JP5219086B2 - Process for producing trifluoromethylarenes - Google Patents
Process for producing trifluoromethylarenes Download PDFInfo
- Publication number
- JP5219086B2 JP5219086B2 JP2009072188A JP2009072188A JP5219086B2 JP 5219086 B2 JP5219086 B2 JP 5219086B2 JP 2009072188 A JP2009072188 A JP 2009072188A JP 2009072188 A JP2009072188 A JP 2009072188A JP 5219086 B2 JP5219086 B2 JP 5219086B2
- Authority
- JP
- Japan
- Prior art keywords
- iodo
- copper
- general formula
- reaction
- group
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 238000000034 method Methods 0.000 title description 23
- -1 arene iodide Chemical class 0.000 claims description 23
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 claims description 14
- 239000005749 Copper compound Substances 0.000 claims description 12
- 150000001880 copper compounds Chemical class 0.000 claims description 12
- 229910001512 metal fluoride Inorganic materials 0.000 claims description 10
- 150000004673 fluoride salts Chemical class 0.000 claims description 9
- 229910017464 nitrogen compound Inorganic materials 0.000 claims description 8
- 150000002830 nitrogen compounds Chemical class 0.000 claims description 8
- 125000003118 aryl group Chemical group 0.000 claims description 7
- 235000003270 potassium fluoride Nutrition 0.000 claims description 7
- 239000011698 potassium fluoride Substances 0.000 claims description 7
- XJHCXCQVJFPJIK-UHFFFAOYSA-M caesium fluoride Chemical group [F-].[Cs+] XJHCXCQVJFPJIK-UHFFFAOYSA-M 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 claims description 4
- ODWXUNBKCRECNW-UHFFFAOYSA-M bromocopper(1+) Chemical compound Br[Cu+] ODWXUNBKCRECNW-UHFFFAOYSA-M 0.000 claims description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- 239000003054 catalyst Substances 0.000 claims description 3
- 238000006243 chemical reaction Methods 0.000 description 31
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 14
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 238000004817 gas chromatography Methods 0.000 description 8
- 229910052757 nitrogen Inorganic materials 0.000 description 8
- 239000002904 solvent Substances 0.000 description 7
- 241001120493 Arene Species 0.000 description 6
- NHPPIJMARIVBGU-UHFFFAOYSA-N 1-iodonaphthalene Chemical compound C1=CC=C2C(I)=CC=CC2=C1 NHPPIJMARIVBGU-UHFFFAOYSA-N 0.000 description 5
- MWKJTNBSKNUMFN-UHFFFAOYSA-N trifluoromethyltrimethylsilane Chemical compound C[Si](C)(C)C(F)(F)F MWKJTNBSKNUMFN-UHFFFAOYSA-N 0.000 description 5
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- GOBHSUAEQGWYBT-UHFFFAOYSA-N 1-(trifluoromethyl)naphthalene Chemical compound C1=CC=C2C(C(F)(F)F)=CC=CC2=C1 GOBHSUAEQGWYBT-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 239000007810 chemical reaction solvent Substances 0.000 description 3
- 238000010813 internal standard method Methods 0.000 description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 3
- 239000012299 nitrogen atmosphere Substances 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 2
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 2
- 230000032683 aging Effects 0.000 description 2
- 239000003905 agrochemical Substances 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 125000006575 electron-withdrawing group Chemical group 0.000 description 2
- 239000012776 electronic material Substances 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 229910000040 hydrogen fluoride Inorganic materials 0.000 description 2
- 230000026045 iodination Effects 0.000 description 2
- 238000006192 iodination reaction Methods 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 239000004973 liquid crystal related substance Substances 0.000 description 2
- PQXKHYXIUOZZFA-UHFFFAOYSA-M lithium fluoride Chemical compound [Li+].[F-] PQXKHYXIUOZZFA-UHFFFAOYSA-M 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- AHLATJUETSFVIM-UHFFFAOYSA-M rubidium fluoride Chemical compound [F-].[Rb+] AHLATJUETSFVIM-UHFFFAOYSA-M 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
- PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
- SYSZENVIJHPFNL-UHFFFAOYSA-N (alpha-D-mannosyl)7-beta-D-mannosyl-diacetylchitobiosyl-L-asparagine, isoform B (protein) Chemical compound COC1=CC=C(I)C=C1 SYSZENVIJHPFNL-UHFFFAOYSA-N 0.000 description 1
- 125000005919 1,2,2-trimethylpropyl group Chemical group 0.000 description 1
- BBOLNFYSRZVALD-UHFFFAOYSA-N 1,2-diiodobenzene Chemical compound IC1=CC=CC=C1I BBOLNFYSRZVALD-UHFFFAOYSA-N 0.000 description 1
- 125000005918 1,2-dimethylbutyl group Chemical group 0.000 description 1
- SFPQFQUXAJOWNF-UHFFFAOYSA-N 1,3-diiodobenzene Chemical compound IC1=CC=CC(I)=C1 SFPQFQUXAJOWNF-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- LFMWZTSOMGDDJU-UHFFFAOYSA-N 1,4-diiodobenzene Chemical compound IC1=CC=C(I)C=C1 LFMWZTSOMGDDJU-UHFFFAOYSA-N 0.000 description 1
- UCCUXODGPMAHRL-UHFFFAOYSA-N 1-bromo-4-iodobenzene Chemical compound BrC1=CC=C(I)C=C1 UCCUXODGPMAHRL-UHFFFAOYSA-N 0.000 description 1
- HQHHKYXPFKHLBF-UHFFFAOYSA-N 1-bromo-4-iodonaphthalene Chemical compound C1=CC=C2C(Br)=CC=C(I)C2=C1 HQHHKYXPFKHLBF-UHFFFAOYSA-N 0.000 description 1
- FNDCCCBLANSNBS-UHFFFAOYSA-N 1-butoxy-2-iodobenzene Chemical compound CCCCOC1=CC=CC=C1I FNDCCCBLANSNBS-UHFFFAOYSA-N 0.000 description 1
- QTGWXJRPACQBDC-UHFFFAOYSA-N 1-butoxy-3-iodobenzene Chemical compound CCCCOC1=CC=CC(I)=C1 QTGWXJRPACQBDC-UHFFFAOYSA-N 0.000 description 1
- QMEHOMNBEJNMHD-UHFFFAOYSA-N 1-butoxy-4-iodobenzene Chemical compound CCCCOC1=CC=C(I)C=C1 QMEHOMNBEJNMHD-UHFFFAOYSA-N 0.000 description 1
- MPEOPBCQHNWNFB-UHFFFAOYSA-N 1-chloro-2-iodobenzene Chemical compound ClC1=CC=CC=C1I MPEOPBCQHNWNFB-UHFFFAOYSA-N 0.000 description 1
- JMLWXCJXOYDXRN-UHFFFAOYSA-N 1-chloro-3-iodobenzene Chemical compound ClC1=CC=CC(I)=C1 JMLWXCJXOYDXRN-UHFFFAOYSA-N 0.000 description 1
- GWQSENYKCGJTRI-UHFFFAOYSA-N 1-chloro-4-iodobenzene Chemical compound ClC1=CC=C(I)C=C1 GWQSENYKCGJTRI-UHFFFAOYSA-N 0.000 description 1
- UFDGEFUTYSMTPD-UHFFFAOYSA-N 1-chloro-4-iodonaphthalene Chemical compound C1=CC=C2C(Cl)=CC=C(I)C2=C1 UFDGEFUTYSMTPD-UHFFFAOYSA-N 0.000 description 1
- PSIKFNDJOGHVHP-UHFFFAOYSA-N 1-ethenyl-2-iodobenzene Chemical compound IC1=CC=CC=C1C=C PSIKFNDJOGHVHP-UHFFFAOYSA-N 0.000 description 1
- UENCBLICVDCSAB-UHFFFAOYSA-N 1-ethenyl-3-iodobenzene Chemical compound IC1=CC=CC(C=C)=C1 UENCBLICVDCSAB-UHFFFAOYSA-N 0.000 description 1
- KWHSBYQFELZKKS-UHFFFAOYSA-N 1-ethenyl-4-iodobenzene Chemical compound IC1=CC=C(C=C)C=C1 KWHSBYQFELZKKS-UHFFFAOYSA-N 0.000 description 1
- YKIFNMZOYJYZCT-UHFFFAOYSA-N 1-ethenyl-4-iodonaphthalene Chemical compound C1=CC=C2C(I)=CC=C(C=C)C2=C1 YKIFNMZOYJYZCT-UHFFFAOYSA-N 0.000 description 1
