕-1-甲氨基-2-硝基乙烯(化合物29)
(1) 使用N-(6-氯-3-吡啶甲基)-N-甲胺,重复实例8(1)的步骤,得到晶体状的N-(6-氯-3-吡啶甲基)-N-甲基-N′-甲基硫脲。
m.p.:109-110℃
NMR(CDCl3)δ:3.06(s,3H),3.16(d,J=4.8Hz,3
H),5.22(s,2H),5.8-6.3(br,1H),7.30(d,
J=8.6Hz,1H),7.76(dd,J=8.6&2.7Hz,1H),
8.30(d,J=2.7Hz,1H)
(2) 使用步骤(1)得到的N-(6-氯-3-吡啶甲基)-N-甲基-N′-甲硫脲重复实例8(2)的步骤,得到油状的S-甲基-N-(6-氯-3-吡啶甲基)-N-甲基-N′-甲基异硫脲。NMR(CDCl3)δ:2.36(s,3H),2.94(s,3H),3.27
(s,3H),4.63(s,2H),7.30(d,J=8.6Hz,1
H),7.62(dd,J=8.6&2.7Hz,1H),8.31(d,
J=2.7Hz,1H)
(3) 使用步骤(2)得到的S-甲基-N-(6-氯-3-吡啶甲基)-N-甲基-N′-甲基异硫脲,重复实例8(3)的步骤,得到晶体状的标题化合物。m.p.:103-104℃NMR(CDCl3)δ:2.80(s,3H),3.07(d,J=4.8Hz,3
H),4.38(s,2H),6.51(s,1H),7.37(d,
J=8.6Hz,1H),7.58(dd,J=8.6&2.7Hz,
1H),8.31(d,J=2.7Hz,1H),9.5-9.9(br,1
H)
实例12
1-甲氧基-1-(3-吡啶甲基)氨基-2-硝基乙烯(化合物30)
在加热下,将16.5g(0.1mol)1,1-双(甲硫基)-2-硝基乙烯溶于1升MeOH中,在回流条件下,以1小时的间隔时间分四次滴加11.0g(0.1mol)3-吡啶甲胺于200ml MeOH中的溶液。再回流混合物3小时,蒸除MeOH。用硅胶柱色谱法提纯残余物,得到白色棱晶状的标题化合物。在该过程中,还生产了实例1所述的化合物1-1,为副产品。m.p.:129-130℃NMR(CDCl3)δ:3.86(s,OMe),4.60(d,CH2N),6.68
(s,=CHNO2),10.15(br,NH)
实例13
1-〔N-乙基-N-(3-吡啶甲基)〕氨基-1-甲氨基-2-硝基乙烯(化合物31)
(1) 在50ml乙醚中溶解2.4g N-乙基-N-(3-吡啶甲基)胺,接着加入1.3g异硫氰酸甲酯。在室温(25℃)搅拌混合物1小时。过滤收集产生的沉淀,用少量乙醚洗涤,干燥,得到3.7g N-甲基-N′-乙基-N′-(3-吡啶甲基)硫脲,为白色棱晶体。
m.p.:122-123℃
NMR(CDCl3)δ:1.16(t,CH2CH3),3.16(d,MeN),
(br s,NH)
(2) 在30ml干燥四氢呋喃中溶解3.1g步骤(1)获得的N-甲基-N′-乙基-N′-(3-吡啶甲基)硫脲,接着加入0.6g60%氢化钠。在室温下(25℃)搅拌混合物1小时。然后滴加2.1g甲基碘,再搅拌反应混合物3小时。浓缩反应混合物,用50ml饱和NaCl溶液稀释残余物,用乙酸乙酯提取三次,每次用量为50ml。汇集提取液,用MgSO4干燥,然后蒸除溶剂,得到3.1g S-甲基-N-甲基-N′-乙基-N′-(3-吡啶甲基)异硫脲,为黄色油状的粗产品。NMR(CDCl3)δ:1.06(t,CH2CH3),2.30(s,MeS),
3.23(s,MeN),3.35(q,CH2CH3),4.53(s,
(3) 将10ml硝基甲烷加入2.2g步骤(2)获得的S-甲基-N-甲基-N′-乙基-N′-(3-吡啶甲基)异硫脲中,回流混合物16小时。浓缩反应混合物,用甲醇-氯仿(1∶5)作洗脱液,对残余物进行硅胶柱色谱分离,得到1.4g黄色粘油状的标题化合物。
NMR(CDCl3)δ:1.20(t,CH2CH3),3.08(d,MeN),
3.18(q,CH2CH3),4.46(s,
),6.53
(s,=CHNO2),9.86(br s,NH)
实例14
1-〔N-(2-二甲氧乙基)-N-(3-吡啶甲基)〕氨基-1-甲氨基-2-硝基乙烯(化合物32)
用N-(2-二甲氧基乙基)-N-(3-吡啶甲基)胺代替N-乙基-N-(3-吡啶甲基)胺,重复实例13的(1)、(2)和(3),各步分别获得下列化合物。
(1) N-甲基-N′-(2-二甲氧乙基)-N ′-(3-吡啶甲基)-硫脲(浅黄色粘油状)NMR(CDCl3)δ:3.13(d,MeN),3.37(s,MeO),3.53
(2) S-甲基-1-甲基-N′-(2-二甲氧乙基)-N′-(3-吡啶甲基)异硫脲(黄色油状)NMR(CDCl3)δ:2.26(s,MeS),3.24
(s,MeN),3.35(s,MeO),3.46(d,CH2CH),
(3) 标题化合物(黄色粘油状)
NMR(CDCl3)δ:1.20(t,CH2CH3),3.08(d,MeN),
3.18(q,CH2CH3),4.46(s,
),6.53
(s,=CHNO2),9.86(br s,NH)
实例15
1-乙氨基-1-〔N-甲基-N-(3-吡啶甲基)〕氨基-2-硝基乙烯(化合物33)
除了用N-甲基-N-(3-吡啶甲基)胺和异硫氰酸乙酯分别代替N-乙基-N-(3-吡啶甲基)胺和异硫氰酸甲酯之外,重复实例13的步骤(1)、(2)和(3),各步分别得到下列化合物。
(1) N-乙基-N′-甲基-N′-(3-吡啶甲基)硫脲
m.p.:110-111℃
NMR(CDCl3)δ:1.23(3H,t,J=7.5Hz),3.05(3H,
s),3.5-3.9(2H,m),5.20(2H,s),5.8-6.2
(1H,br),7.26(1H,dd,J=8.4&5.4Hz),
7.72(1H,dt,J=8.4&1.5Hz),8.4-8.6(2H,
m)
IR(Nujol):3180cm-1
(2) S-甲基-N-乙基-N′-甲基-N′-(3-吡啶甲基)异硫脲(黄色油状)
NMR(CDCl3)δ:1.16(3H,t,J=7.5Hz),2.36(3H,
s),2.93(3H,s),3.56(2H,q,J=7.5Hz),
4.64(2H,s),7.26(1H,dd,J=8.4&5.4
Hz),7.63(1H,dt,J=8.4&1.5Hz),8.4-8.6
(2H,m)
(3) 标题化合物(粘油状)
NMR(CDCl3)δ:1.34(3H,t,J=7.5Hz),2.82(3H,
s),3.1-3.6(2H,m),4.43(2H,s),6.52(1
H,s),7.32(1H,dd,J=8.4&5.4Hz),7.58
(1H,dt,J=8.4&1.5Hz),8.4-8.7(2H,m),
9.3-9.8(1H,br)
IR(neat):3220cm-1
实例16
1-正丁氨基-1-〔N-甲基-N-(3-吡啶甲基)〕-氨基-2-硝基乙烯(化合物34)
用N-甲基-N-(3-吡啶甲基)胺和异硫氰酸正丁酯分别代替N-乙基-N-(3-吡啶甲基)胺和异硫氰酸甲酯之外,各步分别得到下列化合物。
(1) N-正丁基-N′-甲基-N′-(3-吡啶甲基)硫脲(浅黄色油状)
NMR(CDCl3)δ:0.93(3H,t,J=7.8Hz),1.2-1.9(4
H,m),3.06(3H,s),3.4-3.9(2H,m),5.21
(2H,s),5.5-6.1(1H,br),7.28(1H,dd,
J=8.4&5.4Hz),7.74(1H,dt,J=8.4&1.5
Hz),8.4-8.7(2H,m)
IR(neat):3270cm-1
(2) S-甲基-N-正丁基-N′-甲基-N′-(3-吡啶甲基)-异硫脲(黄色油状)NMR(CDCl3)δ:0.90(3H,t,J=7.8Hz),1.1-1.9(4
H,m),2.30(3H,s),2.85(3H,s),3.49(2
H,t,J=6.8Hz),4.56(2H,s),7.23(1H,
dd,J=8.4&5.4Hz),7.60(1H,dt,J=8.4&
1.5Hz),8.4-8.6(2H,m)
(3) 标题化合物(粘油状)
NMR(CDCl3)δ:0.94(3H,t,J=7.8Hz),1.2-1.9(4
H,m),2.80(3H,s),3.34(2H,m),4.42(2
H,s),6.54(1H,s),7.34(1H,dd,J=8.4&
5.4Hz),7.58(1H,dt,J=8.4&1.5Hz),
8.4-8.7(2H,m),9.4-9.9(1H,br)
IR(neat):3210cm-1
实例17
1-甲氨基-1-〔N-(2-甲氧乙基)-N-(3-吡啶甲基)〕氨基-2-硝基乙烯(化合物35)
除了用N-(2-甲氧乙基)-N-(3-吡啶甲基)胺代替N-乙基-N-(3-吡啶甲基)胺之外,重复实例13的步骤(1)、(2)和(3),各步分别获得下列化合物。
(1) N-甲基-N′-(2-甲氧基乙基)-N′-(3-吡啶甲基)-硫脲(无色油状)
NMR(CDCl3)δ:3.33(s,MeO),3.50(m,CH2CH2),5.20(s,
7.26(br s,NH)
(2) S-甲基-N-甲基-N′-(2-甲氧乙基)-N′-(3-吡啶甲基)异硫脲(油状)
NMR(CDCl3)δ:2.27(s,MeS),3.23(s,MeN),3.30
(3) 标题化合物(黄色粘油状)
NMR(CDCl3)δ:3.06(d,MeN),3.35(s,MeO),3.43
=CHNO2),9.10(br s,NH)
实例18
1-烯丙基氨基-1-〔N-甲基-N-(3-吡啶甲基〕氨基-2-硝基乙烯(化合物36)
除了用N-甲基-N-(3-吡啶甲基)胺和异硫氰酸烯丙酯分别代替N-甲基-N-(3-吡啶甲基)胺和异硫氰酸甲酯外,重复实例13的步骤(1)、(2)和(3),各步分别获得下列化合物。
(1) N-烯丙基-N′-甲基-N′-(3-吡啶甲基)硫脲
m.p.:8 2-84℃
NMR(CDCl3)δ:3.07(3H,s),4.34(2H,m),
5.0-5.4(2H,m),5.21(2H,s),5.6-6.3(2H,
m),7.27(1H,dd,J=8.4&5.4Hz),7.73(1
H,dt,J=8.4&1.5Hz),8.4-8.6(2H,m)
IR(Nujol):3280cm-1
(2) S-甲基-N-烯丙基-N′-甲基-N ′-(3-吡啶甲基)异硫脲(黄色油状)
NMR(CDCl3)δ:2.30(3H,s),2.90(3H,s),
4.1-4.3(2H,m),4.62(2H,s),4.9-5.3(2
H,m),5.7-6.3(1H,m),7.26(1H,dd,J=8.4
&5.4Hz),7.62(1H,dt,J=8.4&1.5Hz),
8.4-8.7(2H,m)
(3) 标题化合物(油状)
NMR(CDCl3)δ:2.81(3H,s),3.9-4.2(2H,m),
4.43(2H,s),5.1-5.6(2H,m),5.7-6.2(1
H,m),6.55(1H,s),7.35(1H,dd,J=8.4&
5.1Hz),7.60(1H,dt,J=8.4&1.5Hz),
8.4-8.7(2H,m),9.4-9.9(1H,br)
实例19
1-异丙氨基-1-〔N-甲基-N-(3-吡啶甲基)〕-氨基-2-硝基乙烯(化合物37)
除了用N-甲基-N-(3-吡啶甲基)胺和异硫氰酸异丙酯分别代替N-乙基-N-(3-吡啶甲基)胺和异硫氰酸甲酯外,重复实例13的步骤(1)、(2)和(3),各步分别得到下列化合物。
(1) N-异丙基-N′-甲基-N′-(3-吡啶基甲基)硫脲
m.p.:135-136℃
NMR(CDCl3)δ:1.26(6H,d,J=6.3Hz),3.03(3H,
s),4.4-4.9(1H,m),5.21(2H,s),5.0-5.5
(1H,br),7.27(1H,dd,J=8.4&5.1Hz),
7.74(1H,dt,J=8.4&1.5Hz),8.4-8.7(2H,
m)
IR(Nujol):3200cm-1
(2) S-甲基-N-异丙基-N′-甲基-N′-(3-吡啶甲基)-异硫脲(油状)
NMR(CDCl3)δ:1.07(6H,d,J=6.3Hz),2.30(3H,
s),2.84(3H,s),3.6-4.1(1H,m),4.50(2
H,s),7.23(1H,dd,J=8.4&5.1Hz),7.61
(1H,dt,J=8.4&1.5Hz),8.4-8.6(2H,m)
(3)标题化合物
m.p.:119-121℃
NMR(CDCl3)δ:1.31(6H,d,J=6.6Hz),2.83(3H,
s),3.5-4.0(1H,m),4.44(2H,s),6.52(1
H,s),7.33(1H,dd,J=8.4&5.1Hz),7.57
(1H,dt,J=8.4&1.5Hz),8.4-8.7(2H,m),
8.9-9.4(1H,br d,J=9.6Hz)
IR(Nujol):3080cm-1
实例20
1-苯甲氨基-1-〔N-甲基-N-(3-吡啶甲基)〕氨基-2-硝基乙烯(化合物38)
除了用N-甲基-N-(3-吡啶甲基)胺和异硫氰酸苄酯分别代替N-乙基-N-(3-吡啶甲基)胺和异硫氰酸甲酯外,重复实例13的步骤(1)、(2)和(3),各步分别获得下列化合物。
(1) N-苄基-N′-甲基-N ′-(3-吡啶甲基)硫脲(浅黄色油状)
NMR(CDCl3)δ:3.03(3H,s),4.90(2H,d,J=5.1
Hz),5.21(2H,s),6.10(1H,br),7.1-7.5
(6H,m),7.74(1H,dt,J=8.4&1.5Hz),
8.4-8.6(2H,m)
IR(neat):3250cm-1
(2) S-甲基-N-苄基-N′-甲基-N′-(3-吡啶甲基)异硫脲(油状)
NMR(CDCl3)δ:2.29(3H,s),2.92(3H,s),4.62
(2H,s),4.77(2H,s),7.1-7.5(6H,m),
7.59(1H,dt,J=8.4&1.5Hz),8.4-8.7(2H,
m)
(3) 标题化合物
NMR(CDCl3)δ:2.78(3H,s),4.36(2H,s),4.53
(2H,d,J=6.0Hz),6.56(1H,s),7.1-7.5(7
H,m),8.3=8.5(1H,m),8.57(1H,dd,J=5.2
&1.5Hz),9.7-10.2(1H,br)
实例21
1-甲氨基-1-〔N-甲基-N-(3-喹啉甲基)〕-氨基-2-硝基乙烯(化合物39)
除了用N-甲基-N-(3喹啉甲基)胺代替N-乙基-N-(3-吡啶甲基)胺外,重复实例1 3的步骤(1)、(2)和(3),各步分别获得下列化合物。
(1) N-甲基-N′-甲基-N′-(3-喹啉基甲基)硫脲m.p.:138-139℃
NMR(CDCl3)δ:3.09(s,
MeNCH2),3.18(d,J=5
Hz,
MeNH),5.35(s,NCH2),6.00(br,NH),
7.4-7.9(m,3H,quinoline-H3),8.0-8.2(m,
2H,quinoline-H2),8.33(d,J=2Hz,1H,
quinoline-H1)
IR(Nujol):3200,1545,1530,1495,1445,1375,
1335,1240,1050cm-1
(2) S-甲基-N-甲基-N′-甲基-N′-(3-喹啉甲基)异硫脲(油状)
NMR(CDCl3)δ:2.33(s,MeS),2.89(s,
MeNCH2),
3.28(s,MeN=),4.73(s,NCH2),7.2-7.9(m,3
H,quinoline-H3),7.9-8.2(m,2H,quinoline-
H2),8.85(d,J=2Hz,1H,quinoline-H1)
IR(neat):1600,1490,1370,1340,1060,1020,755
cm-1
(3) 标题化合物
m.p.:145-157℃
NMR(CDCl3)δ:2.85(s,
MeNCH2),3.08(d,J=6Hz,
MeNH),4.58(s,NCH2),6.59(s,=CHNO2),
7.5-7.95(m,3H,quinoline-H3),7.95-8.25
(m,2H,quinoline-H2),8.81(d,J=2Hz,1H,
quinoline-H1),9.80(br,NH)
IR(Nujol):1590,1545,1405,1310,1280,1230
cm-1
实例22
1-甲氨基-1-〔N-甲基-N-〔1-(3-吡啶基)乙基〕〕-氨基-2-硝基乙烯(化合物40)
除了用N-甲基-N-〔1-(3-吡啶基)乙基〕胺代替N-乙基-N-(3-吡啶甲基)胺外,重复实例13的步骤(1)、(2)和(3),各步分别获得下列化合物。
(1) N-甲基-N′-甲基-N′-〔1-(3-吡啶基)乙基〕硫脲(浅黄色粘油状)
NMR CDCl3)δ:1.56(d,J=7Hz,
MeCH),2.76(s,
MeNCH2),3.18(d,J=5Hz,
MeNH),6.30(br,
NH),7.04(q,J=7Hz,MeC
H),7.28(dd,J=7
and 5Hz,1H,pyridine-H1),7.70(m,1H
pyridine-H1),8.5(m,2H,pyridine-H2)
IR(neat):3270,1550(sh.),1530,1480,1420,
1375,1340,1295cm-1
(2) S-甲基-N-甲基-N′-甲基-N ′-〔1-(3-吡吡基)乙基〕硫脲(油状)
NMR(CDCL3)δ:1.54(d,J=7Hz,
MeCH),2.31(s,
MeS),2.63(s,
MeNCH2),3.27(s,MeN=),5.66
(q,J=7Hz,MeC
H),7.24(dd,J=5&8Hz,1H,
pyridine-H1),7.62(m,1H,pyridine-H1),
8.48(dd,J=5&2Hz,1H,pyridine-H1),
8.59(d,J=2Hz,1H,pyridine-H1)
IR(neat):2910,1600,1415,1390,1370,1235,
1070,1010,710cm-1
(3) 标题化合物(粘油状)
NMR(CDCl3)δ:1.70(d,J=7Hz,
MeCH),2.63(S,
MeN),3.02(d,J=5Hz,
MeNH),4.93(q,J=7
Hz,MeC
H),6.50(s,=CHNO2),7.33(dd,J=5
&8Hz,1H,pyridine-H1),7.60(m,1H,
pyridine-H1),8.6(m,2H,pyridine-H2),9.77
(br,NH)
IR(neat):1585,1420,1400,1340,1240,1020,750
cm-1
实例23
1-〔2,2-二甲基-1-(3-吡啶甲基)〕肼基-1-甲氨基-2-硝基乙烯(化合物41)
(1)在30ml甲苯中溶解2.5g 1,1-二甲基-2-(3-吡啶甲基)肼,接着加入1.2g异硫氰酸甲酯,回流混合物1小时。浓缩反应混合物,过滤收集得到的结晶体,用乙醚洗涤,干燥,得到白色棱晶状的2.6g 1,1-二甲基-4-甲基-2-(3-吡啶甲基)氨基硫脲。
m.p.:101-102℃
NMR(CDCl3)δ:2.45(s,Me2N),3.17(d,J=5Hz,
MeNH),5.28(s,CH2N),7.20(dd,J=8and5
Hz,1H,pyridine-H1),7.89(m,1H,
pyridine-H1),8.10(br,NH),8.50(dd,J=5
&2Hz,1H,pyridine-H1),8.62(d,J=2Hz,1
H,pyridine-H1)
IR(Nujol):3200,1514,1420,1370,1320,975cm-1
(2) 用石油醚洗涤0.52g 60%的氢化钠,然后将其悬浮在20ml干燥四氢呋喃中,接着加入步骤(1)制得的2.9g 1,1-二甲基-4-甲基-2-(3-吡啶甲基)氨基硫脲,在50℃搅拌混合物2小时。冷却和加入1.8g甲基碘后,在室温(25℃)搅拌混合物2小时,然后浓缩。往残余物中加入50ml乙酸乙酸,滤去不溶性物质。用MgSO4干燥滤液,浓缩,得到2.2g S-甲基-1,1-二甲基-4-甲基-2-(吡啶甲基)氨基异硫脲,为油状物。NMR(CDCl3)δ:2.41(s,MeS),2.60(s,Me2N),3.06
(s,MeN),4.30(s,CH2N),7.18(dd,J=5&8
Hz,1H,pyridine-H1),7.60(m,1H,
pyridine-H1),8.10(dd,J=5&2Hz,1H,
pyridine-H1),8.21(d,J=2Hz,pyridine-H1)IR(neat):1600,1420,1240,1020,710cm-1
(3) 将10ml硝基甲烷加入到步骤(2)制得的2.2g S-甲基-1,1-二甲基-4-甲基-2-(吡啶甲基)氨基异硫脲中,回流混合物7小时。浓缩反应混合物,用氯仿-甲醇(5∶1)作洗脱液,对残余物进行硅胶柱色谱分离,得到1.0g黄色棱晶状的标题化合物。
m.p.:109-110℃
NMR(CDCl3)δ:2.62(s,Me2N),3.16(d,J=6Hz,
MeN),4.43(s,CH2N),6.43(s,=CHNO2),7.27
(dd,J=8&5Hz,1H,pyridine-H1),7.60(m,
1H,pyridine-H1),8.5-8.65(m,2H,
pyridine-H2),10.1(br,NH)
IR(Nujol):1585,1405,1340,1315,1235cm-1
实例24
1-甲氨基-1-〔N-(正丙基)-N-(3-吡啶甲基〕氨基-2-硝基乙烯(化合物42)
除了用N-正丙基-N-(3-吡啶甲基)胺代替N-乙基-N-(3-吡啶甲基)胺外,重复实例13的步骤(1)、(2)和(3),各步分别得到下列化合物。
(1) N-甲基-N′-(正丙基)-N′-(3-吡啶甲基)硫脲(浅黄色粘油状)NMR(CDCl3)δ:0.90(t),1.4-1.9(m),3.16(d.
