JP3560905B2 - Method for producing 2-trialkylsilyl 2,2-difluoroacetic acid ester - Google Patents
Method for producing 2-trialkylsilyl 2,2-difluoroacetic acid ester Download PDFInfo
- Publication number
- JP3560905B2 JP3560905B2 JP2000232572A JP2000232572A JP3560905B2 JP 3560905 B2 JP3560905 B2 JP 3560905B2 JP 2000232572 A JP2000232572 A JP 2000232572A JP 2000232572 A JP2000232572 A JP 2000232572A JP 3560905 B2 JP3560905 B2 JP 3560905B2
- Authority
- JP
- Japan
- Prior art keywords
- group
- general formula
- trialkylsilyl
- reaction
- acid ester
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 238000004519 manufacturing process Methods 0.000 title claims description 9
- 238000006243 chemical reaction Methods 0.000 claims description 18
- 229910052751 metal Inorganic materials 0.000 claims description 17
- 239000002184 metal Substances 0.000 claims description 16
- 239000002904 solvent Substances 0.000 claims description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
- 229910052794 bromium Inorganic materials 0.000 claims description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 125000000962 organic group Chemical group 0.000 claims description 5
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 239000000460 chlorine Substances 0.000 claims description 4
- 229910052740 iodine Chemical group 0.000 claims description 4
- 239000011630 iodine Chemical group 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- 238000000034 method Methods 0.000 description 11
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 9
- 229910052749 magnesium Inorganic materials 0.000 description 9
- 239000011777 magnesium Substances 0.000 description 9
- -1 difluoromethylene group Chemical group 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 5
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 5
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 5
- 229910052772 Samarium Inorganic materials 0.000 description 4
- 125000000217 alkyl group Chemical group 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 230000035484 reaction time Effects 0.000 description 4
- 238000006722 reduction reaction Methods 0.000 description 4
- KZUNJOHGWZRPMI-UHFFFAOYSA-N samarium atom Chemical compound [Sm] KZUNJOHGWZRPMI-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
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 3
- 125000003545 alkoxy group Chemical group 0.000 description 3
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 229910052725 zinc Inorganic materials 0.000 description 3
- 239000011701 zinc Substances 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- 238000003747 Grignard reaction Methods 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- ATHHXGZTWNVVOU-UHFFFAOYSA-N N-methylformamide Chemical compound CNC=O ATHHXGZTWNVVOU-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 2
- 229910045601 alloy Inorganic materials 0.000 description 2
- 239000000956 alloy Substances 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- 125000000753 cycloalkyl group Chemical group 0.000 description 2
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 150000002894 organic compounds Chemical class 0.000 description 2
- DVCMYAIUSOSIQP-UHFFFAOYSA-N phenyl 2,2,2-trifluoroacetate Chemical compound FC(F)(F)C(=O)OC1=CC=CC=C1 DVCMYAIUSOSIQP-UHFFFAOYSA-N 0.000 description 2
- SUSQOBVLVYHIEX-UHFFFAOYSA-N phenylacetonitrile Chemical compound N#CCC1=CC=CC=C1 SUSQOBVLVYHIEX-UHFFFAOYSA-N 0.000 description 2
