CN101952253A - 取代的酰联苯胺的制备方法 - Google Patents
取代的酰联苯胺的制备方法 Download PDFInfo
- Publication number
- CN101952253A CN101952253A CN2009801060257A CN200980106025A CN101952253A CN 101952253 A CN101952253 A CN 101952253A CN 2009801060257 A CN2009801060257 A CN 2009801060257A CN 200980106025 A CN200980106025 A CN 200980106025A CN 101952253 A CN101952253 A CN 101952253A
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- Prior art keywords
- palladium
- compound
- chloro
- carboxamide
- iii
- Prior art date
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Links
- 238000004519 manufacturing process Methods 0.000 title abstract 2
- JVRMUFJCFLXSMJ-UHFFFAOYSA-N n,2-diphenylbenzamide Chemical class C=1C=CC=C(C=2C=CC=CC=2)C=1C(=O)NC1=CC=CC=C1 JVRMUFJCFLXSMJ-UHFFFAOYSA-N 0.000 title abstract 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims abstract description 104
- 229910052763 palladium Inorganic materials 0.000 claims abstract description 51
- 150000001875 compounds Chemical class 0.000 claims abstract description 25
- 239000003054 catalyst Substances 0.000 claims abstract description 22
- 239000003446 ligand Substances 0.000 claims abstract description 16
- 239000002904 solvent Substances 0.000 claims abstract description 10
- 230000003647 oxidation Effects 0.000 claims abstract description 6
- 238000007254 oxidation reaction Methods 0.000 claims abstract description 6
- 150000003839 salts Chemical class 0.000 claims abstract 2
- 238000000034 method Methods 0.000 claims description 41
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims description 38
- QQVIHTHCMHWDBS-UHFFFAOYSA-N perisophthalic acid Natural products OC(=O)C1=CC=CC(C(O)=O)=C1 QQVIHTHCMHWDBS-UHFFFAOYSA-N 0.000 claims description 23
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims description 19
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 18
- 239000000203 mixture Substances 0.000 claims description 16
- ANQSYQOHGAJRKN-UHFFFAOYSA-N 1,1'-biphenyl;boric acid Chemical compound OB(O)O.C1=CC=CC=C1C1=CC=CC=C1 ANQSYQOHGAJRKN-UHFFFAOYSA-N 0.000 claims description 14
- -1 1-C 4-thiazolinyl Chemical group 0.000 claims description 11
- 239000003513 alkali Substances 0.000 claims description 10
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 claims description 9
- 239000004327 boric acid Substances 0.000 claims description 9
- 239000011737 fluorine Chemical group 0.000 claims description 9