MeN),3.42(t),5.15(s),5.87(br s,NH),
7.26(dd),7.74(dt),8.46-8.60(m,2H)IR(neat):3270,1525,1340,1235,1020,710cm-1
(2) S-甲基-N-甲基-N′-(正丙基)-N′-(3-吡啶甲基)异硫脲(黄色油状)NMR(CDCl3)δ:0.84(t),1.33-1.80(m),2.29(s,
MeS),3.23(s,MeN),3.26(t),4.55(s),7.22
(dd),7.56(dt),8.43-8.60(m,2H)IR(neat):1600,1425,1210,715cm-1
(3) 标题化合物
NMR(CDCl3)δ:0.86(t),1.40-1.90(m,2H),
2.95-3.30(m,2H),3,05(d,MeN),4.53(s,2
H),6.55(s,=CHNO2),7.34(dd),7.66(dt),
8.43-8.66(m,2H),9.56(br d,NH)
实例25
1-〔N-(正丁基-N-(3-吡啶基)〕氨基--1-甲氨基-2-硝基乙烯(化合物43)
除了用N-(正丁基)-N-(3-吡啶甲基)胺代替N-乙基-N-(3-吡啶甲基)胺外,重复实例13的步骤(1)、(2)和(3),各步分别获得下列化合物。
(1) N-(正丁基)-N-(3-吡啶甲基-N′-甲基硫脲(浅黄色粘油状)
NMR(CDCl3)δ:0.90(t),1.1-1.8(m,4H),3.15
(d,MeN),3.30-3.56(m),5.13(s),5.82(br
s,NH),7.25(dd),7.73(dt),8.43-8.60(m,2
H)
IR(neat):3280,1525,1345,1230,1030,710cm-1
(2) S-甲基-N-甲基-N′-(正丁基)-N ′-(3-吡啶甲基)异硫脲(黄色油状)
NMR(CDCl3)δ:0.86(t),1.03-1.70(m,4H),2.28
(s,MeS),3.23(s,MeN),3.30(t),4.54(s),
7.22(dd),7.56(dt),8.40-8.56(m,2H)
IR(neat):1605,1425,1190,1020,715cm-1
(3) 标题化合物(粘油状)
NMR(CDCl3)δ:0.90(t),1.06-1.80(m,4H),
2.96-3.23(m,2H),3.07(d,MeN),4.40(s),6.56
(s,=CHNO2),7.33(dd),7.60(dt),8.46-8.66(m,2
H),9.82(br d,NH)
实例26
1-〔N-苄基-N-(3-吡啶甲基)〕氨基-1-甲氨基-2-硝基乙烯(化合物44)
除了用N-苄基-N-(3-吡啶甲基)胺代替N-乙基-N-(3-吡啶甲基)胺外,重复实例13的步骤(1)、(2)和(3),各步分别获得下列化合物。
(1) N-苄基-N-(3-吡啶甲基)-N′-甲基硫脲(白色棱晶状)
m.p.:141-143℃(white prisms)
(2) S-甲基-N-甲基-N′-苄基-N′-(3-吡啶甲基)异硫脲(黄色油状)
NMR(CDCl3)δ:2.32(s,MeS),3.26(s,MeN),4.45
(s),4.52(s),7.06-7.36(m,6H),7.50(dt),
8.36-8.53(m,2H)
IR(neat):1600,1425,1180,1020,700cm-1
(3) 标题化合物
m.p.:118-119℃(pale yellow scales)
NMR(CDCl3)δ:3.16(d,J=5Hz,MeN),4.22(s,CH2
and CH2),6.53(s,=CHNO2),7.06-7.60(m,7
H),8.40(br s),8.60(br d),9.76(br d,J=5
Hz,NH)
IR(Nujol):1590,1520,1450,1360,1280cm-1
实例27
1-氨基-1-〔N-(6-氯-3-吡啶甲基)-N-甲基〕-氨基-2-硝基乙烯(化合物45)
(1)在200ml EtOH中加热溶解5.0g 1,1-双(甲硫基)-2-硝基乙烯,回流条件下,以30分钟的时间间隔分三批滴加4.7g N-(6-氯-3-吡啶甲基)-N-甲胺于50mlEtOH形成的溶液。滴加完毕,再回流混合物3小时,然后蒸除EtOH。用CHCl3-MeOH(20∶1)作洗脱液,对残余物进行硅胶柱色谱分离,得到3.5g黄色粘油状的1-〔N-(6-氯-3-吡啶甲基)-N-甲基〕氨基-1-甲硫基-2-硝基乙烯。 NMR(CDCl3)δ:2.46(s,MeS),3.03(s,MeN),4.76
(s,CH2),6.76(s,=CHNO2),7.35(d),7.60
(dd),8.30(d)
IR(neat):1750,1540,1260,1100,1020cm-1
(2) 在20ml MeOH中溶解1.1g步骤(1)制得的1-〔N-(6-氯-3-吡啶甲基)-N-甲基〕氨基-1-甲硫基-2-硝基乙烯,接着加入1.0ml 25%氨水,在室温下搅拌混合物1小时。过滤收集产生的晶体,用少量MeOH洗涤,干燥,得到0.85g淡黄色鳞片状的标题化合物。
m.p.:206-207℃
NMR(DMSO-d6)δ:3.03(s,MeN),4.65(s,CH2),
6.60(s,=CHNO2),7.45(d),7.68(dd),8.31
(d),8.92(br s,NH2)
IR(Nujol):3280,3140,1625,1580,1420,1225
cm-1
实例28
1-(6-氯-3-吡啶甲基)氨基-1-二甲氨基-2-硝基乙烯(化合物46)
(1) 在50ml EtOH中溶解3.3g 1,1-双(甲硫基)-2-硝基乙烯,并在回流下以30分钟的间隔时间分2次滴加20ml 40%二甲胺水溶液。滴加完毕,再回流混合物30分钟,然后蒸除EtOH,用CHCl3-MeOH(20∶1)作洗脱液,对残余物进行硅胶柱色谱分离,得到黄色油状的1.0g 1-二甲氨基-1-甲硫基-2-硝基乙烯。NMR(CDCl3)δ:2.46(s,3H),3.21(s,6H),6.69
(s,1H)
(2) 将步骤1制得的1-二甲氨基-1-甲硫基-2-硝基乙烯(1.0g)和1.0g 6-氯-3-吡啶甲胺在30ml EtOH中回流2小时,然后蒸除EtOH,用CHCl3-MeOH(10∶1)作洗脱液,对残余物进行硅胶柱色谱分离。用EtOH对获得的晶体进行重结晶,得到0.82g浅黄色结晶状标题化合物。
m.p.:124-125℃
NMR(CDCl3)δ:2.99(s,6H),4.53(d,J=5.4Hz,2
H),6.46(s,1H),7.34(d,J=8.4Hz,1H),
7.72(dd,J=8.4&2.4Hz,1H),8.35(d,
J=2.4Hz,1H),9.2-9.8(br,1H)
IR(Nujol):1585,1440,1380,1260cm-1
实例29
将1.2g(0.007mol)(2,6-二氯-3-吡啶甲基)胺和1g(0.007mol)1-甲氨基-1-甲硫基-2-硝基乙烷的混合物在50ml EtOH中回流6小时。冷却后,浓缩反应混合物,过滤收集得到的晶体,用CH2Cl2洗涤,再用少量EtOH洗涤,干燥,得到0.53g白色粉末状的标题化合物。
m.p.:211-213℃(decompn.)
NMR(DMSO-d6)δ:2.83(br,3H),4.50(br d,2
H),6.43(s,1H),7.58(d,J=8.5Hz),7.80
(d,J=8.5Hz),7.0-7.93(br,NH),9.50-10.50
(br,NH)
IR(Nujol):3170,1630,1580,1375,1210cm-1
实例30
1-氨基-1-〔N-(2,6-二氯-3-吡啶甲基)-N-甲基〕氨基-2-硝基乙烯(化合物48)
在30ml MeOH中溶解0.9g(0.003mol)1-〔N-(2,6-二氯-3-吡啶甲基)-N-甲基〕-氨基-1-甲硫基-2-硝基乙烯,接着在50℃加入0.6ml(0.0045mol)25%的氨水,在相同温度下搅拌混合物1小时。冷却后,浓缩反应混合物,过滤收集产生的晶体,用少量EtOH洗涤,干燥,得到0.7g白色粉末状的标题化合物。m.p.:214-215℃(decompn.)NMR(DMSO-d6)δ:3.05(s,3H),4.63(s,2H),
6.56(s,1H),7.46-7.70(m,2H),8.90(br
s,NH2)IR(Nujol):3350,1610,1565,1410,1290,1220
cm-1
实例31
1-氨基-1-〔N-(6-氯-3-吡啶甲基)-N-异丙基〕氨基-2-硝基乙烯(化合物49)
在8ml EtOH中溶解0.59g(0.00196mol)1-〔N-(6-氯-3-吡啶甲基)-N-异丙基〕氨基-1-甲硫基-2-硝基乙烯,接着加入0.20ml 25%的氨水。在室温下搅拌混合物2小时40分钟。浓缩反应混合物,用MeOH-CHCl3(1∶7)作洗脱液,对残余物进行硅胶(100g)柱色谱分离,得到油状的标题化合物。用Et2O研磨油状物,过滤收集产生的粉末,用Et2O洗涤,干燥,得到0.19g标题化合物。
NMR(DMSO-d6)δ:1.13(d,J=7Hz,
Me 2CH),4.30
(septet,J=7Hz,Me2C
H),4.62(s,CH2),6.50
(s,=CHNO2),7.49(d,J=8Hz,1H),7.69(dd,
J=8&2Hz,1H),8.30(d,J=2Hz,1H),9.04
(br,NH2)
IR(Nujol):1610,1540,1280,1230,1100cm-1
实例32
除了用1-(N-乙基-N-甲基)氨基-1-甲硫基-2-硝基乙烯代替1-二甲氨基-1-甲硫基-2-硝基乙烯外,重复实例28的步骤(2),得到浅黄色晶状标题化合物。
m.p.:87-88℃
NMR(CDCl3)δ:1.18(t,J=6.5Hz,3H),2.89(s,3
H),3.23(q,J=6.5Hz,2H),4.46(d,J=5.7
Hz,2H),6.53(s,1H),7.34(d,J=8.4Hz,1
H),7.69(dd,J=8.4&2.4Hz,1H),8.33(d,
J=2.4Hz,1H),9.5-10.0(br,1H)
IR(Nujol):1600,1460cm-1
实例33
1-(6-氯-3-吡啶甲基)氨基-1-肼基-2-硝基乙烯(化合物51)
除了用1-(6-氯-3-吡啶甲基)氨基-1-甲硫基-2-硝基乙烯和水合肼分别代替1-甲硫基-1-(3-吡啶甲基)氨基-2-硝基乙烯和甲胺水溶液外,得到浅黄色晶状的标题化合物。m.p.:188-190℃(decompn.)NMR(DMSO-d6)δ:4.43(br s,2H),4.3-5.2(br,2
H),6.49(s,1H),7.50(d,J=8.4Hz,1H),
7.81(dd,J=8.4&2.4Hz,1H),8.39(d,
J=2.4Hz,1H),9.9-10.8(br,1H)IR(Nujol):3260,1650,1560,1450cm-1
实例34
除了用6-氯-3-吡啶甲胺代替3-吡啶甲胺外,重复实例6的反应步骤,得到浅棕色棱晶状的标题化合物。
m.p.:170-172℃
NMR(DMSO-D6)δ:2.59(S,6H),4.43(d,J=6.6Hz,
2H),6.2-6.7(br,1H),7.47(d,J=8.4Hz,1
H),7.79(dd,J=8.4&2.4Hz,1H),8.38(d,
J=2.4Hz,1H),8.0-8.5(br,1H),9.9-10.5
(br,1H)
IR(Nujol):3200,1590,1560,1460,1390,1350
cm-1
实例35
1-(6-氯-3-吡啶甲基)氨基-1-(2-甲氧羰基)肼基-2-硝基乙烯(化合物53)
往0.4g(0.0016mol)1-(6-氯-3-吡啶甲基)氨基-1-肼基-2-硝基乙烯于15ml DMF中的溶液中加入0.14ml(0.0018mol)氯甲酸甲酯,并在室温回流混合物30分钟,减压蒸除DMF,用EtOH-CHCl3(1∶7)作洗脱液对残余物进行硅胶柱色谱分离,得到0.14g浅黄色固体状标题化合物。
m.p.:198-201℃(decompn.)
NMR(DMSO-d6)δ:3.67(s,3H),4.48(br d,J=6
Hz,2H),6.43(s,1H),7.52(d,J=8.4Hz,1
H),7.80(dd,J=8.4&2.4Hz,1H),8.38(d,
J=2.4Hz,1H),9.1-9.6(br,1H),10.0-10.9
(br,1H)
IR(Nujol):3110,1740,1570,1455cm-1
实例36
往0.3g(0.0012mol)1-(6-氯-3-吡啶甲基)氨基-1-肼基-2-硝基乙烯于5ml DMF中的溶液中加入0.15ml(0.0025mol)异氰酸甲酯,将混合物在室温下放置2小时。减压蒸除DMF,用硅胶柱色谱法提纯残余物,得到0.08g白色固态的标题化合物。
m.p.:190-192℃(decompn.)
