CN106032369A - 卤代s-(全氟烷基)-二苯并噻吩盐及其制备方法 - Google Patents
卤代s-(全氟烷基)-二苯并噻吩盐及其制备方法 Download PDFInfo
- Publication number
- CN106032369A CN106032369A CN201510112921.1A CN201510112921A CN106032369A CN 106032369 A CN106032369 A CN 106032369A CN 201510112921 A CN201510112921 A CN 201510112921A CN 106032369 A CN106032369 A CN 106032369A
- Authority
- CN
- China
- Prior art keywords
- dibenzothiophenes
- perfluoroalkyl
- formula
- salt
- preparation
- 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
- 238000002360 preparation method Methods 0.000 title claims description 36
- 238000000034 method Methods 0.000 claims abstract description 68
- 238000006243 chemical reaction Methods 0.000 claims abstract description 43
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims abstract description 41
- 150000001875 compounds Chemical class 0.000 claims abstract description 21
- 239000006227 byproduct Substances 0.000 claims abstract description 12
- 150000002894 organic compounds Chemical class 0.000 claims abstract description 7
- 238000006477 desulfuration reaction Methods 0.000 claims abstract description 4
- 230000023556 desulfurization Effects 0.000 claims abstract description 4
- 125000005843 halogen group Chemical group 0.000 claims description 43
- -1 ammonium radical ion Chemical class 0.000 claims description 31
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 27
- 150000008064 anhydrides Chemical class 0.000 claims description 26
- 229910052731 fluorine Inorganic materials 0.000 claims description 24
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 23
- 239000003960 organic solvent Substances 0.000 claims description 22
- 125000005010 perfluoroalkyl group Chemical group 0.000 claims description 22
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 21
- 150000003839 salts Chemical class 0.000 claims description 21
- 239000011737 fluorine Substances 0.000 claims description 20
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 19
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 claims description 19
- 239000000203 mixture Substances 0.000 claims description 17
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 14
- IYYZUPMFVPLQIF-UHFFFAOYSA-N dibenzothiophene Chemical class C1=CC=C2C3=CC=CC=C3SC2=C1 IYYZUPMFVPLQIF-UHFFFAOYSA-N 0.000 claims description 13
- DOUHZFSGSXMPIE-UHFFFAOYSA-N hydroxidooxidosulfur(.) Chemical compound [O]SO DOUHZFSGSXMPIE-UHFFFAOYSA-N 0.000 claims description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical group CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 9
- 125000001153 fluoro group Chemical group F* 0.000 claims description 9
- 239000011541 reaction mixture Substances 0.000 claims description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 8
- 150000002148 esters Chemical class 0.000 claims description 8
- 229910052708 sodium Inorganic materials 0.000 claims description 8
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims description 8
- 238000005406 washing Methods 0.000 claims description 8
- 150000008065 acid anhydrides Chemical class 0.000 claims description 7
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 7
- 238000002156 mixing Methods 0.000 claims description 7
- 239000007848 Bronsted acid Substances 0.000 claims description 6
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 6
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 6
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical group CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 claims description 5
- 125000004429 atom Chemical group 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical class CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 4
- SZNYYWIUQFZLLT-UHFFFAOYSA-N 2-methyl-1-(2-methylpropoxy)propane Chemical compound CC(C)COCC(C)C SZNYYWIUQFZLLT-UHFFFAOYSA-N 0.000 claims description 4
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 4
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 claims description 3
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 229910021645 metal ion Inorganic materials 0.000 claims description 3
- 150000004816 dichlorobenzenes Chemical class 0.000 claims description 2
- POLCUAVZOMRGSN-UHFFFAOYSA-N dipropyl ether Chemical compound CCCOCCC POLCUAVZOMRGSN-UHFFFAOYSA-N 0.000 claims description 2
- 229940093499 ethyl acetate Drugs 0.000 claims description 2
- 125000003709 fluoroalkyl group Chemical group 0.000 claims description 2
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Chemical group CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 claims description 2
- 229940011051 isopropyl acetate Drugs 0.000 claims description 2
- PYLWMHQQBFSUBP-UHFFFAOYSA-N monofluorobenzene Chemical compound FC1=CC=CC=C1 PYLWMHQQBFSUBP-UHFFFAOYSA-N 0.000 claims description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 2
- YKYONYBAUNKHLG-UHFFFAOYSA-N n-Propyl acetate Chemical group CCCOC(C)=O YKYONYBAUNKHLG-UHFFFAOYSA-N 0.000 claims description 2
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 claims description 2
- 229940090181 propyl acetate Drugs 0.000 claims description 2
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical group CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 claims description 2
- 125000002521 alkyl halide group Chemical group 0.000 claims 2
- OBHWOLDGXCOBAK-UHFFFAOYSA-N [F].CS(O)(=O)=O Chemical compound [F].CS(O)(=O)=O OBHWOLDGXCOBAK-UHFFFAOYSA-N 0.000 claims 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Chemical group CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims 1
- GWYFCOCPABKNJV-UHFFFAOYSA-M isovalerate Chemical group CC(C)CC([O-])=O GWYFCOCPABKNJV-UHFFFAOYSA-M 0.000 claims 1
- 229910052744 lithium Inorganic materials 0.000 claims 1
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical group COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 claims 1
- 229910052700 potassium Inorganic materials 0.000 claims 1
- 235000019260 propionic acid Nutrition 0.000 claims 1
- 229910052709 silver Inorganic materials 0.000 claims 1
- UWNWYIUODRPXKH-UHFFFAOYSA-N toluene;hydrofluoride Chemical compound F.CC1=CC=CC=C1 UWNWYIUODRPXKH-UHFFFAOYSA-N 0.000 claims 1
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 46
- 238000001914 filtration Methods 0.000 abstract description 10
- 230000008569 process Effects 0.000 abstract description 8
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical class C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 abstract description 5
- 239000003795 chemical substances by application Substances 0.000 abstract description 5
- 238000007039 two-step reaction Methods 0.000 abstract description 2
- 238000005580 one pot reaction Methods 0.000 abstract 1
- XPDWGBQVDMORPB-UHFFFAOYSA-N Fluoroform Chemical compound FC(F)F XPDWGBQVDMORPB-UHFFFAOYSA-N 0.000 description 99
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 52
- JXLHNMVSKXFWAO-UHFFFAOYSA-N azane;7-fluoro-2,1,3-benzoxadiazole-4-sulfonic acid Chemical compound N.OS(=O)(=O)C1=CC=C(F)C2=NON=C12 JXLHNMVSKXFWAO-UHFFFAOYSA-N 0.000 description 50
- 239000000047 product Substances 0.000 description 36
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 30
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 25
- 239000002904 solvent Substances 0.000 description 25
- 238000004293 19F NMR spectroscopy Methods 0.000 description 23
- 238000003756 stirring Methods 0.000 description 23
- 239000000376 reactant Substances 0.000 description 18
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 15
- GETTZEONDQJALK-UHFFFAOYSA-N (trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1 GETTZEONDQJALK-UHFFFAOYSA-N 0.000 description 14
- 238000001514 detection method Methods 0.000 description 14
- 239000000463 material Substances 0.000 description 13
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
- 239000007788 liquid Substances 0.000 description 11
- 239000000243 solution Substances 0.000 description 11
- 238000005160 1H NMR spectroscopy Methods 0.000 description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- 238000004364 calculation method Methods 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 10
- 238000006692 trifluoromethylation reaction Methods 0.000 description 10
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 9
- OHZAHWOAMVVGEL-UHFFFAOYSA-N 2,2'-bithiophene Chemical compound C1=CSC(C=2SC=CC=2)=C1 OHZAHWOAMVVGEL-UHFFFAOYSA-N 0.000 description 9
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- 238000001953 recrystallisation Methods 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- 239000002253 acid Substances 0.000 description 8
- 239000000460 chlorine Substances 0.000 description 8
- 238000004440 column chromatography Methods 0.000 description 8
- 230000000977 initiatory effect Effects 0.000 description 8
- 238000001556 precipitation Methods 0.000 description 8
- 238000000926 separation method Methods 0.000 description 8
- 239000011734 sodium Substances 0.000 description 8
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- 229910052801 chlorine Inorganic materials 0.000 description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
- 230000003595 spectral effect Effects 0.000 description 7
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 6
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 235000010290 biphenyl Nutrition 0.000 description 6
- 239000004305 biphenyl Substances 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 6
- TXXYRYVOWXBCAE-UHFFFAOYSA-N 1-(trifluoromethyl)dibenzothiophene Chemical class S1C2=CC=CC=C2C2=C1C=CC=C2C(F)(F)F TXXYRYVOWXBCAE-UHFFFAOYSA-N 0.000 description 5
- RJFFOUXHWKEKIU-UHFFFAOYSA-N 2,6-bis(trifluoromethyl)dibenzothiophene Chemical class FC(C1=CC=CC2=C1SC1=C2C=C(C=C1)C(F)(F)F)(F)F RJFFOUXHWKEKIU-UHFFFAOYSA-N 0.000 description 5
- UVFIXEGOSUKAPD-UHFFFAOYSA-N 5-(trifluoromethyl)dibenzothiophen-5-ium Chemical class C1=CC=C2[S+](C(F)(F)F)C3=CC=CC=C3C2=C1 UVFIXEGOSUKAPD-UHFFFAOYSA-N 0.000 description 5
- DRLZVZFVNBYRCB-UHFFFAOYSA-N FC(C1=CC2=C(SC3=C2C=C(C=C3)C(F)(F)F)C=C1)(F)F Chemical class FC(C1=CC2=C(SC3=C2C=C(C=C3)C(F)(F)F)C=C1)(F)F DRLZVZFVNBYRCB-UHFFFAOYSA-N 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 125000000524 functional group Chemical group 0.000 description 5
- 229910052751 metal Inorganic materials 0.000 description 5
- 239000002184 metal Substances 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 238000012805 post-processing Methods 0.000 description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
- AWBAEJYMKODJAE-UHFFFAOYSA-N 2,3,7,8-tetrafluorodibenzothiophene Chemical class FC1=CC2=C(SC3=C2C=C(C(=C3)F)F)C=C1F AWBAEJYMKODJAE-UHFFFAOYSA-N 0.000 description 4
- RPBFCRYJDBMRAW-UHFFFAOYSA-N FC(F)F.S1C=CC=C1 Chemical compound FC(F)F.S1C=CC=C1 RPBFCRYJDBMRAW-UHFFFAOYSA-N 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 239000005864 Sulphur Substances 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 150000001244 carboxylic acid anhydrides Chemical class 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 239000000575 pesticide Substances 0.000 description 4