- JUJREUXKABNEFA-UHFFFAOYSA-N 1-ethoxy-2-iodobenzene Chemical compound CCOC1=CC=CC=C1I JUJREUXKABNEFA-UHFFFAOYSA-N 0.000 description 1
- UIGQMEPFSWIPHM-UHFFFAOYSA-N 1-ethoxy-3-iodobenzene Chemical compound CCOC1=CC=CC(I)=C1 UIGQMEPFSWIPHM-UHFFFAOYSA-N 0.000 description 1
- VSIIHWOJPSSIDI-UHFFFAOYSA-N 1-ethoxy-4-iodobenzene Chemical compound CCOC1=CC=C(I)C=C1 VSIIHWOJPSSIDI-UHFFFAOYSA-N 0.000 description 1
- TZZCAXOOMCXIPJ-UHFFFAOYSA-N 1-ethynyl-2-iodobenzene Chemical compound IC1=CC=CC=C1C#C TZZCAXOOMCXIPJ-UHFFFAOYSA-N 0.000 description 1
- MYGXITKLGQBZBV-UHFFFAOYSA-N 1-ethynyl-4-iodobenzene Chemical compound IC1=CC=C(C#C)C=C1 MYGXITKLGQBZBV-UHFFFAOYSA-N 0.000 description 1
- TYHUGKGZNOULKD-UHFFFAOYSA-N 1-fluoro-2-iodobenzene Chemical compound FC1=CC=CC=C1I TYHUGKGZNOULKD-UHFFFAOYSA-N 0.000 description 1
- VSKSBSORLCDRHS-UHFFFAOYSA-N 1-fluoro-3-iodobenzene Chemical compound FC1=CC=CC(I)=C1 VSKSBSORLCDRHS-UHFFFAOYSA-N 0.000 description 1
- KGNQDBQYEBMPFZ-UHFFFAOYSA-N 1-fluoro-4-iodobenzene Chemical compound FC1=CC=C(I)C=C1 KGNQDBQYEBMPFZ-UHFFFAOYSA-N 0.000 description 1
- BKXQUMOQBPPDMT-UHFFFAOYSA-N 1-fluoro-4-iodonaphthalene Chemical compound C1=CC=C2C(F)=CC=C(I)C2=C1 BKXQUMOQBPPDMT-UHFFFAOYSA-N 0.000 description 1
- DVQWNQBEUKXONL-UHFFFAOYSA-N 1-iodo-2-methoxybenzene Chemical compound COC1=CC=CC=C1I DVQWNQBEUKXONL-UHFFFAOYSA-N 0.000 description 1
- XZAWOOAVCQUZBG-UHFFFAOYSA-N 1-iodo-2-methoxynaphthalene Chemical compound C1=CC=CC2=C(I)C(OC)=CC=C21 XZAWOOAVCQUZBG-UHFFFAOYSA-N 0.000 description 1
- RINOYHWVBUKAQE-UHFFFAOYSA-N 1-iodo-2-methylbenzene Chemical compound CC1=CC=CC=C1I RINOYHWVBUKAQE-UHFFFAOYSA-N 0.000 description 1
- QFUYDAGNUJWBSM-UHFFFAOYSA-N 1-iodo-2-phenylbenzene Chemical compound IC1=CC=CC=C1C1=CC=CC=C1 QFUYDAGNUJWBSM-UHFFFAOYSA-N 0.000 description 1
- LAPWDCHUQSJIRB-UHFFFAOYSA-N 1-iodo-2-phenylmethoxybenzene Chemical compound IC1=CC=CC=C1OCC1=CC=CC=C1 LAPWDCHUQSJIRB-UHFFFAOYSA-N 0.000 description 1
- CWFKVZQHQYTVJS-UHFFFAOYSA-N 1-iodo-2-prop-2-enylbenzene Chemical compound IC1=CC=CC=C1CC=C CWFKVZQHQYTVJS-UHFFFAOYSA-N 0.000 description 1
- RSHBAGGASAJQCH-UHFFFAOYSA-N 1-iodo-3-methoxybenzene Chemical compound COC1=CC=CC(I)=C1 RSHBAGGASAJQCH-UHFFFAOYSA-N 0.000 description 1
- VLCPISYURGTGLP-UHFFFAOYSA-N 1-iodo-3-methylbenzene Chemical compound CC1=CC=CC(I)=C1 VLCPISYURGTGLP-UHFFFAOYSA-N 0.000 description 1
- KAQUBIATNWQNRE-UHFFFAOYSA-N 1-iodo-3-phenylbenzene Chemical compound IC1=CC=CC(C=2C=CC=CC=2)=C1 KAQUBIATNWQNRE-UHFFFAOYSA-N 0.000 description 1
- QMKHOPJXDQAHBG-UHFFFAOYSA-N 1-iodo-3-phenylmethoxybenzene Chemical compound IC1=CC=CC(OCC=2C=CC=CC=2)=C1 QMKHOPJXDQAHBG-UHFFFAOYSA-N 0.000 description 1
- NWQJUCCQFUTQMK-UHFFFAOYSA-N 1-iodo-4-methoxynaphthalene Chemical compound C1=CC=C2C(OC)=CC=C(I)C2=C1 NWQJUCCQFUTQMK-UHFFFAOYSA-N 0.000 description 1
- UDHAWRUAECEBHC-UHFFFAOYSA-N 1-iodo-4-methylbenzene Chemical compound CC1=CC=C(I)C=C1 UDHAWRUAECEBHC-UHFFFAOYSA-N 0.000 description 1
- SOOPESABWKAQTM-UHFFFAOYSA-N 1-iodo-4-methylnaphthalene Chemical compound C1=CC=C2C(C)=CC=C(I)C2=C1 SOOPESABWKAQTM-UHFFFAOYSA-N 0.000 description 1
- NXYICUMSYKIABQ-UHFFFAOYSA-N 1-iodo-4-phenylbenzene Chemical compound C1=CC(I)=CC=C1C1=CC=CC=C1 NXYICUMSYKIABQ-UHFFFAOYSA-N 0.000 description 1
- MPWFGAWFTAZWKZ-UHFFFAOYSA-N 1-iodo-4-phenylmethoxybenzene Chemical compound C1=CC(I)=CC=C1OCC1=CC=CC=C1 MPWFGAWFTAZWKZ-UHFFFAOYSA-N 0.000 description 1
- CVCXKFYYXBHGNV-UHFFFAOYSA-N 1-iodonaphthalene-2-carboxylic acid Chemical compound C1=CC=CC2=C(I)C(C(=O)O)=CC=C21 CVCXKFYYXBHGNV-UHFFFAOYSA-N 0.000 description 1
- LSGGPELKXXFMGO-UHFFFAOYSA-N 2,9-dibutyl-1,10-phenanthroline Chemical compound C1=C(CCCC)N=C2C3=NC(CCCC)=CC=C3C=CC2=C1 LSGGPELKXXFMGO-UHFFFAOYSA-N 0.000 description 1
- QAFFBUBNQSNVSZ-UHFFFAOYSA-N 2-bromo-1-iodonaphthalene Chemical compound C1=CC=CC2=C(I)C(Br)=CC=C21 QAFFBUBNQSNVSZ-UHFFFAOYSA-N 0.000 description 1
- VYMNCOOEVDIPTL-UHFFFAOYSA-N 2-bromo-6-iodonaphthalene Chemical compound C1=C(I)C=CC2=CC(Br)=CC=C21 VYMNCOOEVDIPTL-UHFFFAOYSA-N 0.000 description 1
- IADZLCGWHPOQBP-UHFFFAOYSA-N 2-butoxy-6-iodonaphthalene Chemical compound C1=C(I)C=CC2=CC(OCCCC)=CC=C21 IADZLCGWHPOQBP-UHFFFAOYSA-N 0.000 description 1
- AMNAGCDWTIMWRF-UHFFFAOYSA-N 2-chloro-1-iodonaphthalene Chemical compound C1=CC=CC2=C(I)C(Cl)=CC=C21 AMNAGCDWTIMWRF-UHFFFAOYSA-N 0.000 description 1
- LKWKYFPFZOBUIC-UHFFFAOYSA-N 2-chloro-6-iodonaphthalene Chemical compound C1=CC2=C(C=C1I)C=CC(Cl)=C2 LKWKYFPFZOBUIC-UHFFFAOYSA-N 0.000 description 1
- ARHVJMCTZHYRPB-UHFFFAOYSA-N 2-fluoro-1-iodonaphthalene Chemical compound FC1=C(C2=CC=CC=C2C=C1)I ARHVJMCTZHYRPB-UHFFFAOYSA-N 0.000 description 1
- GZJOGXPGLUVDPX-UHFFFAOYSA-N 2-fluoro-6-iodonaphthalene Chemical compound C1=C(I)C=CC2=CC(F)=CC=C21 GZJOGXPGLUVDPX-UHFFFAOYSA-N 0.000 description 1
- RATKEICSZQPVCV-UHFFFAOYSA-N 2-iodo-6-methoxynaphthalene Chemical compound C1=C(I)C=CC2=CC(OC)=CC=C21 RATKEICSZQPVCV-UHFFFAOYSA-N 0.000 description 1
- LCYRLTYZSPYTFC-UHFFFAOYSA-N 2-iodo-6-methylnaphthalene Chemical compound C1=C(I)C=CC2=CC(C)=CC=C21 LCYRLTYZSPYTFC-UHFFFAOYSA-N 0.000 description 1
- DDQWSLFKVLTRDN-UHFFFAOYSA-N 2-iodo-n,n-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1I DDQWSLFKVLTRDN-UHFFFAOYSA-N 0.000 description 1
- LIJKCLMUVWTDKS-UHFFFAOYSA-N 2-iodo-n,n-dimethylbenzamide Chemical compound CN(C)C(=O)C1=CC=CC=C1I LIJKCLMUVWTDKS-UHFFFAOYSA-N 0.000 description 1
- CJNZAXGUTKBIHP-UHFFFAOYSA-N 2-iodobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1I CJNZAXGUTKBIHP-UHFFFAOYSA-N 0.000 description 1
- JDDAFHUEOVUDFJ-UHFFFAOYSA-N 2-iodobenzonitrile Chemical compound IC1=CC=CC=C1C#N JDDAFHUEOVUDFJ-UHFFFAOYSA-N 0.000 description 1
- ICWZZNUEYMBBRB-UHFFFAOYSA-N 2-iodofuran Chemical compound IC1=CC=CO1 ICWZZNUEYMBBRB-UHFFFAOYSA-N 0.000 description 1
- FRNLBIWVMVNNAZ-UHFFFAOYSA-N 2-iodonaphthalene Chemical compound C1=CC=CC2=CC(I)=CC=C21 FRNLBIWVMVNNAZ-UHFFFAOYSA-N 0.000 description 1
- CCZWSTFVHJPCEM-UHFFFAOYSA-N 2-iodopyridine Chemical compound IC1=CC=CC=N1 CCZWSTFVHJPCEM-UHFFFAOYSA-N 0.000 description 1
- ROIMNSWDOJCBFR-UHFFFAOYSA-N 2-iodothiophene Chemical compound IC1=CC=CS1 ROIMNSWDOJCBFR-UHFFFAOYSA-N 0.000 description 1
- OHJPGUSXUGHOGE-UHFFFAOYSA-N 2-methyl-6-(6-methylpyridin-2-yl)pyridine Chemical compound CC1=CC=CC(C=2N=C(C)C=CC=2)=N1 OHJPGUSXUGHOGE-UHFFFAOYSA-N 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
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- LVWARGSJDSRDRQ-UHFFFAOYSA-N 3-bromo-1-iodonaphthalene Chemical compound C1=CC=CC2=CC(Br)=CC(I)=C21 LVWARGSJDSRDRQ-UHFFFAOYSA-N 0.000 description 1
- IOXFJUVIRCUTFK-UHFFFAOYSA-N 3-chloro-1-iodonaphthalene Chemical compound ClC=1C=C(C2=CC=CC=C2C=1)I IOXFJUVIRCUTFK-UHFFFAOYSA-N 0.000 description 1