NMR(DMSO-d6)δ:2.63(d,J=4.5Hz,3H),4.49
(br d,J=6.0Hz,2H),6.47(s,1H),6.5-6.8
(br d,J=4.5Hz,1H),7.51(d,J=8.4Hz,1
H),7.82(dd,J=8.4&2.4Hz,1H),8.10(s,
1H),8.40(d,J=2.4Hz,1H)
IR(Nujol):3200,1680,1550,1455,1380cm-1
实例37
除了用N-甲基-N-〔2-3-吡啶基)乙基〕-胺代替N-乙基-N-(3-吡啶甲基甲基)-胺外,重复实例13的步骤(1)、(2)和(3),各步分别获得下列化合物。
(1) N-甲基-N′-甲基-N ′-〔2-(3-吡啶基)乙基〕硫脲
m.p.:104-105℃
NMR(CDCl3)δ:3.02(m,
CH 2-pyridine),3.04(s,
MeNCH2),4.10( m,CH2N),5.90(brd,J=5Hz,NH),
7.26(dd,J=5&8Hz,1H),7.67(m,1H),8.50
(m,2H)
(2) S-甲基-N-甲基-N′-甲基-N′-〔2-(3-吡啶基)-乙基〕异硫脲(棕黄色油状)
(注:在加入60%氢化钠(油状)后,在50℃搅拌混合物1小时)
NMR(CDCl3)δ:2.15(s,MeS),2.84(m,
CH 2-
pyridine),2.93(s,
MeNCH2),3.21(s,MeN=),
3.61(m,NCH2),7.20(dd,J=5&8Hz,1H),
7.53(m,1H),8.45(m,2H)
(3) 标题化合物(黄色粘油状)
NMR(CDCl3)δ:2.93(d,J=5Hz,
MeNH),2.96(s,
MeNCH2),2.97(m,
CH 2-pyridine),3.50(m,
MeN
CH 2),6.52(s,=CHNO2),7.27(dd,J=5&8
Hz,1H),7.57(m,1H),8.50(m,2H),9.67
(br,NH)
实例38
将2.0g(0.012mol)1-二甲氨基-1-甲硫基-2-硝基乙烯和1.5g(0.012mol)N-甲基-N-3-吡啶甲胺的混合物在120℃搅拌40分钟。用柱色谱法分离反应混合物,用MeOH-CHCl3(1∶10)洗脱,得到分别含所需化合物的两种馏分。相继用MeOH-CHCl3(1∶10)和丙酮-CHCl3(2∶1)作洗脱液,用硅胶柱色谱法对馏份之一进一步提纯,从而获得0.40g浅黄色晶体状的标题化合物(化合物56)。相继用MeOH-CHCl3(1∶10)和丙酮-CHCl3(2∶1)作洗脱液,用硅胶柱色谱对另一馏份进行分离,得到0.35g黄色油状的标题化合物(化合物57)(化合物56)m.p.:103-105℃NMR(CDCl3)δ:2.81(s,3H),2.98(s,6H),4.44
(s,3H),6.41(s,1H),7.33(dd,J=8.4&
5.1Hz,1H),7.64(dt,J=8.4&1.5Hz,1H),
8.4-8.7(m,2H)
IR(Nujol):1545,1520,1450,1300,1265cm-1(化合物57)NMR(CDCl3)δ:2.83(s,6H),4.48(s,4H),6.52
(s,1H),7.34(dd,J=8.4&5.1Hz,2H),
7.62(dt,J=8.4&1.5Hz,2H),8.4-8.8(m,4
H)
实例39
1-〔N-(6-氯-3-吡啶甲基)-N-甲基〕氨基-1-二甲氨基-2-硝基乙烯(化合物58)
将1.6g(0.0099mol)1-二甲氨基-1-甲硫基-2-硝基乙烯和1.4g(0.0089mol)N-(6-氯-3-吡啶甲基)-N-甲胺的混合物在80℃搅拌3小时。用硅胶柱色谱法分离反应混合物,用MeOH-CHCl3(1∶10)洗脱二次,用丙酮-CHCl3(2∶1)洗脱一次,得到0.33g浅黄色晶体状的标题化合物。
m.p.:110-112℃
NMR(CDCl3)δ:2.79(s,3H),2.97(s,6H),
4.40(s,2H),6.38(s,1H),7.36(d,J=8.4
Hz,1H),7.72(dd,J=8.4&2.4Hz,1H),
8.30(d,J=2.4Hz,1H)
IR(Nujol):1545,1520,1460,1300,1260cm-1
实例40
(1) 在200ml EtOH中加热溶解9.68g 1,1-双(甲硫基)-2-硝基乙烯,回流下滴加6.66g(0.039mol)N-(6-氯-3-吡啶甲基)-N-乙胺于30mlEtOH中的溶液。回流45小时后,蒸除EtOH,用EtOH-CHCl3(1∶20)作洗脱液,对残余物进行硅胶(420g)柱色谱分离,得到2.28g 1-〔N-(6-氯-3-吡啶甲基)-N-乙基〕氨基-1-甲硫基-2-硝基乙烯,为棕色油状粗产品。NMR(CDCl3)δ:1.24(t,J=7Hz,CH2CH3),2.46(s,
MeS),3.52(q,J=7Hz,CH2CH3),4.72(s,
CH 2-pyridine),6.82(s,=CHNO2),7.31(d,J=8
Hz,1H),7.57(dd,J=8&2Hz,1H),8.30
(d,J=2Hz,1H)
(2) 在30ml EtOH中溶解2.16g步骤(1)制备的粗产物1-〔N-(6-氯-3-吡啶甲基)-N-乙基〕氨基-1-甲硫基-2-硝基乙烯,接着加入0.766ml 25%的氨水。在室温搅拌混合物3小时。蒸除溶剂,用硅胶(200g)柱色谱法分离残余物,用MeOH-CHCl3(1∶5)洗脱,得到0.69g浅黄色粘油状的标题化合物。用乙醚研磨该产物,过滤,干燥,得到白色粉末晶体状的标题化合物。
m.p.:159-161℃
NMR(CDCl3-DMSO-d6[4∶1])δ:1.22(t,J=7Hz,
CH2CH3),3.43(q,CH2CH3),4.62(s,
CH2-pyridine),6.61(s,=CHNO2),7.38(d,J=8
Hz,1H),7.62(dd,J=8&2Hz,1H),8.30
(d,J=2Hz,1H),8.97(br,NH2)
IR(Nujol):1610,1565,1455,1445,1305,1235
cm-1
实例41
除了用N-(6-氯-3-吡啶甲基)-N-乙胺代替N-甲基-N-〔2-(3-吡啶基)乙基〕胺外,重复实例3 7的步骤(1)、(2)和(3),各步分别得到下列化合物。
(1) N-(6-氯-3-吡啶甲基)-N-乙基-N′-甲基硫脲(黄色晶体状)
m.p.:133-134℃
NMR(CDCL3)δ:1.16(t,J=7Hz,CH2CH3),3.15(d,
J=5Hz,MeN),3.50(q,J=7Hz,CH2CH3),5.12
(s,
CH 2-pyridine),5.84(br d,J=5Hz,NH),
7.30(d,J=8Hz,1H),7.80(dd,J=8&2Hz,
1H),8.27(d,J=2Hz,1H)
(2) S-甲基-N-(6-氯-3-吡啶甲基)-N-乙基-N′-甲基异硫脲(棕黄色油状)
NMR(CDCl3)δ:1.09(t,J=7Hz,CH2CH3),2.29(s,
MeS),3.21(s,MeN=),3.38(q,J=7Hz,
CH2CH3),4.49(s,
CH 2-pyridine),7.27(d,J=8
Hz,1H),7.61(dd,J=8&2Hz,1H),8.30
(d,J=2Hz,1H)
(3) 标题化合物(白色晶体状)
m.p.:83-84℃
NMR(CDCl3)δ:1.20(t,J=7Hz,CH2CH3),3.08(d,
J=5Hz,
MeNH),3.18(q,J=7Hz,CH2CH3),4.40
(s,
CH 2-pyridine),6.54(s,=CHNO2),7.39(d,
J=8Hz,1H),7.63(dd,J=8&2Hz,1H),
8.33(d,J=2Hz,1H),9.79(br d,J=5Hz,
NH)
IR(Nujol):1595,1530,1455,1340,1270,1240
cm-1
实例42
1-〔N-(6-甲氧基-3-吡啶甲基)-N-甲基〕氨基-1-甲氨基-2-硝基乙烯(化合物61)
在20ml DMF中溶解0.67g(0.0026mol)1-〔N-(6-氯-3-吡啶甲基)-N-甲基〕-氨基-1-甲氨基-2-硝基乙烯,接着加入1.00g 28%的甲醇钠甲醇溶液,在100℃搅拌混合物5.5小时。蒸除甲醇和DMF,用氯化钠水溶液稀释残余物,用CH2Cl2提取。用MgSO4干燥提取液,蒸除CH2Cl2。用MeOH-CHCl3(1∶5)作洗脱液,对残余物进行硅胶(230g)柱色谱分离,得到0.22g棕色粘油状物。往油状物中加入少量乙醚,冷却混合物并研磨,用乙醚稀释所得结晶,过滤和干燥,得到0.128g白色-浅棕色晶状的标题化合物。
m.p.:77-78℃
NMR(CDCl3)δ:2.75(s,MeN),3.07(d,J=5Hz,
MeNH),3.93(s,OMe),4.30(s,
CH 2-pyridine),
6.53(s,=CHNO2),6.78(d,J=8Hz,1H),7.45
(dd,J=8&2Hz,1H),8.05(d,J=2Hz,1H),
9.80(br,NH)
IR(Nujol):1605,1455,1310,1250,1025cm-1
实例43
1-甲氨基-1-〔N-甲基-N-(4-吡啶甲基)-氨基-2-硝基乙烯(化合物62)
除了用N-甲基-N-(4-吡啶甲基)胺代替N-甲基-N-〔2-(3-吡啶)乙基〕胺外,重复实例37的步骤(1)、(2)和(3),各步分别获得下列化合物。
(1) N-甲基-N′-甲基-N′-(4-吡啶甲基)硫脲
m.p.:123-124℃
NMR(CDCl3)δ:3.07(s,
MeNCH2),3.16(d,J=5Hz,
MeNH),5.19(s,CH2),6.29(br d,J=5Hz,
NH),7.19(m,2H),8.52(m,2H)
(2) S-甲基-N-甲基-N′-甲基-N′-(4-吡啶甲基)异硫脲(棕色油状物)NMR(CDCl3)δ:2.30(s,MeS),2.87(s,
MeNCH2,
3.27(s,MeN=),4.59(s,CH2),7.18(m,2H),
8.54(m,2H)
(3) 标题化合物
m.p.:145-146℃
NMR(CDCl3)δ:2.88(s,
MeNCH2),3.07(d,J=5
Hz,MeNH),4.43(s,CH2),6.54(s,=CHNO2),
7.21(m,2H),8.65(m,2H),9.78(br,NH)
IR(Nujol):1600,1565,1455,1435,1410,1320,
1260cm-1
实例44
除了用N-甲基-N-(2-吡啶甲基)胺代替N-甲基-N-〔2-(3-吡啶基)乙基〕胺外,重复实例37的步骤(1)、(2)和(3),各步分别获得下列化合物。
(1) N-甲基-N′-甲基-N′-(2-吡啶甲基)硫脲(黄棕色粘油状)
NMR(CDCl3)δ:3.15(d,J=5Hz,
MeNH),3.31(s,
MeNCH2),4.90(s,CH2),7.15-7.6(m,3H,
pyridine-H2&NH),7.73(t,J=7Hz,1H),
8.55(d,J=5Hz,1H)
(2) S-甲基-N-甲基-N′-甲基-N′-(2-吡啶甲基)异硫脲(棕色油状)
NMR(CDCl3)δ:2.30(s,MeS),2.91(s,
MeNCH2),
3.28(s,MeN=1,4.77(s,CH2),7.05-7.45(m,
2H),7.67(m,1H),8.56(d,J=5Hz,1H)
(3) 标题化合物
m.p.:96-97℃
NMR(CDCl3)δ:2.96(s,
MeNCH2),3.08(d,J=5Hz,
MeNH),4.53(s,CH2),6.57(s,=CHNO2,7.30
(m,2H),7.78(m,11H),8.63(m,1H),9.61
(br,NH)
IR(Nujol):1580,1545,1425,1380,1280cm-1
实例45
除了用O-甲基-N-(3-吡啶甲基)羟胺代替N-甲基-N-〔2-(3-吡啶基)乙基〕胺外,重复实例37的步骤(1)、(2)和(3),各步分别得到下列化合物
(1) N-甲氧基-N-(3-吡啶甲基)-N′-甲基硫脲(但倘若用乙腈作反应溶剂,反应在50℃进行5小时)
m.p.:95-96℃
NMR(CDCl3)δ:3.15(d,J=5Hz,3H),3.63(s,3
H),5.32(s,2H),7.03-7.46(br,NH),7.27
(dd,J=8&5Hz,1H),7.86(dt,J=8&2
Hz,1H),8.56(dd,J=5&2Hz,1H),8.66
(d,J=2Hz,1H)
(2) S-甲基-N-甲氧基-N-(3-吡啶甲基)-N′-甲基一异硫脲(浅黄色油状)NMR(CDCl3)δ:2.23&2.45(each s,total 3H),
3.26&3.32(each s,total 3H),3.40&3.50
(each s,total 3H),4.08&4.52(each s,
total 2H),7.20-7.43(m,1H),7.76(m,1
H),8.50-8.76(m,2H)
(3) 标题化合物
m.p.100-101℃
NMR(CDCl3)δ:3.18(d,J=5Hz,3H),3.45(s,3
H),4.30(s,2H),6.90(s,1H),7.33(dd,
J=8&5Hz,1H),7.73(dt,J=8&2Hz,1H),
8.56-8.73(m,2H),9.73(br,NH)
IR(Nujol):1613,1460,1360,1250,1080cm-1
实例46
1-(N-甲酰基-N-甲基)氨基-1-〔N-甲基-N-(3-吡啶甲基)〕氨基-2-硝基乙烯(化合物65)
在10ml干燥THF中悬浮0.1g石油醚洗过的60%的氢化钠,接着加入0.51g(0.0023mol)1-甲氨基-1-〔N-甲基-N-(3-吡啶甲基)〕氨基-2-硝基乙烯。在室温下搅拌混合物过夜。然后在冰冷却下加入0.6g甲酸乙酸酐,在该温度下搅拌混合物1小时。蒸除溶剂,用30ml水稀释残余物,用NaHCO3中和,用CH2Cl3(30ml×3)提取。用MgSO4干燥提取液,蒸除CH2Cl2。用硅胶柱色谱法分离残余物,用MeOH-CHCl3(1∶5)洗脱,得到0.25g浅黄色棱晶状标题化合物。
m.p.:97-98℃
NMR(DMSO-d6)δ:2.93(s,3H),3.03(s,3H),
4.62(br,2H),6.86(s,1H),7.42(dd,J=8
&5Hz,1H),7.73(br d,J=8Hz,1H),8.25
(s,1H),8.55(br,2H)
IR(Nujol):1700,1560,1350,1285,1260,890cm-1
实例47
往3ml异丁醇中加入0.75g(0.0033mol)1-甲硫基-1-(3-吡啶甲基)氨基-2-硝基乙烯,接着在100-110℃中加入0.56g O-甲基羟胺盐酸盐。然后在相同温度和搅拌下,在30分钟内滴加0.93ml三乙胺于1ml异丁醇中的溶液。滴加完毕,使反应混合物冷却至室温,蒸除溶剂,用硅胶柱色谱法〔洗脱液:先用MeOH-CHCl3(1∶3),再用MeOH-CHCl3(1∶10)〕提纯残余物,得到0.23g黄色晶状的标题化合物。
m.p.:77-78℃
NMR(CDCl3)δ:3.86(s,3H),4.37(d,J=6.3Hz,2
H),5.04(s,2H),5.2-5.8(br,1H),7.32
(dd,J=8.4&5.1Hz,1H),7.65(dt,J=8.4&
1.5Hz,1H),8.4-8.8(2H,m)
实例48
除了用N-甲基-N-(3-吡啶甲基)胺和异硫氰酸(2-甲氧基)乙酯分别代替N-乙基-N-(3-吡啶甲基)胺和异硫氰酸甲酯外,重复实例13的步骤(1)、(2)和(3),各步分别获得下列化合物。
(1) N-(2-甲氧乙基)-N′-甲基-N′-(3-吡啶甲基)-硫脲(无色油状)NMR(CDCl3)δ:3.06(s,3H),3.36(s,3H),3.57
(t,J=5.1Hz,2H),3.91(dt,J=5.1&5.1Hz,
2H),5.21(s,2H),5.9-6.3(br,1H),7.28
(dd,J=8.4&5.1Hz,1H),7.75(dt,J=8.4&
1.5Hz,1H),8.5-8.7(m,2H)
(2) S-甲基-N-(2-甲氧乙基)-N′-甲基-N ′-(3-吡啶甲基)异硫脲(黄色油状)NMR(CDCl3)δ:2.30(s,3H),2.88(s,3H),3.37
(s,3H),3.4-3.8(m,4H),4.59(s,2H),
7.25(dd,J=8.4&5.1Hz,1H),7.62(dt,
J=8.4&1.5Hz,1H),8.4-8.7(m,2H)
(3) 标题化合物
m.p.55-57℃
NMR(CDCl3)δ:2.79(s,3H),3.3-3.7(m,4H),
3.41(s,3H),4.43(s,2H),6.53(s,1H),
7.35(dd,J=8.4&1.5Hz,1H),7.60(dt,
J=8.4&1.5Hz,1H),8.5-8.7(m,2H),
9.4-9.9(br,1H)
实例49
(1)在50ml干燥THF中溶解4.69g(0.0205mol)N-(4-氯苄基)-N-甲基-N′-甲硫脲,接着加入0.82g 60%氢化钠(油状),回流混合物1小时。然后在冰-水冷却和搅拌下,滴加1.277ml甲基碘,滴加完毕,在室温下再搅拌混合物45分钟。蒸除THF,用水(约50ml)稀释残余物,用NaCl饱和,用AcOEt(100ml×3)提取。用MgSO4干燥提取液,蒸除溶剂,得到5.11g S-甲基-N-(4-氯苄基)-N-甲基-N′-甲基异硫脲,为无色浅黄色油状的粗产物。NMR(CDCl3)δ:2.28(s,MeS),2.80(s,
MeNCH2),
3.26(s,MeN=),4.53(s,CH2),7.14&7.31
(each d,J=9Hz,each 2H)(2)向4.98g(0.0205mol)(1)步制备的S-甲基-N-(4-氯苄基)-N-甲基-N′-甲基异硫脲中加25ml硝基甲烷,回流此混合物6.5小时。蒸除硝基甲烷,残余物经硅胶(240g)柱色谱分离〔洗脱剂为MeOH-CHCl3(1∶10)〕,得到5.23g橙色油状物。向该油状物中加少量EtOH和乙醚,在干冰-丙酮液中冷却并研磨,得结晶体。加乙醚,过滤收集,乙醚洗涤,干燥,得3.69g浅黄色晶状标题化合物。
m.p.:98-99℃
NMR(CDCl3)δ:2.79(s,
MeNCH2),3.05(d,J=5Hz,
MeNH),4.34(s,CH2),6.53(s,=CHNO2),7.17
&7.38(each d,J=8Hz,each 2H),9.79(br,
NH)
IR(Nujol):1450,1310,1235,1070,1025cm-1
实例50
1-氨基-1-(4-氯苄基)氨基-2-硝基乙烯(化合物69)将45ml EtOH、10ml THF和1.02g 25%氨水加入到2.59g(0.01mol)1-(4-氯苄基)氨基-1-甲硫基-2-硝基乙烯中,在外温为60℃下搅拌混合物5.5小时。在这期间,在反应1、2和3小时后各加入1.02g 25%氨水。用冰冷却反应混合物,搅拌,这时析出晶体。过滤收集晶体,用EtOH,再用乙醚洗涤,干燥。得到1.1g白色晶状的标题化合物。
m.p.:215-216℃(decompn.)
NMR(DMSO-d6)δ:4.47(d,J=7Hz,CH2),6.45(s,
=CHNO2),7.34&7.44(each d,J=9Hz,each 2
H),8.02(br,NH2),9.25(br,NH)
IR(Nujol):3100,1560,1430,1405,1195,1030
cm-1
实例51
1-(4-氯苄基)氨基-1-甲氨基-2-硝基乙烯(化合物70)
回流下在100ml EtOH中溶解2.59g(0.01mol)1-(4-氯苄基)氨基-1-甲硫基-2-硝基乙烯,继续回流,在50分钟内滴加1.94g 40%甲胺水溶液于10ml EtOH中的溶液。滴加完毕,再回流混合物15分钟,然后立即用冰-水冷却,这时析出晶体。过滤收集晶体,用EtOH,再用乙醚洗涤,干燥,得到1.66g白色晶体状标题化合物。
m.p.:219-220℃(decompn.)