- 238000006722 reduction reaction Methods 0.000 description 4
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 4
- 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 4
- ZRNSSRODJSSVEJ-UHFFFAOYSA-N 2-methylpentacosane Chemical compound CCCCCCCCCCCCCCCCCCCCCCCC(C)C ZRNSSRODJSSVEJ-UHFFFAOYSA-N 0.000 description 3
- XDASUTQDWUULOY-UHFFFAOYSA-N 3,4-diphenyl-2-thiophen-2-ylthiophene Chemical class C1=CSC(C2=C(C(=CS2)C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 XDASUTQDWUULOY-UHFFFAOYSA-N 0.000 description 3
- ZFSHDTLSXRUGFP-UHFFFAOYSA-N 4-(3,4-difluorophenyl)-1,2-difluorobenzene Chemical group C1=C(F)C(F)=CC=C1C1=CC=C(F)C(F)=C1 ZFSHDTLSXRUGFP-UHFFFAOYSA-N 0.000 description 3
- 0 C*1CCCC1 Chemical compound C*1CCCC1 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- XJUMDBLQGAPNIM-UHFFFAOYSA-N FC1=CC2=C(C=C1)[S+](C1=C2C=CC=C1F)C(F)(F)F Chemical class FC1=CC2=C(C=C1)[S+](C1=C2C=CC=C1F)C(F)(F)F XJUMDBLQGAPNIM-UHFFFAOYSA-N 0.000 description 3
- CIEWFGFOOVLQBA-UHFFFAOYSA-N FC1=CC2=C([S+](C3=C2C=C(C(=C3)F)F)C(F)(F)F)C=C1F Chemical class FC1=CC2=C([S+](C3=C2C=C(C(=C3)F)F)C(F)(F)F)C=C1F CIEWFGFOOVLQBA-UHFFFAOYSA-N 0.000 description 3
- 229910004039 HBF4 Inorganic materials 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 3
- 229910019785 NBF4 Inorganic materials 0.000 description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 3
- 150000002170 ethers Chemical class 0.000 description 3
- 230000001815 facial effect Effects 0.000 description 3
- 238000005342 ion exchange Methods 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- YBKCOFSJGXNOKP-UHFFFAOYSA-N methyl 3-oxo-1,2-dihydroindene-2-carboxylate Chemical compound C1=CC=C2C(=O)C(C(=O)OC)CC2=C1 YBKCOFSJGXNOKP-UHFFFAOYSA-N 0.000 description 3
- NBVXSUQYWXRMNV-UHFFFAOYSA-N monofluoromethane Natural products FC NBVXSUQYWXRMNV-UHFFFAOYSA-N 0.000 description 3
- 239000012299 nitrogen atmosphere Substances 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 229910001495 sodium tetrafluoroborate Inorganic materials 0.000 description 3
- 239000012265 solid product Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- KIFOXEQDAPALIF-UHFFFAOYSA-N trifluoromethyl methanesulfonate Chemical compound CS(=O)(=O)OC(F)(F)F KIFOXEQDAPALIF-UHFFFAOYSA-N 0.000 description 3
- 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 description 3
- UOCLXMDMGBRAIB-UHFFFAOYSA-N 1,1,1-trichloroethane Chemical compound CC(Cl)(Cl)Cl UOCLXMDMGBRAIB-UHFFFAOYSA-N 0.000 description 2
- UEMGWPRHOOEKTA-UHFFFAOYSA-N 1,3-difluorobenzene Chemical compound FC1=CC=CC(F)=C1 UEMGWPRHOOEKTA-UHFFFAOYSA-N 0.000 description 2
- FRZREWXLFSOOCD-UHFFFAOYSA-N 1-fluoro-5-(trifluoromethyl)dibenzothiophen-5-ium Chemical class FC1=CC=CC=2[S+](C3=C(C=21)C=CC=C3)C(F)(F)F FRZREWXLFSOOCD-UHFFFAOYSA-N 0.000 description 2
- BWZVCCNYKMEVEX-UHFFFAOYSA-N 2,4,6-Trimethylpyridine Chemical compound CC1=CC(C)=NC(C)=C1 BWZVCCNYKMEVEX-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 229910016861 F9SO3 Inorganic materials 0.000 description 2
- 229910004713 HPF6 Inorganic materials 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 235000011158 Prunus mume Nutrition 0.000 description 2
- 244000018795 Prunus mume Species 0.000 description 2
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- QEPQVPXPBBKTRC-UHFFFAOYSA-N [K].FS(=O)(O)(F)F Chemical compound [K].FS(=O)(O)(F)F QEPQVPXPBBKTRC-UHFFFAOYSA-N 0.000 description 2
- VAEKCRNUAQJBHN-UHFFFAOYSA-N [Na].FS(=O)(O)(F)F Chemical compound [Na].FS(=O)(O)(F)F VAEKCRNUAQJBHN-UHFFFAOYSA-N 0.000 description 2
- AXNBHOOQHIIQFA-UHFFFAOYSA-N [S].C(F)(F)F Chemical compound [S].C(F)(F)F AXNBHOOQHIIQFA-UHFFFAOYSA-N 0.000 description 2
- GANYMSDHMBJFIL-UHFFFAOYSA-N acetonitrile;ethoxyethane Chemical group CC#N.CCOCC GANYMSDHMBJFIL-UHFFFAOYSA-N 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 150000003863 ammonium salts Chemical class 0.000 description 2
- 125000006267 biphenyl group Chemical group 0.000 description 2
- SXDBWCPKPHAZSM-UHFFFAOYSA-M bromate Inorganic materials [O-]Br(=O)=O SXDBWCPKPHAZSM-UHFFFAOYSA-M 0.000 description 2
- SXDBWCPKPHAZSM-UHFFFAOYSA-N bromic acid Chemical compound OBr(=O)=O SXDBWCPKPHAZSM-UHFFFAOYSA-N 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- RJCQBQGAPKAMLL-UHFFFAOYSA-N bromotrifluoromethane Chemical compound FC(F)(F)Br RJCQBQGAPKAMLL-UHFFFAOYSA-N 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- JNGZXGGOCLZBFB-IVCQMTBJSA-N compound E Chemical compound N([C@@H](C)C(=O)N[C@@H]1C(N(C)C2=CC=CC=C2C(C=2C=CC=CC=2)=N1)=O)C(=O)CC1=CC(F)=CC(F)=C1 JNGZXGGOCLZBFB-IVCQMTBJSA-N 0.000 description 2
- 230000000779 depleting effect Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- FKRCODPIKNYEAC-UHFFFAOYSA-N ethyl propionate Chemical compound CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- UQSQSQZYBQSBJZ-UHFFFAOYSA-N fluorosulfonic acid Chemical compound OS(F)(=O)=O UQSQSQZYBQSBJZ-UHFFFAOYSA-N 0.000 description 2
- 125000001188 haloalkyl group Chemical group 0.000 description 2
- 150000008282 halocarbons Chemical class 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 2
- 238000001819 mass spectrum Methods 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- 239000012046 mixed solvent Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 238000003541 multi-stage reaction Methods 0.000 description 2
- 239000002798 polar solvent Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- HGJLYMGBCAKBLK-UHFFFAOYSA-N sodium;trifluoromethanesulfonic acid Chemical compound [Na].OS(=O)(=O)C(F)(F)F HGJLYMGBCAKBLK-UHFFFAOYSA-N 0.000 description 2
- 238000004611 spectroscopical analysis Methods 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 238000010183 spectrum analysis Methods 0.000 description 2
- BUUPQKDIAURBJP-UHFFFAOYSA-N sulfinic acid Chemical compound OS=O BUUPQKDIAURBJP-UHFFFAOYSA-N 0.000 description 2
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 2
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 2
- BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical compound OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 description 2
- 239000001117 sulphuric acid Substances 0.000 description 2
- 235000011149 sulphuric acid Nutrition 0.000 description 2
- NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 description 2
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 2
- VPAYJEUHKVESSD-UHFFFAOYSA-N trifluoroiodomethane Chemical compound FC(F)(F)I VPAYJEUHKVESSD-UHFFFAOYSA-N 0.000 description 2
- MEFKFJOEVLUFAY-UHFFFAOYSA-N (2,2,2-trichloroacetyl) 2,2,2-trichloroacetate Chemical compound ClC(Cl)(Cl)C(=O)OC(=O)C(Cl)(Cl)Cl MEFKFJOEVLUFAY-UHFFFAOYSA-N 0.000 description 1
- PNVPNXKRAUBJGW-UHFFFAOYSA-N (2-chloroacetyl) 2-chloroacetate Chemical compound ClCC(=O)OC(=O)CCl PNVPNXKRAUBJGW-UHFFFAOYSA-N 0.000 description 1
- CLZAEVAEWSHALL-UHFFFAOYSA-N 1,1,1,2,2,3,3-heptafluoropropane Chemical compound F[C](F)C(F)(F)C(F)(F)F CLZAEVAEWSHALL-UHFFFAOYSA-N 0.000 description 1
- BYEAHWXPCBROCE-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoropropan-2-ol Chemical compound FC(F)(F)C(O)C(F)(F)F BYEAHWXPCBROCE-UHFFFAOYSA-N 0.000 description 1
- PKPFSEKZHLTYTE-UHFFFAOYSA-N 1,2,3-trifluoro-5-(3-fluorophenyl)benzene Chemical group FC1=CC=CC(C=2C=C(F)C(F)=C(F)C=2)=C1 PKPFSEKZHLTYTE-UHFFFAOYSA-N 0.000 description 1
- XQQBYHQZTZWNMQ-UHFFFAOYSA-N 1,2-difluoro-4-(3-fluorophenyl)benzene Chemical group FC1=CC=CC(C=2C=C(F)C(F)=CC=2)=C1 XQQBYHQZTZWNMQ-UHFFFAOYSA-N 0.000 description 1
- XCLAKSVLIDPYOA-UHFFFAOYSA-N 1,2-difluoro-4-(4-fluorophenyl)benzene Chemical group C1=CC(F)=CC=C1C1=CC=C(F)C(F)=C1 XCLAKSVLIDPYOA-UHFFFAOYSA-N 0.000 description 1
- KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- JSZOAYXJRCEYSX-UHFFFAOYSA-N 1-nitropropane Chemical compound CCC[N+]([O-])=O JSZOAYXJRCEYSX-UHFFFAOYSA-N 0.000 description 1
- PXFBZOLANLWPMH-UHFFFAOYSA-N 16-Epiaffinine Natural products C1C(C2=CC=CC=C2N2)=C2C(=O)CC2C(=CC)CN(C)C1C2CO PXFBZOLANLWPMH-UHFFFAOYSA-N 0.000 description 1
- XGMDYIYCKWMWLY-UHFFFAOYSA-N 2,2,2-trifluoroethanesulfonic acid Chemical compound OS(=O)(=O)CC(F)(F)F XGMDYIYCKWMWLY-UHFFFAOYSA-N 0.000 description 1
- OVOJUAKDTOOXRF-UHFFFAOYSA-N 2,4-dinitrobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=C([N+]([O-])=O)C=C1[N+]([O-])=O OVOJUAKDTOOXRF-UHFFFAOYSA-N 0.000 description 1
- MIECVJDZXBUVSN-UHFFFAOYSA-N 2,4-diphenyl-1,3-thiazole Chemical class C=1SC(C=2C=CC=CC=2)=NC=1C1=CC=CC=C1 MIECVJDZXBUVSN-UHFFFAOYSA-N 0.000 description 1
- UYQIZODVNYRYOE-UHFFFAOYSA-N 2,8-dimethyl-5-(trifluoromethyl)dibenzothiophen-5-ium Chemical class CC1=CC2=C([S+](C3=C2C=C(C=C3)C)C(F)(F)F)C=C1 UYQIZODVNYRYOE-UHFFFAOYSA-N 0.000 description 1
- PPDFQRAASCRJAH-UHFFFAOYSA-N 2-methylthiolane 1,1-dioxide Chemical compound CC1CCCS1(=O)=O PPDFQRAASCRJAH-UHFFFAOYSA-N 0.000 description 1
- FGLBSLMDCBOPQK-UHFFFAOYSA-N 2-nitropropane Chemical compound CC(C)[N+]([O-])=O FGLBSLMDCBOPQK-UHFFFAOYSA-N 0.000 description 1
- GWOGSJALVLHACY-UHFFFAOYSA-N 2-pyridin-2-ylpyridine;ruthenium Chemical compound [Ru].N1=CC=CC=C1C1=CC=CC=N1 GWOGSJALVLHACY-UHFFFAOYSA-N 0.000 description 1
- MGAAHAGXOWKGJE-UHFFFAOYSA-N 3,7-dinitro-5-(trifluoromethyl)dibenzothiophen-5-ium Chemical class [O-][N+](=O)C1=CC=C2C3=CC=C([N+](=O)[O-])C=C3[S+](C(F)(F)F)C2=C1 MGAAHAGXOWKGJE-UHFFFAOYSA-N 0.000 description 1
- FVRSUUXIMNRMPL-UHFFFAOYSA-N 3-nitro-5-(trifluoromethyl)dibenzothiophen-5-ium Chemical class [N+](=O)([O-])C=1C=CC2=C([S+](C3=C2C=CC=C3)C(F)(F)F)C=1 FVRSUUXIMNRMPL-UHFFFAOYSA-N 0.000 description 1
- QGHDLJAZIIFENW-UHFFFAOYSA-N 4-[1,1,1,3,3,3-hexafluoro-2-(4-hydroxy-3-prop-2-enylphenyl)propan-2-yl]-2-prop-2-enylphenol Chemical group C1=C(CC=C)C(O)=CC=C1C(C(F)(F)F)(C(F)(F)F)C1=CC=C(O)C(CC=C)=C1 QGHDLJAZIIFENW-UHFFFAOYSA-N 0.000 description 1
- GGZZISOUXJHYOY-UHFFFAOYSA-N 8-amino-4-hydroxynaphthalene-2-sulfonic acid Chemical compound C1=C(S(O)(=O)=O)C=C2C(N)=CC=CC2=C1O GGZZISOUXJHYOY-UHFFFAOYSA-N 0.000 description 1
- HWTDMFJYBAURQR-UHFFFAOYSA-N 80-82-0 Chemical compound OS(=O)(=O)C1=CC=CC=C1[N+]([O-])=O HWTDMFJYBAURQR-UHFFFAOYSA-N 0.000 description 1
- 229910017744 AgPF6 Inorganic materials 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 241001044369 Amphion Species 0.000 description 1
- 229910017048 AsF6 Inorganic materials 0.000 description 1
- 229910014271 BrF5 Inorganic materials 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- UMIVDQOVSJFWOH-UHFFFAOYSA-N C1(=CC=CC=C1)C1=CC=CC=C1.[F] Chemical group C1(=CC=CC=C1)C1=CC=CC=C1.[F] UMIVDQOVSJFWOH-UHFFFAOYSA-N 0.000 description 1
- DYCLSQQVBPHMTJ-UHFFFAOYSA-N CC(CC(F)(F)F)(c1ccccc1)O Chemical compound CC(CC(F)(F)F)(c1ccccc1)O DYCLSQQVBPHMTJ-UHFFFAOYSA-N 0.000 description 1
- 229910001558 CF3SO3Li Inorganic materials 0.000 description 1
- COTOUBYYTMGCGA-UHFFFAOYSA-N CN(C)[S] Chemical compound CN(C)[S] COTOUBYYTMGCGA-UHFFFAOYSA-N 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
- FRVLEKZVYARCOV-UHFFFAOYSA-N FC(F)(F)S(c(ccc(F)c1)c1-c1c2)c1ccc2F Chemical compound FC(F)(F)S(c(ccc(F)c1)c1-c1c2)c1ccc2F FRVLEKZVYARCOV-UHFFFAOYSA-N 0.000 description 1
- JJPVDGSBBIBTGT-UHFFFAOYSA-N FC1=C(C2=C([S+](C3=C2C=CC=C3)C(F)(F)F)C=C1)F Chemical class FC1=C(C2=C([S+](C3=C2C=CC=C3)C(F)(F)F)C=C1)F JJPVDGSBBIBTGT-UHFFFAOYSA-N 0.000 description 1
