WO2021054414A1 - 含フッ素化合物の製造方法 - Google Patents
含フッ素化合物の製造方法 Download PDFInfo
- Publication number
- WO2021054414A1 WO2021054414A1 PCT/JP2020/035360 JP2020035360W WO2021054414A1 WO 2021054414 A1 WO2021054414 A1 WO 2021054414A1 JP 2020035360 W JP2020035360 W JP 2020035360W WO 2021054414 A1 WO2021054414 A1 WO 2021054414A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- group
- formula
- compound
- fluorine
- producing
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 147
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 55
- 229910052731 fluorine Inorganic materials 0.000 title claims abstract description 52
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 title claims abstract description 45
- 239000011737 fluorine Substances 0.000 title claims abstract description 45
- 150000004795 grignard reagents Chemical class 0.000 claims abstract description 25
- 239000007818 Grignard reagent Substances 0.000 claims abstract description 24
- 150000003623 transition metal compounds Chemical class 0.000 claims abstract description 13
- 125000001273 sulfonato group Chemical group [O-]S(*)(=O)=O 0.000 claims abstract description 9
- 125000005842 heteroatom Chemical group 0.000 claims description 15
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 13
- 125000000217 alkyl group Chemical group 0.000 claims description 13
- 125000001424 substituent group Chemical group 0.000 claims description 13
- 125000003709 fluoroalkyl group Chemical group 0.000 claims description 11
- 125000005843 halogen group Chemical group 0.000 claims description 11
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 10
- 125000002827 triflate group Chemical group FC(S(=O)(=O)O*)(F)F 0.000 claims description 9
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 6
- 229910052802 copper Inorganic materials 0.000 claims description 6
- 239000010949 copper Substances 0.000 claims description 6
- 125000005010 perfluoroalkyl group Chemical group 0.000 claims description 6
- 125000002947 alkylene group Chemical group 0.000 claims description 4
- 125000006551 perfluoro alkylene group Chemical group 0.000 claims description 3
- 125000001183 hydrocarbyl group Chemical group 0.000 claims 2
- 238000006243 chemical reaction Methods 0.000 abstract description 18
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 32
- 230000015572 biosynthetic process Effects 0.000 description 25
- 238000003786 synthesis reaction Methods 0.000 description 25
- 239000000203 mixture Substances 0.000 description 17
- 239000002904 solvent Substances 0.000 description 17
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 16
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- 229910052799 carbon Inorganic materials 0.000 description 14
- 150000002430 hydrocarbons Chemical group 0.000 description 13
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- 238000005481 NMR spectroscopy Methods 0.000 description 11
- 150000001721 carbon Chemical group 0.000 description 11
- 125000004432 carbon atom Chemical group C* 0.000 description 11
- 125000001153 fluoro group Chemical group F* 0.000 description 11
- 238000005160 1H NMR spectroscopy Methods 0.000 description 10
- 238000001914 filtration Methods 0.000 description 10
- -1 perfluoroalkyl bromide Chemical compound 0.000 description 10
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
- 238000003818 flash chromatography Methods 0.000 description 7
- 239000003446 ligand Substances 0.000 description 7
- 239000000741 silica gel Substances 0.000 description 7
- 229910002027 silica gel Inorganic materials 0.000 description 7
- 229910052938 sodium sulfate Inorganic materials 0.000 description 7
- 235000011152 sodium sulphate Nutrition 0.000 description 7
- KAKZBPTYRLMSJV-UHFFFAOYSA-N Butadiene Chemical compound C=CC=C KAKZBPTYRLMSJV-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000012039 electrophile Substances 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 125000003118 aryl group Chemical group 0.000 description 5
- 125000000962 organic group Chemical group 0.000 description 5
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 125000000753 cycloalkyl group Chemical group 0.000 description 4
- ZQBFAOFFOQMSGJ-UHFFFAOYSA-N hexafluorobenzene Chemical compound FC1=C(F)C(F)=C(F)C(F)=C1F ZQBFAOFFOQMSGJ-UHFFFAOYSA-N 0.000 description 4
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 238000005406 washing Methods 0.000 description 4
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical group [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical group [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 239000011777 magnesium Substances 0.000 description 3
- 229910052749 magnesium Inorganic materials 0.000 description 3
- QUXHCILOWRXCEO-UHFFFAOYSA-M magnesium;butane;chloride Chemical compound [Mg+2].[Cl-].CCC[CH2-] QUXHCILOWRXCEO-UHFFFAOYSA-M 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 description 3
- 229910052710 silicon Inorganic materials 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 229910052717 sulfur Inorganic materials 0.000 description 3
- 125000004434 sulfur atom Chemical group 0.000 description 3
- 230000002194 synthesizing effect Effects 0.000 description 3
- SJBBXFLOLUTGCW-UHFFFAOYSA-N 1,3-bis(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC(C(F)(F)F)=C1 SJBBXFLOLUTGCW-UHFFFAOYSA-N 0.000 description 2
- STLNAVFVCIRZLL-UHFFFAOYSA-N 2,2,3,3,4,4,5,5,6,6,7,7,7-tridecafluoroheptan-1-ol Chemical compound OCC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F STLNAVFVCIRZLL-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical group CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- PMOWTIHVNWZYFI-WAYWQWQTSA-N cis-2-coumaric acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1O PMOWTIHVNWZYFI-WAYWQWQTSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- NBVXSUQYWXRMNV-UHFFFAOYSA-N fluoromethane Chemical compound FC NBVXSUQYWXRMNV-UHFFFAOYSA-N 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
- IUYHWZFSGMZEOG-UHFFFAOYSA-M magnesium;propane;chloride Chemical compound [Mg+2].[Cl-].C[CH-]C IUYHWZFSGMZEOG-UHFFFAOYSA-M 0.000 description 2
- 239000008204 material by function Substances 0.000 description 2
- 239000012046 mixed solvent Substances 0.000 description 2
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 2
- 125000004430 oxygen atom Chemical group O* 0.000 description 2
- 239000000575 pesticide Substances 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 238000007348 radical reaction Methods 0.000 description 2
- 230000009257 reactivity Effects 0.000 description 2
- HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 2
- USCSECLOSDIOTA-UPHRSURJSA-N (Z)-1-chloro-2,3,3-trifluoroprop-1-ene Chemical compound Cl\C=C(\C(F)F)/F USCSECLOSDIOTA-UPHRSURJSA-N 0.000 description 1
- USCSECLOSDIOTA-OWOJBTEDSA-N (e)-1-chloro-2,3,3-trifluoroprop-1-ene Chemical compound FC(F)C(\F)=C/Cl USCSECLOSDIOTA-OWOJBTEDSA-N 0.000 description 1
- XJSRKJAHJGCPGC-UHFFFAOYSA-N 1,1,1,2,2,3,3,4,4,5,5,6,6-tridecafluorohexane Chemical compound FC(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F XJSRKJAHJGCPGC-UHFFFAOYSA-N 0.000 description 1
- OKIYQFLILPKULA-UHFFFAOYSA-N 1,1,1,2,2,3,3,4,4-nonafluoro-4-methoxybutane Chemical compound COC(F)(F)C(F)(F)C(F)(F)C(F)(F)F OKIYQFLILPKULA-UHFFFAOYSA-N 0.000 description 1
- RIQRGMUSBYGDBL-UHFFFAOYSA-N 1,1,1,2,2,3,4,5,5,5-decafluoropentane Chemical compound FC(F)(F)C(F)C(F)C(F)(F)C(F)(F)F RIQRGMUSBYGDBL-UHFFFAOYSA-N 0.000 description 1
- WZLFPVPRZGTCKP-UHFFFAOYSA-N 1,1,1,3,3-pentafluorobutane Chemical compound CC(F)(F)CC(F)(F)F WZLFPVPRZGTCKP-UHFFFAOYSA-N 0.000 description 1
- LKLFXAVIFCLZQS-UHFFFAOYSA-N 1,1,2,2,3,3,4,4-octafluorobutane Chemical compound FC(F)C(F)(F)C(F)(F)C(F)F LKLFXAVIFCLZQS-UHFFFAOYSA-N 0.000 description 1
- CWIFAKBLLXGZIC-UHFFFAOYSA-N 1,1,2,2-tetrafluoro-1-(2,2,2-trifluoroethoxy)ethane Chemical compound FC(F)C(F)(F)OCC(F)(F)F CWIFAKBLLXGZIC-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- PDCBZHHORLHNCZ-UHFFFAOYSA-N 1,4-bis(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=C(C(F)(F)F)C=C1 PDCBZHHORLHNCZ-UHFFFAOYSA-N 0.000 description 1
- DFUYAWQUODQGFF-UHFFFAOYSA-N 1-ethoxy-1,1,2,2,3,3,4,4,4-nonafluorobutane Chemical compound CCOC(F)(F)C(F)(F)C(F)(F)C(F)(F)F DFUYAWQUODQGFF-UHFFFAOYSA-N 0.000 description 1
- CDZXJJOGDCLNKX-UHFFFAOYSA-N 2,2,3,3-tetrafluorobutane-1,4-diol Chemical compound OCC(F)(F)C(F)(F)CO CDZXJJOGDCLNKX-UHFFFAOYSA-N 0.000 description 1
- XXZCIYUJYUESMD-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-3-(morpholin-4-ylmethyl)pyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C(=NN(C=1)CC(=O)N1CC2=C(CC1)NN=N2)CN1CCOCC1 XXZCIYUJYUESMD-UHFFFAOYSA-N 0.000 description 1
- XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- COAUHYBSXMIJDK-UHFFFAOYSA-N 3,3-dichloro-1,1,1,2,2-pentafluoropropane Chemical compound FC(F)(F)C(F)(F)C(Cl)Cl COAUHYBSXMIJDK-UHFFFAOYSA-N 0.000 description 1
- HPJSELOMFUCUAH-UHFFFAOYSA-N CCCCCNNNN(C)NN Chemical compound CCCCCNNNN(C)NN HPJSELOMFUCUAH-UHFFFAOYSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 238000003747 Grignard reaction Methods 0.000 description 1
- IUHFWCGCSVTMPG-UHFFFAOYSA-N [C].[C] Chemical group [C].[C] IUHFWCGCSVTMPG-UHFFFAOYSA-N 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 229910017052 cobalt Inorganic materials 0.000 description 1
- 239000010941 cobalt Substances 0.000 description 1
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 150000001879 copper Chemical class 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000004210 ether based solvent Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 150000002222 fluorine compounds Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 238000010813 internal standard method Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- CQRPUKWAZPZXTO-UHFFFAOYSA-M magnesium;2-methylpropane;chloride Chemical compound [Mg+2].[Cl-].C[C-](C)C CQRPUKWAZPZXTO-UHFFFAOYSA-M 0.000 description 1
- IWCVDCOJSPWGRW-UHFFFAOYSA-M magnesium;benzene;chloride Chemical compound [Mg+2].[Cl-].C1=CC=[C-]C=C1 IWCVDCOJSPWGRW-UHFFFAOYSA-M 0.000 description 1
- CCERQOYLJJULMD-UHFFFAOYSA-M magnesium;carbanide;chloride Chemical compound [CH3-].[Mg+2].[Cl-] CCERQOYLJJULMD-UHFFFAOYSA-M 0.000 description 1
- YCCXQARVHOPWFJ-UHFFFAOYSA-M magnesium;ethane;chloride Chemical compound [Mg+2].[Cl-].[CH2-]C YCCXQARVHOPWFJ-UHFFFAOYSA-M 0.000 description 1
- IJMWREDHKRHWQI-UHFFFAOYSA-M magnesium;ethene;chloride Chemical compound [Mg+2].[Cl-].[CH-]=C IJMWREDHKRHWQI-UHFFFAOYSA-M 0.000 description 1
- CYSFUFRXDOAOMP-UHFFFAOYSA-M magnesium;prop-1-ene;chloride Chemical compound [Mg+2].[Cl-].[CH2-]C=C CYSFUFRXDOAOMP-UHFFFAOYSA-M 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 125000004043 oxo group Chemical group O=* 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- GHUURDQYRGVEHX-UHFFFAOYSA-N prop-1-ynylbenzene Chemical compound CC#CC1=CC=CC=C1 GHUURDQYRGVEHX-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- 125000005490 tosylate group Chemical group 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
- C07C309/01—Sulfonic acids
- C07C309/02—Sulfonic acids having sulfo groups bound to acyclic carbon atoms
- C07C309/03—Sulfonic acids having sulfo groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
- C07C309/04—Sulfonic acids having sulfo groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton containing only one sulfo group
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C19/00—Acyclic saturated compounds containing halogen atoms
- C07C19/08—Acyclic saturated compounds containing halogen atoms containing fluorine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/26—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton
- C07C17/263—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton by condensation reactions
- C07C17/2632—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton by condensation reactions involving an organo-magnesium compound, e.g. Grignard synthesis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B49/00—Grignard reactions
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C19/00—Acyclic saturated compounds containing halogen atoms
- C07C19/08—Acyclic saturated compounds containing halogen atoms containing fluorine
- C07C19/14—Acyclic saturated compounds containing halogen atoms containing fluorine and bromine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
- C07C41/30—Preparation of ethers by reactions not forming ether-oxygen bonds by increasing the number of carbon atoms, e.g. by oligomerisation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C43/00—Ethers; Compounds having groups, groups or groups
- C07C43/02—Ethers
- C07C43/03—Ethers having all ether-oxygen atoms bound to acyclic carbon atoms
- C07C43/14—Unsaturated ethers
- C07C43/17—Unsaturated ethers containing halogen
Definitions
- the present invention relates to a method for producing a fluorine-containing compound.
- Fluorine compounds are used in various fields such as pesticides, pharmaceuticals, and functional materials, and it is required to synthesize various structures by a simpler method.
- Patent Document 1 discloses a method for producing a fluorine-containing compound in which a perfluoroalkyl bromide is added to an olefin compound by a radical reaction.
- Patent Document 2 discloses a method of reacting a Grignard reagent with an electrophile R f- CF 2 CH 2 CH 2- I (R f is a perfluoroalkyl group).
- Non-Patent Document 1 discloses a compound represented by the following formula as an electrophilic perfluoroalkylating agent.
- R f is n ⁇ C m F 2 m + 1
- T f is SO 2 CF 3
- R is H or F.
- Patent Document 1 Since the method of Patent Document 1 reacts with an olefin, it is not suitable for synthesizing a compound having a carbon-carbon double bond, and the type of electrophile is limited. In addition, since the product can undergo further radical reaction to terrorize, various by-products are produced. The electrophile of Patent Document 2 was not easily available. Further, the electrophile perfluoroalkylating agent of Non-Patent Document 1 requires a multi-step process for synthesis, the yield is low, and the electrophile is expensive.
- An object of the present invention is to provide a method for producing a fluorine-containing compound, which produces a fluorine-containing compound under relatively mild reaction conditions using an easily available compound.
- the present invention relates to the following [1] to [8] as a configuration for achieving the above object.
- L is a sulfonate group.
- G 1 is a monovalent group having a (poly) oxyfluoroalkylene chain, a hydrogen atom, an alkyl group, or a fluoroalkyl group.
- G 2 is a divalent group, a single bond, an alkylene group, or a fluoroalkylene group having a (poly) oxyfluoroalkylene chain.
- L is a sulfonate group, and a plurality of Ls in the formula (A2) may be the same or different.
- n is 0 or 1.
- n is 0 or The method for producing a fluorine-containing compound according to [2], wherein n is 1 and G 2 is a divalent group having a (poly) oxyfluoroalkylene chain, a single bond, or a perfluoroalkylene group.
- the partial structure represented by the formula (a) is referred to as a partial structure (a).
- the compound represented by the formula (A1) is referred to as a compound (A1).
- Compounds and the like represented by other formulas are also similar to these.
- “(Poly) oxyfluoroalkylene” is a general term for oxyfluoroalkylene and polyoxyfluoroalkylene.
- the perfluoroalkyl group means a group in which all hydrogen atoms of the alkyl group are substituted with fluorine atoms.
- the fluoroalkyl group is a general term for a combination of a partial fluoroalkyl group and a perfluoroalkyl group.
- a partial fluoroalkyl group is an alkyl group in which one or more hydrogen atoms are substituted with fluorine atoms and one or more hydrogen atoms are present. That is, the fluoroalkyl group is an alkyl group having one or more fluorine atoms. “ ⁇ ” Indicates a numerical range means that the numerical values described before and after the numerical range are included as the lower limit value and the upper limit value.
- R-MgX formula (B) R is a hydrocarbon group which may have a substituent and may have a hetero atom in the carbon chain, and X is a halogen atom.
- the reaction of the above scheme (1) can be carried out under relatively mild reaction conditions by using a sulfonate group as the leaving group L of the partial structure (a) that reacts with the Grignard reagent.
- a sulfonate group as the leaving group L of the partial structure (a) that reacts with the Grignard reagent.
- the L of the partial structure (a) is a sulfonate group (-O-SO 2 -R 2) , leaving by reaction with a Grignard reagent.
- R 2 is an organic group.
- Specific examples of the sulfonate group include tosylate group (OTs), mesylate group (OMs), triflate group (OTf), nonaflate group (ONf) and the like. Of these, a triflate group is preferable from the viewpoint of the reaction yield of the scheme (1).
- a compound having a partial structure (a) (hereinafter, also referred to as a compound (A)) is a compound having one or more partial structures (a).
- the number of the partial structures (a) in the compound (A) is preferably 1 to 6, more preferably 1 to 4, and even more preferably 1 to 2 from the viewpoint of reaction yield.
- the structure of the compound (A) may be appropriately selected depending on the use of the fluorine-containing compound obtained by this production method and the like.