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 239000010936 titanium Substances 0.000 description 2
- 229910052719 titanium Inorganic materials 0.000 description 2
- WKEZNQRZCGFQIE-UHFFFAOYSA-N (4-chlorophenyl) 2,2,2-trifluoroacetate Chemical compound FC(F)(F)C(=O)OC1=CC=C(Cl)C=C1 WKEZNQRZCGFQIE-UHFFFAOYSA-N 0.000 description 1
- USKCDUZMASNBCQ-UHFFFAOYSA-N (4-methoxyphenyl) 2,2,2-trifluoroacetate Chemical compound COC1=CC=C(OC(=O)C(F)(F)F)C=C1 USKCDUZMASNBCQ-UHFFFAOYSA-N 0.000 description 1
- HGHGGPKMLBWNBI-UHFFFAOYSA-N (4-methylphenyl) 2,2,2-trifluoroacetate Chemical compound CC1=CC=C(OC(=O)C(F)(F)F)C=C1 HGHGGPKMLBWNBI-UHFFFAOYSA-N 0.000 description 1
- FOZVXADQAHVUSV-UHFFFAOYSA-N 1-bromo-2-(2-bromoethoxy)ethane Chemical compound BrCCOCCBr FOZVXADQAHVUSV-UHFFFAOYSA-N 0.000 description 1
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- JARXNQUBGBXALE-UHFFFAOYSA-N C(C)[SiH](CC)CC.Cl Chemical compound C(C)[SiH](CC)CC.Cl JARXNQUBGBXALE-UHFFFAOYSA-N 0.000 description 1
- BNSJULSSXRHPGB-UHFFFAOYSA-N CC[SiH](CC)CC.Br Chemical compound CC[SiH](CC)CC.Br BNSJULSSXRHPGB-UHFFFAOYSA-N 0.000 description 1
- NTIUZMQTVYPKIB-UHFFFAOYSA-N C[SiH](C)C1=CC=CC=C1.Cl Chemical compound C[SiH](C)C1=CC=CC=C1.Cl NTIUZMQTVYPKIB-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 229910000881 Cu alloy Inorganic materials 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- TUZHYMRMIXIBNI-UHFFFAOYSA-N FC(C(=O)O[SiH3])F Chemical compound FC(C(=O)O[SiH3])F TUZHYMRMIXIBNI-UHFFFAOYSA-N 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 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
- 229910000861 Mg alloy Inorganic materials 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- STSCVKRWJPWALQ-UHFFFAOYSA-N TRIFLUOROACETIC ACID ETHYL ESTER Chemical compound CCOC(=O)C(F)(F)F STSCVKRWJPWALQ-UHFFFAOYSA-N 0.000 description 1
- BOTDANWDWHJENH-UHFFFAOYSA-N Tetraethyl orthosilicate Chemical compound CCO[Si](OCC)(OCC)OCC BOTDANWDWHJENH-UHFFFAOYSA-N 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 229910001297 Zn alloy Inorganic materials 0.000 description 1
- OWXLRKWPEIAGAT-UHFFFAOYSA-N [Mg].[Cu] Chemical compound [Mg].[Cu] OWXLRKWPEIAGAT-UHFFFAOYSA-N 0.000 description 1
- UUDSRSBRGWIGSG-UHFFFAOYSA-N [SiH3]C(C1=CC=CC=C1)C1=CC=CC=C1.Cl Chemical compound [SiH3]C(C1=CC=CC=C1)C1=CC=CC=C1.Cl UUDSRSBRGWIGSG-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 229910001515 alkali metal fluoride Inorganic materials 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 1
- 229940073608 benzyl chloride Drugs 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
- CQESPDFZIFJLII-UHFFFAOYSA-N butan-2-yl 2,2,2-trifluoroacetate Chemical compound CCC(C)OC(=O)C(F)(F)F CQESPDFZIFJLII-UHFFFAOYSA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229910052793 cadmium Inorganic materials 0.000 description 1
- BDOSMKKIYDKNTQ-UHFFFAOYSA-N cadmium atom Chemical compound [Cd] BDOSMKKIYDKNTQ-UHFFFAOYSA-N 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- XBWRJSSJWDOUSJ-UHFFFAOYSA-L chromium(ii) chloride Chemical class Cl[Cr]Cl XBWRJSSJWDOUSJ-UHFFFAOYSA-L 0.000 description 1
- 239000003426 co-catalyst Substances 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- TVZPLCNGKSPOJA-UHFFFAOYSA-N copper zinc Chemical compound [Cu].[Zn] TVZPLCNGKSPOJA-UHFFFAOYSA-N 0.000 description 1
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 1