NMR(DMSO-d6)δ:2.88(br d,J=3Hz,Me),4.43
(d,J=6Hz,CH2),6.43(s,=CHNO2),7.40(s,
4H),7.7(br,MeN
H),9.9(br,HNCH2)
IR(Nujol):1455,1425,1375,1360,1215,995cm-1
实例52
1-(4-氯苄基)氨基-1-二甲氨基-2-硝基乙烯(化合物71)
在100ml EtOH中加热溶解2.59g(0.01mol)1-(4-氯苄基)氨基-1-甲硫基-2-硝基乙烯。然后,在回流和搅拌条件下,在35分钟内滴加2.25g 50%二甲胺水溶液于10ml EtOH中的溶液。滴加完毕,再搅拌和回流混合物2.5小时。然后蒸除溶剂,用乙醚稀释残余物并研磨,这时析出结晶。加入EtOH和乙醚(约1∶5),过滤收集结晶体,用乙醚洗涤,干燥,得到1.21g白色晶状的标题化合物。
m.p.:133-135℃
NMR(CDCl3)δ:2.91(s,Me2N),4.45(d,J=6Hz,
CH2),6.51(s,=CHNO2),7.30(s,4H),9.79
(br,NH)
IR(Nujol):1620,1500,1435,1420,1370,1220,
1195cm-1
实例53
将0.1g 60%的氢化钠(油状)悬浮于10ml干燥THF,接着加入0.56g(0.0025mol)1-二甲氨基-1-(3-吡啶甲基)氨基-2-硝基乙烯,在室温下搅拌混合物过夜。然后,在冰冷却下加入0.7g甲酸乙酸酐,接着在相同温度下搅拌2小时。蒸除溶剂,用30ml水稀释残余物,用NaHCO3中和,用CH2Cl2(30ml×3)提取。用MgSO4干燥提取液,蒸除溶剂,用MeOH-CHCl3(1∶5)作洗脱液,对残余物进行硅胶柱色谱分离,得到0.2g浅黄色粘油状标题化合物。
NMR(DMSO-d6)δ:2.90(s,6H),4.40-5.06(m,2
H),6.73(s,1H),7.33(dd,J=8&5Hz,1
H),7.75(br d,J=8Hz,1H),8.26(s,1H),
8.55(br,2H)
IR(neat):1685,1570,1500,1350,1270cm-1
实例54
除了用N-甲基-N-(2-吡嗪基)甲胺代替N-乙基-N-(3-吡啶甲基)胺外,重复实例13的步骤(1)、(2)和(3),各步分别得到下列化合物。
(1) N-甲基-N′-甲基-N′-〔(2-吡嗪基)甲基〕硫脲
m.p.:123-124℃
NMR(CDCl3)δ:3.17(d,J=5Hz,3H),3.26(s,2
H),5.12(s,2H),6.42(br,1H),8.53(s,2
H),8.72(s,1H)
(2) S-甲基-N-甲基-N′-甲基-N′-〔(2-吡嗪基)甲基〕异硫脲(浅黄色油状)
NMR(CDCl3)δ:2.32(s,3H),2.98(s,3H),3.26
(s,3H),4.76(s,2H),8.45-8.66(m,3H)
(3) 标题化合物
m.p.:132-133℃
NMR(CDCl3)δ:2.93(s,3H),3.09(d,J=5Hz,3
H),4.56(s,2H),6.60(s,1H),8.62(s,3
H),9.60(br,1H)
IR(Nujol):3150,1580,1410,1280,1240,1020,
990cm-1
实例55
在90-100℃搅拌4.3g(0.024mol)1-(2,2-二甲基-1-腓基)-1-甲硫基-2-硝基乙烯与3.6g N-甲基-N-(3-吡啶甲基)胺的混合物4小时,然后对其进行硅胶柱色谱分离,用MeOH-CHCl3(1∶10)作洗脱液。所得晶体用乙醚洗,干燥,得0.7g标题化合物。此产物的NMR谱表明它是标题化合物与N2-二甲氨基-N′-甲基-2-硝基-N′-(3-吡啶甲基)乙脒的3∶2混合物。
m.p.:80-82℃
NMR(CDCl3)δ:2.40(s,2.4H),2.59(s,3.6H),
2.87(s,1.2H),2.90(s,1.8H),4.61(s,
0.8H),4.63(s,1.2H),6.00(s,0.8H),
6.47(s,0.6H),7.15-7.45(m,1H),
7.45-7.80(m,1H),8.45-8.70(m,2H),
10.1-10.5(br s,0.6H)
IR(Nujol):3130,1585,1570,1445,1425cm-1
实例56
1-氨基-1-〔N-(6-氯-3-吡啶甲基)-N-正丙基〕氨基-2-硝基乙烯(化合物75)
在40ml EtoH中溶入2.83g(0.0094mol)1-〔N-(6-氯-3-吡啶甲基)-N-正丙基〕氨基-1-甲硫基-2-硝基乙烯,再加入0.96ml 25%氨水。混合物于室温搅拌3小时。过滤收集所得晶体,依次用少量EtOH和乙醚洗,干燥,得1.35g标题化合物,为淡黄色晶体。m.p:185-186℃(decompn.)NMR(DMSO-d6)δ:0.87(t,J=7Hz,CH2CH3),1.59
(sextet,J=7Hz,CH2CH3),3.31(t,J=7Hz,
NCH2CH2),4.68(s,CH2-pyridine),6.59(s,
=CHNO2),7.50(d,J=8Hz,1H),7.71(dd,J=8
&2Hz,1H),8.31(d,J=2Hz,1H),8.99
(br,NH2)IR(Nujol):1615,1550,1455,1335,1320,1300,
1285cm-1
实例57
1〔N-(6-氯-3-吡啶甲基)-N-正丙基〕氨基-1-甲氨基-2-硝基乙烯(化合物76)
重复实例13的步骤(1)、(2)和(3),但用N-(6-氯-3-吡啶甲基)-N-正丙基胺代替N-乙基-N-(3-吡啶甲基)胺,在各步分别得到下列化合物:
(1)N-(6-氯-3-吡啶甲基)-N-正丙基-N′-甲基硫脲(淡黄色晶体)
m.p.:95-96℃
NMR(CDCl3)δ:0.89(t,J=8Hz,CH2CH3),1.63
(sextet,J=8Hz,CH2CH3),3.17(d,J=5Hz,
MeN),3.36(t,J=8Hz,CH2CH2N),5.16(s,
CH2-pyridine),5.87(br q,J=5Hz,NH),7.30
(d,J=8Hz,1H),7.78(dd,J=8&2Hz,1H),
8.30(d,J=2Hz,1H)
(2) S-甲基-N-(6-氯-3-吡啶甲基)-N-正丙基-N ′-甲基异硫脲(黄色油状物)
(但若在加入60%NaH(油状)后,要在50℃搅拌混合物1小时。)NMR(CDCl3)δ:0.85(t,J=7Hz,CH2CH3),1.55
(sextet,J=7Hz,CH2CH3),2.26(s,MeS),3.21
(s,MeN=),3.29(t,J=7Hz,CH2CH2N),4.52
(s,CH2-pyridine),7.26(d,J=8Hz,1H),
7.60(dd,J=8&2Hz,1H),8.30(d,J=2Hz,
1H)
(3) 标题化合物(淡黄-浅褐黄晶体)(反应混合物应在硝基甲烷中回流34小时)m.p.:102-103℃NMR(CDCl3)δ:0.88(t,J=7Hz,CH2CH3),1.63
(sextet,J=7Hz,CH2CH3),3.04(t,J=7Hz,
CH2CH2N),3.08(d,J=5Hz,MeN),4.40(s,
CH2-pyridine),6.54(s,=CHNO2),7.38(d,J=8
Hz,1H),7.60(dd,J=8&2Hz,1H),8.33
(dd,J=2Hz,1H),9.78(br q,J=5Hz,NH)IR(Nujol):1590,1520,1450,1350,1270,1245,
1095cm-1
实例58
1-〔N-(6-氯-3-吡啶甲基)-N-异丙基〕氨基-1-甲氨基-2-硝基乙烯(化合物77)重复实例13中的步骤())、(2)、(3),但用N-(6-氯-3-吡啶甲基)-N-异丙胺代替N-乙基-N-(3-吡啶甲基)胺,各步分别得到下列化合物:
(1)N-(6-氯-3-吡啶甲基)-N-异丙基-N ′-甲基硫脲(淡黄头晶体)
m.p.:92-93℃
NMR(CDCl3)δ:1.17(d,J=7Hz,
Me 2CH),3.12(d,
J=5Hz,MeN),4.87(s,CH2),5.08(septet,
J=7Hz,Me2C
H),5.80(br q,J=5Hz,NH),7.30
(d,J=8Hz,1H),7.65(dd,J=8&2Hz,1H),
8.27(d,J=2Hz,1H)
(2) S-甲基-N-(6-氯-3-吡啶甲基)-N-异丙基-N′-甲基异硫脲(浅褐色油状)(加入60%NaH(油状)后,应在50℃搅拌混合物1小时) NMR(CDCl3)δ:1.20(d,J-7Hz,
Me 2CH),2.23(s,
MeS),3.10(s,MeN=),4.24(s,CH2-pyridine),
4.44(septet,J=7Hz,Me2CH),7.23(d,J=8
Hz,1H),7.56(dd,J=8&2Hz,1H),8.30
(d,J=2Hz,1H)
(3) 标题化合物(白-浅褐色晶体)
(反应混合物应在硝基甲烷中回流130小时)m.p.:119-120℃NMR(CDCl3)δ:1.31(d,J=7Hz,
Me 2CH),3.04(d,
J=5Hz,MeN),3.79(septet,J=7Hz,Me2 CH),
4.20(s,CH2),6.56(s,=CHNO2),7.30(d,J=8
Hz,1H),7.56(dd,J=8&2Hz,1H),8.30
(d,J=2Hz,1H),9.78(br q,J=5Hz,NH)IR(Nujol):1590,1450,1360,1335,1270,1235,
1105cm-1
实例59
(1)在50ml乙腈中,回流4.0g(0.28mol)2-氯-5-甲氨基吡啶和3.7g异硫氰酸甲酯52.5小时,再浓缩混合物。残余物中加入30ml冰-水和2ml 3N-HCl,再用AcOEt(50ml×3)提取。合并各提取液,依次用3N-HCl(4次)、NaCl水溶液(4次)、NaHCO3水溶液(1次)洗,用MgSO4干燥、减压蒸去AcOEt,并在加入乙醚后过滤收集晶体,干燥之,得2.8g N-(6-氯-3-吡啶基)-N-甲基-N′-甲基硫脲,为白色晶体。m.p.:87.5-88℃NMR(CDCl3)5:3.09(d,J=4.5Hz,3H),3.65(s,3
H),5.3-6.0(m,1H),7.47(d,J=8.4Hz,1
H),7.61(dd,J=8.4&2.4Hz,1H),8.33(d,
J=2.4Hz,1H)
(2) 将已用石油醚洗过2次的60%NaH(油状)悬浮在10ml无水四氢呋喃(THF)中,在搅拌下滴加2.5g(0.012mol)N-(6-氯-3-吡啶基)-N-甲基-N′-甲基硫脲在30ml无水THF中的溶液。滴加完后,在50℃搅拌混合物半小时,再于室温滴加2.2g甲基碘,混合物再搅拌3小时。减压浓缩反应混合物。加入50ml冰水和3ml 3N-HCl后,用AcOEt(50ml×3)提取浓缩液。合并提取液,用水洗两次,用MgSO4干燥。最后减压蒸去AcOEt,回收到2.6g S-甲基-N-(6-氯-3-吡啶基)-N-甲基-N′-甲基硫脲,为褐色油状粗品。NMR(CDCl3)δ:2.07&2.38(each s,3H),3.06&
3.27(each s,3H),3.17&3.30(each s,3
H),6.9-7.6(m,2H),7.90&8.24(each d,
J=3.0Hz,1H)
(3) 在40ml硝基甲烷中,回流2.6g(0.011mol)S-甲基-N-(6-氯-3-吡啶基)-N-甲基-N′-甲基异硫脲63小时。然后浓缩反应混合物,残余物进行硅胶柱色谱分离,用己烷-丙酮(1∶2 )洗脱。所得晶体用乙醚洗,干燥,得1.3g标题化合物,为淡黄色晶体。
m.p.:108-109℃
NMR(CDCl3)δ:2.75(d,J=5.1Hz,3H),3.30(s,3
H),6.63(s,1H),7.2-7.6(m,2H),8.2-8.3
(m,1H),9.6-10.3(m,1H)
IR(Nujol):3120,1600cm-1
实例60
重复实例59的步骤(1)、(2)、(3),但用3-甲氨基吡啶,各步分别得到下列化合物:
(1) N-甲基-N′-甲基-N′-(3-吡啶基)硫脲(白色晶体)m.p.:93-94℃NMR(CDCl3)δ:3.08(d,J=4.5Hz,3H),3.69(s,3
H),5.2-5.8(m,1H),7.47(dd,J=8.1&4.7
Hz,1H),7.64(dt,J=8.4&2.3Hz,1H),
8.4-8.8(m,2H)
(2) S-甲基-N-甲基-N′-甲基-N ′-(3-吡啶基)异硫脲(红棕色油状)NMR(CDCl3)δ:2.01&2.37(each s,3H),3.05&
3.27(each s,3H),3.17&3.29(each s,3
H),6.9-7.6(m,2H),8.0-8.6(m,2H)
(3) 标题化合物(浅褐色晶体)
m.p.:113-114℃
NMR(DMSO-d6)δ:2.66(d,J=5.1Hz,3H),3.29(s,
3H),6.53(s,1H),7.41(dd,J=8.4&4.5
Hz,1H),7.5-7.8(m,1H),8.2-8.7(m,2H),
9.4-10.0(m,1H)
IR(Nujol):3190,3140,1595cm-1
实例61
1-〔N-(6-氯-3-吡啶甲基)-N-甲基〕氨基-1-乙氨基-2-硝基乙烯(化合物80)
使用N-(6-氯-3-吡啶甲基)-N-甲基胺和异硫氟酸乙酯分别代替N-乙基-N-(3-吡啶甲基)胺和异硫氰酸甲酯,重复实例13的步骤(1)、(2)、(3),各步分别得到以下化合物:
(1)N-(6-氯-3-吡啶甲基)-N′-乙基-N-甲基硫脲(白色晶体)
m.p.82-83℃
NMR(CDCl3)δ:1.24(t,J=7Hz,CH2CH3),3.04(s,
MeN),3.72(dq,J=5&7Hz,CH2CH3),5.22(s,
CH2-pyridine),5.66(br,NH),7.33(d,J=8
Hz,1H),7.79(dd,J=8&2Hz,1H),8.33(d,
J=2Hz,1H)
(2) S-甲基-N-(6-氯-3-吡啶甲基)-N′-乙基-N-甲基异硫脲(褐色油状)NMR(CDCl3)δ:1.12(t,J=7Hz,CH2CH3),2.30(s,
MeS),2.87(s,
MeNCH2),3.51(q,J=7Hz,
CH2CH3),4.52(s,CH2-pyridine),7.30(d,J=8
Hz,1H),7.62(dd,J=8&2Hz,1H),8.33
(d,J=2Hz,1H)
(3) 标题化合物(白色-淡黄色晶体)
m.p.:132-133℃
NMR(CDCl3)δ:1.33(t,J=7Hz,CH2CH3),2.80(s,
MeN),3.38(dq,J=5&7Hz,CH2CH3),4.40(s,
CH2-pyridine),6.49(s,=CHNO2),7.38(d,J=8
Hz,1H),7.59(dd,J=8&2Hz,1H),8.30
(d,J=2Hz,1H),9.51(br t,J=5Hz,NH)
IR(Nujol):1600,1535,1445,1305,1290cm-1
实例62
重复实例13的步骤(1)、(2)、(3),但用N-(2,6-二甲基-4-吡啶甲基)-N-甲胺代替N-乙基-N-(3-吡啶甲基)胺,各步分别得到如下化合物:
(1)N-(2,6-二甲基-4-吡啶甲基)-N-甲基-N′-甲基硫脲(白色晶体)
m.p.:207-208℃
NMR(CDCl3)δ:2.49(s,pyridine-Mex2),3.09(s,
MeNCH2),3.18(d,J=5Hz,
MeNH),5.10(s,
CH2-pyridine),5.91(br q,J=5Hz,NH),6.86
(s,pyridine-H2)
(2) S-甲基-N-(2,6-二甲基-4-吡啶甲基)-N-甲基-N ′-甲基异硫脲(褐色油状)
(加入60%NaH(油状)后,在50℃搅拌混合物1小时,再回流温度下搅拌1小时。)
NMR(CDCl3)δ:2.30(s,MeS),2.50(s,
pyridien-Mex2),2.86(s,
MeNH),3.27(s,
MeN=),4.53(s,pyridine-CH2),6.84(s,
pyridine-H2)
(3) 标题化合物(白色晶体)
m.p.:131-133℃
NMR(CDCl3)δ:2.53(s,pyridine-Mex2),2.87(s,
MeNCH2),3.05(d,J=5Hz,
MeNH),4.34(s,
CH2),6.54(s,=CHNO2),6.83(s,pyridine-H2)
IR(Nujol):1570,1460,1395,1310,1230cm-1
实例63
1-〔N-(2-氯-3-吡啶甲基)-N-甲基〕氨基-1-甲氨基-2-硝基乙烯(化合物82)
重复进行实例13的步骤(1)、(2)、(3),但用N-(2-氯-3-吡啶甲基)-N-甲胺代替N-乙基-N-(3-吡啶甲基)胺,各步分别得以下化合物:
(1)N-(2-氯-3-吡啶甲基)-N-甲基-N ′-甲基硫脲(白色晶体)
m.p.:143-144℃
NMR(CDCl3)δ:3.17(s,
MeNCH2),3.18(d,J=5Hz,
MeNH),5.29(s,CH2),5.98(br q,J=5Hz,
NH),7.26(dd,J=8&5Hz,1H),7.66(d,J=8
&1Hz,1H),8.31(dd,J=5&1Hz,1H)
(2) S-甲基-N-(2-氯-3-吡啶甲基)-N-甲基-N ′-甲基异硫脲(淡黄色油状)
(加60%NaH(油状)后,在50℃搅拌混合物1小时。)
NMR(CDCl3)δ:2.29(s,MeS),2.95(s,
MeNCH2),
3.26(s,MeN=),4.67(s,CH2-pyridine),7.24
(dd,J=8&5Hz,1H),7.62(dd,J=8&1Hz,
1H),8.32(dd,J=5&1Hz,1H)
(3) 标题化合物(淡黄色晶体)
(反应混合物在硝基甲烷中回流2.25小时)
经NMR测定,此产物纯度为约75%
m.p.:106-113℃
NMR(CDCl3)δ:(for the title compound only)2.90
(s,
MeNCH2),3.04(d,J=5Hz,
MeNH),4.50(s,
CH2),6.54(s,=CHNO2),7.37(dd,J=8&5
Hz),7.68(dd,J=8&1Hz),8.43(dd,J=5&1
Hz),9.78(br q,J=5Hz,NH)
IR(Nujol):1560,1450,1405,1310,1260cm-1
实例64
1-(6-氯-3-吡啶甲基)氨基-1-甲氨基-2-硝基乙烯(化合物28)
重复实例8步骤(1)、(2)、(3),但用6-氯-3-吡啶甲基胺代替N-甲基-N-3吡啶甲基胺,各步分别得以下化合物:
(1)N-(6-氯-3-吡啶甲基)-N′-甲基硫脲(白色晶体)
m.p.:133-134℃
NMR(CDCl3)δ:3.01(d,J=5Hz,Me),4.80(d,J=6
Hz,CH2),7.25(br,NHCH3),7.32(d,J=8Hz,
1H),7.66(br t,J=6Hz,NHCH2),7.78(dd,
J=8&2Hz,1H),8.37(d,J=2Hz,1H)
(2)S-甲基-N-(6-氯-3-吡啶甲基)-N′-甲基异硫脲(油状)NMR(CDCl3)δ:2.39(s,MeS),2.93(s,MeN),4.22
(br,NH),4.50(s,CH2),7.27(d,J=8Hz,1
H),7.69(dd,J=8&2Hz,1H),8.39(d,J=2
Hz,1H)
(3)标题化合物(白色-浅黄色晶体)
经测定此产物的熔点、NMR、IR及TLC Rf值与实例10制备的化合物28一致。
实例65
1-甲氨基-1-〔N-甲基-N-(2-噻唑基)〕氨基-2-硝基乙烯(化合物83)
重复实例59步骤(1)、(2)、(3),但用2-甲基噻唑代替2-氯-5-甲氨基吡啶,各步分别得以下化合物:
(1)N-甲基-N′-甲基-N′-(2-噻唑基)硫脲(白色晶体)
(反应混合物应在甲苯中回流8小时,产物用硅胶柱色谱法纯化)
m.p.:68-69℃
NMR(CDCl3)δ:3.24(d,J=4Hz,3H),3.95(s,3
H),6.69(d,J=4H,1H),7.42(d,J=4Hz,1
H),11.95(br,1H)
(2)S-甲基-N-甲基-N′-甲基-N′-(2-噻唑基)异硫脲(淡黄色油状)
NMR(CDCl3)δ:2.33(s,3H),3.41(s,3H),3.75
(s,3H),6.74(d,J=4Hz,1H),7.40(d,J=4
Hz,1H)
(3)标题化合物(淡黄色晶体)
(反应进行25小时,浓缩产品得到晶体)
m.p.:155-156℃
NMR(CDCl3):2.98(d,J=5Hz,3H),3.42(s,3H),
6.71(s,3H),6.91(d,J=4Hz,1H),7.36
(d,J=4Hz,1H),9.87(br,1H)
IR(Nujol):3050,1610,1500,1400,1320,1260,
1100,1010cm-1
实例66
(1)把4.3g(0.02mol)2-甲基-5-甲氨基吡啶草酸盐溶于1.9g NaOH在30ml水中的溶液内;混合物用AcOEt提取(50ml,30ml×2)。合并AcOEt层,水洗,用MgSO4干燥。浓缩后,加30ml甲卷1.8g异硫氰酸甲酯于浓缩液中,混合物回流8小时。再另加0.8g异硫氰酸甲酯,回流混合物7.5小时。把反应混合物冷至-20℃,过滤收集所得晶体,用冷甲苯洗,干燥。得2.2g N-甲基-N′-甲基-N ′-(6-甲基-3-吡啶基)硫脲,为白色晶体。m.p.:134-135℃NMR(CDCl3)δ:2.62(3H,s),3.06(3H,d,J=4.2
Hz),3.66(3H,s),5.2-5.9(1H,m,NH),
7.30(1H,d,J=8.4Hz),7.49(1H,dd,J=8.4
&2.7Hz),8.42(1H,d,J=2.7Hz)
(2)重复实例59的反应步骤(2),但用N-甲基-N′-甲基-N′-(6-甲基-3-吡啶基)硫脲代替N-(6-氯-3-吡啶基)-N-甲基-N′-甲基硫脲,得S-甲基-N-甲基-N ′-甲基-N′-(6-甲基-3-吡啶基)异硫脲,为油状物。NMR(CDCl3)δ:2.01&2.37(3H,each s),2.49&
2.53(3H,each s),3.04&3.17&3.24&3.30
(6H,each s),6.9-7.6(2H,m),8.0-8.5(1
H,m)
(3)重复实例59的反应步骤(3),但用S-甲基-N-甲基-N′-甲基-N′-(6-甲基-3-吡啶基)异硫脲代替S-甲基-N-(6-氯-3-吡啶基)-N-甲基-N′-甲基异硫脲,反应进行23小时。得标题化合物,为黄褐色晶体。m.p.:120-121℃NMR(CDCl3)δ:2.57(3H,s),2.65(3H,d,J=5.4
Hz),3.30(3H,s),6.67(1H,s),7.23(1H,
d,J=8.7Hz),7.39(1H,dd,J=8.4&2.7Hz),
8.38(1H,d,J=2.7Hz),9.7-10.4(1H,m,
NH)IR(Nujol):3110,1600cm-1
实例67
1-〔N-(6-氯-3-吡啶基)-N-甲基〕氨基-1-乙氨基-2-硝基乙烯(化合物85)
重复实例59的步骤(1)、(2)、(3),但用异硫氰酸乙酯代替异硫氰酸甲酯,各步分别得到下述化合物:
(1)N-(6-氯-3-吡啶基)-N-甲基-N′-乙基硫脲(黄色油状物)
(反应混合物在甲苯中回流78小时,产物用硅胶柱色谱法纯化)NMR(CDCl3)δ:1.13(3H,t,J=6.6Hz),3.4-3.9(2
H,m),3.63(3H,s),5.0-5.8(1H,br),7.46
(1H,d,J=8.4Hz),7.61(1H,dd,J=8.4&
2.7Hz),8.33(1H,d,J=2.7Hz)
(2)S-甲基-N-(6-氯-3-吡啶基)-N-甲基-N′-乙基异硫脲(黄色油状物)NMR(CDCl3)δ:[主要成分…76%]1.23(3
H,t,J=7.2Hz),2.04(3H,s),3.28(3H,
s),3.53(2H,q,J=7.2Hz),6.9-7.6(2H,
m),8.22(1H,d,J=2.7Hz)[少量异
构体…24%],2.73(3H,s),3.13(3H,
s),3.1-3.4(2H,m),7.89(1H,d,J=2.7Hz)
(3)标题化合物(淡黄晶体)
(反应进行64小时,浓缩反应混合物,得到晶体)
m.p.:118-119℃
NMR(CDCl3)δ:1.19(3H,t,J=7.5Hz),3.00(2H,
dt,J=7.5&6.3Hz),3.29(3H,s),6.61(1
H,s),7.3-7.6(2H,m),8.1-8.4(1H,m)
IR(Nujol):3200,1605,1375,1300cm-1
实例68
重复实例13步骤(1)-(3),但用N-(5-溴-3-吡啶甲基)-N-甲胺代替N-乙基-N-(3-吡啶甲基)胺,各步分别得以下化合物:
(1)N-(5-溴-3-吡啶甲基)-N-甲基-N′-甲基硫脲(淡黄色油状)
(产物用硅胶柱色谱法提纯)
NMR(CDCl3)δ:3.05(s,
MeNCH2),3.19(d,J=5Hz,
MeNH),5.24(s,CH2),5.88(br q,J=5Hz,
NH),7.91(m,1H),8.47(d,J=2Hz,1H),
8.62(d,J=2Hz,1H)
(2)S-甲基-N-(5-溴-3-吡啶甲基)-N-甲基-N′-甲基异硫脲(油状)NMR(CDCl3)δ:2,31(s,MeS),2.88(s,
MeNCH2),
3.26(s,MeN=),4.56(s,CH2),7.77(m,1H),
8.47(d,J=2Hz,1H),8.60(d,J=2Hz,1H)
(3)标题化合物(浅黄褐色晶体) m.p.:116-117℃NMR(CDCl3)δ:2.84(s,
MeNCH2),3.08(d,J=5Hz,
MeNH),4.42(s,CH2),6.54(s,=CHNO2),7.76
(m,1H),8.48(d,J=2Hz,1H),8.68(d,J=2
Hz,1H),9.72(br q,J=5Hz,NH)IR(Nujol):1595,1465,1425,1405,1260cm-1
实例69
重复实例13步骤(1)-(3),但用N-(2-甲硫基-3-吡啶甲基)-N-甲胺代替N-乙基-N-(3-吡啶甲基)胺,各步中分别得下列化合物:
(1)N-甲基-N′-甲基-N′-(2-甲硫基-3-吡啶甲基)硫脲(白色-淡黄色晶体)
m.p.:105-106℃
NMR(CDCl3)δ:2.61(s,MeS),3.15(d,J=5Hz,
MeNH),3.17(s,
MeNCH2),5.00(s,CH2),5.77
(br,NH),7.01(dd,J=8&5Hz,1H),7.36
(dd,J=8&1Hz,1H),8.40(dd,J=5&1Hz,
1H)
(2)S-甲基-N-甲基-N′-甲基-N′-(2-甲硫基-3-吡啶甲基)异硫脲(黄色油状)NMR(CDCl3)δ:2.28(s,MeS),2.59(s,pyridine-
S
Me),2.89(s,
MeNCH2),3.27(s,MeN=),4.53
(s,CH2),6.98(dd,J=8&5Hz,1H),7.40
(dd,J=8&1Hz,1H),8.37(dd,J=5&1Hz,
1H)
(3)标题化合物(浅黄色晶体)
m.p.:131-132℃
NMR(CDCl3)δ:2.60(s,MeS),2.84(s,
MeNCH2),
3.03(d,J=5Hz,
MeNH),4.34(s,CH2),6.57
(s,=CHNO2),7.07(dd,J=8&5Hz,1H),7.43
(dd,J=8&1Hz,1H),8.46(dd,J=5&1Hz,
1H)
IR(Nujol):1600,1530,1395,1375,1245cm-1
实例70
重复实例13步骤(1)-(3),但用N-甲基-N-(4-噻唑基)甲基胺代替N-乙基-N-(3-吡啶甲基)胺,各步分别得下列化合物:
(1)N-甲基-N ′-甲基-N′-(4-噻唑甲基)硫脲(油状,冰箱中静置结晶而得)
(产物用硅胶柱色谱法提纯)NMR(CDCl3)δ:3.15(d,J=5Hz,
MeNH),3.30
(s,
MeNCH2),4.98(s,CH2),6.87(br,NH),
7.38(d,J=2Hz,1H),8.81(d,J=2Hz,1H)
(2)S-甲基-N-甲基-N′-甲基-N′-(4-噻唑甲基)异硫脲(油状)NMR(CDCl3)δ:2.31(s,MeS),2.91(s,
MeNCH2),
3.27(s,MeN=),4.79(s,CH2),7.17(m,1H),
8.80(d,J=2Hz,1H)
(3)标题化合物(黄色晶体)
(反应进行4.5小时)
m.p.:155-156℃
NMR(DMSO-d6)δ:2.89(s,
MeNCH2),2.98(d,J=5
Hz,
MeNH),4.60(s,CH2),6.55(s,=CHNO2),
7.70(d,J=2Hz,1H),8.95(br q,J=5Hz,1
H),9.12(d,J=2Hz,1H)IR(Nujol):1580,1530,1290,1270,1255cm-1
实例71
(1)回流7.0g(0.042mol)1,1-双(甲硫基)-2-硝基乙烯、4.5g N,O-二甲基羟胺盐酸盐和80mlEtOH的混合物,同时1小时滴加6.4ml Et3N(三乙胺)。滴加完毕后,混合物继续回流2小时。再浓缩反应混合物,滤出所得晶体。浓缩滤液,残余物进行硅胶柱色谱分离,用EtOH-CHCl3(1∶30)洗脱。得到1.0g 1-(N-甲基-N-甲氧基)氨基-1-甲硫基-2-硝基乙烯,为黄色油状物。NMR(CDCl3)δ:2.43(3H,s),3.26(3H,s),3.68
(3H,s),7.16(1H,s)
(2)回流0.8g(0.0045mol)1-(N-甲基-N-甲氧基)氨基-1-甲硫基-2-硝基乙烯、0.7g(6-氯-3-吡啶甲基)胺和30ml EtOH的混合物4小时,过滤收集所得晶体,干燥,得150mg晶体状标题化合物。m.p.:238-240℃(decompn.)NMR(DMSO-d6)δ:4.53(4H,d,J=5.7Hz),6.51(1
H,s),7.50(2H,d,J=8.7Hz),7.76(2H,
dd,J=8.7&2.4Hz),8.37(2H,d,J=2.4Hz),
9.7-10.8(2H,br)IR(Nujol):3240,1620,1575,1460,1395,1220
cm-1
实例72
(1)把2.4g(0.015mo1)2-氯-5-乙氨基吡啶溶于30ml甲苯中,再加3.4g异氰酸甲酯。混合物回流15小时。冷却后,过滤收集所得晶体,用少量乙醚洗,干燥,得3.0gN-(6-氯-3-吡啶基)-N-乙基-N ′-甲基脲,为淡黄色晶体。 m.p.:135-136℃NMR(CDCl3)δ:1.11(t,J=7Hz,3H),2.75(d,J=5
Hz,3H),3.72(q,J=7Hz,2H),4.36(br,1
H),7.40(d,J=8Hz,1H),7.59(dd,J=8&3
Hz,1H),8.28(d,J=3Hz,1H)
(2)在30ml乙腈中溶入1.5g(0.007mol)N-(6-氯-3-吡啶基)-N-乙基-N ′-甲基脲,再加入3.1g五硫化磷。混合物回流3小时。滤去不溶物,浓缩滤液,再用20ml水稀释。混合物用NaHCO3中和,用CH2Cl2(50ml×3)提取,提取液用MgSO4干燥。浓缩后,残余物用硅胶柱色谱法提纯,回收到0.52g N-(6-氯-3-吡啶基)-N-乙基-N′-甲基硫脲,为淡黄色晶体。
m.p.:110-111℃
NMR(CDCl3)δ:1.20(t,J=7Hz,3H),3.06(d,J=5
Hz,3H),4.22(q,J=7Hz,2H),5.42(br,1
H),7.40-7.70(m,2H),8.28(d,J=3Hz,1H)
(3)重复实例59的反应步骤(2),但是用N-(6-氯-3-吡啶基)-N-乙基-N′-甲基硫脲代替N-(6-氯-3-吡啶基)-N-甲基-N′-甲基硫脲,得S-甲基-N-(6-氯-3-吡啶基)-N-乙基-N′-甲基异硫脲,为淡黄色油状物。NMR(CDCl3)δ:1.06-1.43(m,3H),2.02&2.39
(each s,3H),3.03&3.30(each s,3H), 3.46-3.93(m,2H),6.90-7.53(m,2H),7.88&8.20(each d,J=3Hz,1H)
(4)重复实例59的反应步骤(3),但用S-甲基-N-(6-氯-3-吡啶基)-N-乙基-N′-甲基异硫脲代替S-甲基-N-(6-氯-3-吡啶基)-N-甲基-N′-甲基异硫脲,得标题化合物,为淡黄色晶体。m.p.:95-96℃NMR(CDCl3)δ:1.23(t,J=7Hz,3H),2.71(d,J=5
Hz,3H),3.75(q,J=7Hz,2H),6.67(s,1
H),7.26-7.53(m,2H),8.20(d,J=3Hz,1
H),10.05(br,1H)IR(Nujol):3100,1600,1505,1320,1220,1170,
1120,1020cm-1
实例73
1-〔N-(6-氯-3-吡啶基)-N-正丙基〕氨基-1-甲氨基-2-硝基乙烯(化合物91)
重复实例72的步骤(1)-(4),但用2-氯-5-正丙氨基吡啶代替2-氯-5-乙氨基吡啶,各步分别得到以下化合物:
(1)N-(6-氯-3-吡啶基)-N-正丙基-N′-甲基脲(淡黄色晶体)m.p.:84-85℃NMR(CDCl3)δ:0.87(t,J=7Hz,3H),1.26-1.80(m,
2H),2.75(d,J=5Hz,3H),3.62(t,J=7Hz,
2H),4.40(br,1H),7.38(d,J=8Hz,1H),
7.66(dd,J=8&3Hz,1H),8.28(d,J=3Hz,
1H)
(2)N-(6-氯-3-吡啶基)-N-正丙基-N ′-甲基硫脲(淡黄色晶体)m.p.:145-146℃NMR(CDCl3)δ:0.90(t,J=7Hz,3H),1.40-1.93
(m,2H),3.07(d,J=5Hz,3H),4.12(t,J=7
Hz,2H),5.33(br,1H),7.40-7.70(m,2H),
8.30(d,J=3Hz,1H)
(3)S-甲基-N-(6-氯-3-吡啶基)-N-正丙基-N′-甲基异硫脲(淡黄色油状物)NMR(CDCl3)δ:0.80-1.10(m,3H),1.40-1.90(m,2
H),2.01&2.37(each s,3H),3.00&3.28
(各为s,3H),3.36-3.83(m,2H),6.90-7.53
(m,2H),7.86&8.18(各为d,J=3Hz,1H)
(4)标题化合物(淡黄色晶体)m.p.:94-95℃NMR(CDCl3)δ:0.95(t,J=7Hz,3H),1.43-1.93
(m,2H),2.68(d,J=5Hz,3H),3.61(t,J=7
Hz,2H),6.69(s,1H),7.26-7.50(m,2H),
8.21(d,J=3Hz,1H),10.06(br,1H)IR(Nujol):3100,1590,1520,1360,1310,1225,
1120,1020cm-1
实例74
重复实例72步骤(1)-(4),但用2-氯-5-正丁氨基吡啶代替2-氯-5-乙氨基吡啶,各步分别得到下列化合物:
(1)N-正丁基-N-(6-氯-3-吡啶基)-N′-甲基脲(淡黄色油状)NMR(CDCl3)δ:0.86-1.06(m,3H),1.10-1.73(m,4
H),2.75(d,J=5Hz,3H),3.66(t,J=7Hz,2
H),4.30(d,J=5Hz,1H),7.40(d,J=8Hz,1
H),7.60(dd,J=8&3Hz,1H),8.29(d,J=3
Hz,1H)
(2)N-正丁基-N-(6-氯-3-吡啶基)-N′-甲基硫脲(淡黄色晶体)
(反应在甲苯中进行1小时)m.p.:129-130℃NMR(CDCl3)δ:0.90(t,J=7Hz,3H),1.10-1.83
(m,4H),3.07(d,J=5Hz,3H),4.15(t,J=7
Hz,2H),5.52(d,J=5Hz,1H),7.36-7.70
(m,2H),8.25(d,J=3Hz,1H)
(3)S-甲基-N-正丁基-N-(6-氯-3-吡啶基)-N ′-甲基异硫脲(淡黄色油状物)NMR(CDCl3)δ:0.80-1.06(m,3H),1.10-1.80(m,4
H),2.00&2.36(each s,3H),3.00&3.27
(each s,3H),3.42-3.82(m,2H),6.90-7.50
(m,2H),7.86&8.18(each d,J=3Hz,1H)
(4)标题化合物(淡黄色晶体)
m.p.:87-88℃
NMR(CDCl3)δ:0.93(t,J=7Hz,3H),1.10-1.85
(m,4H),2.68(d,J=5Hz,3H),3.65(t,J=7
Hz,2H),6.69(s,1H),7.26-7.52(m,2H),
8.21(d,J=3Hz,1H),10.05(br,1H)IR(Nujol):3100,1590,1520,1360,1310,1250,
1120,1020cm-1
实例75
1-〔N-(6-氯-3-吡啶基)-N-乙基〕氨基-1-乙氨基-2-硝基乙烯(化合物93)
重复实例59的步骤(1)-(3),但用2-氧-5-乙氨基吡啶和异硫氰酸乙酯分别代替2-氯-5-甲氨基吡啶和异硫氰酸甲酯,在相应步骤各得以下化合物:
(1)N-(6-氯-3-吡啶基)-N-乙基-N′-乙基硫脲(浅红色晶体)
(反应在甲苯中进行66小时)m.p.:84-86℃NMR(CDCl3)δ:1.11(3H,t,J=7.1Hz),1.19(3H,
t,J=7.2Hz),3.63(2H,dq,J=5.6&7.1Hz),
4.21(2H,q,J=7.1Hz),4.9-5.5(1H,m,
NH),7.4-7.7(2H,m),8.29(1H,d,J=2.4Hz)
(2)S-甲基-N-(6-氯-3-吡啶基)-N-乙基-N ′-乙基异硫脲(油状)
NMR(CDCl3)δ:1.0-1.6(6H,m),2.00&2.38(3H,
each s,),3.1-4.5(4H,m),6.8-7.6(2H,
m),7.7-8.5(1H,m)
(3)标题化合物(淡黄色晶体)
m.p:105℃
NMR(CDCl3)δ:1.0-1.5(6H,m),2.94(2H,dq,
J=5.2&7.0Hz),3.74(2H,q,J=7.1Hz),
6.65(1H,s),7.2-7.6(2H,m),8.1-8.4(1
H,m),9.6-10.2(1H,m,NH)
IR(Nujol):3110,1600cm-1
实例76
(1)重复实例59的反应步骤(1),但用3-甲氨基-5-三氟甲基吡啶代替2-氯-5-甲氨基吡啶(在甲苯中回流61.5小时),得N-甲基-N ′-甲基-N ′-(5 -三氟甲基-3-吡啶基)硫脲,为浅褐色晶体。m.p.:86-90℃NMR(CDCl3)δ:3.12(3H,d,J=4.2Hz),3.67(3H,
s),5.3-5.8(1H,m,NH),7.8-8.0(1H,m),
8.77(1H,d,J=2.1Hz),8.88(1H,br s)
(2)室温下搅拌0.2g(0.0008mol)N-甲基-N′-甲基-N′-(5-三氟甲基-3-吡啶基)硫脲、0.3g甲基碘和10ml CH3CN的混合物13.5小时。另加0.3g甲基碘,搅拌混合物18.5小时。浓缩反应混合物,残余物用50ml AcOEt和NaHCO3水溶液稀释。振荡后,分离混合物中各相。AcOEt层用NaCl水溶液洗,用MgSO4干燥,浓缩。得0.2g S-甲基-N-甲基-N′-甲基-N′-(5-三氟甲基-3-吡啶基)异硫脲粗油状物。
(3)回流0.2g S-甲基-N-甲基-N′-甲基-N′-(5-三氟甲基-3-吡啶基)异硫脲粗品和10ml CH3NO2的混合物36.5小时。浓缩反应混合物,对残余物进行硅胶柱色谱分离,用己烷-丙酮(2∶1)洗脱。得18mg标题化合物,为黄褐色晶体。m.p:114-115℃NMR(CDCl3)δ:2.81(3H,d,J=5.1Hz),3.36(3H,
s),6.63(1H,s),7.5-7.7(1H,m),8.5-8.7
(2H,m),9.6-10.1(1H,m,NH)
实例77
重复实例59步骤(1)-(3),但用异硫氰酸正丙酯代替异硫氰酸甲酯,各步分别得到下述化合物:
(1)N-(6-氯-3-吡啶基)-N-甲基-N′-正丙基硫脲(黄色油状)
(反应混合物在甲苯中回流121小时,产物用硅胶柱色谱法纯化)NMR(CDCl3)δ:0.86(3H,t,J=6.6Hz),1.2-1.8(2
H,m),3.63(3H,s),3.4-3.9(2H,m),
5.1-5.7(1H,br),7.45(1H,d,J=8.4Hz),
7.61(1H,dd,J=8.4&2.7Hz),8.34(1H,d,
J=2.7Hz)
(2)S-甲基-N-(6-氯-3-吡啶基)-N-甲基-N′-正丙基异硫脲(黄色油状)NMR(CDCl3)δ:〔主要成份…74%]0.96(3H,
t,J=7.5Hz),1.3-1.9(2H,m),2.03(3H,
s),3.28(3H,s),3.47(2H,t,J=7.5Hz),
7.25(1H,d,J=8.4Hz),7.45(1H,dd,J=8.4
&2.7Hz),8.23(1H,d,J=2.7Hz)[次要
成分(异构体)…26%]2.38(3H,s),3.14
(3H,s),3.0-3.4(2H,m),6.9-7.4(2H,m)
(3)标题化合物(油状物)
NMR(CDCl3)δ:0.93(3H,t,J=7.2Hz),1.59(2H,
tq,J=7.2&7.2Hz),2.95(2H,dt,J=6.0&
7.2Hz),3.30(3H,s),6.60(1H,s),
7.2-7.6(2H,m),8.23(1H,d,J=3.0Hz),
9.6-10.1(1H,br)
IR(neat):3110,2950,1595,1450,1360cm-1
实例78
(1)在130℃加热3.9g(0.0303mol)5-氨基-2-氯吡啶、5.0g 1,1-双(甲硫基)-2-硝基乙烯和80ml乙苯的混合物2小时。减压蒸去乙苯,晶形残余物用AcOEt洗,再用硅胶柱色谱法分离,用EtOH-CHCl3(1∶30)洗脱,回收粗晶体。此晶体用AcOEt重结晶,用乙醚洗,干燥,得到0.5g 1-(6-氯-3-吡啶基)氨基-甲硫基-2-硝基乙烯,为淡黄色晶体。m.p.:169-171℃MNR(CDCl3)δ:2.42(3H,s),6.70(1H,s),7.41
(1H,d,J=9.0Hz),7.65(1H,dd,J=9.0&
2.4Hz),8.41(1H,d,J=2.4Hz),11.3-11.8
(1H,br)
(2)将0.42g(0.00171mol)1-(6-氯-3-吡啶基)氨基-1-甲硫基-2-硝基乙烯溶于25ml EtOH中,再加入0.2g 40%的甲胺甲醇溶液。混合物回流1.5小时。蒸去溶剂,晶形残余物用AcOEt洗,干燥,得0.33g标题化合物,为白色晶体。m.p.:185℃(decompn.)NMR(DMSO-d6)δ:2.94(3H,d,J=5.4Hz),6.24(1
H,s),7.57(1H,d,J=9.0Hz),7.80(1H,
dd,J=9.0&2.7Hz),8.34(1H,d,J=2.7Hz),
8.8-9.7(1H,br),9.2-10.3(1H,br)IR(Nujol):3150,1635,1210cm-1
实例79
重复实例13步骤(1)-(3),但用N-甲基-N-(6-甲基-3-吡啶甲基)胺粗品代替N-乙基-N-(3-吡啶甲基)胺,各步分别得到下列化合物:
(1)N-甲基-N′-甲基-N′-(6-甲基-3-吡啶甲基)硫脲(浅粉红色晶体)m.p.:120-122℃NMR(CDCl3)δ:2.53(s,pyridine-Me),3.06(s,
MeNCH2),3.16(d,J=5Hz,
MeNH),5.16(s,
CH2),6.14(br q,J=5Hz,NH),7.15(d,J=8
Hz,1H),7.64(dd,J=8&2Hz,1H),8.40(d,
J=2Hz,1H)
(2)S-甲基-N-甲基-N′-甲基-N′-(6-甲基-3-吡啶甲基)异硫脲(油状)
NMR(CDCl3)δ:2.31(s,MeS),2.53(s,pyridine-Me),
2.81(s,
MeNCH2),3.25(s,NeN=),4.53(s,
CH2),7.11(d,J=8Hz,1H),7.48(dd,J=8&
2Hz,1H),8.40(d,J=2Hz,1H)
(3)标题化合物(黄色晶体)m.p.:102-103℃NMR(CDCl3)δ:2.57(s,pyridine-Me),2.80(s,
MeNCH2),3.08(d,J=5Hz,
MeNH),4.39(s,
CH2),6.54(s,=CHNO2),7.21(d,J=8Hz,1
H),7.48(dd,J=8&2Hz,1H),9.78(br,NH)IR(Nujol):1600,1550,1310,1250,1090cm-1
实例80
1-〔N-(6-氟-3-吡啶甲基)-N-甲基〕氨基-1-甲氨基-2-硝基乙烯(化合物98)
重复实例13步骤(1)-(3),但用N-(6-氟-3-吡啶甲基)-N-甲基胺粗品代替N-乙基-N-(3-吡啶甲基)胺,各步分别得下述化合物:
(1)N-(6-氟-3-吡啶甲基)-N-甲基-N′-甲基硫脲(无色油状)
(反应在CHCl3中进行过夜,产物用硅胶柱色谱法纯化)NMR(CDCl3)δ:3.04(3H,s,
MeNCH2),3.18(3H,
d,
MeNH),5.22(2H,s,CH2),6.88(1H,br,
NH),7.93(1H,dd,J=8.4&2.7Hz),8.54(1
H,ddd,J=8.4,2.4&8.4Hz),8.15(1H,d,
J=2.4Hz)
(2)S-甲基-N-(6-氟-3-吡啶甲基)-N-甲基-N′-甲基异硫脲(油状物)NMR(CDCl3)δ:2.30(3H,s,MeS),2.83(3H,s,
MeNCH2),3.24(3H,s,MeN=),4.53(2H,s,
CH2),6.90(1H,dd),7.72(1H,ddd),8.12
(1H,d)
(3)标题化合物(浅褐色晶体)m.p.:100-100.5℃NMR(CDCl3)δ:2.78(3H,s,
MeNCH2),3.07(3H,
d,
MeNH),4.39(2H,s,CH2),6.52(1H,s,
=CHNO2),7.00(1H,dd,J=8.4&2.7Hz),7.71
(1H,ddd,J=8.4,2.4&8.4Hz),8.14(1H,
d,J=2.4Hz),9.74(1H,br,NH)IR(Nujol):1593,1548,1477,1465,1437,1405,
1390,1310,1250,1230,1165,1083,1029cm-1
实例81
1-〔N-乙基-N-(6-氟-3-吡啶甲基)〕氨基-1-甲氨基-2-硝基乙烯(化合物99)
(1)把4.2g 70%乙胺水溶液溶于30ml CH3CN中,在冰冷却下滴加3.0g(按纯物质计为0.016mol)(6-氟-3-吡啶基)甲基溴粗品。室温下静置混合物过夜,蒸去CH3CN。残余物用20ml水稀释,用CHCl3(30ml)提取。提取液用MgSO4干燥,蒸去CHCl3,回收得1.38g红色油状物。将油状物溶于30ml CHCl3中,再加入0.68g异硫氰酸甲酯。混合物室温搅拌3小时。用活性炭处理反应混合物,浓缩之。对残余物进行硅胶柱色谱分离,用AcOEt-己烷(3.5∶1)洗脱。得0.6g N-乙基-N-(6-氟-3-吡啶甲基)-N ′-甲基硫脲,为无色晶体。m.p.:123-124℃NMR(CDCl3)δ:1.18(3H,t,CH2CH3),3.19(3H,
d,
MeNH),3.48(2H,q,CH2CH3),5.15(2H,
s,pyridine-CH2),5.70(1H,br,NH),6.92(1
H,dd,J=8.4&2.7Hz),7.96(1H,ddd,
J=8.4,2.4&8.4Hz),8.15(1H,d,J=2.4Hz)
(2)重复实例13的反应步骤(2),但是用N-乙基-N-(6-氟-3-吡啶甲基)-N′-甲基硫脲代替N-甲基-N ′-乙基-N′-(3-吡啶甲基)硫脲,得到S-甲基-N-乙基-N-(6-氟-3-吡啶甲基)-N′-甲基异硫脲,为浅褐色油状物。NMR(CDCl3)δ:1.08(3H,t,CH2CH3),2.29(3H,
s,MeS),3.22(3H,s,MeN=),3.36(2H,q,
CH2CH3),4.49(2H,s,CH2),6.87(1H,dd),
7.71(1H,ddd),8.11(1H,d)
(3)重复实例13的反应步骤(3),但是用S-甲基-N-乙基-N-(6-氟-3-吡啶甲基)-N ′-甲基异硫脲代替S-甲基-N-甲基-N′-乙基-N′-(3-吡啶甲基)异硫脲,得油状标题化合物。NMR(CDCl3)δ:1.19(3H,t,CH2CH3),3.08(3H,
d,
MeNH),3.16(2H,q,CH2CH3),4.37(2H,
s,CH2),6.54(1H,s,=CHNO2),6.98(1H,
dd,J=8.4&2.7Hz),7.80(1H,ddd,J=8.4,
2.4&8.4Hz),8.15(1H,d,J=2.4Hz)IR(neat):3230,1593,1510,1480,1395,1335,
1235,1120,1020cm-1
实例82
重复进行实例13的步骤(1)-(3),只是用N-(6-溴-3-吡啶甲基)-N-甲基胺粗品代替N-乙基-N-(3-吡啶甲基)胺,各步分别得以下化合物:
(1)N-(6-溴-3-吡啶甲基)-N-甲基-N′-甲基硫脲(白色晶体)
(产物用硅胶柱色谱法纯化)m.p.:107-108℃NMR(CDCl3)δ:3.04(3H,s),3.18(3H,d,J=4.8
Hz),5.19(2H,s),5.6-6.1(1H,br),7.46
(1H,d,J=8.4Hz),7.66(1H,dd,J=8.4&
2.4Hz),8.29(1H,d,J=2.4Hz)
(2)S-甲基-N-(6-溴-3-吡啶甲基)-N-甲基-N′-甲基异硫脲(无色油状)
NMR(CDCl3)δ:2.29(3H,s),2.84(3H,s),3.23
(3H,s),4.50(2H,s),7.3-7.6(2H,m),
8.29(1H,d,J=2.4Hz)
(3)标题化合物(浅褐色晶体)m.p.:130-131℃NMR(CDCl3)δ:2.80(3H,s),3.06(3H,d,J=5.4
Hz),4.36(2H,s),6.51(1H,s),7.35-7.70
(2H,m),8.2-8.4(1H,m),9.4-10.0(1H,
br)IR(Nujol):3200,1580,1390,1280,1245,1205,
1075cm-1
实例83
1-〔N-(6-溴-3-吡啶甲基)-N-乙基〕氨基-1-甲氨基-2-硝基乙烯(化合物101)
重复实例13步骤(1)-(3),但用N-(6-溴-3-吡啶甲基)-N-乙基胺粗品代替N-乙基-N-(3-吡啶甲基)胺,各步分别得到的化合物如下:
(1)N-(6-溴-3-吡啶甲基)-N-乙基-N′-甲基硫脲(淡黄色晶体)m.p.:130-131℃NMR(CDCl3)δ:1.18(3H,t,J=7.8Hz),3.18(3H,
d,J=5.0Hz),3.46(2H,q,J=7.8Hz),5.12
(2H,s),5.5-6.0(1H,br),7.46(1H,d,
J=8.7Hz),7.69(1H,dd,J=8.7&2.1Hz),
8.29(1H,d,J=2.1Hz)
(2)S-甲基-N-(6-溴-3-吡啶甲基)-N-乙基-N ′-甲基异硫脲(黄色油状物)NMR(CDCl3)δ:1.08(3H,t,J=6.3Hz),2.29(3H,
s),3.21(3H,s),3.36(2H,q,J=6.3Hz),
4.46(2H,s),7.3-7.6(2H,m),8.28(1H,
br s)
(3)标题化合物
(反应进行38小时)
m.p.:79-80℃
NMR(CDCl3)δ:1.18(3H,t,J=6.3Hz),3.06(3H,
d,J=5.7Hz),3.16(2H,q,J=6.3Hz),4.34
(2H,s),6.53(1H,s),7.3-7.7(2H,m),
8.30(1H,br s),9.5-10.1(1H,br q,J=5.7
Hz)
IR(Nujol):3200,1580,1240,1080cm-1
实例84
重复实例13步骤(1)-(3),只是用N-(2-氯-5-噻唑甲基)-N-甲基胺粗品代替N-乙基-N-(3-吡啶甲基)胺,各步分别得到的化合物如下:
(1)N-(2-氯-5-噻唑甲基)-N-甲基-N ′-甲基硫脲(白色-浅褐色晶体)
(用硅胶柱纯化)m.p.:129-131℃NMR(CDCl3)δ:3.06(s,
MeNCH2),3,16(d,J=4Hz,
MeNH),5.21(s,CH2),5.83(br,NH),7.48(s,
噻唑-H)
(2)S-甲基-N-(2-氯-5-噻唑甲基)-N-甲基-N′-甲基异硫脲(黄色油状物)NMR(CDCl3)δ:2.30(s,MeS),2.90(s,
MeNCH2),
3.24(s,MeN=),4.50(s,CH2),7.39(s,
噻唑-H)
(3)标题化合物(浅褐色晶体)m.p.:131-133℃NMR(CDCl3)δ:2.84(s,
MeNCH2),3.09(d,J=5Hz,
MeN=),4.49(s,CH2),6.51(s,=CHNO2),7.50
(s,噻唑-H),9.66(br,NH)IR(Nujol):1585,1395,1260,1070,1050,1025
cm-1
实例85
重复实例13步骤(1)-(3),但是用N-(2-氯-5-噻唑甲基)-N-乙基胺代替N-乙基-N-(3-吡啶甲基)胺,各步分别得到的化合物如下:
(1)N-(2-氯-5-噻唑甲基)-N-乙基-N′-甲基硫脲(白色晶体)m.p.:116-118℃NMR(CDCl3)δ:1.19(t,J=7Hz,CH2CH3),3.16(d,
J=4Hz,
MeNH),3,44(q,J=7Hz,CH2CH3),5.15
(s,噻唑-CH2),5.79(br,NH),7.47
(噻唑-H)
(2)S-甲基-N-(2-氯-5-噻唑甲基)-N-乙基-N′-甲基异硫脲(油状物)NMR(CDCl3)δ:1.11(t,J=7Hz,CH2CH3),2.28(s,
MeS),3.26(s,MeN),3.40(q,J=7Hz,
CH2CH3),4.50(s,噻唑-CH2),7.39(s,
噻唑-H)
(3)标题化合物(浅褐色晶体)
(反应进行24小时)
m.p.:91-92℃
(该产物用AcOEt-己烷重结晶,得到m.p.为110-112℃的产物〕
NMR(CDCl3)δ:1.18(t,J=7Hz,CH2CH3),3.07(d,
J=5Hz,
MeNH),3.17(q,J=7Hz,CH2CH3),4,46
(s,噻唑-CH2),6.52(s,=CHNO2),7.47(s,
噻唑-H),9.75(br,NH)
IR(Nujol):1585,1450,1405,1360,1255,1225,
1050cm-1
实例86
回流0.60g(0.0037mol)1-二甲氨基-1-甲硫基-2-硝基乙基、0.55g 2-氯-5-噻唑甲基胺和30mlEtOH的混合物1.5小时。冷却后,滤去析出的1-N-(2-氯-5-噻唑甲基)氨基-1-甲硫基-2-硝基乙烯晶体(0.2g),滤液浓缩后进行硅胶柱色谱分离,用EtOH-CHCl3(1∶10)洗脱。得0.07g化合物104和0.034g化合物105。
(1-(2-氯-5-噻唑甲基)氨基-1-甲硫基-2-硝基乙烯)m.p.:150-152℃NMR(CDCl3)δ:2.49(3H,s),4.78(2H,d,J=6.0
Hz),6.58(1H,s),7.52(1H,s),10.3-10.8
(1H,br)
(化合物104)m.p.:101-102℃NMR(CDCl3)δ:2.97(6H,s),4.58(2H,d,J=6.3
Hz),6.51(1H,s),7.50(1H,s),9.3-9.8(1
H,br)IR(Nujol):3100,1585,1380,1255,1030cm-1
(化合物105)
m.p.:211℃(decompn.).