- DRRPJYFCPWBZDG-UHFFFAOYSA-N 3-fluoro-1-iodonaphthalene Chemical compound Fc1cc(I)c2ccccc2c1 DRRPJYFCPWBZDG-UHFFFAOYSA-N 0.000 description 1
- FQVDXLYJTMHMCG-UHFFFAOYSA-N 3-iodo-1h-indole Chemical compound C1=CC=C2C(I)=CNC2=C1 FQVDXLYJTMHMCG-UHFFFAOYSA-N 0.000 description 1
- TVFNKBQQVHGWAF-UHFFFAOYSA-N 3-iodo-n,n-dimethylaniline Chemical compound CN(C)C1=CC=CC(I)=C1 TVFNKBQQVHGWAF-UHFFFAOYSA-N 0.000 description 1
- KVBWBCRPWVKFQT-UHFFFAOYSA-N 3-iodobenzoic acid Chemical compound OC(=O)C1=CC=CC(I)=C1 KVBWBCRPWVKFQT-UHFFFAOYSA-N 0.000 description 1
- BGARPMGQRREXLN-UHFFFAOYSA-N 3-iodobenzonitrile Chemical compound IC1=CC=CC(C#N)=C1 BGARPMGQRREXLN-UHFFFAOYSA-N 0.000 description 1
- RIXNIROIHWVYKM-UHFFFAOYSA-N 3-iodofuran Chemical compound IC=1C=COC=1 RIXNIROIHWVYKM-UHFFFAOYSA-N 0.000 description 1
- XDELKSRGBLWMBA-UHFFFAOYSA-N 3-iodopyridine Chemical compound IC1=CC=CN=C1 XDELKSRGBLWMBA-UHFFFAOYSA-N 0.000 description 1
- WGKRMQIQXMJVFZ-UHFFFAOYSA-N 3-iodothiophene Chemical compound IC=1C=CSC=1 WGKRMQIQXMJVFZ-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
- 125000005917 3-methylpentyl group Chemical group 0.000 description 1
- DHDHJYNTEFLIHY-UHFFFAOYSA-N 4,7-diphenyl-1,10-phenanthroline Chemical compound C1=CC=CC=C1C1=CC=NC2=C1C=CC1=C(C=3C=CC=CC=3)C=CN=C21 DHDHJYNTEFLIHY-UHFFFAOYSA-N 0.000 description 1
- CSFRCLYFVINMBZ-UHFFFAOYSA-N 4-iodo-1,2-dimethylbenzene Chemical group CC1=CC=C(I)C=C1C CSFRCLYFVINMBZ-UHFFFAOYSA-N 0.000 description 1
- QYOPPZJZMFMBDN-UHFFFAOYSA-N 4-iodo-n,n-dimethylaniline Chemical compound CN(C)C1=CC=C(I)C=C1 QYOPPZJZMFMBDN-UHFFFAOYSA-N 0.000 description 1
- ZPTKPSCMQWCYSN-UHFFFAOYSA-N 4-iodo-n,n-dimethylbenzamide Chemical compound CN(C)C(=O)C1=CC=C(I)C=C1 ZPTKPSCMQWCYSN-UHFFFAOYSA-N 0.000 description 1
- GHICCUXQJBDNRN-UHFFFAOYSA-N 4-iodobenzoic acid Chemical compound OC(=O)C1=CC=C(I)C=C1 GHICCUXQJBDNRN-UHFFFAOYSA-N 0.000 description 1
- XOKDXPVXJWTSRM-UHFFFAOYSA-N 4-iodobenzonitrile Chemical compound IC1=CC=C(C#N)C=C1 XOKDXPVXJWTSRM-UHFFFAOYSA-N 0.000 description 1
- IKUGXOILLMFCRF-UHFFFAOYSA-N 4-iodonaphthalene-1-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=CC=C(I)C2=C1 IKUGXOILLMFCRF-UHFFFAOYSA-N 0.000 description 1
- RTLUPHDWSUGAOS-UHFFFAOYSA-N 4-iodopyridine Chemical compound IC1=CC=NC=C1 RTLUPHDWSUGAOS-UHFFFAOYSA-N 0.000 description 1
- TVQLYTUWUQMGMP-UHFFFAOYSA-N 5-iodo-1h-indole Chemical compound IC1=CC=C2NC=CC2=C1 TVQLYTUWUQMGMP-UHFFFAOYSA-N 0.000 description 1
- WVEYKBNTOLJDMY-UHFFFAOYSA-N 6-iodonaphthalene-2-carboxylic acid Chemical compound C1=C(I)C=CC2=CC(C(=O)O)=CC=C21 WVEYKBNTOLJDMY-UHFFFAOYSA-N 0.000 description 1
- VBKAPLYISDSUCE-UHFFFAOYSA-N 7-iodo-1h-indole Chemical compound IC1=CC=CC2=C1NC=C2 VBKAPLYISDSUCE-UHFFFAOYSA-N 0.000 description 1
- ROFVEXUMMXZLPA-UHFFFAOYSA-N Bipyridyl Chemical compound N1=CC=CC=C1C1=CC=CC=N1 ROFVEXUMMXZLPA-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- SRGCPPWCCVQWCF-UHFFFAOYSA-N C(C1=CC=CC=C1)N(C1=CC(=CC=C1)I)CC1=CC=CC=C1 Chemical compound C(C1=CC=CC=C1)N(C1=CC(=CC=C1)I)CC1=CC=CC=C1 SRGCPPWCCVQWCF-UHFFFAOYSA-N 0.000 description 1
- XOBFYOAQSITNFE-UHFFFAOYSA-N C(CC)[Si](C(F)(F)F)(CCC)CCC Chemical compound C(CC)[Si](C(F)(F)F)(CCC)CCC XOBFYOAQSITNFE-UHFFFAOYSA-N 0.000 description 1
- MZGWXNJLPAOZIK-UHFFFAOYSA-N C1=CC(C(C(=C1)Br)Br)(I)I Chemical compound C1=CC(C(C(=C1)Br)Br)(I)I MZGWXNJLPAOZIK-UHFFFAOYSA-N 0.000 description 1
- DEDLRZHCKAPPJZ-UHFFFAOYSA-N C1=CC=C2C(I)=C(C=C)C=CC2=C1 Chemical compound C1=CC=C2C(I)=C(C=C)C=CC2=C1 DEDLRZHCKAPPJZ-UHFFFAOYSA-N 0.000 description 1
- GSMIQWFQWPCBPO-UHFFFAOYSA-N C=CC1=CC2=C(C=C1)C=C(C=C2)I Chemical compound C=CC1=CC2=C(C=C1)C=C(C=C2)I GSMIQWFQWPCBPO-UHFFFAOYSA-N 0.000 description 1
- IPOBSTCINSZOAY-UHFFFAOYSA-N CCCCOCl(N(C)C)(N(CC)CC)(N(C1=CC=CC=C1)C2=C(C(=C(C=C2)OC)OCC)OCCC)(N(OCC3=CC=CC=C3)OCC4=CC=CC=C4)(OCC5=CC=CC=C5)OC(C)(C)C Chemical compound CCCCOCl(N(C)C)(N(CC)CC)(N(C1=CC=CC=C1)C2=C(C(=C(C=C2)OC)OCC)OCCC)(N(OCC3=CC=CC=C3)OCC4=CC=CC=C4)(OCC5=CC=CC=C5)OC(C)(C)C IPOBSTCINSZOAY-UHFFFAOYSA-N 0.000 description 1
- QPLDLSVMHZLSFG-UHFFFAOYSA-N Copper oxide Chemical compound [Cu]=O QPLDLSVMHZLSFG-UHFFFAOYSA-N 0.000 description 1
- 239000005751 Copper oxide Substances 0.000 description 1
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- FXROQSCGTOUNEH-UHFFFAOYSA-N IC1=CC=CC=C1N(CC=1C=CC=CC=1)CC1=CC=CC=C1 Chemical compound IC1=CC=CC=C1N(CC=1C=CC=CC=1)CC1=CC=CC=C1 FXROQSCGTOUNEH-UHFFFAOYSA-N 0.000 description 1
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-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
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 150000001343 alkyl silanes Chemical class 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 125000005427 anthranyl group Chemical group 0.000 description 1
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 description 1
- YCOXTKKNXUZSKD-UHFFFAOYSA-N as-o-xylenol Natural products CC1=CC=C(O)C=C1C YCOXTKKNXUZSKD-UHFFFAOYSA-N 0.000 description 1
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 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
- XKXXFZLAZILJJE-UHFFFAOYSA-M bromocopper;1,10-phenanthroline;triphenylphosphane Chemical compound Br[Cu].C1=CN=C2C3=NC=CC=C3C=CC2=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 XKXXFZLAZILJJE-UHFFFAOYSA-M 0.000 description 1
- 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
- WUKWITHWXAAZEY-UHFFFAOYSA-L calcium difluoride Chemical compound [F-].[F-].[Ca+2] WUKWITHWXAAZEY-UHFFFAOYSA-L 0.000 description 1
- 229910001634 calcium fluoride Inorganic materials 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- ZPNKUACRPIJETF-UHFFFAOYSA-M chlorocopper;1,10-phenanthroline Chemical compound [Cu]Cl.C1=CN=C2C3=NC=CC=C3C=CC2=C1 ZPNKUACRPIJETF-UHFFFAOYSA-M 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 229910000431 copper oxide Inorganic materials 0.000 description 1
- 229910000365 copper sulfate Inorganic materials 0.000 description 1
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
- XTVVROIMIGLXTD-UHFFFAOYSA-N copper(II) nitrate Chemical compound [Cu+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O XTVVROIMIGLXTD-UHFFFAOYSA-N 0.000 description 1
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 1
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 1
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000004210 ether based solvent Substances 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- SNHMUERNLJLMHN-UHFFFAOYSA-N iodobenzene Chemical compound IC1=CC=CC=C1 SNHMUERNLJLMHN-UHFFFAOYSA-N 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 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
