JP2008156347A - Novel acetophenone compound and manufacturing method of acetophenones - Google Patents
Novel acetophenone compound and manufacturing method of acetophenones Download PDFInfo
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- JP2008156347A JP2008156347A JP2007309255A JP2007309255A JP2008156347A JP 2008156347 A JP2008156347 A JP 2008156347A JP 2007309255 A JP2007309255 A JP 2007309255A JP 2007309255 A JP2007309255 A JP 2007309255A JP 2008156347 A JP2008156347 A JP 2008156347A
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- alkyl
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- -1 acetophenone compound Chemical class 0.000 title claims abstract description 158
- 150000008062 acetophenones Chemical class 0.000 title claims abstract description 21
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 18
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Natural products CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 title claims abstract description 10
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims abstract description 49
- 229910052763 palladium Inorganic materials 0.000 claims abstract description 24
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 22
- 150000001875 compounds Chemical class 0.000 claims abstract description 19
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000003054 catalyst Substances 0.000 claims abstract description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000003446 ligand Substances 0.000 claims abstract description 6
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims abstract description 6
- 150000004982 aromatic amines Chemical class 0.000 claims abstract description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 20
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 20
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 16
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 11
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 11
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 10
- 229910052731 fluorine Inorganic materials 0.000 claims description 10
- 125000001153 fluoro group Chemical group F* 0.000 claims description 10
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 10
- 239000002904 solvent Substances 0.000 claims description 10
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 8
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 7
- 125000004741 (C1-C6) haloalkylsulfonyl group Chemical group 0.000 claims description 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims description 5
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 4
- 125000006771 (C1-C6) haloalkylthio group Chemical group 0.000 claims description 4
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 3
- 125000003368 amide group Chemical group 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 229910052740 iodine Inorganic materials 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 239000012046 mixed solvent Substances 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- 125000005951 trifluoromethanesulfonyloxy group Chemical group 0.000 claims description 2
- 230000000397 acetylating effect Effects 0.000 claims 4
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 4
- NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 claims 3
- 239000007858 starting material Substances 0.000 claims 2
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims 1
- 238000002955 isolation Methods 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 abstract description 40
- 239000002253 acid Substances 0.000 abstract description 4
- 150000001412 amines Chemical class 0.000 abstract 1
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 36
- 125000004432 carbon atom Chemical group C* 0.000 description 31
- LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-bis(diphenylphosphino)propane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 description 22
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 20
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
- 239000000203 mixture Substances 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- 229910000027 potassium carbonate Inorganic materials 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 239000012299 nitrogen atmosphere Substances 0.000 description 9
- 239000010410 layer Substances 0.000 description 8
- ZBTMRBYMKUEVEU-UHFFFAOYSA-N 1-bromo-4-methylbenzene Chemical compound CC1=CC=C(Br)C=C1 ZBTMRBYMKUEVEU-UHFFFAOYSA-N 0.000 description 7
- HMBNQNDUEFFFNZ-UHFFFAOYSA-N 4-ethenoxybutan-1-ol Chemical compound OCCCCOC=C HMBNQNDUEFFFNZ-UHFFFAOYSA-N 0.000 description 7
- 239000000543 intermediate Substances 0.000 description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 238000004445 quantitative analysis Methods 0.000 description 6
- 238000006640 acetylation reaction Methods 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-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
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- 125000005843 halogen group Chemical group 0.000 description 4
- 150000002430 hydrocarbons Chemical group 0.000 description 4
- IJZSFOIZVXCSFP-UHFFFAOYSA-N n-(4-bromo-2-methylphenyl)acetamide Chemical compound CC(=O)NC1=CC=C(Br)C=C1C IJZSFOIZVXCSFP-UHFFFAOYSA-N 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 239000012345 acetylating agent Substances 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 125000003545 alkoxy group Chemical group 0.000 description 3
- 150000001721 carbon Chemical group 0.000 description 3
- QVQGTNFYPJQJNM-UHFFFAOYSA-N dicyclohexylmethanamine Chemical compound C1CCCCC1C(N)C1CCCCC1 QVQGTNFYPJQJNM-UHFFFAOYSA-N 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 238000009776 industrial production Methods 0.000 description 3
- UMWGYGAELKNLHK-UHFFFAOYSA-N n-(4-acetyl-2-methylphenyl)acetamide Chemical compound CC(=O)NC1=CC=C(C(C)=O)C=C1C UMWGYGAELKNLHK-UHFFFAOYSA-N 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- GNKZMNRKLCTJAY-UHFFFAOYSA-N 4'-Methylacetophenone Chemical compound CC(=O)C1=CC=C(C)C=C1 GNKZMNRKLCTJAY-UHFFFAOYSA-N 0.000 description 2
- NTPLXRHDUXRPNE-UHFFFAOYSA-N 4-methoxyacetophenone Chemical compound COC1=CC=C(C(C)=O)C=C1 NTPLXRHDUXRPNE-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 239000003905 agrochemical Substances 0.000 description 2
- 150000001335 aliphatic alkanes Chemical class 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 2
- 150000008041 alkali metal carbonates Chemical class 0.000 description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 2
- 238000005893 bromination reaction Methods 0.000 description 2
- WERYXYBDKMZEQL-UHFFFAOYSA-N butane-1,4-diol Chemical compound OCCCCO WERYXYBDKMZEQL-UHFFFAOYSA-N 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 125000000753 cycloalkyl group Chemical group 0.000 description 2
- 238000007872 degassing Methods 0.000 description 2
- 229910001873 dinitrogen Inorganic materials 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- UWDMTHJPTMJZNG-UHFFFAOYSA-N ethyl 4-bromo-2-methylbenzoate Chemical compound CCOC(=O)C1=CC=C(Br)C=C1C UWDMTHJPTMJZNG-UHFFFAOYSA-N 0.000 description 2
- 125000006125 ethylsulfonyl group Chemical group 0.000 description 2
- 239000002638 heterogeneous catalyst Substances 0.000 description 2
- ZSIAUFGUXNUGDI-UHFFFAOYSA-N hexan-1-ol Chemical compound CCCCCCO ZSIAUFGUXNUGDI-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- FSPSELPMWGWDRY-UHFFFAOYSA-N m-Methylacetophenone Chemical compound CC(=O)C1=CC=CC(C)=C1 FSPSELPMWGWDRY-UHFFFAOYSA-N 0.000 description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- BKIMMITUMNQMOS-UHFFFAOYSA-N nonane Chemical compound CCCCCCCCC BKIMMITUMNQMOS-UHFFFAOYSA-N 0.000 description 2
- RNVCVTLRINQCPJ-UHFFFAOYSA-N o-toluidine Chemical compound CC1=CC=CC=C1N RNVCVTLRINQCPJ-UHFFFAOYSA-N 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 239000000575 pesticide Substances 0.000 description 2
- 239000003444 phase transfer catalyst Substances 0.000 description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- YPFDHNVEDLHUCE-UHFFFAOYSA-N propane-1,3-diol Chemical compound OCCCO YPFDHNVEDLHUCE-UHFFFAOYSA-N 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 2
- HVLLSGMXQDNUAL-UHFFFAOYSA-N triphenyl phosphite Chemical compound C=1C=CC=CC=1OP(OC=1C=CC=CC=1)OC1=CC=CC=C1 HVLLSGMXQDNUAL-UHFFFAOYSA-N 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- BWHDROKFUHTORW-UHFFFAOYSA-N tritert-butylphosphane Chemical compound CC(C)(C)P(C(C)(C)C)C(C)(C)C BWHDROKFUHTORW-UHFFFAOYSA-N 0.000 description 2
- ZKWQSBFSGZJNFP-UHFFFAOYSA-N 1,2-bis(dimethylphosphino)ethane Chemical compound CP(C)CCP(C)C ZKWQSBFSGZJNFP-UHFFFAOYSA-N 0.000 description 1
- QFMZQPDHXULLKC-UHFFFAOYSA-N 1,2-bis(diphenylphosphino)ethane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCP(C=1C=CC=CC=1)C1=CC=CC=C1 QFMZQPDHXULLKC-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- BUZYGTVTZYSBCU-UHFFFAOYSA-N 1-(4-chlorophenyl)ethanone Chemical compound CC(=O)C1=CC=C(Cl)C=C1 BUZYGTVTZYSBCU-UHFFFAOYSA-N 0.000 description 1
- ZDPAWHACYDRYIW-UHFFFAOYSA-N 1-(4-fluorophenyl)ethanone Chemical compound CC(=O)C1=CC=C(F)C=C1 ZDPAWHACYDRYIW-UHFFFAOYSA-N 0.000 description 1
- QSSXJPIWXQTSIX-UHFFFAOYSA-N 1-bromo-2-methylbenzene Chemical compound CC1=CC=CC=C1Br QSSXJPIWXQTSIX-UHFFFAOYSA-N 0.000 description 1
- WJIFKOVZNJTSGO-UHFFFAOYSA-N 1-bromo-3-methylbenzene Chemical compound CC1=CC=CC(Br)=C1 WJIFKOVZNJTSGO-UHFFFAOYSA-N 0.000 description 1
- NHDODQWIKUYWMW-UHFFFAOYSA-N 1-bromo-4-chlorobenzene Chemical compound ClC1=CC=C(Br)C=C1 NHDODQWIKUYWMW-UHFFFAOYSA-N 0.000 description 1
- AITNMTXHTIIIBB-UHFFFAOYSA-N 1-bromo-4-fluorobenzene Chemical compound FC1=CC=C(Br)C=C1 AITNMTXHTIIIBB-UHFFFAOYSA-N 0.000 description 1
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 1
- TZBZZWBYDXSQTP-UHFFFAOYSA-N 1-dimethylphosphanylethyl(dimethyl)phosphane Chemical compound CP(C)C(C)P(C)C TZBZZWBYDXSQTP-UHFFFAOYSA-N 0.000 description 1
- UZKWTJUDCOPSNM-UHFFFAOYSA-N 1-ethenoxybutane Chemical compound CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
- 125000006432 1-methyl cyclopropyl group Chemical group [H]C([H])([H])C1(*)C([H])([H])C1([H])[H] 0.000 description 1
- YXWWHNCQZBVZPV-UHFFFAOYSA-N 2'-methylacetophenone Chemical compound CC(=O)C1=CC=CC=C1C YXWWHNCQZBVZPV-UHFFFAOYSA-N 0.000 description 1
- 125000000453 2,2,2-trichloroethyl group Chemical group [H]C([H])(*)C(Cl)(Cl)Cl 0.000 description 1
- 125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 description 1
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- 125000004781 2,2-dichloro-2-fluoroethyl group Chemical group [H]C([H])(*)C(F)(Cl)Cl 0.000 description 1
- 125000004778 2,2-difluoroethyl group Chemical group [H]C([H])(*)C([H])(F)F 0.000 description 1
- YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 1
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
- 125000005999 2-bromoethyl group Chemical group 0.000 description 1
- 125000004780 2-chloro-2,2-difluoroethyl group Chemical group [H]C([H])(*)C(F)(F)Cl 0.000 description 1
- 125000004779 2-chloro-2-fluoroethyl group Chemical group [H]C([H])(*)C([H])(F)Cl 0.000 description 1
- 125000006012 2-chloroethoxy group Chemical group 0.000 description 1
- 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 description 1
- MIOCUERTSIJEDP-UHFFFAOYSA-N 2-diethylphosphanylethyl(diethyl)phosphane Chemical compound CCP(CC)CCP(CC)CC MIOCUERTSIJEDP-UHFFFAOYSA-N 0.000 description 1
- 125000004791 2-fluoroethoxy group Chemical group FCCO* 0.000 description 1
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
- 125000005916 2-methylpentyl group Chemical group 0.000 description 1
- BPEXTIMJLDWDTL-UHFFFAOYSA-N 2`-Methylacetanilide Chemical compound CC(=O)NC1=CC=CC=C1C BPEXTIMJLDWDTL-UHFFFAOYSA-N 0.000 description 1
- GZDVNUHKYJNVNT-UHFFFAOYSA-N 3-dimethylphosphanylpropyl(dimethyl)phosphane Chemical compound CP(C)CCCP(C)C GZDVNUHKYJNVNT-UHFFFAOYSA-N 0.000 description 1
- FWXAUDSWDBGCMN-UHFFFAOYSA-N 3-diphenylphosphanylbutan-2-yl(diphenyl)phosphane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)C(C)C(C)P(C=1C=CC=CC=1)C1=CC=CC=C1 FWXAUDSWDBGCMN-UHFFFAOYSA-N 0.000 description 1
- 125000003542 3-methylbutan-2-yl group Chemical group [H]C([H])([H])C([H])(*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- QGXDUDDPMXVLOO-UHFFFAOYSA-N 4-acetyl-2-methylbenzoic acid Chemical compound CC(=O)C1=CC=C(C(O)=O)C(C)=C1 QGXDUDDPMXVLOO-UHFFFAOYSA-N 0.000 description 1
- NLPHXWGWBKZSJC-UHFFFAOYSA-N 4-acetylbenzonitrile Chemical compound CC(=O)C1=CC=C(C#N)C=C1 NLPHXWGWBKZSJC-UHFFFAOYSA-N 0.000 description 1
- PCHYYOCUCGCSBU-UHFFFAOYSA-N 4-bromo-2-methylaniline Chemical compound CC1=CC(Br)=CC=C1N PCHYYOCUCGCSBU-UHFFFAOYSA-N 0.000 description 1
- RVCJOGNLYVNRDN-UHFFFAOYSA-N 4-bromo-2-methylbenzoic acid Chemical compound CC1=CC(Br)=CC=C1C(O)=O RVCJOGNLYVNRDN-UHFFFAOYSA-N 0.000 description 1
- QJPJQTDYNZXKQF-UHFFFAOYSA-N 4-bromoanisole Chemical compound COC1=CC=C(Br)C=C1 QJPJQTDYNZXKQF-UHFFFAOYSA-N 0.000 description 1
- HQSCPPCMBMFJJN-UHFFFAOYSA-N 4-bromobenzonitrile Chemical compound BrC1=CC=C(C#N)C=C1 HQSCPPCMBMFJJN-UHFFFAOYSA-N 0.000 description 1
- MJQKAQFGSBAFJG-UHFFFAOYSA-N 4-diethylphosphanylbutyl(diethyl)phosphane Chemical compound CCP(CC)CCCCP(CC)CC MJQKAQFGSBAFJG-UHFFFAOYSA-N 0.000 description 1
- FNAYAXPWEKXHQU-UHFFFAOYSA-N 4-dimethylphosphanylbutyl(dimethyl)phosphane Chemical compound CP(C)CCCCP(C)C FNAYAXPWEKXHQU-UHFFFAOYSA-N 0.000 description 1
- CTYPJIUQROQJBG-UHFFFAOYSA-N 4-diphenylphosphanylpentan-2-yl(diphenyl)phosphane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)C(C)CC(C)P(C=1C=CC=CC=1)C1=CC=CC=C1 CTYPJIUQROQJBG-UHFFFAOYSA-N 0.000 description 1
- 0 CC(c1ccc(*)cc1)=O Chemical compound CC(c1ccc(*)cc1)=O 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- 238000007341 Heck reaction Methods 0.000 description 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
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- SCWUJLADLJRRDX-UHFFFAOYSA-M [Na+].[Br-].OO Chemical compound [Na+].[Br-].OO SCWUJLADLJRRDX-UHFFFAOYSA-M 0.000 description 1
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- 239000007864 aqueous solution Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- KTLFENNEPHBKJD-UHFFFAOYSA-K benzyl(trimethyl)azanium;tribromide Chemical compound [Br-].[Br-].[Br-].C[N+](C)(C)CC1=CC=CC=C1.C[N+](C)(C)CC1=CC=CC=C1.C[N+](C)(C)CC1=CC=CC=C1 KTLFENNEPHBKJD-UHFFFAOYSA-K 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
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- 125000005997 bromomethyl group Chemical group 0.000 description 1
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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- 125000002668 chloroacetyl group Chemical group ClCC(=O)* 0.000 description 1
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- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
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- 125000004774 dichlorofluoromethyl group Chemical group FC(Cl)(Cl)* 0.000 description 1
- 125000004772 dichloromethyl group Chemical group [H]C(Cl)(Cl)* 0.000 description 1
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- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
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- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
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- 238000001914 filtration Methods 0.000 description 1
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- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000003104 hexanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000012456 homogeneous solution Substances 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- OKNLBTNZLUNRDW-UHFFFAOYSA-N hydrogen peroxide;hydrobromide Chemical compound Br.OO OKNLBTNZLUNRDW-UHFFFAOYSA-N 0.000 description 1
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- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
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- JPGRRURDXMILEX-UHFFFAOYSA-N methyl 4-acetyl-2-methylbenzoate Chemical compound COC(=O)C1=CC=C(C(C)=O)C=C1C JPGRRURDXMILEX-UHFFFAOYSA-N 0.000 description 1
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- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
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- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
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- TVZIWRMELPWPPR-UHFFFAOYSA-N n-(2-methylphenyl)-3-oxobutanamide Chemical compound CC(=O)CC(=O)NC1=CC=CC=C1C TVZIWRMELPWPPR-UHFFFAOYSA-N 0.000 description 1
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- IYRGXJIJGHOCFS-UHFFFAOYSA-N neocuproine Chemical compound C1=C(C)N=C2C3=NC(C)=CC=C3C=CC2=C1 IYRGXJIJGHOCFS-UHFFFAOYSA-N 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
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- 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
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- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- AQSJGOWTSHOLKH-UHFFFAOYSA-N phosphite(3-) Chemical class [O-]P([O-])[O-] AQSJGOWTSHOLKH-UHFFFAOYSA-N 0.000 description 1
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- 239000000047 product Substances 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
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- 238000011084 recovery Methods 0.000 description 1
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- CRWJEUDFKNYSBX-UHFFFAOYSA-N sodium;hypobromite Chemical compound [Na+].Br[O-] CRWJEUDFKNYSBX-UHFFFAOYSA-N 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
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- 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
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- 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
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
Description
本発明は、医農薬および各種化学品の製造中間体として有用なアセトフェノン化合物及びアセトフェノン類の製造方法に関するものである。
ヘック反応を利用してアセトフェノン類を合成する場合、式（１３）に示すように、その後の酸加水分解によりアセトフェノン類に誘導されるα−置換体、及び副生成物であるβ−置換体が生成するため、このα−選択性の向上が主要な研究課題となってきた。
The present invention relates to an acetophenone compound and a method for producing acetophenones that are useful as intermediates for the production of medical pesticides and various chemicals.
When synthesizing acetophenones using the Heck reaction, as shown in formula (13), α-substituents derived from acetophenones by subsequent acid hydrolysis and β-substituents as by-products are obtained. Therefore, the improvement of α-selectivity has been a major research issue.
高いα−選択性を達成した例としては、非特許文献１〜５などが知られている。しかし、これらの反応では酢酸パラジウム等の均一系パラジウム触媒を用いており、その回収は容易ではなく工業的な製造方法として実用的ではない。不均一系パラジウム触媒での反応例として非特許文献６及び７が挙げられるが、α−置換体の収率は５０％程度にとどまっており、高いα−選択性を達成した例はない。
医農薬および各種化学品の製造中間体として有用な新規アセトフェノン化合物及びアセトフェノン類の工業的に適した新規製造方法を提供する。 Provided are a novel acetophenone compound useful as an intermediate for the production of medical pesticides and various chemicals, and a novel industrially suitable production method for acetophenones.
本発明者らは、このような状況に鑑み、鋭意検討した結果、不均一系触媒である担持パラジウム触媒を用いて、高収率、高選択的にアセトフェノン類を製造できることを見いだし、発明に至った。
すなわち、本発明は、
式（１）：
As a result of intensive studies in view of such circumstances, the present inventors have found that acetophenones can be produced with high yield and high selectivity using a supported palladium catalyst that is a heterogeneous catalyst, leading to the invention. It was.
That is, the present invention
Formula (1):
［式中、Xは、塩素原子、臭素原子、ヨウ素原子又はトリフルオロメタンスルホニルオキシを表し、
Yは、フッ素原子、塩素原子、シアノ、ニトロ、C１〜C６アルキル、C３〜C８シクロアルキル、C１〜C６ハロアルキル、C１〜C６アルコキシ、C１〜C６ハロアルコキシ、C１〜C６アルキルチオ、C１〜C６ハロアルキルチオ、ホルミル、カルボキシル、C１〜C６アルキルカルボニル、C１〜C６ハロアルキルカルボニル、C１〜C６アルコキシカルボニル、C１〜C６アルキルチオカルボニル、C１〜C６アルコキシチオカルボニル、C１〜C６アルキルジチオカルボニル、C１〜C６アルキルスルホニル、C１〜C６ハロアルキルスルホニル、‐CH2N(R2)R1、‐CON(R2)R1又は‐N(R2)R1（ただし、Ｘが塩素原子のとき塩素原子を除く）を表し、nが２以上を表すとき、各々のYは互いに同一であっても又は互いに相異なっていてもよく、
Zは、水素原子、フッ素原子、塩素原子、シアノ、ニトロ、C１〜C６アルキル、C３〜C８シクロアルキル、C１〜C６ハロアルキル、C１〜C６アルコキシ、C１〜C６ハロアルコキシ、C１〜C６アルキルチオ、C１〜C６ハロアルキルチオ、ホルミル、カルボキシル、C１〜C６アルキルカルボニル、C１〜C６ハロアルキルカルボニル、C１〜C６アルコキシカルボニル、C１〜C６アルキルチオカルボニル、C１〜C６アルコキシチオカルボニル、C１〜C６アルキルジチオカルボニル、C１〜C６アルキルスルホニル、C１〜C６ハロアルキルスルホニル、‐CH2N(R2)R1、‐CON(R2)R1又は‐N(R2)R1（ただし、Xが塩素原子のとき塩素原子を除く）を表し、
R1は、水素原子、C１〜C６アルキル、ホルミル、C１〜C６アルキルカルボニル、C１〜C６ハロアルキルカルボニル、C１〜C６アルコキシカルボニル、C１〜C６アルキルチオカルボニル、C１〜C６アルコキシチオカルボニル、C１〜C６アルキルジチオカルボニル、C１〜C６アルキルスルホニル又はC１〜C６ハロアルキルスルホニルを表し、
R2は、水素原子、C１〜C６アルキル、ホルミル、C１〜C６アルキルカルボニル、C１〜C６ハロアルキルカルボニル又はC１〜C６アルコキシカルボニルを表し、R1及びR2は、互いに同一であっても又は互いに相異なっていてもよく、
nは、０から４の整数を表す。］
で表される化合物と式（２）：
[Wherein X represents a chlorine atom, a bromine atom, an iodine atom or trifluoromethanesulfonyloxy,
Y is fluorine atom, chlorine atom, cyano, nitro, C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, C 1 -C 6 alkylthio, C 1 -C 6 haloalkylthio, formyl, carboxyl, C 1 -C 6 alkylcarbonyl, C 1 -C 6 haloalkylcarbonyl, C 1 -C 6 alkoxycarbonyl, C 1 -C 6 alkylthiocarbonyl , C 1 -C 6 alkoxythiocarbonyl, C 1 -C 6 alkyl dithio carbonyl, C 1 -C 6 alkylsulfonyl, C 1 -C 6 haloalkylsulfonyl, -CH 2 N (R 2) R 1, -CON (R 2 ) R 1 or —N (R 2 ) R 1 (excluding a chlorine atom when X is a chlorine atom), and when n is 2 or more, each Y may be the same as each other or They may be different,
Z is a hydrogen atom, a fluorine atom, a chlorine atom, a cyano, nitro, C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, C 1 -C 6 alkylthio, C 1 -C 6 haloalkylthio, formyl, carboxyl, C 1 -C 6 alkylcarbonyl, C 1 -C 6 haloalkylcarbonyl, C 1 -C 6 alkoxycarbonyl, C 1 -C 6 alkylthiocarbonyl, C 1 -C 6 alkoxythiocarbonyl, C 1 -C 6 alkyl dithio carbonyl, C 1 -C 6 alkylsulfonyl, C 1 -C 6 haloalkylsulfonyl, -CH 2 N (R 2) R 1, - CON (R 2 ) R 1 or -N (R 2 ) R 1 (however, when X is a chlorine atom, excluding a chlorine atom)
R 1 is a hydrogen atom, C 1 -C 6 alkyl, formyl, C 1 -C 6 alkylcarbonyl, C 1 -C 6 haloalkylcarbonyl, C 1 -C 6 alkoxycarbonyl, C 1 -C 6 alkylthiocarbonyl, C 1 -C 6 alkoxythiocarbonyl, C 1 -C 6 alkyl dithio carbonyl, represents C 1 -C 6 alkylsulfonyl or C 1 -C 6 haloalkylsulfonyl,
R 2 represents a hydrogen atom, C 1 -C 6 alkyl, formyl, C 1 -C 6 alkylcarbonyl, C 1 -C 6 haloalkylcarbonyl, or C 1 -C 6 alkoxycarbonyl, and R 1 and R 2 represent each other They may be the same or different from each other,
n represents an integer of 0 to 4. ]
And a compound represented by formula (2):
［式（２）中、Ｗは、‐OR３、‐N(R４) COR５又は式（３）： [In Formula (2), W is -OR 3 , -N (R 4 ) COR 5 or Formula (3):
を表し、
R３は、C１〜C１２アルキル、C１〜C６ハロアルキル、ビニルオキシ（C１〜C１２）アルキル、ヒドロキシ（C２〜C１２）アルキル又はC１〜C６アルコキシ（C１〜C１２）アルキルを表し、
R４およびR５は、各々独立に、水素原子、C１〜C６アルキル、C１〜C６ハロアルキル、C１〜C６アルコキシ又は、R４およびR５が結合しているアミド基とともにC２〜C５アルキルで形成する４〜７員環を表す。］
で表される化合物を塩基、ホスフィン又は芳香族アミン配位子及び担持パラジウム触媒の存在下で反応を行い、反応系内で得られる式（４）：
Represents
R 3 is C 1 -C 12 alkyl, C 1 -C 6 haloalkyl, vinyloxy (C 1 -C 12 ) alkyl, hydroxy (C 2 -C 12 ) alkyl or C 1 -C 6 alkoxy (C 1 -C 12 ) Represents alkyl,
R 4 and R 5 are each independently a hydrogen atom, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, or an amide group to which R 4 and R 5 are bonded. It represents a 4 to 7 membered ring formed by 2 to C 5 alkyl. ]
A compound represented by formula (4) obtained by reacting in the presence of a base, a phosphine or an aromatic amine ligand and a supported palladium catalyst:
［式（４）中、W、Y、Z及びnは前記と同じ意味を表す。］
で表される中間体または式（５）：
[In formula (4), W, Y, Z and n represent the same meaning as described above. ]
Or an intermediate represented by formula (5):
［式（５）中、Y、Z及びnは前記と同じ意味を表し、R６はC２〜C１２アルキルを表す。］
で表される中間体を酸と反応させることによる式（６）：
[In formula (5), Y, Z, and n represent the same meaning as described above, and R 6 represents C 2 -C 12 alkyl. ]
Formula (6) by reacting an intermediate represented by
［式（６）中、Y、Z及びnは前記と同じ意味を表す。］
で表されるアセトフェノン類の製造方法及び式（１２）：
[In Formula (6), Y, Z, and n represent the same meaning as the above. ]
A process for producing acetophenones represented by formula (12):
[式（１２）中、VはC１〜C６アルキル、C１〜C６ハロアルキル又はC１〜C６シクロアルキルを表す。］
で表されるアセトフェノン化合物。
Wherein (12), V represents a C 1 -C 6 alkyl, C 1 -C 6 haloalkyl or C 1 -C 6 cycloalkyl. ]
An acetophenone compound represented by:
本発明により、医農薬及び各種化学品の中間体として有用なアセトフェノン類を不均一系触媒用いて製造する、工業的生産に有益な方法を提供できる。また、本発明の新規なアセトフェノン化合物は、農医薬の中間体として有用である。 INDUSTRIAL APPLICABILITY According to the present invention, it is possible to provide a method useful for industrial production, in which acetophenones useful as intermediates for medicines and agricultural chemicals and various chemicals are produced using a heterogeneous catalyst. Further, the novel acetophenone compound of the present invention is useful as an intermediate for agricultural medicine.
以下に本発明を詳細に説明する。 The present invention is described in detail below.
本明細書において、n-はノルマル、i-はイソ、s-はセカンダリー及びt-はターシャリーを各々意味する。 In the present specification, n- means normal, i- means iso, s- means secondary, and t- means tertiary.
本明細書中の「ハロ」の表記は、フッ素原子、塩素原子、臭素原子及びヨウ素原子を表す。 The expression “halo” in the present specification represents a fluorine atom, a chlorine atom, a bromine atom and an iodine atom.
本明細書におけるCa〜Cbアルキルの表記は、炭素原子数がa〜b個よりなる直鎖状又は分岐鎖状の炭化水素基を表し、例えばメチル基、エチル基、n-プロピル基、i-プロピル基、n-ブチル基、i-ブチル基、s-ブチル基、t-ブチル基、n-ペンチル基、1-メチルブチル基、2-メチルブチル基、3-メチルブチル基、1-エチルプロピル基、1,1-ジメチルプロピル基、1,2-ジメチルプロピル基、2,2-ジメチルプロピル基、n-ヘキシル基、1-メチルペンチル基、2-メチルペンチル基、1,1-ジメチルブチル基、1,3-ジメチルブチル基、ヘプチル基、オクチル基、ノニル基、デシル基、ウンデシル基、ドデシル基等が具体例として挙げられ、各々の指定の炭素原子数の範囲で選択される。 The notation of C a to C b alkyl in the present specification represents a linear or branched hydrocarbon group having a carbon number of a to b , for example, methyl group, ethyl group, n-propyl group, i-propyl group, n-butyl group, i-butyl group, s-butyl group, t-butyl group, n-pentyl group, 1-methylbutyl group, 2-methylbutyl group, 3-methylbutyl group, 1-ethylpropyl group 1,1-dimethylpropyl group, 1,2-dimethylpropyl group, 2,2-dimethylpropyl group, n-hexyl group, 1-methylpentyl group, 2-methylpentyl group, 1,1-dimethylbutyl group, Specific examples include 1,3-dimethylbutyl group, heptyl group, octyl group, nonyl group, decyl group, undecyl group, dodecyl group and the like, and each is selected within the range of the designated number of carbon atoms.
本明細書におけるCa〜Cbシクロアルキルの表記は、炭素原子数がa〜b個よりなる環状の炭化水素基を表し、３員環から６員環までの単環又は複合環構造を形成することが出来る。また、各々の環は指定の炭素原子数の範囲でアルキル基によって任意に置換されていてもよい。例えばシクロプロピル基、1-メチルシクロプロピル基、2-メチルシクロプロピル基、2,2-ジメチルシクロプロピル基、2,2,3,3-テトラメチルシクロプロピル基、シクロブチル基、シクロペンチル基、2-メチルシクロペンチル基、3-メチルシクロペンチル基、シクロヘキシル基、2-メチルシクロヘキシル基、3-メチルシクロヘキシル基、4-メチルシクロヘキシル基、ビシクロ[2.2.1]ヘプタン-2-イル基等が具体例として挙げられ、各々の指定の炭素原子数の範囲で選択される。 In the present specification, C a to C b cycloalkyl represents a cyclic hydrocarbon group having a to b carbon atoms, and forms a monocyclic or complex ring structure having 3 to 6 members. I can do it. Each ring may be optionally substituted with an alkyl group within the range of the specified number of carbon atoms. For example, cyclopropyl group, 1-methylcyclopropyl group, 2-methylcyclopropyl group, 2,2-dimethylcyclopropyl group, 2,2,3,3-tetramethylcyclopropyl group, cyclobutyl group, cyclopentyl group, 2- Specific examples include methylcyclopentyl group, 3-methylcyclopentyl group, cyclohexyl group, 2-methylcyclohexyl group, 3-methylcyclohexyl group, 4-methylcyclohexyl group, bicyclo [2.2.1] heptan-2-yl group, etc. , Each selected range of carbon atoms.
本明細書におけるCa〜Cbハロアルキルの表記は、炭素原子に結合した水素原子が、ハロゲン原子によって任意に置換された、炭素原子数がa〜b個よりなる直鎖状又は分岐鎖状の炭化水素基を表し、このとき、２個以上のハロゲン原子によって置換されている場合、それらのハロゲン原子は互いに同一でも、または互いに相異なっていてもよい。例えばフルオロメチル基、クロロメチル基、ブロモメチル基、ヨードメチル基、ジフルオロメチル基、クロロフルオロメチル基、ジクロロメチル基、ブロモフルオロメチル基、トリフルオロメチル基、クロロジフルオロメチル基、ジクロロフルオロメチル基、トリクロロメチル基、ブロモジフルオロメチル基、ブロモクロロフルオロメチル基、ジブロモフルオロメチル基、2-フルオロエチル基、2-クロロエチル基、2-ブロモエチル基、2,2-ジフルオロエチル基、2-クロロ-2-フルオロエチル基、2,2-ジクロロエチル基、2-ブロモ-2-フルオロエチル基、2,2,2-トリフルオロエチル基、2-クロロ-2,2-ジフルオロエチル基、2,2-ジクロロ-2-フルオロエチル基、2,2,2-トリクロロエチル基、2-ブロモ-2,2-ジフルオロエチル基、2-ブロモ-2-クロロ-2-フルオロエチル基、2-ブロモ-2,2-ジクロロエチル基、1,1,2,2-テトラフルオロエチル基、ペンタフルオロエチル基、1-クロロ-1,2,2,2-テトラフルオロエチル基、2-クロロ-1,1,2,2-テトラフルオロエチル基、1,2-ジクロロ-1,2,2-トリフルオロエチル基、2-ブロモ-1,1,2,2-テトラフルオロエチル基、2-フルオロプロピル基、2-クロロプロピル基、2-ブロモプロピル基、2-クロロ-2-フルオロプロピル基、2,3-ジクロロプロピル基、2-ブロモ-3-フルオロプロピル基、3-ブロモ-2-クロロプロピル基、2,3-ジブロモプロピル基、3,3,3-トリフルオロプロピル基、3-ブロモ-3,3-ジフルオロプロピル基、2,2,3,3-テトラフルオロプロピル基、2-クロロ-3,3,3-トリフルオロプロピル基、2,2,3,3,3-ペンタフルオロプロピル基、1,1,2,3,3,3-ヘキサフルオロプロピル基、ヘプタフルオロプロピル基、2,3-ジクロロ-1,1,2,3,3-ペンタフルオロプロピル基、2-フルオロ-1-メチルエチル基、2-クロロ-1-メチルエチル基、2-ブロモ-1-メチルエチル基、2,2,2-トリフルオロ-1-(トリフルオロメチル)エチル基、1,2,2,2-テトラフルオロ-1-(トリフルオロメチル)エチル基、2-フルオロブチル基、2-クロロブチル基、2,2,3,3,4,4-ヘキサフルオロブチル基、2,2,3,4,4,4-ヘキサフルオロブチル基、2,2,3,3,4,4-ヘキサフルオロブチル基、2,2,3,3,4,4,4-ヘプタフルオロブチル基、1,1,2,2,3,3,4,4-オクタフルオロブチル基、ノナフルオロブチル基、4-クロロ-1,1,2,2,3,3,4,4-オクタフルオロブチル基、2-フルオロ-2-メチルプロピル基、1,2,2,3,3,3-ヘキサフルオロ-1-(トリフルオロメチル)プロピル基、2-クロロ-1,1-ジメチルエチル基、2-ブロモ-1,1-ジメチルエチル基、5-クロロ-2,2,3,4,4,5,5-ヘプタフルオロペンチル基、トリデカフルオロヘキシル基等が具体例として挙げられ、各々の指定の炭素原子数の範囲で選択される。 In the present specification, C a -C b haloalkyl is represented by a linear or branched chain consisting of a to b carbon atoms in which a hydrogen atom bonded to a carbon atom is optionally substituted with a halogen atom. Represents a hydrocarbon group, and when substituted by two or more halogen atoms, the halogen atoms may be the same as or different from each other. For example, fluoromethyl group, chloromethyl group, bromomethyl group, iodomethyl group, difluoromethyl group, chlorofluoromethyl group, dichloromethyl group, bromofluoromethyl group, trifluoromethyl group, chlorodifluoromethyl group, dichlorofluoromethyl group, trichloromethyl Group, bromodifluoromethyl group, bromochlorofluoromethyl group, dibromofluoromethyl group, 2-fluoroethyl group, 2-chloroethyl group, 2-bromoethyl group, 2,2-difluoroethyl group, 2-chloro-2-fluoroethyl Group, 2,2-dichloroethyl group, 2-bromo-2-fluoroethyl group, 2,2,2-trifluoroethyl group, 2-chloro-2,2-difluoroethyl group, 2,2-dichloro-2 -Fluoroethyl group, 2,2,2-trichloroethyl group, 2-bromo-2,2-difluoroethyl group, 2-bromo-2-chloro-2-fluoroethyl group, 2-butyl Lomo-2,2-dichloroethyl group, 1,1,2,2-tetrafluoroethyl group, pentafluoroethyl group, 1-chloro-1,2,2,2-tetrafluoroethyl group, 2-chloro-1 1,2,2-tetrafluoroethyl group, 1,2-dichloro-1,2,2-trifluoroethyl group, 2-bromo-1,1,2,2-tetrafluoroethyl group, 2-fluoropropyl Group, 2-chloropropyl group, 2-bromopropyl group, 2-chloro-2-fluoropropyl group, 2,3-dichloropropyl group, 2-bromo-3-fluoropropyl group, 3-bromo-2-chloropropyl group Group, 2,3-dibromopropyl group, 3,3,3-trifluoropropyl group, 3-bromo-3,3-difluoropropyl group, 2,2,3,3-tetrafluoropropyl group, 2-chloro- 3,3,3-trifluoropropyl group, 2,2,3,3,3-pentafluoropropyl group, 1,1,2,3,3,3-hexafluoropropyl group, heptafluoropropyl group, 2, 3-dichloro-1,1,2,3,3-pentaph Oropropyl group, 2-fluoro-1-methylethyl group, 2-chloro-1-methylethyl group, 2-bromo-1-methylethyl group, 2,2,2-trifluoro-1- (trifluoromethyl) ethyl Group, 1,2,2,2-tetrafluoro-1- (trifluoromethyl) ethyl group, 2-fluorobutyl group, 2-chlorobutyl group, 2,2,3,3,4,4-hexafluorobutyl group 2,2,3,4,4,4-hexafluorobutyl group, 2,2,3,3,4,4-hexafluorobutyl group, 2,2,3,3,4,4,4-hepta Fluorobutyl group, 1,1,2,2,3,3,4,4-octafluorobutyl group, nonafluorobutyl group, 4-chloro-1,1,2,2,3,3,4,4- Octafluorobutyl group, 2-fluoro-2-methylpropyl group, 1,2,2,3,3,3-hexafluoro-1- (trifluoromethyl) propyl group, 2-chloro-1,1-dimethylethyl Group, 2-bromo-1,1-dimethylethyl group, 5-chloro-2,2,3,4,4,5,5-heptafluoropentyl group, tridecafluorohexyl Group, etc. As a specific example, it may be selected from the range of the specified number of carbon atoms.
本明細書におけるCa〜Cbアルコキシの表記は、炭素原子数がa〜b個よりなる前記の意味であるアルキル-O-基を表し、例えばメトキシ基、エトキシ基、n-プロピルオキシ基、i-プロピルオキシ基、n-ブチルオキシ基、i-ブチルオキシ基、s-ブチルオキシ基、t-ブチルオキシ基等が具体例として挙げられ、各々の指定の炭素原子数の範囲で選択される。 The notation of C a -C b alkoxy in the present specification represents an alkyl-O— group having the above-mentioned meaning consisting of a to b carbon atoms, for example, methoxy group, ethoxy group, n-propyloxy group, Specific examples include i-propyloxy group, n-butyloxy group, i-butyloxy group, s-butyloxy group, t-butyloxy group and the like, and each is selected within the range of the designated number of carbon atoms.
本明細書におけるCa〜Cbハロアルコキシの表記は、炭素原子数がa〜b個よりなる前記の意味であるハロアルキル-O-基を表し、例えばジフルオロメトキシ基、トリフルオロメトキシ基、クロロジフルオロメトキシ基、ブロモジフルオロメトキシ基、2-フルオロエトキシ基、2-クロロエトキシ基、2,2,2-トリフルオロエトキシ基、1,1,2,2,-テトラフルオロエトキシ基、2-クロロ-1,1,2-トリフルオロエトキシ基、2-ブロモ-1,1,2-トリフルオロエトキシ基、ペンタフルオロエトキシ基、2,2-ジクロロ-1,1,2-トリフルオロエトキシ基、2,2,2-トリクロロ-1,1-ジフルオロエトキシ基、2-ブロモ-1,1,2,2-テトラフルオロエトキシ基、2,2,3,3-テトラフルオロプロピルオキシ基、1,1,2,3,3,3-ヘキサフルオロプロピルオキシ基、2,2,2-トリフルオロ-1-(トリフルオロメチル)エトキシ基、ヘプタフルオロプロピルオキシ基、2-ブロモ-1,1,2,3,3,3-ヘキサフルオロプロピルオキシ基等が具体例として挙げられ、各々の指定の炭素原子数の範囲で選択される。 The notation of C a -C b haloalkoxy in the present specification represents a haloalkyl-O— group having the above-mentioned meaning consisting of a to b carbon atoms, for example, difluoromethoxy group, trifluoromethoxy group, chlorodifluoro Methoxy group, bromodifluoromethoxy group, 2-fluoroethoxy group, 2-chloroethoxy group, 2,2,2-trifluoroethoxy group, 1,1,2,2, -tetrafluoroethoxy group, 2-chloro-1 , 1,2-trifluoroethoxy group, 2-bromo-1,1,2-trifluoroethoxy group, pentafluoroethoxy group, 2,2-dichloro-1,1,2-trifluoroethoxy group, 2,2 , 2-trichloro-1,1-difluoroethoxy group, 2-bromo-1,1,2,2-tetrafluoroethoxy group, 2,2,3,3-tetrafluoropropyloxy group, 1,1,2, 3,3,3-hexafluoropropyloxy group, 2,2,2-trifluoro-1- (trifluoromethyl) ethoxy group, Data fluoropropyl group, 2-bromo-1,1,2,3,3,3-hexafluoro-propyloxy group, etc. As a specific example, may be selected from the range of the specified number of carbon atoms.
本明細書におけるCa〜Cbアルキルチオの表記は、炭素原子数がa〜b個よりなる前記の意味であるアルキル-S-基を表し、例えばメチルチオ基、エチルチオ基、n-プロピルチオ基、i-プロピルチオ基、n-ブチルチオ基、i-ブチルチオ基、s-ブチルチオ基、t-ブチルチオ基、n-ペンチルチオ基、n-ヘキシルチオ基等が具体例として挙げられ、各々の指定の炭素原子数の範囲で選択される。 The notation of C a -C b alkylthio in the present specification represents an alkyl-S-group having the above-mentioned meaning consisting of a to b carbon atoms, for example, methylthio group, ethylthio group, n-propylthio group, i Specific examples include -propylthio group, n-butylthio group, i-butylthio group, s-butylthio group, t-butylthio group, n-pentylthio group, n-hexylthio group, etc. Selected.
本明細書におけるCa〜Cbハロアルキルチオの表記は、炭素原子数がa〜b個よりなる前記の意味であるハロアルキル-S-基を表し、例えばジフルオロメチルチオ基、トリフルオロメチルチオ基、クロロジフルオロメチルチオ基、ブロモジフルオロメチルチオ基、2,2,2-トリフルオロエチルチオ基、1,1,2,2-テトラフルオロエチルチオ基、2-クロロ-1,1,2-トリフルオロエチルチオ基、ペンタフルオロエチルチオ基、2-ブロモ-1,1,2,2-テトラフルオロエチルチオ基、1,1,2,3,3,3-ヘキサフルオロプロピルチオ基、ヘプタフルオロプロピルチオ基、1,2,2,2-テトラフルオロ-1-(トリフルオロメチル)エチルチオ基、ノナフルオロブチルチオ基等が具体例として挙げられ、各々の指定の炭素原子数の範囲で選択される。 The notation of C a -C b haloalkylthio in the present specification represents a haloalkyl-S— group having the above-mentioned meaning consisting of a to b carbon atoms, for example, difluoromethylthio group, trifluoromethylthio group, chlorodifluoro Methylthio group, bromodifluoromethylthio group, 2,2,2-trifluoroethylthio group, 1,1,2,2-tetrafluoroethylthio group, 2-chloro-1,1,2-trifluoroethylthio group, Pentafluoroethylthio group, 2-bromo-1,1,2,2-tetrafluoroethylthio group, 1,1,2,3,3,3-hexafluoropropylthio group, heptafluoropropylthio group, 1, Specific examples include 2,2,2-tetrafluoro-1- (trifluoromethyl) ethylthio group, nonafluorobutylthio group and the like, and each is selected within the range of the designated number of carbon atoms.
本明細書におけるCa〜Cbアルキルスルホニルの表記は、炭素原子数がa〜b個よりなる前記の意味であるアルキル-SO2-基を表し、例えばメチルスルホニル基、エチルスルホニル基、n-プロピルスルホニル基、i-プロピルスルホニル基、n-ブチルスルホニル基、i-ブチルスルホニル基、s-ブチルスルホニル基、t-ブチルスルホニル基、n-ペンチルスルホニル基、n-ヘキシルスルホニル基等が具体例として挙げられ、各々の指定の炭素原子数の範囲で選択される。 The notation of C a -C b alkylsulfonyl in the present specification represents an alkyl-SO 2 -group having the above-mentioned meaning consisting of a to b carbon atoms, such as methylsulfonyl group, ethylsulfonyl group, n-propyl. Specific examples include a sulfonyl group, i-propylsulfonyl group, n-butylsulfonyl group, i-butylsulfonyl group, s-butylsulfonyl group, t-butylsulfonyl group, n-pentylsulfonyl group, n-hexylsulfonyl group and the like. Selected within a range of each specified number of carbon atoms.
本明細書におけるCa〜Cbハロアルキルスルホニルの表記は、炭素原子数がa〜b個よりなる前記の意味であるハロアルキル-SO2-基を表し、例えばジフルオロメチルスルホニル基、トリフルオロメチルスルホニル基、クロロジフルオロメチルスルホニル基、ブロモジフルオロメチルスルホニル基、2,2,2-トリフルオロエチルスルホニル基、1,1,2,2-テトラフルオロエチルスルホニル基、2-クロロ-1,1,2-トリフルオロエチルスルホニル基、2-ブロモ-1,1,2,2-テトラフルオロエチルスルホニル基等が具体例として挙げられ、各々の指定の炭素原子数の範囲で選択される。 The notation of C a -C b haloalkylsulfonyl in the present specification represents a haloalkyl-SO2- group having the above-mentioned meaning consisting of a to b carbon atoms, such as a difluoromethylsulfonyl group, a trifluoromethylsulfonyl group, Chlorodifluoromethylsulfonyl group, bromodifluoromethylsulfonyl group, 2,2,2-trifluoroethylsulfonyl group, 1,1,2,2-tetrafluoroethylsulfonyl group, 2-chloro-1,1,2-trifluoro Specific examples include an ethylsulfonyl group, a 2-bromo-1,1,2,2-tetrafluoroethylsulfonyl group, and the like, and each is selected within the range of the designated number of carbon atoms.
本明細書におけるCa〜Cbアルキルカルボニルの表記は、炭素原子数がa〜b個よりなる前記の意味であるアルキル-C(O)-基を表し、例えばアセチル基、プロピオニル基、ブチリル基、イソブチリル基、バレリル基、イソバレリル基、2-メチルブタノイル基、ピバロイル基、ヘキサノイル基等が具体例として挙げられ、各々の指定の炭素原子数の範囲で選択される。 The notation of C a -C b alkylcarbonyl in the present specification represents an alkyl-C (O) — group having the above-mentioned meaning consisting of a to b carbon atoms, for example, acetyl group, propionyl group, butyryl group. , Isobutyryl group, valeryl group, isovaleryl group, 2-methylbutanoyl group, pivaloyl group, hexanoyl group, and the like are listed as specific examples, and each is selected within the range of the designated number of carbon atoms.
本明細書におけるCa〜Cbハロアルキルカルボニルの表記は、炭素原子数がa〜b個よりなる前記の意味であるハロアルキル-C(O)-基を表し、例えばフルオロアセチル基、クロロアセチル基、ジフルオロアセチル基、ジクロロアセチル基、トリフルオロアセチル基、クロロジフルオロアセチル基、ブロモジフルオロアセチル基、トリクロロアセチル基、ペンタフルオロプロピオニル基、ヘプタフルオロブタノイル基、3-クロロ-2,2-ジメチルプロパノイル基等が具体例として挙げられ、各々の指定の炭素原子数の範囲で選択される。 The notation of C a -C b haloalkylcarbonyl in the present specification represents a haloalkyl-C (O) — group having the above-mentioned meaning consisting of a to b carbon atoms, such as a fluoroacetyl group, a chloroacetyl group, Difluoroacetyl group, dichloroacetyl group, trifluoroacetyl group, chlorodifluoroacetyl group, bromodifluoroacetyl group, trichloroacetyl group, pentafluoropropionyl group, heptafluorobutanoyl group, 3-chloro-2,2-dimethylpropanoyl group Etc. are given as specific examples, and each is selected within the range of the designated number of carbon atoms.
本明細書におけるCa〜Cbアルコキシカルボニルの表記は、炭素原子数がa〜b個よりなる前記の意味であるアルキル-O-C(O)-基を表し、例えばメトキシカルボニル基、エトキシカルボニル基、 n-プロピルオキシカルボニル基、i-プロピルオキシカルボニル基、n-ブトキシカルボニル基、i-ブトキシカルボニル基、t-ブトキシカルボニル基等が具体例として挙げられ、各々の指定の炭素原子数の範囲で選択される。 The notation of C a -C b alkoxycarbonyl in the present specification represents an alkyl-OC (O) — group having the above-mentioned meaning consisting of a to b carbon atoms, such as a methoxycarbonyl group, an ethoxycarbonyl group, Specific examples include n-propyloxycarbonyl group, i-propyloxycarbonyl group, n-butoxycarbonyl group, i-butoxycarbonyl group, t-butoxycarbonyl group, etc., selected within the range of each designated number of carbon atoms Is done.
本明細書におけるCa〜Cbアルキルチオカルボニルの表記は、炭素原子数がa〜b個よりなる前記の意味であるアルキル-S-C(O)-基を表し、例えばメチルチオ-C(O)-基、エチルチオ-C(O)-基、n-プロピルチオ-C(O)-基、i-プロピルチオ-C(O)-基、n-ブチルチオ-C(O)-基、i-ブチルチオ-C(O)-基、t-ブチルチオ-C(O)-基等が具体例として挙げられ、各々の指定の炭素原子数の範囲で選択される。 The notation of C a -C b alkylthiocarbonyl in the present specification represents an alkyl-SC (O) -group having the above-mentioned meaning consisting of a to b carbon atoms, for example, methylthio-C (O) -group , Ethylthio-C (O)-group, n-propylthio-C (O)-group, i-propylthio-C (O)-group, n-butylthio-C (O)-group, i-butylthio-C (O ) -Group, t-butylthio-C (O) -group and the like are listed as specific examples, and each group is selected within the range of the designated number of carbon atoms.
本明細書におけるCa〜Cbアルコキシチオカルボニルの表記は、炭素原子数がa〜b個よりなる前記の意味であるアルキル-O-C(S)-基を表し、例えばメトキシ-C(S)-基、エトキシ-C(S)-基、n-プロピルオキシ-C(S)-基、i-プロピルオキシ-C(S)-基等が具体例として挙げられ、各々の指定の炭素原子数の範囲で選択される。 The notation of C a -C b alkoxythiocarbonyl in the present specification represents an alkyl-OC (S) — group having the above-mentioned meaning consisting of a to b carbon atoms, for example, methoxy-C (S) — Groups, ethoxy-C (S) -groups, n-propyloxy-C (S) -groups, i-propyloxy-C (S) -groups, etc. Selected by range.
本明細書におけるCa〜Cbアルキルジチオカルボニルの表記は、炭素原子数がa〜b個よりなる前記の意味であるアルキル-S-C(S)-基を表し、例えばメチルチオ-C(S)-基、エチルチオ-C(S)-基、n-プロピルチオ-C(S)-基、i-プロピルチオ-C(S)-基等が具体例として挙げられ、各々の指定の炭素原子数の範囲で選択される。 In the present specification, the expression C a -C b alkyldithiocarbonyl represents an alkyl-SC (S) -group having the above-mentioned meaning consisting of a to b carbon atoms, for example, methylthio-C (S) — Group, ethylthio-C (S)-group, n-propylthio-C (S)-group, i-propylthio-C (S)-group, etc. Selected.
本明細書におけるビニルオキシ(Ca〜Cb)アルキルの表記は、炭素数がa〜b個よりなる前記の意味であるビニル-O-アルキル基を表し、例えば2-(ビニルオキシ)エチル基、3-(ビニルオキシ)-n-プロピル基、4-(ビニルオキシ)-n-ブチル基、5-(ビニルオキシ)-n-ペンチル基、6-(ビニルオキシ)-n-ヘキシル基等があげられ、各々の指定の炭素数の範囲内で選択される。 The notation of vinyloxy (C a -C b ) alkyl in the present specification represents a vinyl-O-alkyl group having the above-mentioned meaning consisting of a to b carbon atoms, such as a 2- (vinyloxy) ethyl group, 3 -(Vinyloxy) -n-propyl group, 4- (vinyloxy) -n-butyl group, 5- (vinyloxy) -n-pentyl group, 6- (vinyloxy) -n-hexyl group, etc. Is selected within the range of carbon number.
本明細書におけるヒドロキシ(Ca〜Cb)アルキルの表記は、炭素数がa〜b個よりなる前記の意味である炭素原子に置換した水素原子が、水酸基によって任意に置換された、炭素数がa〜b個よりなる直鎖状または分岐状の炭化水素基を表し、例えば2-ヒドロキシエチル基、3-ヒドロキシ-n-プロピル基、2-ヒドロキシ-n-プロピル基、4-ヒドロキシ-n-ブチル基、5-ヒドロキシ-n-ペンチル基、6-ヒドロキシ-n-ヘキシル基等があげられ、各々の指定の炭素数の範囲内で選択される。 In the present specification, the notation of hydroxy (C a -C b ) alkyl is the number of carbon atoms in which a hydrogen atom substituted with a carbon atom as defined above consisting of a to b carbon atoms is optionally substituted with a hydroxyl group. Represents a linear or branched hydrocarbon group consisting of a to b, for example, 2-hydroxyethyl group, 3-hydroxy-n-propyl group, 2-hydroxy-n-propyl group, 4-hydroxy-n -Butyl group, 5-hydroxy-n-pentyl group, 6-hydroxy-n-hexyl group and the like are listed, and they are selected within the range of each designated carbon number.
本明細書におけるCa〜Cbアルコキシ (Cｄ〜Cｅ)アルキルの表記は、それぞれ前記の意味である任意のCa〜Cbアルコキシ基によって炭素原子に結合した水素原子が任意に置換された炭素原子数がd〜e個よりなる前記の意味であるアルキル基を表し、例えば2-メトキシエチル基、2-エトキシエチル基、3-メトキシ-n-プロピル基、4-エトキシ-n-プロピル基、6-メトキシ-n-ヘキシル基等があげられ、各々の指定の炭素数の範囲内で選択される。 In the present specification, the notation of C a -C b alkoxy (C d -C e ) alkyl is that a hydrogen atom bonded to a carbon atom is optionally substituted by any C a -C b alkoxy group having the aforementioned meaning, respectively. Represents an alkyl group having the above-mentioned meaning consisting of d to e, for example, 2-methoxyethyl group, 2-ethoxyethyl group, 3-methoxy-n-propyl group, 4-ethoxy-n-propyl Group, 6-methoxy-n-hexyl group and the like, and each is selected within the range of the designated number of carbon atoms.
本発明の反応に使用できる担持パラジウム触媒としては、活性炭担持パラジウム、アルミナ担持パラジウム、ゼオライト担持パラジウム、ペロブスカイト酸化物担持パラジウム等が挙げられる。このうち活性炭担持パラジウムが特に好ましい。 Examples of the supported palladium catalyst that can be used in the reaction of the present invention include palladium on activated carbon, palladium on alumina, palladium on zeolite, palladium on perovskite oxide, and the like. Of these, palladium on activated carbon is particularly preferred.
本発明の反応に使用する担持パラジウム触媒の使用量は、原料である一般式（１）で表される化合物１ｇに対して０．００００１〜０．５ｇ、好ましくは０．０００１から０．１０ｇである。０．００００１ｇよりも少ないと反応の進行が遅く実用的でないので好ましくなく、また、０．５ｇより多いことは反応の点では問題ないが経済的に不利であるので好ましくない。 The amount of the supported palladium catalyst used in the reaction of the present invention is 0.00001 to 0.5 g, preferably 0.0001 to 0.10 g, based on 1 g of the compound represented by the general formula (1) as a raw material. is there. If it is less than 0.00001 g, the reaction proceeds slowly and is not practical because it is not practical, and if it is more than 0.5 g, there is no problem in terms of the reaction, but it is economically disadvantageous.
本発明の反応に使用できるホスフィン配位子としては、例えば、トリ-t-ブチルホスフィン、トリ-n-ブチルホスフィン、トリ-i-プロピルホスフィンなどのトリアルキルホスフィン類、トリフェニルホスフィン、トリパラメチルフェニルホスフィン、トリオルソメチルフェニルホスフィン等のトリアリールホスフィン類、1,1-ビス（ジメチルホスフィノ）エタン、1,1-ビス（ジエチルホスフィノ）メタン、1,2-ビス（ジメチルホスフィノ）エタン、1,2-ビス（ジエチルホスフィノ）エタン、1,3-ビス（ジメチルホスフィノ）プロパン、1,4-ビス（ジメチルホスフィノ）ブタン、1,4-ビス（ジエチルホスフィノ）ブタン等のビス（ジアルキルホスフィノ）アルカン類、1,2-ビス（ジフェニルホスフィノ）エタン、1,3-ビス（ジフェニルホスフィノ）プロパン、1,4-ビス（ジフェニルホスフィノ）ブタン、2,4-ビス（ジフェニルホスフィノ）ペンタン等のビス（ジフェニルホスフィノ）アルカン類、トリフェニルホスファイト等のホスファイト類、1,1’-ビス（ジフェニルホスフィノ）フェロセン、芳香族アミン配位子としては、1,10-フェナントロリン、2,9-ジメチル-1,10-フェナントロリン等が挙げられる。これらのうち1,3-ビス（ジフェニルホスフィノ）プロパンが特に好ましい。 Examples of the phosphine ligand that can be used in the reaction of the present invention include trialkylphosphines such as tri-t-butylphosphine, tri-n-butylphosphine, and tri-i-propylphosphine, triphenylphosphine, and triparamethylphenyl. Triarylphosphines such as phosphine and triorthomethylphenylphosphine, 1,1-bis (dimethylphosphino) ethane, 1,1-bis (diethylphosphino) methane, 1,2-bis (dimethylphosphino) ethane, Bis such as 1,2-bis (diethylphosphino) ethane, 1,3-bis (dimethylphosphino) propane, 1,4-bis (dimethylphosphino) butane, 1,4-bis (diethylphosphino) butane (Dialkylphosphino) alkanes, 1,2-bis (diphenylphosphino) ethane, 1,3-bis (diphenylphosphino) propane, 1,4- Bis (diphenylphosphino) alkanes such as bis (diphenylphosphino) butane, 2,4-bis (diphenylphosphino) pentane, phosphites such as triphenylphosphite, 1,1'-bis (diphenylphosphino) ) Examples of ferrocene and aromatic amine ligands include 1,10-phenanthroline and 2,9-dimethyl-1,10-phenanthroline. Of these, 1,3-bis (diphenylphosphino) propane is particularly preferred.
本発明の反応に使用するホスフィン又は芳香族アミン配位子の使用量は、パラジウム１モルに対して１モル以上使用し、１〜１０モル程度でよく、好ましくは２〜５モル程度を使用する。 The amount of the phosphine or aromatic amine ligand used in the reaction of the present invention is 1 mol or more per 1 mol of palladium, and may be about 1 to 10 mol, preferably about 2 to 5 mol. .
本発明の反応に使用できる溶媒は、反応に不活性であれば特に制限はないが、メタノール、エタノール、n-プロパノール、i-プロパノール、n-ブタノール、n-ペンタノール、n-ヘキサノール、エチレングリコール、トリメチレングリコール、プロピレングリコール、テトラメチレングリコール、2-メトキシエタノール等のアルコール類、ベンゼン、トルエン、キシレン等の芳香族類、ジエチルエーテル、ジブチルエーテル、テトラヒドロフラン、1,4-ジオキサン、1,2-ジメトキシエタン、シクロペンチルメチルエーテル、t-ブチルメチルエーテル、ジエチレングリコールジメチルエーテル等のエーテル類、ヘキサン、ヘプタン、オクタン、ノナン等の炭化水素類、N,N-ジメチルホルムアミド、N-メチルピロリドン、ジメチルスルホキシド等の極性溶媒、水が挙げられ、これらの混合溶媒も使用できる。これらのうち、アルコール類またはアルコール類と他の溶媒の混合溶媒が特に好ましい。 The solvent that can be used in the reaction of the present invention is not particularly limited as long as it is inert to the reaction, but methanol, ethanol, n-propanol, i-propanol, n-butanol, n-pentanol, n-hexanol, ethylene glycol , Alcohols such as trimethylene glycol, propylene glycol, tetramethylene glycol, 2-methoxyethanol, aromatics such as benzene, toluene, xylene, diethyl ether, dibutyl ether, tetrahydrofuran, 1,4-dioxane, 1,2- Polarities such as dimethoxyethane, cyclopentyl methyl ether, t-butyl methyl ether, ethers such as diethylene glycol dimethyl ether, hydrocarbons such as hexane, heptane, octane, nonane, N, N-dimethylformamide, N-methylpyrrolidone, dimethyl sulfoxide, etc. solvent, Water is mentioned, and these mixed solvents can also be used. Of these, alcohols or mixed solvents of alcohols and other solvents are particularly preferable.
本発明の反応に使用する溶媒の量は、原料である一般式（１）で表される化合物１重量部に対して０．５〜１００重量部の範囲で使用し、好ましくは１．０〜１０．０重量部の範囲で使用する。 The amount of the solvent used in the reaction of the present invention is in the range of 0.5 to 100 parts by weight, preferably 1.0 to 1 part by weight with respect to 1 part by weight of the compound represented by the general formula (1) as a raw material. It is used in the range of 10.0 parts by weight.
本発明の反応温度は２０℃以上２００℃以下が好ましく、８０℃以上１５０℃以下が更に好ましい。 The reaction temperature of the present invention is preferably 20 ° C. or higher and 200 ° C. or lower, and more preferably 80 ° C. or higher and 150 ° C. or lower.
本発明の反応は、１〜５０気圧の範囲内で行うことが好ましい。 The reaction of the present invention is preferably performed within a range of 1 to 50 atm.
本発明の反応は、窒素、アルゴン、キセノン等の不活性ガスの雰囲気下で行うことが好ましい。 The reaction of the present invention is preferably carried out in an atmosphere of an inert gas such as nitrogen, argon or xenon.
本発明の反応に用いる塩基としては、水酸化ナトリウム及び水酸化カリウム等のアルカリ金属水酸化物、炭酸ナトリウム及び炭酸カリウム等のアルカリ金属炭酸塩、トリエチルアミン、ジイソプロピルエチルアミン、ジシクロヘキシルメチルアミン、トリブチルアミン等の有機塩基、ナトリウムメトキシド、ナトリウムエトキシド及びt-ブトキシカリウム等のアルカリ金属アルコキシド類等が挙げられる。 Examples of the base used in the reaction of the present invention include alkali metal hydroxides such as sodium hydroxide and potassium hydroxide, alkali metal carbonates such as sodium carbonate and potassium carbonate, triethylamine, diisopropylethylamine, dicyclohexylmethylamine, and tributylamine. Examples include organic bases, alkali metal alkoxides such as sodium methoxide, sodium ethoxide, and t-butoxy potassium.
本発明の反応に使用する、式（２）で表される化合物の使用量は、式（１）で表される化合物１モルに対して１モル以上使用し、１．０〜２０モル程度でよく、好ましくは１．０〜５．０モル程度を使用する。 The amount of the compound represented by the formula (2) used in the reaction of the present invention is 1 mol or more per 1 mol of the compound represented by the formula (1), and is about 1.0 to 20 mol. Well, preferably about 1.0-5.0 mol is used.
反応液中に相間移動触媒を加えると好ましい場合がある。用いる相間移動触媒としては、テトラエチルアンモニウムクロライド、テトラ-n-ブチルアンモニウムクロライド、テトラ-n-ブチルアンモニウムブロマイド及びベンジルジメチルアンモニウムクロライド等の４級アンモニウム塩並びにテトラエチルホスホニウムブロマイド、テトラ-n-ブチルホスホニウムブロマイド、テトラ-n-ブチルホスホニウムクロライド等の４級ホスホニウム塩等が挙げられる。 It may be preferable to add a phase transfer catalyst to the reaction solution. Examples of the phase transfer catalyst used include quaternary ammonium salts such as tetraethylammonium chloride, tetra-n-butylammonium chloride, tetra-n-butylammonium bromide and benzyldimethylammonium chloride, tetraethylphosphonium bromide, tetra-n-butylphosphonium bromide, And quaternary phosphonium salts such as tetra-n-butylphosphonium chloride.
本発明の反応に用いる酸としては、例えば硫酸、塩酸、臭化水素酸、沃化水素酸、酢酸、トリフルオロ酢酸等を使用することができる。 Examples of the acid used in the reaction of the present invention include sulfuric acid, hydrochloric acid, hydrobromic acid, hydroiodic acid, acetic acid, trifluoroacetic acid and the like.
本発明の反応に用いる酸の使用量は反応系が酸性を示すのに必要な程度でよい。 The amount of acid used in the reaction of the present invention may be as much as necessary for the reaction system to be acidic.
本発明の酸添加後の反応温度は０℃以上１００℃以下の範囲から選択できる。 The reaction temperature after the acid addition of the present invention can be selected from the range of 0 ° C. or higher and 100 ° C. or lower.
本発明のアセチル化反応に使用することができるアセチル化剤としては、無水酢酸及び塩化アセチルがあげられる。 Examples of the acetylating agent that can be used in the acetylation reaction of the present invention include acetic anhydride and acetyl chloride.
本発明のアセチル化反応に用いるアセチル化剤の使用量はアニリン類１モルに対して１．０〜５．０モルの範囲で使用し、好ましくは１．０〜２．０モルの範囲で使用する。 The amount of the acetylating agent used in the acetylation reaction of the present invention is 1.0 to 5.0 mol, preferably 1.0 to 2.0 mol, per mol of anilines. To do.
本発明のアセチル化反応では、塩基を加えた方が好ましい場合がある。その際用いる塩基としては、水酸化ナトリウム及び水酸化カリウム等のアルカリ金属水酸化物、炭酸ナトリウム及び炭酸カリウム等のアルカリ金属炭酸塩、トリエチルアミン、ジイソプロピルエチルアミン、ジシクロヘキシルメチルアミン、トリブチルアミン等の有機塩基、ナトリウムメトキシド、ナトリウムエトキシド及びt-ブトキシカリウム等のアルカリ金属アルコキシド類等が挙げられる。 In the acetylation reaction of the present invention, it may be preferable to add a base. Examples of the base used at that time include alkali metal hydroxides such as sodium hydroxide and potassium hydroxide, alkali metal carbonates such as sodium carbonate and potassium carbonate, organic bases such as triethylamine, diisopropylethylamine, dicyclohexylmethylamine, and tributylamine. And alkali metal alkoxides such as sodium methoxide, sodium ethoxide and t-butoxy potassium.
本発明のアセチル化反応において塩基を用いる場合の使用量はアセチル化剤１モルに対して０．００１〜５．０モルの範囲で使用し、好ましくは０．０１〜２．０モルの範囲で使用する。 When the base is used in the acetylation reaction of the present invention, the amount used is in the range of 0.001 to 5.0 mol, preferably in the range of 0.01 to 2.0 mol, with respect to 1 mol of the acetylating agent. use.
本発明のアセチル化反応の温度は０℃以上１５０℃以下の範囲から選択できる。 The temperature of the acetylation reaction of the present invention can be selected from the range of 0 ° C. or higher and 150 ° C. or lower.
本発明の臭素化反応に使用することができる臭化剤としては、臭素、次亜臭素酸ナトリウム、Ｎ‐ブロモスクシンイミド、臭化水素酸−ジメチルスルホキシド、臭化水素酸−過酸化水素水、臭化ナトリウム−過酸化水素水、臭化カリウム−過酸化水素水及びベンジルトリメチルアンモニウムトリブロミド等が挙げられる。 Examples of the brominating agent that can be used in the bromination reaction of the present invention include bromine, sodium hypobromite, N-bromosuccinimide, hydrobromic acid-dimethylsulfoxide, hydrobromic acid-hydrogen peroxide solution, odor And sodium bromide-hydrogen peroxide, potassium bromide-hydrogen peroxide, and benzyltrimethylammonium tribromide.
本発明の臭素化反応に用いる臭化剤の使用量はアセトアニリド類１モルに対して１．０〜２．０モルの範囲で使用する。 The amount of the brominating agent used in the bromination reaction of the present invention is in the range of 1.0 to 2.0 mol per 1 mol of acetanilides.
以下、本発明を実施例を挙げて具体的に述べるが、本発明はこれによって限定されるものではない。
〔実施例１〕
4’-ブロモ-2’-メチルアセトアニリド２５．０ｇ（１１０ミリモル）にn-ブタノール１００ｇ、炭酸カリウム１８．２ｇ（１３２ミリモル）、1,4-ブタンジオールモノビニルエーテル３８．３ｇ（３３０ミリモル）、1,3-ビス（ジフェニルホスフィノ）プロパン０．４３７ｇ（１．０６ミリモル）及び活性炭担持５％パラジウム１．５７ｇ（含水率52.27重量％、ＮＥケムキャット社製）を加え、反応系内を脱気したのち、窒素雰囲気下で１０時間還流させた。反応終了後、室温まで冷却し、n-ブタノール１２５ｇ、１Ｎ塩酸１２５ｇを加え、３０分攪拌した後、セライトろ過し、水層を分離した。有機層を高速液体クロマトグラフィーを用いた定量分析法で分析したところ、4’-アセチル-2’-メチルアセトアニリドの含有量は１９．８ｇ（収率９４％）であった。
〔実施例２〕
4’-ブロモ-2’-メチルアセトアニリド１１．４ｇ（５０ミリモル）にn-ブタノール４５．６ｇ、炭酸カリウム８．４８ｇ（６０ミリモル）、1,4-ブタンジオールモノビニルエーテル１４．５ｇ（１２５ミリモル）、1,3-ビス（ジフェニルホスフィノ）プロパン０．２０ｇ（０．４９ミリモル）及び活性炭担持５％パラジウム０．７１７ｇ（含水率52.27重量％、ＮＥケムキャット社製）を加え、反応系内を脱気したのち、窒素雰囲気下で８時間還流させた。反応終了後、５０℃まで冷却し、n-ブタノール５７ｇ及び水５７ｇを加え、３０分間攪拌した後、セライトろ過し、水層を分離した。有機層に酢酸３ｇ（５０ミリモル）を加え、５０℃にて３時間攪拌した。減圧下溶媒を留去し、トルエン３４．２ｇを加え０℃に冷却し、３０分間攪拌した。得られたスラリーから濾取した固体を減圧下乾燥し、4’-アセチル-2’-メチルアセトアニリド７．７０ｇ（収率８１％）を白色結晶として得た。
〔実施例３〕
ｐ-ブロモトルエン０．６８４ｇ（４．０ミリモル）にn-ブタノール５．０ｍｌ、炭酸カリウム０．６６ｇ（４．８ミリモル）、1,4-ブタンジオールモノビニルエーテル１．３９ｇ（１２ミリモル）、1,3-ビス（ジフェニルホスフィノ）プロパン０．０１６５ｇ（０．０４ミリモル）及び活性炭担持５％パラジウム（含水率52.27重量％、ＮＥケムキャット社製）０．０５７４ｇを加え、反応系内を脱気したのち、窒素雰囲気下で６時間還流させた。反応終了後、室温まで冷却し、１Ｎ塩酸１０ｇを加え、３０分攪拌した後、セライトろ過し、アセトニトリルを加え均一にした溶液をＨＰＬＣを用いた定量分析法で分析したところ、4’-メチルアセトフェノンの含有量は０．４２ｇ（収率７８％）であった。
〔実施例４〕
o-ブロモトルエンをｐ-ブロモトルエンの代わりに用い、実施例３と同様の操作を行い、2’-メチルアセトフェノンを収率８５％で得た。
〔実施例５〕
m-ブロモトルエンをｐ-ブロモトルエンの代わりに用い、実施例３と同様の操作を行い、3’-メチルアセトフェノンを収率９３％で得た。
〔実施例６〕
ｐ-ブロモアニソールをｐ-ブロモトルエンの代わりに用い、実施例３と同様の操作を行い、4’-メトキシアセトフェノンを収率８６％で得た。
〔実施例７〕
ｐ-フルオロブロモベンゼンをｐ-ブロモトルエンの代わりに用い、実施例３と同様の操作を行い、4’-フルオロアセトフェノンを収率３９％で得た。
〔実施例８〕
ｐ-クロロブロモベンゼンをｐ-ブロモトルエンの代わりに用い、実施例３と同様の操作を行い、4’-クロロアセトフェノンを収率２０％で得た。
〔実施例９〕
ｐ-ブロモベンゾニトリルをｐ-ブロモトルエンの代わりに用い、実施例３と同様の操作を行い、4’-シアノアセトフェノンを収率１７％で得た。
〔実施例１０〕
4-ブロモ-2-メチル安息香酸０．８６０ｇ（４．０ミリモル）にn-ブタノール５．０ｍｌ、炭酸カリウム０．６６ｇ（４．８ミリモル）、1,4-ブタンジオールモノビニルエーテル１．３９ｇ（１２．０ミリモル）、1,3-ビス（ジフェニルホスフィノ）プロパン０．０１５４ｇ（０．０４ミリモル）及び活性炭担持５％パラジウム（含水率53.67重量％、ＮＥケムキャット社製）０．０５５７ｇを加え、反応系内を脱気したのち、窒素雰囲気下で６時間還流させた。反応終了後、室温まで冷却し、１Ｎ塩酸１０ｇ及び酢酸エチル３０ｍｌを加え、３０分攪拌した後、セライトろ過し、水層を分離した。減圧下溶媒を留去し、クロロホルム３０ｍｌ、５％ＮａＯＨ水溶液３０ｍｌを加え、有機層を分離して得られた水層を１Ｎ塩酸で中和し、酢酸エチル３０ｍｌで抽出した。無水硫酸マグネシウムで乾燥した後、減圧下溶媒を留去し、4-アセチル-2-メチル安息香酸０．４４ｇ（収率６１％）を白色結晶として得た。
〔実施例１１〕
耐圧性の反応容器に、4’-ブロモ-2’-メチルアセトアニリド０．４５６ｇ（２ミリモル）、n-ブタノール３．０ｍｌ、炭酸カリウム０．３３ｇ（２．４ミリモル）、n-ブチルビニルエーテル１．０ｇ（１０ミリモル）、1,3-ビス（ジフェニルホスフィノ）プロパン０．０１３３ｇ（０．０３２ミリモル）及び活性炭担持５％パラジウム０．０４７８ｇ（含水率52.27重量％、ＮＥケムキャット社製）を加え、反応系内を脱気したのち、窒素ガスにより１ＭＰａに加圧し、１４０℃にて６時間反応させた。室温まで冷却後、大気圧まで減圧し、１Ｎ塩酸１０ｇを加え、３０分攪拌した後、セライトろ過し、アセトニトリルを加え均一にした溶液をＨＰＬＣを用いた定量分析法で分析したところ、4’-アセチル-2’-メチルアセトアニリドの含有量は０．３３６ｇ（収率８８％）であった。
〔実施例１２〕
耐圧性の反応容器に、4’-ブロモ-2’-メチルアセトアニリド５．７ｇ（２５ミリモル）、n-ブタノール２０ｇ、ジメチルホルムアミド１０ｇ、炭酸カリウム４．１４ｇ（３０ミリモル）、n-ブチルビニルエーテル１２．５ｇ（１２５ミリモル）、1,3-ビス（ジフェニルホスフィノ）プロパン０．１０ｇ（０．２４ミリモル）及び活性炭担持５％パラジウム０．３５８ｇ（含水率52.27重量％、ＮＥケムキャット社製）を加え、反応系内を脱気したのち、窒素ガスにより１ＭＰａに加圧し、１２０℃にて６時間反応させた。室温まで冷却後、大気圧まで減圧し、n-ブタノール３０ｇ、１Ｎ塩酸３０ｇを加え、３０分攪拌した後、セライトろ過し、水層を分離した。有機層を高速液体クロマトグラフィーを用いた定量分析法で分析したところ、4’-アセチル-2’-メチルアセトアニリドの含有量は４．５１ｇ（収率９５％）であった。
〔実施例１３〕
窒素雰囲気下、4-ブロモ-2-メチルアニリン０．３７２ｇ（２ミリモル）のn-ブタノール２ｍｌ及びジメチルスルホキシド１ｍｌの混合溶液に室温にて無水酢酸２．１４ｇ（２．１ミリモル）を滴下した。２時間攪拌したのち、炭酸カリウム０．６１ｇ（４．４ミリモル）、1,4-ブタンジオールモノビニルエーテル０．７０ｇ（６ミリモル）、1,3-ビス（ジフェニルホスフィノ）プロパン０．００８ｇ（０．０２ミリモル）及び活性炭担持５％パラジウム０．０２８７ｇ（含水率52.27重量％、ＮＥケムキャット社製）を加え、反応系内を脱気したのち、窒素雰囲気下で７時間還流させた。反応終了後、室温まで冷却し、１Ｎ塩酸１０ｇを加え、３０分攪拌した後、セライトろ過し、アセトニトリルを加え均一にした溶液をＨＰＬＣを用いた定量分析法で分析したところ、4’-アセチル-2’-メチルアセトアニリドの含有量は０．３４４ｇ（収率９０％）であった。
〔実施例１４〕
窒素雰囲気下、2-メチルアニリン２１．４ｇ(２００ミリモル)にn-ブタノール１２８．４gを加え、５０℃まで加熱し、無水酢酸２１．４ｇ（２１０ミリモル）を滴下した。５０℃にて２時間反応させた後、３０℃まで冷却し、n-ブタノール８５．６g、４７％臭化水素酸４１．４ｇ（２４０ミリモル）を加え、３０％過酸化水素水２６．１ｇ(２３０ミリモル)を滴下した。３０℃にて３時間反応させた後、水１０７ｇ、n-ブタノール２１４g及び亜硫酸ナトリウム５．０４ｇ(４０ミリモル)を加え、３０分攪拌した後、水層を分離し、4’-ブロモ-2’-メチルアセトアニリドのn-ブタノール溶液５５０．３ｇを得た。n-ブタノール３３４gを減圧下留去し、炭酸カリウム３１．４ｇ（２２８ミリモル）、1,4-ブタンジオールモノビニルエーテル５５．１ｇ（４７４ミリモル）、1,3-ビス（ジフェニルホスフィノ）プロパン０．５０３ｇ（０．４０６ミリモル）及び活性炭担持５％パラジウム１．８７ｇ（含水率53.67重量％、ＮＥケムキャット社製）を加え、反応系内を脱気したのち窒素雰囲気下で８時間還流させた。反応終了後、５０℃まで冷却し、n-ブタノール８７ｇ及び水１７３ｇを加え、３０分間攪拌した後、セライトろ過し、水層を分離した。有機層に酢酸１２．０ｇ（２００ミリモル）を加え、５０℃にて３時間攪拌した後、室温まで冷却した溶液をHPLCを用いた定量分析法で分析したところ、4’-アセチル-2’-メチルアセトアニリドの含有量は３６．４ｇ（収率９５％）であった。
〔実施例１５〕
4-ブロモ-2-メチル安息香酸エチル０．４８６ｇ（２．０ミリモル）にn-ブタノール３．０ｍｌ、ジシクロヘキシルメチルアミン０．４７ｇ（２．４ミリモル）、1,4-ブタンジオールモノビニルエーテル０．７０ｇ（６．０ミリモル）、1,3-ビス（ジフェニルホスフィノ）プロパン０．０１６５ｇ（０．０４ミリモル）及び活性炭担持５％パラジウム（含水率55.95重量％、ＮＥケムキャット社製）０．０３３ｇを加え、反応系内を脱気したのち、窒素雰囲気下で３０時間還流させた。反応終了後、室温まで冷却し、１Ｎ塩酸１０ｇ及び酢酸エチル２０ｍｌを加え、３０分攪拌した後、セライトろ過し、水層を分離して得られた溶液を減圧下溶媒を留去し、シリカゲルカラムクロマトグラフィー（ヘキサン酢酸エチル＝５：１）により精製し、4-アセチル-2-メチル安息香酸エチル０．３８ｇを淡黄色液体として得た。（収率９２％、１H-NMR(CDCl3):δ(ppm)[7.96(d, 1H, 8.0Hz), 7.95-7.78(m, 2H), 4.39(q, 2H, 7.2Hz), 2.65(s, 3H), 2.62(s, 3H), 1.41(t, 3H, 7.2Hz)]）
〔実施例１６〕
4-ブロモ-2-メチル安息香酸エチルの代わりに4-ブロモ-2-メチル安息香酸メチルを用い、実施例１５と同様の操作を行い、4-アセチル-2-メチル安息香酸メチル０．１４ｇを淡黄色液体として得た。（収率３７％、１H-NMR(CDCl3):δ(ppm)[7.97(d, 1H, 8.0Hz), 7.82-7.78(m, 2H), 3.93(s, 3H), 2.65(s, 3H), 2.62(s, 3H)]）
Hereinafter, the present invention will be specifically described with reference to examples, but the present invention is not limited thereto.
[Example 1]
4'-bromo-2'-methylacetanilide 25.0 g (110 mmol), n-butanol 100 g, potassium carbonate 18.2 g (132 mmol), 1,4-butanediol monovinyl ether 38.3 g (330 mmol), 1 , 3-bis (diphenylphosphino) propane 0.437 g (1.06 mmol) and activated carbon-supported 5% palladium 1.57 g (water content 52.27 wt%, manufactured by NE Chemcat) were added to degas the reaction system. Thereafter, the mixture was refluxed for 10 hours under a nitrogen atmosphere. After completion of the reaction, the reaction mixture was cooled to room temperature, 125 g of n-butanol and 125 g of 1N hydrochloric acid were added, stirred for 30 minutes, filtered through Celite, and the aqueous layer was separated. When the organic layer was analyzed by a quantitative analysis method using high performance liquid chromatography, the content of 4′-acetyl-2′-methylacetanilide was 19.8 g (yield 94%).
[Example 2]
45.6 g of n-butanol, 8.48 g (60 mmol) of potassium carbonate, 14.5 g (125 mmol) of 1,4-butanediol monovinyl ether are added to 11.4 g (50 mmol) of 4′-bromo-2′-methylacetanilide. 1,3-bis (diphenylphosphino) propane (0.20 g, 0.49 mmol) and activated carbon-supported 5% palladium (0.717 g, water content: 52.27% by weight, manufactured by NE Chemcat) were removed from the reaction system. After gassing, the mixture was refluxed for 8 hours under a nitrogen atmosphere. After completion of the reaction, the reaction mixture was cooled to 50 ° C., 57 g of n-butanol and 57 g of water were added, and the mixture was stirred for 30 minutes, filtered through celite, and the aqueous layer was separated. 3 g (50 mmol) of acetic acid was added to the organic layer and stirred at 50 ° C. for 3 hours. The solvent was distilled off under reduced pressure, 34.2 g of toluene was added, the mixture was cooled to 0 ° C., and stirred for 30 minutes. The solid collected by filtration from the resulting slurry was dried under reduced pressure to obtain 7.70 g (yield 81%) of 4′-acetyl-2′-methylacetanilide as white crystals.
Example 3
0.684 g (4.0 mmol) of p-bromotoluene, 5.0 ml of n-butanol, 0.66 g (4.8 mmol) of potassium carbonate, 1.39 g (12 mmol) of 1,4-butanediol monovinyl ether, 1 , 3-bis (diphenylphosphino) propane 0.0165 g (0.04 mmol) and activated carbon-supported 5% palladium (water content 52.27% by weight, manufactured by NE Chemcat) 0.0574 g were added to degas the reaction system. Thereafter, the mixture was refluxed for 6 hours under a nitrogen atmosphere. After completion of the reaction, the reaction mixture was cooled to room temperature, 10 g of 1N hydrochloric acid was added, and the mixture was stirred for 30 minutes, filtered through Celite, and analyzed by quantitative analysis using HPLC. The solution was homogenized with 4′-methylacetophenone. The content of was 0.42 g (yield 78%).
Example 4
The same operation as in Example 3 was carried out using o-bromotoluene instead of p-bromotoluene to obtain 2′-methylacetophenone in a yield of 85%.
Example 5
The same operation as in Example 3 was carried out using m-bromotoluene instead of p-bromotoluene to obtain 3′-methylacetophenone in a yield of 93%.
Example 6
Using p-bromoanisole instead of p-bromotoluene, the same operation as in Example 3 was performed to obtain 4′-methoxyacetophenone in a yield of 86%.
Example 7
Using p-fluorobromobenzene instead of p-bromotoluene, the same operation as in Example 3 was performed to obtain 4′-fluoroacetophenone in a yield of 39%.
Example 8
Using p-chlorobromobenzene in place of p-bromotoluene, the same procedure as in Example 3 was performed to obtain 4′-chloroacetophenone in a yield of 20%.
Example 9
Using p-bromobenzonitrile in place of p-bromotoluene, the same procedure as in Example 3 was performed to obtain 4′-cyanoacetophenone in a yield of 17%.
Example 10
To 0.860 g (4.0 mmol) of 4-bromo-2-methylbenzoic acid, 5.0 ml of n-butanol, 0.66 g (4.8 mmol) of potassium carbonate, 1.39 g of 1,4-butanediol monovinyl ether ( 12.0 mmol), 1,3-bis (diphenylphosphino) propane 0.0154 g (0.04 mmol) and activated carbon-supported 5% palladium (water content 53.67% by weight, manufactured by NE Chemcat) 0.0557 g were added, The reaction system was degassed and then refluxed for 6 hours under a nitrogen atmosphere. After completion of the reaction, the reaction mixture was cooled to room temperature, 10 g of 1N hydrochloric acid and 30 ml of ethyl acetate were added, stirred for 30 minutes, filtered through celite, and the aqueous layer was separated. The solvent was distilled off under reduced pressure, 30 ml of chloroform and 30 ml of 5% NaOH aqueous solution were added, the aqueous layer obtained by separating the organic layer was neutralized with 1N hydrochloric acid, and extracted with 30 ml of ethyl acetate. After drying over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure to obtain 0.44 g (yield 61%) of 4-acetyl-2-methylbenzoic acid as white crystals.
Example 11
In a pressure-resistant reaction vessel, 4'-bromo-2'-methylacetanilide 0.456 g (2 mmol), n-butanol 3.0 ml, potassium carbonate 0.33 g (2.4 mmol), n-butyl vinyl ether 1. 0 g (10 mmol), 0.013 g (0.032 mmol) of 1,3-bis (diphenylphosphino) propane and 0.0478 g of 5% palladium on activated carbon (water content 52.27 wt%, manufactured by NE Chemcat) were added. After degassing the reaction system, it was pressurized to 1 MPa with nitrogen gas and reacted at 140 ° C. for 6 hours. After cooling to room temperature, the pressure was reduced to atmospheric pressure, 10 g of 1N hydrochloric acid was added, the mixture was stirred for 30 minutes, filtered through celite, and the homogeneous solution added with acetonitrile was analyzed by quantitative analysis using HPLC. The content of acetyl-2′-methylacetanilide was 0.336 g (yield 88%).
Example 12
In a pressure-resistant reaction vessel, 5.7 g (25 mmol) of 4′-bromo-2′-methylacetanilide, 20 g of n-butanol, 10 g of dimethylformamide, 4.14 g (30 mmol) of potassium carbonate, 12. 5 g (125 mmol), 1,3-bis (diphenylphosphino) propane 0.10 g (0.24 mmol) and activated carbon-supported 5% palladium 0.358 g (water content 52.27 wt%, manufactured by NE Chemcat) were added. After degassing the reaction system, it was pressurized to 1 MPa with nitrogen gas and reacted at 120 ° C. for 6 hours. After cooling to room temperature, the pressure was reduced to atmospheric pressure, 30 g of n-butanol and 30 g of 1N hydrochloric acid were added, and the mixture was stirred for 30 minutes, filtered through celite, and the aqueous layer was separated. When the organic layer was analyzed by quantitative analysis using high performance liquid chromatography, the content of 4′-acetyl-2′-methylacetanilide was 4.51 g (yield 95%).
Example 13
Under a nitrogen atmosphere, 2.14 g (2.1 mmol) of acetic anhydride was added dropwise at room temperature to a mixed solution of 0.372 g (2 mmol) of 4-bromo-2-methylaniline in 2 ml of n-butanol and 1 ml of dimethyl sulfoxide. After stirring for 2 hours, potassium carbonate 0.61 g (4.4 mmol), 1,4-butanediol monovinyl ether 0.70 g (6 mmol), 1,3-bis (diphenylphosphino) propane 0.008 g (0 0.02 g of activated carbon-supported 5% palladium (water content: 52.27% by weight, manufactured by NE Chemcat) was deaerated in the reaction system and then refluxed for 7 hours in a nitrogen atmosphere. After completion of the reaction, the reaction mixture was cooled to room temperature, 10 g of 1N hydrochloric acid was added, and the mixture was stirred for 30 minutes, filtered through Celite, and analyzed by quantitative analysis using HPLC. The content of 2′-methylacetanilide was 0.344 g (yield 90%).
Example 14
Under a nitrogen atmosphere, 128.4 g of n-butanol was added to 21.4 g (200 mmol) of 2-methylaniline, heated to 50 ° C., and 21.4 g (210 mmol) of acetic anhydride was added dropwise. After reacting at 50 ° C. for 2 hours, the mixture was cooled to 30 ° C., 85.6 g of n-butanol and 41.4 g (240 mmol) of 47% hydrobromic acid were added, and 26.1 g of 30% hydrogen peroxide ( 230 mmol) was added dropwise. After reacting at 30 ° C. for 3 hours, 107 g of water, 214 g of n-butanol and 5.04 g (40 mmol) of sodium sulfite were added and stirred for 30 minutes, and then the aqueous layer was separated and 4′-bromo-2 ′. 550.3 g of an n-butanol solution of -methylacetanilide was obtained. 334 g of n-butanol was distilled off under reduced pressure, 31.4 g (228 mmol) of potassium carbonate, 55.1 g (474 mmol) of 1,4-butanediol monovinyl ether, 0.13 of 1,3-bis (diphenylphosphino) propane. 503 g (0.406 mmol) and 1.87 g of activated carbon-supported 5% palladium (water content 53.67% by weight, manufactured by NE Chemcat) were added, and the reaction system was degassed and then refluxed for 8 hours under a nitrogen atmosphere. After completion of the reaction, the mixture was cooled to 50 ° C., added with 87 g of n-butanol and 173 g of water, stirred for 30 minutes, filtered through celite, and the aqueous layer was separated. 12.0 g (200 mmol) of acetic acid was added to the organic layer, and the mixture was stirred at 50 ° C. for 3 hours, and then the solution cooled to room temperature was analyzed by quantitative analysis using HPLC. As a result, 4′-acetyl-2′- The content of methylacetanilide was 36.4 g (yield 95%).
Example 15
0.486 g (2.0 mmol) of ethyl 4-bromo-2-methylbenzoate, 3.0 ml of n-butanol, 0.47 g (2.4 mmol) of dicyclohexylmethylamine, 1,4-butanediol monovinyl ether 70 g (6.0 mmol), 0.013-g (0.04 mmol) of 1,3-bis (diphenylphosphino) propane and 0.033 g of activated carbon-supported 5% palladium (water content 55.95 wt%, manufactured by NE Chemcat) In addition, the reaction system was degassed and then refluxed for 30 hours under a nitrogen atmosphere. After completion of the reaction, the mixture was cooled to room temperature, 10 g of 1N hydrochloric acid and 20 ml of ethyl acetate were added, stirred for 30 minutes, filtered through Celite, the aqueous layer was separated, and the solvent was distilled off under reduced pressure. Purification by chromatography (hexane ethyl acetate = 5: 1) gave 0.38 g of ethyl 4-acetyl-2-methylbenzoate as a pale yellow liquid. (Yield 92%, 1 H-NMR (CDCl 3 ): δ (ppm) [7.96 (d, 1H, 8.0 Hz), 7.95-7.78 (m, 2H), 4.39 (q, 2H, 7.2 Hz), 2.65 (s, 3H), 2.62 (s, 3H), 1.41 (t, 3H, 7.2Hz)])
Example 16
The same operation as in Example 15 was carried out using methyl 4-bromo-2-methylbenzoate instead of ethyl 4-bromo-2-methylbenzoate, and 0.14 g of methyl 4-acetyl-2-methylbenzoate was obtained. Obtained as a pale yellow liquid. (Yield 37%, 1 H-NMR (CDCl 3 ): δ (ppm) [7.97 (d, 1H, 8.0 Hz), 7.82-7.78 (m, 2H), 3.93 (s, 3H), 2.65 (s, 3H), 2.62 (s, 3H)])
本発明の製造方法は、医農薬及び各種化学品の中間体として有用なアセトフェノン類の工業的製造方法として有用である。
The production method of the present invention is useful as an industrial production method for acetophenones that are useful as intermediates for medical and agricultural chemicals and various chemicals.
