CN117916223A - Method for producing tetrafluorothio-containing aryl compound - Google Patents
Method for producing tetrafluorothio-containing aryl compound Download PDFInfo
- Publication number
- CN117916223A CN117916223A CN202280061322.XA CN202280061322A CN117916223A CN 117916223 A CN117916223 A CN 117916223A CN 202280061322 A CN202280061322 A CN 202280061322A CN 117916223 A CN117916223 A CN 117916223A
- Authority
- CN
- China
- Prior art keywords
- group
- thio
- tetrafluorothio
- chlorotetrafluoroethyltetrafluoro
- lambda
- 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.)
- Pending
Links
- -1 aryl compound Chemical class 0.000 title claims abstract description 74
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 10
- 125000003118 aryl group Chemical group 0.000 claims abstract description 22
- 125000001153 fluoro group Chemical group F* 0.000 claims abstract description 20
- 125000001424 substituent group Chemical group 0.000 claims abstract description 18
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 14
- 238000006243 chemical reaction Methods 0.000 claims abstract description 13
- 239000003999 initiator Substances 0.000 claims abstract description 13
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 claims abstract description 12
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 11
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 10
- 125000001309 chloro group Chemical group Cl* 0.000 claims abstract description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 8
- 238000000034 method Methods 0.000 claims description 24
- 238000007259 addition reaction Methods 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 10
- 125000002252 acyl group Chemical group 0.000 claims description 9
- 239000000460 chlorine Substances 0.000 claims description 8
- 125000005843 halogen group Chemical group 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 125000003277 amino group Chemical group 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 230000002194 synthesizing effect Effects 0.000 claims description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 86
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 50
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 28
- 238000003818 flash chromatography Methods 0.000 description 24
- 230000015572 biosynthetic process Effects 0.000 description 23
- 238000003786 synthesis reaction Methods 0.000 description 23
- 238000004293 19F NMR spectroscopy Methods 0.000 description 22
- 150000001875 compounds Chemical class 0.000 description 22
- 238000005160 1H NMR spectroscopy Methods 0.000 description 20
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 20
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 20
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 239000007788 liquid Substances 0.000 description 18
- 239000000741 silica gel Substances 0.000 description 18
- 229910002027 silica gel Inorganic materials 0.000 description 18
- 238000000746 purification Methods 0.000 description 16
- 239000000243 solution Substances 0.000 description 13
- PYLWMHQQBFSUBP-UHFFFAOYSA-N monofluorobenzene Chemical compound FC1=CC=CC=C1 PYLWMHQQBFSUBP-UHFFFAOYSA-N 0.000 description 12
- 235000019439 ethyl acetate Nutrition 0.000 description 11
- QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 10
- 239000012043 crude product Substances 0.000 description 10
- 150000003254 radicals Chemical class 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 8
- YTZKOQUCBOVLHL-UHFFFAOYSA-N tert-butylbenzene Chemical compound CC(C)(C)C1=CC=CC=C1 YTZKOQUCBOVLHL-UHFFFAOYSA-N 0.000 description 8
- BFKJFAAPBSQJPD-UHFFFAOYSA-N tetrafluoroethene Chemical group FC(F)=C(F)F BFKJFAAPBSQJPD-UHFFFAOYSA-N 0.000 description 8
- 239000007787 solid Substances 0.000 description 7
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 229920006395 saturated elastomer Polymers 0.000 description 6
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- XGCDHPDIERKJPT-UHFFFAOYSA-N [F].[S] Chemical group [F].[S] XGCDHPDIERKJPT-UHFFFAOYSA-N 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- OZAIFHULBGXAKX-VAWYXSNFSA-N AIBN Substances N#CC(C)(C)\N=N\C(C)(C)C#N OZAIFHULBGXAKX-VAWYXSNFSA-N 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- IPBVNPXQWQGGJP-UHFFFAOYSA-N acetic acid phenyl ester Natural products CC(=O)OC1=CC=CC=C1 IPBVNPXQWQGGJP-UHFFFAOYSA-N 0.000 description 4
- 150000001336 alkenes Chemical class 0.000 description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 239000011737 fluorine Substances 0.000 description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
- 229940049953 phenylacetate Drugs 0.000 description 4
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 3
- WYGWHHGCAGTUCH-UHFFFAOYSA-N 2-[(2-cyano-4-methylpentan-2-yl)diazenyl]-2,4-dimethylpentanenitrile Chemical compound CC(C)CC(C)(C#N)N=NC(C)(C#N)CC(C)C WYGWHHGCAGTUCH-UHFFFAOYSA-N 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 230000005587 bubbling Effects 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- 229910052717 sulfur Inorganic materials 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- 239000004342 Benzoyl peroxide Substances 0.000 description 2
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 2
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- KYIKRXIYLAGAKQ-UHFFFAOYSA-N abcn Chemical compound C1CCCCC1(C#N)N=NC1(C#N)CCCCC1 KYIKRXIYLAGAKQ-UHFFFAOYSA-N 0.000 description 2
- 239000003905 agrochemical Substances 0.000 description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 description 2
- 235000019400 benzoyl peroxide Nutrition 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
- 239000007810 chemical reaction solvent Substances 0.000 description 2
- ZQMIGQNCOMNODD-UHFFFAOYSA-N diacetyl peroxide Chemical compound CC(=O)OOC(C)=O ZQMIGQNCOMNODD-UHFFFAOYSA-N 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 125000001183 hydrocarbyl group Chemical group 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 229910052742 iron Inorganic materials 0.000 description 2
- 239000012046 mixed solvent Substances 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 239000011368 organic material Substances 0.000 description 2
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
- 150000002978 peroxides Chemical class 0.000 description 2
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 2
- 239000002798 polar solvent Substances 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 125000004434 sulfur atom Chemical group 0.000 description 2
- SCHZCUMIENIQMY-UHFFFAOYSA-N tris(trimethylsilyl)silicon Chemical compound C[Si](C)(C)[Si]([Si](C)(C)C)[Si](C)(C)C SCHZCUMIENIQMY-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- FVQMJJQUGGVLEP-UHFFFAOYSA-N (2-methylpropan-2-yl)oxy 2-ethylhexaneperoxoate Chemical compound CCCCC(CC)C(=O)OOOC(C)(C)C FVQMJJQUGGVLEP-UHFFFAOYSA-N 0.000 description 1
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- HTHNTJCVPNKCPZ-UHFFFAOYSA-N 2-chloro-1,1-difluoroethene Chemical compound FC(F)=CCl HTHNTJCVPNKCPZ-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- LRRBANSQUYNJTH-UHFFFAOYSA-N 2-tert-butylperoxy-2-methylpropane;2-ethylhexanoic acid Chemical compound CCCCC(CC)C(O)=O.CC(C)(C)OOC(C)(C)C LRRBANSQUYNJTH-UHFFFAOYSA-N 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- YIIMEMSDCNDGTB-UHFFFAOYSA-N Dimethylcarbamoyl chloride Chemical compound CN(C)C(Cl)=O YIIMEMSDCNDGTB-UHFFFAOYSA-N 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 239000007875 V-40 Substances 0.000 description 1
- PRPAGESBURMWTI-UHFFFAOYSA-N [C].[F] Chemical group [C].[F] PRPAGESBURMWTI-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 125000003647 acryloyl group Chemical group O=C([*])C([H])=C([H])[H] 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
- 125000003943 azolyl group Chemical group 0.000 description 1
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 125000004369 butenyl group Chemical group C(=CCC)* 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
- 239000004202 carbamide Substances 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- IGBSAAYMSMEDQY-UHFFFAOYSA-N carboxy hydrogen carbonate;2-propan-2-ylperoxypropane Chemical compound OC(=O)OC(O)=O.CC(C)OOC(C)C IGBSAAYMSMEDQY-UHFFFAOYSA-N 0.000 description 1
- UUAGAQFQZIEFAH-UHFFFAOYSA-N chlorotrifluoroethylene Chemical compound FC(F)=C(F)Cl UUAGAQFQZIEFAH-UHFFFAOYSA-N 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- VBWIZSYFQSOUFQ-UHFFFAOYSA-N cyclohexanecarbonitrile Chemical compound N#CC1CCCCC1 VBWIZSYFQSOUFQ-UHFFFAOYSA-N 0.000 description 1
- LSXWFXONGKSEMY-UHFFFAOYSA-N di-tert-butyl peroxide Chemical compound CC(C)(C)OOC(C)(C)C LSXWFXONGKSEMY-UHFFFAOYSA-N 0.000 description 1
- QDGONURINHVBEW-UHFFFAOYSA-N dichlorodifluoroethylene Chemical compound FC(F)=C(Cl)Cl QDGONURINHVBEW-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000003682 fluorination reaction Methods 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 238000007306 functionalization reaction Methods 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 125000006038 hexenyl group Chemical group 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 235000020061 kirsch Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 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
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 238000001308 synthesis method Methods 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
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The present invention relates to a method for producing an aryl compound containing a tetrafluorothio group, wherein a reaction of adding a thioaryl compound represented by the following general formula (2) to an olefin compound represented by the following general formula (3) is performed in the presence of a radical initiator to synthesize an aryl compound containing a tetrafluorothio group represented by the following general formula (1) [ wherein a 1 is an aryl group which may have a substituent or a heteroaryl group which may have a substituent; r 1、R2、R3 and R 4 are each independently a hydrogen atom, a fluorine atom or a chlorine atom, and 2 or more of R 1、R2、R3 and R 4 are fluorine atoms. ].
Description
Technical Field
The present invention relates to a method for producing an aryl compound containing a tetrafluorothio group, wherein a tetrafluorothio group is introduced into an aryl group.
The present application claims priority based on japanese patent application No. 2021-154611 of the application in japan at 9/22/2021, japanese patent application No. 2021-171007 of the application in 2021/10/19/2022/3/23 and japanese patent application No. 2022-046766 of the application in japan, and the contents thereof are incorporated herein.
Background
The fluorine-containing compound shows specific material characteristics and biological activity. As an example, it was found that by introducing a fluorine atom or a trifluoromethyl group into an organic compound, not only metabolic stability but also hydrophobicity can be improved. Therefore, the application of the compound having fluorine atoms is remarkable particularly in the development of pharmaceutical and agricultural chemicals. In recent years, from the viewpoint of high functionalization of fluorine-containing compounds, the subject has been moving to functional groups having greater effect of improving hydrophobicity. For example, sulfur-fluorine functional groups having a structure in which a plurality of fluorine atoms are bonded to hexavalent sulfur are attracting attention as being endowed with high hydrophobicity as compared with corresponding carbon-fluorine functional groups (non-patent document 1).
On the other hand, it is difficult to introduce sulfur-fluorine functional groups into conventional compounds, and therefore, although the sulfur-fluorine functional groups are attractive, the sulfur-fluorine functional groups have not been developed at a later time in application to pharmaceutical ingredients, organic materials, and the like for pharmaceuticals or agricultural chemicals. As a method of introducing pentafluoro-lambda 6 -sulfanyl (SF 5) as a sulfur-fluorine functional group, studies have been conducted. As a practical synthesis method of an aromatic SF 5 compound, a two-step synthesis using a chlorotetrafluoro- λ 6 -sulfanyl (SF 4 Cl) compound as an intermediate has been developed (patent document 1). Further, an aromatic SF 4CF3 compound was synthesized, and it was found to have a greater hydrophobicity than an aromatic SF 5 compound (non-patent document 2).
Prior art literature
Patent literature
Patent document 1: international publication No. 2010/014665
Non-patent literature
Non-patent document 1: savoie and Welch, CHEMICAL REVIEWS, vol.115, p.1130-1190.
Non-patent document 2: KIRSCH AND HAHN, EUR.J.ORG.CHEM.2006, vol.2006 (5), p.1125-1131.
Disclosure of Invention
The purpose of the present invention is to provide a novel method for producing a tetrafluorothio-containing aryl compound, wherein a tetrafluorothio group is introduced into an aryl group, with high efficiency.
The present inventors have found that an aryl compound containing a tetrafluorothio group can be synthesized in a single step by reacting an SF 4 Cl compound with a fluorine-substituted olefin in the presence of a radical initiator, and have completed the present invention.
Namely, the present invention is as follows.
[1] A process for producing a tetrafluorothio-containing aryl compound, comprising the step of synthesizing a tetrafluorothio-containing aryl compound represented by the following general formula (1) by the addition reaction of a thioaryl compound represented by the following general formula (2) with an olefin compound represented by the following general formula (3) in the presence of a radical initiator,
A1-SF4Cl (2)
[ Wherein A 1 is an aryl group which may have a substituent or a heteroaryl group which may have a substituent ]
[ Wherein R 1、R2、R3 and R 4 are each independently a hydrogen atom, a fluorine atom or a chlorine atom. Wherein, more than 2 of R 1、R2、R3 and R 4 are fluorine atoms. ]
[ Wherein A 1、R1、R2、R3 and R 4 are the same as described above ].
[2] The method for producing a tetrafluorothio-containing aryl compound according to the above [1], wherein the A 1 is an aryl group which may have 1 or more substituents selected from the group consisting of a halogen atom, an alkyl group, an alkenyl group, an aryl group, an alkoxy group, a hydroxyl group, a carboxyl group, an acyl group, a cyano group, an amino group and a nitro group.
[3] The process for producing a tetrafluorothio-containing aryl compound according to the above [1] or [2], wherein the above reaction is carried out at a temperature of-40 to 130 ℃.
[4] An aryl compound containing tetrafluorothio group represented by the following general formula (1),
[ Wherein A 1 is an aryl group which may have a substituent or a heteroaryl group which may have a substituent; r 1、R2、R3 and R 4 are each independently a hydrogen atom, a fluorine atom or a chlorine atom, and 2 or more of R 1、R2、R3 and R 4 are fluorine atoms. ].
According to the method of the present invention, an addition reaction of SF 4 Cl compound and fluorine substituted olefin can be performed in a single step, and an aryl compound containing tetrafluorothio group can be efficiently synthesized.
Detailed Description
In the present application and in the present specification, "C p1-p2" (p 1 and p2 are positive integers satisfying p1 < p 2) means a group having p1 to p2 carbon atoms.
In the present application and the description of the present application, the "C 1-6 alkyl" is an alkyl group having 1 to 6 carbon atoms, and may be a straight chain or a branched chain. Examples of the C 1-6 alkyl group include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, tert-pentyl, hexyl and the like.
In the present application and the description of the present application, "C 1-6 alkoxy" means a group having an oxygen atom bonded to the bonding end of a C 1-6 alkyl group. The C 1-6 alkoxy group may be straight chain or branched. Examples of the C 1-6 alkoxy group include methoxy, ethoxy, propoxy, butoxy, t-butoxy, pentoxy, hexoxy and the like.
In the present application and the description of the present application, "C 2-6 alkenyl" means a group in which at least 1 carbon-carbon bond of an alkyl group having 2 to 6 carbon atoms becomes an unsaturated bond. The C 2-6 alkenyl group may be straight-chain or branched. Examples of the C 2-6 alkenyl group include vinyl, allyl, butenyl, pentenyl, hexenyl, and the like.
In the present application and in the present specification, "C 2-7 acyl" refers to a group in which the hydrocarbyl moiety after removal of the carbonyl group from the acyl group is a C 1-6 alkyl group, a C 2-6 alkenyl group, an aryl group of a 5-or 6-membered ring, or a heteroaryl group of a 5-or 6-membered ring. The hydrocarbyl portion of the acyl group may be straight or branched. Examples of the C 2-7 acyl group include formyl, acetyl, propionyl, acryloyl, and benzoyl.
In the present application and the description of the present application, "halogen atom" means a fluorine atom, a chlorine atom, a bromine atom or an iodine atom. "halogen atom other than fluorine atom" means a chlorine atom, a bromine atom or an iodine atom. As examples of the "halogen atom other than fluorine atom", a chlorine atom or a bromine atom is preferable, and a chlorine atom is particularly preferable.
Hereinafter, "compound (n)" refers to a compound represented by formula (n).
Addition reaction of SF 4 Cl Compound with fluorine substituted olefins
The method for producing a tetrafluorothio group-containing aryl compound (hereinafter, sometimes referred to as "SF 4 -containing aryl compound") according to the present invention is to add a sulfur atom in the SF 4 Cl group in an SF 4 Cl group-containing aryl compound to a fluorine-substituted olefin. Specifically, the reaction of adding the thioaryl compound represented by the following general formula (2) to the olefin compound represented by the following general formula (3) is performed in the presence of a radical initiator. Thus, the tetrafluorothio-containing aryl compound (1) having higher hydrophobicity than the SF 5 -containing aryl compound was obtained.
In the general formulae (2) and (1), a 1 is an aryl group which may have a substituent or a heteroaryl group which may have a substituent. The aryl group is not particularly limited, and examples thereof include phenyl, naphthyl, anthracenyl, 9-fluorenyl and the like, and phenyl is particularly preferred. The heteroaryl group is not particularly limited, and examples thereof include pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, pyrazolyl, quinolinyl, isoquinolinyl, pyrrolyl, imidazolyl, indolyl, furyl, benzofuryl, thienyl, benzothienyl, and the like,Azolyl, i/>Oxazolyl, thiazolyl, isothiazolyl, and the like.
An "aryl group which may be substituted" is a group in which 1 or more, preferably 1 to 3, of the hydrogen atoms bonded to the carbon atom of the aryl group are substituted with other functional groups. Likewise, a "heteroaryl group which may be substituted" is a group in which 1 or more, preferably 1 to 3, of the hydrogen atoms bonded to a carbon atom of the heteroaryl group are substituted with other functional groups. When there are 2 or more substituents, the substituents may be the same or different from each other.
The aryl and heteroaryl groups of a 1 may have 1 or 2 or more substituents in addition to the sulfur atom for fluorination purposes. Examples of the substituent include a halogen atom, an alkyl group, an alkenyl group, an alkoxy group, an aryl group, an acyl group, a hydroxyl group, a carboxyl group, an alkoxycarbonyl group, an aryloxycarbonyl group, a cyano group, an amino group, and a nitro group. The alkyl group is preferably a C 1-6 alkyl group, the alkenyl group is preferably a C 2-6 alkyl group, the alkoxy group is preferably a C 1-6 alkoxy group, and the acyl group is preferably a C 2-7 acyl group. As the alkoxycarbonyl group, a group having an alkyl moiety of C 1-6 alkyl group is preferable, and a group having an alkyl moiety of C 1-3 alkyl group is more preferable. As the aryloxycarbonyl group, a group in which the aryl moiety is phenyl is preferable.
In the general formula (3), R 1、R2、R3 and R 4 are each independently a hydrogen atom, a fluorine atom or a chlorine atom. Wherein, more than 2 of R 1、R2、R3 and R 4 are fluorine atoms. Examples of the compound (3) include CF2＝CF2、CF2＝CFCl、CF2＝CHF、CF2＝CCl2、CF2＝CHCl、CF2＝CH2、CFCl＝CFCl、CFCl＝CHF、CHF＝CHF.
The amount of the thioaryl compound (2) added to the reaction system may be a stoichiometric amount or more. The amount of the thioaryl compound (2) used is preferably 1 to 10 equivalents, more preferably 1 to 6 equivalents, of the olefin compound (3) from the viewpoints of reaction efficiency and cost.
The addition reaction of the thioaryl compound (2) with the olefin compound (3) is carried out in the presence of a radical initiator. As the radical initiator, conventionally known initiators can be used. Specifically, for example, azo compounds, radical initiators of peroxides can be used. The radical initiator used in the addition reaction of the thioaryl compound represented by the general formula (2) and the olefin compound represented by the general formula (3) preferably contains an azo compound.
Examples of the radical initiator for azo compounds include azobisisobutyronitrile (hereinafter also referred to as "AIBN"), 2' -azobis-2-methylbutyronitrile, 2' -azobis-2, 4-dimethylvaleronitrile (ADVN), 2' -azobis-N-butyl-2-methylpropionamide, dimethyl-2, 2' -azobis-2-methylpropionamide, and 1,1' -azobis-cyclohexane-1-carbonitrile. From the viewpoint of solubility in the reaction system, AIBN, 2 '-azobis-2-methylbutanenitrile, 2' -azobis-2, 4-dimethylvaleronitrile are preferable.
Examples of the radical initiator for the peroxide include benzoyl peroxide, t-butyl peroxide, acetyl peroxide, diisopropyl peroxide dicarbonate, t-butyl peroxide-2-ethylhexanoate, 2-hexyl peroxide-2-ethylhexanoate, and 1, 3-tetramethylbutyl peroxide-2-ethylhexanoate. From the viewpoint of easy control of the reaction, benzoyl peroxide, t-butyl peroxy-2-ethylhexanoate, 2-hexyl peroxy-2-ethylhexanoate are preferable.
The addition reaction of the thioaryl compound (2) and the olefin compound (3) may be performed in a solvent inactive to the reaction. The non-active solvent is not particularly limited, but an aprotic polar solvent is preferable. Examples of aprotic polar solvents include acetonitrile (MeCN), N' -Dimethylformamide (DMF), N-dimethylacetamide, dimethylsulfoxide (DMSO), tetrahydrofuran (THF), dichloromethane (DCM), 1, 2-Dichloroethane (DCE), diethyl ether, and the like. The solvent used in the reaction may be a mixed solvent of two or more solvents.
The addition reaction is a reaction in which a reaction solution obtained by mixing the thioaryl compound (2), the olefin compound (3), and the radical initiator in a reaction solvent is allowed to react at an appropriate temperature and time. The addition reaction is carried out under mild conditions. For example, the reaction temperature is not particularly limited as long as it is a temperature at which the reaction solvent is liquid, and may be carried out at-40 to 130 ℃, preferably at 0 to 80 ℃, more preferably at 20 to 50 ℃, or at room temperature (0 to 30 ℃). For example, the addition reaction can produce the desired tetrafluorothio-containing aryl compound (1) in a substantially quantitative yield by reacting at 20 to 50 ℃ for less than 3 hours.
Examples
The present invention will be described below with reference to examples, but the present invention is not limited to these examples.
The NMR apparatus used in the analyses of examples and comparative examples was JNM-ECZ400S (400 MHz) manufactured by Japan electronics, and in 1 H NMR, tetramethylsilane was used as a reference value of 0PPM, and in 19 F NMR, C 6F6 was used as a reference value of-162 PPM.
Synthesis of tetrafluorothio-containing aryl Compound
An aryl compound containing a tetrafluorothio group is synthesized by the following synthesis procedure.
A solution of compound (1) (0.20 mmol) and VN (10 mol%) dissolved in DCE (0.1M) was stirred in a microwave flask (microwave vial,10 mL) under nitrogen and cooled to 0deg.C. Subsequently, tetrafluoroethylene (TFE) was filled into the solution (1.0 atm) by bubbling. After stirring on an oil bath at 40 ℃ for 72 hours, insoluble solids were removed by filtration, and the filtrate was evaporated under reduced pressure. The obtained crude product was purified by flash column chromatography (n-hexane/etoac=9/1 (volume ratio)) to give the objective compound (2).
EXAMPLE 1 Synthesis of (2-chlorotetrafluoroethyltetrafluoro-lambda 6 -thio) benzene
(2-Chlorotetrafluoroethyltetrafluoro-lambda 6 -thio) benzene is obtained from (chlorotetrafluoro-lambda 6 -thio) benzene according to the procedure described above. Purification by flash column chromatography on silica gel (n-hexane/etoac=9/1 (volume ratio)) gave (2-chlorotetrafluoroethyltetrafluoro- λ 6 -thio) benzene (0.024 g, yield 37%) as colorless crystals.
1H NMR(400MHz,CDCl3)δ7.71-7.83(m,2H),7.42-7.54(m,3H).
19F NMR(376MHz,CDCl3)δ47.7(m,4F),-67.9(t,J＝10.8Hz,2F),-90.8(m,2F).
EXAMPLE 2 Synthesis of 4- (2-chlorotetrafluoroethyltetrafluoro-lambda 6 -thio) nitrobenzene
4- (2-Chlorotetrafluoroethyltetrafluoro-lambda 6 -thio) nitrobenzene is obtained from 4- (chlorotetrafluoro-lambda 6 -thio) nitrobenzene according to the procedure described above. Purification by flash column chromatography on silica gel (n-hexane/etoac=9/1 (vol.)) gave 4- (2-chlorotetrafluoroethyltetrafluoro- λ 6 -thio) nitrobenzene as colorless crystals (0.040 g, yield 55%).
1H NMR(400MHz,CDCl3)δ8.33(d,J＝8.7Hz,2H),8.00(d,J＝9.2Hz,2H).
13C NMR(100MHz,CDCl3)δ159.4(quint,JC-F＝21.9Hz),149.2,127.7(quint,JC-F＝4.8Hz),124.2,122.1(tt,JC-F＝303.4,35.6Hz),121.3(ttquint,JC-F＝312.1,37.6,36.6Hz).
19F NMR(376MHz,CDCl3)δ48.0(m,4F),-68.1(t,J＝10.7Hz,2F),-90.7(m,2F).
EXAMPLE 3 Synthesis of 3- (2-chlorotetrafluoroethyltetrafluoro-lambda 6 -thio) nitrobenzene
3- (2-Chlorotetrafluoroethyltetrafluoro-lambda 6 -thio) nitrobenzene is obtained from 3- (chlorotetrafluoro-lambda 6 -thio) nitrobenzene according to the procedure described above. Purification by flash column chromatography on silica gel (n-hexane/etoac=9/1 (vol.)) gave 3- (2-chlorotetrafluoroethyltetrafluoro- λ 6 -thio) nitrobenzene as a colourless liquid (0.034 g, 46% yield).
1H NMR(400MHz,CDCl3)δ8.67(s,1H),8.41(d,J＝8.2Hz,1H),8.13(d,J＝8.2Hz,1H),7.71(t,J＝8.2Hz,1H).
19F NMR(376MHz,CDCl3)δ48.3(m,4F),-68.1(t,J＝10.8Hz,2F),-90.6(m,2F).
Example 4]4 Synthesis of- (2-chlorotetrafluoroethyltetrafluoro-lambda 6 -thio) fluorobenzene
According to the above procedure, 4- (2-chlorotetrafluoroethyltetrafluoro-lambda 6 -thio) fluorobenzene is obtained from 4- (chlorotetrafluoro-lambda 6 -thio) fluorobenzene. Purification by flash column chromatography on silica gel (n-hexane/etoac=9/1 (vol.)) gave 4- (2-chlorotetrafluoroethyltetrafluoro- λ 6 -thio) fluorobenzene (0.035 g, yield 51%) as a colorless liquid.
1H NMR(400MHz,CDCl3)δ7.77-7.82(m,2H),7.11-7.16(m,2H).
19F NMR(376MHz,CDCl3)δ49.0(m,4F),-68.0(t,J＝10.8Hz,2F),-90.7(m,2F).
Example 5]3 Synthesis of- (2-chlorotetrafluoroethyltetrafluoro-lambda 6 -thio) fluorobenzene
According to the above procedure, 3- (2-chlorotetrafluoroethyltetrafluoro-lambda 6 -thio) fluorobenzene is obtained from 3- (chlorotetrafluoro-lambda 6 -thio) fluorobenzene. Purification by flash column chromatography on silica gel (n-hexane/etoac=9/1 (volume ratio)) gave 3- (2-chlorotetrafluoroethyltetrafluoro- λ 6 -thio) fluorobenzene (0.012 g, yield 18%) as a colourless liquid.
1H NMR(400MHz,CDCl3)δ7.58-7.61(m,1H),7.50-7.55(m,1H),7.42-7.49(m,1H),7.20-7.26(m,1H).
19F NMR(376MHz,CDCl3)δ48.0(m,4F),-68.0(t,J＝10.8Hz,2F),-90.8(m,2F).
EXAMPLE 6 Synthesis of 2- (2-chlorotetrafluoroethyltetrafluoro-lambda 6 -thio) fluorobenzene
According to the above procedure, 2- (2-chlorotetrafluoroethyltetrafluoro-lambda 6 -thio) fluorobenzene is obtained from 2- (chlorotetrafluoro-lambda 6 -thio) fluorobenzene. Purification by flash column chromatography on silica gel (n-hexane/etoac=9/1 (vol)) gave 2- (2-chlorotetrafluoroethyltetrafluoro- λ 6 -thio) fluorobenzene (0.009 g, yield 13%) as a colourless liquid.
1H NMR(400MHz,CDCl3)δ7.79(m,1H),7.51(m,1H),7.19-7.26(m,2H).
19F NMR(376MHz,CDCl3)δ49.0(m,4F),-68.0(t,J＝10.8Hz,2F),-90.7(m,2F).
Example 7]4 Synthesis of- (2-chlorotetrafluoroethyltetrafluoro-lambda 6 -thio) chlorobenzene
According to the above procedure, 4- (2-chlorotetrafluoroethyltetrafluoro-lambda 6 -thio) chlorobenzene was obtained from 4- (chlorotetrafluoro-lambda 6 -thio) chlorobenzene. Purification by flash column chromatography on silica gel (n-hexane/etoac=9/1 (vol.)) gave 4- (2-chlorotetrafluoroethyltetrafluoro- λ 6 -thio) chlorobenzene (0.035 g, yield 50%) as a colourless liquid.
1H NMR(400MHz,CDCl3)δ7.72(d,J＝9.1Hz,2H),7.43(d,J＝9.1Hz,2H).
19F NMR(376MHz,CDCl3)δ48.4(m,4F),-68.0(t,J＝10.8Hz,2F),-90.7(m,2F).
Example 8]4 Synthesis of- (2-chlorotetrafluoroethyltetrafluoro-lambda 6 -thio) bromobenzene
Following the procedure described above, 4- (2-chlorotetrafluoroethyltetrafluoro- λ 6 -thio) bromobenzene is obtained from 4- (chlorotetrafluoro- λ 6 -thio) bromobenzene. Purification by flash column chromatography on silica gel (n-hexane/etoac=9/1 (vol.)) gave 4- (2-chlorotetrafluoroethyltetrafluoro- λ 6 -thio) bromobenzene as a colourless liquid (0.019 g, yield 24%).
1H NMR(400MHz,CDCl3)δ7.65(d,J＝9.1Hz,2H),7.60(d,J＝9.1Hz,2H).
19F NMR(376MHz,CDCl3)δ48.3(m,4F),-68.0(t,J＝10.8Hz,2F),-90.8(m,2F).
Example 9]4 Synthesis of Ethyl- (2-chlorotetrafluoroethyltetrafluoro-lambda 6 -thio) benzoate
According to the above procedure, ethyl 4- (2-chlorotetrafluoroethyltetrafluoro-lambda 6 -thio) benzoate was obtained from ethyl 4- (chlorotetrafluoro-lambda 6 -thio) benzoate. Purification by flash column chromatography on silica gel (n-hexane/etoac=9/1 (vol)) afforded ethyl 4- (2-chlorotetrafluoroethyltetrafluoro- λ 6 -thio) benzoate (0.038 g, yield 48%) as a colourless liquid.
1H NMR(400MHz,CDCl3)δ8.12(d,J＝8.7Hz,2H),7.85(d,J＝9.0Hz,2H),4.42(q,J＝7.0Hz,2H),1.41(d,J＝7.1Hz,3H).
19F NMR(376MHz,CDCl3)δ47.6(m,4F),-68.0(t,J＝10.8Hz,2F),-90.8(m,2F).
EXAMPLE 10 Synthesis of 4- (2-chlorotetrafluoroethyltetrafluoro-lambda 6 -thio) tert-butylbenzene
According to the above procedure, 4- (2-chlorotetrafluoroethyltetrafluoro-lambda 6 -thio) tert-butylbenzene is obtained from 4- (chlorotetrafluoro-lambda 6 -thio) tert-butylbenzene. Purification by flash column chromatography on silica gel (n-hexane/etoac=9/1 (vol.)) gave 4- (2-chlorotetrafluoroethyltetrafluoro- λ 6 -thio) tert-butylbenzene (0.014 g, 18% yield) as a colourless liquid.
1H NMR(400MHz,CDCl3)δ7.70(d,J＝9.1Hz,2H),7.45(d,J＝7.8Hz,2H),1.34(s,9H).
19F NMR(376MHz,CDCl3)δ48.2(m,4F),-67.9(t,J＝10.8Hz,2F),-90.8(m,2F).
EXAMPLE 11 Synthesis of 2- (2-chlorotetrafluoroethyltetrafluoro-lambda 6 -thio) -5-nitropyridine
Following the procedure described above, 2- (2-chlorotetrafluoroethyltetrafluoro- λ 6 -thio) -5-nitropyridine is obtained from 2- (chlorotetrafluoro- λ 6 -thio) -5-nitropyridine. Purification by flash column chromatography on silica gel (n-hexane/etoac=9/1 (vol)) afforded 2- (2-chlorotetrafluoroethyltetrafluoro- λ 6 -thio) -5-nitropyridine (0.024 g, 33% yield) as a colorless liquid.
1H NMR(400MHz,CDCl3)δ9.39(d,J＝2.7Hz,1H),8.72(m,1H),8.02(d,J＝8.7Hz,1H).
19F NMR(376MHz,CDCl3)δ38.5(m,4F),-68.3(m,2F),-91.2(m,2F).
Synthesis example 1
(2-Chlorotetrafluoroethyltetrafluoro-lambda 6 -thio) benzene (0.07 mmol), AIBN (50 mol%) and tris (trimethylsilyl) silane (3.0 eq) were dissolved in toluene (1.3 mL) under nitrogen atmosphere in a glass vial (15 mL) and stirred on an oil bath at 100℃for 1 hour. Thereafter, the solvent was evaporated under reduced pressure, and the obtained crude product was purified by flash column chromatography (n-hexane/etoac=9/1 (volume ratio)) to obtain the desired (1, 2-tetrafluoroethyltetrafluoro- λ 6 -thio) benzene (0.014 g, yield 40%) as a colorless liquid.
1H NMR(400MHz,CDCl3)δ7.76-7.81(m,2H),7.44-7.51(m,3H),6.18(m,1H).
19F NMR(376MHz,CDCl3)δ42.7(m,4F),-98.0(m,2F),-134.3(m,2F).
EXAMPLE 12 Synthesis of 4- (2-chlorotetrafluoroethyltetrafluoro-lambda 6 -thio) aniline
To a solution of 4- (2-chlorotetrafluoroethyltetrafluoro-lambda 6 -thio) nitrobenzene (0.98 mmol) in ethanol (20 mL) was added iron (11 eq) and saturated aqueous ammonium chloride (5 mL) and stirred on an oil bath at 80℃for 2 hours. Thereafter, insoluble solids were removed by filtration through celite, and the filtrate was evaporated under reduced pressure. The crude product obtained was dissolved in ethyl acetate, washed with water, the aqueous layer was extracted 2 times with ethyl acetate, and the combined organic extracts were dried over sodium sulfate, and the solvent was evaporated under reduced pressure. The resulting crude product was purified by flash column chromatography (n-hexane/etoac=4/1 (volume ratio)) to give the desired 4- (2-chlorotetrafluoroethyltetrafluoro- λ 6 -thio) aniline as a pale yellow liquid (0.311 g, yield 95%).
1H NMR(400MHz,CDCl3)δ7.55(d,J＝8.7Hz,2H),6.58(d,J＝9.1Hz,2H),3.97(br,2H)
19F NMR(376MHz,CDCl3)δ49.5(m,4F),-67.9(t,J＝10.8Hz,2F),-90.7(m,2F).
Example 13
An aryl compound containing a tetrafluorothio group is synthesized by the following synthesis procedure.
A solution of compound (1) and ADVN (10 mol%) dissolved in EtOAc (0.25M) was stirred in a microwave flask (25 mL) under nitrogen and then cooled to 0 ℃. Subsequently, tetrafluoroethylene (TFE) was filled into the solution (1.0 gas pressure) by bubbling. After stirring on an oil bath at 40 ℃ for 72 hours, insoluble solids were removed by filtration, and the filtrate was evaporated under reduced pressure. The crude product obtained was purified by flash column chromatography on silica gel (n-hexane/EtOAc) to give the target compound (2).
(1) Synthesis of 4- (2-chlorotetrafluoroethyltetrafluoro-lambda 6 -thio) phenyl acetate
According to the above procedure, 4- (2-chlorotetrafluoroethyltetrafluoro-lambda 6 -thio) phenyl acetate was obtained from 4- (chlorotetrafluoro-lambda 6 -thio) phenyl acetate (0.6 mmol). Purification by flash column chromatography on silica gel (n-hexane/etoac=19/1 (vol.)) gave 4- (2-chlorotetrafluoroethyltetrafluoro- λ 6 -thio) phenyl acetate as colourless crystals (0.164 g, yield 72%).
1H NMR(400MHz,CDCl3)δ7.80(d,J＝9.2Hz,2H),7.19(d,J＝8.7Hz,2H),2.32(s,3H).
19F NMR(376MHz,CDCl3)δ49.2(m,4F),-67.4(t,J＝11.6Hz,2F),-90.2(m,2F).
(2) Synthesis of 2- (2-chlorotetrafluoroethyltetrafluoro-lambda 6 -thio) pyridine
According to the above procedure, 2- (2-chlorotetrafluoroethyltetrafluoro-lambda 6 -thio) pyridine was obtained from 2- (chlorotetrafluoro-lambda 6 -thio) pyridine (1.0 mmol). Purification by flash column chromatography on silica gel (n-hexane/etoac=4/1 (volume ratio)) afforded 2- (2-chlorotetrafluoroethyltetrafluoro- λ 6 -thio) pyridine (0.230 g, yield 72%) as a colourless liquid.
1H NMR(400MHz,CDCl3)δ8.57(d,J＝4.1Hz,1H),7.92(t,J＝7.3Hz,1H),7.77(d,J＝8.2Hz,1H),7.49(dd,J＝7.3,4.6Hz,1H).
19F NMR(376MHz,CDCl3)δ38.0(m,4F),-67.5(m,2F),-90.7(m,2F).
(3) Synthesis of 2- (2-chlorotetrafluoroethyltetrafluoro-lambda 6 -thio) pyrimidine
According to the above procedure, 2- (2-chlorotetrafluoroethyltetrafluoro-lambda 6 -thio) pyrimidine was obtained from 2- (chlorotetrafluoro-lambda 6 -thio) pyrimidine (0.5 mmol). Purification by flash column chromatography on silica gel (n-hexane/etoac=1/1 (volume ratio)) afforded 2- (2-chlorotetrafluoroethyltetrafluoro- λ 6 -thio) pyrimidine as a colourless liquid (0.129 g, 80% yield).
1H NMR(400MHz,CDCl3)δ8.93(d,J＝4.6Hz,2H),7.57(t,J＝4.6Hz,1H).
19F NMR(376MHz,CDCl3)δ33.7(m,4F),-67.5(m,2F),-91.1(m,2F).
(4) Synthesis of 1- (2-chlorotetrafluoroethyltetrafluoro-lambda 6 -thio) -2,3,4,5, 6-pentafluorobenzene
Following the procedure described above, 1- (2-chlorotetrafluoroethyltetrafluoro- λ 6 -thio) -2,3,4,5, 6-pentafluorobenzene was obtained from 1- (chlorotetrafluoro- λ 6 -thio) -2,3,4,5, 6-pentafluorobenzene (0.5 mmol, cis: trans = 2:3 mixture). Purification by flash column chromatography on silica gel (n-hexane/etoac=19/1 (vol.)) gave 1- (2-chlorotetrafluoroethyltetrafluoro- λ 6 -thio) -2,3,4,5, 6-pentafluorobenzene (0.072 g, yield 58%) as a colorless liquid.
19F NMR(376MHz,CDCl3)δ59.2(m,4F),-67.9(t,J＝10.8Hz,2F),-91.4(m,2F),-132.4(m,2F),-146.8(m,1F),-159.0(m,2F).
Example 14
An aryl compound containing a tetrafluorothio group is synthesized by the following synthesis procedure.
A solution of compound (1) and AIBN (10 mol%) dissolved in EtOAc (0.25M) was stirred in a microwave bottle (25 mL) under nitrogen and cooled to 0 ℃. Subsequently, tetrafluoroethylene (TFE) was filled into the solution (1.0 gas pressure) by bubbling. After stirring on an oil bath at 60 ℃ for 48 hours, insoluble solids were removed by filtration and the filtrate was evaporated under reduced pressure. The crude product obtained was purified by flash column chromatography on silica gel (n-hexane/EtOAc) to give the target compound (2).
(1) Synthesis of 4- (2-chlorotetrafluoroethyltetrafluoro-lambda 6 -thio) toluene
According to the above procedure, 4- (2-chlorotetrafluoroethyltetrafluoro-lambda 6 -thio) toluene was obtained from 4- (chlorotetrafluoro-lambda 6 -thio) toluene (1.0 mmol). Purification by flash column chromatography on silica gel (n-hexane/etoac=19/1 (volume ratio)) afforded 4- (2-chlorotetrafluoroethyltetrafluoro- λ 6 -thio) toluene (0.225 g, 67% yield) as colorless crystals.
1H NMR(400MHz,CDCl3)δ7.66(d,J＝8.7Hz,2H),7.24(d,J＝8.2Hz,2H),2.40(s,3H).
19F NMR(376MHz,CDCl3)δ48.8(m,4F),-67.3(t,J＝11.6Hz,2F),-90.2(m,2F).
Example 15
A solution of 2-chlorotetrafluoroethyltetrafluoro-lambda 6 -mercaptobenzene (0.20 mmol) and ADVN (10 mol%) dissolved in EtOAc (0.05M) was frozen with liquid nitrogen and degassed under reduced pressure. Subsequently, the solution was stirred at 0℃while Tetrafluoroethylene (TFE) was charged up to 1.1MPa. The target compound (3) was obtained in 42% yield in NMR by stirring at 40 ℃ for 24 hours on an oil bath. A compound (3) satisfying 1.ltoreq.n.ltoreq.7 was detected in the GC/MS analysis.
19F NMR(376MHz,CDCl3)δ48.3-47.3(m,4F),-67.9--67.3(m,2F),-90.5--90.2(m,2F),-121.5--118.4(m,4(n-1)F).
Example 16
To a solution of 3- (2-chlorotetrafluoroethyltetrafluoro-lambda 6 -thio) nitrobenzene (0.75 mmol) in ethanol (15 mL) was added iron (10 eq) and saturated aqueous ammonium chloride (3.7 mL) and stirred on an oil bath at 80℃for 2 hours. Thereafter, insoluble solids were removed by filtration through celite, and the filtrate was evaporated under reduced pressure. The crude product obtained was dissolved in ethyl acetate, washed with water, the aqueous layer was extracted 2 times with ethyl acetate, and the combined organic extracts were dried over sodium sulfate, and the solvent was evaporated under reduced pressure. The resulting crude product was purified by flash column chromatography (n-hexane/etoac=4/1 (vol)) to give the desired 3- (2-chlorotetrafluoroethyltetrafluoro- λ 6 -thio) aniline as a pale yellow liquid (0.209 g, yield 83%).
1H NMR(400MHz,CDCl3)δ7.20(t,J＝7.8Hz,1H),7.14(d,J＝8.2Hz,1H),7.07(t,J＝2.0Hz,1H),6.76(d,J＝7.8Hz,1H),3.84(br,2H).
19F NMR(376MHz,CDCl3)δ48.0(m,4F),-67.3(t,J＝10.0Hz,2F),-90.3(m,2F).
Example 17
3- (2-Chloroethyltetrafluoro-lambda 6 -thio) aniline (0.40 mmol), 1' -azobis (cyclohexane-1-carbonitrile) (V-40) (15 mol%) and tris (trimethylsilyl) silane (5.0 eq) were dissolved in toluene (2.0 mL) under a nitrogen atmosphere and stirred on an oil bath at 100℃for 2 hours. Thereafter, the solvent was evaporated under reduced pressure, and the obtained crude product was dissolved in tetrahydrofuran (2.0 mL) together with dimethylcarbamoyl chloride (6.0 eq) and triethylamine (2.0 eq) and stirred at room temperature for 20 hours. The crude product obtained was extracted 3 times with a mixed solvent of ethyl acetate/hexane, and then washed 3 times with a saturated aqueous solution of citric acid and a saturated aqueous solution of sodium chloride, respectively. The resulting organic extract was dried over sodium sulfate, and after evaporating the solvent under reduced pressure, it was purified by flash column chromatography (N-hexane/etoac=2/1 (volume ratio)) to give the desired N, N-dimethyl-N' - [3- (1, 2-tetrafluoroethyltetrafluoro- λ 6 -thio) phenyl ] urea (0.045 g, yield 30%) as a pale yellow liquid.
1H NMR (400MHz,CDCl3)δ7.83(m,1H),7.52(m,1H),7.38(m,1H),7.30(m,1H),6.70(br,1H),6.14(m,1H),3.00(s,6H).
19F NMR(376MHz,CDCl3)δ43.4(m,4F),-97.5(t,J＝10.0Hz,2F),-133.6(d,J＝55.2Hz,2F).
Example 18
4- (2-Chloroethyltetrafluoro-lambda 6 -thio) bromobenzene (0.50 mmol) was dissolved in dimethoxyethane (1.0 mL) together with tetrakis (triphenylphosphine) palladium (0) (3 mol%) and stirred for 10 minutes. Thereafter, a saturated ethanol solution of phenylboronic acid (1.1 equivalent) and a saturated aqueous solution of sodium carbonate (2.0 equivalent) were added, and stirred on an oil bath at 80℃for 18 hours. Thereafter, insoluble solids were removed by filtration, and the filtrate was dissolved in ethyl acetate and washed 3 times with a saturated aqueous sodium chloride solution. The resulting organic extract was dried over sodium sulfate, and after evaporating the solvent under reduced pressure, it was purified by flash column chromatography (n-hexane/etoac=19/1 (volume ratio)) to give the desired 4- (2-chlorotetrafluoroethyltetrafluoro- λ 6 -thio) biphenyl (0.182 g, yield 92%) as a colorless solid.
1H NMR(400MHz,CDCl3)δ7.87(d,J＝8.2Hz,2H),7.66(d,J＝8.2Hz,2H),7.60(d,J＝8.2Hz,2H),7.50(t,J＝7.8Hz,2H),7.44(t,J＝7.8Hz,1H).
19F NMR(376MHz,CDCl3)δ48.9(m,4F),-67.3(t,J＝11.6Hz,2F),-90.1(m,2F).
Industrial applicability
The present invention provides a method for producing an aryl compound containing SF 4 by a single step under relatively mild conditions. The present invention is used for introducing SF 4 group into medicinal components, organic materials, etc. of medicines or pesticides.
Claims (4)
1. A process for producing a tetrafluorothio-containing aryl compound, comprising the step of synthesizing a tetrafluorothio-containing aryl compound represented by the following general formula (1) by the addition reaction of a thioaryl compound represented by the following general formula (2) with an olefin compound represented by the following general formula (3) in the presence of a radical initiator,
A1-SE4Cl (2)
In the formula (2), A 1 is an aryl group which may have a substituent or a heteroaryl group which may have a substituent,
In the formula (3), R 1、R2、R3 and R 4 are each independently a hydrogen atom, a fluorine atom or a chlorine atom, wherein 2 or more of R 1、R2、R3 and R 4 are fluorine atoms,
In formula (1), a 1、R1、R2、R3 and R 4 are the same as described above.
2. The method for producing a tetrafluorothio group-containing aryl compound according to claim 1, wherein a 1 is an aryl group which may have 1 or more substituents selected from a halogen atom, an alkyl group, an alkenyl group, an aryl group, an alkoxy group, a hydroxyl group, a carboxyl group, an acyl group, a cyano group, an amino group and a nitro group.
3. The method for producing a tetrafluorothio-containing aryl compound according to claim 1 or 2, wherein the reaction is performed at-40 to 130 ℃.
4. An aryl compound containing tetrafluorothio group represented by the following general formula (1),
In the formula (1), a 1 is an aryl group which may have a substituent or a heteroaryl group which may have a substituent; r 1、R2、R3 and R 4 are each independently a hydrogen atom, a fluorine atom or a chlorine atom, and 2 or more of R 1、R2、R3 and R 4 are fluorine atoms.
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| JP2022-046766 | 2022-03-23 | ||
| PCT/JP2022/035414 WO2023048244A1 (en) | 2021-09-22 | 2022-09-22 | Method for producing tetrafluorosulfanyl group-containing aryl compound |
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