- MJNDVDVTLSBDLB-UHFFFAOYSA-N cyclohexyl 2,2,2-trifluoroacetate Chemical compound FC(F)(F)C(=O)OC1CCCCC1 MJNDVDVTLSBDLB-UHFFFAOYSA-N 0.000 description 1
- KOMDZQSPRDYARS-UHFFFAOYSA-N cyclopenta-1,3-diene titanium Chemical compound [Ti].C1C=CC=C1.C1C=CC=C1 KOMDZQSPRDYARS-UHFFFAOYSA-N 0.000 description 1
- 238000010908 decantation Methods 0.000 description 1
- NZZFYRREKKOMAT-UHFFFAOYSA-N diiodomethane Chemical compound ICI NZZFYRREKKOMAT-UHFFFAOYSA-N 0.000 description 1
- AASUFOVSZUIILF-UHFFFAOYSA-N diphenylmethanone;sodium Chemical compound [Na].C=1C=CC=CC=1C(=O)C1=CC=CC=C1 AASUFOVSZUIILF-UHFFFAOYSA-N 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 235000019439 ethyl acetate Nutrition 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000012025 fluorinating agent Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
- DTTIQEHOYLOWDU-UHFFFAOYSA-N hexyl 2,2,2-trifluoroacetate Chemical compound CCCCCCOC(=O)C(F)(F)F DTTIQEHOYLOWDU-UHFFFAOYSA-N 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 230000001678 irradiating effect Effects 0.000 description 1
- LRDFRRGEGBBSRN-UHFFFAOYSA-N isobutyronitrile Chemical compound CC(C)C#N LRDFRRGEGBBSRN-UHFFFAOYSA-N 0.000 description 1
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- VMVNZNXAVJHNDJ-UHFFFAOYSA-N methyl 2,2,2-trifluoroacetate Chemical compound COC(=O)C(F)(F)F VMVNZNXAVJHNDJ-UHFFFAOYSA-N 0.000 description 1
- 125000006606 n-butoxy group Chemical group 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- SAVQQRYWWAGSQW-UHFFFAOYSA-N n-methyl-n-(trifluoro-$l^{4}-sulfanyl)methanamine Chemical compound CN(C)S(F)(F)F SAVQQRYWWAGSQW-UHFFFAOYSA-N 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 150000002901 organomagnesium compounds Chemical class 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 235000003270 potassium fluoride Nutrition 0.000 description 1
- 239000011698 potassium fluoride Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- CDXJNCAVPFGVNL-UHFFFAOYSA-N propyl 2,2,2-trifluoroacetate Chemical compound CCCOC(=O)C(F)(F)F CDXJNCAVPFGVNL-UHFFFAOYSA-N 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- VAPOOUIHAISUEO-UHFFFAOYSA-N s-phenyl 2,2,2-trifluoroethanethioate Chemical compound FC(F)(F)C(=O)SC1=CC=CC=C1 VAPOOUIHAISUEO-UHFFFAOYSA-N 0.000 description 1
- UAWABSHMGXMCRK-UHFFFAOYSA-L samarium(ii) iodide Chemical class I[Sm]I UAWABSHMGXMCRK-UHFFFAOYSA-L 0.000 description 1
- 125000005920 sec-butoxy group Chemical group 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- BSWGGJHLVUUXTL-UHFFFAOYSA-N silver zinc Chemical compound [Zn].[Ag] BSWGGJHLVUUXTL-UHFFFAOYSA-N 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- QLUMLEDLZDMGDW-UHFFFAOYSA-N sodium;1h-naphthalen-1-ide Chemical compound [Na+].[C-]1=CC=CC2=CC=CC=C21 QLUMLEDLZDMGDW-UHFFFAOYSA-N 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- UQJLSMYQBOJUGG-UHFFFAOYSA-N tert-butyl 2,2,2-trifluoroacetate Chemical compound CC(C)(C)OC(=O)C(F)(F)F UQJLSMYQBOJUGG-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001302 tertiary amino group Chemical group 0.000 description 1
- 125000005309 thioalkoxy group Chemical group 0.000 description 1
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 1
- 229910052718 tin Inorganic materials 0.000 description 1
- 239000011135 tin Substances 0.000 description 1
- YONPGGFAJWQGJC-UHFFFAOYSA-K titanium(iii) chloride Chemical class Cl[Ti](Cl)Cl YONPGGFAJWQGJC-UHFFFAOYSA-K 0.000 description 1
- 125000004665 trialkylsilyl group Chemical group 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 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 1