- ORUIBWPALBXDOA-UHFFFAOYSA-L magnesium fluoride Chemical compound [F-].[F-].[Mg+2] ORUIBWPALBXDOA-UHFFFAOYSA-L 0.000 description 1
- 229910001635 magnesium fluoride Inorganic materials 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- SKTCDJAMAYNROS-UHFFFAOYSA-N methoxycyclopentane Chemical compound COC1CCCC1 SKTCDJAMAYNROS-UHFFFAOYSA-N 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- KVKFRMCSXWQSNT-UHFFFAOYSA-N n,n'-dimethylethane-1,2-diamine Chemical compound CNCCNC KVKFRMCSXWQSNT-UHFFFAOYSA-N 0.000 description 1
- NOUUUQMKVOUUNR-UHFFFAOYSA-N n,n'-diphenylethane-1,2-diamine Chemical compound C=1C=CC=CC=1NCCNC1=CC=CC=C1 NOUUUQMKVOUUNR-UHFFFAOYSA-N 0.000 description 1
- MAISKLKPHLZVBC-UHFFFAOYSA-N n,n-dibenzyl-4-iodoaniline Chemical compound C1=CC(I)=CC=C1N(CC=1C=CC=CC=1)CC1=CC=CC=C1 MAISKLKPHLZVBC-UHFFFAOYSA-N 0.000 description 1
- UQUPIHHYKUEXQD-UHFFFAOYSA-N n,n′-dimethyl-1,3-propanediamine Chemical compound CNCCCNC UQUPIHHYKUEXQD-UHFFFAOYSA-N 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 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
- 238000007344 nucleophilic reaction Methods 0.000 description 1
- 125000005575 polycyclic aromatic hydrocarbon group Chemical group 0.000 description 1
- 238000012805 post-processing Methods 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000010992 reflux 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
- 235000013024 sodium fluoride Nutrition 0.000 description 1
- 239000011775 sodium fluoride Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- QHHNHUWOOFETNQ-UHFFFAOYSA-N tert-butyl 4-iodobenzoate Chemical compound CC(C)(C)OC(=O)C1=CC=C(I)C=C1 QHHNHUWOOFETNQ-UHFFFAOYSA-N 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000000101 thioether group Chemical group 0.000 description 1
- 125000004014 thioethyl group Chemical group [H]SC([H])([H])C([H])([H])* 0.000 description 1
- 125000004055 thiomethyl group Chemical group [H]SC([H])([H])* 0.000 description 1
- OFHCMIAMEFGCTH-UHFFFAOYSA-N tributyl(trifluoromethyl)silane Chemical compound CCCC[Si](CCCC)(CCCC)C(F)(F)F OFHCMIAMEFGCTH-UHFFFAOYSA-N 0.000 description 1
- ZHSKFONQCREGOG-UHFFFAOYSA-N triethyl(trifluoromethyl)silane Chemical compound CC[Si](CC)(CC)C(F)(F)F ZHSKFONQCREGOG-UHFFFAOYSA-N 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Description
本発明は、医薬・農薬分野、または液晶等の電子材料分野で有用なトリフルオロメチルアレーン類の製造方法に関するものである。 The present invention relates to a method for producing trifluoromethylarenes useful in the field of medicine / agrochemicals or electronic materials such as liquid crystals.
従来、アレーン類にトリフルオロメチル基（ＣＦ３基）を導入する手法としては、メチル基の変換、即ち、メチル基を一旦、塩素化によりＣＣｌ３基とした後、フッ化水素によりＣＦ３基に誘導する手法が知られている（非特許文献１）。しかしながら、この手法は、２つの工程を経て合成される上、取扱いが難しく、極めて危険な化合物であるフッ化水素を用いるという点において、安全で効率の良い合成法ではない。
また、ハロゲン化アレーンからトリフルオロメチルトリメチルシラン（ルパート試薬）等のＣＦ３化剤により、直接ＣＦ３基を導入する手法が知られている（非特許文献２）。しかしながら、この手法は、当量以上のヨウ化銅を用いることから、後処理の煩雑さ及び多量の金属含有廃棄物を出す問題点を有し、工業的な製造法としては満足できるものではない。
一方、この問題点を解決する手法として、触媒量のヨウ化銅を用い、ハロゲン化アレーンから、ルパート試薬によりＣＦ３基を導入する手法が知られている（非特許文献３）。しかしながら、この文献では、強力な電子吸引性基であるニトロ基を持つヨウ化アレーンを基質として使用している（アレーンは一般にニトロ基等の強力な電子吸引性基が存在すると、上記の様な求核的な反応が起こり易くなる性質を有している）。そのため、同手法をそのまま広範な基質に適用できるものではなく、やはりＣＦ３基の導入手法としては決して満足できるものではない。
Conventionally, as a method for introducing a trifluoromethyl group (CF 3 group) into arenes, conversion of a methyl group, that is, a methyl group is temporarily converted into a CCl 3 group by chlorination, and then a CF 3 group by hydrogen fluoride is used. There is known a technique for guiding to the above (Non-Patent Document 1). However, this method is not a safe and efficient synthesis method in that it is synthesized through two steps and is difficult to handle and uses hydrogen fluoride, which is a very dangerous compound.
Further, a method is known in which a CF 3 group is directly introduced from a halogenated arene by a CF 3 agent such as trifluoromethyltrimethylsilane (Rupert reagent) (Non-patent Document 2). However, since this method uses copper iodide in an equivalent amount or more, it has a problem of post-processing complexity and a large amount of metal-containing waste, which is not satisfactory as an industrial production method.
On the other hand, as a technique for solving this problem, a technique is known in which a catalytic amount of copper iodide is used and a CF 3 group is introduced from a halogenated arene by a Rupert reagent (Non-patent Document 3). However, in this document, an iodinated arene having a nitro group which is a strong electron-withdrawing group is used as a substrate (in general, if a strong electron-withdrawing group such as a nitro group is present, Nucleophilic reaction is likely to occur). Therefore, this method cannot be applied to a wide range of substrates as it is, and it is never satisfactory as a method for introducing a CF 3 group.
本発明は、上記の課題に鑑みてなされたものであり、その目的は、従来の方法では満足できなかったトリフルオロメチルアレーン類の製造方法を提供することにある。すなわち、従来の問題点を解決し、アレーン類に広範な基質に適用可能なＣＦ３基を高収率かつ経済的に導入する方法を提供することにある。 This invention is made | formed in view of said subject, The objective is to provide the manufacturing method of trifluoromethylarene which was not satisfied with the conventional method. That is, an object of the present invention is to solve the conventional problems and to provide a method for introducing CF 3 groups applicable to a wide range of substrates into arenes in a high yield and economically.
本発明者らは、従来の問題点を解決すべく鋭意検討した結果、ヨウ化アレーンと、トリフルオロメチルトリアルキルシランをフッ化金属塩の存在下、銅化合物または、銅化合物及び窒素化合物を触媒として反応を行い、トリフルオロメチルアレーン類を製造する方法において、トリフルオロメチルトリアルキルシランを反応系中へ分割添加、または連続添加することにより、高収率で幅広い置換基を有するトリフルオロメチルアレーン類が得られることを見出し、本発明を完成させるに至った。
即ち、本発明は、一般式（１）
ＡｒＩ （１）
（式中、Ａｒは置換又は無置換のアリール基を表す。）
で表されるヨウ化アレーン（以下「（１）ヨウ化アレーン」ともいう）と、
一般式（２）
ＣＦ３ＳｉＲ３ （２）
（式中、Ｒは炭素数１〜４までの低級アルキル基を表す。）
で表されるトリフルオロメチルトリアルキルシラン（以下「（２）トリフルオロメチルトリアルキルシラン」ともいう）を、フッ化金属塩の存在下、銅化合物または、銅化合物及び窒素化合物を触媒として反応を行い、
一般式（３）
ＡｒＣＦ３ （３）
（式中、Ａｒは一般式（１）に同じである。）
で表されるトリフルオロメチルアレーン類を製造する方法において、一般式（２）で表されるトリフルオロメチルトリアルキルシランを反応系中へ分割添加、または連続添加し反応することを特徴とするトリフルオロメチルアレーン類の製造方法に関する。
As a result of diligent studies to solve the conventional problems, the present inventors have determined that arene iodide and trifluoromethyltrialkylsilane in the presence of a metal fluoride salt, a copper compound or a copper compound and a nitrogen compound as a catalyst. In the method of producing trifluoromethyl arenes by reacting as follows, trifluoromethyl arene having a wide range of substituents in high yield by adding trifluoromethyltrialkylsilane into the reaction system in portions or continuously. The present invention has been completed.
That is, the present invention relates to the general formula (1)
ArI (1)
(In the formula, Ar represents a substituted or unsubstituted aryl group.)