- Examples of the compound (A) having n5 partial structures (a) include a compound represented by the following formula (An5).
- the organic group in G is a substituent containing one or more carbon atoms.
- the organic group include a hydrocarbon group which may have a substituent and may have a bond other than a heteroatom or a hydrocarbon group in the carbon chain or at the end bonded to the partial structure (a). Be done.
- the hydrocarbon group include linear or branched alkyl groups, cycloalkyl groups, aryl groups and combinations thereof.
- the hydrocarbon group may have a double bond or a triple bond in the carbon chain. Examples of the combination include those in which an alkyl group and an aryl group are directly bonded via a hetero atom or a bond other than a hydrocarbon group.
- hetero atom examples include an oxygen atom, a nitrogen atom, a sulfur atom, and a silicon atom. Heteroatoms may form part of the ring structure. Further, among the heteroatoms, the nitrogen atom, the sulfur atom, and the silicon atom may form a branch point for bonding with three or more carbon atoms. Examples of the bond other than the hydrocarbon group include an amide bond, a urea bond, and a urethane bond. Examples of the substituent that the hydrocarbon group may have include a halogen atom, a hydroxy group, an amino group, a nitro group, a sulfo group and the like, and the halogen atom is preferable from the viewpoint of the stability of the compound in the present production method. Of these, a fluorine atom is more preferable.
- the ring structure When the organic group has a ring structure such as a cycloalkyl group or an aryl group, the ring structure includes an aliphatic ring of 3 to 8 members, an aromatic ring of 6 to 8 members, and a ring structure of 3 to 8 members. Examples thereof include a heterocycle and a fused ring composed of two or more of these rings, and the ring structure shown in the following formula is preferable.
- the ring structure may have a halogen atom, an alkyl group which may have an ether bond, a cycloalkyl group, an alkenyl group, an allyl group, an alkoxy group, an oxo group and the like as a substituent.
- the following are preferable specific examples of the compound containing a ring structure.
- the compound (A) is preferably a compound represented by the following formula (A1) or formula (A2).
- G 1- CF 2- CH 2- L formula (A1) L-CH 2 (-CF 2- G 2 ) n- CF 2- CH 2- L formula (A2)
- G 1 is a monovalent group having a (poly) oxyfluoroalkylene chain, a hydrogen atom, an alkyl group, or a fluoroalkyl group.
- G 2 is a divalent group, a single bond, an alkylene group, or a fluoroalkylene group having a (poly) oxyfluoroalkylene chain.
- L is a sulfonate group, and a plurality of Ls in the formula (A2) may be the same or different.
- n is 0 or 1.
- the number of carbon atoms of the alkyl group or fluoroalkyl group of G 1 is preferably 1 to 30, more preferably 1 to 20, further preferably 1 to 10, and 1 to 6 from the viewpoint of increasing the yield of the present production method. Is particularly preferable.
- G 1 Monovalent group having a (poly) oxy-fluoroalkylene chain in G 1, in formula (A1), or with a -O- terminated to bind to CF 2, carbons of 2 or more carbon chain carbon - carbon atoms A fluoroalkyl group having —O— in between or containing both.
- G 1 preferably has a structure represented by the following formula (G1-1).
- R f0 O-[(R f1 O) m1 (R f2 O) m2 (R f3 O) m3 (R f4 O) m4 (R f5 O) m5 (R f6 O) m6 ]-(R f7 ) m7 -Formula (G1-1)
- R f0 is a fluoroalkyl group having 1 to 20 carbon atoms.
- R f1 is a fluoroalkylene group having 1 carbon atom.
- R f2 is a fluoroalkylene group having 2 carbon atoms.
- R f3 is a fluoroalkylene group having 3 carbon atoms.
- R f4 is a fluoroalkylene group having 4 carbon atoms.
- R f5 is a fluoroalkylene group having 5 carbon atoms.
- R f6 is a fluoroalkylene group having 6 carbon atoms and has 6 carbon atoms.
- R f7 is a fluoroalkylene group having 1 to 6 carbon atoms.
- m1, m2, m3, m4, m5, and m6 independently represent an integer of 0 or 1, respectively, m7 is an integer of 0 or 1, and m1 + m2 + m3 + m4 + m5 + m6 + m7 is an integer of 0 to 200.
- the bonding order of (R f1 O) to (R f6 O) in the formula (G1-1) is arbitrary.
- M1 to m6 of the formula (G1-1) represent the number of (R f1 O) to (R f6 O), respectively, and do not represent the arrangement.
- (R f5 O) m5 is, (R f5 O)
- the number of stands that the m5 amino, (R f5 O) does not represent a block arrangement of m5.
- the description order of (R f1 O) to (R f6 O) does not represent the binding order of each unit.
- end that binds to CF 2 in G 1 is -O-.
- the terminal bonded to CF 2 of G 1 is a carbon atom (carbon atom at the end of R f7).
- G 1 examples include CH 3- , CH 3 CH 2- , CH 3 CH 2 CH 2- , CH 3 CH 2 CH 2 CH 2- , CH 3 CH 2 CH 2 CH 2- , CH 3 CH 2 CH 2 CH 2 CH 2- , CF 3- , CF 3 CF 2- , CF 3 CF 2 CF 2- , CF 3 CF 2 CF 2 CF 2- , CF 3 CF 2 CF 2 CF 2 -, CF 3 CF 2 CF 2 CF 2 CF 2 CF 2- , CF 3 CF 2 CF 2- O-[(CF 2- O) m1 (CF 2 CF 2- O) m2 ]-, CF 3 CF 2 CF 2- O-CF 2 CF 2- O-[(CF 2- O) m1 (CF 2 CF 2- O) m2 ]-, CF 3- O (-CF 2 CF 2- O-CF 2 CF 2 CF 2 CF 2- O-CF 2 CF 2- O-[(CF 2- O) m1 (CF 2 CF 2- O)
- G 1 is a monovalent group having a (poly) oxyfluoroalkylene chain or a perfluoroalkyl group in the formula (A1) from the viewpoint of yield and the like.
- the carbon number of the alkylene group or fluoroalkylene group of G 2 is preferably 1 to 30, more preferably 1 to 20, further preferably 1 to 10, and 1 to 6 from the viewpoint of increasing the yield of the present production method. Is particularly preferable.
- Divalent group having at G 2 a (poly) oxy-fluoroalkylene chain, in Formula (A2), or two terminal binding to CF 2 has a -O- each independently 2 or more carbon chain atoms It is a fluoroalkylene group having —O— between carbon-carbon atoms or a combination thereof.
- G 2 preferably has a structure represented by the following formula (G2-1).
- m0 is an integer of 0 or 1
- R f1 , R f2 , R f3 , R f4 , R f5 , R f6 , R f7 , m1, m2, m3, m4, m5, m6, and m7 are described above. it is the same as those in G 1.
- the bonding order of (R f1 O) to (R f6 O) in the formula (G2-1) is arbitrary, as described in the above formula (G1-1).
- m7 the one-sided end that binds to CF 2 of G 2 is -O-.
- m7 the one-sided end bonded to CF 2 of G 2 is a carbon atom (carbon atom at the end of R f7).
- m0 1, the one-sided end that binds to CF 2 of G 2 is ⁇ O ⁇ .
- the one-sided end bonded to CF 2 of G 2 is a carbon atom (a carbon atom at any end of R f1 to R f7).
- m0 and m7 are independently 0 or 1, respectively.
- G 2 Specific examples of G 2, -CH 2 -, - CH 2 CH 2 -, - CH 2 CH 2 CH 2 -, - CH 2 CH 2 CH 2 CH 2 -, - CH 2 CH 2 CH 2 CH 2- , -CH 2 CH 2 CH 2 CH 2 CH 2- , -CF 2- , -CF 2 CF 2- , -CF 2 CF 2 CF 2- , -CF 2 CF 2 CF 2- , -CF 2 CF 2 CF 2 CF 2- , -CF 2 CF 2 CF 2 CF 2 CF 2 -, -CF 2 CF 2 CF 2 CF 2 CF 2 -, - O - [(CF 2 -O) m1 (CF 2 CF 2 -O) m2] - And so on.
- compound (A) when n is 0, compound (A) is L-CH 2 -CF 2 -CH 2 -L. Further, in the equation (A2), n is 1, if G 2 is a single bond, compound (A) is L-CH 2 -CF 2 -CF 2 -CH 2 -L.
- n 0 or n is 1
- G 2 is a divalent having a (poly) oxyfluoroalkylene chain. It is preferably a group, a single bond, or a perfluoroalkylene group.
- compound (A) include the following.
- n1, n2, n3, and n4 are integers from 1 to 100.
- this production method can be applied even when G 1 is a fluorine atom, that is, when compound (A) is CF 3- CH 2-L.
- one of the features of this production method is that two fluorine atoms are bonded to ⁇ carbon with respect to the leaving group L, and the structure has excellent reactivity with a structure in which a carbon chain or the like is extended.
- G 1 the case of a fluorine atom is excluded.
- Compound (A) is a compound represented by the following formula (A1-2) or formula (A2-2) in the presence of an organic amine compound such as triethylamine or pyridine, and trifluoromethanesulfonic anhydride and tosyl lolide. , Mesylate, etc. can be reacted to form a sulfonate.
- G 1- CF 2- CH 2- OH formula (A1-2) HO-CH 2 (-CF 2- G 2 ) n- CF 2- CH 2- OH formula (A2-2)
- G 1 , G 2 and n in the formula are as described above.
- the Grignard reagent may be any as long as it can react with the partial structure (a).
- the Grignard reagent is preferably a compound represented by the following formula (B) from the viewpoint of suppressing side reactions and the like.
- R-MgX formula (B) R is a hydrocarbon group which may have a substituent and may have a hetero atom in the carbon chain, and X is a halogen atom.
- R can be appropriately selected and used from those having a desired structure to be introduced into the compound (A).
- the hydrocarbon group in R may have a heteroatom based on a linear alkyl group, a branched alkyl group, a cycloalkyl group, an aryl group, and a group composed of a combination thereof, and may have a hetero atom as a substituent. It may have a double bond or a triple bond.
- the hetero atom include a nitrogen atom (N), an oxygen atom (O), a sulfur atom (S), and a silicon atom (Si), and N, O, or S is preferable from the viewpoint of compound stability.
- a fluorine atom is preferable.
- the carbon number of R is preferably 1 to 30, more preferably 1 to 20, and even more preferably 1 to 15 from the viewpoint of improving the yield in this production method.
- the halogen atom in X is preferably a chlorine atom, a bromine atom, or an iodine atom from the viewpoint of reactivity, and more preferably a chlorine atom or a bromine atom.
- Grignard reagents examples include primary alkyl Grignard reagents in which the carbon atom to be magnesium-bonded is a primary carbon atom such as methylmagnesium chloride, ethylmagnesium chloride, and allylmagnesium chloride; a second such as isopropylmagnesium chloride.
- the Grignard reagent is preferably a Grignard reagent represented by the following formula (B1) from the viewpoint that the target product can be obtained in a high yield.
- R 1- CH 2- MgX formula (B1) R 1 is a hydrocarbon group which may be a hydrogen atom or may have a substituent and may have a hetero atom in the carbon chain, and X is a halogen atom. is there.
- R 1 is preferably a residue obtained by removing ⁇ CH 2 from R.
- this production method can be carried out under relatively mild reaction conditions.
- the Grignard reagent can be produced, for example, by reacting the following formula (B2) with metallic magnesium. Further, a commercially available product having a desired structure may be used. RX formula (B2) However, R and X are as described above.
- the amount of the Grignard reagent used is preferably 1 equivalent to 30 equivalents with respect to the total number of leaving groups L of the compound (A) from the viewpoint of improving the yield of the target product. Equivalent to 20 equivalents are more preferred, and 5 to 15 equivalents are even more preferred.
- the transition metal compound can be appropriately selected and used from known catalysts used in the Grignard reaction.
- a compound containing elements of Groups 3 to 12 of the periodic table is preferable as the transition metal, and among them, a compound containing elements of Groups 8 to 11 is preferable.
- the Group 8 to Group 11 elements preferably contain one or more elements selected from copper, nickel, palladium, cobalt, and iron, and more preferably copper.
- the copper may be any of 0-valent, monovalent, divalent and trivalent compounds, but from the viewpoint of catalytic ability, monovalent or divalent copper salt or Complex salts are preferred. Further, copper chloride is more preferable from the viewpoint of easy availability. As copper chloride , either CuCl or CuCl 2 can be preferably used. Copper chloride may be anhydrous or hydrate, but copper chloride anhydride is more preferable from the viewpoint of catalytic ability.
- the amount of the transition metal compound used is, for example, 0.1 to 50 mol%, preferably 1 to 30 mol%, and more preferably 2 to 20 mol% with respect to the total number of leaving groups L contained in the compound (A). Is.
- a ligand may be used in combination with a transition metal compound serving as a catalyst, if necessary.
- the yield of the target product is improved by using the ligand.
- the ligand since a sufficient yield can be obtained without using a ligand, the ligand may not be used.
- the ligand include 1,3-butadiene, phenylpropine, tetramethylethylenediamine (TMEDA) and the like.
- TEDA tetramethylethylenediamine
- the amount used is preferably 0.01 to 2.0 equivalents with respect to the total number of leaving groups L contained in the compound (A) from the viewpoint of improving the yield of the target product. More preferably 0.1 to 1.2 equivalents.
- the reaction of this production method is usually carried out in a solvent.
- the solvent can be appropriately selected from the solvents capable of dissolving the compound (A) and the Grignard reagent.
- the solvent may be a mixed solvent of one type alone or a combination of two or more types.
- the solvent is not particularly limited as long as it is an inert solvent for the reaction.
- ether solvents such as diethyl ether, tetrahydrofuran and dioxane are preferable, and tetrahydrofuran is more preferable.
- the compound (A) is a compound having a relatively high fluorine atom content
- a mixed solvent in which the ether solvent and the fluorine solvent are combined is preferable.
- the fluorocarbon solvent include hydrofluorocarbons (1H, 4H-perfluorobutane, 1H-perfluorohexane, 1,1,1,3,3-pentafluorobutane, 1,1,2,2,3,3).
- Hydrochlorofluoroolefins ((Z) -1-chloro-2,3,3,4,5,5-heptafluoro-1-pentene (HCFO-1437dycc (Z) form), (E)- 1-Chloro-2,3,3,4,5,5-heptafluoro-1-pentene (HCFO-1437dycc (E) form), (Z) -1-chloro-2,3,3-trifluoro -1-Propen (HCFO-1233yd (Z) form), (E) -1-chloro-2,3,3-trifluoro-1-propen (HCFO-1233yd (E) form), etc.), Fluorocarbon-containing aromatics Examples thereof include compounds (perfluorobenzene, m-bis (trifluoromethyl) benzene (SR-solvent), p-bis (trifluoromethyl) benzene, etc.).
- This production method can be carried out, for example, by preparing a solution containing the compound (A), adding a transition metal compound and a ligand if necessary, and then adding a separately prepared Grignard reagent solution.
- the reaction temperature of the compound (A) and the Grignard reagent may be appropriately adjusted according to the combination of the compound (A) and the Grignard reagent.
- the temperature may be ⁇ 20 ° C. to 66 ° C. (boiling point of tetrahydrofuran), preferably ⁇ 20 ° C. to 40 ° C.
- Example 1 Production of fluorine-containing compound (1)
- the compound (A1-1) 241 mg), CuCl 2 (12.1 mg), and a 1,3-butadiene THF solution (2.0 M, 0.25 mL) are added, cooled to 10 ° C., and then n-butylmagnesium chloride. (0.88 M, 5.1 mL) of THF was added dropwise, and the mixture was stirred at room temperature. After cooling to 0 ° C., 1M hydrochloric acid was added, and the mixture was extracted with AE-3000. After adding sodium sulfate and drying, filtration and concentration were carried out, and 84.0 mg of the following fluorine-containing compound (1) was obtained by flash column chromatography using silica gel.
- the THF is tetrahydrofuran.
- Example 2 to 9 Method for producing fluorine-containing compound (1)
- the fluorine-containing compound (1) was produced in the same manner as in Example 1 except that the blending amounts of n-butylmagnesium chloride, 1,3-butadiene, and CuCl 2 were changed as shown in Table 1 below. ..
- Example 10 Method for producing fluorine-containing compound (1)
- CuCl was used instead of CuCl 2
- the fluorine-containing compound (1) was produced in the same manner as in Example 1 except that the blending amount was changed as shown in Table 1 below.
- Example 11 Production of fluorine-containing compound
- Triphenylphosphine and carbon tetrabromide were added to 1H, 1H-Tridecafluoro-1-heptanol and reacted in dichloromethane to synthesize the following compound (X1), but the compound (X1) was unstable and decomposed during purification. I went back to alcohol. Therefore, it was found that it is not suitable for the synthesis of the fluorine-containing compound (1).
- Table 1 shows the blending ratio of each component and the yield of the obtained target product in the synthesis of Examples 1 to 10.
- e. q. (Equivalent) and mol% are based on the number of triflate groups in the electrophile.
- a hyphen (-) in the table indicates that it is not added.
- Examples 1 and 3 include reacting a compound (A1-1), which is a compound having a partial structure represented by the formula (a), with a Grignard reagent in the presence of a transition metal compound.
- A1-1 a compound having a partial structure represented by the formula (a)
- a Grignard reagent a compound having a partial structure represented by the formula (a)
- the target fluorine-containing compound can be synthesized under relatively mild reaction conditions.
- Examples 12 to 13 below show that various compounds can be synthesized by this production method.
- fluorine-containing compounds used in various fields such as pesticides, pharmaceuticals, and functional materials can be synthesized under relatively mild reaction conditions using easily available compounds. Further, for example, by using a Grignard reagent having a carbon-carbon double bond, a double bond can be easily added to the compound (A), and a compound useful as a raw material for synthesizing various compounds can be obtained. Obtainable.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
例えば特許文献1には、オレフィン化合物にペルフルオロアルキルブロミドをラジカル反応で付加する、含フッ素化合物の製造方法が開示されている。
上記特許文献2の求電子剤は入手が容易でなかった。
また上記非特許文献1の求電子性ペルフルオロアルキル化剤は合成に多段階の工程が必要であり、収率が低くなり、また求電子剤として高価なものであった。
[1] 下記式(a)で表される部分構造を有する化合物と、
グリニャール試薬とを、遷移金属化合物存在下で反応させることを含む、
含フッ素化合物の製造方法。
-CF2-CH2-L (a)
ただし、式中、Lはスルホナート基である。
G1-CF2-CH2-L 式(A1)
L-CH2(-CF2-G2)n-CF2-CH2-L 式(A2)
ただし、式中、
G1は、(ポリ)オキシフルオロアルキレン鎖を有する1価の基、水素原子、アルキル基、又はフルオロアルキル基であり、
G2は、(ポリ)オキシフルオロアルキレン鎖を有する2価の基、単結合、アルキレン基、又はフルオロアルキレン基であり、
Lはスルホナート基であって、式(A2)において複数あるLは、各々同一であっても異なっていてもよく、
nは0又は1である。
nが1であって、G2が(ポリ)オキシフルオロアルキレン鎖を有する2価の基、単結合、若しくはペルフルオロアルキレン基である、[2]に記載の含フッ素化合物の製造方法。
R-MgX 式(B)
ただし、式中、Rは置換基を有していてもよく、炭素鎖中にヘテロ原子を有していてもよい炭化水素基であり、Xはハロゲン原子である。
R1-CH2-MgX 式(B1)
ただし、式中、R1は、水素原子であるか、又は置換基を有していてもよく、炭素鎖中にヘテロ原子を有していてもよい炭化水素基であり、Xはハロゲン原子である。
「(ポリ)オキシフルオロアルキレン」とは、オキシフルオロアルキレンとポリオキシフルオロアルキレンとの総称である。
ペルフルオロアルキル基とは、アルキル基の水素原子が全てフッ素原子で置換された基を意味する。またフルオロアルキル基とは、パーシャルフルオロアルキル基とペルフルオロアルキル基とを合わせた総称である。パーシャルフルオロアルキル基とは、水素原子の1個以上がフッ素原子で置換され、かつ、水素原子を1個以上有するアルキル基である。
すなわちフルオロアルキル基は1個以上のフッ素原子を有するアルキル基である。
数値範囲を示す「~」は、その前後に記載された数値を下限値及び上限値として含むことを意味する。
本発明の含フッ素化合物の製造方法(以下、「本製造方法」とも記す。)は、前記式(a)で表される部分構造を有する化合物と、グリニャール試薬とを、遷移金属化合物存在下で反応させることを含む。
R-MgX 式(B)
ただし、式中、Rは置換基を有していてもよく、炭素鎖中にヘテロ原子を有していてもよい炭化水素基であり、Xはハロゲン原子である。
-CF2-CH2-L + R-MgX → -CF2-CH2-R
ただし、スキーム(1)中の各符号は前述のとおりである。
n5個の部分構造(a)を有する化合物(A)としては、下式(An5)で表される化合物が挙げられる。
G(-CF2-CH2-L)n5 式(An5)
ただし、式中
Gは、水素原子(ただしn5=1)、又はn5価の有機基であり、
n5は、1以上の整数であり、
Lは、前述のとおりである。
当該炭化水素基としては、直鎖又は分岐のアルキル基、シクロアルキル基、アリール基及びこれらの組み合わせが挙げられる。炭化水素基は炭素鎖中に二重結合又は三重結合を有していてもよい。組み合わせとしては、例えばアルキル基とアリール基が直接、ヘテロ原子を介して、又は炭化水素基以外の結合を介して結合したものなどが挙げられる。
ヘテロ原子としては、酸素原子、窒素原子、硫黄原子、ケイ素原子などが挙げられる。
ヘテロ原子は環構造の一部を構成していてもよい。また、ヘテロ原子のうち、窒素原子、硫黄原子、及びケイ素原子は、3つ以上の炭素原子と結合する分岐点を構成していてもよい。
炭化水素基以外の結合としては、例えば、アミド結合、ウレア結合、ウレタン結合などが挙げられる。
炭化水素基が有していてもよい置換基としては、ハロゲン原子、ヒドロキシ基、アミノ基、ニトロ基、スルホ基などが挙げられ、本製造方法における化合物の安定性の点から、ハロゲン原子が好ましく、中でもフッ素原子がより好ましい。
環構造は、置換基として、ハロゲン原子、エーテル結合を有していてもよいアルキル基、シクロアルキル基、アルケニル基、アリル基、アルコキシ基、オキソ基等を有してもよい。
G1-CF2-CH2-L 式(A1)
L-CH2(-CF2-G2)n-CF2-CH2-L 式(A2)
ただし、式中、
G1は、(ポリ)オキシフルオロアルキレン鎖を有する1価の基、水素原子、アルキル基、又はフルオロアルキル基であり、
G2は、(ポリ)オキシフルオロアルキレン鎖を有する2価の基、単結合、アルキレン基、又はフルオロアルキレン基であり、
Lはスルホナート基であって、式(A2)において複数あるLは、各々同一であっても異なっていてもよく、
nは0又は1である。
Rf0O-[(Rf1O)m1(Rf2O)m2(Rf3O)m3(Rf4O)m4(Rf5O)m5(Rf6O)m6]-(Rf7)m7- 式(G1-1)
ただし、
Rf0は、炭素数1~20のフルオロアルキル基であり、
Rf1は、炭素数1のフルオロアルキレン基であり、
Rf2は、炭素数2のフルオロアルキレン基であり、
Rf3は、炭素数3のフルオロアルキレン基であり、
Rf4は、炭素数4のフルオロアルキレン基であり、
Rf5は、炭素数5のフルオロアルキレン基であり、
Rf6は、炭素数6のフルオロアルキレン基であり、
Rf7は、炭素数1~6のフルオロアルキレン基であり、
m1、m2、m3、m4、m5、m6は、それぞれ独立に0又は1以上の整数を表し、m7は0又は1の整数であり、m1+m2+m3+m4+m5+m6+m7は0~200の整数である。
なお、式(G1-1)における(Rf1O)~(Rf6O)の結合順序は任意である。
式(G1-1)のm1~m6は、それぞれ、(Rf1O)~(Rf6O)の個数を表すものであり、配置を表すものではない。例えば、(Rf5O)m5は、(Rf5O)の数がm5個であることを表し、(Rf5O)m5のブロック配置構造を表すものではない。同様に、(Rf1O)~(Rf6O)の記載順は、それぞれの単位の結合順序を表すものではない。
m7が0のとき、G1のCF2に結合する末端は-O-である。m7が1のとき、G1のCF2に結合する末端は炭素原子(Rf7の末端の炭素原子)である。
-(O)m0-[(Rf1O)m1(Rf2O)m2(Rf3O)m3(Rf4O)m4(Rf5O)m5(Rf6O)m6]-(Rf7)m7- 式(G2-1)
ただし、m0は0又は1の整数であり、Rf1、Rf2、Rf3、Rf4、Rf5、Rf6、Rf7、m1、m2、m3、m4、m5、m6、及びm7は、前記G1におけるものと同様である。なお、式(G2-1)における(Rf1O)~(Rf6O)の結合順序は任意であり、前記式(G1-1)で説明したとおりである。
m7が0のとき、G2のCF2に結合する片側末端は-O-である。m7が1のとき、G2のCF2に結合する片側末端は炭素原子(Rf7の末端の炭素原子)である。また、m0が1のとき、G2のCF2に結合する片側末端は-O-である。m0が0のとき、G2のCF2に結合する片側末端は炭素原子(Rf1~Rf7のいずれかの末端の炭素原子)である。なお、m0とm7は各々独立に0又は1である。
G1-CF2-CH2-OH 式(A1-2)
HO-CH2(-CF2-G2)n-CF2-CH2-OH 式(A2-2)
ただし、式中のG1、G2及びnは前述のとおりである。
R-MgX 式(B)
ただし、式中、Rは置換基を有していてもよく、炭素鎖中にヘテロ原子を有していてもよい炭化水素基であり、Xはハロゲン原子である。
Rにおける炭化水素基は、直鎖アルキル基、分岐を有するアルキル基、シクロアルキル基、アリール基、及びこれらの組み合わせからなる基を基本骨格として、ヘテロ原子を有していてもよく、置換基を有していてもよく、二重結合又は三重結合を有していてもよい。
ヘテロ原子としては、窒素原子(N)、酸素原子(O)、硫黄原子(S)、ケイ素原子(Si)などが挙げられ、化合物の安定性の点から、N、O又はSが好ましい。また置換基としては、フッ素原子が好ましい。本製造方法における収率を向上するなどの点から、Rの炭素数は1~30が好ましく、1~20がより好ましく1~15がさらに好ましい。
R1-CH2-MgX 式(B1)
ただし、式中、R1は、水素原子であるか、又は置換基を有していてもよく、炭素鎖中にヘテロ原子を有していてもよい炭化水素基であり、Xはハロゲン原子である。R1は、Rから-CH2を除いた残基であることが好ましい。
R-X 式(B2)
ただし、R及びXは前述のとおりである。
上記配位子としては、例えば、1,3-ブタジエン、フェニルプロピン、テトラメチルエチレンジアミン(TMEDA)などが挙げられる。配位子を使用する場合、使用量は目的物の収率向上の点から、化合物(A)が有する脱離基Lの総数に対して、0.01~2.0当量用いることが好ましく、0.1~1.2当量がより好ましい。
例えば、化合物(A)が比較的フッ素原子含有量(化合物分子の分子量に占めるフッ素原子の割合)の低い化合物である場合、溶媒としては反応に不活性な溶媒であれば特に限定されない。反応に不活性な溶媒としては、中でも、ジエチルエーテル、テトラヒドロフラン、ジオキサン等のエーテル系溶媒が好ましく、テトラヒドロフランがより好ましい。
また、化合物(A)が比較的フッ素原子含有量の高い化合物である場合には、前記エーテル系溶媒と、フッ素系溶媒とを組み合わせた混合溶媒が好ましい。
フッ素系溶媒としては、例えば、ハイドロフルオロカーボン類(1H,4H-ペルフルオロブタン、1H-ペルフルオロヘキサン、1,1,1,3,3-ペンタフルオロブタン、1,1,2,2,3,3,4-ヘプタフルオロシクロペンタン、2H,3H-ペルフルオロペンタン等)、ハイドロクロロフルオロカーボン類(3,3-ジクロロ-1,1,1,2,2-ペンタフルオロプロパン、1,3-ジクロロ-1,1,2,2,3-ペンタフルオロプロパン(HCFC-225cb)等)、ハイドロフルオロエーテル類(CF3CH2OCF2CF2H(AE-3000)、(ペルフルオロブトキシ)メタン、(ペルフルオロブトキシ)エタン等)、ハイドロクロロフルオロオレフィン類((Z)-1-クロロ-2,3,3,4,4,5,5-ヘプタフルオロ-1-ペンテン(HCFO-1437dycc(Z)体)、(E)-1-クロロ-2,3,3,4,4,5,5-ヘプタフルオロ-1-ペンテン(HCFO-1437dycc(E)体)、(Z)-1-クロロ-2,3,3-トリフルオロ-1-プロペン(HCFO-1233yd(Z)体)、(E)-1-クロロ-2,3,3-トリフルオロ-1-プロペン(HCFO-1233yd(E)体)等)、含フッ素芳香族化合物類(ペルフルオロベンゼン、m-ビス(トリフルオロメチル)ベンゼン(SR-ソルベント)、p-ビス(トリフルオロメチル)ベンゼン等)等が挙げられる。
化合物(A)とグリニャール試薬との反応温度は、化合物(A)とグリニャール試薬との組み合わせに応じて適宜調整すればよい。例えば、-20℃~66℃(テトラヒドロフランの沸点)とすればよく、-20℃~40℃が好ましい。
1H,1H-Tridecafluoro-1-heptanol(10.5g)、ジクロロメタン(100mL)、トリエチルアミン(6.0mL)を加え、0℃に冷却した。トリフルオロメタンスルホン酸無水物(5.6mL)を加え、室温で撹拌した。水で洗浄した後、硫酸ナトリウムで乾燥した。ろ過後、溶媒を留去し、シリカゲルを用いたフラッシュカラムクロマトグラフィーを行うことで、下記化合物(A1-1)の4.73gを得た。
化合物(A1-1)のNMR測定結果を以下に示す。
1H-NMR(400MHz,Chloroform-d)δ 4.84(t,J=12.3Hz,2H).
19F-NMR(376MHz,Chloroform-d)δ -74.50,-81.04~-81.61(m),-120.19(t,J=14.3Hz),-122.08~-122.94(m),-122.94~-123.72(m),-126.21~-126.94(m).
前記化合物(A1-1)(241mg)、CuCl2(12.1mg)、1,3-ブタジエンTHF溶液(2.0M,0.25mL)を加え、10℃に冷却した後、n-ブチルマグネシウムクロリドのTHF溶液(0.88M,5.1mL)を滴下し、室温で撹拌した。0℃に冷却した後、1M塩酸を加え、AE-3000で抽出した。硫酸ナトリウムを加え乾燥させた後、ろ過と濃縮を行い、シリカゲルを用いたフラッシュカラムクロマトグラフィーによって、下記含フッ素化合物(1)を84.0mg得た。なお、THFはテトラヒドロフランである。
含フッ素化合物(1)のNMR測定結果を以下に示す。
1H-NMR(400MHz,Chloroform-d)δ 2.49~1.84(m,2H),1.63~1.11(m,6H),1.00~0.81(m,3H).
19F-NMR(376MHz,Chloroform-d)δ -81.57(t,J=9.7Hz),-115.20(ddd,J=18.7,14.6,4.6Hz),-122.73,-123.65,-124.35,-126.92.
上記例1において、n-ブチルマグネシウムクロリド、1,3-ブタジエン、CuCl2の配合量を下表1のように変更した以外は、例1と同様にして、含フッ素化合物(1)を製造した。
上記例1において、CuCl2の代わりにCuClを用い、配合量を下表1のよう変更した以外は例1と同様にして、含フッ素化合物(1)を製造した。
下記化合物(X1)を用いて、前記含フッ素化合物(1)の製造を試みた。
1H,1H-Tridecafluoro-1-heptanolにトリフェニルホスフィン、四臭化炭素を加え、ジクロロメタン中で反応させて、下記化合物(X1)を合成したが、当該化合物(X1)は不安定で精製時に分解しアルコールに戻った。そのため含フッ素化合物(1)の合成には不適であることが分かった。
なお、表1中のe.q.(当量)及びmol%は、求電子剤のトリフラート基の数を基準とする。表中のハイフン(-)は添加していないことを示す。
また、収率は、目的物を19F-NMRを用いて内部標準法(内部標準:ヘキサフルオロベンゼン)により定量し、下式により求めた。例1については単離収率も求めた(表1カッコ内)。
収率 = 目的物 / 化合物(A1-1) ×100[%]
下記例12~13では、本製造方法により種々の化合物が合成できることを示す。
(合成例12-1:化合物(12-1)の合成)
2,2,3,3-Tetrafluoro-1,4-butanediol(1.58g)、ジクロロメタン(100 mL)、ピリジン(2.2mL)を加え、0℃に冷却した。トリフルオロメタンスルホン酸無水物(7.18g)を加え、室温で3時間撹拌した。水で2度洗浄した後、硫酸ナトリウムで乾燥した。ろ過後、溶媒を留去し、ヘキサンを加えた。30分撹拌後、ろ過、減圧乾燥を行うことで、下記化合物(12-1)の3.70gを得た。
化合物(12-1)のNMR測定結果を以下に示す。
1H-NMR(400MHz,Chloroform-d)δ:4.93~4.75(m,4H).
19F-NMR(376MHz,Chloroform-d)δ:-74.68,-120.99~-121.24(m).
上記化合物(12-1)(213mg)、CuCl2(1.3mg)、を加え、10℃に冷却した後、n-ブチルマグネシウムクロリドのTHF溶液(0.88M, 5.1mL)を滴下し、室温で1時間撹拌した。0℃に冷却した後、1M塩酸を加え、AE-3000で抽出した。硫酸ナトリウムを加え乾燥させた後、ろ過と濃縮を行い、シリカゲルを用いたフラッシュカラムクロマトグラフィーによって、下記含フッ素化合物(2)を30.1mg得た。
化合物(2)のNMR測定結果を以下に示す。
1H-NMR(400MHz,Chloroform-d)δ:2.17~1.88(m,4H),1.60~1.31(m,12H),0.99~0.83(m,6H).
19F-NMR(376MHz,Chloroform-d)δ:-116.28~-116.59(m).
(合成例13-1:化合物(13-1)の合成)
国際公開2013/121984号の実施例7に記載の方法に従い、下記化合物(13-1)を得た。
CF3-O-(CF2CF2O-CF2CF2CF2CF2O)n(CF2CF2O)-CF2CF2CF2-CH2OH ・・・式(13-1)
繰り返し単位数nの平均値は13である。
前記化合物(13-1)(6.80g)、2,6-ルチジン(0.759g),AE-3000(28.0g)を加え、0℃で撹拌した。無水トリフルオロメタンスルホン酸(0.987g)を加えた後、室温で撹拌した。水で洗浄した後、溶媒を留去し、シリカゲルを用いたフラッシュカラムクロマトグラフィーを行うことで、下記化合物(13-2)を6.81g得た。
CF3-O-(CF2CF2O-CF2CF2CF2CF2O)n(CF2CF2O)-CF2CF2CF2-CH2OTf ・・・式(13-2)
繰り返し単位数nの平均値は13であり、OTfはトリフラート:-O-S(=O)2(-CF3)である。
1H-NMR(400MHz,Chloroform-d) δ(ppm):4.78(t,J=12.3Hz,2H).
19F-NMR(376MHz,Chloroform-d) δ(ppm):-55.28,-74.11,-82.86,-88.07,-90.20,-119.84,-125.28,-126.16.
DiethylDiallylmalonate(60.0g)、塩化リチウム(23.7g)、水(6.45g)、ジメチルスルホキシド(263g)を加え、160℃で撹拌した。室温まで冷却した後、水を加え、酢酸エチルで抽出した。ヘキサンを有機層に加え、飽和食塩水で洗浄し、硫酸ナトリウムで乾燥した。ろ過後、溶媒を留去することで、下記化合物(13-3)を39.5g得た。
1H-NMR(400MHz,Chloroform-d) δ(ppm):(ddt,J=17.1,10.1,7.0Hz,2H),5.06~4.94(m,4H),4.09(q,J=7.1Hz,2H),2.47(ddd,J=14.0,8.0,6.1Hz,1H),2.33(dt,J=14.9,7.5Hz,2H),2.22(dt,J=14.1,6.5Hz,2H),1.21(t,J=7.1Hz,3H).
THF(260mL)、ジイソプロピルアミン(29.8g)を加えた後、溶液を-78℃まで冷却した。n-ブチルリチウムヘキサン溶液(2.76M,96.6mL)を加え、0℃まで昇温した。撹拌した後、-78℃まで冷却し、リチウムジイソプロピルアミド(LDA)のTHF溶液を調製した。上記化合物(13-3)(39.5g)をTHF溶液に加え、撹拌した後、臭化アリル(24.1mL)を加えた。0℃に昇温し、1M塩酸(100mL)を加え、THFを減圧留去した。ジクロロメタンで抽出した後、硫酸ナトリウムを加えた。ろ過後、溶媒を留去し、シリカゲルを用いたフラッシュカラムクロマトグラフィーを行うことで、化合物(13-4)を45.0g得た。
1H-NMR(400MHz,Chloroform-d) δ(ppm):5.74~5.62(m,3H),5.04(dd,J=13.6,1.9Hz,6H),4.10(q,J=7.1Hz,2H),2.29(d,J=7.4Hz,6H),1.22(t,J=7.1Hz,3H).
上記化合物(13-4)(45.0g)をTHF(620mL)に溶解させ、0℃に冷却した。水素化リチウムアルミニウムのTHF溶液(104mL)を加え、撹拌した。水、15%水酸化ナトリウム水溶液を加え、室温で撹拌した後、ジクロロメタンで希釈した。ろ過後、溶媒を留去し、シリカゲルを用いたフラッシュカラムクロマトグラフィーを行うことで、下記化合物(13-5)を31.3g得た。
1H-NMR(400MHz,Chloroform-d) δ(ppm):5.90~5.76(m,3H),5.10~5.02(m,6H),3.38(s,2H),2.03(dt,J=7.5,1.2Hz,6H),1.45(s,1H).
アセトニトリル(380mL)、前記化合物(13-5)(31.3g)、トリフェニルホスフィン(64.3g)、四塩化炭素(33.9g)を加え、90℃で撹拌した。濃縮後、酢酸エチル/ヘキサンを加え撹拌した。ろ過、濃縮後、蒸留によって、下記化合物(13-6)を28.2g得た。
1H-NMR(400MHz,Chloroform-d) δ(ppm):5.83~5.67(m,3H),5.16~5.01(m,6H),3.32(s,2H),2.05(dt,J=7.5,1.1Hz,6H).
マグネシウム(2.36g)にTHF(35mL)、ヨウ素(0.180g)を加えて、室温で撹拌した。前記化合物(13-6)(14.0g)のTHF(35mL)溶液を加え、2時間加熱還流することで、下記化合物(13-7)の溶液(1.0M)を調製した。
CuCl2(16.0mg)、1-フェニル-1-プロピン(0.052g)、1,3-ビストリフルオロメチルベンゼン(24mL)、前記化合物(13-1)(4.00g)を加えた後、前記化合物(13-7)(5.0mL,1.0M)を加えた。室温で撹拌した後、1M塩酸で洗浄し、硫酸ナトリウムで乾燥した。ろ過後、溶媒を留去し、AC-6000を加えた。MeOHで洗浄した後、シリカゲルを用いたフラッシュカラムクロマトグラフィーを行うことで、下記含フッ素化合物(3)を0.139g得た。なお、AC-6000はC6F13C2H5である。
1H-NMR(400MHz,Chloroform-d) δ(ppm):5.77(ddt,J=14.9,10.7,7.4Hz,3H),5.07~4.99(m,6H),2.19~2.05(m,2H),1.97(d,J=7.4Hz,6H),1.59~1.50(m,2H).
19F-NMR(376MHz,Chloroform-d) δ(ppm):-55.29,-82.90,-88.13,-90.24(d,J=8.0Hz),-114.62,-125.34,-126.49.
Claims (8)
- 下記式(a)で表される部分構造を有する化合物と、
グリニャール試薬とを、遷移金属化合物存在下で反応させることを含む、
含フッ素化合物の製造方法。
-CF2-CH2-L 式(a)
ただし、式中、Lはスルホナート基である。 - 前記式(a)で表される部分構造を有する化合物が、下記式(A1)又は式(A2)で表される化合物である、請求項1に記載の含フッ素化合物の製造方法。
G1-CF2-CH2-L 式(A1)
L-CH2(-CF2-G2)n-CF2-CH2-L 式(A2)
ただし、式中、
G1は、(ポリ)オキシフルオロアルキレン鎖を有する1価の基、水素原子、アルキル基、又はフルオロアルキル基であり、
G2は、(ポリ)オキシフルオロアルキレン鎖を有する2価の基、単結合、アルキレン基、又はフルオロアルキレン基であり、
Lはスルホナート基であって、式(A2)において複数あるLは、各々同一であっても異なっていてもよく、
nは0又は1である。 - 式(A1)において、G1が(ポリ)オキシフルオロアルキレン鎖を有する1価の基、又はペルフルオロアルキル基である、請求項2に記載の含フッ素化合物の製造方法。
- 式(A2)において、nが0であるか、又は、
nが1であって、G2が(ポリ)オキシフルオロアルキレン鎖を有する2価の基、単結合、若しくはペルフルオロアルキレン基である、請求項2に記載の含フッ素化合物の製造方法。 - 前記グリニャール試薬が、下記式(B)で表される、請求項1~4のいずれか一項に記載の含フッ素化合物の製造方法。
R-MgX 式(B)
ただし、式中、Rは置換基を有していてもよく、炭素鎖中にヘテロ原子を有していてもよい炭化水素基であり、Xはハロゲン原子である。 - 前記グリニャール試薬が、下記式(B1)で表される、請求項5に記載の含フッ素化合物の製造方法。
R1-CH2-MgX 式(B1)
ただし、式中、R1は、水素原子であるか、又は置換基を有していてもよく、炭素鎖中にヘテロ原子を有していてもよい炭化水素基であり、Xはハロゲン原子である。 - Lがトリフラート基である、請求項1~6のいずれか一項に記載の含フッ素化合物の製造方法。
- 前記遷移金属化合物が銅を含む、請求項1~7のいずれか一項に記載の含フッ素化合物の製造方法。
Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1020227011860A KR20220064992A (ko) | 2019-09-20 | 2020-09-17 | 함불소 화합물의 제조 방법 |
EP20864465.8A EP4032872A4 (en) | 2019-09-20 | 2020-09-17 | METHOD FOR PRODUCING FLUORINE-CONTAINING COMPOUNDS |
JP2021546960A JP7468536B2 (ja) | 2019-09-20 | 2020-09-17 | 含フッ素化合物の製造方法 |
CN202080065496.4A CN114423727A (zh) | 2019-09-20 | 2020-09-17 | 含氟化合物的制造方法 |
US17/698,102 US20220204444A1 (en) | 2019-09-20 | 2022-03-18 | Method of manufacturing fluorine-containing compound |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2019171578 | 2019-09-20 | ||
JP2019-171578 | 2019-09-20 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US17/698,102 Continuation US20220204444A1 (en) | 2019-09-20 | 2022-03-18 | Method of manufacturing fluorine-containing compound |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2021054414A1 true WO2021054414A1 (ja) | 2021-03-25 |
Family
ID=74883257
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP2020/035360 WO2021054414A1 (ja) | 2019-09-20 | 2020-09-17 | 含フッ素化合物の製造方法 |
Country Status (7)
Country | Link |
---|---|
US (1) | US20220204444A1 (ja) |
EP (1) | EP4032872A4 (ja) |
JP (1) | JP7468536B2 (ja) |
KR (1) | KR20220064992A (ja) |
CN (1) | CN114423727A (ja) |
TW (1) | TW202116713A (ja) |
WO (1) | WO2021054414A1 (ja) |
Citations (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH10204004A (ja) * | 1997-01-23 | 1998-08-04 | Sumitomo Chem Co Ltd | アリール置換芳香族類の製造方法 |
JPH11228454A (ja) * | 1998-02-17 | 1999-08-24 | Sumitomo Chem Co Ltd | アルキニル置換アリールブロミド類の製造方法 |
JP2004051595A (ja) * | 2002-07-23 | 2004-02-19 | Shin Etsu Chem Co Ltd | 片末端にビニリデン基を有するパーフルオロアルキレンエーテル誘導体 |
WO2005075384A1 (ja) * | 2004-02-10 | 2005-08-18 | Japan Science And Technology Agency | 芳香族化合物の製造方法 |
JP2008214199A (ja) * | 2007-02-28 | 2008-09-18 | Chisso Corp | 鉄触媒による芳香族化合物の製造方法 |
JP2013060417A (ja) * | 2011-08-25 | 2013-04-04 | Jnc Corp | ペルフルオロアルキル鎖を有する液晶化合物、液晶組成物および液晶表示素子 |
WO2013121984A1 (ja) | 2012-02-17 | 2013-08-22 | 旭硝子株式会社 | 含フッ素エーテル化合物、含フッ素エーテル組成物およびコーティング液、ならびに表面処理層を有する基材およびその製造方法 |
CN103265403A (zh) * | 2013-05-03 | 2013-08-28 | 西安彩晶光电科技股份有限公司 | 一种4,4,4-三氟丁醇的合成方法 |
JP2018043940A (ja) | 2016-09-13 | 2018-03-22 | 国立大学法人お茶の水女子大学 | 含フッ素化合物の製造方法 |
WO2018228975A1 (en) * | 2017-06-12 | 2018-12-20 | Novaliq Gmbh | Process for the preparation of semifluorinated alkanes using grignard reagents |
JP2019171578A (ja) | 2018-03-27 | 2019-10-10 | 三菱ケミカル株式会社 | シリコーンゴム複合体及びそれを使用した成形体の製造方法 |
-
2020
- 2020-09-17 WO PCT/JP2020/035360 patent/WO2021054414A1/ja unknown
- 2020-09-17 KR KR1020227011860A patent/KR20220064992A/ko active Search and Examination
- 2020-09-17 CN CN202080065496.4A patent/CN114423727A/zh active Pending
- 2020-09-17 JP JP2021546960A patent/JP7468536B2/ja active Active
- 2020-09-17 EP EP20864465.8A patent/EP4032872A4/en active Pending
- 2020-09-18 TW TW109132436A patent/TW202116713A/zh unknown
-
2022
- 2022-03-18 US US17/698,102 patent/US20220204444A1/en active Pending
Patent Citations (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH10204004A (ja) * | 1997-01-23 | 1998-08-04 | Sumitomo Chem Co Ltd | アリール置換芳香族類の製造方法 |
JPH11228454A (ja) * | 1998-02-17 | 1999-08-24 | Sumitomo Chem Co Ltd | アルキニル置換アリールブロミド類の製造方法 |
JP2004051595A (ja) * | 2002-07-23 | 2004-02-19 | Shin Etsu Chem Co Ltd | 片末端にビニリデン基を有するパーフルオロアルキレンエーテル誘導体 |
WO2005075384A1 (ja) * | 2004-02-10 | 2005-08-18 | Japan Science And Technology Agency | 芳香族化合物の製造方法 |
JP2008214199A (ja) * | 2007-02-28 | 2008-09-18 | Chisso Corp | 鉄触媒による芳香族化合物の製造方法 |
JP2013060417A (ja) * | 2011-08-25 | 2013-04-04 | Jnc Corp | ペルフルオロアルキル鎖を有する液晶化合物、液晶組成物および液晶表示素子 |
WO2013121984A1 (ja) | 2012-02-17 | 2013-08-22 | 旭硝子株式会社 | 含フッ素エーテル化合物、含フッ素エーテル組成物およびコーティング液、ならびに表面処理層を有する基材およびその製造方法 |
CN103265403A (zh) * | 2013-05-03 | 2013-08-28 | 西安彩晶光电科技股份有限公司 | 一种4,4,4-三氟丁醇的合成方法 |
JP2018043940A (ja) | 2016-09-13 | 2018-03-22 | 国立大学法人お茶の水女子大学 | 含フッ素化合物の製造方法 |
WO2018228975A1 (en) * | 2017-06-12 | 2018-12-20 | Novaliq Gmbh | Process for the preparation of semifluorinated alkanes using grignard reagents |
JP2019171578A (ja) | 2018-03-27 | 2019-10-10 | 三菱ケミカル株式会社 | シリコーンゴム複合体及びそれを使用した成形体の製造方法 |
Non-Patent Citations (2)
Title |
---|
See also references of EP4032872A4 |
TERUO UMEMOTO: "Electrophilic Perfluoroalkylating Agents", CHEM. REV., vol. 96, 1996, pages 1757 - 1777 |
Also Published As
Publication number | Publication date |
---|---|
KR20220064992A (ko) | 2022-05-19 |
TW202116713A (zh) | 2021-05-01 |
CN114423727A (zh) | 2022-04-29 |
JP7468536B2 (ja) | 2024-04-16 |
EP4032872A4 (en) | 2023-10-25 |
JPWO2021054414A1 (ja) | 2021-03-25 |
EP4032872A1 (en) | 2022-07-27 |
US20220204444A1 (en) | 2022-06-30 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6396462B2 (ja) | フラン−2,5−ジメタノールおよび(テトラヒドロフラン−2,5−ジイル)ジメタノールのモノおよびジアルキルエーテルならびにその両親媒性誘導体 | |
KR20110019440A (ko) | 아폽토시스 프로모터 abt-263의 제조 방법 | |
CN114409515B (zh) | 一种偕二氟烯烃化合物的制备方法 | |
JP2007314546A (ja) | 五フッ化硫黄化合物とその製法および利用 | |
WO2022186271A1 (ja) | 含フッ素化合物の製造方法及び表面処理剤の製造方法 | |
WO2021054414A1 (ja) | 含フッ素化合物の製造方法 | |
JP6443708B2 (ja) | E−オレフィン化合物の製造方法 | |
WO2022186264A1 (ja) | 含フッ素化合物の製造方法及び含フッ素化合物 | |
JP3459892B2 (ja) | フッ素系界面活性化合物及びその製造方法 | |
JP2022116175A (ja) | 含フッ素シラン化合物 | |
JP6498048B2 (ja) | 含フッ素有機化合物及びこれとグリニャール試薬によるビアリール化合物の製造方法 | |
JPWO2018061677A1 (ja) | 置換ビス(トリフルオロビニル)ベンゼン化合物 | |
JP2010280637A (ja) | B−アリールボラジンの製造方法 | |
JP4092111B2 (ja) | 含フッ素芳香族化合物及びその製法 | |
JP7007999B2 (ja) | ジエステル化合物およびその製造方法 | |
JP4547898B2 (ja) | 求電子的パーフルオロアルキル化剤、及びパーフルオロアルキル化有機化合物の製造方法 | |
JPS62103034A (ja) | 含フツ素化合物およびその製造法 | |
JP2017122072A (ja) | 化合物の製造方法 | |
EP3438090A1 (en) | Novel method for producing hydroxamic acid derivative, and intermediate thereof | |
JPH08325226A (ja) | ビタミンd3 誘導体の製造法 | |
JP6461914B2 (ja) | 3−ハロアラインを生成するための合成中間体及びその合成方法 | |
JP4839678B2 (ja) | ジハロゲン化ビアリール誘導体の製造方法 | |
JP2015048322A (ja) | ビス(トリフルオロメチル)亜鉛・dmpu錯体、その製造方法並びにそれを用いたトリフルオロメチル基含有化合物の製造方法 | |
JP2019108304A (ja) | デスモシンおよびイソデスモシンの製造方法 | |
JP2019218279A (ja) | 有機シリコン化合物の製造方法、アミノアリール基含有有機シリコン化合物の製造方法および有機シリコン化合物 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 20864465 Country of ref document: EP Kind code of ref document: A1 |
|
ENP | Entry into the national phase |
Ref document number: 2021546960 Country of ref document: JP Kind code of ref document: A |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
ENP | Entry into the national phase |
Ref document number: 20227011860 Country of ref document: KR Kind code of ref document: A |
|
ENP | Entry into the national phase |
Ref document number: 2020864465 Country of ref document: EP Effective date: 20220420 |