- 239000008096 xylene Substances 0.000 description 1
Landscapes
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Description
【０００１】
【発明の属する技術分野】
本発明は、２−トリアルキルシリル２，２−ジフルオロ酢酸エステル類の製造方法に関する。２−トリアルキルシリル２，２−ジフルオロ酢酸エステルは有機化合物中にジフルオロメチレン基を導入する反応試剤または有機化合物の製造中間体として有用である。
【０００２】
【従来の技術】
近年、ジフルオロメチレン基を有する化合物は特有の生物学的活性を持つことからその合成法が注目されている。これまで、カルボニル基、チオカルボニル基またはチオセタール基にＤＡＳＴ（ジメチルアミノサルファトリフルオライド）や同様の作用をする酸化的フッ素化剤を反応させてジフルオロメチレン基に変換することがしばしば行われている。また、ハロジフルオロメチル基を脱ハロゲンしてジフルオロメチレン基とする方法もよく知られている。しかしながら、トリフルオロメチル基からの選択的脱モノフルオリネーションは殆ど知られていない。
【０００３】
本出願人は、特願平１１−３０８４３号において、トリフルオロ酢酸エステル類を塩化トリメチルシランの存在下で電解還元すると２−トリアルキルシリル２，２−ジフルオロ酢酸エステル類が得られることを開示した。
【０００４】
【発明が解決しようとする課題】
上記の電解還元による方法は収率のよい優れた方法であるが、電解還元法は工業的には一般的とは言い難い方法であるので、それに代わる合成方法の出現は望ましい。
【０００５】
したがって、本発明では、従来多くの反応で行われている操作を適用することで工業的プロセスを構成できる、収率のよい２−トリアルキルシリル２，２−ジフルオロ酢酸エステル類の製造方法を提供する。
【０００６】
【課題を解決するための手段】
本発明者らは、トリフルオロ酢酸エステル類とハロゲン化トリアルキルシランを低原子価金属と溶媒の存在下で反応させると２−トリアルキルシリル２，２−ジフルオロ酢酸エステルの生成することを見いだし本発明に至った。
【０００７】
すなわち、本発明は一般式（１）
【０００８】
【化４】
（式中、Ｒ１は一価の有機基を表す。）
で表されるトリフルオロ酢酸エステルを一般式（２）
（Ｒ２）３ＳｉＸ （２）
（式中、Ｒ２はそれぞれ独立にメチル基、エチル基、プロピル基、イソプロピル基またはフェニル基を表し、Ｘは塩素、臭素またはヨウ素を表す。）で表されるハロゲン化トリアルキルシランと低原子価金属と溶媒の存在下で反応させることからなる一般式（３）
【００１０】
【化５】
（式中、ＴＡＳは（Ｒ２）３Ｓｉ−を表し、Ｒ１、Ｒ２はそれぞれ式（１）、式（２）と同じ、）で表される２−トリアルキルシリル２，２−ジフルオロ酢酸エステルの製造方法である。
【００１２】
本発明にかかる一般式（１）で表されるトリフルオロ酢酸エステル類は、特に限定されず、Ｒ１で表される一価の有機基が還元反応の条件下で不活性であればよい。その様な有機基としては、炭素数１〜２０の分岐を有することもあるアルキル基、アルケニル基またはアルキニル基、炭素数１〜２０の置換基を有することもあるシクロアルキル基、炭素数１〜２０の置換基を有することもあるアリール基、一般式（４）
−（ＣＨ２）ｎ−Ｒ３ （４）
（式中、Ｒ３は炭素数１〜１０のシクロアルキル基、アリール基、アルコキシル基、チオアルコキシル基、３級アミノ基、アシル基、アルコキシカルボニル基、複素芳香族基を表し、ｎは１以上の整数を表す。）で表される有機基などを挙げることができる。
【００１３】
一般式（１）で表されるトリフルオロ酢酸エステル類を具体的に例示すると、トリフルオロ酢酸メチル、トリフルオロ酢酸エチル、トリフルオロ酢酸ｎ−プロピル、トリフルオロ酢酸ｉ−プロピル、トリフルオロ酢酸ｎ−ブチル、トリフルオロ酢酸ｓ−ブチル、トリフルオロ酢酸ｔ−ブチル、トリフルオロ酢酸ｎ−ヘキシル、トリフルオロ酢酸シクロヘキシル、トリフルオロ酢酸フェニル、トリフルオロチオ酢酸Ｓ−ｔ−ブチル、トリフルオロチオ酢酸Ｓ−フェニル、を挙げることができるが、これらに限られないのは言うまでもない。
【００１４】
Ｒ１としては、フェニル基または置換フェニル基が好ましく、そのようなトリフルオロ酢酸エステルは一般式（５）
【００１５】
【化６】
（式中、Ｒ４は反応において不活性な基を表し、ｍは１〜５の整数を表す。）で表される。Ｒ４としては水素原子、ハロゲン（塩素、フッ素、臭素、ヨウ素）、アルキル基、アルコキシ基などが例示できるがこれらに限られない。アルキル基としてはメチル基、エチル基、プロピル基、イソプロピル基、ｎ−ブチル基、ｓｅｃ−ブチル基、ｔｅｒｔ−ブチル基など、アルコキシとしてはメトキシ基、エトキシ基、プロポキシ基、イソプロポキシ基、ｎ−ブトキシ基、ｓｅｃ−ブトキシ基、ｔｅｒｔ−ブトキシ基などが挙げられる。
【００１７】
本発明に使用するハロゲン化トリアルキルシランとしては、特に限定されないが、一般式（２）
（Ｒ２）３ＳｉＸ （２）
において、Ｒ２がそれぞれ独立にメチル基、エチル基、プロピル基、イソプロピル基またはフェニル基を表し、Ｘは塩素、臭素またはヨウ素を表すものが好ましい。好ましいハロゲン化トリアルキルシランとしては、塩化トリメチルシラン、塩化トリエチルシラン、塩化フェニルジメチルシラン、塩化ジフェニルメチルシラン、臭化トリエチルシランなどを挙げることができる。これらの内、塩化トリメチルシランは入手が容易で最も好ましい。本明細書において、ＴＡＳはトリアルキルシリル基を表す。
【００１８】
本発明にかかる一般式（３）で表される２−トリアルキルシリル２，２−ジフルオロ酢酸エステルは、それぞれ一般式（１）のＲ１と同じ置換基Ｒ１を持つ対応する２−トリアルキルシリル２，２−ジフルオロ酢酸エステルである。
【００１９】
好ましい２−トリアルキルシリル２，２−ジフルオロ酢酸エステルは一般式（６）
【００２０】
【化７】
（式中、Ｒ４、ｍは一般式（５）と同じ）で表される２−トリアルキルシリル２，２−ジフルオロ酢酸エステルである。ＴＡＳとしては、アルキル基ががそれぞれ独立にメチル基、エチル基、プロピル基、イソプロピル基またはフェニル基であり、好ましくはトリメチルシリル基が挙げられる。
【００２２】
本発明の方法において使用する溶媒は、本発明反応応条件で不活性であればよく、脂肪族炭化水素系溶媒、例えば、ペンタン、ヘキサン、ヘプタン等、芳香族炭化水素類、例えば、ベンゼン、トルエン、キシレン等、ニトリル類、例えば、アセトニトリル、プロピオニトリル、フェニルアセトニトリル、イソブチロニトリル、ベンゾニトリル、酸アミド類、例えば、ジメチルホルムアミド、ジメチルアセトアミド、メチルホルムアミド、ホルムアミド、ヘキサメチルリン酸トリアミド、Ｎ−メチルピロリドン、低級エーテル類、例えば、テトラヒドロフラン、１，２−ジメトキシエタン、１，４−ジオキサン、ジエチルエーテル、１，２−エポキシエタン、１、４−ジオキサン、ジブチルエーテル、ｔ−ブチルメチルエーテル、置換テトラヒドロフラン等などが使用され、ジメチルホルムアミド、テトラヒドロフランが好ましい。これらの溶媒を組み合わせて使用することもできる。溶媒の量は、出発原料の１重量部に対して１〜１００重量部程度、好ましくは１〜１０重量部である。
【００２３】
使用する溶媒はでき得る限り水分を除去した方が好ましいが、必ずしも完全に除く必要はない。工業的に入手可能な溶媒に通常混入している程度の水分は、本製造方法の実施において特に問題にならず、従って水分を除去することなくそのまま使用できる。
【００２４】