An iodinated arene (hereinafter also referred to as “(1) iodinated arene”),
General formula (2)
CF 3 SiR 3 (2)
(In the formula, R represents a lower alkyl group having 1 to 4 carbon atoms.)
Is reacted with a copper compound, or a copper compound and a nitrogen compound as a catalyst in the presence of a metal fluoride salt, (hereinafter also referred to as “(2) trifluoromethyltrialkylsilane”). Done
General formula (3)
ArCF 3 (3)
(In the formula, Ar is the same as in the general formula (1).)
In which the trifluoromethyltrialkylsilane represented by the general formula (2) is added to the reaction system in a divided or continuous manner and reacted. The present invention relates to a method for producing fluoromethylarenes.
本発明の方法によれば、従来の問題点を解決して、幅広い置換基を有するトリフルオロメチルアレーン類を高収率かつ経済的に得ることが可能となる。 According to the method of the present invention, it is possible to solve conventional problems and obtain trifluoromethylarenes having a wide range of substituents in a high yield and economically.
以下、本発明を詳細に説明する。
本発明の方法において使用されるヨウ化アレーンは、上記一般式（１）で表される化合物である。
ここで、「アレーン」とは、単環式および多環式芳香族炭化水素の総称であり、一価の当該芳香族炭化水素基を「アリール基」と総称する。
上記一般式（１）において、Ａｒは置換または無置換のアリール基を示す。アリール基としては、フェニル、ナフチル、アントラニル、ピリジル、チエニル、インドリル、フラニル等を挙げることができ、また、アリール基の置換基としては、アルキル基、アルコキシ基、Ｎ，Ｎ−ジアルキルアミノ基、Ｎ，Ｎ−ジアリールアミノ基、シアノ基、ハロゲン基、アルケニル基、アルキニル基、アミド基、カルボキシル基、アリール基、チオエーテル基、ニトロ基等が挙げられ、具体的には、メチル、エチル、ｎ−プロピル、イソプロピル、ｎ−ブチル、ｓｅｃ−ブチル、ｔｅｒｔ−ブチル、２−メチルプロピル、ｎ−ペンチル、ｓｅｃ−ペンチル、２−メチルブチル、３−メチルブチル、２，２−ジメチルプロピル、１，１−ジメチルプロピル、１，２−ジメチルプロピル、ｎ−ヘキシル、ｓｅｃ−ヘキシル、２−メチルペンチル、３−メチルペンチル、４−メチルペンチル、１，１−ジメチルブチル、２，２−ジメチルブチル、３，３−ジメチルブチル、１，２−ジメチルブチル、１，３−ジメチルブチル、２，３−ジメチルブチル、１，１，２−トリメチルプロピル、１，２，２−トリメチルプロピル、２−エチルヘキシル、シクロプロピル、シクロブチル、シクロペンチル、シクロヘキシル、ベンジル、メトキシ、エトキシ、プロポキシ、ｎ−ブトキシ、ｔ−ブトキシ、ベンジロキシ、ジメチルアミノ、ジエチルアミノ、ジベンジロキシアミノ、ジフェニルアミノ、塩素、臭素、フッ素、ビニル、アリル、エチニル、プロピニル、ブチニル、アセチル、ベンゾイル、チオメチル、チオエチル、フェニル、ナフチル等が例示される。
Hereinafter, the present invention will be described in detail.
The iodinated arene used in the method of the present invention is a compound represented by the above general formula (1).
Here, “arene” is a generic name for monocyclic and polycyclic aromatic hydrocarbons, and the monovalent aromatic hydrocarbon group is generically called an “aryl group”.
In the general formula (1), Ar represents a substituted or unsubstituted aryl group. Examples of the aryl group include phenyl, naphthyl, anthranyl, pyridyl, thienyl, indolyl, furanyl and the like, and examples of the substituent of the aryl group include an alkyl group, an alkoxy group, an N, N-dialkylamino group, an N , N-diarylamino group, cyano group, halogen group, alkenyl group, alkynyl group, amide group, carboxyl group, aryl group, thioether group, nitro group, etc., specifically, methyl, ethyl, n-propyl , Isopropyl, n-butyl, sec-butyl, tert-butyl, 2-methylpropyl, n-pentyl, sec-pentyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, n-hexyl, sec-hexyl, 2-methyl Pentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,3 -Dimethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 2-ethylhexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, benzyl, methoxy, ethoxy, propoxy, n-butoxy, t-butoxy Benzyloxy, dimethylamino, diethylamino, dibenzyloxyamino, diphenylamino, chlorine, bromine, fluorine, vinyl, allyl, ethynyl, propynyl, butynyl, acetyl, benzoyl, thiomethyl, thioethyl, phenyl, naphthyl and the like.
上記一般式（１）で表されるヨウ化アレーンの具体例としては、ヨードベンゼン、１−ヨードナフタレン、２−ヨードナフタレン、２−ヨードトルエン、３−ヨードトルエン、４−ヨードトルエン、３−ヨード−ｏ−キシレン、４−ヨード−ｏ−キシレン、１−ヨード−２−メトキシベンゼン、１−ヨード−３−メトキシベンゼン、１−ヨード−４−メトキシベンゼン、１−ヨード−２−エトキシベンゼン、１−ヨード−３−エトキシベンゼン、１−ヨード−４−エトキシベンゼン、１−ヨード−２−ブトキシベンゼン、１−ヨード−３−ブトキシベンゼン、１−ヨード−４−ブトキシベンゼン、１−ヨード−２−ベンジロキシベンゼン、１−ヨード−３−ベンジロキシベンゼン、１−ヨード−４−ベンジロキシベンゼン、１−ヨード−２−メチルナフタレン、１−ヨード−４−メチルナフタレン、２−ヨード−６−メチルナフタレン、１−ヨード−２−メトキシナフタレン、１−ヨード−４−メトキシナフタレン、２−ヨード−６−メトキシナフタレン、２−ヨード−６−ブトキシナフタレン、１−ヨード−２−（Ｎ，Ｎ−ジメチルアミノ）ベンゼン、１−ヨード−３−（Ｎ，Ｎ−ジメチルアミノ）ベンゼン、１−ヨード−４−（Ｎ，Ｎ−ジメチルアミノ）ベンゼン、１−ヨード−２−（Ｎ，Ｎ−ジベンジルアミノ）ベンゼン、１−ヨード−３−（Ｎ，Ｎ−ジベンジルアミノ）ベンゼン、１−ヨード−４−（Ｎ，Ｎ−ジベンジルアミノ）ベンゼン、１−ヨード−２−シアノベンゼン、１−ヨード−３−シアノベンゼン、１−ヨード−４−シアノベンゼン、１−ヨード−２−ブロモベンゼン、１−ヨード−３−ブロモベンゼン、１−ヨード−４−ブロモベンゼン、１−ヨード−２−クロロベンゼン、１−ヨード−３−クロロベンゼン、１−ヨード−４−クロロベンゼン、１−ヨード−２−フルオロベンゼン、１−ヨード−３−フルオロベンゼン、１−ヨード−４−フルオロベンゼン、１，２−ジヨードベンゼン、１，３−ジヨードベンゼン、１，４−ジヨードベンゼン、１−ヨード−２−ブロモナフタレン、１−ヨード−３−ブロモナフタレン、１−ヨード−４−ブロモナフタレン、２−ヨード−６−ブロモナフタレン、１−ヨード−２−クロロナフタレン、１−ヨード−３−クロロナフタレン、１−ヨード−４−クロロナフタレン、２−ヨード−６−クロロナフタレン、１−ヨード−２−フルオロナフタレン、１−ヨード−３−フルオロナフタレン、１−ヨード−４−フルオロナフタレン、２−ヨード−６−フルオロナフタレン、２−ヨードスチレン、３−ヨードスチレン、４−ヨードスチレン、１−ヨード−２−アリルベンゼン、１−ヨード−３−アリルベンゼン、１−ヨード−４−アリルベンゼン、１−ヨード−２−ビニルナフタレン、１−ヨード−４−ビニルナフタレン、２−ヨード−６−ビニルナフタレン、１−ヨード−２−エチニルベンゼン、１−ヨード−４−エチニルベンゼン、１−ヨード−２−ジメチルカルバモイルベンゼン、１−ヨード−４−ジメチルカルバモイルベンゼン、２−ヨード安息香酸、３−ヨード安息香酸、４−ヨード安息香酸、１−ヨード−２−ナフトエ酸、１−ヨード−４−ナフトエ酸、２−ヨード−６−ナフトエ酸、１−ヨード−２−ｔ−ブトキシカルボニルベンゼン、１−ヨード−４−ｔ−ブトキシカルボニルベンゼン、１−ヨード−２−フェニルベンゼン、１−ヨード−３−フェニルベンゼン、１−ヨード−４−フェニルベンゼン、２−ヨードピリジン、３−ヨードピリジン、４−ヨードピリジン、３−ヨードインドール、５−ヨードインドール、７−ヨードインドール、２−ヨードチオフェン、３−ヨードチオフェン、２−ヨードフラン、３−ヨードフラン等が例示される。 Specific examples of the iodinated arenes represented by the general formula (1) include iodobenzene, 1-iodonaphthalene, 2-iodonaphthalene, 2-iodotoluene, 3-iodotoluene, 4-iodotoluene, and 3-iodo. -O-xylene, 4-iodo-o-xylene, 1-iodo-2-methoxybenzene, 1-iodo-3-methoxybenzene, 1-iodo-4-methoxybenzene, 1-iodo-2-ethoxybenzene, 1 -Iodo-3-ethoxybenzene, 1-iodo-4-ethoxybenzene, 1-iodo-2-butoxybenzene, 1-iodo-3-butoxybenzene, 1-iodo-4-butoxybenzene, 1-iodo-2- Benzyloxybenzene, 1-iodo-3-benzyloxybenzene, 1-iodo-4-benzyloxybenzene, 1-iodo-2- Tylnaphthalene, 1-iodo-4-methylnaphthalene, 2-iodo-6-methylnaphthalene, 1-iodo-2-methoxynaphthalene, 1-iodo-4-methoxynaphthalene, 2-iodo-6-methoxynaphthalene, 2- Iodo-6-butoxynaphthalene, 1-iodo-2- (N, N-dimethylamino) benzene, 1-iodo-3- (N, N-dimethylamino) benzene, 1-iodo-4- (N, N- Dimethylamino) benzene, 1-iodo-2- (N, N-dibenzylamino) benzene, 1-iodo-3- (N, N-dibenzylamino) benzene, 1-iodo-4- (N, N- Dibenzylamino) benzene, 1-iodo-2-cyanobenzene, 1-iodo-3-cyanobenzene, 1-iodo-4-cyanobenzene, 1-iodo-2-bromo , 1-iodo-3-bromobenzene, 1-iodo-4-bromobenzene, 1-iodo-2-chlorobenzene, 1-iodo-3-chlorobenzene, 1-iodo-4-chlorobenzene, 1-iodo-2- Fluorobenzene, 1-iodo-3-fluorobenzene, 1-iodo-4-fluorobenzene, 1,2-diiodobenzene, 1,3-diiodobenzene, 1,4-diiodobenzene, 1-iodo-2 -Bromonaphthalene, 1-iodo-3-bromonaphthalene, 1-iodo-4-bromonaphthalene, 2-iodo-6-bromonaphthalene, 