Claims (12)
［式中、Xは、塩素原子、臭素原子、ヨウ素原子又はトリフルオロメタンスルホニルオキシを表し、
Yは、フッ素原子、塩素原子、シアノ、ニトロ、C１〜C６アルキル、C３〜C８シクロアルキル、C１〜C６ハロアルキル、C１〜C６アルコキシ、C１〜C６ハロアルコキシ、C１〜C６アルキルチオ、C１〜C６ハロアルキルチオ、ホルミル、カルボキシル、C１〜C６アルキルカルボニル、C１〜C６ハロアルキルカルボニル、C１〜C６アルコキシカルボニル、C１〜C６アルキルチオカルボニル、C１〜C６アルコキシチオカルボニル、C１〜C６アルキルジチオカルボニル、C１〜C６アルキルスルホニル、C１〜C６ハロアルキルスルホニル、‐CH2N(R2)R1、‐CON(R2)R1又は‐N(R2)R1（ただし、Ｘが塩素原子のとき塩素原子を除く）を表し、nが２以上を表すとき、各々のYは互いに同一であっても又は互いに相異なっていてもよく、
Zは、水素原子、フッ素原子、塩素原子、シアノ、ニトロ、C１〜C６アルキル、C３〜C８シクロアルキル、C１〜C６ハロアルキル、C１〜C６アルコキシ、C１〜C６ハロアルコキシ、C１〜C６アルキルチオ、C１〜C６ハロアルキルチオ、ホルミル、カルボキシル、C１〜C６アルキルカルボニル、C１〜C６ハロアルキルカルボニル、C１〜C６アルコキシカルボニル、C１〜C６アルキルチオカルボニル、C１〜C６アルコキシチオカルボニル、C１〜C６アルキルジチオカルボニル、C１〜C６アルキルスルホニル、C１〜C６ハロアルキルスルホニル、‐CH2N(R2)R1、‐CON(R2)R1又は‐N(R2)R1（ただし、Xが塩素原子のとき塩素原子を除く）を表し、
R1は、水素原子、C１〜C６アルキル、ホルミル、C１〜C６アルキルカルボニル、C１〜C６ハロアルキルカルボニル、C１〜C６アルコキシカルボニル、C１〜C６アルキルチオカルボニル、C１〜C６アルコキシチオカルボニル、C１〜C６アルキルジチオカルボニル、C１〜C６アルキルスルホニル又はC１〜C６ハロアルキルスルホニルを表し、
R2は、水素原子、C１〜C６アルキル、ホルミル、C１〜C６アルキルカルボニル、C１〜C６ハロアルキルカルボニル又はC１〜C６アルコキシカルボニルを表し、R1及びR2は、互いに同一であっても又は互いに相異なっていてもよく、
nは、０から４の整数を表す。］
で表される化合物と式（２）：
［式（２）中、Ｗは、‐OR３、‐N(R４) COR５又は式（３）：
を表し、
R３は、C１〜C１２アルキル、C１〜C６ハロアルキル、ビニルオキシ（C１〜C１２）アルキル、ヒドロキシ（C２〜C１２）アルキル又はC１〜C６アルコキシ（C１〜C１２）アルキルを表し、
R４およびR５は、各々独立に、水素原子、C１〜C６アルキル、C１〜C６アルコキシ、C１〜C６ハロアルキル又は、R４およびR５が結合しているアミド基とともにC２〜C５アルキルで形成する４〜７員環を表す。］
で表される化合物を塩基、ホスフィン又は芳香族アミン配位子及び担持パラジウム触媒の存在下で反応を行い、反応系内で得られる式（４）：
［式（４）中、W、Y、Z及びnは前記と同じ意味を表す。］
で表される中間体または式（５）：
［式（５）中、Y、Z及びnは前記と同じ意味を表し、R６はC２〜C１２アルキルを表す。］
で表される中間体を酸と反応させることによる式（６）：
［式（６）中、Y、Z及びnは前記と同じ意味を表す。］
で表されるアセトフェノン類の製造方法。 Formula (1):
[Wherein X represents a chlorine atom, a bromine atom, an iodine atom or trifluoromethanesulfonyloxy,
Y is fluorine atom, chlorine atom, cyano, nitro, C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, C 1 -C 6 alkylthio, C 1 -C 6 haloalkylthio, formyl, carboxyl, C 1 -C 6 alkylcarbonyl, C 1 -C 6 haloalkylcarbonyl, C 1 -C 6 alkoxycarbonyl, C 1 -C 6 alkylthiocarbonyl , C 1 -C 6 alkoxythiocarbonyl, C 1 -C 6 alkyl dithio carbonyl, C 1 -C 6 alkylsulfonyl, C 1 -C 6 haloalkylsulfonyl, -CH 2 N (R 2) R 1, -CON (R 2 ) R 1 or —N (R 2 ) R 1 (excluding a chlorine atom when X is a chlorine atom), and when n is 2 or more, each Y may be the same as each other or They may be different,
Z is a hydrogen atom, a fluorine atom, a chlorine atom, a cyano, nitro, C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, C 1 -C 6 alkylthio, C 1 -C 6 haloalkylthio, formyl, carboxyl, C 1 -C 6 alkylcarbonyl, C 1 -C 6 haloalkylcarbonyl, C 1 -C 6 alkoxycarbonyl, C 1 -C 6 alkylthiocarbonyl, C 1 -C 6 alkoxythiocarbonyl, C 1 -C 6 alkyl dithio carbonyl, C 1 -C 6 alkylsulfonyl, C 1 -C 6 haloalkylsulfonyl, -CH 2 N (R 2) R 1, - CON (R 2 ) R 1 or -N (R 2 ) R 1 (however, when X is a chlorine atom, excluding a chlorine atom)
R 1 is a hydrogen atom, C 1 -C 6 alkyl, formyl, C 1 -C 6 alkylcarbonyl, C 1 -C 6 haloalkylcarbonyl, C 1 -C 6 alkoxycarbonyl, C 1 -C 6 alkylthiocarbonyl, C 1 -C 6 alkoxythiocarbonyl, C 1 -C 6 alkyl dithio carbonyl, represents C 1 -C 6 alkylsulfonyl or C 1 -C 6 haloalkylsulfonyl,
R 2 represents a hydrogen atom, C 1 -C 6 alkyl, formyl, C 1 -C 6 alkylcarbonyl, C 1 -C 6 haloalkylcarbonyl, or C 1 -C 6 alkoxycarbonyl, and R 1 and R 2 represent each other They may be the same or different from each other,
n represents an integer of 0 to 4. ]
And a compound represented by formula (2):
[In Formula (2), W is -OR 3 , -N (R 4 ) COR 5 or Formula (3):
Represents
R 3 is C 1 -C 12 alkyl, C 1 -C 6 haloalkyl, vinyloxy (C 1 -C 12 ) alkyl, hydroxy (C 2 -C 12 ) alkyl or C 1 -C 6 alkoxy (C 1 -C 12 ) Represents alkyl,
R 4 and R 5 are each independently a hydrogen atom, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, or an amide group to which R 4 and R 5 are bonded. It represents a 4 to 7 membered ring formed by 2 to C 5 alkyl. ]
A compound represented by formula (4) obtained by reacting in the presence of a base, a phosphine or an aromatic amine ligand and a supported palladium catalyst:
[In formula (4), W, Y, Z and n represent the same meaning as described above. ]
Or an intermediate represented by formula (5):
[In formula (5), Y, Z, and n represent the same meaning as described above, and R 6 represents C 2 -C 12 alkyl. ]
Formula (6) by reacting an intermediate represented by
[In Formula (6), Y, Z, and n represent the same meaning as the above. ]
The manufacturing method of acetophenone represented by these.
Yは、フッ素原子、塩素原子、シアノ、ニトロ、C１〜C６アルキル、C３〜C８シクロアルキル、C１〜C６ハロアルキル、C１〜C６アルコキシ、C１〜C６ハロアルコキシ、ホルミル、カルボキシル、C１〜C６アルキルカルボニル、C１〜C６ハロアルキルカルボニル、C１〜C６アルコキシカルボニル、C１〜C６アルキルスルホニル、C１〜C６ハロアルキルスルホニル、‐CH2N(R2)R1、‐CON(R2)R1又は‐N(R2)R1を表し、nが２以上を表すとき、各々のYは互いに同一であっても又は互いに相異なっていてもよく、Zは、‐N(R2)R1、フッ素原子、塩素原子、シアノ、C１〜C４アルキル、C１〜C４アルコキシ、C１〜C４アルコキシカルボニル又はカルボキシルを表す、請求項１記載のアセトフェノン類の製造方法。 X represents a bromine atom,
Y is fluorine atom, chlorine atom, cyano, nitro, C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, formyl, carboxyl, C 1 -C 6 alkylcarbonyl, C 1 -C 6 haloalkylcarbonyl, C 1 -C 6 alkoxycarbonyl, C 1 -C 6 alkylsulfonyl, C 1 -C 6 haloalkylsulfonyl, -CH 2 N (R 2 ) R 1 , —CON (R 2 ) R 1 or —N (R 2 ) R 1, and when n represents 2 or more, each Y may be the same or different from each other Often Z represents —N (R 2 ) R 1 , fluorine atom, chlorine atom, cyano, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 alkoxycarbonyl or carboxyl. A process for producing acetophenones according to 1.
Yは、フッ素原子、塩素原子、C１〜C４アルキル、C１〜C４ハロアルキル又はC１〜C４アルコキシを表し、Zは、‐N(R2)R1又はカルボキシルを表し、R１は、水素原子、C１〜C６アルキルカルボニル又はC１〜C６アルコキシカルボニル、R２は、水素原子、ホルミル又はC１〜C６アルキルカルボニル、nは、０から４の整数を表し、
Ｗは、‐OR3、‐N(R4) COR5又は式（３）を表し、R3は、C１〜C１２アルキル、ビニルオキシ（C１〜C８）アルキル、ヒドロキシ（C２〜C８）アルキルを表し、R4およびR5は、各々独立に、水素原子、C１〜C６アルキル又は、R4およびR5が結合しているアミド基とともにC２〜C５アルキルで形成する４〜７員環を表し、
R６はC２〜C８アルキルを表す、請求項１記載のアセトフェノン類の製造方法。 X represents a bromine atom,
Y is a fluorine atom, a chlorine atom, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl or C 1 -C 4 alkoxy, Z is, -N (R 2) R 1 or a carboxyl, R 1 Is a hydrogen atom, C 1 -C 6 alkylcarbonyl or C 1 -C 6 alkoxycarbonyl, R 2 is a hydrogen atom, formyl or C 1 -C 6 alkylcarbonyl, n is an integer of 0 to 4,
W represents —OR 3 , —N (R 4 ) COR 5 or formula (3), and R 3 represents C 1 -C 12 alkyl, vinyloxy (C 1 -C 8 ) alkyl, hydroxy (C 2 -C 8 ) represents alkyl, and R 4 and R 5 are each independently formed of C 2 -C 5 alkyl together with a hydrogen atom, C 1 -C 6 alkyl or an amide group to which R 4 and R 5 are bonded. Represents a 4-7 membered ring,
The method for producing acetophenones according to claim 1, wherein R 6 represents C 2 -C 8 alkyl.
Yは、フッ素原子、塩素原子、トリフルオロメチル、メチル又はエチルを表し、Zは、‐N(R2)R1を表し、R１は、アセチルを表し、R２は、水素原子を表し、nは、０から４の整数を表し、
Ｗは‐OR３を表し、R３は、C１〜C１２アルキル、ビニルオキシ（C１〜C８）アルキル、ヒドロキシ（C２〜C４）アルキルを表し、
R６はC２〜C４アルキルを表す、請求項１記載のアセトフェノン類の製造方法。 X represents a bromine atom,
Y represents a fluorine atom, a chlorine atom, trifluoromethyl, methyl or ethyl, Z represents —N (R 2 ) R 1 , R 1 represents acetyl, R 2 represents a hydrogen atom, n represents an integer of 0 to 4,
W represents —OR 3 , R 3 represents C 1 -C 12 alkyl, vinyloxy (C 1 -C 8 ) alkyl, hydroxy (C 2 -C 4 ) alkyl,
The method for producing acetophenones according to claim 1, wherein R 6 represents C 2 -C 4 alkyl.
［式（７）中、X、Y及びnは請求項４と同じ意味を表す。］
で表される化合物をアセチル化して得られる、式（８）：
［式（８）中、X、Y及びnは請求項４と同じ意味を表す。］
で表される化合物を出発原料として用いる、請求項４記載のアセトフェノン類の製造方法。 Formula (7):
[In Formula (7), X, Y, and n represent the same meaning as Claim 4. ]
Formula (8) obtained by acetylating a compound represented by the formula:
[In the formula (8), X, Y and n represent the same meaning as in claim 4. ]
The method for producing acetophenones according to claim 4, wherein a compound represented by the formula:
[式（９）中、Y及びnは請求項４と同じ意味を表す。］
で表される化合物をアセチル化して得られる、式（１０）：
［式（１０）中、Y及びnは請求項４と同じ意味を表す。］
で表される化合物を臭素化して得られる、式（１１）：
［式（１１）中、Y及びnは請求項４と同じ意味を表す。］
で表される化合物を出発原料として用いる、請求項４記載のアセトフェノン類の製造方法。 Formula (9):
[In formula (9), Y and n represent the same meaning as in claim 4. ]
Formula (10) obtained by acetylating a compound represented by:
[In formula (10), Y and n represent the same meaning as in claim 4. ]
Formula (11) obtained by brominating a compound represented by:
[In formula (11), Y and n represent the same meaning as in claim 4. ]
The method for producing acetophenones according to claim 4, wherein a compound represented by the formula:
Yは、フッ素原子、塩素原子、トリフルオロメチル、メチル又はエチルを表し、Zは、カルボキシルまたはC１〜C６アルコキシカルボニルを表し、R１は、アセチルを表し、R２は、水素原子を表し、nは、０から４の整数を表し、
Ｗは‐OR３を表し、R３は、C１〜C１２アルキル、ビニルオキシ（C１〜C８）アルキル、ヒドロキシ（C２〜C４）アルキルを表し、
R６はC２〜C４アルキルを表す、請求項１記載のアセトフェノン類の製造方法。 X represents a bromine atom,
Y represents a fluorine atom, a chlorine atom, trifluoromethyl, methyl or ethyl, Z represents carboxyl or C 1 -C 6 alkoxycarbonyl, R 1 represents acetyl, R 2 represents a hydrogen atom. , N represents an integer from 0 to 4,
W represents —OR 3 , R 3 represents C 1 -C 12 alkyl, vinyloxy (C 1 -C 8 ) alkyl, hydroxy (C 2 -C 4 ) alkyl,
The method for producing acetophenones according to claim 1, wherein R 6 represents C 2 -C 4 alkyl.
[式（１２）中、VはC１〜C４アルキルを表す。］
で表されるアセトフェノン化合物。 Formula (12)
Wherein (12), V represents a C 1 -C 4 alkyl. ]
An acetophenone compound represented by:
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| WO2012007426A1 (en) | 2010-07-13 | 2012-01-19 | Basf Se | Azoline substituted isoxazoline benzamide compounds for combating animal pests |
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| US8853410B2 (en) | 2009-04-30 | 2014-10-07 | Basf Se | Process for preparing substituted isoxazoline compounds and their precursors |
| US9085541B2 (en) | 2010-06-23 | 2015-07-21 | Basf Se | Process for producing imine compounds for combating invertebrate pests |
| WO2012007426A1 (en) | 2010-07-13 | 2012-01-19 | Basf Se | Azoline substituted isoxazoline benzamide compounds for combating animal pests |
| US9006447B2 (en) | 2010-11-03 | 2015-04-14 | Basf Se | Method for preparing substituted isoxazoline compounds and their precursors 4-chloro, 4-bromo- or 4-iodobenzaldehyde oximes |
| KR20150062910A (en) | 2013-11-29 | 2015-06-08 | 롯데케미칼 주식회사 | Preparation method of acetophenone |
| CN109553528A (en) * | 2018-12-21 | 2019-04-02 | 荆门医药工业技术研究院 | A kind of synthetic method of 2- methyl -4- acetylbenzoic acid methyl esters |
| CN115477577A (en) * | 2022-10-25 | 2022-12-16 | 台州臻挚生物科技有限公司 | Novel method for preparing 2-methyl-4-acetylbenzoic acid and derivatives thereof |
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