EP0984935A1 - Procede de fabrication de thiopyridines substituees - Google Patents
Procede de fabrication de thiopyridines substitueesInfo
- Publication number
- EP0984935A1 EP0984935A1 EP98929326A EP98929326A EP0984935A1 EP 0984935 A1 EP0984935 A1 EP 0984935A1 EP 98929326 A EP98929326 A EP 98929326A EP 98929326 A EP98929326 A EP 98929326A EP 0984935 A1 EP0984935 A1 EP 0984935A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- alkyl
- halogen
- substituted
- phenyl
- cyano
- 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.)
- Withdrawn
Links
- 238000004519 manufacturing process Methods 0.000 title abstract description 7
- -1 thio compound Chemical class 0.000 claims abstract description 194
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims abstract description 27
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims abstract description 23
- 239000003054 catalyst Substances 0.000 claims abstract description 19
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 19
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims abstract description 17
- 238000000034 method Methods 0.000 claims abstract description 17
- 239000000460 chlorine Substances 0.000 claims abstract description 16
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 16
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 14
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims abstract description 11
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims abstract description 11
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 11
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 11
- 239000011737 fluorine Substances 0.000 claims abstract description 11
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims abstract description 10
- 239000010949 copper Substances 0.000 claims abstract description 9
- 229910052802 copper Inorganic materials 0.000 claims abstract description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 57
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 30
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 28
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 20
- 239000000203 mixture Substances 0.000 claims description 19
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
- 150000003457 sulfones Chemical class 0.000 claims description 18
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 16
- 150000002367 halogens Chemical class 0.000 claims description 16
- 230000003647 oxidation Effects 0.000 claims description 16
- 238000007254 oxidation reaction Methods 0.000 claims description 16
- 150000003462 sulfoxides Chemical class 0.000 claims description 16
- 150000005749 2-halopyridines Chemical class 0.000 claims description 12
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 12
- 239000001257 hydrogen Substances 0.000 claims description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims description 10
- 238000002360 preparation method Methods 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 125000003342 alkenyl group Chemical group 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 125000000304 alkynyl group Chemical group 0.000 claims description 5
- 125000005843 halogen group Chemical group 0.000 claims description 5
- 125000001624 naphthyl group Chemical group 0.000 claims description 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 2
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 2
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 2
- 125000001931 aliphatic group Chemical group 0.000 claims description 2
- 150000001447 alkali salts Chemical class 0.000 claims description 2
- 125000003118 aryl group Chemical group 0.000 claims description 2
- 125000005842 heteroatom Chemical group 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- QWPPOHNGKGFGJK-UHFFFAOYSA-N hypochlorous acid Chemical compound ClO QWPPOHNGKGFGJK-UHFFFAOYSA-N 0.000 claims description 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 2
- UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims 1
- 125000001424 substituent group Chemical group 0.000 abstract description 3
- ATTZFSUZZUNHBP-UHFFFAOYSA-N Piperonyl sulfoxide Chemical compound CCCCCCCCS(=O)C(C)CC1=CC=C2OCOC2=C1 ATTZFSUZZUNHBP-UHFFFAOYSA-N 0.000 abstract 2
- 125000001174 sulfone group Chemical group 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 39
- 238000006243 chemical reaction Methods 0.000 description 23
- 229960000583 acetic acid Drugs 0.000 description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
- 238000003756 stirring Methods 0.000 description 18
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 18
- 150000001875 compounds Chemical class 0.000 description 16
- 239000002904 solvent Substances 0.000 description 16
- 239000007800 oxidant agent Substances 0.000 description 15
- 239000011541 reaction mixture Substances 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical group CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 12
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 description 9
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- 239000012362 glacial acetic acid Substances 0.000 description 8
- 150000003573 thiols Chemical class 0.000 description 8
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
- QPFMBZIOSGYJDE-UHFFFAOYSA-N 1,1,2,2-tetrachloroethane Chemical compound ClC(Cl)C(Cl)Cl QPFMBZIOSGYJDE-UHFFFAOYSA-N 0.000 description 6
- ABNQGNFVSFKJGI-UHFFFAOYSA-N 2,3-dichloro-5-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CN=C(Cl)C(Cl)=C1 ABNQGNFVSFKJGI-UHFFFAOYSA-N 0.000 description 6
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000005457 ice water Substances 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- 239000005708 Sodium hypochlorite Substances 0.000 description 5
- OUUQCZGPVNCOIJ-UHFFFAOYSA-M Superoxide Chemical compound [O-][O] OUUQCZGPVNCOIJ-UHFFFAOYSA-M 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 239000012071 phase Substances 0.000 description 5
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 238000009835 boiling Methods 0.000 description 4
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 150000003568 thioethers Chemical class 0.000 description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- XYPISWUKQGWYGX-UHFFFAOYSA-N 2,2,2-trifluoroethaneperoxoic acid Chemical compound OOC(=O)C(F)(F)F XYPISWUKQGWYGX-UHFFFAOYSA-N 0.000 description 3
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 3
- STPADWRNLPKPIE-UHFFFAOYSA-N 3-chloro-2-phenylsulfanyl-5-(trifluoromethyl)pyridine Chemical compound ClC1=CC(C(F)(F)F)=CN=C1SC1=CC=CC=C1 STPADWRNLPKPIE-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 3
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 229930195733 hydrocarbon Natural products 0.000 description 3
- 150000002430 hydrocarbons Chemical class 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
- 235000019341 magnesium sulphate Nutrition 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 229910017604 nitric acid Inorganic materials 0.000 description 3
- 238000005580 one pot reaction Methods 0.000 description 3
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 3
- 150000005359 phenylpyridines Chemical class 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- 125000001272 (C1-C4)-alkylene-phenyl group Chemical group 0.000 description 2
- 125000004776 1-fluoroethyl group Chemical group [H]C([H])([H])C([H])(F)* 0.000 description 2
- 125000004778 2,2-difluoroethyl group Chemical group [H]C([H])(*)C([H])(F)F 0.000 description 2
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 2
- TZZAVCNQQCDVKI-UHFFFAOYSA-N 3-chloro-2-propylsulfanyl-5-(trifluoromethyl)pyridine Chemical compound CCCSC1=NC=C(C(F)(F)F)C=C1Cl TZZAVCNQQCDVKI-UHFFFAOYSA-N 0.000 description 2
- MGWGWNFMUOTEHG-UHFFFAOYSA-N 4-(3,5-dimethylphenyl)-1,3-thiazol-2-amine Chemical compound CC1=CC(C)=CC(C=2N=C(N)SC=2)=C1 MGWGWNFMUOTEHG-UHFFFAOYSA-N 0.000 description 2
- PERMDYZFNQIKBL-UHFFFAOYSA-N 5-chloro-2,3-difluoropyridine Chemical compound FC1=CC(Cl)=CN=C1F PERMDYZFNQIKBL-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- 206010034972 Photosensitivity reaction Diseases 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 125000002490 anilino group Chemical class [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 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 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- WFPZPJSADLPSON-UHFFFAOYSA-N dinitrogen tetraoxide Chemical compound [O-][N+](=O)[N+]([O-])=O WFPZPJSADLPSON-UHFFFAOYSA-N 0.000 description 2
- LZDSILRDTDCIQT-UHFFFAOYSA-N dinitrogen trioxide Chemical compound [O-][N+](=O)N=O LZDSILRDTDCIQT-UHFFFAOYSA-N 0.000 description 2
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 2
- 150000005748 halopyridines Chemical class 0.000 description 2
- 230000002363 herbicidal effect Effects 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- BHIWKHZACMWKOJ-UHFFFAOYSA-N methyl isobutyrate Chemical compound COC(=O)C(C)C BHIWKHZACMWKOJ-UHFFFAOYSA-N 0.000 description 2
- JCXJVPUVTGWSNB-UHFFFAOYSA-N nitrogen dioxide Inorganic materials O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 description 2
- SYQBFIAQOQZEGI-UHFFFAOYSA-N osmium atom Chemical compound [Os] SYQBFIAQOQZEGI-UHFFFAOYSA-N 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- KMUONIBRACKNSN-UHFFFAOYSA-N potassium dichromate Chemical compound [K+].[K+].[O-][Cr](=O)(=O)O[Cr]([O-])(=O)=O KMUONIBRACKNSN-UHFFFAOYSA-N 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 2
- 239000011814 protection agent Substances 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- JPJALAQPGMAKDF-UHFFFAOYSA-N selenium dioxide Chemical compound O=[Se]=O JPJALAQPGMAKDF-UHFFFAOYSA-N 0.000 description 2
- XMVONEAAOPAGAO-UHFFFAOYSA-N sodium tungstate Chemical compound [Na+].[Na+].[O-][W]([O-])(=O)=O XMVONEAAOPAGAO-UHFFFAOYSA-N 0.000 description 2
- HHVIBTZHLRERCL-UHFFFAOYSA-N sulfonyldimethane Chemical compound CS(C)(=O)=O HHVIBTZHLRERCL-UHFFFAOYSA-N 0.000 description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 1
- SNDGLCYYBKJSOT-UHFFFAOYSA-N 1,1,3,3-tetrabutylurea Chemical compound CCCCN(CCCC)C(=O)N(CCCC)CCCC SNDGLCYYBKJSOT-UHFFFAOYSA-N 0.000 description 1
- UWHSPZZUAYSGTB-UHFFFAOYSA-N 1,1,3,3-tetraethylurea Chemical compound CCN(CC)C(=O)N(CC)CC UWHSPZZUAYSGTB-UHFFFAOYSA-N 0.000 description 1
- RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 description 1
- LZDKZFUFMNSQCJ-UHFFFAOYSA-N 1,2-diethoxyethane Chemical compound CCOCCOCC LZDKZFUFMNSQCJ-UHFFFAOYSA-N 0.000 description 1
- 125000005918 1,2-dimethylbutyl group Chemical group 0.000 description 1
- CYSGHNMQYZDMIA-UHFFFAOYSA-N 1,3-Dimethyl-2-imidazolidinon Chemical compound CN1CCN(C)C1=O CYSGHNMQYZDMIA-UHFFFAOYSA-N 0.000 description 1
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 1
- OCJBOOLMMGQPQU-UHFFFAOYSA-N 1,4-dichlorobenzene Chemical compound ClC1=CC=C(Cl)C=C1 OCJBOOLMMGQPQU-UHFFFAOYSA-N 0.000 description 1
- 125000006218 1-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004812 1-ethylethylene group Chemical group [H]C([H])([H])C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- MBDUIEKYVPVZJH-UHFFFAOYSA-N 1-ethylsulfonylethane Chemical compound CCS(=O)(=O)CC MBDUIEKYVPVZJH-UHFFFAOYSA-N 0.000 description 1
- 125000006018 1-methyl-ethenyl group Chemical group 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- 125000000453 2,2,2-trichloroethyl group Chemical group [H]C([H])(*)C(Cl)(Cl)Cl 0.000 description 1
- 125000004781 2,2-dichloro-2-fluoroethyl group Chemical group [H]C([H])(*)C(F)(Cl)Cl 0.000 description 1
- CNLIIAKAAMFCJG-UHFFFAOYSA-N 2,3,5-trichloropyridine Chemical compound ClC1=CN=C(Cl)C(Cl)=C1 CNLIIAKAAMFCJG-UHFFFAOYSA-N 0.000 description 1
- QMLGIISDLTUPLS-UHFFFAOYSA-N 2,3-dichloro-5-(1,1,2,2,2-pentafluoroethyl)pyridine Chemical compound FC(F)(F)C(F)(F)C1=CN=C(Cl)C(Cl)=C1 QMLGIISDLTUPLS-UHFFFAOYSA-N 0.000 description 1
- NXSGPBQUZKGBRZ-UHFFFAOYSA-N 2,3-dichloro-5-(3,3,3-trifluoropropyl)pyridine Chemical compound FC(F)(F)CCC1=CN=C(Cl)C(Cl)=C1 NXSGPBQUZKGBRZ-UHFFFAOYSA-N 0.000 description 1
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- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- IXZDIALLLMRYOU-UHFFFAOYSA-N tert-butyl hypochlorite Chemical compound CC(C)(C)OCl IXZDIALLLMRYOU-UHFFFAOYSA-N 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- YONPGGFAJWQGJC-UHFFFAOYSA-K titanium(iii) chloride Chemical compound Cl[Ti](Cl)Cl YONPGGFAJWQGJC-UHFFFAOYSA-K 0.000 description 1
- 229910000314 transition metal oxide Inorganic materials 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- WFKWXMTUELFFGS-UHFFFAOYSA-N tungsten Chemical compound [W] WFKWXMTUELFFGS-UHFFFAOYSA-N 0.000 description 1
- 229910052721 tungsten Inorganic materials 0.000 description 1
- 239000010937 tungsten Substances 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 229910052720 vanadium Inorganic materials 0.000 description 1
- GPPXJZIENCGNKB-UHFFFAOYSA-N vanadium Chemical compound [V]#[V] GPPXJZIENCGNKB-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 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
- C07D213/60—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 hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/70—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B45/00—Formation or introduction of functional groups containing sulfur
- C07B45/06—Formation or introduction of functional groups containing sulfur of mercapto or sulfide groups
-
- 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
- C07D213/60—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 hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/70—Sulfur atoms
- C07D213/71—Sulfur atoms to which a second hetero atom is attached
Definitions
- the invention relates to a process for the preparation of thiopyridines of the general formula I.
- n 0, 1 or 2
- R - * -, R 2 , R 3 and R 4 are the same or different and are for
- R 5 is an unsubstituted or halogen radical
- R 6 , R 7 , R 8 are identical or different from one another and
- the thiopyridines I are important intermediates for the production of crop protection agents having a herbicidal action, as are known from WO-A-95/02580.
- EP-A 320448 describes the reaction of a 2 -halogenopyridine with anilines without adding base to the corresponding 2 -arylaminopyridine in 11 or 37% yield. It is also mentioned in the same document that in addition to anilines, thiophenols can also be used. However, EP-A 320 448 does not list a specific exemplary embodiment which describes the reaction of a 2 -halopyridine with a thiophenol.
- the object of the present invention was to find a simple and inexpensive process for the preparation of thiopyridine derivatives which, in turn, are suitable as a coupling component for the preparation of substituted phenylpyridines, as are described in WO-A-95/02580.
- R 1 , R 2 , R 3 and R 4 have the abovementioned meaning and Hai is fluorine, chlorine or bromine, in a first step with a thio compound of the formula III
- R 5 has the abovementioned meaning in the presence of a copper catalyst first converted to a pyridine thioether of the formula Ia and then stepwise to the sulfoxide Ib or sulfone Ic
- the process according to the invention provides the pyridine thioethers of the formula Ia in a surprisingly high yield.
- the purity of the formed pyrid thioethers la is so high that they can generally be oxidized to the sulfoxides 1b and 1c without intermediate cleaning with oxidizing agents.
- Hydrogen peroxide in acetic acid or acetic acid / trifluoroacetic acid mixtures has proven to be particularly advantageous for the stepwise oxidation of the pyridine thioethers la to the sulfoxides Ib and the sulfones Ic.
- For the direct oxidation of the Pyrid thioether la to the sulfones Ic is particularly suitable for hypochlorous acid or its alkali salt.
- the thiopyridines I are particularly preferably obtained if sub * substituted 2-halopyridines of the formula II
- R 5 has the abovementioned meaning first in the presence of 0.001 to 1 mol% of a copper catalyst to give a pyridine thioether of the formula Ia and then this stepwise to give the sulfoxide Ib
- Particularly preferred compound II is 2,3,5-trichloropyridine, 5-chloro-2,3-difluoropyridine, 2,3-dichloro-5-difluoromethylpyridine, 2,3-dichloro-5 - (3,3,3-trifluoropropyl ) -pyridine, 2,3-dichloro-5-tri-fluoromethylpyridine or 2,3-dichloro-5-pentafluoroethylpyridine.
- the preparation of the compounds I is exemplified by the reaction described in the following scheme, starting from 2,3-dichloro-5-trifluoromethylpyridine and thiophenol as the nucleophile using hydrogen peroxide as the oxidizing agent.
- the reaction of the 2-halopyridines II with a thiol III is advantageously carried out in the presence of a solvent at temperatures in the range from 80-250 ° C., preferably 120-200 ° C., particularly preferably 140-180 ° C.
- the solvents used for these reactions are hydrocarbons such as toluene, xylene, chlorinated hydrocarbons such as 1, 2-dichloroethane, 1, 1, 2, 2-tetrachloroethane, chlorobenzene, 1,2-, 1,3- or 1, 4-dichlorobenzene, ethers such as 1,4-dioxane, anisole, glycol ethers such as dirnethyl glycol ether, diethyl glycol ether, diethylene glycol dimethyl ether, esters such as ethyl acetate, propyl acetate, methyl isobutyrate, isobutyl acetate, carboxamides such as DMF, N-methylpyrrolidone, nitrocarbons, hydrocarbons such as tetraethyl urea, tetrabutyl urea, dimethyl ethylene urea, dimethyl propylene urea, sulfoxides such as dimethyl s
- the molar ratios in which the starting compounds are reacted with one another are generally 0.9-1.4, preferably 0.95-1.1, particularly preferably 0.98-1.04, for the ratio of thiol to 2-halopyridine II.
- tration of the starting materials in the solvent is 0.1-5 mol / 1, preferably 0.2-2 mol / 1.
- Suitable catalysts are copper oxide, salts such as copper (II) chloride, copper sulfate, copper nitrate, copper acetate, copper carbonate. It is particularly preferred to use metallic copper in fine distribution, e.g. B. copper powder or copper - bronze.
- the molar amount of catalyst based on the 2-halopyridine II is 0.001-10, preferably 0.001-1 mol% and particularly preferably 0.001 to 0.1 mol%.
- the reaction is preferably carried out under acidic conditions, in which the hydrogen halide split off in the reaction is removed from the reaction mixture by means of an inert gas, for example nitrogen, or is allowed to escape into a washing device under autogenous pressure.
- an inert gas for example nitrogen
- the 2-halopyridine II is advantageously added for 10 to 60 min. to a mixture of the thiol III and the catalyst at 20-80 ° C and then stirred to complete the reaction for 0.5 to 12 hours, preferably 1 to 8 hours at 140-180 ° C.
- the thiol III can also be added to a mixture of 2-halopyridine II and catalyst and the reaction can then be completed as above.
- reaction can also be carried out in an autoclave.
- the higher-boiling component can be introduced together with the catalyst and the lower-boiling component - depending on its consumption - directly at the reaction temperature of preferably 120-200 ° C., particularly preferably 140-180 ° Add C or introduce in gaseous form.
- reaction can also be carried out in an aqueous two-phase system, preferably in the presence of phase transfer catalysts such as quaternary ammonium or phosphonium salts.
- phase transfer catalysts such as quaternary ammonium or phosphonium salts.
- the reaction can be carried out under pressure or under pressure, continuously or batchwise.
- the oxidation of the pyridine thioethers of the formula Ia to the sulfoxides Ib and sulfones Ic can preferably be carried out with hydrogen peroxide, the sulfoxides Ib being obtained with approximately equivalent amounts of oxidant and the sulfones Ic being obtained with approximately twice molar amounts.
- the reaction can also be catalyzed by adding stronger acids such as trifluoroacetic acid or perchloric acid.
- metal compounds are also suitable as catalysts, e.g. B. transition metal oxides such as vanadium pentaoxide, sodium tungstate, potassium dichromate, iron oxide tungstate, sodium tungstate-molybdic acid, osmic acid, titanium trichloride, selenium dioxide, phenyleneselenic acid, oxovanadinyl-2, 4-pentanedionate.
- the catalysts are generally used in an amount of 0.5 to 10%, but because of the easy filterability and recovery of the inorganic catalysts, stoichiometric amounts can also be used.
- Another preferred oxidizing agent is peracetic acid or hydrogen peroxide / acetic anhydride, optionally also the peracetic acid present in equilibrium in a hydrogen peroxide / acetic acid mixture.
- a preferred oxidizing agent also provides the Pertrifluor- acetic acid or the mixture of hydrogen peroxide / trifluoroacetic acid ⁇ or the mixture of hydrogen peroxide / anhydride is Trifluoracet-.
- Oxidation with hydrogen peroxide in glacial acetic acid is generally very selective, but often slow.
- Trifluoroacetic acid can generally shorten the reaction time. Oxidation with hydrogen peroxide in pure trifluoroacetic acid frequently leads, as also described in Chimia 29 (1975) 466, to the formation of the corresponding N-oxides. A rapid and selective oxidation of the pyridine thioethers la to the corresponding sulfoxides Ib and sulfones Ic is possible, for example, with solutions of hydrogen superoxide in mixtures of acetic acid and trifluoroacetic acid in a volume ratio of 10: 1 to 1: 1, in particular 6: 1 to 4: 1. These mixtures are therefore particularly preferred as solvents.
- Petroleum ether the abovementioned solvents and the catalysts listed above can also be used as solvents.
- perbenzoic acid In addition to peracetic acid and pertrifluoroacetic acid, perbenzoic acid, monoperphthalic acid or 3-chloroperbenzoic acid can also advantageously be used in chlorinated hydrocarbons such as methylene chloride or 1,2-dichloroethane.
- Chlorine and bromine are also very suitable for the oxidation of the thiols to sulfoxides or sulfones.
- Favorable solvents are water, acetonitrile, dioxane, two-phase systems such as aqueous potassium hydrogen carbonate solution / dichloromethane and, in the case of pyridine alkyl thioether, also acetic acid.
- active halogen can also tert. -Butyl hypochlorite, hypochlorous and bromonic acid, the salts thereof, and also N-halogen compounds such as N-bromine and N-chlorosuccinimide or sulfuryl chloride.
- Nitrogen tetroxide e.g. in the process-technically simple variant with air / nitrogen dioxide or trioxide and, for example, osmium (VIII) oxide as catalyst.
- the oxidation can also be carried out directly with nitric acid, with acetic anhydride, acetic acid as additional solvents and copper (I) and (I ⁇ ) bromide and chloride as catalysts.
- Photosensitized oxygen transfer is also suitable for the oxidation, chlorophyll, protoporphyrin, Rose Bengal or methylene blue being recommended as photosensitizers.
- Inert solvents are hydrocarbons such as pentane, hexane, heptane, cyclohexane, chlorinated hydrocarbons such as methylene chloride, 1, 2-dichloroethane, 1, 1, 2, 2-tetrachloroethane, alcohols such as methanol, ethanol, n-propanol or isopropanol, ketones such as acetone , Methyl ethyl ketone, polar aprotic solvents such as acetonitrile, propionitrile or aromatic hydrocarbons such as benzene, toluene, chlorobenzene or xylene are suitable.
- ozone in the abovementioned solvents, in addition to ether, 1,4-dioxane or THF.
- catalysts are also recommended for oxygen oxidation.
- pyridine sulfoxides Ib or their pyridine sulfones Ic are obtained.
- the molar ratios in which the starting compounds are reacted with one another are generally 0.9-1.8, preferably 1.05-1.3 for the ratio of pyridine thioether la to oxidizing agent in the case of oxidation to pyridine sulfoxide and in general 1.9-3.5, preferably 2.05-2.9 in the case of oxidation to pyridine sulfone.
- the concentration of the starting materials in the solvent is generally 0.1-5 mol / 1, preferably 0.2-2 mol / 1.
- the pyridine thioether or the pyridine sulfoxide if appropriate with one of the abovementioned catalysts, is initially introduced in one of the abovementioned solvents, and the oxidizing agent is then added with stirring for 0.25-20 hours.
- the addition and reaction temperature depends on the optimal efficiency of the respective oxidizing agent and the avoidance of side reactions. If photosensitized oxygen is used, the procedure is generally from -20 to 80 ° C, but metal-catalyzed generally from 50 to 140 ° C and when using ozone generally from -78 to 60 ° C.
- a staggered addition of the liquid or dissolved oxidizing agent is also preferred.
- work is generally carried out at 0 - 90 ° C with tert. -Butyl hypochlorite in general at - 78 to 30 ° C, with N-halogen compounds in generally at 0 - 30 ° C and with nitric acid generally at 20 to 140 ° C.
- a reaction temperature of 0 - 40 ° C is recommended.
- the oxidations can be operated without pressure or under pressure, continuously or batchwise.
- the multistage reaction can advantageously also be carried out as a one-pot process, the pyridethioethers la obtained in the first synthesis step in the reaction of the 2-halopyridines II with the thiols III being converted directly to the sulfoxides Ib or the sulfones Ic without isolation and purification.
- the reaction product 1 a is allowed to cool to 90 to 20 ° C., if appropriate, a solvent is optionally added, for.
- the end products I are generally taken up in a water-immiscible solvent, acidic impurities or oxidizing agents are extracted with dilute alkali metal or water, dried and the solvent is removed under reduced pressure.
- R 2 chlorine, -CC 3 fluoroalkyl, cyano or methylsulfonyl
- R 4 is fluorine or trifluoromethyl
- R 5 is an unsubstituted or substituted by halogen, C 1 -C 4 -alkoxy-, C 1 -C 4 -alkoxycarbonyl, di- (C 1 -C 4 -alkylamino) carbonyl, cyano or nitro C 1 -C -o ⁇ alkyl, C 2 -C ⁇ o alkenyl or C -C ⁇ 0 alkynyl group, a C 3 -C 8 ⁇ cycloalkyl radical, an unsubstituted or in the phenyl moiety by halogen, C ⁇ -C 3 alkyl, C 1 -C 3 alkoxy, trifluoromethyl, cyano or nitro substituted C 1 -C 4 alkylenephenyl, phenyl or naphthyl radical.
- Halogen fluorine, chlorine, bromine and iodine preferably fluorine and chlorine
- C 2 -C ⁇ o-alkynyl ethynyl and C 3 -C 6 -alkynyl such as prop-1-in-l-yl, prop-2-in-3-yl, n-but-1-in-l-yl, n- But-l-in-4-yl, n-but-2-in-l-yl, n-pent-1-in-l-yl, n-pent-l-in-3-yl, n-pent l-in-4-yl, n-pent-l-in-5-yl, n-pent-2-in-l-yl, n-pent-2-in-4-yl, n-pent-2- in-5-yl, 3-methyl-but-1-in-l-yl, 3-methyl-but-l-in-3-yl, 3-methyl-but-l-in-4-yl, n- Hex-1-in-l-yl, n-hex-l-in-3-
- C ⁇ -C 3 alkyl as mentioned above, where 1-5 hydrogen atoms are replaced by fluorine, for example, fluoromethyl, difluoromethyl, trifluoromethyl, 1-fluoroethyl, 2-fluoroethyl, 2, 2-difluoroethyl, 2, 2, 2 -trifluoroethyl , Pentafluoroethyl, 3, 3, 3 -trifluoropropyl, preferably difluoromethyl, trifluoromethyl, 2, 2, 2 -trifluoroethyl, pentafluoroethyl, 3, 3, 3 -trifluoropropyl, particularly preferred is trifluoromethyl;
- C ⁇ -C ⁇ o-haloalkyl C ⁇ -C ⁇ 0 -alkyl as mentioned above, where in each case 1-6 hydrogen atoms are replaced by fluorine, chlorine and / or bromine, for example chloromethyl, dichloromethyl, trichloromethyl, fluoromethyl, Difluoromethyl, trifluoromethyl, chlorofluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, 1-fluoroethyl, 2-fluoroethyl, 2, 2-difluoroethyl, 2, 2, 2-trifluoroethyl, 2-chloro-2-fluoroethyl, 2-chloro-2,2-difluoroethyl, 2, 2-dichloro-2-fluoroethyl, 2,2,2-trichloroethyl, pentafluoroethyl and 3-chloropropyl, preferably trifluoromethyl;
- Cyclooctyl preferably cyclopropyl, cyclopentyl and cyclohexyl
- each hydrogen is ⁇ atom replaced by the cyano group, eg cyano - methyl, 1-Cyanoeth-l-yl, 2-Cyanoeth-l-yl, 1-cyanoprop-l-yl , 2-cyanoprop-l-yl, 3-cyanoprop-l-yl, l-cyanoprop-2-yl, 2-cyano-prop-2-yl, 1-cyanobut-l-yl, 2-cyanobut-l-yl , 3-cyanobut-l-yl, 4-cyanobut-l-yl, l-cyanobut-2-yl, 2-cyanobut-2-yl, 1-cyano-but-3-yl, 2-cyanobut-3-yl , l-cyano-2-methyl-prop-3-yl, 2-cyano-2-methyl-prop-3-yl, 3-cyano-2-methyl-prop-3-yl, and 2-cyanomethyl-prop- 2-yl,
- C ⁇ -C 4 alkoxy and the alkoxy parts of C ⁇ -C 4 alkoxycarbonyl methoxy, ethoxy, n-propoxy, 1-methylethoxy, n-butoxy, 1-methylpropoxy, 2-methylpropoxy and 1, 1-dimethylethoxy, preferably Methoxy, ethoxy and 1-methylethoxy;
- Methylene ethylene, propylene, 1-methylethylene, butylene, 1,2-dimethylethyl and 1-ethylethylene;
- R 2 is chlorine or trifluoromethyl
- R 5 is an unsubstituted or substituted by halogen, C ⁇ -C 4 alkoxy C ⁇ -Cs-alkyl, C 2 -C 8 alkenyl or C 3 -Cs alkynyl radical, an unsubstituted C 3 -C 8 cycloalkyl radical or is a benzyl or phenyl radical which is unsubstituted in the phenyl moiety or substituted by halogen, C ⁇ -C 3 alkyl, C ⁇ -C 3 alkoxy, nitro, cyano or trifluoromethyl. and particularly preferably of compounds I in which
- R 2 is chlorine or trifluoromethyl
- R 5 is an unsubstituted or substituted by chlorine or methoxy C ⁇ -C 8 alkyl radical, a benzyl or phenyl radical unsubstituted in the phenyl part or substituted by chlorine, methyl, methoxy or trifluoromethyl.
- the thiopyridines I 'according to the invention are valuable precursors for the production of crop protection agents, in particular herbicides from the class of the phenylpyridines, as are described in WO-A 95/02580.
- Variant a starting from 2,3-dichloro-5-trifluoromethylpyridine
- the amount of catalyst (amount of copper in the first step of the one-pot synthesis could be reduced to 0.01% without loss of yield. If it was reduced again to 0.003% 35 Cu, the reaction time of the thioether synthesis increased to 6 hours and the yield decreased to 95.1% isolated sulfone.
- Variant b starting from 3-chloro-2-phenylthio-5-trifluoromethylpyridine
Abstract
Procédé de fabrication de thiopyridines de formule générale (I), dans laquelle les substituants peuvent avoir les significations données dans la description, caractérisé en ce qu'on fait réagir la 2-halogénopyridine substituée, de formule (II) dans laquelle Hal désigne le fluor, le chlore ou le brome, dans une première étape, avec un composé thio de formule (III) HS-R5, en présence d'un catalyseur au cuivre, de manière à obtenir tout d'abord un thioéther de pyridine de formule (Ia), et en ce qu'on oxyde ensuite celui-ci progressivement en sulfoxyde (Ib) ou en sulfone (Ic).
Applications Claiming Priority (3)
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DE19722661 | 1997-05-30 | ||
DE19722661 | 1997-05-30 | ||
PCT/EP1998/002879 WO1998054139A1 (fr) | 1997-05-30 | 1998-05-15 | Procede de fabrication de thiopyridines substituees |
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EP98929326A Withdrawn EP0984935A1 (fr) | 1997-05-30 | 1998-05-15 | Procede de fabrication de thiopyridines substituees |
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US (1) | US6191280B1 (fr) |
EP (1) | EP0984935A1 (fr) |
JP (1) | JP2002507197A (fr) |
WO (1) | WO1998054139A1 (fr) |
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DE102004042607A1 (de) * | 2004-09-03 | 2006-03-09 | Bayer Healthcare Ag | Substituierte Phenylaminothiazole und ihre Verwendung |
DE102006042143A1 (de) * | 2006-09-08 | 2008-03-27 | Bayer Healthcare Aktiengesellschaft | Neue substituierte Bipyridin-Derivate und ihre Verwendung |
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DE102006056740A1 (de) * | 2006-12-01 | 2008-06-05 | Bayer Healthcare Ag | Cyclisch substituierte 3,5-Dicyano-2-thiopyridine und ihre Verwendung |
DE102007035367A1 (de) | 2007-07-27 | 2009-01-29 | Bayer Healthcare Ag | Substituierte Aryloxazole und ihre Verwendung |
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DE102007061764A1 (de) * | 2007-12-20 | 2009-06-25 | Bayer Healthcare Ag | Anellierte Cyanopyridine und ihre Verwendung |
DE102007061763A1 (de) * | 2007-12-20 | 2009-06-25 | Bayer Healthcare Ag | Substituierte azabicyclische Verbindungen und ihre Verwendung |
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US3894035A (en) * | 1974-04-15 | 1975-07-08 | Dow Chemical Co | Bis-(thioalkylthio cyanato)halo pyridines |
EP0036638A3 (fr) * | 1980-03-24 | 1982-10-20 | Diamond Shamrock Corporation | 2-Sulfinyl et 2-sulfonyl pyridine N-oxydes à activité herbicide et régulatrice de la croissance des plantes |
GB2189485B (en) | 1986-04-17 | 1990-11-28 | Ici Plc | Derivatives of acrylic acid useful in agriculture |
EP0320448B1 (fr) | 1987-12-07 | 1994-12-28 | Ciba-Geigy Ag | 3-Aminobenzoylphénylurées |
DE4323916A1 (de) | 1993-07-16 | 1995-01-19 | Basf Ag | Substituierte 2-Phenylpyridine |
DE19636995A1 (de) | 1996-09-12 | 1998-03-19 | Basf Ag | Verfahren zur Herstellung substituierter Phenylpyridine |
US6262273B1 (en) | 1996-09-12 | 2001-07-17 | Basf Aktiengesellschaft | Substituted thiopyridines |
US6022884A (en) * | 1997-11-07 | 2000-02-08 | Amgen Inc. | Substituted pyridine compounds and methods of use |
-
1998
- 1998-05-15 US US09/423,961 patent/US6191280B1/en not_active Expired - Fee Related
- 1998-05-15 JP JP50016799A patent/JP2002507197A/ja active Pending
- 1998-05-15 EP EP98929326A patent/EP0984935A1/fr not_active Withdrawn
- 1998-05-15 WO PCT/EP1998/002879 patent/WO1998054139A1/fr not_active Application Discontinuation
Non-Patent Citations (1)
Title |
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See references of WO9854139A1 * |
Also Published As
Publication number | Publication date |
---|---|
JP2002507197A (ja) | 2002-03-05 |
WO1998054139A1 (fr) | 1998-12-03 |
US6191280B1 (en) | 2001-02-20 |
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