1-iodo-2-chloronaphthalene, 1-iodo-3-chloronaphthalene, 1 -Iodo-4-chloronaphthalene, 2-iodo-6-chloronaphthalene, 1-iodo-2-fluoronaphthalene, 1-iodo -3-fluoronaphthalene, 1-iodo-4-fluoronaphthalene, 2-iodo-6-fluoronaphthalene, 2-iodostyrene, 3-iodostyrene, 4-iodostyrene, 1-iodo-2-allylbenzene, 1- Iodo-3-allylbenzene, 1-iodo-4-allylbenzene, 1-iodo-2-vinylnaphthalene, 1-iodo-4-vinylnaphthalene, 2-iodo-6-vinylnaphthalene, 1-iodo-2-ethynyl Benzene, 1-iodo-4-ethynylbenzene, 1-iodo-2-dimethylcarbamoylbenzene, 1-iodo-4-dimethylcarbamoylbenzene, 2-iodobenzoic acid, 3-iodobenzoic acid, 4-iodobenzoic acid, 1 -Iodo-2-naphthoic acid, 1-iodo-4-naphthoic acid, 2-iodo-6-naphthoic acid, 1-iodo Do-2-t-butoxycarbonylbenzene, 1-iodo-4-t-butoxycarbonylbenzene, 1-iodo-2-phenylbenzene, 1-iodo-3-phenylbenzene, 1-iodo-4-phenylbenzene, 2 -Iodopyridine, 3-iodopyridine, 4-iodopyridine, 3-iodoindole, 5-iodoindole, 7-iodoindole, 2-iodothiophene, 3-iodothiophene, 2-iodofuran, 3-iodofuran, etc. The
本発明の方法において使用されるトリフルオロメチルトリアルキルシランは、上記一般式（２）で表される化合物である。
上記一般式（２）において、Ｒは炭素数１〜４までの低級アルキル基を表し、具体的には、メチル、エチル、ｎ−プロピル、イソプロピル、ｎ−ブチル、ｓｅｃ−ブチル、ｔｅｒｔ−ブチル等である。
上記一般式（２）で表されるトリフルオロメチルトリアルキルシランの具体例としては、トリフルオロメチルトリメチルシラン、トリフルオロメチルトリエチルシラン、トリフルオロメチルトリプロピルシラン、トリフルオロメチルトリブチルシラン等が例示される。
The trifluoromethyltrialkylsilane used in the method of the present invention is a compound represented by the above general formula (2).
In the general formula (2), R represents a lower alkyl group having 1 to 4 carbon atoms, specifically, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, and the like. It is.
Specific examples of the trifluoromethyltrialkylsilane represented by the general formula (2) include trifluoromethyltrimethylsilane, trifluoromethyltriethylsilane, trifluoromethyltripropylsilane, and trifluoromethyltributylsilane. The
ここで、（１）ヨウ化アレーンと（２）トリフルオロメチルトリアルキルシランとのモル比は、通常、（１）：（２）＝１：１〜１：５、好ましくは１：１〜１：３である。（１）ヨウ化アレーン１モルに対し、（２）トリフルオロメチルトリアルキルシランが１モル未満では、十分な転化率が得られず、一方、５モルを超えると、反応成績の割に効果がなく経済的にも好ましくない。 Here, the molar ratio of (1) arene iodide and (2) trifluoromethyltrialkylsilane is usually (1) :( 2) = 1: 1 to 1: 5, preferably 1: 1 to 1. : 3. (1) When 1 mole of arene arene is less than 1 mole of (2) trifluoromethyltrialkylsilane, a sufficient conversion rate cannot be obtained. It is not economically preferable.
本発明の方法では、添加剤としてフッ化金属塩の存在下で反応が実施される。使用されるフッ化金属塩に特に限定はなく、具体的には、フッ化リチウム、フッ化ナトリウム、フッ化カリウム、フッ化ルビジウム、フッ化セシウム、フッ化マグネシウム、フッ化カルシウム等のアルカリ、またはアルカリ土類金属塩が例示されるが、良好な反応収率が得られることから、フッ化カリウムまたはフッ化セシウムの使用が好ましい。フッ化金属塩の使用量に格別の限定はないが、上記一般式（１）で示されるヨウ化アレーンに対して、１倍モル〜５倍モル、好ましくは１倍モル〜３倍モルが選ばれる。１倍モル未満では、反応収率が低下し、一方、５倍モルを超えると、反応成績の割に効果がなく経済的にも好ましくない。 In the method of the present invention, the reaction is carried out in the presence of a metal fluoride salt as an additive. There is no particular limitation on the metal fluoride salt used, specifically, alkali such as lithium fluoride, sodium fluoride, potassium fluoride, rubidium fluoride, cesium fluoride, magnesium fluoride, calcium fluoride, or Alkaline earth metal salts are exemplified, but use of potassium fluoride or cesium fluoride is preferable because a good reaction yield can be obtained. Although there is no special limitation in the usage-amount of a metal fluoride salt, 1 time mole-5 times mole, Preferably 1 time mole-3 times mole are chosen with respect to the iodination arene shown by the said General formula (1). It is. If the amount is less than 1 mole, the reaction yield decreases. On the other hand, if it exceeds 5 moles, the reaction results are not effective and economically undesirable.
本発明の方法において使用される銅化合物は、特に限定されないが、具体例として、銅粉、ブロモ（１，１０−フェナンスロリン）（トリフェニルホスフィン）銅（Ｉ）、酢酸銅、ヨウ化銅、臭化銅、塩化銅、シアン化銅、酸化銅、硝酸銅、硫酸銅等が挙げられるが、経済性及び入手性を考慮すると、塩化銅、臭化銅、ヨウ化銅の使用が好ましい。また、銅化合物の使用量に格別の限定はないが、上記一般式（１）で示されるヨウ化アレーンに対して、１．０モル％〜２０．０モル％、好ましくは３モル％〜１５モル％の範囲が選ばれる。ここで、１．０モル％未満では、触媒活性が不十分であり、一方、２０．０モル％を超えると、反応成績の割に効果がなく経済的にも好ましくない。 Although the copper compound used in the method of the present invention is not particularly limited, as specific examples, copper powder, bromo (1,10-phenanthroline) (triphenylphosphine) copper (I), copper acetate, copper iodide , Copper bromide, copper chloride, copper cyanide, copper oxide, copper nitrate, copper sulfate and the like, but considering the economical efficiency and availability, the use of copper chloride, copper bromide and copper iodide is preferred. Moreover, although there is no special limitation in the usage-amount of a copper compound, it is 1.0 mol%-20.0 mol% with respect to the iodination arene shown by the said General formula (1), Preferably it is 3 mol%-15 A range of mol% is selected. Here, if it is less than 1.0 mol%, the catalytic activity is insufficient. On the other hand, if it exceeds 20.0 mol%, there is no effect on the reaction results, which is not preferable economically.
また、使用される窒素化合物に格別の限定はなく、銅に配位可能な窒素系の任意の化合物が選ばれる。窒素化合物の具体例として、１，１０−フェナンスロリン、２，２’−ビピリジン、２，９−ジ−ｎ−ブチル−１，１０−フェナンスロリン、６，６’−ジメチル−２，２’−ビピリジン、４，７−ジフェニル−１，１０−フェナンスロリン、Ｎ，Ｎ’−ジメチルエチレンジアミン、Ｎ，Ｎ’−ジメチル−１，２−シクロヘキシルジアミン、Ｎ，Ｎ，Ｎ’，Ｎ’−テトラメチルエチレンジアミン、Ｎ，Ｎ’−ジメチル−１，３−プロパンジアミン、Ｎ，Ｎ’−ジベンジルエチレンジアミン、エチレンジアミン、ピペラジン、Ｎ，Ｎ’−ジフェニルエチレンジアミン等が例示される。窒素化合物の使用量に格別の限定はないが、銅化合物に対して、０．５倍モル〜５倍モル、好ましくは１倍モル〜３倍モルである。ここで、０．５倍モル未満では、触媒活性が不十分であり、一方、５倍モルを超えると、反応成績の割に効果がなく経済的にも好ましくない。 Further, there is no particular limitation on the nitrogen compound used, and any nitrogen-based compound capable of coordinating with copper is selected. Specific examples of nitrogen compounds include 1,10-phenanthroline, 2,2′-bipyridine, 2,9-di-n-butyl-1,10-phenanthroline, 6,6′-dimethyl-2,2 '-Bipyridine, 4,7-diphenyl-1,10-phenanthroline, N, N'-dimethylethylenediamine, N, N'-dimethyl-1,2-cyclohexyldiamine, N, N, N', N'- Examples thereof include tetramethylethylenediamine, N, N′-dimethyl-1,3-propanediamine, N, N′-dibenzylethylenediamine, ethylenediamine, piperazine, N, N′-diphenylethylenediamine and the like. Although there is no special limitation in the usage-amount of a nitrogen compound, it is 0.5 times mole-5 times mole with respect to a copper compound, Preferably it is 1 time mole-3 times mole. Here, when the amount is less than 0.5 times mol, the catalytic activity is insufficient. On the other hand, when the amount exceeds 5 times mol, the reaction results are not effective and economically undesirable.