- 229910052731 fluorine Inorganic materials 0.000 claims description 9
- 230000008569 process Effects 0.000 claims description 9
- 239000000460 chlorine Chemical group 0.000 claims description 7
- 229910052801 chlorine Chemical group 0.000 claims description 7
- 150000002940 palladium Chemical class 0.000 claims description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
- 229910052751 metal Inorganic materials 0.000 claims description 6
- 239000002184 metal Substances 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 5
- 239000003960 organic solvent Substances 0.000 claims description 5
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- JKDRQYIYVJVOPF-FDGPNNRMSA-L palladium(ii) acetylacetonate Chemical compound [Pd+2].C\C([O-])=C\C(C)=O.C\C([O-])=C\C(C)=O JKDRQYIYVJVOPF-FDGPNNRMSA-L 0.000 claims description 4
- FOUDIDNRZBCJFZ-UHFFFAOYSA-N 2-chloro-n-(2-chlorophenyl)pyridine-3-carboxamide Chemical compound ClC1=CC=CC=C1NC(=O)C1=CC=CN=C1Cl FOUDIDNRZBCJFZ-UHFFFAOYSA-N 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- CTHCTLCNUREAJV-UHFFFAOYSA-N heptane-2,4,6-trione Chemical compound CC(=O)CC(=O)CC(C)=O CTHCTLCNUREAJV-UHFFFAOYSA-N 0.000 claims description 3
- 125000000623 heterocyclic group Chemical group 0.000 claims description 3
- 238000006467 substitution reaction Methods 0.000 claims description 3
- TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 claims description 3
- CFPFMAGBHTVLCZ-UHFFFAOYSA-N (4-chlorophenoxy)boronic acid Chemical compound OB(O)OC1=CC=C(Cl)C=C1 CFPFMAGBHTVLCZ-UHFFFAOYSA-N 0.000 claims description 2
- 125000006728 (C1-C6) alkynyl group Chemical group 0.000 claims description 2
- UENGBOCGGKLVJJ-UHFFFAOYSA-N 2-chloro-1-(2,4-difluorophenyl)ethanone Chemical compound FC1=CC=C(C(=O)CCl)C(F)=C1 UENGBOCGGKLVJJ-UHFFFAOYSA-N 0.000 claims description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 claims description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims 1
- 125000001033 ether group Chemical group 0.000 claims 1
- 150000002431 hydrogen Chemical group 0.000 claims 1
- VIGVRXYWWFPORY-UHFFFAOYSA-N diphenylborinic acid Chemical compound C=1C=CC=CC=1B(O)C1=CC=CC=C1 VIGVRXYWWFPORY-UHFFFAOYSA-N 0.000 abstract 1
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 40
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 20
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical class C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 6
- 229910052783 alkali metal Inorganic materials 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 4
- 150000001335 aliphatic alkanes Chemical class 0.000 description 4
- 150000001340 alkali metals Chemical class 0.000 description 4
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 3
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 3
- 235000010290 biphenyl Nutrition 0.000 description 3
- 239000004305 biphenyl Substances 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical class CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Chemical compound [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 150000002170 ethers Chemical class 0.000 description 2
- JEIPFZHSYJVQDO-UHFFFAOYSA-N ferric oxide Chemical compound O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 150000002430 hydrocarbons Chemical class 0.000 description 2
- 235000012204 lemonade/lime carbonate Nutrition 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
- QWUWMCYKGHVNAV-UHFFFAOYSA-N 1,2-dihydrostilbene Chemical group C=1C=CC=CC=1CCC1=CC=CC=C1 QWUWMCYKGHVNAV-UHFFFAOYSA-N 0.000 description 1
- BFCFYVKQTRLZHA-UHFFFAOYSA-N 1-chloro-2-nitrobenzene Chemical class [O-][N+](=O)C1=CC=CC=C1Cl BFCFYVKQTRLZHA-UHFFFAOYSA-N 0.000 description 1
- YOJKKXRJMXIKSR-UHFFFAOYSA-N 1-nitro-2-phenylbenzene Chemical group [O-][N+](=O)C1=CC=CC=C1C1=CC=CC=C1 YOJKKXRJMXIKSR-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- YLMFXCIATJJKQL-UHFFFAOYSA-N 2-bromo-4-fluoroaniline Chemical compound NC1=CC=C(F)C=C1Br YLMFXCIATJJKQL-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- PRELXWWNUSISME-UHFFFAOYSA-N 3-methyl-1-(trifluoromethyl)cyclohex-4-ene-1,3-dicarboxylic acid Chemical compound FC(C1(CC(C(=O)O)(C=CC1)C)C(=O)O)(F)F PRELXWWNUSISME-UHFFFAOYSA-N 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 1
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 1
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- SVYKKECYCPFKGB-UHFFFAOYSA-N N,N-dimethylcyclohexylamine Chemical compound CN(C)C1CCCCC1 SVYKKECYCPFKGB-UHFFFAOYSA-N 0.000 description 1
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical group OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 1
- 239000004721 Polyphenylene oxide Substances 0.000 description 1
- CUJRVFIICFDLGR-UHFFFAOYSA-N acetylacetonate Chemical compound CC(=O)[CH-]C(C)=O CUJRVFIICFDLGR-UHFFFAOYSA-N 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- 125000005210 alkyl ammonium group Chemical group 0.000 description 1
- 229910000323 aluminium silicate Inorganic materials 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- AYJRCSIUFZENHW-DEQYMQKBSA-L barium(2+);oxomethanediolate Chemical compound [Ba+2].[O-][14C]([O-])=O AYJRCSIUFZENHW-DEQYMQKBSA-L 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 229910000085 borane Inorganic materials 0.000 description 1
- 150000001642 boronic acid derivatives Chemical class 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical class CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 1
- 239000001273 butane Substances 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000007942 carboxylates Chemical group 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000009841 combustion method Methods 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000006880 cross-coupling reaction Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- GUJOJGAPFQRJSV-UHFFFAOYSA-N dialuminum;dioxosilane;oxygen(2-);hydrate Chemical compound O.[O-2].[O-2].[O-2].[Al+3].[Al+3].O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O GUJOJGAPFQRJSV-UHFFFAOYSA-N 0.000 description 1
- LCSNDSFWVKMJCT-UHFFFAOYSA-N dicyclohexyl-(2-phenylphenyl)phosphane Chemical group C1CCCCC1P(C=1C(=CC=CC=1)C=1C=CC=CC=1)C1CCCCC1 LCSNDSFWVKMJCT-UHFFFAOYSA-N 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
- HNPSIPDUKPIQMN-UHFFFAOYSA-N dioxosilane;oxo(oxoalumanyloxy)alumane Chemical compound O=[Si]=O.O=[Al]O[Al]=O HNPSIPDUKPIQMN-UHFFFAOYSA-N 0.000 description 1
- GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 description 1
- 239000002019 doping agent Substances 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 description 1
- OTCKOJUMXQWKQG-UHFFFAOYSA-L magnesium bromide Chemical class [Mg+2].[Br-].[Br-] OTCKOJUMXQWKQG-UHFFFAOYSA-L 0.000 description 1
- IWCVDCOJSPWGRW-UHFFFAOYSA-M magnesium;benzene;chloride Chemical compound [Mg+2].[Cl-].C1=CC=[C-]C=C1 IWCVDCOJSPWGRW-UHFFFAOYSA-M 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 229910052901 montmorillonite Inorganic materials 0.000 description 1
- 230000002371 mycocidal effect Effects 0.000 description 1
- NZKCGJMEQDDBFJ-UHFFFAOYSA-N n-(2-bromo-4-fluorophenyl)-3-(difluoromethyl)-1-methylpyrazole-4-carboxamide Chemical compound FC(F)C1=NN(C)C=C1C(=O)NC1=CC=C(F)C=C1Br NZKCGJMEQDDBFJ-UHFFFAOYSA-N 0.000 description 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 1
- 235000005152 nicotinamide Nutrition 0.000 description 1
- 239000011570 nicotinamide Substances 0.000 description 1
- JVJQPDTXIALXOG-UHFFFAOYSA-N nitryl fluoride Chemical compound [O-][N+](F)=O JVJQPDTXIALXOG-UHFFFAOYSA-N 0.000 description 1
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 125000002524 organometallic 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
- 239000012071 phase Substances 0.000 description 1
- 238000005191 phase separation Methods 0.000 description 1
- 150000003009 phosphonic acids Chemical class 0.000 description 1
- 229920000570 polyether Polymers 0.000 description 1
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 125000001273 sulfonato group Chemical group [O-]S(*)(=O)=O 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- UORVGPXVDQYIDP-UHFFFAOYSA-N trihydridoboron Substances B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 239000003021 water soluble solvent Substances 0.000 description 1
- 238000004857 zone melting Methods 0.000 description 1
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- 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
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
- C07D213/82—Amides; Imides in position 3
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members 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
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Abstract
本发明涉及一种制备式(I)的取代的酰联苯胺的方法，所述方法包括在碱和钯催化剂存在下，使式(II)的化合物与式(III)的二苯基硼酸在溶剂中反应，所述钯催化剂选自：a)其中钯为零氧化态的钯-三芳基膦或钯-三烷基膦络合物，b)在作为配位配体的三芳基膦或三烷基膦存在下的钯盐，或者c)在三芳基膦或三烷基膦存在下任选地施用于载体上的金属钯。
Description
本发明涉及一种制备式(I)的取代的酰联苯胺(biphenylanilide)的方法，
其中取代基的定义如下：
Het为选自以下的杂环基残基：
其中“#”表示所述残基的取代位置；
X为氢、氟或氯；
R1为C1-C6-卤代烷基；
R2为氰基、硝基、卤素、C1-C6-烷基、C1-C6-烯基、C1-C6-炔基、C1-C6-烷氧基、C1-C6-卤代烷基、(C1-C6-烷基)羰基或苯基；
n为1、2或3，其中在n为2或3的情况下，R2基团也可以不同，所述方法包括在碱和钯催化剂存在下使式(II)的化合物与式(III)的二苯基硼酸在溶剂中反应，
在式(II)中，Hal为卤素，且X和Het的定义同上，
在式(III)中，R2和n的定义同上，
其中所述钯催化剂选自：a)其中钯为零氧化态的钯-三芳基膦或钯-三烷基膦络合物，b)在作为配位配体的三芳基膦或三烷基膦存在下的钯盐，或者c)在三芳基膦或三烷基膦存在下任选地施用于载体上的金属钯，其中所用的三芳基膦或三烷基膦可以被取代。
Tetrahedron Lett.32，第2277页(1991)声称使用[1，4-二(二苯基膦)-丁烷]二氯化钯(II)催化剂进行的苯基硼酸和氯苯之间的偶联反应的产率仅为28％。
EP-A 0 888 261披露了一种通过使氯代硝基苯类与苯基硼酸在钯催化剂和碱存在下反应来制备硝基联苯的方法。在该方法中，需要非常高的催化剂浓度。
WO 2006/092429和WO 2007/138089各自涉及一种通过在钯催化剂存在下使取代的二苯基硼酸类和二卤代芳基化合物偶联来制备取代联苯的方法。
因此，本发明的一个目的是提供一种经济上可行的方法，其可以使用降低的钯催化剂浓度，以工业规模实施，用于区域选择性地制备取代的酰联苯胺。
因此，发现了在本文一开始所定义的方法。
根据WO 2007/138089，二苯基硼酸(III)通过任选取代的苯基氯化镁V与硼酸三烷基酯(优选硼酸三甲基酯)在作为溶剂的四氢呋喃中反应来获得，如方案1所述。
方案1
R4为C1-C4-烷基，优选甲基。
二苯基硼酸(III)的高收率的关键在于，基于所用的取代氯苯(IV)，仅采用0.7当量的硼酸三烷基酯。如EP-A 0 888 261中所述，使用1.1当量的硼酸三烷基酯产生苯基硼酸。
该过程阶段的反应温度为20至60℃，优选40至50℃。
由本发明方法制备的取代联苯具有以下优选的取代基，在每种情形下，所述取代基可单独存在或组合存在。
Het为选自以下的杂环基残基：
其中“#”表示所述残基的取代位置；
R1为三氟甲基或二氟甲基，更优选二氟甲基；
R2为氰基、硝基、氟、氯、溴、甲基、乙基、丙基、丁基、烯丙基、炔丙基、甲氧基、乙氧基、三氟甲基或苯基，更优选氟、氯、甲基或甲氧基，最优选氟或氯；
n为1或2，优选2。
根据方案2进行随后的均匀催化的铃木(Suzuki)联芳基交叉偶联反应。
方案2
优选从式(III)的二苯基硼酸开始，其中R2和n的定义同上。
进一步优选的原料是其中n为1或2，特别是2的二苯基硼酸(III)。特别优选的是3-位和4-位上或者仅在4-位上被取代的二苯基硼酸(III)。
非常特别优选二(2，3-二氟苯基)硼酸、二(3，4-二氟苯基)硼酸、二(2，3-二氯苯基)硼酸以及尤其是二(3，4-二氯苯基)硼酸和(4-氯苯基)硼酸作为起始化合物(III)。
优选从以下化合物(II)开始：
N-(2-氯-4-氟苯基)-3-(二氟甲基)-1-甲基-1H-吡唑-4-甲酰胺、N-(2-溴-4-氟苯基)-3-(二氟甲基)-1-甲基-1H-吡唑-4-甲酰胺、N-(2-氯-4-氟苯基)-3-(三氟甲基)-1-甲基-1H-吡唑-4-甲酰胺、N-(2-溴-4-氟苯基)-3-(三氟甲基)-1-甲基-1H-吡唑-4-甲酰胺、N-(2-氯-6-氟苯基)-3-(二氟甲基)-1-甲基-1H-吡唑-4-甲酰胺、N-(2-溴-6-氟苯基)-3-(二氟甲基)-1-甲基-1H-吡唑-4-甲酰胺、N-(2-氯-6-氟苯基)-3-(三氟甲基)-1-甲基-1H-吡唑-4-甲酰胺、N-(2-溴-6-氟苯基)-3-(三氟甲基)-1-甲基-1H-吡唑-4-甲酰胺、N-(2-氯苯基)-3-(二氟甲基)-1-甲基-1H-吡唑-4-甲酰胺、N-(2-溴苯基)-3-(二氟甲基)-1-甲基-1H-吡唑-4-甲酰胺、N-(2-氯苯基)-3-(三氟甲基)-1-甲基-1H-吡唑-4-甲酰胺、N-(2-溴苯基)-3-(三氟甲基)-1-甲基-1H-吡唑-4-甲酰胺、2-氯-N-(2-氯苯基)吡啶-3-甲酰胺、2-氯-N-(2-溴苯基)吡啶-3-甲酰胺，特别优选的是N-(2-氯-4-氟苯基)-3-(二氟甲基)-1-甲基-1H-吡唑-4-甲酰胺、N-(2-溴-4-氟苯基)-3-(二氟甲基)-1-甲基-1H-吡唑-4-甲酰胺、2-氯-N-(2-氯苯基)吡啶-3-甲酰胺和2-氯-N-(2-溴苯基)吡啶-3-甲酰胺。
式(II)的化合物可以如WO 03/070705所述进行制备。例如，使用1-甲基-3-(三氟甲基)-1H-吡唑-4-羰基氯和2-溴-4-氟苯胺作为原料以及碱，如下述方程式所示：
基于二苯基硼酸类(III)(二苯基硼酸等同物)，通常以等摩尔量，优选过量高达20％，特别是过量高达50％来使用化合物(II)。所用的碱可以是有机碱，例如叔胺。优选使用例如三乙胺或二甲基环己胺。所用的碱优选为碱金属氢氧化物、碱土金属氢氧化物、碱金属碳酸盐、碱土金属碳酸盐、碱金属碳酸氢盐、碱金属乙酸盐、碱土金属乙酸盐、碱金属醇盐和碱土金属醇盐，其混合物，特别是单独使用。特别优选的碱为碱金属氢氧化物、碱土金属氢氧化物、碱金属碳酸盐、碱土金属碳酸盐和碱金属碳酸氢盐。尤其优选的碱为碱金属氢氧化物(例如氢氧化钠和氢氧化钾)以及碱金属碳酸盐和碱金属碳酸氢盐(例如碳酸锂、碳酸钠和碳酸钾)。基于二苯基硼酸(III)的量，本发明方法中所用的碱的份数优选为100至500摩尔％，更优选150至400摩尔％。合适的钯催化剂为其中钯为零氧化态的钯-配体络合物、在配位配体存在下的钯盐，或者优选在配位配体存在下任选地施用于载体的金属钯。合适的配位配体为不带电荷的配体，例如三芳基膦和三烷基膦，其可以任选地在芳环上被取代，例如三苯基膦(TPP)、二-1-金刚烷基-正丁基膦、三叔丁基膦(TtBP)或2-(二环己基膦基)联苯。
此外，文献中也已经进一步描述了来自其他结构类的独特反应性配位配体，包括1，3-双(2，6-二异丙基苯基)-4，5-H2-氯化咪
(参见例如G.A.Grasa等，Organometallics 2002，21，2866)和三(2，4-二叔丁基苯基)亚磷酸酯(参见A.Zapf等，Chem.Eur.J.2000，6，1830)。
通过添加季铵盐例如四正丁基溴化铵(TBAB)，可以提高配位配体的反应性(参见例如D.Zim等，Tetrahedron Lett.2000，41，8199)。必要时，通过各种取代基例如磺酸或磺酸盐基团，羧酸或羧酸盐基团，膦酸、
或膦酸盐基团，全烷基铵，羟基和聚醚基，可以提高钯络合物的水溶性。在其中钯为零氧化态的钯-配体络合物中，优选使用四(三苯基膦)钯以及另外的四[三(邻甲苯基)膦]钯。在配位配体存在下使用的钯盐中，钯通常以正二价的氧化态存在。优选使用氯化钯、乙酸钯、乙酰丙酮钯(Pd(acac)2)或者双乙腈氯化钯。特别优选使用二乙酰丙酮钯(Pd(acac)2)。
一般而言，使1至60当量、优选1至25当量上述配位配体(特别是三苯基膦)与1当量钯盐相结合。
在本发明的一个最优选的实施方案中，以等摩尔量使用二乙酰丙酮钯和三叔丁基膦。
EP-A 0 888 261描述了每当量钯催化剂使用2至6当量三苯基膦。文献中通常认为使用高过量的配体是不利的，这是因为预计这将导致催化活性的络合物失活(参见例如J.Hassan等，Chem.Rev.2002，102，1359)。因此，这种高的三苯基膦用量结合低的催化剂用量导致本发明方法的总产率增加并因此提高经济可行性是出乎意料的。所用的金属钯优选为粉碎形式或在载体材料上，例如活性炭上的钯、氧化铝上的钯、碳酸钡上的钯、硫酸钡上的钯、碳酸钙上的钯、钯铝硅酸盐例如蒙脱石、SiO2上的钯和碳酸钙上的钯的形式，在每种情形下，钯含量为0.5至12wt％。除了钯和载体材料之外，这些催化剂可含有其他掺杂剂(例如铅)。
当使用任选地施用于载体的金属钯时，同样特别优选使用上述配位配体，特别是在作为配位配体的三苯基膦的存在下使用活性炭上的钯，其中三苯基膦中的苯基优选被总共1至3个磺酸根/酯基团所取代。在本发明的方法中，，使用基于化合物(II)之量的0.001至1.0摩尔％、优选0.005至0.5摩尔％或0.01至0.5摩尔％、特别是0.005至0.05摩尔％的低份数的钯催化剂。
低用量的钯盐结合高用量的配位配体构成该方法相比于现有技术方法的显著成本优势。
本发明的方法可以在由水相和固体相(即催化剂)构成的两相体系中进行。在这种情况下，水相中除了水之外，还可以含有水溶性有机溶剂。
适用于本发明方法的有机溶剂为醚类，例如二甲氧基乙烷、二甘醇二甲醚、四氢呋喃、二
烷和叔丁基甲醚；烃类，例如正己烷、正庚烷、环己烷、苯、甲苯和二甲苯；醇类，例如甲醇、乙醇、1-丙醇、2-丙醇、乙二醇、1-丁醇、2-丁醇和叔丁醇；酮类，例如丙酮、甲乙酮和异丁基甲基酮；酰胺类，例如二甲基甲酰胺、二甲基乙酰胺和N-甲基吡咯烷酮，在每种情形下都可以单独使用或者以混合物使用。
优选的溶剂为醚类，例如二甲氧基乙烷、四氢呋喃和二
烷；烃类，例如环己烷、甲苯和二甲苯；醇类，例如乙醇、1-丙醇、2-丙醇、1-丁醇和叔丁醇，在每种情形下都可以单独使用或者以混合物使用。在本发明方法的一个特别优选的变化方案中，使用水、一种或多种不溶于水的溶剂以及一种或多种水溶性溶剂，例如水和
烷的混合物，或者水和四氢呋喃的混合物，或者水、二烷和乙醇的混合物，或者水、四氢呋喃和甲醇的混合物，或者水、甲苯和四氢呋喃的混合物，优选水和四氢呋喃的混合物，或者水、四氢呋喃和甲醇的混合物。
溶剂的总量通常以1摩尔化合物(II)计为3000至500g，优选为2000至700g。
适当地，如下实施所述方法：向水和一种或更多种惰性有机溶剂的混合物中添加化合物(II)、二苯基硼酸类(III)、碱和催化量的钯催化剂，并且在50℃至120℃、优选70℃至110℃、更优选90℃至100℃的温度下搅拌1至50小时、优选2至24小时。
取决于所用的溶剂和温度，确定1巴至6巴、优选1巴至4巴的压力。优选在水和四氢呋喃中反应。可以在适于这类方法的常规设备中进行反应。反应完成后，例如通过过滤去除作为固体获得的钯催化剂，并且从溶剂或更多种溶剂中获得粗产物。在产物不完全溶于水的情况下，在水相分离时从粗产物中完全除去水溶性的钯催化剂或配位配体。随后，可以通过本领域技术人员已知的且适用于特定产物的方法(例如重结晶、蒸馏、升华、区域熔化、熔融结晶或色谱法)实现进一步纯化。
在本发明的又一优选实施方案中，反应是在甲苯中或者在水和甲苯的混合物例如1/1混合物(水/甲苯)中进行的。反应完成后，可以通过相分离对产物和催化剂进行分离。
通过本发明的方法，可以制备例如：2-氯-N-(4′-氯联苯基-2-基)吡啶-3-甲酰胺、N-(3′，4′-二氯联苯基-2-基)-3-(二氟甲基)-1-甲基-1H-吡唑-4-甲酰胺、N-(3′，4′-二氯-5-氟联苯基-2-基)-3-(二氟甲基)-1-甲基-1H-吡唑-4-甲酰胺、3-(三氟甲基)-1-甲基-1H-吡唑-4-甲酰胺、N-(3′，4′-二氯-5-氟联苯基-2-基)-3-(三氟甲基)-1-甲基-1H-吡唑-4-甲酰胺。
本发明方法提供非常高的高达定量产率的并且纯度非常好的化合物I。可由本发明方法获得的取代联苯适合用作杀真菌的作物保护活性成分的前体(参见WO 03/070705)。
实施例
实施例1：合成二(3，4-二氯苯基)硼酸
向干烧瓶中加入在DCM中的三溴硼烷(13ml，13mmol，1M)。将该溶液冷却至-62℃，并且向该***液中逐滴加入(3，4-二氯苯基)溴化镁(50ml，25mmol，0.5M在THF中)。使反应混合物升温至室温并搅拌过夜。真空下除去溶剂，并将残余物溶解在DCM中且通过缓慢加入INHCl水解。分离有机层并用盐水清洗，真空下除去溶剂。通过硅胶色谱采用25％乙酸乙酯作为洗脱剂纯化所得油，得到固体的标题化合物(3.34g，10.4mmol，产率80％)。
实施例2：合成N-(3’，4’-二氯-5-氟联苯基-2-基)-3-(二氟甲基)-1-甲基-1H-吡唑-4-甲酰胺(DMI 3-5)
在0.5L的双夹套反应器中加入178g在THF/甲苯混合物(2/3w/w)中的二(3，4-二氯苯基)硼酸(0.2mol)溶液和13g水。加入10％氢氧化钠水溶液(32g)将pH调至7.4。加入N-(2-溴-4-氟苯基)-1-甲基-3-(二氟甲基)-1H-吡唑-4-甲酰胺(56g，0.2mol)，随后使反应混合物脱氧并加热到75至80℃。在该温度下加入溶于水和甲苯的1/1混合物中的0.06g(0.2mmol)乙酰丙酮钯和0.06g(0.2mmol)四氟硼酸三叔丁基
。将pH调到8.0至8.5并且通过加入10％w/w氢氧化钠溶液(消耗98g)将pH保持在该范围内。在反应结束后，将反应混合物冷却至20℃并分离掉水相(195g)。有机层(190g)含有22％w/w(HPLC)的N-(3’，4’-二氯-5-氟联苯基-2-基)-3-(二氟甲基)-1-甲基-1H-吡唑-4-甲酰胺(产率50％)。
Claims (18)
1.一种制备式(I)的取代的酰联苯胺的方法，
Het为选自以下的杂环基残基：
其中“#”表示所述残基的取代位置；
X为氢、氟或氯；
R1为C1-C6-卤代烷基；
R2为氰基、硝基、卤素、C1-C6-烷基、C1-C6-烯基、C1-C6-炔基、C1-C6-烷氧基、C1-C6-卤代烷基、(C1-C6-烷基)羰基或苯基；
R3为C1-C4-烷基、C1-C4-烯基或C1-C4-炔基；
n为1、2或3，其中在n为2或3的情况下，R2基团也可以不同，
所述方法包括在碱和钯催化剂存在下使式(II)的化合物与式(III)的二苯基硼酸在溶剂中反应，
在式(II)中，Hal为卤素，且X和Het的定义同上，
在式(III)中，R2和n的定义同上，
其中所述钯催化剂选自：
a)其中钯为零氧化态的钯-三芳基膦或钯-三烷基膦络合物，
b)在作为配位配体的三芳基膦或三烷基膦存在下的钯盐，或者
c)在三芳基膦或三烷基膦存在下任选地施用于载体上的金属钯，
其中所用的三芳基膦或三烷基膦可以被取代。
2.根据权利要求1的方法，其中所用化合物(II)选自N-(2-氯-4-氟苯基)-3-(二氟甲基)-1-甲基-1H-吡唑-4-甲酰胺、N-(2-溴-4-氟苯基)-3-(二氟甲基)-1-甲基-1H-吡唑-4-甲酰胺、2-氯-N-(2-氯苯基)吡啶-3-甲酰胺和2-氯-N-(2-溴苯基)吡啶-3-甲酰胺。
3.根据权利要求1或2的方法，其中起始化合物(III)为3-位和4-位上被取代的二苯基硼酸。
4.根据权利要求1或2的方法，其中使用在3-位和4-位上带有氟或氯的二苯基硼酸(III)。
5.根据权利要求1或2的方法，其中起始化合物(III)为二(3，4-二氯苯基)硼酸。
6.根据权利要求1至5的方法，其中所用的权利要求1的钯催化剂a)为四(三苯基膦)钯或四(三叔丁基膦)钯。
7.根据权利要求1至5的方法，其中使用权利要求1的钯催化剂b)。
8.根据权利要求1至5的方法，其中所用的权利要求1的钯催化剂c)为在三苯基膦存在下在活性炭上的金属钯，所述三苯基膦的苯基总共被1至3个磺酸根/酯基团所取代。
9.根据权利要求7的方法，其中所用的钯催化剂b)的盐为氯化钯、醋酸钯、二乙酰丙酮钯(Pd(acac)2)或双乙腈氯化钯。
10.根据权利要求7的方法，其中使用钯催化剂b)，对于每当量钯盐，使用6至60当量三苯基膦。
11.根据权利要求1的方法，其中基于化合物(II)的量，使用0.001至1.0摩尔％的钯催化剂。
12.根据权利要求1的方法，其中反应在50至120℃的温度下进行。
13.根据权利要求1的方法，其中反应在水和有机溶剂的混合物中进行。
14.根据权利要求13的方法，其中所用的有机溶剂为醚。
15.根据权利要求1的方法，其中反应在1至6巴的压力下进行。
16.根据权利要求1的方法，其中化合物(II)为N-(2-氯-4-氟苯基)-3-(二氟甲基)-1-甲基-1H-吡唑-4-甲酰胺，化合物(III)为二(3，4-二氯苯基)硼酸。
17.根据权利要求1的方法，其中化合物(II)为N-(2-氯苯基)-3-(二氟甲基)-1-甲基-1H-吡唑-4-甲酰胺，化合物(III)为二(3，4-二氯苯基)硼酸。
18.根据权利要求1的方法，其中化合物(II)为2-氯-N-(2-溴苯基)吡啶-3-甲酰胺，化合物(III)为(4-氯苯基)硼酸。
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| PCT/EP2009/000986 WO2009106234A1 (en) | 2008-02-25 | 2009-02-12 | Process for preparing substituted biphenylanilides |
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| KR102082532B1 (ko) | 2012-08-20 | 2020-02-27 | 마낙 가부시끼가이샤 | 보린산 유도체의 제조 방법 및 신규 보린산 유도체 |
| ES2860673T3 (es) | 2013-11-29 | 2021-10-05 | Basf Se | Sistema de poliuretano con un largo tiempo de tratamiento y un curado rápido. |
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| KR20100136455A (ko) | 2010-12-28 |
| EP2257530B1 (en) | 2011-10-12 |
| JP5512551B2 (ja) | 2014-06-04 |
| KR101652360B1 (ko) | 2016-08-30 |
| BRPI0908261A2 (pt) | 2015-07-21 |
| MX2010008663A (es) | 2010-09-24 |
| EP2257530A1 (en) | 2010-12-08 |
| DK2257530T3 (da) | 2012-02-06 |
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