- 208000035126 Facies Diseases 0.000 description 1
- 229910020261 KBF4 Inorganic materials 0.000 description 1
- 229910021135 KPF6 Inorganic materials 0.000 description 1
- 229910001290 LiPF6 Inorganic materials 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- 229910017971 NH4BF4 Inorganic materials 0.000 description 1
- 229910017673 NH4PF6 Inorganic materials 0.000 description 1
- 229910019398 NaPF6 Inorganic materials 0.000 description 1
- 241001597008 Nomeidae Species 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 description 1
- 229910021608 Silver(I) fluoride Inorganic materials 0.000 description 1
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical class OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 description 1
- KZKVXSDFKSCTIU-UHFFFAOYSA-N [Li].FS(=O)(O)(F)F Chemical compound [Li].FS(=O)(O)(F)F KZKVXSDFKSCTIU-UHFFFAOYSA-N 0.000 description 1
- WRLRISOTNFYPMU-UHFFFAOYSA-N [S].CC1=CC=CC=C1 Chemical compound [S].CC1=CC=CC=C1 WRLRISOTNFYPMU-UHFFFAOYSA-N 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 150000001263 acyl chlorides Chemical class 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 230000002152 alkylating effect Effects 0.000 description 1
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium chloride Substances Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 1
- 150000001412 amines Chemical group 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 239000003849 aromatic solvent Substances 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 125000006269 biphenyl-2-yl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C1=C(*)C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- YHASWHZGWUONAO-UHFFFAOYSA-N butanoyl butanoate Chemical compound CCCC(=O)OC(=O)CCC YHASWHZGWUONAO-UHFFFAOYSA-N 0.000 description 1
- 229910052792 caesium Inorganic materials 0.000 description 1
- TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical compound [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 229910001914 chlorine tetroxide Inorganic materials 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- AZSZCFSOHXEJQE-UHFFFAOYSA-N dibromodifluoromethane Chemical compound FC(F)(Br)Br AZSZCFSOHXEJQE-UHFFFAOYSA-N 0.000 description 1
- JXTHNDFMNIQAHM-UHFFFAOYSA-N dichloro-acetic acid Natural products OC(=O)C(Cl)Cl JXTHNDFMNIQAHM-UHFFFAOYSA-N 0.000 description 1
- 229960005215 dichloroacetic acid Drugs 0.000 description 1
- 125000004772 dichloromethyl group Chemical group [H]C(Cl)(Cl)* 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- MDKXBBPLEGPIRI-UHFFFAOYSA-N ethoxyethane;methanol Chemical compound OC.CCOCC MDKXBBPLEGPIRI-UHFFFAOYSA-N 0.000 description 1
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 238000003682 fluorination reaction Methods 0.000 description 1
- 125000001475 halogen functional group Chemical group 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- MBAKFIZHTUAVJN-UHFFFAOYSA-I hexafluoroantimony(1-);hydron Chemical compound F.F[Sb](F)(F)(F)F MBAKFIZHTUAVJN-UHFFFAOYSA-I 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- MVKMNFHMJSZTLD-UHFFFAOYSA-N hydron trifluoro-oxido-oxo-lambda6-sulfane Chemical compound FS(=O)(O)(F)F MVKMNFHMJSZTLD-UHFFFAOYSA-N 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 208000015181 infectious disease Diseases 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
- LSACYLWPPQLVSM-UHFFFAOYSA-N isobutyric acid anhydride Chemical compound CC(C)C(=O)OC(=O)C(C)C LSACYLWPPQLVSM-UHFFFAOYSA-N 0.000 description 1
- 238000006317 isomerization reaction Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 1
- FZLIPJUXYLNCLC-UHFFFAOYSA-N lanthanum atom Chemical group [La] FZLIPJUXYLNCLC-UHFFFAOYSA-N 0.000 description 1
- 229910001547 lithium hexafluoroantimonate(V) Inorganic materials 0.000 description 1
- 229910001496 lithium tetrafluoroborate Inorganic materials 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L magnesium sulphate Substances [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 1
- MCSAJNNLRCFZED-UHFFFAOYSA-N nitroethane Chemical compound CC[N+]([O-])=O MCSAJNNLRCFZED-UHFFFAOYSA-N 0.000 description 1
- LYGJENNIWJXYER-BJUDXGSMSA-N nitromethane Chemical group [11CH3][N+]([O-])=O LYGJENNIWJXYER-BJUDXGSMSA-N 0.000 description 1
- 150000004812 organic fluorine compounds Chemical class 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Chemical compound [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 description 1
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 1
- JGTNAGYHADQMCM-UHFFFAOYSA-N perfluorobutanesulfonic acid Chemical compound OS(=O)(=O)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F JGTNAGYHADQMCM-UHFFFAOYSA-N 0.000 description 1
- 125000005004 perfluoroethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 229910001546 potassium hexafluoroantimonate(V) Inorganic materials 0.000 description 1
- GLGXXYFYZWQGEL-UHFFFAOYSA-M potassium;trifluoromethanesulfonate Chemical compound [K+].[O-]S(=O)(=O)C(F)(F)F GLGXXYFYZWQGEL-UHFFFAOYSA-M 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011946 reduction process Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 239000011833 salt mixture Substances 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
- 229910052711 selenium Inorganic materials 0.000 description 1
- 239000011669 selenium Substances 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 229910001544 silver hexafluoroantimonate(V) Inorganic materials 0.000 description 1
- REYHXKZHIMGNSE-UHFFFAOYSA-M silver monofluoride Chemical compound [F-].[Ag+] REYHXKZHIMGNSE-UHFFFAOYSA-M 0.000 description 1
- 229910001494 silver tetrafluoroborate Inorganic materials 0.000 description 1
- 229910001545 sodium hexafluoroantimonate(V) Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- XGPOMXSYOKFBHS-UHFFFAOYSA-M sodium;trifluoromethanesulfonate Chemical compound [Na+].[O-]S(=O)(=O)C(F)(F)F XGPOMXSYOKFBHS-UHFFFAOYSA-M 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- AKEJUJNQAAGONA-UHFFFAOYSA-N sulfur trioxide Inorganic materials O=S(=O)=O AKEJUJNQAAGONA-UHFFFAOYSA-N 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 150000003497 tellurium Chemical class 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- 125000002827 triflate group Chemical group FC(S(=O)(=O)O*)(F)F 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D333/76—Dibenzothiophenes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B39/00—Halogenation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/35—Preparation of halogenated hydrocarbons by reactions not affecting the number of carbon or of halogen atoms in the reaction
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/68—Preparation of compounds containing amino groups bound to a carbon skeleton from amines, by reactions not involving amino groups, e.g. reduction of unsaturated amines, aromatisation, or substitution of the carbon skeleton
- C07C209/74—Preparation of compounds containing amino groups bound to a carbon skeleton from amines, by reactions not involving amino groups, e.g. reduction of unsaturated amines, aromatisation, or substitution of the carbon skeleton by halogenation, hydrohalogenation, dehalogenation, or dehydrohalogenation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/62—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by introduction of halogen; by substitution of halogen atoms by other halogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
- C07C303/26—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of esters of sulfonic acids
- C07C303/30—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of esters of sulfonic acids by reactions not involving the formation of esterified sulfo groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C315/00—Preparation of sulfones; Preparation of sulfoxides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
- C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/50—Organo-phosphines
- C07F9/5022—Aromatic phosphines (P-C aromatic linkage)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/50—Organo-phosphines
- C07F9/505—Preparation; Separation; Purification; Stabilisation
- C07F9/5063—Preparation; Separation; Purification; Stabilisation from compounds having the structure P-H or P-Heteroatom, in which one or more of such bonds are converted into P-C bonds
- C07F9/5072—Preparation; Separation; Purification; Stabilisation from compounds having the structure P-H or P-Heteroatom, in which one or more of such bonds are converted into P-C bonds from starting materials having the structure P-H
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/582—Recycling of unreacted starting or intermediate materials
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Crystallography & Structural Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
本发明涉及一种通式如下的卤代S-(全氟烷基)-二苯并噻吩盐的化合物。
Description
技术领域
本发明涉及一种名为卤代S-(全氟烷基)-二苯并噻吩盐的新化合物及其制备方法,此类化合物是一种有用的亲电全氟烷基化试剂。
背景技术
由于具备独特的性能,如高亲电性,高稳定性和高亲油性,全氟烷基是一个非常有用的官能团(例如,见P.Kirsch,“Modern Fluoroorganic Chemistry,Synthesis,Reactivity,Applications”,Wiley-VCH Verlag GmbH&Co.KGaA,Weinheim,2004)。在全氟烷基官能团中,1~4个碳的小的全氟烷基,特别地,三氟甲基对开发有效的药物,农药和其他有用的材料非常重要。因此,已经开发了很多含三氟甲基官能团的医药,农药(例如,见K.L.Kirk,J.FluorineChem.2006,127,1013-1029;S.Purser et al.,Chem.Soc.Rev.,2008,37,237-432;G.Theodoridis,Fluorine and the environment,Vol.2,Chapter 4,pp 121-175(2006)(ISSN 1872-0358))。因此,为了改进他们的生产工艺和制备更多的有效的医药,农药等,对制备全氟有机化合物的合成新方法的研究和开发一直都很活跃(例如,见,J.-A.Ma,D.Cahard,Journal of Fluorine Chemistry,2007,128,975-996;G.K.S.Prakash,A.K.Yudin,Chem.Rev.,1997,97,757-786;T.Umemoto,Chem.Rev.,1996,96,1757-1778)。其中,由于能对有机分子直接进行亲电三氟甲基化,亲电三氟试剂特别的有用。因此,已经报道了很多三氟甲基化试剂制备三氟甲基化有机化合物(例如,见S.Barata-Vallejo,B.Lantano,A.Postigo,Chem.Eur.J.2014,DOI:10.1002/chem.201404005;Y.Mace,E.Magnier,Eur.J.Org.Chem.2012,2479-2494;N.Shibata etal.,Beilstein J.Org.Chem.,2010,6,No.65)。
在这些亲电三氟甲基化试剂中,S-(三氟甲基)-二苯并噻吩盐(A),又称为Umemoto试剂,是制备三氟甲基有机化合物特别有用的试剂,(例如,见,C.Zhang,Organic&BiomolecularChemistry,2014,DOI:10.1039/c4ob00671b;H.Li,Synlett,2012,23,2289-2290;T.Umemoto et al.J.Am.Chem.Soc.,1993,115,2156-2164(1993))
现已开发了烷基和硝基系列,如2,8-二甲基-S-(三氟甲基)-二苯并噻吩盐,3,7-二叔丁基-S-(三氟甲基)-二苯并噻吩盐,3-硝基-S-(三氟甲基)-二苯并噻吩盐和3,7-二硝基-S-(三氟甲基)-二苯并噻吩盐和相应的硒和碲盐,(见,T.Umemoto et al.,J.Am.Chem.Soc.,1993,115,2156-2164(1993)),也制备了两性离子类型的Umemoto试剂(见,T.Umemoto et al.,J.FluorineChem.,1995,74,77-82)。
但是,梅本试剂(Umemoto试剂)的实际制备方法有明显的缺陷,如路线1所示:以2-羟基联苯为起始原料,需要多步反应,(步骤1),2-羟基联苯与二甲胺基硫代甲酰氯反应;(步骤2),高温下加热异构化;(步骤3),碱水解;(步骤4),硫酸二甲酯甲基化;(步骤5),氯气氯化;(步骤6),三乙胺三(氢氟酸)盐氟化;(步骤7),双氧水氧化;(步骤8),发烟硫酸关环;(步骤9)三氟甲磺酸盐或者四氟硼酸钠离子交换反应(见,T.Umemoto et al.,J.Fluorine Chem.1999,98,75-81)。
式1.梅本试剂(Umemoto试剂,A)实际生产流程:
虽然有文献报道了较短的由化合物E到化合物H的路线,此方法包括化合物E转化为其钠盐(2-联苯巯化钠),接着用CF3Br或者CF3I处理(见,T.Umemoto et al.,J.Fluorine Chem.,1999,98,75-81)。但是此工艺需要使用CF3Br,其所产生的副产物由于破坏臭氧层物质而被禁止使用或受到管制,或者需要使用昂贵的CF3I。
中间体化合物(H)也能由路线2所示的的工艺制备(见,S.S.Aiken,J.A.H.Lainton,andD.A.Widdowson,Electronic Conference on Trends in Organic Chemistry 1995,(ECTOC-1),EdsH.S.Rzepa and J.M.Goodman(CD-ROM),RSC Publications,http://www.ch.ic.ac.uk/ectoc/papers/22/)。但是,此方法需要使用CF2Br2,此物质为破坏臭氧层物质而受到管制,也要使用昂贵的氟化银。这个方法同样需要多步反应去制备Umemoto试剂。
式2.
Umemoto试剂(A:X=CF3SO3,BF4)也可以由化合物(H)与F2在三氟甲磺酸或HBF4***络合物存在下在CFCl3溶剂中进行反应制备得到,该反应会产生破坏臭氧层物质而被禁止使用(详见,T.Umemoto et al.,J.Am.Chem.Soc.,1993,115,2156-2164(1993))。并且该方法需要使用极毒及易***的F2。Umemoto试剂(A:X=CF3SO3)也可以由化合物(I)与三氟甲磺酸酐反应制备得到(请见T.Umemoto et al.,J.Am.Chem.Soc.,1993,115,2156-2164(1993)),然而,该方法仍然需要很多步才可以制备得到Umemoto试剂。
为了解决上述路线较长的缺点,如表1和Eq.1所示,最近开发了一锅法制备Umemoto试剂(A;X=CF3SO3)(见,Y.Mace et al.,Eur.J.Org.Chem.2009,1390-1397)。利用此方法,制备了Umemoto系列试剂,即甲基取代S-(三氟甲基)-二苯并噻吩盐(N)-(Q)(见表1)。但是此反应收率很低(可参加后文中的对比实施例1),并且需要柱层析分离产物。柱层析分离过程并不适合大量生产经济产品,因为工业上使用柱层析费用很高。此类化合物活性也很低,因为,甲基为给电子集团,降低了S-(三氟甲基)-二苯并噻吩盐的三氟甲基化的能力。吸电子基团取代能增强三氟甲基化活性(见,T.Umemoto et al.,J.Am.Chem.Soc.,1993,115,2156-2164)。
表1.一锅法制备S-(三氟甲基)-二苯并噻吩,包括Umemoto试剂(A;X=CF3SO3)及其衍生物(N)-(Q):
最近,另一个Umemoto系列,2,4-二甲基-7-五氟化硫-S-(三氟甲基)-二苯并噻吩三氟甲磺酸盐,通过一锅法制备得到(见,T.Okazaki et al.,Journal of Fluorine Chemistry,2014,165,91-95)。但是,尽管收率稍许提高(55%),但仍需要成本较高的柱层析分离产品。此外,所用起始原料3,5-二甲基-4’-(五氟化硫)联苯价格昂贵。
Umemoto试剂及其系列化合物还有个显著的缺点,如路线3所示,当他们被用作全氟烷基化试剂时,除全氟烷基化产物外,同时产出了当量或更高收率的二苯并噻吩(R)及其系列副产物。此只能作为废弃物,对当前的环境是个显著的问题。
式3.亲和有机化合物与Umemoto试剂的三氟甲基化反应
理想的Umemoto试剂必须具备以下特点:(1)路线短,成本低,(2)全氟烷基化能力强,(3)全氟烷基化后所得到的二苯并噻吩能循环使用。但是当前的Umemoto试剂及其系列试剂还有很多缺点,因为他们不能满足以上特点。
发明内容
为解决上述问题,发明人全面深入的研究了一种制备特定取代S-(全氟烷基)二苯并噻吩盐的想法,此盐需要满足上述所有要求。结果,他们成功制备了一种新的能满足上述特点的卤代S-(全氟烷基)-二苯并噻吩盐。
本发明涉及具有如下通式(I)的卤代S-(全氟烷基)-二苯并噻吩盐,其为有用且活性高的全氟烷基化试剂,
通式(I)
上述结构通式,Rf表示C1~4全氟烷基,R1,R2,R3,R4,R5,R6,R7,R8分别代表氢原子或卤原子,总的卤原子数为1~5个;X-是质子酸的共轭碱。
上述由发明人开发的结构通式,优选地,Rf为C1~4直链或支链全氟官能团,如CF3,C2F5,n-C3F7,iso-C3F7,n-C4F9,sec-C4F9,和iso-C4F9。这些官能团中,优选为CF3,C2F5和iso-C3F7;最优选为CF3,因为其在生化如医药,农药使用中为最重要的官能团。
上述通式(I),R1~8卤原子总数为1~5个,优选2~4个。所述卤原子为氟,氯,溴或碘;优选为氟或氯,因为其分子量小和吸电子能力强;最优选为氟,因为氟是其中最小的原子,而吸电子能力是最强的,此外氟与碳形成的碳C-F键是最稳定的。氟原子的分子量小,全氟化过程中所使用的质量单位的全氟烷基化试剂更为有效。吸电子能力越强,全氟化试剂活性越高。因此,本发明的卤代S-(全氟烷基)-二苯并噻吩盐比Umemoto试剂(A)活性更强。稳定的C-F键使氟化后的联苯由于对还原条件稳定,可以通过还原反应回收(见如下实施例15)。
上述通式(I),X-是质子酸(HX)的共轭碱。这些质子酸包括强酸如硫酸,硫酸单甲酯,氯磺酸,氟磺酸,甲磺酸,三氟甲磺酸,二氟甲磺酸,三氯甲磺酸,三氟乙磺酸,全氟乙磺酸,全氟丁磺酸,苯磺酸,甲基苯磺酸,硝基苯磺酸,二硝基苯磺酸,三氟乙酸,三氯乙酸,盐酸,HBr,HBF4,HBF3Cl,HBFCl3,HBCl4,HSbF6,HSbCl5F,HSbCl6,HAsF6,HAlCl4,HAlCl3F,HPF6,HPF5Cl-或HClO4。因此共轭碱X-的实例为HSO4 -,CH3OSO3 -,ClSO3 -,FSO3 -,CH3SO3 -,CF3SO3 -,CF2HSO3 -,CCl3SO3 -,CF3CH2SO3 -,CF2HCF2SO3 -,C2F5SO3 -,C3F7SO3 -,C4F9SO3 -,C6H5SO3 -,CH3C6H4SO3 -,O2NC6H4SO3 -,(O2N)2C6H3SO3 -,CF3CO2 -,CCl3CO2 -,Cl-,Br-,BF4 -,BF3Cl-,BFCl3 -,BCl4 -,SbF6 -,SbCl5F-,SbCl6 -,AsF6 -,AlCl4 -,AlCl3F-,PF6 -,PF5Cl-或ClO4 -。其中,X-优选为CF3SO3 -,Cl-,Br-,BF4 -,PF6 -或HSO4 -。原因为易交换,稳定性高,更优选X-为CF3SO3 -,Cl-或BF4 -,最优选为CF3SO3 -,因为其制备过程最短(如下实施例1~6)。
式(I)化合物的优选实例可用下式(Ia)表示:
在上述通式(Ia)中,Rf和X-的定义与前文定义相同,R2,R3,R4,R5,R6和R7分别为氢原子或卤原子,并且R2~7卤原子总数为2~4个。
上述通式(Ia),R2~7卤原子总数为2~4个,所述卤原子为氟,氯,溴或碘;优选为氟或氯,因为其分子量小,吸电子能力强。最优选氟,因为氟原子分子量最小,吸电子能力最强,而且能形成最稳定的C-F键。氟的小分子能使质量单位的全氟烷基化试剂更为有效。最强的吸电子能力使得卤代S-(全氟烷基)-二苯并噻吩盐成为全氟烷基化试剂中活性最高。因此,本发明的卤代S-(全氟烷基)-二苯并噻吩盐比Umemoto试剂(A)活性更强。最稳定的C-F键,使其全氟烷基化后得到的副产物在还原过程中更稳定,便于回收(见如下实施例15)。
如下面通式(I')所示的化合物,即通式(I)中X=CF3SO3,可以由下示4的方法1制备得到。
式4:
方法1
所述方法中,Rf与R1~8的定义与上述定义相同,M为金属离子或铵根离子,R为C1~4烷烃或卤代烷烃。
此方法组成如下:式(II)所示的卤代联苯,式RfSO2M所示的全氟烷基亚磺酸盐和三氟甲磺酸酐,三氟甲磺酸(CF3SO3H)和通式(RCO)2O所示的羧酸酐中的任一或几个的组合进行反应。
优选地,当前发明由几种工艺方法组成,式(II)所示的卤代联苯与式RfSO2M所代表的全氟烷基亚磺酸盐和三氟甲磺酸酐反应(见,式5,工艺1a);式(II)所示的卤代联苯与式RfSO2M所代表的全氟烷基亚磺酸盐和三氟甲磺酸反应(见,式5,工艺1b);式(II)所示的卤代联苯与式RfSO2M所代表的全氟烷基亚磺酸盐和式(RCO)2O所代表的羧酸酐反应(见,式5,工艺1c);式(II)所示的卤代联苯,式RfSO2M所代表的全氟烷基亚磺酸盐,三氟甲磺酸和式(RCO)2O所代表的羧酸酐反应(见,式5,工艺1d);式(II)所示的卤代联苯与式RfSO2M所代表的全氟烷基亚磺酸盐,三氟甲磺酸酐,三氟甲磺酸和式(RCO)2O所代表的羧酸酐反应(见,式5,工艺1e)。
式5:
工艺1a
工艺1b
工艺1c
工艺1d
工艺1e
方法1a包含下面的工艺过程(步骤1)混合通式RfSO2M所代表的全氟烷基亚磺酸盐和三氟甲磺酸酐,(步骤2)混合通式(II)所代表的卤代联苯与上述第一步的混合液。
方法1a也包含下面的工艺过程(步骤1)混合通式RfSO2M所代表的全氟烷基亚磺酸盐和三氟甲磺酸酐,(步骤2)混合通式(II)所代表的卤代联苯,三氟甲磺酸酐与上述第一步的混合液。
方法1中使用的通式(II)所示的化合物为已知化合物,或者可以从已经公开的方法中轻易制备得到(例如,见,V.Penalva et al.,Teterahedron Lett.,1998,37,2559-2560;Y.Ding et al,Tetrahedron Lett.,2012,53,6269-6272;B.Kaboudin et al.,Synthesis,2001,91-96;J.Zhou et al.,Journal of Chemical Research,2012,672-674;B.Kurscheid et al.,Organometallics,2012,31,1329-1334)。优选为3,3’-二氟联苯,4,4’-二氟联苯,3,4’-二氟联苯,3-氟-4’-氯联苯,3,3’-二氯联苯,4,4’-二氯联苯,3,4-二氟-3’-氟-联苯,3,4-二氟-4’-氟-联苯,3,4,3’,4’-四氟联苯,3,4,5,3’-四氟联苯或3,4,5,3’,4’-五氟联苯;更优选为3,3’二氟联苯,4,4’二氟联苯或3,4,3’,4’-四氟联苯,因为他们容易得到且活性较高;最优选为3,3’-二氟联苯或3,4,3’,4’-四氟联苯,因为他们容易制备,并且他们对应的卤代S-(全氟烷基)-二苯并噻吩盐(通式I)效果最好。
此方法中通式RfSO2M所表示的全氟烷基亚磺酸盐可以商业购买,或者由公开的方法中顺利制备得到。(见R.N.Hazeldine et al.,J.Chem.Soc.,1955,2901-2910;M.Tordeux et al.,J.Org.Chem.,1989,54,2452-2453;R.P.Singh et al.,Chem,Commun.,2002,1818-1819;H.W.Roesky et al.,J.Fluorine Chem.,1976,7,77-84;B.R.Langlois et al.,J.Fluorine Chem.,2007,128,851-856)。如全氟亚磺酸盐,可用1~4个碳全氟亚磺酸对应的金属盐或胺盐。适合的金属,如碱金属,碱土金属,过渡金属。胺片段有NH4,CH3NH3,C2H5NH3,(C2H5)3NH,(CH3)4N,(C2H5)4N,(C4H9)4N。这些中,优选碱金属盐如,三氟亚磺酸锂,三氟亚磺酸钠,三氟亚磺酸钾,三氟亚磺酸铯,因为他们更易交换。更优选为三氟亚磺酸钠,三氟亚磺酸钾,因为他们可以商业购买。以化合物(II)为基准,通式(III)所表示的全氟烷基亚磺酸合适用量约为0.8mol~10mol当量,优选约1mol~5mol当量。
方法1中使用的三氟甲磺酸酐可以商业购买,以化合物(II)为基准,所使用量约为0.5mol~10mol当量,优选约1mol~5mol当量。
方法1中所用的三氟甲磺酸可以商业购买,以通式RfSO2M所表示的全氟烷基亚磺酸盐为基准,所使用量约为1mol~20mol当量,优选约2mol~10mol当量。
方法1中所使用的式(RCO)2O所代表的羧酸酐,可以商业购买。其中R为C1~4烷基或卤代烷基,烷基有甲基,乙基,丙基,异丙基,正丁基,异丁基,叔丁基,仲丁基;卤代烷基有氯甲基,二氯甲基,三氯甲基和五氟乙基。因此羧酸酐有乙酸酐,氯乙酸酐,二氯乙酸酐,三氯乙酸酐,三氟乙酸酐,丙酸酐,五氟丙酸酐,丁酸酐,异丁酸酐。其中,由于容易得到,优选乙酸酐和三氟乙酸酐。以通式RfSO2M所表示的全氟烷基亚磺酸盐为基准,所使用量约为0.5mol~20mol当量,优选约1mol~10mol当量。
方法1所示反应可使用也可不使用溶剂。若此反应使用溶剂,优选的,可以为极性溶剂,如硝基甲烷,硝基乙烷,1-硝基丙烷,2-硝基丙烷,硝基苯,环丁砜,2-甲基环丁砜,甲磺酸乙酯等;含卤烷基溶剂,有二氯甲烷,氯仿,四氯化碳,二氯乙烷,三氯乙烷等;或者这些溶剂的混合溶剂;其中优选的极性溶剂为硝基甲烷或环丁砜,原因为产物收率高;其中最优选为硝基甲烷,因为容易除去,因此,由于其沸点低,产物容易分离。
方法1所示反应温度可以约为-50℃~+150℃。反应时间根据反应完全情况而定,例如可以约为0.5小时至几天,优选约为几天。
例如,方法1a的反应机理可由如下式6所解释。第一步,全氟烷基化亚磺酸盐与三氟甲磺酸酐反应得到全氟烷基亚磺酰基三氟甲磺酸混酐(III)[RfS(O)OSO2CF3];第二步,得到的混酐与通式(II)所示的卤代联苯反应得到通式(IV)所示的中间体;第三步,得到的中间体与另一分子存在反应混合液中的全氟烷基亚磺酰基三氟甲磺酸混酐和/或三氟甲磺酸酐反应得到通式(I’)所示的最终产物卤代S-(全氟烷基)-二苯并噻吩三氟甲磺酸盐。
式6.[方法1a]的反应机理:
(第一步)
(第二步)
(第三步)
本发明同时涉及通式(I’)所示的卤代S-(全氟烷基)-二苯并噻吩三氟甲磺酸盐的分离方法。本方法包含用水和有机溶剂洗涤式(II)所代表的卤代联苯与上述反应试剂所得到的反应混合物,其中所述的有机溶剂不溶于水或微溶于水,式(I’)所示的卤代S-(全氟烷基)-二苯并噻吩三氟甲磺酸盐不溶或微溶于此有机溶剂。当使用有机溶剂时,所述反应混合物为反应完毕后蒸干溶剂;当不使用溶剂时,所述反应混合物为反应完毕后的反应体系。反应溶剂如上所述。
洗涤反应混合物的溶剂为水和产品不溶或微溶于其中。优选溶剂为,醚类有***,丙醚,异丙醚,正丁醚,异丁醚,仲丁醚,叔丁醚,甲基叔丁基醚等;酯有乙酸乙酯,乙酸丙酯,乙酸异丙酯,丙酸乙酯等;碳卤溶剂有二氯甲烷,氯仿,四氯化碳,二氯乙烷等;芳烃类溶剂有苯,甲苯,二甲苯,氯苯,二氯苯,氟苯,三氟甲苯等;烷烃类有正戊烷,正己烷,正庚烷,正辛烷和他们的异构体等;及其它们的混合物。优选醚类,酯类和芳香类,更优选醚类和酯类溶剂。反应混合物可由水和有机溶剂的混合体系洗涤。也可由水和有机溶剂分开洗涤;如先用水洗再用有机溶剂洗,或先有机溶剂洗涤,再水洗涤。由于水和有机溶剂混合体系洗涤效果更好,优选水和有机溶剂的混合体系。反应混合物中,水能洗掉副产物三氟甲磺酸及其盐,烷烃羧酸及其盐,起始原料和其他的反应物仍然存在,如三氟甲基亚磺酸及其盐,三氟甲磺酸酐,三氟甲磺酸,羧酸酐,羧酸及其盐。水能洗掉溶于水的其他化合物。有机溶剂能除掉残留原料卤代联苯和溶于有机溶剂的副产物。有机溶剂能除掉其他溶于有机溶剂的化合物。根据上述仅通过水和有机溶剂洗涤,能非常容易的得到产物卤代S-(全氟烷基)-二苯并噻吩三氟甲磺酸盐,而不需要过柱分离过程。
如下面通式(I)所示的化合物卤代S-(全氟烷基)-二苯并噻吩三氟甲磺酸盐,可以由下面式7所示的方法2制备得到。
式7
方法2
其中Rf和R1~8与上文定义相同,M’氢原子为金属或铵离子,(X’)-和X-分别为质子酸的共轭碱,并且(X’)-和X-不相同。
该方法通过式(I”)所示的卤代S-(全氟烷基)-二苯并噻吩盐与(M’)+X-发生离子交换反应制备得到式(I)所示的卤代S-(全氟烷基)-二苯并噻吩盐。
[方法2]
用于方法2的S-(全氟烷基)-二苯并噻吩盐(其中X=CF3SO3)可由上述方法1制备得到。当X不同于CF3SO3时,用于方法2的S-(全氟烷基)-二苯并噻吩盐可由X为CF3SO3的S-(全氟烷基)-二苯并噻吩盐通过离子交换制备得到。X’优选为CF3SO3,Cl,Br,和HSO4。
(M’)+X-可以商业购买。优选(M’)+X-的实例为强酸及其金属和铵盐;优选的强酸为硫酸,氟硫酸,氯硫酸,三氟甲磺酸,全氟丁基磺酸,HCl,HBr,HBF4,HPF6,HSbF6等;优选的金属和铵盐包括CF3SO3Li,CF3SO3Na,CF3SO3K,CF3SO3Ag,CF3SO3NH4,C4F9SO3Na,(C2H5)3NHCl,(CH3)4NCl,(C2H5)4NCl,(C4H9)4NCl,(C4H9)4NBr,LiBF4,NaBF4,KBF4,AgBF4,NH4BF4,(C2H5)3NHBF4,,(CH3)4NBF4,(C2H5)4NBF4,(C4H9)4NBF4,LiPF6,NaPF6,KPF6,AgPF6,NH4PF6,LiSbF6,NaSbF6,KSbF6,AgSbF6等。
优选的,此反应使用溶剂,反应可顺利进行且收率很高。合适的溶剂有,腈类化合物如乙腈,丙腈等;卤碳溶剂有,二氯甲烷,氯仿,四氯化碳,二氯乙烷,三氯乙烷;醚类溶剂有***,四氢呋喃,二氧六环,二(异丙基)醚,甲基叔丁基醚等;芳香溶剂有苯,甲苯,氯苯,三氟甲苯等;醇类溶剂有,甲醇,乙醇,2,2,2-三氟乙醇,丙醇,异丙醇,1,1,1,3,3,3-六氟-2-丙醇,丁醇,异丁醇,叔丁醇等;水;或者上述溶剂的混合溶剂。
相比于1mol当量的S-(全氟烷基)-二苯并噻唑盐,此反应(M’)+X-(M’=H)的用量可以为1mol当量至很大的过量,优选约为1mol~10mol当量;(M’)+X-(M’为金属或铵离子)的用量可以约为0.8mol~2mol当量,优选约0.9mol~1.5mol当量,反应温度约为0℃~100℃,优选约为室温至80℃,反应时间以反应完全为准,可以约为10分钟至几天,优选为1天内。
本发明同时涉及如下面通式(VI)所示的卤代二苯并噻吩的回收利用,此化合物是全氟烷基化试剂如通式(V)所示的卤代S-(全氟烷基)-二苯并噻吩使用后的副产物。
其中R1~8的定义与上文定义相同。
当卤代S-(全氟烷基)-二苯并噻吩盐用于有机化合物的全氟烷基化时,如下面式8所示,除生成了全氟烷基化化合物外,还生成了当量的或更高收率的如式(V)所示的卤代二苯并噻吩副产物(见如下实施例11~14)。
式8.有机化合物与卤代S-(全氟烷基)-二苯并噻唑盐(I)的全氟烷基化:形成卤代二苯并噻唑(V),
如下面式9所示,式(V)所示的卤代二苯并噻吩经还原制备得到式(II)所示的卤代联苯。
式9.从卤代二苯并噻唑(V)中回收卤代联苯(II)
式9所示的反应可以采用硫化合物的脱硫还原反应完成(见实施例15)。脱硫化后得到的卤代联苯可以重复利用来制备本发明中的S-(全氟烷基)-二苯并噻吩盐。
本发明同时涉及使用回收的式(II)所示的卤代联苯制备式(I)所示产品卤代S-(全氟烷基)-二苯并噻吩盐。卤代S-(全氟烷基)-二苯并噻吩盐使用后所得到的式(V)卤代二苯并噻吩直接脱硫得到回收的卤代联苯。
使用回收的式(II)所示卤代联苯可以通过方法1制备卤代S-(全氟烷基)二苯并噻吩盐,并使用同样的方式,仅原料为回收的卤代联苯。
当式(I’)卤代S-(全氟烷基)二苯并噻吩三氟甲磺酸盐(X=CF3SO3)被用作全氟化试剂时,除得到全氟烷基有机化合物和式(V)所示的卤代苯并噻吩外,还得到三氟甲磺酸及其盐。三氟甲磺酸酐可由回收的三氟甲磺酸及其盐通过常规的合成方法制备得到,如与P2O5进行脱水反应制备得到(见T.Gramstad,R.N.Haszeldine,J.Chem.Soc,1957,4069-4079):CF3SO3H+P2O5→(CF3SO2)2O。
本发明的工业应用
本发明上述通式(I)所示的卤代S-(全氟烷基)-二苯并噻吩盐作为亲电全氟化试剂制备全氟化有机化合物有广泛的应用,(见实施例11~14)。本发明的卤代S-(全氟烷基)-二苯并噻吩盐可以由非常短的工艺(例如一锅法法或两步反应,见实施例1~6)及简单的过滤技术制备得到(见实施例1,2,3,4和6)。这在工业上经济化生产亲电全氟烷基化试剂非常有用。
此外,如路线7所示,卤代S-(全氟烷基)-二苯并噻吩盐全氟化有机化合物后回收得到的卤代苯并噻吩(见实施例10),再通过直接还原脱硫反应回收卤代联苯。卤代S-(全氟烷基)-二苯并噻吩盐被应用后得到的三氟甲磺酸或其盐,也能回收另一个原料三氟甲磺酸酐。
式10.卤代S-(全氟烷基)-二苯并噻唑盐循环图
如式10环所示,本发明能提供低成本,环境友好的产品卤代S-(全氟烷基)-二苯并噻吩盐,并且能够低成本绿色环保的使用全氟烷基化试剂制备全氟烷基化合物。因此,本发明的新化合物卤代S-(全氟烷基)-二苯并噻吩盐及其制备方法,能够提供高效率的,环境友好的全氟烷基化试剂,这在工业上非常重要。
当前发明提供了一种新的卤代S-(全氟烷基)-二苯并噻吩盐及其低成本的绿色生产方法。此盐为一种非常强大的亲电子全氟化试剂,全氟化活性高。
具体实施方式
为了更好的理解本发明的内容,下面结合具体实施例来做进一步的说明,但具体的实施方式并不是对本发明的内容所做的限制。
苯并噻吩结构数字编号如下所示:
实施例1:2,8-二氟-S-(三氟甲基)-二苯并噻吩三氟甲磺酸盐及2,6-二氟-S-(三氟甲基)-二苯并噻吩三氟甲磺酸盐的制备
于室温下(20℃),氮气保护中将3,3’-二氟联苯(14.2g,74.7mmol)加入到干燥的三氟甲磺酸钠(14g,90mmol)和干燥的100mL硝基甲烷混合液中,后置于水浴中冷却.该混合液搅拌40分钟,然后将三氟甲磺酸酐(50.6g,179.4mmol)加入混合液中,10分钟滴毕,然后该混合液在室温下搅拌46小时,以三氟甲苯为基准19F NMR分析反应液,显示仍有8%的起始原料3,3’-二氟联苯未反应,2,8-二氟-S-(三氟甲基)-二苯并噻吩三氟甲磺酸盐与2,6-二氟-S-(三氟甲基)-二苯并噻吩三氟甲磺酸盐收率分别为58%(63%*)和13%(14%*),即总收率71%(77%*)。反应完毕后,蒸干溶剂,加入30ml二氯甲烷,再次蒸干.然后加入100ml水和125ml二氯甲烷,搅拌45分钟,过滤收集产生的沉淀,得到产物20.1g,分离收率61%(66%*),该产物为晶状固体形式的2,8-二氟-S-(三氟甲基)-二苯并噻吩三氟甲磺酸盐与2,6-二氟-S-(三氟甲基)-二苯并噻吩三氟甲磺酸盐(87:13)的混合物。
*表示的收率为基于消耗的起始原料计算得到.
经重结晶得到纯的晶体形态的2,8-二氟-S-(三氟甲基)-二苯并噻吩三氟甲磺酸盐,
降解起始温度为204℃(TGA/DSC检测)(重结晶溶剂为CH3CN-***)。
该产物的谱图数据及理化数据如下:
19F NMR(1H照射)(376.5MHz,DMSO-d6)δ-53.25(3F,s,CF3),-77.78(3F,s,SO2CF3),-101.81ppm(2F,s,2,8-F);
1H-NMR(400.2MHz,DMSO-d6)δ8.76(2H,dd,J=9.0,4.8Hz,4,6-H),8.56(2H,dd,J=8.8,2.8Hz,1,9-H),7.84ppm(2H,dt,J=2.8,9.0Hz,3,7–H)
13C-NMR(100.6MHz,DMSO-d6)δ66.9(d,J=261.6Hz),143.8(dd,J=11.6,2.5Hz),132.9(d,J=10.1Hz),123.4(quartet,J=332.3Hz),123.0(d,J=2.0Hz),121.1(quartet,J=321.9Hz),120.1(d,J=24.1Hz),113.7ppm(d,J=27.2Hz);
IR(KBr)3112,3057,1593,1584,1583,1263,1237,1178,1157,1090,1029,903,838,757,636,571,517,492,465cm-1;
质谱分析(ESI方法)m/z,289(M+-OSO2CF3);
高分辨质谱(ESI方法)C13H6F5S(M-OSO2CF3)+,计算值289.0105.测量值289.0129.
元素分析C14H6F8O3S2:计算值:C,38.36%;H,1.38%.测量值:C,38.45%;H.1.67%.
混合物中2,6-二氟-S-(三氟甲基)二苯并噻吩三氟甲磺酸盐NMR检测数据如下:
19F NMR(1H照射)(376.5MHz,DMSO-d6)δ-52.45(3F,d,J=6.6Hz,CF3),-77.78(s,CF3SO2),-100.76(1F,s,2-F),-108.23ppm(1F,quartet,J=6.6Hz,6-F).
另一个实验按照如下的方法分离得到纯的2,6-二氟-S-(三氟甲基)二苯并噻吩三氟甲磺酸盐.蒸干反应液,加入水和二氯甲烷,过滤掉析出的固体,滤液分离出有机层,浓缩,过柱分离(洗脱溶剂为二氯甲烷:甲醇=10:1)得到纯的固体2,6-二氟-S-(三氟甲基)二苯并噻吩三氟甲磺酸盐.
降解起始温度为135℃(TGA/DSC检测)(重结晶溶剂为CH3CN-***)。
19F NMR(1H照射)(376.5MHz,DMSO-d6)δ-53.25(3F,s,CF3),-77.78(3F,s,SO2CF3),-101.81ppm(2F,s,2,8-F);
1H-NMR(400.2MHz,DMSO-d6)δ8.77(1H,dd,J=8.9,4.6Hz,4-H),8.67(1H,dd,J=8.9,2.6Hz,1-H),8.47(1H,d,J=8.4Hz,9-H),8.26(1H,dt,J=5.2,8.4Hz,8-H),7.95(1H,t,J=8.4Hz,7-H),7.88ppm(1H,dt,J=2.6,8.9Hz,3-H);
13C NMR(100.6MHz,DMSO-d6)δ163.3(d,J=255.9Hz,2-C),159.5(d,J=257.5Hz,6-C),144.1(dd,J=11.2,1.9Hz),143.0(d,J=2.5Hz),140.2(d,J=8.3Hz),133.2(d,J=10.8Hz),123.5(quartet,J=333.1Hz,CF3),122.5(d,J=2.8Hz),121.1(quartet,J=322.2Hz,SO2CF3),120.8(d,J=2.1Hz),120.6(d,J=24.8Hz),119.7(d,J=18.0Hz),114.5(d,J=26.8Hz),113.3ppm(d,J=17.1Hz);
IR(KBr)3059,1603,1583,1490,1474,1447,1267,1224,1169,1155,1103,1075,1027,904,838,815,804,758,733,665,634,573,516,495,454,435,404cm-1.
元素分析C14H6F8O3S2:计算值:C,38.36%;H,1.38%.测量值:C,38.28%;H.1.45%.
本发明所得产物经简单的过滤即可从反应混合物中以较好的收率分离得到,而经济化大生产中过滤步骤非常实用。
实施例2:2,8-二氟-S-(三氟甲基)-二苯并噻吩三氟甲磺酸盐及2,6-二氟-S-(三氟甲基)-二苯并噻吩三氟甲磺酸盐的制备
于室温下(20℃),氮气保护中将3,3’-二氟联苯(28.4g,149.5mmol)加入到干燥的三氟甲磺酸钠(25.3g,162mmol)和干燥的100mL硝基甲烷混合液中,后置于水浴中冷却.该混合液搅拌35分钟,然后将三氟甲磺酸酐(49.9g,177mmol)加入混合液中,10分钟滴毕,混合液搅拌30分钟.一次性加入三氟乙酸酐(37.2g,177mmol),然后撤除水浴.然后该混合液在室温下搅拌22小时,以三氟甲苯为基准19F NMR分析反应液,显示仍22%的起始原料3,3’-二氟联苯未反应,2,8-二氟-S-(三氟甲基)-二苯并噻吩三氟甲磺酸盐与2,6-二氟-S-(三氟甲基)-二苯并噻吩三氟甲磺酸盐收率分别为53%(68%*)和6%(8%*),即总收率59%(76%*)。反应完毕后,蒸干溶剂,加入50ml甲苯,再次蒸干.此操作再重复一次.然后加入100ml水搅拌5分钟,过滤收集产生的沉淀,得到产物36.3g,分离收率55%(71%*),该产物为晶状固体形式的2,8-二氟-S-(三氟甲基)-二苯并噻吩三氟甲磺酸盐与2,6-二氟-S-(三氟甲基)-二苯并噻吩三氟甲磺酸盐(92:8)的混合物。
*表示的收率为基于消耗的起始原料3,3’-二氟联苯计算得到.
产品的理化性质如例1所示.
实施例3:2,8-二氟-S-(三氟甲基)-二苯并噻吩三氟甲磺酸盐及2,6-二氟-S-(三氟甲基)-二苯并噻吩三氟甲磺酸盐的制备
于室温下(20℃),氮气保护中将3,3’-二氟联苯(14.2g,74.7mmol)加入到干燥的三氟甲磺酸钠(15.2g,97.4mmol)和干燥的100mL硝基甲烷混合液中,后置于水浴中冷却.该混合液搅拌20分钟,然后将三氟甲磺酸酐(29.5g,105mmol)加入混合液中,6分钟滴毕,混合液搅拌50分钟.一次性加入乙酸酐(37.2g,177mmol),搅拌47分钟,然后撤除水浴.然后该混合液在室温下搅拌46小时.以三氟甲苯为基准19F NMR分析反应液,显示仍有49%的起始原料3,3’-二氟联苯未反应,2,8-二氟-S-(三氟甲基)-二苯并噻吩三氟甲磺酸盐与2,6-二氟-S-(三氟甲基)-二苯并噻吩三氟甲磺酸盐收率分别为31%(60%*)和7%(13%*),即总收率38%(73%*)。蒸干反应液溶剂,加入50ml甲苯,再次蒸干.此操作再重复一次.然后加入100ml水搅拌45分钟,过滤收集产生的沉淀,100ml甲苯洗涤滤饼,干燥得到产物11.7g,分离收率36%(71%*),该产物为晶状固体形式的2,8-二氟-S-(三氟甲基)-二苯并噻吩三氟甲磺酸盐与2,6-二氟-S-(三氟甲基)-二苯并噻吩三氟甲磺酸盐(86:14)的混合物。
*表示的收率为基于消耗的起始原料3,3’-二氟联苯计算得到.
产品的理化性质如例1所示.
实施例4:2,8-二氟-S-(三氟甲基)-二苯并噻吩三氟甲磺酸盐及2,6-二氟-S-(三氟甲基)-二苯并噻吩三氟甲磺酸盐的制备
于冰水浴中,氮气保护下将三氟甲磺酸酐(60.8g,216mmol)加到干燥的三氟甲磺酸钠(28.1g,180mmol)和干燥的200mL硝基甲烷混合液中,该混合液在室温下搅拌5小时,然后将3,3’-二氟联苯(11.4g,60mmol)加入混合液中,然后该混合液在室温下搅拌41小时,以三氟甲苯为基准19F NMR分析反应液,显示2,8-二氟-S-(三氟甲基)-二苯并噻吩三氟甲磺酸盐与2,6-二氟-S-(三氟甲基)-二苯并噻吩三氟甲磺酸盐收率分别为54%和12%,即总收率66%。反应完毕后,蒸干溶剂,然后加入水和二氯甲烷各100mL,搅拌30分钟,过滤收集产生的沉淀,得到产物15.0g,分离收率57%,该产物为晶状固体形式的2,8-二氟-S-(三氟甲基)-二苯并噻吩三氟甲磺酸盐与2,6-二氟-S-(三氟甲基)-二苯并噻吩三氟甲磺酸盐(93:7)的混合物。
产品的理化性质如例1所示.
实施例5:4,4’-二氟-S-(三氟甲基)-二苯并噻吩三氟甲磺酸盐的制备
于室温在氮气保护下将三氟甲磺酸酐(6.08g,21.6mmol)加入到干燥的三氟甲磺酸钠(2.81g,18mmol)与干燥的15mL环丁砜的混合液中,该混合液在室温搅拌24小时后,将溶解在5mL环丁砜中的4,4’-二氟联苯(1.14g,6.0mmol)溶液加入上述混合液中,该混合液在室温下搅拌23小时,以三氟甲苯为标准,经19F NMR检测反应液中产物3,7-二氟-S-(三氟甲基)-二苯并噻吩三氟甲磺酸盐收率为72%,产物经常规后处理即可得到,如,柱层析法,其谱图数据及物理性质如下:
降解起始温度为164℃(TGA/DSC检测)(乙腈-***重结晶);
19F NMR(1H照射)(376.5MHz,DMSO-d6)δ-52.10(3F,s,CF3S),-77.78(3F,s,CF3SO2),-107.03ppm(2F,s,3,7-F);
1H NMR(400.2MHz,DMSO-d6)δ8.59-8.62(4H,m.1,4,6,9-H),8.01ppm(2H,dt,J=2.4,8.8Hz,2,8-H);
13C NMR(100.6MHz,DMSO-d6)δ162.7(d,J=252.0Hz),137.5(s),128.5(d,J=11.6Hz),127.1(d,J=9.3Hz),123.8(d,J=23.0Hz),123.4(quartet,J=333.3Hz),121.2(quartet,J=322.5Hz),117.8ppm(d,J=29.1Hz);
IR(KBr)3096,1595,1467,1269,1232,1215,1069,1034,873,841,758,694,575,516,459cm-1;
高分辨质谱(ESI方法)C13H6F5S(M-OSO2CF3)计算值289.0105.测量值289.0116.
元素分析C14H6F8O3S2:计算值:C,38.36%;H,1.38%.测量值:C,38.40%;H.1.43%.
实施例6:2,3,7,8-四氟-S-(三氟甲基)-二苯并噻吩三氟甲磺酸盐的制备
冰浴冷却,氮气氛围内将三氟甲磺酸酐(30.4g,108mmol)加入到干燥的三氟甲基亚磺酸钠(14.1g,90.4mmol)与70mL干燥的硝基甲烷混合液中,该混合液在室温下搅拌6小时之后,将溶解在30mL干燥的硝基甲烷中的3,3’,4,4’-四氟联苯(6.8g 30.1mmol)溶液加入上述混合液中,形成的反应混合液室温搅拌43小时,以三氟甲苯为基准,19F NMR分析反应液显示产物2,3,7,8-四氟-S-(三氟甲基)-二苯并噻吩三氟甲磺酸盐收率68%,反应完成后,蒸干反应混合液,然后加入水100mL,二氯甲烷125ml,然后搅拌80分钟,过滤收集产生的沉淀,得到晶状固体产物2,3,7,8-四氟-S-(三氟甲基)-二苯并噻吩三氟甲磺酸盐8.3g,分离收率为58%,其谱图数据及理化数据如下:
降解起始温度为171℃(TGA/DSC检测)(乙腈-***重结晶);
19F NMR(1H照射)(376.5MHz,DMSO-d6)δ-51.48(3F,s,CF3S),-77.82(3F,s,CF3SO2),-124.89(2F,d,J=21.5Hz,2,8-F),-129.47ppm(2F,d,J=21.5Hz,3,7-F);
1H NMR(400.2MHz,DMSO-d6)δ8.81(2H,dd,J=8.8,7.2Hz,4,6-H),8.72ppm(2H,dd,J=10.2,7.0Hz,1,9-H);
13C NMR(100.6MHz,DMSO-d6)δ155.0(dd,J=257.4,13.2Hz),151.0(dd,J=255.7,14.2Hz),138.4(d,J=10.5Hz),123.5(d,J=7.5Hz),123.2(quartet,J=333.7Hz),121.1(quartet,J=322.5Hz),120.1(d,J=24.2Hz),115.2ppm(d,J=22.0Hz);
IR(KBr)3102,3038,1608,1493,1438,1277,1256,1242,1224,1172,1073,1029,1001,882,784,756,639,573,521,455cm-1.
高分辨光谱(ESI方法)[C13H4F7S]+(M-OSO2CF3)+计算值324.9916.测量值324.9935.
元素分析C14H4F10O3S2:计算值:C,35.45%;H,0.85%.测量值:C,35.65%;H.0.88%.
本发明所得产物经简单的过滤即可从反应混合物中分离,而经济化大生产中过滤步骤非常有用。
对比实施例1:S-(三氟甲基)-二苯并噻唑三氟甲基甲磺酸盐的制备
在室温条件下氮气氛围内将三氟甲磺酸酐(6.08g,21.6mmol)加入到干燥的三氟甲基亚磺酸钠(2.80g,18mmol)与干燥的硝基甲烷(15mL)的混合液中,该反应液搅拌3小时后,将溶解在干燥的硝基甲烷(5mL)中的联苯(0.93g,6.0mmol)溶液加入上述混合液,然后在室温下搅拌60小时,以三氟甲苯为基准,19F NMR分析反应液显示产物S-(三氟甲基)-二苯并噻唑三氟甲基甲磺酸盐(Umemoto试剂)收率仅为3%,同时有大量的副产物产生。
如前文所述,按照实施例4的方法同法操作,以联苯替换3,3’-二氟联苯试图制备Umemoto试剂,S-(三氟甲基)-二苯并噻唑三氟甲基甲磺酸盐,仅得到3%的Umemoto试剂并伴有大量的副产物。与此相反,以实施例1-6为例,本发明提供的卤代S-(全氟烷基)-二苯并噻吩盐可以以很好的收率制备得到,因此与现有技术中的Umemoto试剂相比,本发明提供的化合物十分有用。
实施例7:2,8-二氟-S-(三氟甲基)-二苯并噻吩盐酸盐的制备
将四丁基氯化铵(2.54g,9.15mmol),乙腈(10mL)溶液加入搅拌的2,8-二氟-S-(三氟甲基)-二苯并噻吩三氟甲磺酸盐(4.0g,9.13mmol)乙腈(120mL)溶液中,反应混合液搅拌过夜,产生的沉淀过滤得到2.88g的2,8-二氟-S-(三氟甲基)-二苯并噻吩盐酸盐,收率97%,谱图数据及理化数据如下:
降解起始温度为230℃(TGA/DSC检测)(甲醇-***重结晶);
19F NMR(1H照射)(376.5MHz,DMSO-d6)δ-53.51(3F,s,CF3),-102.80ppm(2F,s,2,8-F);1H NMR(400.2MHz,DMSO-d6)δ7.81(2H,dt,J=2.6,8.8Hz,3,7-H),8.55(2H,dd,J=8.8,2.6Hz,1,9-H),8.78ppm(2H,dd,J=8.8,4.8Hz,4,6-H);
13C NMR(100.6MHz,DMSO-d6)δ113.5(d,J=26.6Hz),119.7(d,J=24.7Hz),123.3(quartet,J=334.9Hz),124.9(d,J=2.3Hz),132.4(d,J=10.5Hz),143.7(dd,J=11.1,2.3Hz),166.6ppm(d,J=253.8Hz);
IR(KBr)3010,2985,1590,1581,1475,1434,1220,1206,1179,1124,1113,1079,1042,940,912,828,749,569,491,445,410cm-1.
元素分析C13H6F5ClS:计算值:C,48.09%;H,1.86%.测量值:C,48.03%;H.1.92%.
实施例8:2,8-二氟-S-(三氟甲基)-二苯并噻吩溴酸盐的制备
将四丁基溴化铵(1.47g,4.57mmol),乙腈(6mL)溶液加入搅拌的2,8-二氟-S-(三氟甲基)-二苯并噻吩三氟甲磺酸盐(2.0g,4.57mmol)乙腈(60mL)溶液中,反应混合液搅拌过夜,产生的沉淀过滤得到1.28g黄色固体的2,8-二氟-S-(三氟甲基)-二苯并噻吩溴酸盐,收率76%,甲醇重结晶,得到甲醇化物C13H6BrS·1/2(CH3OH).谱图数据及理化数据如下:
降解起始温度为182℃(TGA/DSC检测)(甲醇重结晶);
19F NMR(1H照射)(376.5MHz,DMSO-d6)δ-53.17(3F,s,CF3),-102.42ppm(2F,s,2,8-F);
1H NMR(400.2MHz,DMSO-d6)δ8.82(2H,dd,J=4.6,8.8Hz,4,6-H),8.57(2H,dd,J=2.8,8.8Hz,1,9-H),7.81(2H,dt,J=2.8,8.8Hz,3,7-H),4.0(宽峰,OH),3.17ppm(1.4H,s,CH3);
13C NMR(100.6MHz,DMSO-d6)δ166.7(d,J=254.5Hz),143.7(dd,J=2.0,11.1Hz),132.6(d,J=10.1Hz),127.6(s),122.6(quartet,J=334.3Hz),119.9(d,J=24.1Hz),113.6(d,J=27.2Hz),48.9ppm(s);
IR(KBr)3443,3019,2990,1583,1475,1438,1300,1217,1178,1124,1081,1041,945,902,829,750,721,568,491,441,411cm-1.
元素分析C13H6BrF5S·1/2CH3OH:计算值:C,42.10%;H,2.09%.测量值:C,41.90%;H.1.94%.
实施例9:2,8-二氟-S-(三氟甲基)-二苯并噻吩四氟硼酸盐的制备
于40℃,将2,8-二氯-S-(三氟甲基)-二苯并噻吩氯(0.30g,0.924mmol)加入到搅拌的四氟硼酸钠(0.101g,0.92mmol)甲醇(5mL)溶液中,当该混合液变成均一溶液后,冷却到室温,然后慢慢加入15mL乙腈,过滤除去产生的白色沉淀(NaCl),蒸发滤液,加入15mL乙腈后,过滤除去不溶固体,蒸发滤液得到晶状固体产物,然后用乙腈/***重结晶,得到0.27g纯的2,8-二氟-S-(三氟甲基)-二苯并噻吩四氟硼酸盐,收率78%,其理化数据及谱图数据如下:降解起始温度为185℃(TGA/DSC检测)(乙腈-***重结晶);
19F NMR(1H照射)(376.5MHz,DMSO-d6)δ-53.24(3F,s,CF3),-101.80(2F,s,2,8-F),-148.24ppm(4F,s,BF4);
1H NMR(400.2MHz,DMSO-d6)δ7.82(2H,dt,J=2.6,8.8Hz,3,7-H),8.55(2H,dd,J=8.8,2.6Hz,1,9-H),8.75ppm(2H,dd,J=8.8,4.8Hz,4,6-H);
13C NMR(100.6MHz,DMSO-d6)δ113.7(d,J=26.6Hz),120.1(d,J=24.6Hz),123.0(d,J=2.1Hz),123.4(quartet,J=332.2Hz),132.9(d,J=10.7Hz),143.8(dd,J=11.0,2.3Hz),166.9ppm(d,J=254.7Hz).
IR(KBr)3101,2984,1591,1479,1437,1300,1252,1223,1182,1082,943,881,829,756,573,522,490,456,441,429,409cm-1.
元素分析:C13H6F9SB:计算值C,41.52%;H,1.61%.测量值:C,41.78%;H,1.64%.
实施例10:2,8-二氟-S-(三氟甲基)-二苯并噻吩六氟磷酸盐的制备
于一圆底烧瓶中加入六氟磷酸钠(1.09g,6.47mmol)和20ml甲醇.搅拌至均相,加入2,8-二氯-S-(三氟甲基)-二苯并噻吩氯(2.1g,6.47mmol),搅拌1小时,然后慢慢加入150mL乙腈,再搅拌2小时,过滤除去产生的白色沉淀(NaCl),滤液蒸干,加入120mL乙腈后,过滤除去不溶固体,蒸发滤液得到晶状固体产物,然后用乙腈/***重结晶,得到1.84g纯的2,8-二氟-S-(三氟甲基)-二苯并噻吩四氟硼酸盐,收率66%,其理化数据及谱图数据如下:
降解起始温度为186℃(TGA/DSC检测)(乙腈-***重结晶);
19F NMR with 1H-irradiation(376.5MHz,DMSO-d6)δ-53.23(3F,s,CF3),-70.13(6F,d,J=711.2Hz,PF6),-101.80(2F,s,2,8-F);
1H NMR(400.2MHz,DMSO-d6)δ8.76(2H,dd,J=4.6,8.9Hz,4,6-H),8.56(2H,dd,J=2.7,8.9Hz,1,9-H),7.83(2H,dt,J=2.7,8.9Hz,3,7-H);
13C NMR(100.6MHz,DMSO-d6)δ166.9(d,J=254.7Hz,2,8-C),143.7(dd,J=11.1,2.0Hz,10,11-C),132.9(d,J=10.6Hz,4,6-C),123.4(quartet,J=331.4Hz,CF3),123.0(d,J=2.2Hz,12,13-C),120.1(d,J=24.6Hz,1,9-or 3,8-C),113.7ppm(d,J=26.2Hz,1,9-or 3,8-C);IR(KBr)3101,1596,1481,1440,1413,1302,1260,1233,1178,1128,1067,1043,944,894,845,822,756,742,571,558,491,454,431,409cm-1.
实施例11:2,8(2,6)-二氟-S-(三氟甲基)-二苯并噻吩三氟甲磺酸盐试剂三氟甲基化1-氧代-2-茚满-2-羧酸甲酯
在室温条件下,向搅拌的1-氧代-2-茚满羧酸甲酯(190mg,1mmol),K2CO3(430mg,3mmol)和四丁基碘化铵(20mg,0.05mmol)的N,N-二甲基甲酰胺(10mL)溶液中加入比例为97:3的2,8-二氟-S-(三氟甲基)-二苯并噻吩三氟甲磺酸盐与2,6-二氟-S-(三氟甲基)-二苯并噻吩三氟甲磺酸盐的混合液(65mg,1.5mmol),该反应混合搅拌3小时,以三氟甲苯为标准,经19F NMR检测混合液中三氟甲基化产物,即1-氧代-2-(三氟甲基)-茚满-2-羧酸甲酯收率94%,产物经常规后处理即可得到,如,萃取和柱层析法,经光谱分析19F NMR(CDCl3)δ-69.3(s,CF3),19F NMR分析表明,以二氟-S-(三氟甲基)-二苯并噻吩三氟甲磺酸盐为基准,2,8-二氟苯并噻吩和2,6-二氟苯并噻吩收率分别为91%和3%,结构鉴定数据如下:
2,8-二氟苯并噻吩:
19F NMR(1H照射)(376.5MHz,CDCl3)δ-117.81ppm(s);
1H NMR(400.2MHz,CDCl3)δ7.24(2H,dt,J=2.4,8.8Hz,3,7-H),7.75(2H,dd,J=2.4,9.2Hz,1.9-H),7.78ppm(2H,dd,J=4.8,8.8Hz,4,6-H).
2,6-二氟苯并噻吩:
19F NMR(1H照射)(376.5MHz,DMSO-d6)δ-115.33(s,6-F),-117.32ppm(s,2-F).
实施例12:2,3,7,8-四氟-S-(三氟甲基)-二苯并噻吩三氟甲磺酸盐试剂三氟甲基化1-氧代-2-茚满-2-羧酸甲酯
在室温条件下,向搅拌的1-氧代-2-茚满羧酸甲酯(114mg,0.6mmol),K2CO3(249mg,1.8mmol)和四丁基碘化铵(10mg,0.03mmol)的N,N-二甲基甲酰胺(30mL)溶液中加入2,3,7,8-四氟-S-(三氟甲基)二苯并噻吩三氟甲磺酸盐(43mg,0.9mmol)。反应混合液搅拌4小时,以三氟甲苯为基准,19F NMR分析反应液显示,相对于应用的1-氧代-2-茚满羧酸甲酯,1-氧代-2-三氟甲基--茚满-2-羧酸甲酯收率为61%;相对于应用的2,3,7,8-四氟-S-(三氟甲基)二苯并噻吩三氟甲磺酸盐,2,3,7,8-四氟二苯并噻吩收率为91%。然后反应液用水(30mL)稀释,用乙酸乙酯(3X30mL)萃取,合并有机相用MgSO4干燥,过滤,蒸干溶剂,剩余物硅胶柱层析,分离产物并用光谱分析法鉴定。1-氧代-2-三氟甲基--茚满-2-羧酸甲酯分析数据如实施例6。2,3,7,8-四氟二苯并噻吩的理化数据及光谱数据如下,
Mp 145.3℃~147.3℃;
19F NMR(1H照射)(376.5MHz,CDCl3)δ-136.41(2F,d,J=20.7Hz,3,7或2,8-F),-139.69ppm(2F,d,J=20.7Hz,2,8或3,7-F);
1H NMR(400.2MHz,CDCl3)δ7.61(2H,dd,J=9.6,6.8Hz,4,6或1,9-H),7.77ppm(2H,dd,J=10.0,7.2Hz,1,9或4,6-H);
13C NMR(100.6MHz,CDCl3)δ109.4(d,J=19.4Hz),111.0(d,J=21.2Hz),130.7(m),135.1(d,J=7.8Hz),149.4(dd,J=247.0,14.2Hz),150.1ppm(dd,J=250.7,14.7Hz);
IR(KBr)3076,1577,1490,1439,1263,1151,1059,907,861,831,774,666,625,572,520,438cm-1.
实施例13:2,8(2,6)-二氟-S-(三氟甲基)-二苯并噻吩三氟甲磺酸盐试剂三氟甲基化对甲苯磺酸-3-丁炔酯
将CuCl(0.2mmol),2,4,6-三甲基吡啶(2mmol),比例为97:3的2,8-二氟-S-(三氟甲基)二苯并噻吩三氟甲磺酸盐和2,6-二氟-S-(三氟甲基)二苯并噻吩三氟甲磺酸盐混合物(52.5mg,1.2mmol)和对甲苯磺酸-3-丁炔酯(1mmol)加入配有搅拌子的希丁克管中,在氩气氛围内将N,N-二甲基乙酰胺(5mL)加入希丁克管中,然后该混合液在30℃搅拌24小时,以三氟甲苯为标准,经19F NMR检测混合液中三氟甲基化产物,即对甲苯磺酸-4-三氟甲基-3-丁炔酯,收率65%,产物经常规后处理即可得到,如,萃取和柱层析法,用已报道的已知光谱数据进行鉴定。
实施例14:2,3,7,8-四氟‐S‐(三氟甲基)‐二苯并噻吩三氟甲磺酸盐试剂三氟甲基化ɑ-甲基苯乙烯
在氮气氛围下,将装有ɑ-甲基苯乙烯(236mg,2.0mmol),2,3,7,8-四氟-S-(三氟甲基)-二苯并噻吩三氟甲磺酸盐(1.04g,2.2mmol),三(2,2'-联吡啶)钌二(六氟磷酸)盐(9mg,0.01mmol),丙酮(16mL)和水(2mL)的希丁克管置于距离4W LED灯小于1cm的位置,该反应液在室温下照射4.5小时,以三氟甲苯为标准,19F NMR检测反应液表明相对于所应用的ɑ-甲基苯乙烯,3,3,3-三氟-1-甲基-1-苯基-1-丙醇产率为87%;相对于所应用的2,3,7,8-四氟-S-(三氟甲基)-二苯并噻吩三氟甲磺酸盐,2,3,7,8-四氟二苯并噻吩收率为93%,这些产物通过常规后处理即可分离,如萃取和柱层析法,并且用光谱法鉴定产物。
实施例15:2,8(2,6)-二氟-S-(三氟甲基)-二苯并噻吩回收3,3’-二氟联苯
将比例为98:2的2,8-与2,6-二氟二苯并噻吩混合物(0.1g,0.45mmol),兰尼镍(来源于美国Johnson Matthey的镍催化剂A-4F00)甲醇(0.8mL)液和20mL甲醇混合,该混合体加热回流4小时,然后以三氟甲苯为标准,19F NMR检测反应液表明产生的3,3’-二氟联苯收率为88%,这些产物通过常规后处理即可分离,如萃取和柱层析法,并且用光谱法鉴定产物。
尽管已经结合了具体实施方式对本发明进行了充分的描述,应当注意的是对于本领域技术人员来说其各种变化和修改是显而易见的。这样的变化和修改将可以理解为包括在由所附权利要求所定义的本发明的范围内。
Claims (20)
1.一种具有如下通式(I)结构的卤代S-(全氟烷基)-二苯并噻吩盐:
其中Rf表示C1~4全氟烷基,R1,R2,R3,R4,R5,R6,R7,R8分别代表氢原子或卤原子,且卤原子总数为1~5个,X-是质子酸的共轭碱。
2.根据权利要求1所述的卤代S-(全氟烷基)-二苯并噻吩盐,其中Rf为三氟甲基。
3.根据权利要求1所述的卤代S-(全氟烷基)-二苯并噻吩盐,其中R1~8卤原子总数为2~4。
4.根据权利要求1所述的卤代S-(全氟烷基)-二苯并噻吩盐,其中所述卤原子为氟。
5.根据权利要求1所述的卤代S-(全氟烷基)-二苯并噻吩盐,其中所述X-为CF3SO3 -,Cl-,Br-,BF4 -,PF6 -或HSO4 -。
6.一种具有如下通式(I’)结构的卤代S-(全氟烷基)-二苯并噻吩盐的制备方法,
此方法组成如下:由下列式(II)表示的卤代联苯,式RfSO2M所示的全氟烷基亚磺酸盐和三氟甲磺酸酐[(CF3SO)2],三氟甲磺酸(CF3SO3H)或通式(RCO)2O所代表的羧酸酐任一或几个的组合进行反应:
其中Rf表示C1~4全氟烷基,R1,R2,R3,R4,R5,R6,R7,R8分别代表氢原子或卤原子,且卤原子总数为1~5个,M为金属离子或铵根离子;R为C1~4的烷基或卤烷基。
7.根据权利要求6所述的制备方法,为卤代联苯,三氟甲基亚磺酸盐和三氟甲磺酸酐进行反应。
8.根据权利要求6所述的制备方法,为卤代联苯,三氟甲基亚磺酸盐和三氟甲磺酸进行反应。
9.根据权利要求6所述的制备方法,为卤代联苯,三氟甲基亚磺酸盐,三氟甲磺酸酐和通式(RCO)2O所代表的羧酸酐进行反应,其中R的定义与权利要求6相同。
10.根据权利要求6所述的制备方法,为卤代联苯,三氟甲基亚磺酸盐,三氟甲磺酸和通式(RCO)2O所代表的羧酸酐进行反应,其中R的定义与权利要求6相同。
11.根据权利要求6所述的制备方法,为卤代联苯,三氟甲基亚磺酸盐,三氟甲磺酸酐,三氟甲磺酸和通式(RCO)2O所代表的羧酸酐进行反应,其中R的定义与权利要求6相同。
12.根据权利要求6所述的制备方法,为(步骤1)混合全氟烷基亚磺酸盐和三氟甲磺酸酐;和(步骤2)步骤1所得混合液与所述卤代联苯混合。
13.根据权利要求6所述的制备方法,包括(步骤1)混合全氟烷基亚磺酸盐和三氟甲磺酸酐;和(步骤2)步骤1所得混合液与所述卤代联苯和三氟甲磺酸酐混合。
14.根据权利要求6至13任一权利要求所述的制备方法,其中所述Rf为CF3,所述卤原子为氟原子,且R1至R8氟原子的总数为2~4。
15.根据权利要求6至13任一权利要求所述的制备方法,其中所述卤代联苯为式(V)所示的S‐(全氟烷基)二苯并噻吩脱硫回收得到,式(V)所示化合物由式(I)所示的卤代S‐(全氟烷基)‐二苯并噻吩盐与有机化合物反应得到,
16.根据权利要求1-13任一权利要求所述的制备方法,进一步包括如下分离步骤,用水和有机溶剂洗涤反应混合物,其中所述有机溶剂不溶或微溶于水,产物式(I’)所代表的卤代S-(全氟烷基)-二苯并噻吩盐不溶或微溶于此有机溶剂,
17.根据权利要求15所述的制备方法,进一步包括如下分离步骤,用水和有机溶剂洗涤反应混合物,其中所述有机溶剂不溶或微溶于水,产物式(I’)所代表的卤代S-(全氟烷基)-二苯并噻吩盐不溶或微溶于此有机溶剂,
18.根据权利要求16或17所述的制备方法,所述有机溶剂选自***,丙醚,异丙醚,正丁醚,异丁醚,叔丁醚,仲丁醚,甲基叔丁基醚,乙酸乙酯,乙酸丙酯,乙酸异丙酯,丙酸乙酯,二氯甲烷,氯仿,四氯化碳,二氯乙烷,苯,甲苯,二甲苯,氯苯,二氯苯,氟苯,三氟甲苯,正戊烷及其异构体,正己烷及其异构体,正庚烷及其异构体,正辛烷及其异构体。
19.一种具有如下式(I)结构的卤代S‐(全氟烷基)‐二苯并噻吩盐的制备方法,
由式(I”)表示的卤代S‐(全氟烷基)‐二苯并噻吩盐
与(M’)+X‐反应,
其中Rf表示C1~4全氟烷基,R1,R2,R3,R4,R5,R6,R7,R8分别代表氢原子或卤原子,且卤原子总数为1~5个,M’为氢,金属离子或铵根离子,(X’)-和X-分别为质子酸的共轭碱,并且(X’)-和X-不相同。
20.根据权利要求19所述的制备方法,其中M’为H,Li,Na,K或Ag,X’为CF3SO3,Cl,Br,或HSO4。
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2017534695A JP6735278B2 (ja) | 2014-12-31 | 2015-12-30 | ハロゲン化s−(パーフルオロアルキル)ジベンゾチオフェニウム塩およびその生成方法 |
US15/539,145 US10155739B2 (en) | 2014-12-31 | 2015-12-30 | Halogenated S-(perfluoroalkyl)dibenzothiophenium salt and its production methods |
PCT/CN2015/099798 WO2016107578A1 (en) | 2014-12-31 | 2015-12-30 | Halogenated s-(perfluoroalkyl) dibenzothiophenium salt and its production methods |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201410853220 | 2014-12-31 | ||
CN2014108532209 | 2014-12-31 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN106032369A true CN106032369A (zh) | 2016-10-19 |
Family
ID=56296345
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201510112921.1A Pending CN106032369A (zh) | 2014-12-31 | 2015-03-16 | 卤代s-(全氟烷基)-二苯并噻吩盐及其制备方法 |
CN201511023299.3A Active CN105732573B (zh) | 2014-12-31 | 2015-12-30 | 卤代s-(全氟烷基)-二苯并噻吩盐及其制备方法 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201511023299.3A Active CN105732573B (zh) | 2014-12-31 | 2015-12-30 | 卤代s-(全氟烷基)-二苯并噻吩盐及其制备方法 |
Country Status (3)
Country | Link |
---|---|
US (1) | US10155739B2 (zh) |
JP (1) | JP6735278B2 (zh) |
CN (2) | CN106032369A (zh) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108997306A (zh) * | 2017-06-06 | 2018-12-14 | 浙江九洲药物科技有限公司 | 一种工业化生产制备氟取代二苯并噻吩s,s-二氧化物的方法 |
CN111393406A (zh) * | 2019-01-03 | 2020-07-10 | 浙江瑞博制药有限公司 | 工业化制备2,3,7,8-四氟-s-(三氟甲基)-二苯并噻吩三氟甲磺酸盐的方法 |
CN113636918A (zh) * | 2021-08-13 | 2021-11-12 | 上海兆维科技发展有限公司 | 一种全氟烷基化芳基化合物的制备方法 |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN106032369A (zh) * | 2014-12-31 | 2016-10-19 | 浙江九洲药业股份有限公司 | 卤代s-(全氟烷基)-二苯并噻吩盐及其制备方法 |
CN108239021B (zh) * | 2016-12-27 | 2021-04-06 | 瑞博(杭州)医药科技有限公司 | 一种溴代吡啶及其衍生物的三氟甲基化工艺 |
CN109134216A (zh) * | 2017-06-28 | 2019-01-04 | 浙江九洲药业股份有限公司 | 一种三氟甲基取代羧酸化合物的制备方法 |
JP2022042967A (ja) | 2020-09-03 | 2022-03-15 | 信越化学工業株式会社 | ポジ型レジスト材料及びパターン形成方法 |
EP4232025A1 (en) | 2020-10-21 | 2023-08-30 | Colorado State University Research Foundation | Phosphine reagents for azine fluoroalkylation |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH10182632A (ja) * | 1996-12-20 | 1998-07-07 | Daikin Ind Ltd | (ハロアルキル)ジベンゾオニウム塩の製造方法、及びその硫酸水素塩とその製造方法 |
CN105732573A (zh) * | 2014-12-31 | 2016-07-06 | 浙江九洲药业股份有限公司 | 卤代s-(全氟烷基)-二苯并噻吩盐及其制备方法 |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5066795A (en) * | 1989-02-10 | 1991-11-19 | Sagami Chemical Research Center | Perfluoroalkyl-containing compound |
JPH05339261A (ja) * | 1992-06-03 | 1993-12-21 | Daikin Ind Ltd | (ハロアルキル)ジベンゾチオ又はセレノフェニウムハロアルカンスルホナートの製造方法 |
JP3536864B2 (ja) * | 1992-07-17 | 2004-06-14 | ダイキン工業株式会社 | ハロアルキル置換カルボニル化合物の製造方法 |
JP2001255647A (ja) * | 2000-03-13 | 2001-09-21 | Daikin Ind Ltd | エネルギー線照射によりカチオンまたは酸を発生するフルオロアルキルオニウム塩型のカチオンまたは酸発生剤 |
US20040265733A1 (en) * | 2003-06-30 | 2004-12-30 | Houlihan Francis M. | Photoacid generators |
JP5146212B2 (ja) * | 2008-09-12 | 2013-02-20 | Jsr株式会社 | 感放射線性組成物 |
JP2010134126A (ja) * | 2008-12-03 | 2010-06-17 | Jsr Corp | 感放射線性組樹脂組成物 |
-
2015
- 2015-03-16 CN CN201510112921.1A patent/CN106032369A/zh active Pending
- 2015-12-30 JP JP2017534695A patent/JP6735278B2/ja active Active
- 2015-12-30 US US15/539,145 patent/US10155739B2/en active Active
- 2015-12-30 CN CN201511023299.3A patent/CN105732573B/zh active Active
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH10182632A (ja) * | 1996-12-20 | 1998-07-07 | Daikin Ind Ltd | (ハロアルキル)ジベンゾオニウム塩の製造方法、及びその硫酸水素塩とその製造方法 |
CN105732573A (zh) * | 2014-12-31 | 2016-07-06 | 浙江九洲药业股份有限公司 | 卤代s-(全氟烷基)-二苯并噻吩盐及其制备方法 |
Non-Patent Citations (4)
Title |
---|
MACE YOHAN等: "Benchmark and solvent-free preparation of sulfonium salt based electrophilic trifluoromethylating reagents", 《EUR. J. ORG. CHEM.》 * |
UMEMOTO TERUO等: "CF3 oxonium salts, o-(trifluoromethyl)dibenzofuranium salts: in situ synthesis, properties, and application as a real CF3+ species reagent", 《J. ORG. CHEM.》 * |
UMEMOTO TERUO等: "Power-variable electronphilic trifluoromethylating agents. S-, Se-, Te-(trifluoromethyl)dibenzothio-, -seleno-, and -tellurophenium salt system", 《J. AM. CHEM. SOC.》 * |
柳云骐等: "二苯并噻吩在CoMoNx催化剂上的加氢脱硫", 《催化学报》 * |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108997306A (zh) * | 2017-06-06 | 2018-12-14 | 浙江九洲药物科技有限公司 | 一种工业化生产制备氟取代二苯并噻吩s,s-二氧化物的方法 |
CN111393406A (zh) * | 2019-01-03 | 2020-07-10 | 浙江瑞博制药有限公司 | 工业化制备2,3,7,8-四氟-s-(三氟甲基)-二苯并噻吩三氟甲磺酸盐的方法 |
CN111393406B (zh) * | 2019-01-03 | 2023-07-14 | 浙江瑞博制药有限公司 | 工业化制备2,3,7,8-四氟-s-(三氟甲基)-二苯并噻吩三氟甲磺酸盐的方法 |
CN113636918A (zh) * | 2021-08-13 | 2021-11-12 | 上海兆维科技发展有限公司 | 一种全氟烷基化芳基化合物的制备方法 |
Also Published As
Publication number | Publication date |
---|---|
US20170349567A1 (en) | 2017-12-07 |
JP6735278B2 (ja) | 2020-08-05 |
US10155739B2 (en) | 2018-12-18 |
JP2018503624A (ja) | 2018-02-08 |
CN105732573A (zh) | 2016-07-06 |
CN105732573B (zh) | 2019-09-06 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN106032369A (zh) | 卤代s-(全氟烷基)-二苯并噻吩盐及其制备方法 | |
RU2433992C2 (ru) | Способ получения простых фторгалогенированных эфиров | |
CN103382173A (zh) | 制备多(五氟硫烷基)芳香化合物的方法 | |
WO2016107578A1 (en) | Halogenated s-(perfluoroalkyl) dibenzothiophenium salt and its production methods | |
CN107406374A (zh) | 制备3‑氯‑2‑乙烯基苯基磺酸酯的方法 | |
US20110034719A1 (en) | Process for the preparation of (s)- naproxen 4-nitrooxybutyl ester | |
RU2641294C2 (ru) | Способ получения сульфонимидного соединения и его солей | |
CN108084062A (zh) | 一种2,4-二取代苯磺酰氯的制备方法 | |
JP6029090B2 (ja) | フッ素化物の単離方法 | |
CN110621658B (zh) | 五氟硫烷基芳香族化合物的制造方法 | |
CN105968089A (zh) | 一种3,7-二叔丁基-s-(三氟甲基)二苯并噻吩三氟甲磺酸盐的工业生产方法 | |
JP2006335699A (ja) | モノマー中間体の製造方法 | |
JPH0912508A (ja) | 2−フルオロ−イソ酪酸アルキルの製造方法 | |
JP5214842B2 (ja) | ナフタレン誘導体の製造方法 | |
JP4531561B2 (ja) | ヒドロフルオロメチレンスルホニル基を含む誘導体の合成方法 | |
CN106431824A (zh) | 3,3’‑二氟联苯工业生产方法 | |
US20050014969A1 (en) | Process for producing perfluorovinylcarboxylic acid ester | |
JP4161229B2 (ja) | (ハロアルキル)ジベンゾオニウム塩の製造方法、及びその硫酸水素塩の製造方法 | |
US20120184763A1 (en) | Method for producing perfluorosulfonic acid having ether structure and derivative thereof, and surfactant containing fluorine-containing ether sulfonic acid compound and derivative thereof | |
Tyutyunov et al. | Synthesis of New Floroaliphatic Functionalized Sulfonyl Bromides and Study of Their Chemical Properties | |
JP4465674B2 (ja) | ベンジル(ジフルオロメチル)スルフィド化合物の製造方法 | |
CN106431823A (zh) | 3,3’,4,4’‑四氟联苯工业生产方法 | |
Brace | Preparation, reactions and physical properties of segmented 2-(perfluoroalkyl) ethanesulfinic acids and their derivatives. The role of the perfluoroalkyl group in finding new and useful compounds and in searching out new chemistry | |
CN102105442A (zh) | 制备氟化磺酸酯的水性方法 | |
WO2003106407A1 (ja) | 含フッ素フルオロスルホニルアルキルビニルエーテルの製造方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
WD01 | Invention patent application deemed withdrawn after publication | ||
WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20161019 |