本発明の反応では、反応試剤の添加方法が重要な要素となる。即ち、予め（１）ヨウ化アレーン、フッ化金属塩、銅化合物、窒素化合物、溶媒を反応器に仕込み、所定の温度まで加熱した後、上記一般式（２）で表されるトリフルオロメチルトリアルキルシランを反応系中へ分割添加、または連続的に添加し、反応させることで、反応収率が顕著に改善される。
ここで、（２）トリフルオロメチルトリアルキルシランを反応系中に分割添加する場合は、添加開始から添加終了までの間に、全添加量を５〜５０回、好ましくは１０〜２０回に分割して添加する。なお、分割添加は、各回の添加量を同量にする必要はなく、適宜、変更することができる。
また、（２）トリフルオロメチルトリアルキルシランを反応系中に連続して添加する場合は、添加開始から添加終了までの間に、全添加量を連続的に添加してゆく。なお、連続添加は、添加中、添加量を均一に維持する必要はなく、添加中の添加量を、適宜、変更することができる。
また、添加開始から添加終了までの時間は、０．５時間〜２４時間、好ましくは１〜６時間である。通常、添加終了と同時に反応は終了しているが、未反応原料が残存している場合でも１〜３時間程度の熟成時間を設定することで反応は終了する。
このように、（２）トリフルオロメチルトリアルキルシランを、反応系に分割して、あるいは、連続して添加することにより、反応収率が顕著に改善される。
なお、予め（１）ヨウ化アレーン、（２）トリフルオロメチルトリアルキルシラン、フッ化金属塩、銅化合物、窒素化合物、溶媒を反応器に一括して仕込んで、反応させると、反応収率が劣り、本発明の効果が得られない。
In the reaction of the present invention, the method of adding a reaction reagent is an important factor. That is, (1) an iodine iodide arene, a metal fluoride salt, a copper compound, a nitrogen compound, and a solvent are charged in a reactor in advance and heated to a predetermined temperature, and then the trifluoromethyl trimethyl represented by the general formula (2) is used. The reaction yield is remarkably improved by adding the alkylsilane in the reaction system in a divided manner or by continuously adding and reacting.
Here, when (2) trifluoromethyltrialkylsilane is added into the reaction system in a divided manner, the total addition amount is divided into 5 to 50 times, preferably 10 to 20 times, from the start of addition to the end of addition. And add. In addition, division addition does not need to make the addition amount of each time the same amount, and can be changed suitably.
When (2) trifluoromethyltrialkylsilane is continuously added to the reaction system, all addition amounts are continuously added from the start of addition to the end of addition. In addition, the continuous addition does not need to keep the addition amount uniform during the addition, and the addition amount during the addition can be appropriately changed.
The time from the start of addition to the end of addition is 0.5 to 24 hours, preferably 1 to 6 hours. Usually, the reaction is completed at the same time as the addition is completed, but even when unreacted raw materials remain, the reaction is completed by setting an aging time of about 1 to 3 hours.
Thus, the reaction yield is remarkably improved by adding (2) trifluoromethyltrialkylsilane to the reaction system in a divided manner or continuously.
If (1) arene iodide, (2) trifluoromethyltrialkylsilane, metal fluoride, copper compound, nitrogen compound, and solvent are charged in a reactor and reacted in advance, the reaction yield is increased. The effect of the present invention cannot be obtained.
また、本発明の方法においては、通常、反応溶媒が用いられる。使用される反応溶媒に格別の限定はないが、エーテル系溶媒、芳香族炭化水素系溶媒、アミド系溶媒等が用いられ、具体的には、テトラヒドロフラン（ＴＨＦ）、シクロペンチルメチルエーテル、ジオキサン、トルエン、キシレン、ジメチルホルムアミド、ジメチルアセトアミド、ジメチルスルホキシド等が例示される。ここで、溶媒は、単一で用いても混合溶媒で用いてもどちらでも良い。
反応溶媒の使用量は、一般式（１）で表されるヨウ化アレーンに対し、２．０重量比〜２０重量比、好ましくは５重量比〜１０重量比である。
In the method of the present invention, a reaction solvent is usually used. The reaction solvent used is not particularly limited, but ether solvents, aromatic hydrocarbon solvents, amide solvents, etc. are used. Specifically, tetrahydrofuran (THF), cyclopentyl methyl ether, dioxane, toluene, Examples include xylene, dimethylformamide, dimethylacetamide, dimethyl sulfoxide and the like. Here, the solvent may be used alone or as a mixed solvent.
The amount of the reaction solvent used is 2.0 to 20 weight ratio, preferably 5 to 10 weight ratio with respect to the iodinated arene represented by the general formula (1).
さらに、本発明の方法における反応温度は、室温から溶媒の還流温度の範囲であり、具体的には、２０〜１５０℃、好ましくは５０〜１４０℃の範囲である。
反応終了後は、常法に従い反応液に水を加えて塩類を溶解処理した後、抽出溶媒を添加し、有機層を分離する。続いて、晶析または蒸留等により、目的とするトリフルオロメチルアレーン類を得る。
このようにして得られる本発明のトリフルオロメチルアレーン類は、上記一般式（３）で表され、１Ｈ ＮＭＲ、１３Ｃ ＮＭＲ、質量分析、ガスクロマトグラフィー等によって、その構造を特定することができる。
Furthermore, the reaction temperature in the method of the present invention is in the range of room temperature to the reflux temperature of the solvent, specifically 20 to 150 ° C, preferably 50 to 140 ° C.
After completion of the reaction, water is added to the reaction solution according to a conventional method to dissolve salts, and then an extraction solvent is added to separate the organic layer. Subsequently, the target trifluoromethyl arenes are obtained by crystallization or distillation.
The trifluoromethylarenes of the present invention thus obtained are represented by the above general formula (3), and the structure thereof can be specified by 1 H NMR, 13 C NMR, mass spectrometry, gas chromatography or the like. it can.
以下に、本発明の方法を実施例により具体的に説明するが、本発明はこれら実施例のみに限定されるものではない。
なお、分析用のガスクロマトグラフィーとしては、島津製ＧＣ−１７Ａ（分析カラム：ＮＢ−５）を用いた。
EXAMPLES The method of the present invention will be specifically described below with reference to examples, but the present invention is not limited to these examples.
In addition, as a gas chromatography for analysis, Shimadzu GC-17A (analysis column: NB-5) was used.
実施例１
窒素雰囲気で置換した１００ｍｌフラスコに、ジメチルホルムアミド（ＤＭＦ）２０ｇ、１−ヨードナフタレン２．５４ｇ（１０ｍｍｏｌ）、フッ化カリウム１．１６ｇ（２０ｍｍｏｌ）、塩化銅（Ｉ）０．０４９５ｇ（０．５ｍｍｏｌ）、ピペラジン０．１７ｇ（２ｍｍｏｌ）を仕込み、攪拌しながら反応液を１００℃まで昇温した。昇温後、トリフルオロメチルトリメチルシラン２．１３ｇ（１５ｍｍｏｌ）を１０回に分割し、２時間かけて添加し、同温度にて３時間熟成した。反応終了後冷却、水及び塩化メチレンを添加し生成した塩を溶解し分液した。有機層を分取した後、これをガスクロマトグラフィー（ＧＣ）で内部標準法により分析した結果、目的物である１−トリフルオロメチルナフタレンが４９．８％の収率で生成していた。
Example 1
In a 100 ml flask substituted with a nitrogen atmosphere, 20 g of dimethylformamide (DMF), 2.54 g (10 mmol) of 1-iodonaphthalene, 1.16 g (20 mmol) of potassium fluoride, 0.0495 g (0.5 mmol) of copper (I) chloride Piperazine (0.17 g, 2 mmol) was charged, and the reaction solution was heated to 100 ° C. while stirring. After the temperature increase, 2.13 g (15 mmol) of trifluoromethyltrimethylsilane was divided into 10 portions, added over 2 hours, and aged at the same temperature for 3 hours. After completion of the reaction, the reaction mixture was cooled, water and methylene chloride were added to dissolve the formed salt, and the solution was separated. After the organic layer was separated, it was analyzed by gas chromatography (GC) by an internal standard method. As a result, 1-trifluoromethylnaphthalene, which was the target product, was produced in a yield of 49.8%.