NMR(DMSO-d6)δ:4.5-4.8(4H,m),6.63(1H,s),
7.63(2H,s)
IR(Nujol):3120,1610,1210,1040cm-1
实例87
1-(2-氯-5-噻唑甲基)氨基-1-甲氨基-2-硝基乙烯(化合物106)
在70℃加热25ml EtOH与0.19g(0.00072mol)1-N-(2-氯-5-噻唑甲基)氨基-1-甲硫基-2-硝基乙烯(按实例86制得)的混合物。然后加入0.1g 40%甲胺水溶液,混合物在70℃搅拌半小时。蒸去EtOH,加入AcOEt后滤出晶形残余物,干燥之。得0.12g标题化合物,为白色晶体。m.p.:181℃(decompn.)NMR(DMSO-d6)δ:2.83(3H,d,J=5.1Hz),4.63(2
H,d,J=6.3Hz),6.57(1H,s),7.66(1H,
s),7.3-8.1(1H,br),9.6-10.4(1H,br)IR(Nujol):3140,1620,1415,1210cm-1
实例88
1-(6-氯-3-吡啶甲基)氨基-1-二甲氨基-2-硝基乙烯(化合物46)(1)室温下搅拌4.32g(0.0303mol)6-氯-3-吡啶甲基胺,20ml水、1.78g NaOH的混合物,滴加2.37ml二硫化碳、滴加完成后,在50℃继续搅拌混合物1小时。用冰水冷却后,在约5℃滴加3.49ml氯甲酸乙酯。滴加完成后,在50℃搅拌混合物1小时。冷却后,用NaCl将反应混合物饱和,用乙醚(50ml×3)提取,提取液用MgSO4干燥。再蒸去乙醚,回收到5.38g异硫氰酸(6-氯-3-吡啶基)甲酯粗品,为油状物。 NMR(CDCl3)δ:4.77(s,CH2),7.39(d,J=8Hz,1
H),7.70(dd,J=8&2Hz,1H),8,36(d,J=2
Hz,1H)
(2)在冰水冷却下搅拌5.16g 50%二甲胺水溶液和30ml CH3CN的混合物。然后向其中滴加5.29g(0.0287mol,按纯产品计)异硫氰酸(6-氯-3-吡啶基)甲酯在30mlCH3CN中的溶液。滴加完成后,室温搅拌混合物15分钟,蒸去CH3CN,残余物用NaCl水溶液稀释,再用CH2Cl2(50ml×3)提取。提取液用硫酸镁干燥,蒸去CH2Cl2,得到晶体。加入乙醚后,过滤收集晶体,干燥,用AcOEt重结晶。得到3.82g N-(6-氯-3-吡啶甲基)-N′-二甲基硫脲,为黄色晶体。m.p.:139-141℃NMR(CDCl3)δ:3.27(s,Me2N),4.88(d,J=5Hz,
CH2),6.17(br t,J=5Hz,NH),7.27(d,J=8
Hz,1H),7.76(dd,J=8&2Hz,1H),8.25
(d,J=2Hz,1H)
(3)向3.00g(0.03mol)N-(6-氯-3-吡啶甲基)-N′-二甲基硫脲中加入32ml无水THF,再加入0.52g60%NaH。混合物在50℃搅拌15分钟。用冰水冷却后,滴加0.814ml甲基碘,混合物在室温下搅拌20分钟。蒸去THF,残余物用NaCl水溶液稀释,再用AcOEt(50ml×3)提取。提取液用MgSO4干燥,蒸去AcOEt。得3.30g S-甲基-N-(6-氯-3-吡啶甲基)-N′-二甲基异硫脲粗品,为油状物。NMR(CDCl3)δ:2.30(s,MeS),2.98(s,Me2N),4.69
(s,CH2),7.25(d,J=8Hz,1H),7.65(dd,
J=8&2Hz,1H),8.37(d,J=2Hz,1H)
(4)向3.24g(含0.0133mol纯物质)S-甲基-N-(6-氯-3-吡啶甲基)-N′-二甲基异硫脲粗品中加入14.5ml CH3NO2,混合物回流搅拌14.5小时。然后蒸去CH3NO2,残余物进行硅胶(240g)柱色谱分离,用MeOH-CHCl3(1∶5)洗脱,回收到-油状物。将此油状物溶于AcOEt中,蒸去AcOEt,静置残余物,析出晶体。加入乙醚后,过滤收集晶体,用乙醚洗,干燥。得2.30g标题化合物,为淡黄色晶体。此产物的熔点、NMR及IR谱和TLS Rf值与实例28制得的化合物46一致。
实例89
1-(6-氯-3-吡啶基)氨基-1-二甲氨基-2-硝基乙烯(化合物107)
在110-120℃加热搅拌1.5g(0.0093mol)1-二甲氨基-1-甲硫基-2-硝基乙烯与1.1g 5-氨基-2-氯吡啶的混合物1小时。冷却后,对反应混合物进行硅胶柱色谱分离,用EtOH-CHCl3(1∶40)洗脱,回收到0.38g标题化合物,为浅褐色晶体。此产物的NMR谱表明它是标题化合物与N2-(6-氯-3-吡啶基)-N′-二甲基-2-硝基乙脒的1∶1混合物。m.p.:122-123℃NMR(CDCl3)δ:2.86(3H,s),3.10(3H,s),5.17
(1H,s),6.68(0.5H,s),7.09(0.5H,dd,
J=9.0&2.7Hz),7.24(0.5H,d,J=9.0Hz),
7.3-7.6(1H,m),7.86(0.5H,d,J=2.7Hz),
8.22(0.5H,d,J=2.7Hz),10.8-11.2(0.5H,
br)IR(Nujol):3100,1395,1280cm-1
实例90
1-〔N-(6-甲氧基-3-吡啶基)-N-甲基〕氨基-1-甲氨基-2-硝基乙烯(化合物108)
重复实例59步骤(1)-(3),但用2-甲氧基-5-甲氨基吡啶代替2-氯-5-甲氨基吡啶,各步分别得到下列化合物:
(1)N-(6-甲氧基-3-吡啶基)-N-甲基-N′-甲基硫脲(白色晶体)
(反应在甲苯中进行)m.p.:115.5-116℃NMR(CDCl3)δ:3.06(3H,d,J=4.5Hz),3.65(3H,
s),3.97(3H,s),5.2-5.8(1H,m,NH),6.86
(1H,d,J=8.7Hz),7.46(1H,dd,J=9.0&
3.0Hz),8.08(1H,d,J=2.4Hz)
(2)S-甲基-N-(6-甲氧基-3-吡啶基)-N-甲基-N′-甲基异硫脲(淡黄色油状物)NMR(CDCl3)δ:2.01(3H,s),3.18(3H,s),3.28
(3H,s),3.93(3H,s,),6.72(1H,d,J=9.0
Hz),7.43(1H,dd,J=9.0&3.0Hz),8.02(1
H,d,J=2.4Hz)
(3)标题化合物(淡黄色晶体)
(反应进行16小时)
m.p.:131-132℃
NMR(CDCl3)δ:2.65(3H,d,J=5.4Hz),3.27(3H,
s),3.96(3H,s),6.07(1H,s),6.82(1H,
d,J=9.0Hz),7.43(1H,dd,J=8.4&3.0Hz),
8.04(1H,d,J=2.7Hz),9.8-10.4(1H,m)IR(Nujol):3130,1590cm-1
实例91
在90-100℃加热搅拌2.0g(0.0087mol)S-甲基-N-(6-氯-3-吡啶基)-N-甲基-N′-甲基异硫脲与4.0g硝基乙酸乙酯的混合物6小时。冷却后,加入少量丙酮,过滤收集所得晶体,用丙酮洗,干燥之,得0.3g标题化合物,为白色晶体。蒸去滤液中的丙酮,残余物在90-100℃再加热搅拌16小时,又得-部分(0.2g)标题化合物。
m.p.:225-227℃(decompn.)
NMR(DMSO-d6)δ:1.10(3H,t,J=6.9Hz),2.89(3
H,s),3.45(3H,s),3.93(2H,q,J=7.3
Hz),7.60(1H,d,J=8.4Hz),7.75(1H,dd,
J=8.1&2.7Hz),8.30(1H,d,J=2.1Hz),
9.31(1H,br s)
IR(Nujol):3190,1675,1630cm-1
实例92
重复实例46的反应步骤,但是用1-〔N-(6-氯-3-吡啶甲基)-N-甲基〕氨基-1-甲氨基-2-硝基乙烯代替1-甲氨基-1-〔N-甲基-N-(3-吡啶甲基)〕氨基-2-硝基乙烯,得标题化合物,为黄色树脂块状物。NMR(DMSO-d6)δ:2.92(s,3H),3.03(s,3H),
4.60(br,2H),6.86(s,1H),7.48(d,J=8
Hz,1H),7.80(dd,J=8&2Hz,1H),8.23
(s,1H),8.38(d,J=2Hz,1H)IR(neat):1690,1560,1490,1350,1270,1100cm-1
实例93
重复实例46的反应步骤,但是用1-〔N-(6-氯-3-吡啶甲基)-N-乙基〕氨基-1-甲氨基-2-硝基乙烯代替1-甲氨基-1-〔N-甲基-N-(3-吡啶甲基)〕氨基-2-硝基乙烯,得标题化合物,为黄色树脂块状物。NMR(DMSO-d6)δ:1.13(t,J=7Hz,3H),3.00(s,3
H),3.10-3.53(m,2H),4.60(br,2H),6.96
(s,1H),7.48(d,J=8Hz,1H),7.82(dd,
J=8&2Hz,1H),8.20(s,1H),8.39(d,J=2
Hz,1H)IR(neat):1685,1560,1480,1340,1240,1100cm-1
实例94
1-〔N-(6-氯-3-吡啶基)-N-甲基〕氨基-1-(N-甲酰基-N-甲基)氨基-2-硝基乙烯(化合物112)
重复实例46的反应步骤,但是用1-〔N-(6-氯-3-吡啶基)-N-甲基〕氨基-1-甲氨基-2-硝基乙烯代替1-甲氨基-1-〔N-甲基-N-(3-吡啶甲基)〕氨基-2-硝基乙烯,得标题化合物,为淡黄色晶体。m.p.:134-135℃NMR(DMSO-d6)δ:2.73&2.89(each s,3H),3.32&
3.39(each s,3H),7.03&7.10(each s,1
H),7.46&7.57(各为d,J=8Hz,1H),7.83&
7.92(各为dd,J=8&2Hz,1H),8.35&8.70
(each s,1H),8.37&8.44(各为d,J=2Hz,1
H)IR(Nujol):1685,1560,1305,1280,1250,1135
cm-1
实例95
1-〔N-(6-氯-3-吡啶甲基)-N-甲酰〕氨基-1-二甲氨基-2-硝基乙烯(化合物113)
重复实例46的反应步骤,但是用1-N-(6-氯-3-吡啶甲基)氨基-1-二甲氨基-2-硝基乙烯代替1-甲氨基-1-〔N-甲基-N-(3-吡啶甲基)〕氨基-2-硝基乙烯,得标题化合物,为淡黄色晶体。m.p.:105-106℃NMR(DMSO-d6)δ:2.93(s,6H),4.33-5.10(m,2
H),6.72(s,1H),7.42(d,J=8Hz,1H),
7.80(dd,J=8&2Hz,1H),8.23(s,1H),
3.36(d,J=2Hz,1H)IR(Nujol);1700,1565,1490,1350,1270,1205,
1100cm-1
实例96
1-N-(6-氯-3-吡啶甲基)氨基-1-(N-甲酰基-N-甲基)氨基-2-硝基乙烯(化合物114)与1-〔N-(6-氯-3-吡啶甲基)-N-甲酰基〕氨基-1-甲氨基-2-硝基乙烯(化合物115)的7∶3混合物(化合物114)(化合物115)
在10ml DMF(二甲基甲酰胺)中悬浮0.1g 60%NaH(事先用石油醚洗过),然后滴加0.6g(0.0025mol)1-N-(6-氯-3-吡啶甲基)氨基-1-甲氨基-2-硝基乙烯在5m1 DMF中的溶液。混合物室温搅拌1小时。冷却后,加0.7g甲乙酐,混合物于冷水冷却下搅拌5小时,再于室温下搅拌20小时。减压蒸去DMF,残余物用20ml NaHCO3饱和水溶液稀释,并用CH2Cl2(20ml×3)提取。提取液用MgSO4干燥,蒸去CH2Cl2。最后对残余物进行硅胶柱色谱分离,用EtOH-CHCl3(1∶10)洗脱。得0.15g标题化合物(化合物114和化合物115)的7∶3混合物,为白色晶体。m.p.:80-85℃NMR(DMSO-d6)δ:(化合物114)3.05(s,3H),
4.53(d,J=6Hz,2H),6.76(s,1H),7.49
(d,J=8Hz,1H),7.86(dd,J=8&2Hz,1H),
8.30(s,1H),8.42(d,J=2Hz,1H),9.45
(br,1H)(化合物115)2.95(d,J=5Hz,3
H),4.83(s,2H),6.66(s,1H),7.46(d,
J=8Hz,1H),7.86(dd,J=8&2Hz,1H),
8.30(s,1H),8.42(d,J=2Hz,1H),9.45
(br,1H)IR(Nujol):3200,3100,1685,1600,1340,1250,
1080,1040cm-1
实例97
在75-80℃加热搅拌1.4g(0.0061mol)S-甲基-N-(6-氯-3-吡啶甲基)-N′-甲基异硫脲(在实例64步骤(2)中制得)与2.7g硝基乙酸乙酯的混合物3小时。冷却后,过滤收集晶体,用CH3CN洗,干燥之。得1.1g标题化合物,为白色晶体。m.p.:231-233℃(decompn.)NMR(DMSO-d6)δ:1.07(3H,t,J=7Hz),2.86(3H,
br s),3.94(2H,q,J=7Hz),4.47(2H,br
s),7.51(1H,d,J=8Hz),7.82(1H,dd,J=8
&2.7Hz),8.38(1H,d,J=2.7Hz),9.10-9.60
(2H,brs)IR(Nujol):3250,1660,1500,1320,1230cm-1
实例98
1-(6-氯-3-吡啶甲基)氨基-1-甲氨基-2-甲磺酰硫代氨基甲酰-2-硝基乙烯(化合物117)
将0.50g(0.002mol)1-(6-氯-3-吡啶甲基)氨基-1-甲氨基-2-硝基乙烯溶于50ml CH3CN中,然后加0.30g(0.002mol)异硫氰酸甲磺酰基酯。混合物室温下搅拌2小时。蒸去CH3CN,残余物用硅胶柱色谱法提纯。得0.25g标题化合物黄色晶体。m.p.:129-131℃NMR(DMSO-d6)δ:2.76-3.00(各为d,MeN),3.51&
3.55(各为s,MeSO2),4.36-4.70(各为d),
12.20-13.23(各为s)IR(Nujol):3200,1640,1340,1140,920cm-1
实例99
1-N-(6-溴-3-吡啶甲基)氨基-1-甲氨基-2-硝基乙烯(化合物118)
除了用6-溴-3-吡啶甲胺代替N-乙基-N-(3-吡啶甲基)胺外,重复实例13的步骤(1)、(2)和(3),各步分别得到下列化合物。
(1)N-(6-溴-3-吡啶甲基-N′-甲基烷脲(白色晶状)
(使用Et2O-THF(3∶1)作为反应溶剂)m.p.:117-118℃NMR(DMSO-d6)δ:2.85(d,J=5Hz,MeN),4.67(d,J=6Hz,CH2N),7.54(d,J=8Hz,1H),7.6(br,MeNH),7.69(dd,J=8&2Hz,1H),7.93(t,J=6Hz,CH2NH),8.32(d,J=2Hz,1H)
(2)S-甲基-N-(6-溴-3-吡啶甲基)-N′-甲基-异硫脲(黄色油状)NMR(CDCl3)δ:2.40(s,MeS),2.93(s,MeN=),4.34(br,NH),4.47(S,CH2N),7.42(d,J=8Hz,1H),7.61(dd,J=8&2Hz,1H),8.36(d,J=2Hz,1H)
(3)标题化合物(浅棕色晶状)NMR(DMSO-d6)δ:2.87(br.MeN),4.47(d,J=6Hz,CH2N),6.46(s,=CHNO2),7.61(d,J=8Hz,1H),7.72(dd,J=8&2Hz,1H),8.40(d,J=2Hz,1H)IR(Nujol):1615,1575,1555,1370,1230,1200cm-1
实例100
除了用1-N-(6-溴-3-吡啶甲基)氨基-1-甲氨基-2-硝基乙烯代替1-N-(6-氯-3-吡啶甲基)氨基-2-硝基乙烯外,重复实例96的反应步骤。往通过用硅胶柱色谱提纯得到的油状物中加入少量AcOEt和Et2O,接着用干冰丙酮浴冷却,得到浅棕色粉末状的标题化合物(化合物119和化合物120)的混合物(90∶10)。浓缩滤液,得到标题化合物(化合物119和化合物120)的混合物(40∶60),为粘性产物。
(化合物119和120的90∶10的混合物)m.p.:115-127℃NMR(CDCl3)δ:(Compound 119)3.13(s,MeN),4.48(d,J=6Hz,CH2N),6.57(s,=CHNO2),7.53(m,2H,pyridine-H2)8.33(S,2H,CHO and pyridine-H),9.46(br,NH)IR(Nujol):1690,1620,1250,1240,1080cm-1
(化合物119和120的40∶60的混合物)NMR(CDCl3)δ:(Compound 120)3.01(d,J=5Hz,MeN),4.73(s,CH2N),6.36(s,=CHNO2),7.53(br s,2H,pyridine-H2),8.34(br s,2H,CHO and pyridine-H1),9.35(br,NH)IR(neat):1680,1605,1450,1350,1250,1080cm-1
实例101
1-〔N-(2-氯-5-噻唑甲基-N-甲基)氨基-1-(N-甲酰基-N-甲基)氨基-2-硝基乙烯(化合物121)
除了用1-〔N-(2-氯-5-噻唑甲基-N-甲基〕氨基-1-甲氨基-2-硝基乙烯代替1-甲氨基-1-〔N-甲基-N-(3-吡啶甲基)-氨基-2-硝基乙烯外,重复实例46的反应步骤,得到浅黄色树脂状的标题化合物。NMR(DMSO-d6)δ:2.92(s,3H,
MeNCH2),2.99(s,3H,
MeNCHO),4.74(br s,2H,CH2),6.90(s,1H,=CHNO2),7.71(s,1H,thiazole-H),8.19(s,1H,CHO)IR(neat):1695,1565,1490,1340,1270,1042cm-1
实例102
除了用1-〔N-(2-氯-5-噻唑基甲基)-N-乙基〕氨基-1-甲氨基-2-硝基乙烯代替1-甲氨基-1-〔N-甲基-N-(3-吡啶甲基)〕氨基-2-硝基乙烯外,重复实例46的反应步骤,得到黄色晶状的标题化合物。m.p.:99-100℃.NMR(DMSO-d6)δ:1.15(t,3H,CH2CH3),2.98(s,3H,MeN),3.32(q,2H,CH2CH3),4.76(br s,2H,thiazole-CH2),7.02(s,1H,=CHNO2),7.72(s,1H,thiazole-H),8.17(s,1H,CHO)IR(Nujol):1698,1577,1557,1470,1448,1352,1315,1270,1053cm-1
实例103
除了用1-N-(2-氯-5-噻唑甲基)氨基-1-甲氨基-2-硝基乙烯代替1-N-(6-溴-3-吡啶甲基)氨基-1-甲氨基-2-硝基乙烯外,重复实例100的反应步骤,得到晶状的标题化合物(化合物124)和粘性标题化合物(化合物123和化合物124)的混合物(70∶30)。
(化合物124)m.p.:125-126℃NMR(CDCl3)δ:3.01(3H,d,J=6.0Hz),4.82(2H,s),6.38(1H,s),7.49(1H,s),8.30(1H,s),9.0-9.6(1H,br)IR(Nujol):3220,1675,1620,1245,1100,1050cm-1
(化合物123和124的70∶30的混合物)NMR(CDCl3)δ:(Compound 123) 3.16(3H,s),4.63(2H,d,J=5.7Hz),6.57(1H,s),7.49(1H,s),8.35(1H,s),9.1-9.6(1H,br)IR(neat):3220,1680,1605,1480,1250,1045cm-1
实例104
除了用1-〔N-(6-溴-3-吡啶甲基)-N-甲基〕氨基-1-甲氨基-2-硝基乙烯代替1-甲氨基-1-〔N-甲基-N-(3-吡啶甲基)〕氨基-2-硝基乙烯外,重复实例46的反应步骤,得到黄色树脂状的标题化合物。
(使用THF-DMF作反应溶剂)NMR(DMSO-d6)δ:2.93(s,3H),3.02(s,3H),4.3-4.9(m,2H)6.87(s,=CHNO2),7.68(br s,2H),8.23(s,CHO),8.3-8.5(m,1H)IR(neat):1685cm-1
实例105
除了用1-〔N-(6-溴-3-吡啶甲基)-N-乙基〕氨基-1-甲氨基-2-硝基乙烯代替1-甲氨基-1-〔N-甲基-N-(3-吡啶甲基)〕氨基-2-硝基乙烯外,重复实例46的反应步骤,得到黄色晶状的标题化合物。m.p.:105-108℃NMR(DMSO-d6)δ:1.13(t,J=7.2Hz,3H),3.00(s,3H),3.1-3.7(m,2H),4.3-4.9(m,2H),6.97(s,=CHNO2),7.5-7.9(m,2H),8.21(s,CHO),8.38(br s,1H)IR(Nujol):1705cm-1
实例106
除了用6-溴-3-吡啶甲胺代替6-氯-3-吡啶甲胺外,重复实例48的步聚(1),(2),(3)和(4),各步分别得到下列化合物。
(1) 异硫氰酸(6-溴-3-吡啶)甲酯(黄色油状)
(在添加氯甲酸乙酯后,在50℃搅拌混合物4小时)NMR(CDCl3)δ:4.73(s,2H),7.43-7.70(m,2H),8.35(brs,1H)
(2) N-(6-溴-3-吡啶甲基)-N′-二甲基硫脲(白色晶状)
(用EtOH-CHCl3(1∶10)作洗脱剂,用硅胶柱色谱法提纯产物)m.p.:124-125℃NMR(CDCl3)δ:3.27(s,6H),4.85(d,J=5Hz,2H),6.32(brt,J=5Hz,1H),7.40(d,J=8Hz,1H),7.66(dd,J=8&2Hz,1H),8.21(d,J=2Hz,1H)
(3) S-甲基-N-(6-溴-3-吡啶甲基)-N′-二甲基异硫脲(黄色油状)NMR(CDCl3)δ:2.30(s,3H),3.00(s,6H),4.66(s,2H),7.38(d,J=8Hz,1H),7.55(dd,J=8&2Hz,1H),8.35(d,J=2Hz,1H)
(4) 标题化合物(浅黄色晶状)
(反应进行20小时,用硅胶柱色谱提纯产物,用CH3CN重结晶)
m.p.:158-159℃NMR(CDCl3)δ:2.92(s,6H),4.45(d,J=6Hz,2H),6.50(s,1H),7.48(d,J=8Hz,1H),7.60(dd,J=8&2Hz,1H),8.33(d,J=2Hz,1H),9.70(br,1H)IR(Nujol):3100,1580,1550,1440,1300,1260,1040cm-1
实例107
除了用1-N-(6-溴-3-吡啶甲基)氨基-1-二甲氨基-2-硝基乙烯代替1-甲氨基-1-〔N-甲基-N-(3-吡啶甲基)〕氨基-2-硝基乙烯外,重复实例46的步骤,得到浅黄色晶状标题化合物。
(反应在DMF中进行)m.p.:96-97℃NMR(DMSO-d6)δ:2.92(s,6H),4.30-5.06(m,2H),6.73(s,1H),7.50-7.80(m,2H)8.23(s,1H),8.35(br s,1H)IR(Nujol):1700,1565,1490,1345,1270,1080cm-1
实例108
除了用N-(6-溴-3-吡啶甲基)-N-甲胺代替N-(6-氯-3-吡啶甲基)-N-乙胺外,重复实例40的步骤(1)和(2),各步分别得到下列化合物。
(1) 1-〔N-(6-溴-3-吡啶甲基)-N-甲基〕氨基--甲硫基-2-硝基乙烯(黄色油状)
(反应进行3.5小时)NMR(CDCl3)δ:2.47(s,3H),3.03(s,3H),4.73(s,2H),6.76(s,1H),7.36-7.60(m,2H),8.30(br s,1H)
(2) 标题化合物
(反应在MeOH中进行1小时,过滤收集沉淀的晶体)m.p.:206-207℃NMR(DMSO-d6)δ:3.03(s,3H),4.63(s,2H),6.60(s,1H),7.43-7.80(m,2H),8.30(br s,1H),8.88(br,2H)IR(Nujol):3260,3140,1620,1575,1420,1290,1220cm-1
实例109
1-N-(2-氯-5-噻唑甲基)氨基-1-二甲氨基-2-硝基乙烯(化合物104)
除了用2-氯-5-噻唑甲胺代替6-氯-3-吡啶甲胺外,各步分别得到下列化合物
(1) 异硫氰酸(2-氯-5-噻唑基)甲酯
(滴加氯甲酸乙酯后,在80℃搅拌混合物3小时)
NMR(CDCl3)δ:4.82(2H,s),7.50(1H,s)
(2) N-(2-氯-5-噻唑甲基)-N′-二甲硫脲(黄色晶状)m.p.:125-127℃NMR(CDCl3)δ:3.28(6H,s),4.98(2H,d,J=6.0Hz),5.6-6.1(1H,br),7.40(1H,s)
(3) S-甲基-N-(2-氯-5-噻唑甲基)-N-二甲基异硫脲(黄色油状)NMR(CDCl3)δ:2.31(3H,s),2.99(6H,s),4.79(2H,s),7.36(1H,s)
(4) 标题化合物(浅灰色晶体)
(在37℃进行反应)
该产物的熔点、NMR和IR谱和TLC Rf与实例86获得的化合物104相同)
除了用1-N-(2-氯-5-噻唑甲基)氨基-1-二甲氨基-2-硝基乙烯代替1-甲氨基-1-〔N-甲基-N-(3-吡啶甲基)〕氨基-2-硝基乙烯外,重复实例46的反应步骤,得到白色晶状标题化合物、该产物的NMR值表明,该产物是同分异构体的混合物(6∶1)m.p.:139-142℃NMR(CDCl3)δ:2.92&2.99(total 6H,each s),4.83(2H,s),6.61&6.34(total 1H,s),7.45(1H,s),8.19&8.46(total1H,each s)IR(Nujol):1680,1410,1355,1270,1050cm-1
实例111
将3.79g(0.0169mol)N-(6-氯-3-吡啶甲基)-N-(2,2,2-三氟乙基)胺和2.46g异氰酸甲酯在回流下于35ml甲苯中搅拌18小时。蒸除甲苯,将残余物溶于120ml AcOEt,依次用1N HCl(二次)和氯化钠水溶液洗涤,用MgSO4干燥。蒸除AcOEt,得到油状物,往该油状产物中加入Et2O和己烷,接着冷却,得到晶体。往混合物中加入己烷后,过滤收集晶体,干燥,得到2.78g白色晶状的N-(6-氯-3-吡啶甲基)-N-(2,2,2-三氟乙基-N′-甲基硫脲。m.p.:98-100℃NMR(CDCl3)δ:3.13(d,J=5Hz,MeN),4.37(q,J=9Hz,CF3CH2),5.09(s,pyridine-CH2),6.07(br,NH),7.34(d,J=8Hz,1H),7.67(dd,J=8&2Hz,1H),8.26(d,J=2Hz,1H)
除了用N-(6-氯-3-吡啶甲基)-N-(2,2,2-三氟乙基)-N′-甲基硫脲代替N-甲基-N ′-乙基-N′-(3吡啶甲基)硫脲外,重复实例13的步骤(2)和(3),各步分别得到下列化合物。
(2) S-甲基-N-(6-氯-3-吡啶甲基)-N-(2,2,2-三氟乙基)-N′-甲基异硫脲(浅棕色油状)NMR(CDCl3)δ:2.28(s,MeS),3.24(s,MeN),4.07(q,J=9Hz,CF3CH2),4.66(s,pyridine-CH2),7.28(d,J=8Hz,1H),7.54(dd,J=8&2Hz,1H),8.26(d,J=2Hz,1H)(3) 标题化合物(反应进行96小时)m.p.:110-111℃NMR(CDCl3)δ:3.12(d,J=5Hz,MeN),3.60(q,J=9Hz,CF3CH2),4.42(s,pyridine-CH2),6.51(s,=CHNO2),7.39(d,J=8Hz,1H),7.60(dd,J=8&2Hz,1H),8.33(d,J=2Hz,1H),9.50(br,NH)IR(Nujol):1595,1450,1345,1260,1235,1140,1100cm-1
还可合成下列本发明的目的化合物:
〔1〕1-〔N-(6-氯-3-吡啶甲基〕-N-甲酰基〕氨基-1-〔N-甲酰基-N-甲基〕氨基-2-硝基乙烯
〔2〕1-〔N-〔6-氯-3-吡啶甲基〕-N-乙基〕氨基-1-二甲氨基-2-硝基乙烯
〔3〕1-〔N-〔6-氯-3-吡啶甲基〕-N-〔2-氟乙基〕〕氨基-1-甲氨基-2-硝基乙烯
〔4〕1-〔N-〔6-氯-3-吡啶甲基〕-N-〔2-氟乙基〕〕氨基-1-二甲氨基-2-硝基乙烯
〔5〕1-〔N〔2-氯-5-噻唑甲基〕-N-甲酰基〕氨基-1-〔N-甲酰基-N-甲基〕氨基-2-硝基乙烯
〔6〕1-〔N-〔6-溴-3-吡啶甲基〕-N-〔2-氟乙基〕〕氨基-1-甲氨基-2-硝基乙烯
〔7〕1-〔N-〔6-溴-3-吡啶甲基〕-N-〔2-氟乙基〕〕氨基-1-二甲氨基-2-硝基乙烯
〔8〕1-〔N-〔2-氯-5-噻唑甲基〕-N-〔2-氟乙基〕〕氨基-1-甲氨基-2-硝基乙烯
〔9〕1-〔N-〔2-氯-5-噻唑甲基〕-N-甲基〕氨基-1-二甲氨基-2-硝基乙烯
〔10〕1-〔N-〔2-氯-5-噻唑甲基〕-N-乙基〕氨基-1-二甲氨基-2-硝基乙烯
〔11〕1-〔2-溴-5-噻唑甲基〕氨基-1-甲氨基-2-硝基乙烯
〔12〕1-〔N-〔2-溴-5-噻唑甲基〕-N-甲酰基〕氨基-1-甲氨基-2-硝基乙烯
〔13〕.1-〔N-〔2-溴-5-噻唑甲基〕-N-甲基〕氨基-1-甲氨基-2-硝基乙烯
〔14〕.1-〔N-〔2-溴-5-噻唑甲基〕-N-乙基〕氨基-1-甲氨基-2-硝基乙烯
〔15〕.1-〔2-溴-5-噻唑甲基〕氨基-1-〔N-甲酰基-N-甲基〕氨基-2-硝基乙烯
〔16〕.1-〔N-〔2-溴-5-噻唑甲基〕-N-甲酰基〕氨基-1-〔N-甲酰基-N-甲基〕氨基-2-硝基乙烯
〔17〕.1-〔N-〔2-溴-5-噻唑甲基〕-N-甲酰基〕氨基-1-〔N-甲酰基-N-甲基〕氨基-2-硝基乙烯
〔18〕.1-〔N-〔2-溴-5-噻唑甲基〕-N-乙基〕氨基-1-〔N-甲酰基-N-甲基〕氨基-2-硝基乙烯
〔19〕.1-〔N-〔2-氯-5-噻唑甲基〕-N-〔2-氟乙基〕〕氨基-1-二甲氨基-2-硝基乙烯
〔20〕.1-〔N-〔2-溴-5-噻唑甲基〕-N-甲酰基〕氨基-1-二甲氨基-2-硝基乙烯
〔21〕.1-〔N-〔2-溴-5-噻唑甲基〕-N-甲基〕氨基-1-二甲氨基-2-硝基乙烯
〔22〕.1-〔N-〔2-溴-5-噻唑甲基〕-N-乙基〕氨基-1-二甲氨基-2-硝基乙烯
〔23〕.1-〔N-氯甲基-N-〔6-氯-3-吡啶甲基〕〕氨基-1-甲氨基-2-硝基乙烯
〔24〕1-〔N-〔6-溴-3-吡啶甲基〕-N-氯甲基〕氨基-1-甲氨基-2-硝基乙烯
〔25〕1-〔N-氯甲基-N-〔2-氯-5-噻唑甲基〕〕氨基-1-甲氨基-2-硝基乙烯
〔26〕1-〔N-〔6-溴-3-吡啶甲基〕-N-甲酰基〕氨基-1-〔N-甲酰基-N-甲基〕氨基-2-硝基乙烯
〔27〕1-〔N-〔2-溴-5-噻唑甲基〕-N-〔2-氟乙基〕〕氨基-1-甲氨基-2-硝基乙烯
〔28〕1-〔N-〔2-溴-5-噻唑甲基-N-〔2-氟乙基〕〕氨基-1-二甲氨基-2-硝基乙烯
〔29〕1-〔N-〔2-氯-5-噻唑甲基〕-N-〔2,2,2-三氟乙基〕〕氨基-1-甲氨基-2-硝基乙烯
〔30〕1-〔N-〔6-溴-3-吡啶甲基〕-N-〔2,2,2-三氟甲基〕〕氨基-2-二甲氨基-2-硝基乙烯
(31)1-〔N-(6-溴-3-吡啶甲基)-N-甲基〕氨基-1-二甲氨基-2-硝基乙烯
(32)1-〔N-(6-溴-3-吡啶甲基)-N-乙基〕氨基-1-二甲氨基-2-硝基乙烯
(33)1-(6-氟-3-吡啶甲基)氨基-1-甲氨基-2-硝基乙烯
(34)1-〔N-(6-氟-3-吡啶甲基)-N-甲酰基〕氨基-1-甲氨基-2-硝基乙烯
(35)1-(6-氟-3-吡啶甲基)氨基-1-(N-甲酰基-N-甲基)氨基-2-硝基乙烯
(36)1-〔N-(6-氟-3-吡啶甲基)-N-甲酰基〕氨基-1-(N-甲酰基-N-甲基)氨基-2-硝基乙烯
(37)1-〔N-(6-氟-3-吡啶甲基)-N-甲基〕氨基-1-(N-甲酰基-N-甲基)氨基-2-硝基乙烯
(38)1-〔N-(6-氟-3-吡啶甲基)-N-乙基〕氨基-1-(N-甲酰基-N-甲基)氨基-2-硝基乙烯
(39)1-二甲氨基-1-(6-氟-3-吡啶甲基)氨基-2-硝基乙烯
(40)1-二甲氨基-1-〔N-(6-氟-3-吡啶甲基)-N-甲酰基〕氨基-2-硝基乙烯
(41)1-二甲氨基-1-〔N-(6-氟-3-吡啶甲基)-N-甲基〕氨基-2-硝基乙烯
(42)1-二甲氨基-1-〔N-(6-氟-3-吡啶甲基)-N-乙基〕氨基-2-硝基乙烯
实例112(乳油)
混合以下各成份制成乳油:
化合物17 20%(重)
二甲苯 75%(重)
聚氧乙烯乙二醇醚
(Nonipol) 5%(重)
实例113(可湿性粉剂)
混合以下各成份制成可湿性粉剂:
化合物12 20%(重)
木素磺酸钠 5%(重)
聚氧乙烯乙二醇醚
(Nonipol) 5%(重)
白炭 30%(重)
粘土 40%(重)实例114(粉剂)混合下列成份制成粉剂:化合物19 3%(重)白炭 3%(重)粘土 94%(重)实例115(颗粒剂)将下列成份混合并制粒,制成颗粒产品:化合物25 2%(重)木素磺酸钠 5%(重)粘土 93%(重)
Claims (1)
1.制备下式的α-不饱和胺或其盐的方法:
其中:
X1和X2中的一个为硝基,另一个为氢原子,C1-4烷氧羰基或C1-4烷磺酰硫代氨基甲酰基;
R4为氢,C1-4烷基,C3-6环烷基或C2-4链烯基,
所述基团R3和R4是未取代的或被1-3个下列取代基取代:羟基,C1-4烷氧基,卤素,二-C1-4烷基氨基,C1-4烷硫基,三-C1-4烷基甲硅烷基,可被卤素取代的吡啶基,和可被卤素取代的噻唑基,或者R3和R4与邻近氮原子一起可构成下列环氨基,
R2为氢原子;通过碳连接的基团,该基团选自C1-4酰基,C1 -4烷基,C3-6环烷基,C7-9芳烷基,这些基团可具有1至3个下列取代基:C1-4烷氧基和卤素;通过氮连接的基团;其中,R3′,R4′为C1-6烷基,或通过氧连接的基团,该基团是C1 -4烷氧基;
n为0,1或2;
A°为苯基,吡啶基,噻唑基,吡嗪基,或喹啉基,这些基团可具有1至3个下列取代基;C1-4烷基,C1-4烷氧基,C1-4烷硫基,卤素或C1-4卤代烷基,
其条件是,当R2为氢原子时,A°为下式基团:其中Hal为卤原子该方法包括:
(1)使下式化合物或其盐:其中X1和X2如上定义;R5是C1-4烷基或C7-9芳烷基,与下式化合物或其盐反应:
或。
(2)使下式化合物或其盐:
或
O2N-CH2C(Hal)3 [XII]其中Hal如上定义
R1-Y [V]
其中各符号如上定义,或(ii)与下式化合物或其盐反应:
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JP192793/1987 | 1987-08-01 | ||
JP19279387 | 1987-08-01 | ||
JP192793/87 | 1987-08-01 | ||
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JP16259/88 | 1988-01-26 | ||
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CN88104801A Division CN1027447C (zh) | 1987-08-01 | 1988-08-01 | 一种含α-不饱和胺的杀虫/杀螨组合物 |
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CN1093083A CN1093083A (zh) | 1994-10-05 |
CN1036649C true CN1036649C (zh) | 1997-12-10 |
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CN88104801A Expired - Lifetime CN1027447C (zh) | 1987-08-01 | 1988-08-01 | 一种含α-不饱和胺的杀虫/杀螨组合物 |
CN93114205A Expired - Lifetime CN1083432C (zh) | 1987-08-01 | 1993-11-05 | 制备胺化合物或其盐的方法 |
CN93114206A Expired - Lifetime CN1036649C (zh) | 1987-08-01 | 1993-11-05 | 制备α-不饱和胺或其盐的方法 |
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CN88104801A Expired - Lifetime CN1027447C (zh) | 1987-08-01 | 1988-08-01 | 一种含α-不饱和胺的杀虫/杀螨组合物 |
CN93114205A Expired - Lifetime CN1083432C (zh) | 1987-08-01 | 1993-11-05 | 制备胺化合物或其盐的方法 |
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EP (3) | EP0529680B1 (zh) |
JP (5) | JPH0749424B2 (zh) |
KR (3) | KR970005908B1 (zh) |
CN (3) | CN1027447C (zh) |
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DE (4) | DE3886467T2 (zh) |
ES (2) | ES2161212T3 (zh) |
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1988
- 1988-07-28 ES ES92111470T patent/ES2161212T3/es not_active Expired - Lifetime
- 1988-07-28 DE DE3886467T patent/DE3886467T2/de not_active Expired - Lifetime
- 1988-07-28 IL IL87250A patent/IL87250A/xx not_active IP Right Cessation
- 1988-07-28 AT AT88112210T patent/ATE98955T1/de active
- 1988-07-28 AT AT92111470T patent/ATE206400T1/de not_active IP Right Cessation
- 1988-07-28 DE DE2003199003 patent/DE10399003I2/de active Active
- 1988-07-28 EP EP92115873A patent/EP0529680B1/en not_active Expired - Lifetime
- 1988-07-28 IL IL10068888A patent/IL100688A/en not_active IP Right Cessation
- 1988-07-28 ES ES88112210T patent/ES2061569T3/es not_active Expired - Lifetime
- 1988-07-28 DE DE3856493T patent/DE3856493T2/de not_active Expired - Lifetime
- 1988-07-28 EP EP92111470A patent/EP0509559B1/en not_active Expired - Lifetime
- 1988-07-28 DE DE3856183T patent/DE3856183T2/de not_active Expired - Lifetime
- 1988-07-28 EP EP88112210A patent/EP0302389B1/en not_active Expired - Lifetime
- 1988-07-28 US US07/225,367 patent/US5849768A/en not_active Expired - Lifetime
- 1988-07-28 AT AT92115873T patent/ATE166051T1/de not_active IP Right Cessation
- 1988-07-29 HU HU884040A patent/HU204496B/hu unknown
- 1988-07-29 CA CA000616737A patent/CA1341008C/en not_active Expired - Lifetime
- 1988-07-29 HU HU90722A patent/HU205076B/hu unknown
- 1988-07-29 CA CA000616738A patent/CA1340990C/en not_active Expired - Lifetime
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- 1988-08-01 KR KR1019880009848A patent/KR970005908B1/ko not_active IP Right Cessation
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1989
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1991
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1992
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1993
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- 1993-07-31 KR KR1019930014803A patent/KR0122856B1/ko not_active IP Right Cessation
- 1993-07-31 KR KR1019930014804A patent/KR970011459B1/ko not_active IP Right Cessation
- 1993-11-05 CN CN93114205A patent/CN1083432C/zh not_active Expired - Lifetime
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1994
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1997
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1999
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2003
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