本発明において使用される低原子価金属は、特に限定されないが、金属担体として、例えば、マグネシウム、亜鉛、銅、鉄、カドミウム、スズ、チタン、ナトリウムなど、またはこれらの金属を主成分とする合金、例えば、亜鉛−銅合金、ラネーニッケル、銀−亜鉛合金、銅−マグネシウム合金などが挙げられる。また、酸化状態が複数存在する金属元素の低原子価イオン、例えば、三塩化チタン、二ヨウ化サマリウム、二塩化クロム、金属錯体、例えば、ナトリウムナフタレニド、ナトリウムベンゾフェノンケチル錯体、テトラキス（トリフェニルホスフィン）パラジウムなどが挙げられる。さらにこれら金属担体または合金と金属イオン若しくは金属錯体の混合系、例えば、四塩化チタン−金属亜鉛系、二塩化チタノセン−金属亜鉛系、二ヨウ化サマリウム−金属サマリウム系、二ヨウ化サマリウム−金属マグネシウム系などが挙げられる。これらのうちで、マグネシウムを用いた系、例えば金属マグネシウム、二ヨウ化サマリウム−金属マグネシウム系などが特に好ましいものとして挙げられる。
【００２５】
低原子価金属は、単体で用いる場合には、粉末、粒状、塊状、多孔質状、切削屑状、線状など何れの形状でもかまわない。例えば、金属マグネシウムとしては、グリニャール反応において通常使用される公知の形状のマグネシウムがそのまま使用できる。 反応温度は−７８〜１２０℃程度であり、反応時間は反応試剤により異なるが、通常１０分から２０時間程度で行うのが好都合である。反応圧力は常圧付近でよく、その他の反応条件は、当業者に公知の有機マグネシウム化合物を用いる反応の条件が適用できる。
【００２６】
本発明の方法においては、反応を促進する目的でグリニャール反応で一般的に行われている各種の反応促進法を適用することができる。そのような手段として、例えば、臭素またはヨウ素などのハロゲン、グリニャール試薬、臭化エチル、ヨウ化メチル、ヨウ化メチレン、ヨウ化エチル、β−ブロムエチルエーテルなどの有機ハロゲン化物、あるいはオルト珪酸エチルなどを反応系に添加する方法や攪拌または超音波を照射する方法などを挙げることができる。
【００２７】
本発明の方法によって製造される２−トリアルキルシリル２，２−ジフルオロ酢酸エステルは、下式に示すようにフッ素イオンの存在下において親電子試薬との反応により各種の反応生成物を得ることができる。親電子試薬としては特に限定されず、例えばベンズアルデヒド、ベンゾイルクロライド、ベンジルクロライドなどとアルキル化反応を進行させることができる。
【００２８】
【化８】
ここで、Ｅは前記親電子試薬に対応して、ＰｈＣＨ（ＯＨ）−、ＰｈＣＨ２−、ＰｈＣＯ−をそれぞれ表す。Ｆ−イオンとしては、テトラブチルアンモニウムフルオライド等の四級アンモニウムフルオライド、フッ化カリウム等のアルカリ金属フッ化物（ヨウ化銅等の助触媒を使用することもある。）などを適宜使用できる。また、溶媒としてはＴＨＦ、ＤＭＦなど本発明の方法において使用される前記溶媒を使用できる。反応温度は試剤の種類により異なるが、−７８〜１５０℃程度である。
【００３０】
以下に実施例をもって本発明を説明するが、これらの実施態様に限定されるものではない。
【００３１】
【実施例】
〔実施例１〕
二口反応器内に２００ｍｌの蒸留したＮ，Ｎ−ジメチルホルムアミド（ＤＭＦ）に溶解した塩化トリメチルシラン（３４．７ｇ、３２０ｍｍｏｌ）と市販のマグネシウム（３．９ｇ、１６０ｍｍｏｌ）をはかり入れ、アルゴン雰囲気で０℃まで冷却した。トリフルオロ酢酸フェニル（３．８ｇ、２０ｍｍｏｌ）を滴下しその後２．５時間室温で攪拌を続けた。
【００３２】
過剰の塩化トリメチルシランを減圧下（〜３０ｍｍＨｇ）除去し残ったマグネシウムをデカンテーションにより除き、得られたＤＭＦ溶液から冷エーテル２０ｍｌによる抽出を５回繰り返した。抽出液を冷水で洗った後無水硫酸マグネシウムで乾燥させた。溶媒を留去し１．５ｍｍＨｇ、７０℃でトラップ−トラップ蒸留すると無色の固体（３．２ｇ、６６％）が得られた。
【００３３】
２−トリメチルシリル２，２−ジフルオロ酢酸フェニル
融点６１℃；ＩＲ（ＫＢｒ）１７７０ｃｍ−１；１ＨＮＭＲ（２００ＭＨｚ，ＣＤＣｌ３）δ０．３４（ｓ，９Ｈ）、７．１−７．４（ｍ，５Ｈ）；１９ＦＮＭＲ（１８８ＭＨｚ、ＣＤＣｌ３，Ｃ６Ｆ６内部標準）δ３８．５（ｓ，２Ｆ）。
【００３４】
〔実施例２〕
トリフルオロ酢酸エステルとしてトリフルオロ酢酸ｐ−メトキシフェニルを用い、反応時間を６．５時間として実施例１と同様に反応を行った。２−トリメチルシリル２，２−ジフルオロ酢酸ｐ−メトキシフェニルの収率は６４％であった。
【００３５】
淡黄色油状（沸点１００℃／１．２ｍｍＨｇ）；ＩＲ（ｎｅａｔ）１７７４ｃｍ−１；１ＨＮＭＲ（２００ＭＨｚ，ＣＤＣｌ３）δ０．３２（ｓ，９Ｈ）、３．８（ｓ，３Ｈ）、６．９１（ｄ，Ｊ＝９．２Ｈｚ，２Ｈ）、７．０６（ｄ，Ｊ＝９．２Ｈｚ，２Ｈ）；１９ＦＮＭＲ（１８８ＭＨｚ、ＣＤＣｌ３，Ｃ６Ｆ６内部標準）δ３８．５（ｓ，２Ｆ）。
【００３６】
〔実施例３〕
トリフルオロ酢酸エステルとしてトリフルオロ酢酸ｐ−トリルを用い、反応時間を４．５時間として実施例１と同様に反応を行った。２−トリメチルシリル２，２−ジフルオロ酢酸ｐ−トリルの収率は５６％であった。
【００３７】
淡黄色固体（融点４６℃、沸点８０℃／１．２ｍｍＨｇ）；ＩＲ（ＫＢｒ）１７７６ｃｍ−１；１ＨＮＭＲ（２００ＭＨｚ，ＣＤＣｌ３）δ０．３３（ｓ，９Ｈ）、２．３６（ｓ，３Ｈ）、７．０２（ｄ，Ｊ＝９．２Ｈｚ，２Ｈ）、７．２０（ｄ，Ｊ＝９．２Ｈｚ，２Ｈ）；１９ＦＮＭＲ（１８８ＭＨｚ、ＣＤＣｌ３，Ｃ６Ｆ６内部標準）δ３８．７（ｓ，２Ｆ）。
【００３８】
〔実施例４〕
トリフルオロ酢酸エステルとしてトリフルオロ酢酸ｐ−クロロフェニルを用い、反応時間を１．５時間として実施例１と同様に反応を行った。２−トリメチルシリル２，２−ジフルオロ酢酸ｐ−クロロフェニルの収率は５５％であった。
【００３９】
無色油状（沸点７０℃／０．５ｍｍＨｇ）；ＩＲ（ＫＢｒ）１７７２ｃｍ−１；１ＨＮＭＲ（２００ＭＨｚ，ＣＤＣｌ３）δ０．３２（ｓ，９Ｈ）、７．１０（ｄ，Ｊ＝８．９Ｈｚ，２Ｈ）、７．３８（ｄ，Ｊ＝８．９Ｈｚ，２Ｈ）；１９ＦＮＭＲ（１８８ＭＨｚ、ＣＤＣｌ３，Ｃ６Ｆ６内部標準）δ３８．５（ｓ，２Ｆ）。
【００４０】
【発明の効果】
本発明の製造方法によると、原料入手の容易なトリフルオロ酢酸エステル類を原料として、有機合成反応において有用な２−トリアルキルシリル２，２−ジフルオロ酢酸エステルを収率よく製造できるという効果を奏する。[0001]
TECHNICAL FIELD OF THE INVENTION
The present invention relates to a method for producing 2-trialkylsilyl 2,2-difluoroacetic acid esters. 2-Trialkylsilyl 2,2-difluoroacetic acid ester is useful as a reaction reagent for introducing a difluoromethylene group into an organic compound or as an intermediate for producing an organic compound.
[0002]
[Prior art]
In recent years, a compound having a difluoromethylene group has a particular biological activity, and therefore, its synthetic method has attracted attention. Heretofore, a carbonyl group, a thiocarbonyl group, or a thiocetal group is often converted to a difluoromethylene group by reacting with DAST (dimethylaminosulfur trifluoride) or an oxidizing fluorinating agent having a similar effect. A method of dehalogenating a halodifluoromethyl group to obtain a difluoromethylene group is also well known. However, little is known about the selective demonofluorination from the trifluoromethyl group.
[0003]
The present applicant has disclosed in Japanese Patent Application No. 11-30843 that 2-trifluoroalkylsilyl 2,2-difluoroacetic esters can be obtained by electrolytic reduction of trifluoroacetic esters in the presence of trimethylsilane chloride. .
[0004]
[Problems to be solved by the invention]
Although the above-described method by electrolytic reduction is an excellent method with a good yield, the electrolytic reduction method is a method that is hardly industrially common, and it is desirable to introduce a synthesis method instead.
[0005]
Therefore, the present invention provides a method for producing 2-trialkylsilyl 2,2-difluoroacetic esters with good yield, which can constitute an industrial process by applying operations conventionally performed in many reactions. I do.
[0006]
[Means for Solving the Problems]
The present inventors have found that when a trifluoroacetate is reacted with a halogenated trialkylsilane in the presence of a low-valent metal and a solvent, 2-trialkylsilyl 2,2-difluoroacetate is formed. Invented the invention.
[0007]
That is, the present invention relates to the general formula (1)
[0008]
Embedded image
(In the formula, R 1 represents a monovalent organic group.)
The trifluoroacetic acid ester represented by the general formula (2)
(R 2 ) 3 SiX (2)
(Wherein R 2 independently represents a methyl group, an ethyl group, a propyl group, an isopropyl group or a phenyl group, and X represents chlorine, bromine or iodine) and a low-atom trialkylsilane. General formula (3) comprising reacting with a valent metal in the presence of a solvent
[0010]
Embedded image
(Where TAS represents (R 2 ) 3 Si—, and R 1 and R 2 are the same as in formulas (1) and (2), respectively) This is a method for producing an acetic ester.
[0012]
The trifluoroacetic acid esters represented by the general formula (1) according to the present invention are not particularly limited as long as the monovalent organic group represented by R 1 is inactive under the conditions of the reduction reaction. Examples of such an organic group include an alkyl group, an alkenyl group or an alkynyl group which may have a branch having 1 to 20 carbon atoms, a cycloalkyl group which may have a substituent having 1 to 20 carbon atoms, An aryl group optionally having 20 substituents, represented by the general formula (4)
— (CH 2 ) n —R 3 (4)
(Wherein, R 3 represents a cycloalkyl group having 1 to 10 carbon atoms, an aryl group, an alkoxyl group, a thioalkoxyl group, a tertiary amino group, an acyl group, an alkoxycarbonyl group, a heteroaromatic group, and n is 1 or more. And an organic group represented by the following formula:
[0013]
Specific examples of the trifluoroacetates represented by the general formula (1) include methyl trifluoroacetate, ethyl trifluoroacetate, n-propyl trifluoroacetate, i-propyl trifluoroacetate, and n-trifluoroacetate. Butyl, s-butyl trifluoroacetate, t-butyl trifluoroacetate, n-hexyl trifluoroacetate, cyclohexyl trifluoroacetate, phenyl trifluoroacetate, St-butyl trifluorothioacetate, S-phenyl trifluorothioacetate However, it is needless to say that the present invention is not limited to these.
[0014]
R 1 is preferably a phenyl group or a substituted phenyl group, and such a trifluoroacetic acid ester is represented by the general formula (5)
[0015]
Embedded image
(In the formula, R 4 represents an inactive group in the reaction, and m represents an integer of 1 to 5.) Examples of R 4 include a hydrogen atom, halogen (chlorine, fluorine, bromine, and iodine), an alkyl group, and an alkoxy group, but are not limited thereto. Examples of the alkyl group include a methyl group, an ethyl group, a propyl group, an isopropyl group, an n-butyl group, a sec-butyl group and a tert-butyl group. As the alkoxy group, a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group, and an n- Butoxy group, sec-butoxy group, tert-butoxy group and the like.
[0017]
The halogenated trialkylsilane used in the present invention is not particularly limited, but may be represented by the general formula (2)
(R 2 ) 3 SiX (2)
In the formula, R 2 independently preferably represents a methyl group, an ethyl group, a propyl group, an isopropyl group or a phenyl group, and X preferably represents chlorine, bromine or iodine. Preferable halogenated trialkylsilanes include trimethylsilane chloride, triethylsilane chloride, phenyldimethylsilane chloride, diphenylmethylsilane chloride, and triethylsilane bromide. Among them, trimethylsilane chloride is most preferable because it is easily available. In the present specification, TAS represents a trialkylsilyl group.
[0018]
2-trialkylsilyl-difluoro acid ester represented by the general formula according to the present invention (3) the corresponding 2-trialkyl respectively with the same substituents R 1 and R 1 in the general formula (1) Silyl 2,2-difluoroacetate.
[0019]
Preferred 2-trialkylsilyl 2,2-difluoroacetic acid esters are represented by the general formula (6)
[0020]
Embedded image
(Wherein, R 4 and m are the same as those in the general formula (5)). As the TAS, the alkyl groups are each independently a methyl group, an ethyl group, a propyl group, an isopropyl group or a phenyl group, preferably a trimethylsilyl group.
[0022]
The solvent used in the method of the present invention only needs to be inert under the reaction conditions of the present invention, and may be an aliphatic hydrocarbon-based solvent, for example, pentane, hexane, heptane and the like, aromatic hydrocarbons, for example, benzene, toluene , Xylene and the like, nitriles such as acetonitrile, propionitrile, phenylacetonitrile, isobutyronitrile, benzonitrile, acid amides such as dimethylformamide, dimethylacetamide, methylformamide, formamide, hexamethylphosphoric triamide, N -Methylpyrrolidone, lower ethers such as tetrahydrofuran, 1,2-dimethoxyethane, 1,4-dioxane, diethyl ether, 1,2-epoxyethane, 1,4-dioxane, dibutyl ether, t-butyl methyl ether, Substituted tetrahi Rofuran etc., etc. are used, dimethylformamide, tetrahydrofuran is preferred. These solvents can be used in combination. The amount of the solvent is about 1 to 100 parts by weight, preferably 1 to 10 parts by weight, based on 1 part by weight of the starting material.
[0023]
The solvent used is preferably one from which water is removed as much as possible, but it is not necessary to completely remove it. Moisture to such an extent that it is usually mixed in an industrially available solvent does not cause any particular problem in the practice of the present production method, and thus can be used as it is without removing water.
[0024]
The low-valent metal used in the present invention is not particularly limited, but as a metal carrier, for example, magnesium, zinc, copper, iron, cadmium, tin, titanium, sodium, or an alloy containing these metals as main components For example, a zinc-copper alloy, Raney nickel, a silver-zinc alloy, a copper-magnesium alloy and the like can be mentioned. In addition, low valent ions of metal elements having a plurality of oxidation states, such as titanium trichloride, samarium diiodide, chromium dichloride, metal complexes such as sodium naphthalenide, sodium benzophenone ketyl complex, and tetrakis (triphenyl) (Phosphine) palladium and the like. Further, a mixed system of these metal carriers or alloys and metal ions or metal complexes, for example, titanium tetrachloride-metal zinc system, titanocene dichloride-metal zinc system, samarium diiodide-metal samarium system, samarium diiodide-metal magnesium And the like. Among these, a system using magnesium, for example, a metal magnesium, a samarium diiodide-metal magnesium system and the like are particularly preferable.
[0025]
When used as a single substance, the low-valent metal may be in any shape such as powder, granule, lump, porous, shavings, and wire. For example, as the metallic magnesium, a magnesium having a known shape usually used in a Grignard reaction can be used as it is. The reaction temperature is about -78 to 120 ° C, and the reaction time varies depending on the reaction reagent, but it is usually convenient to carry out the reaction for about 10 minutes to 20 hours. The reaction pressure may be around normal pressure, and the other reaction conditions may be those of a reaction using an organomagnesium compound known to those skilled in the art.
[0026]
In the method of the present invention, various reaction promotion methods generally used in Grignard reactions for the purpose of promoting the reaction can be applied. Such means include, for example, halogens such as bromine or iodine, Grignard reagents, organic halides such as ethyl bromide, methyl iodide, methylene iodide, ethyl iodide, β-bromoethyl ether, and ethyl orthosilicate. Can be added to the reaction system or a method of irradiating with stirring or ultrasonic waves.
[0027]
The 2-trialkylsilyl 2,2-difluoroacetic acid ester produced by the method of the present invention can obtain various reaction products by reacting with an electrophilic reagent in the presence of a fluorine ion as shown in the following formula. it can. The electrophilic reagent is not particularly limited. For example, an alkylation reaction with benzaldehyde, benzoyl chloride, benzyl chloride, or the like can proceed.
[0028]
Embedded image
Here, E is in correspondence with the electrophilic reagent, PhCH (OH) -, PhCH 2 -, respectively represent PhCO-. As the F-ion, a quaternary ammonium fluoride such as tetrabutylammonium fluoride, an alkali metal fluoride such as potassium fluoride (a co-catalyst such as copper iodide may be used), or the like can be appropriately used. The solvent used in the method of the present invention, such as THF and DMF, can be used as the solvent. The reaction temperature varies depending on the type of the reagent, but is about -78 to 150 ° C.
[0030]
Hereinafter, the present invention will be described with reference to Examples, but the present invention is not limited to these Examples.
[0031]
【Example】
[Example 1]
In a two-necked reactor, 200 ml of distilled N, N-dimethylformamide (DMF) dissolved in trimethylsilane chloride (34.7 g, 320 mmol) and commercially available magnesium (3.9 g, 160 mmol) were weighed and placed in an argon atmosphere. Cooled to 0 ° C. Phenyl trifluoroacetate (3.8 g, 20 mmol) was added dropwise, followed by stirring at room temperature for 2.5 hours.
[0032]
Excess trimethylsilane chloride was removed under reduced pressure (（30 mmHg), the remaining magnesium was removed by decantation, and extraction with 20 ml of cold ether was repeated 5 times from the obtained DMF solution. The extract was washed with cold water and dried over anhydrous magnesium sulfate. The solvent was distilled off, and trap-trap distillation was performed at 1.5 mmHg and 70 ° C. to obtain a colorless solid (3.2 g, 66%).
[0033]
2-trimethylsilyl 2,2-difluoroacetic acid phenyl Melting point 61 ° C .; IR (KBr) 1770 cm −1 ; 1 H NMR (200 MHz, CDCl 3 ) δ 0.34 (s, 9H), 7.1-7.4 (m, 5H) ); 19 FNMR (188MHz, CDCl 3, C 6 F 6 internal standard) δ38.5 (s, 2F).
[0034]
[Example 2]
The reaction was carried out in the same manner as in Example 1 except that p-methoxyphenyl trifluoroacetate was used as the trifluoroacetate and the reaction time was 6.5 hours. The yield of p-methoxyphenyl 2-trimethylsilyl 2,2-difluoroacetate was 64%.
[0035]
Pale yellow oil (boiling point 100 ° C./1.2 mmHg); IR (neat) 1774 cm −1 ; 1 H NMR (200 MHz, CDCl 3 ) δ 0.32 (s, 9H), 3.8 (s, 3H), 6.91 (D, J = 9.2 Hz, 2H), 7.06 (d, J = 9.2 Hz, 2H); 19 FNMR (188 MHz, CDCl 3 , C 6 F 6 internal standard) δ 38.5 (s, 2F). .
[0036]
[Example 3]
The reaction was carried out in the same manner as in Example 1, except that p-tolyl trifluoroacetate was used as the trifluoroacetate and the reaction time was set to 4.5 hours. The yield of 2-trimethylsilyl 2,2-difluoroacetic acid p-tolyl was 56%.
[0037]
Pale yellow solid (melting point 46 ° C., boiling point 80 ° C./1.2 mmHg); IR (KBr) 1776 cm −1 ; 1 H NMR (200 MHz, CDCl 3 ) δ 0.33 (s, 9H), 2.36 (s, 3H) , 7.02 (d, J = 9.2 Hz, 2H), 7.20 (d, J = 9.2 Hz, 2H); 19 FNMR (188 MHz, CDCl 3 , C 6 F 6 internal standard) δ 38.7 ( s, 2F).
[0038]
[Example 4]
The reaction was carried out in the same manner as in Example 1 except that p-chlorophenyl trifluoroacetate was used as the trifluoroacetate and the reaction time was 1.5 hours. The yield of p-chlorophenyl 2-trimethylsilyl 2,2-difluoroacetate was 55%.
[0039]
Colorless oil (boiling point 70 ° C./0.5 mmHg); IR (KBr) 1772 cm −1 ; 1 H NMR (200 MHz, CDCl 3 ) δ 0.32 (s, 9 H), 7.10 (d, J = 8.9 Hz, 2 H) ), 7.38 (d, J = 8.9 Hz, 2H); 19 F NMR (188 MHz, CDCl 3 , C 6 F 6 internal standard) δ 38.5 (s, 2F).
[0040]
【The invention's effect】
ADVANTAGE OF THE INVENTION According to the manufacturing method of this invention, there exists an effect that a 2-trifluoroalkylsilyl 2,2-difluoroacetic acid ester useful in an organic synthesis reaction can be manufactured with a good yield, using trifluoroacetates which are easily available as raw materials. .
Claims (3)
（Ｒ２）３ＳｉＸ （２）
（式中、Ｒ２はそれぞれ独立にメチル基、エチル基、プロピル基、イソプロピル基またはフェニル基を表し、Ｘは塩素、臭素またはヨウ素を表す。）で表されるハロゲン化トリアルキルシランと低原子価金属と溶媒の存在下で反応させることからなる一般式（３）
(R 2 ) 3 SiX (2)
(Wherein R 2 independently represents a methyl group, an ethyl group, a propyl group, an isopropyl group or a phenyl group, and X represents chlorine, bromine or iodine) and a low-atom trialkylsilane. General formula (3) comprising reacting with a valent metal in the presence of a solvent
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