実施例２
窒素雰囲気で置換した１００ｍｌフラスコに、ジメチルホルムアミド（ＤＭＦ）２０ｇ、１−ヨードナフタレン２．５４ｇ（１０ｍｍｏｌ）、フッ化カリウム１．１６ｇ（２０ｍｍｏｌ）、塩化銅（Ｉ）０．０４９５ｇ（０．５ｍｍｏｌ）、１，１０−フェナンスロリン０．３６ｇ（２ｍｍｏｌ）を仕込み、攪拌しながら反応液を１００℃まで昇温した。昇温後、トリフルオロメチルトリメチルシラン２．１３ｇ（１５ｍｍｏｌ）を連続的に、２時間かけて滴下し、同温度にて３時間熟成した。反応終了後冷却、水及び塩化メチレンを添加し生成した塩を溶解し分液した。有機層を分取した後、これをガスクロマトグラフィー（ＧＣ）で内部標準法により分析した結果、目的物である１−トリフルオロメチルナフタレンが６７．８％の収率で生成していた。
Example 2
In a 100 ml flask substituted with a nitrogen atmosphere, 20 g of dimethylformamide (DMF), 2.54 g (10 mmol) of 1-iodonaphthalene, 1.16 g (20 mmol) of potassium fluoride, 0.0495 g (0.5 mmol) of copper (I) chloride 1,10-phenanthroline (0.36 g, 2 mmol) was charged, and the reaction solution was heated to 100 ° C. while stirring. After the temperature elevation, 2.13 g (15 mmol) of trifluoromethyltrimethylsilane was continuously added dropwise over 2 hours, followed by aging at the same temperature for 3 hours. After completion of the reaction, the reaction mixture was cooled, water and methylene chloride were added to dissolve the formed salt, and the solution was separated. After separating the organic layer, it was analyzed by gas chromatography (GC) by an internal standard method. As a result, 1-trifluoromethylnaphthalene, which was the target product, was produced in a yield of 67.8%.
実施例３〜１０および比較例１
実施例２の１−ヨードナフタレン、フッ化カリウム、塩化銅および１，１０−フェナントロリンを別表１に記載の条件に変えた他は、実施例２に記載の方法に準じて反応を行った。結果を表１に記す。
Examples 3 to 10 and Comparative Example 1
The reaction was performed according to the method described in Example 2 except that 1-iodonaphthalene, potassium fluoride, copper chloride and 1,10-phenanthroline in Example 2 were changed to the conditions described in Attached Table 1. The results are shown in Table 1.
比較例２
窒素雰囲気で置換した１００ｍｌフラスコに、ＤＭＦ２０ｇ、１−ヨードナフタレン２．５４ｇ（１０ｍｍｏｌ）、トリフルオロメチルトリメチルシラン（ＴＭＳ−ＣＦ３）２．１３ｇ（１５ｍｍｏｌ）、フッ化カリウム１．１６ｇ（２０ｍｍｏｌ）、塩化銅（Ｉ）０．０９９ｇ（１ｍｍｏｌ）、ピペラジン０．１７ｇ（２ｍｍｏｌ）を一括で仕込み、攪拌しながら反応液を１００℃まで昇温した。昇温後、同温度にて３時間熟成した。反応終了後冷却、水及び塩化メチレンを添加し生成した塩を溶解し分液した。有機層を分取した後、これをガスクロマトグラフィー（ＧＣ）で内部標準法により分析した結果、目的物である１−トリフルオロメチルナフタレンが３０．１％の収率で生成していた。
Comparative Example 2
In a 100 ml flask substituted with a nitrogen atmosphere, 20 g of DMF, 2.54 g (10 mmol) of 1-iodonaphthalene, 2.13 g (15 mmol) of trifluoromethyltrimethylsilane (TMS-CF 3 ), 1.16 g (20 mmol) of potassium fluoride, Copper (I) chloride 0.099 g (1 mmol) and piperazine 0.17 g (2 mmol) were charged all at once, and the reaction solution was heated to 100 ° C. while stirring. After the temperature increase, the mixture was aged at the same temperature for 3 hours. After completion of the reaction, the reaction mixture was cooled, water and methylene chloride were added to dissolve the formed salt, and the solution was separated. After the organic layer was collected, it was analyzed by gas chromatography (GC) by an internal standard method. As a result, 1-trifluoromethylnaphthalene which was the target product was produced in a yield of 30.1%.
本発明により得られるトリフルオロメチルアレーン類は、医薬・農薬等の生理活性物質、または液晶等の電子材料として有用である。 The trifluoromethyl arenes obtained by the present invention are useful as physiologically active substances such as pharmaceuticals and agricultural chemicals, or electronic materials such as liquid crystals.
Claims (3)
ＡｒＩ （１）
（式中、Ａｒは置換又は無置換のアリール基を表す。）
で表されるヨウ化アレーンと、
一般式（２）
ＣＦ３ＳｉＲ３ （２）
（式中、Ｒは炭素数１〜４までの低級アルキル基を表す。）
で表されるトリフルオロメチルトリアルキルシランを、フッ化金属塩の存在下、銅化合物または、銅化合物及び窒素化合物を触媒として反応を行い、
一般式（３）
ＡｒＣＦ３ （３）
（式中、Ａｒは一般式（１）に同じである。）
で表されるトリフルオロメチルアレーン類を製造する方法において、一般式（２）で表されるトリフルオロメチルトリアルキルシランを分割添加、または連続添加し反応させることを特徴とするトリフルオロメチルアレーン類の製造方法。 General formula (1)
ArI (1)
(In the formula, Ar represents a substituted or unsubstituted aryl group.)
An arene iodide represented by
General formula (2)
CF 3 SiR 3 (2)
(In the formula, R represents a lower alkyl group having 1 to 4 carbon atoms.)
In the presence of a metal fluoride salt, a copper compound or a copper compound and a nitrogen compound are reacted as a catalyst in the presence of a metal fluoride salt,
General formula (3)
ArCF 3 (3)
(In the formula, Ar is the same as in the general formula (1).)
In which the trifluoromethyltrialkylsilane represented by the general formula (2) is added in portions or continuously and reacted. Manufacturing method.
The method for producing a trifluoromethylarene according to claim 1 or 2, wherein the copper compound is at least one selected from copper chloride, copper bromide, and copper iodide.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2009072188A JP5219086B2 (en) | 2009-03-24 | 2009-03-24 | Process for producing trifluoromethylarenes |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2009072188A JP5219086B2 (en) | 2009-03-24 | 2009-03-24 | Process for producing trifluoromethylarenes |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2010222304A JP2010222304A (en) | 2010-10-07 |
| JP5219086B2 true JP5219086B2 (en) | 2013-06-26 |
Family
ID=43039888
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2009072188A Active JP5219086B2 (en) | 2009-03-24 | 2009-03-24 | Process for producing trifluoromethylarenes |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP5219086B2 (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP5924984B2 (en) * | 2012-03-06 | 2016-05-25 | 国立大学法人東京農工大学 | Trifluoromethylpyridinone compound and method for producing the same |
| CN109776401A (en) * | 2017-11-14 | 2019-05-21 | 成都博腾药业有限公司 | A method of preparing the chloro- 5- trifluoromethyl -2-aminopyridine of 6- |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH03218325A (en) * | 1989-11-02 | 1991-09-25 | Sagami Chem Res Center | Production of perfluoroalkyl group-containing compound |
| JP4334884B2 (en) * | 2003-02-24 | 2009-09-30 | 株式会社日本触媒 | Fluorine-containing aromatic compound and method for producing the same |
| MXPA06002672A (en) * | 2003-09-09 | 2006-06-06 | Hoffmann La Roche | 1-benzoyl-piperazine derivatives as glycine uptake inhibitors for the treatment of psychoses. |
-
2009
- 2009-03-24 JP JP2009072188A patent/JP5219086B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| JP2010222304A (en) | 2010-10-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5219086B2 (en) | Process for producing trifluoromethylarenes | |
| JP2007230999A (en) | Substituted aromatic nitrile compound and method for producing the same | |
| JP4876913B2 (en) | Method for producing fluorine-containing halide | |
| JP2011037803A (en) | Process for production of formyl-substituted aromatic compounds | |
| JP5915607B2 (en) | Method for producing thionocarboxylic acid aryl ester | |
| JP5853771B2 (en) | Method for producing α, α-difluoroaromatic compound | |
| JP6498048B2 (en) | Fluorine-containing organic compound and method for producing biaryl compound using this and Grignard reagent | |
| JP2022116175A (en) | Fluorine-containing silane compound | |
| JP2001354597A (en) | Method of producing cyclopropenes | |
| JP5900182B2 (en) | Method for producing α, α-difluoroaromatic compound | |
| JPH0563456B2 (en) | ||
| JP4649733B2 (en) | Method for producing acetophenone compound containing trifluoromethyl group | |
| TWI719457B (en) | Method for producing trifluoromethylthiohaloalkane compound and composition of trifluoromethylthiohaloalkane compound | |
| JP6399814B2 (en) | Method for producing dichloromethyl alkyl ether compound | |
| JP4709490B2 (en) | Method for producing pyrazolyl alkyne and intermediate in the process | |
| JP2013001653A (en) | Method for producing fluorosulfuric acid enol ester | |
| JP2011256158A (en) | Biaryl compound and method for producing the same, and method for producing carbazole derivative using the biaryl compound | |
| JP4839678B2 (en) | Method for producing dihalogenated biaryl derivative | |
| JP2010064985A (en) | New method for producing nitrile compound | |
| JP4393839B2 (en) | Preparation of 1,3-di-halo substituted benzene derivatives | |
| JP2009234921A (en) | Method for producing benzotrifluoride | |
| JP2020193181A (en) | Method for producing aromatic nitrile compound | |
| JP2021178811A (en) | Production method of aromatic ether compound or aromatic sulfhydryl compound | |
| JP4243683B2 (en) | Method for producing 1-tetralone | |
| Dubost et al. | Cross-Coupling of [2-Aryl-1, 1, 2, 2-tetrafluoroethyl](trimethyl) silanes with Aryl Halides |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20120302 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20120920 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20120926 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20130227 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20130227 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20160315 Year of fee payment: 3 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 5219086 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313115 |
|
| R370 | Written measure of declining of transfer procedure |
Free format text: JAPANESE INTERMEDIATE CODE: R370 |
|
| S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313115 |
|
| R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
| S531 | Written request for registration of change of domicile |
Free format text: JAPANESE INTERMEDIATE CODE: R313531 |
|
| R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
| S531 | Written request for registration of change of domicile |
Free format text: JAPANESE INTERMEDIATE CODE: R313531 |
|
| R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |