CN115710206A - Synthesis method and application of trifluoromethyl sulfoxide reagent - Google Patents
Synthesis method and application of trifluoromethyl sulfoxide reagent Download PDFInfo
- Publication number
- CN115710206A CN115710206A CN202211550947.0A CN202211550947A CN115710206A CN 115710206 A CN115710206 A CN 115710206A CN 202211550947 A CN202211550947 A CN 202211550947A CN 115710206 A CN115710206 A CN 115710206A
- Authority
- CN
- China
- Prior art keywords
- trifluoromethyl
- reaction
- reagent
- cdcl
- nmr
- 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.)
- Granted
Links
- 239000003153 chemical reaction reagent Substances 0.000 title claims abstract description 93
- OCOTWWSGPAHHQW-UHFFFAOYSA-N trifluoro(trifluoromethylsulfinyl)methane Chemical compound FC(F)(F)S(=O)C(F)(F)F OCOTWWSGPAHHQW-UHFFFAOYSA-N 0.000 title claims abstract description 41
- 238000001308 synthesis method Methods 0.000 title claims abstract description 5
- 238000006243 chemical reaction Methods 0.000 claims abstract description 189
- 238000000034 method Methods 0.000 claims abstract description 59
- -1 sulfonic acid ester compound Chemical class 0.000 claims abstract description 20
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 14
- 239000000126 substance Substances 0.000 claims abstract description 12
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 claims abstract description 11
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims abstract description 9
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims abstract description 9
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims abstract description 9
- 125000005520 diaryliodonium group Chemical group 0.000 claims abstract description 9
- MWKJTNBSKNUMFN-UHFFFAOYSA-N trifluoromethyltrimethylsilane Chemical compound C[Si](C)(C)C(F)(F)F MWKJTNBSKNUMFN-UHFFFAOYSA-N 0.000 claims abstract description 9
- KVCGISUBCHHTDD-UHFFFAOYSA-M sodium;4-methylbenzenesulfonate Chemical compound [Na+].CC1=CC=C(S([O-])(=O)=O)C=C1 KVCGISUBCHHTDD-UHFFFAOYSA-M 0.000 claims abstract description 7
- 239000001632 sodium acetate Substances 0.000 claims abstract description 4
- 235000017281 sodium acetate Nutrition 0.000 claims abstract description 4
- 239000000758 substrate Substances 0.000 claims abstract description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 73
- 239000002904 solvent Substances 0.000 claims description 56
- 229910052757 nitrogen Inorganic materials 0.000 claims description 55
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 36
- 239000003960 organic solvent Substances 0.000 claims description 22
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 21
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical group CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 19
- 229910052786 argon Inorganic materials 0.000 claims description 18
- 239000000203 mixture Substances 0.000 claims description 15
- 239000000460 chlorine Substances 0.000 claims description 10
- 229910052801 chlorine Inorganic materials 0.000 claims description 10
- 125000001424 substituent group Chemical group 0.000 claims description 10
- 239000003795 chemical substances by application Substances 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 230000002194 synthesizing effect Effects 0.000 claims description 7
- OFHCXWMZXQBQMH-UHFFFAOYSA-N trifluoro(trifluoromethylsulfanyl)methane Chemical compound FC(F)(F)SC(F)(F)F OFHCXWMZXQBQMH-UHFFFAOYSA-N 0.000 claims description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 6
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims description 6
- 150000001875 compounds Chemical class 0.000 claims description 6
- 229910052731 fluorine Inorganic materials 0.000 claims description 6
- 239000011737 fluorine Substances 0.000 claims description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 claims description 4
- FQTIYMRSUOADDK-UHFFFAOYSA-N ethyl 3-bromopropanoate Chemical compound CCOC(=O)CCBr FQTIYMRSUOADDK-UHFFFAOYSA-N 0.000 claims description 3
- RMWVUWLBLWBQDS-UHFFFAOYSA-N tert-butyl 3-bromopropanoate Chemical compound CC(C)(C)OC(=O)CCBr RMWVUWLBLWBQDS-UHFFFAOYSA-N 0.000 claims description 3
- CQZIEDXCLQOOEH-UHFFFAOYSA-N 3-bromopropanenitrile Chemical compound BrCCC#N CQZIEDXCLQOOEH-UHFFFAOYSA-N 0.000 claims description 2
- 239000004305 biphenyl Substances 0.000 claims description 2
- 235000010290 biphenyl Nutrition 0.000 claims description 2
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 2
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 2
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims description 2
- 239000012046 mixed solvent Substances 0.000 claims description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 2
- 229940077386 sodium benzenesulfonate Drugs 0.000 claims description 2
- MZSDGDXXBZSFTG-UHFFFAOYSA-M sodium;benzenesulfonate Chemical compound [Na+].[O-]S(=O)(=O)C1=CC=CC=C1 MZSDGDXXBZSFTG-UHFFFAOYSA-M 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 3
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims 1
- 238000000926 separation method Methods 0.000 abstract description 19
- 238000004440 column chromatography Methods 0.000 abstract description 8
- 230000000694 effects Effects 0.000 abstract description 6
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- 230000015572 biosynthetic process Effects 0.000 abstract description 2
- 230000011987 methylation Effects 0.000 abstract 1
- 238000007069 methylation reaction Methods 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 165
- 239000012074 organic phase Substances 0.000 description 89
- 239000012299 nitrogen atmosphere Substances 0.000 description 70
- 239000012043 crude product Substances 0.000 description 54
- 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 50
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 48
- 238000002390 rotary evaporation Methods 0.000 description 46
- 239000000243 solution Substances 0.000 description 43
- 239000000047 product Substances 0.000 description 40
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 37
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 36
- 239000012300 argon atmosphere Substances 0.000 description 35
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 34
- 239000007789 gas Substances 0.000 description 33
- 238000010898 silica gel chromatography Methods 0.000 description 33
- 239000007788 liquid Substances 0.000 description 32
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical group O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 28
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 24
- 239000008346 aqueous phase Substances 0.000 description 22
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 22
- 229910000024 caesium carbonate Inorganic materials 0.000 description 22
- 238000001816 cooling Methods 0.000 description 19
- 239000011541 reaction mixture Substances 0.000 description 17
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- 239000012298 atmosphere Substances 0.000 description 14
- 238000001035 drying Methods 0.000 description 14
- 238000001914 filtration Methods 0.000 description 11
- 238000003756 stirring Methods 0.000 description 11
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- 125000005034 trifluormethylthio group Chemical group FC(S*)(F)F 0.000 description 8
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 7
- MGFYSGNNHQQTJW-UHFFFAOYSA-N iodonium Chemical compound [IH2+] MGFYSGNNHQQTJW-UHFFFAOYSA-N 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 5
- 239000012434 nucleophilic reagent Substances 0.000 description 5
- 239000010409 thin film Substances 0.000 description 5
- COTCLZIUSPWWJJ-UHFFFAOYSA-M [Na+].[O-]S(=O)=S Chemical compound [Na+].[O-]S(=O)=S COTCLZIUSPWWJJ-UHFFFAOYSA-M 0.000 description 4
- 239000012267 brine Substances 0.000 description 4
- YXFVVABEGXRONW-UHFFFAOYSA-N toluene Substances CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 4
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 3
- 239000003513 alkali Substances 0.000 description 3
- 230000001588 bifunctional effect Effects 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 150000002431 hydrogen Chemical group 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 238000007789 sealing Methods 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- GETTZEONDQJALK-UHFFFAOYSA-N (trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1 GETTZEONDQJALK-UHFFFAOYSA-N 0.000 description 2
- CRUILBNAQILVHZ-UHFFFAOYSA-N 1,2,3-trimethoxybenzene Chemical compound COC1=CC=CC(OC)=C1OC CRUILBNAQILVHZ-UHFFFAOYSA-N 0.000 description 2
- NQMUGNMMFTYOHK-UHFFFAOYSA-N 1-methoxynaphthalene Chemical compound C1=CC=C2C(OC)=CC=CC2=C1 NQMUGNMMFTYOHK-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 238000006845 Michael addition reaction Methods 0.000 description 2
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 239000012039 electrophile Substances 0.000 description 2
- 125000001153 fluoro group Chemical group F* 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 2
- 239000012038 nucleophile Substances 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- 125000004430 oxygen atom Chemical group O* 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 125000003375 sulfoxide group Chemical group 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 2
- LKUDPHPHKOZXCD-UHFFFAOYSA-N 1,3,5-trimethoxybenzene Chemical compound COC1=CC(OC)=CC(OC)=C1 LKUDPHPHKOZXCD-UHFFFAOYSA-N 0.000 description 1
- HTDQSWDEWGSAMN-UHFFFAOYSA-N 1-bromo-2-methoxybenzene Chemical compound COC1=CC=CC=C1Br HTDQSWDEWGSAMN-UHFFFAOYSA-N 0.000 description 1
- QGRPVMLBTFGQDQ-UHFFFAOYSA-N 1-chloro-2-methoxybenzene Chemical compound COC1=CC=CC=C1Cl QGRPVMLBTFGQDQ-UHFFFAOYSA-N 0.000 description 1
- MLZBESJTTHZAST-UHFFFAOYSA-N 1-chloro-3-(1-phenylethenyl)benzene Chemical group ClC1=CC=CC(C(=C)C=2C=CC=CC=2)=C1 MLZBESJTTHZAST-UHFFFAOYSA-N 0.000 description 1
- QRSXZQQKWIHIHY-UHFFFAOYSA-N 1-chloro-4-(1-phenylethenyl)benzene Chemical group C1=CC(Cl)=CC=C1C(=C)C1=CC=CC=C1 QRSXZQQKWIHIHY-UHFFFAOYSA-N 0.000 description 1
- NLWCWEGVNJVLAX-UHFFFAOYSA-N 1-methoxy-2-phenylbenzene Chemical group COC1=CC=CC=C1C1=CC=CC=C1 NLWCWEGVNJVLAX-UHFFFAOYSA-N 0.000 description 1
- DOLKMMRRGVRVFW-UHFFFAOYSA-N 1-methoxy-4-(1-phenylethenyl)benzene Chemical group C1=CC(OC)=CC=C1C(=C)C1=CC=CC=C1 DOLKMMRRGVRVFW-UHFFFAOYSA-N 0.000 description 1
- QJQCPPAIBVNVHW-UHFFFAOYSA-N 1-methyl-2-(1-phenylethenyl)benzene Chemical group CC1=CC=CC=C1C(=C)C1=CC=CC=C1 QJQCPPAIBVNVHW-UHFFFAOYSA-N 0.000 description 1
- OCINXEZVIIVXFU-UHFFFAOYSA-N 1-methyl-3-[3-methyl-4-[4-(trifluoromethylthio)phenoxy]phenyl]-1,3,5-triazinane-2,4,6-trione Chemical compound CC1=CC(N2C(N(C)C(=O)NC2=O)=O)=CC=C1OC1=CC=C(SC(F)(F)F)C=C1 OCINXEZVIIVXFU-UHFFFAOYSA-N 0.000 description 1
- ZMYIIHDQURVDRB-UHFFFAOYSA-N 1-phenylethenylbenzene Chemical group C=1C=CC=CC=1C(=C)C1=CC=CC=C1 ZMYIIHDQURVDRB-UHFFFAOYSA-N 0.000 description 1
- LUZDYPLAQQGJEA-UHFFFAOYSA-N 2-Methoxynaphthalene Chemical compound C1=CC=CC2=CC(OC)=CC=C21 LUZDYPLAQQGJEA-UHFFFAOYSA-N 0.000 description 1
- OXSSBGISRIDMME-UHFFFAOYSA-N 3-bromopropyl prop-2-enoate Chemical compound BrCCCOC(=O)C=C OXSSBGISRIDMME-UHFFFAOYSA-N 0.000 description 1
- UQRONKZLYKUEMO-UHFFFAOYSA-N 4-methyl-1-(2,4,6-trimethylphenyl)pent-4-en-2-one Chemical group CC(=C)CC(=O)Cc1c(C)cc(C)cc1C UQRONKZLYKUEMO-UHFFFAOYSA-N 0.000 description 1
- ZOCSXAVNDGMNBV-UHFFFAOYSA-N 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(trifluoromethyl)sulfinyl]-1H-pyrazole-3-carbonitrile Chemical compound NC1=C(S(=O)C(F)(F)F)C(C#N)=NN1C1=C(Cl)C=C(C(F)(F)F)C=C1Cl ZOCSXAVNDGMNBV-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 239000005899 Fipronil Substances 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 241000607479 Yersinia pestis Species 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 230000001165 anti-coccidial effect Effects 0.000 description 1
- 230000036528 appetite Effects 0.000 description 1
- 235000019789 appetite Nutrition 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229940013764 fipronil Drugs 0.000 description 1
- UQSQSQZYBQSBJZ-UHFFFAOYSA-M fluorosulfonate Chemical compound [O-]S(F)(=O)=O UQSQSQZYBQSBJZ-UHFFFAOYSA-M 0.000 description 1
- 238000007306 functionalization reaction Methods 0.000 description 1
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical class I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000000749 insecticidal effect Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- AUHZEENZYGFFBQ-UHFFFAOYSA-N mesitylene Substances CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 description 1
- 125000001827 mesitylenyl group Chemical group [H]C1=C(C(*)=C(C([H])=C1C([H])([H])[H])C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- KQEVIFKPZOGBMZ-UHFFFAOYSA-N methyl 3-bromopropanoate Chemical compound COC(=O)CCBr KQEVIFKPZOGBMZ-UHFFFAOYSA-N 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 125000005010 perfluoroalkyl group Chemical group 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 235000020030 perry Nutrition 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 125000005543 phthalimide group Chemical group 0.000 description 1
- 229960005235 piperonyl butoxide Drugs 0.000 description 1
- 125000004591 piperonyl group Chemical group C(C1=CC=2OCOC2C=C1)* 0.000 description 1
- 238000002600 positron emission tomography Methods 0.000 description 1
- 244000144977 poultry Species 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- KQNJUTDIDREYGN-UHFFFAOYSA-N propan-2-yl 3-bromopropanoate Chemical compound CC(C)OC(=O)CCBr KQNJUTDIDREYGN-UHFFFAOYSA-N 0.000 description 1
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
- 238000005086 pumping Methods 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 230000027756 respiratory electron transport chain Effects 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 239000004576 sand Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 125000001174 sulfone group Chemical group 0.000 description 1
- 150000003463 sulfur Chemical class 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 238000005987 sulfurization reaction Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 229960000898 toltrazuril Drugs 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- PQDJYEQOELDLCP-UHFFFAOYSA-N trimethylsilane Chemical compound C[SiH](C)C PQDJYEQOELDLCP-UHFFFAOYSA-N 0.000 description 1
- 229940094989 trimethylsilane Drugs 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a synthesis method and application of a trifluoromethyl sulfoxide reagent. Firstly, reacting sodium toluenesulfonate with bromide to obtain a sulfonic acid ester compound; then reacting a sulfonic acid ester compound with trifluoromethyl trimethylsilane under the condition of sodium acetate to obtain a trifluoro methyl thiolether substance; finally, the trifluoromethyl sulphoxide reagent is obtained by reacting the trifluoromethyl thiolether substance under the condition of m-chloroperoxybenzoic acid. The invention also provides application of the prepared trifluoromethyl sulfoxide reagent as a trifluoromethyl sulfoxide reagent and a trifluoromethyl methylation reagent, wherein an application substrate is a diaryl iodonium salt derivative, a 1, 1-stilbene derivative or electron-rich aromatic hydrocarbon. The method has low synthesis cost and simple reaction, can obtain the trifluoromethyl sulfoxide reagent without complicated column chromatography separation, and realizes adjustable structure and controllable activity by introducing the trifluoromethyl sulfoxide reagents with different leaving groups.
Description
Technical Field
The invention belongs to the technical field of chemistry, and relates to a synthetic method and application of a trifluoromethyl sulfoxide reagent, in particular to a synthetic method of a compound containing trifluoromethyl sulfoxide capable of being subjected to dual-functionalization, which is applied to the preparation of trifluoromethyl sulfuration or trifluoromethyl sulfoxidation products by reacting with different electrophilic reagents and nucleophilic reagents under different reaction conditions.
Background
Fluorine atoms play an important role in organic drugs. The fluorine atom can improve drug properties, such as cell membrane permeability, target specificity and metabolic stability, and isotope 18 F is also used for positron emission tomography. In which trifluoromethyl Sulfide (SCF) in the fluorine-containing group 3 ) And a trifluoromethyl sulfoxide group (S (O) CF) 3 ) Has wide potential application prospect. Like trifluoromethylthio group has the highest known Hansch lipophilicity parameter, with values up to π =1.44. The compound containing the trifluoromethylthio group has higher biological activity and is widely applied to the fields of agricultural chemicals and organic synthesis. In agricultural chemistry, fipronil is a strong pesticide, has a wide insecticidal range, and has contact killing and certain systemic action on pests; toltrazuril is a commonly used anticoccidial drug for poultry and pigs; the teflurex can suppress appetite.
The current methods for synthesizing trifluoromethyl sulfoxide compounds are mainly three types: firstly, oxidizing trifluoromethylthio by m-CPBA or hydrogen peroxide, but the method needs to control the dosage of an oxidant, otherwise, the trifluoromethylthio is easily over-oxidized into a sulfone group; secondly, perfluoroalkyl group is carried out through nucleophilic or electrophilic trifluoromethyl group, and the method has the disadvantages that the precursor is not stable enough, some precursors have larger toxicity and the reaction conditions are harsh; and thirdly, a trifluoromethyl sulfoxide group is directly introduced, the method can well control the reaction amount, the reaction operation is simple and rapid, and the reaction range is wider. However, such agents are currently being developed only in relatively few instances.
The reagents are also mainly divided into three types, the first type is a free radical reagent which is few in research at present and has few reports; the second is trifluoromethyl sulfoxide electrophile, a poorly developed class of reagents. The applicant has created an electrophilic trifluoromethyl sulfoxide reagent with a phthalimide structure in the prior art, and the reagent is simple and convenient to synthesize, stable in structure and high in activity. On this basis, it is desirable to synthesize more challenging nucleophiles. This reagent develops less and is more difficult to generate than the electrophile. And because of the strong electronegativity of oxygen atoms and trifluoromethyl groups, the distribution of electrons is more prone to generate sulfur positive ions, so that single sulfoxide anions are difficult to exist, difficult to generate and unstable, and thus few researches are made. Therefore, in order to overcome this difficulty, the structure of the reagent needs to be designed, and it is desired to generate a highly active trifluoromethyl sulfoxide nucleophile in situ in the reaction.
Currently only reactions referencing non-fluorine containing sulfoxide groups can be found, such as the reaction of methyl sulfoxide with diaryl iodonium salts, to give the corresponding sulfoxide trifluoromethylated aryl group, but this requires a strong base to do (Yu, h.; li, z.; bolm, c.org.lett.2018, 20, 7104-7106 and Wang, l.; chen, m.j.; zhang, j.l.org.chem.front.2019,6, 32-35.).
In recent years, the development of trifluoromethylthio reagent has been more mature than that of trifluoromethylsulfoxide reagent. These reagents are often linked in a molecular structure in which a trifluoromethylthio group is easily detached from a nitrogen atom, an oxygen atom, or the like. In 2020, the Procter topic group developed a novel trifluoromethyl sulfoxide reagent, which is different from other reagents in the method of forming a trifluoromethylthio group by binding a trifluoromethyl group to a sulfoxide group. However, the trifluoromethyl sulfitation reaction mostly requires low temperature and long reaction time in the current research, which results in more strict requirements on the reaction conditions (d.wang, c.g.carlton, m.tayu, j.j.w.mcdouall, g.j.p.perry, d.j.procter, angelw.chem.int.ed.2020, 59, 15918.). These reagents have good activity, but they are all only trifluoromethylthiolation. Applicants have combined the two to develop a fluorosulfonate reagent that is capable of being bifunctional.
According to the application, starting from the trifluoromethyl sulfoxide reagent with the structure, under the condition of alkali promotion, reverse Michael addition is carried out, so that alkali attacks hydrogen on a beta position, a byproduct of reverse Michael addition can be removed after electron transfer, the olefin is stable in property and easy to leave, the reaction is facilitated, and finally, a nucleophilic reagent can attack the nucleophilic reagent to obtain a corresponding trifluoromethyl sulfoxide compound. When the reagent is used as an electrophilic reagent, the reagent is activated by trifluoromethanesulfonic anhydride to generate an electrophilic intermediate. The intermediate then reacts with the arene-interrupted Pummerer to produce the sulfur salt. And finally, selectively removing the leaving group by alkali to form an electrophilic reagent, and then selectively attacking the electrophilic reagent by different nucleophilic reagents to obtain the trifluoromethylthio compound.
Therefore, cheap and easily-obtained 3-bromomethyl propionate is used as an initial raw material, a novel synthesis method of a bifunctional reagent with adjustable structure and controllable activity is developed, and the research and development of the compound have important significance in efficiently and directly introducing trifluoromethylthio or trifluoromethylsulfoxide groups, and the experimental conditions are simple and convenient and easy to operate.
Disclosure of Invention
One object of the present invention is to provide a method for synthesizing a trifluoromethyl sulfoxide reagent.
The method comprises the following steps:
adding sodium p-toluenesulfonate into the container in the step (1), adding bromide and a first organic solvent, and reacting at normal temperature under the protection of nitrogen or argon to 12E to EObtaining a sulfonic acid ester compound after 24 hours; in the reaction system, the molar ratio of the sodium p-toluenesulfonate to the sodium benzenesulfonate is 1. The structural formula of the sodium p-toluenesulfonate is as follows
The structural formula of the bromide is
The reaction formula is as follows:
the bromide is 3-bromomethyl propionate with a structural formula
Or 3-bromopropionic acid ethyl ester with the structural formula
Or 3-bromopropionic acid tert-butyl ester with the structural formula
Or 3-bromopropionic acid isopropyl ester with the structural formula
Or 3-bromopropionitrile, the structural formula is
The first organic solvent is N, N-dimethylformamide solvent DMF or N, N-dimethylacetamide solvent DMAc, and the concentration is 0.1-1.0M.
Adding a sulfonic acid ester compound into the container in the step (2), and then adding sodium acetate and trifluoromethyl trimethylsilane TMSCF 3 Reacting with a second organic solvent for 6 to 18 hours at the temperature of between 10 ℃ below zero and 30 ℃ below zero under the protection of nitrogen or argon to obtain a trifluoro-methyl sulfide substance; in the reaction system, a sulfonic acid ester compound and sodium acetateTrifluoromethyl trimethyl silane TMSCF 3 1 to 10 liters of second organic solvent per mole of sulfonate compound, 1. The reaction formula is as follows:
the second organic solvent is a mixture of a first organic solvent and a second organic solvent, wherein the volume ratio of the second organic solvent to the second organic solvent is 0.5-1.2: 1 of a mixed solvent of redistilled dichloromethane DCM and redistilled dimethyl sulfoxide DMSO, the concentration of which is 0.1-1.0M.
Adding a trifluoromethyl sulfide substance, m-chloroperoxybenzoic acid and a third organic solvent into the container in the step (3), and reacting for 10 to 16 hours at normal temperature under the protection of nitrogen or argon to obtain a trifluoromethyl sulfoxide reagent with the structure of
Wherein EWG is COOMe, COOEt, COO i Pr、COO t Bu and CN. In the reaction system, the mol ratio of m-chloroperoxybenzoic acid to the trifluoro-methyl sulfide substances is 1. The reaction formula is as follows:
the third organic solvent is redistilled dichloromethane DCM with the concentration of 0.1-1.0M.
It is another object of the present invention to provide the use of the trifluoromethyl sulfoxide reagent prepared by the above method as a trifluoromethyl sulfoxylating agent and a trifluoromethylthiolating agent, using as a substrate a diaryliodonium salt derivative, a 1, 1-stilbene derivative, or an electron-rich aromatic hydrocarbon.
The diaryl iodonium salt derivative is diphenyl trifluoromethanesulfonate iodonium salt derivative with the structural formula
Substituent R 1 And R 2 When the same is hydrogen, pOne of bromine, p-chlorine, p-methoxy, o-methyl, o-chlorine and m-methyl; substituent R 1 And R 2 When not identical, the substituents R 1 Is hydrogen, a substituent R 2 Is mesityl or o-methyl.
The 1, 1-stilbene derivative has the structure of
Substituent R 3 And R 4 When the same, the compound is one of p-fluorine, p-bromine, p-chlorine, p-methoxyl and p-methyl; substituent R 3 And R 4 When not identical, the substituent R 3 Is hydrogen, a substituent R 4 Is one of p-methoxy, p-phenyl, 3, 4-dimethyl, p-chlorine, m-chlorine and o-methyl.
The electron-rich aromatic hydrocarbon structure is
The substituent R is one of methoxyl, o-dimethoxy, m-dimethoxy, sym-trimethyl, sym-trimethoxy, 1-chloro-2-methoxyl, 1-bromo-2-methoxyl, 1,2, 3-trimethoxy and 1, 2-methylenedioxy; the main structure of the aromatic hydrocarbon is benzene or naphthalene.
The method overcomes the defects of expensive starting materials and complicated reagent synthesis in the prior method, prepares the trifluoromethyl sulfoxide reagent by using cheap and easily obtained bromide as an initial substance, and further realizes the regulation and control of the reaction activity of the reagent by regulating different groups in a reagent framework. At the same time, the reagent can carry out bifunctional reaction, and can be used as a nucleophilic reagent to react with diaryl iodonium salt derivatives, and can be used as an electrophilic reagent to react with 1, 1-stilbene derivatives and electron-rich aromatic hydrocarbons.
The invention has the following beneficial effects:
(1) The cost is low, and the trifluoromethyl sulfoxide reagent can be obtained without complicated column chromatography separation by starting from bromide and performing simple three-step reaction.
(2) A class of trifluoromethyl sulfoxide reagents with different leaving groups introduced into a reagent framework are prepared, and the adjustable structure and controllable activity are realized.
(3) The reaction of the trifluoromethyl sulfoxide reagent prepared by the invention and diaryl iodonium salt is utilized to realize C (sp) 2 )-S(O)CF 3 Constructing a chemical bond; reaction of trifluoromethyl sulfoxide reagent with 1, 1-stilbene derivative and electron-rich aromatic hydrocarbon realizes C (sp) 2 )-SCF 3 And (5) constructing a chemical bond.
Detailed Description
The present invention is further described in the following examples, which are intended to be illustrative only and not to be limiting as to the scope of the invention, which is to be given the full breadth of the appended claims and any and all equivalent modifications thereof which would occur to persons skilled in the art upon reading the present specification and which fall within the limits of the appended claims.
In the embodiment of the invention, if not specifically mentioned, the normal temperature is 20-25 ℃.
Firstly, the existing method is adopted to prepare a sulfonic acid ester compound, then a trifluoro-methyl-thiolether substance is prepared, and finally a trifluoromethyl sulfoxide reagent is synthesized, wherein the structure is as follows
Example 1 was prepared.
The method comprises the following specific operation steps: firstly, a 200mL round-bottom flask which is baked for 2 hours in an oven at 100 ℃ is cooled, then a magneton is placed, the atmosphere is pumped and exchanged for three times under nitrogen or argon atmosphere, 50mmol of 4-toluene sodium thiosulfonate salt is added, 50mmol of methyl 3-bromopropionate and 1.0M of ultra-dry N, N-dimethylformamide solvent are added, the reaction solution is stirred and reacted for 24 hours at normal temperature, the reaction solution is poured into 50mL of water, the organic phase is extracted by ethyl acetate (50 mL multiplied by 3), the combined organic phase is back-extracted by water for 5 times, then dried by anhydrous sodium sulfate for 15 minutes, then filtered by a sand core funnel, the combined organic phase is combined, and the solvent is removed by rotary evaporation. The final crude product can be recrystallized from dichloromethane and petroleum etherThe desired product 1a was obtained as a white solid in an isolated yield of 84%. 1 H NMR(400MHz，CDCl 3 )δ7.81(2H，d，J＝8.3Hz)，7.35(2H，d，J＝8.1Hz)，3.67(3H，s)，3.18(2H，t，J＝7.0Hz)，2.73(2H，t，J＝7.0Hz)，2.45(3H，s)；
Then a 200mL round bottom flask with a branch opening which is baked for 2 hours in an oven at 100 ℃ is taken, after cooling, magnetons are put into the flask, the flask is vacuumized for three times under the atmosphere of nitrogen or argon, and 40mmol of 1a and 120mmol of NaOAc are mixed at the temperature of-20 ℃ in a 0.1M volume ratio of 1:2 redistilled dichloromethane and dimethyl sulfoxide and 120mmol trimethyltrifluoromethyl silane was added dropwise thereto, after 12 hours of reaction, 50mL of brine was poured into the reaction solution, the organic phase was extracted with dichloromethane (50 mL. Times.3), the combined organic phases were back-extracted 5 times with saturated brine, and then dried over anhydrous sodium sulfate for 15min, and then filtered with a sand-core funnel, the organic phases were combined, and the solvent was removed by rotary evaporation to give crude product 2a.
And finally, taking a 100mL round-bottom flask which is baked for 2 hours in an oven at 100 ℃, cooling, adding magnetons, vacuumizing for three times under the atmosphere of nitrogen or argon, adding 40mmol of M-chloroperoxybenzoic acid into 0.2M dichloromethane, dissolving, directly adding the crude product 2a, and reacting for 12 hours at normal temperature. After the reaction, an appropriate amount of saturated sodium carbonate solution was poured into the reaction solution, then the organic phase was extracted with dichloromethane (50 mL × 3), the combined organic phases were back-extracted with saturated brine for 3 times, and then dried over anhydrous sodium sulfate for 15min, and then filtered with a sand core funnel, and the organic phases were combined, and the solvent was removed by rotary evaporation to obtain a crude product. The crude product was distilled under reduced pressure to afford relatively pure 3a in 65% yield. Column chromatography of 3a may also be performed to further purify 3a. 1 H NMR(400MHz，CDCl 3 )δ3.75(3H，s)，3.28–3.24(2H，m)，3.03–2.79(m，2H)。
Example 2 was prepared.
The method comprises the following specific operation steps: first, the mixture is baked for 1 hour in an oven at 150 DEG CThe method comprises the following steps of cooling a 200mL round-bottom flask, adding magnetons, vacuumizing and ventilating for three times in a nitrogen or argon atmosphere, adding 15mmol of 4-sodium toluenesulfonate, adding 15mmol of ethyl 3-bromopropionate and 0.5M of ultra-dry N, N-dimethylformamide solvent, stirring and reacting for 12 hours at normal temperature, pouring a reaction solution into 30mL of water, extracting an organic phase with ethyl acetate (30 mL multiplied by 3), performing back extraction on the combined organic phase with water for 3 times, drying with anhydrous sodium sulfate for 15 minutes, filtering with a sand core funnel, combining the organic phases, and performing rotary evaporation to remove the solvent. Finally, the crude product can be subjected to silica gel column chromatography to obtain the target product 1b as a white solid with an isolation yield of 78%. 1 H NMR(400MHz，CDCl 3 )δ7.81(2H，d，J＝8.3Hz)，7.35(2H，d，J＝8.3Hz)，4.13(2H，q，J＝7.1Hz)，3.18(2H，t，J＝7.0Hz)，2.71(2H，t，J＝7.0Hz)，2.45(3H，s)，1.24(3H，t，J＝7.1Hz)。
Then, a 100mL round bottom flask with a branch mouth which is baked in an oven at 150 ℃ for 1 hour is taken, after cooling, a magneton is put into the flask, the atmosphere of nitrogen or argon is pumped and exchanged for three times, 10mmol of 1b and 30mmol of NaOAc are mixed in 0.5M dichloromethane and dimethyl sulfoxide which are steamed in a volume ratio of 4 to 5 at-10 ℃,30 mmol of trimethyl trifluoromethyl silicon is dripped into the mixture, after 6 hours of reaction, 50mL of saline solution is poured into the reaction solution, the organic phase is extracted by dichloromethane (50 mL. Times.3), the combined organic phase is back-extracted by saturated saline solution for 5 times, then dried by anhydrous sodium sulfate for 15 minutes, and then filtered by a sand core funnel, the organic phase is combined, and the solvent is removed by rotary evaporation, thus obtaining a crude product 2b.
And finally, taking a 100mL round-bottom flask which is baked for 1 hour in an oven at 150 ℃, cooling, putting in magnetons, vacuumizing for three times under the atmosphere of nitrogen or argon, adding 10mmol of M-chloroperoxybenzoic acid into 0.5M dichloromethane, directly adding the crude product 2b after dissolution, and reacting for 10 hours at normal temperature. After the reaction, an appropriate amount of saturated sodium carbonate solution was poured into the reaction solution, then the organic phase was extracted with dichloromethane (30 mL × 3), the combined organic phase was back-extracted with saturated brine for 3 times, and then dried with anhydrous sodium sulfate for 15min, and then filtered with a sand core funnel, the organic phases were combined, and the solvent was removed by rotary evaporation to obtain a crude product. Performing column chromatography separation on 3b to obtain purified productThe yield of 3b was 51.6%. 1 H NMR(400MHz，CDCl 3 )δ4.20(2H，q，J＝7.1Hz)，3.29–3.24(2H，m)，3.03–2.78(2H，m)，1.28(3H，t，J＝7.1Hz)。
Example 3 was prepared.
The method comprises the following specific operation steps: firstly, a 200mL round-bottom flask which is baked for 1.5 hours in an oven at 120 ℃ is cooled, then a magneton is placed, the atmosphere is pumped and exchanged for three times under nitrogen or argon atmosphere, 15mmol of 4-toluene sodium thiosulfonate salt is added, 15mmol of 3-bromopropyl acrylate and 0.1M of ultra-dry N, N-dimethylacetamide are added, the reaction solution is stirred and reacted for 18 hours at normal temperature, the reaction solution is poured into 300mL of water, the organic phase is extracted by ethyl acetate (300 mL multiplied by 3), the combined organic phase is back-extracted by 3 times by water, then dried for 15 minutes by anhydrous sodium sulfate, then filtered by a sand core funnel, the combined organic phase is spin-evaporated to remove the solvent. The final crude product was subjected to silica gel column chromatography to give the objective product 1c as a colorless liquid in an isolated yield of 61%. 1 H NMR(400MHz，CDCl 3 )δ7.81(2H，d，J＝8.2Hz)，7.35(2H，d，J＝8.0Hz)，3.17(2H，t，J＝7.0Hz)，2.67(2H，t，J＝7.0Hz)，2.45(3H，s)，1.21(3H，s)，1.20(3H，s)。
Then a 100mL round bottom flask with a branch opening which is baked for 1.5 hours in an oven at 120 ℃ is taken, after cooling, a magneton is put into the flask, the atmosphere of nitrogen or argon is pumped and exchanged for three times, 10mmol of 1c and 30mmol of NaOAc are mixed at-18 ℃ in a 0.8M volume ratio of 1: 1-redistilled dichloromethane and dimethyl sulfoxide, and 30mmol trimethyltrifluoromethyl silane was added dropwise thereto, after 18 hours of reaction, 50mL of brine was poured into the reaction solution, the organic phase was extracted with dichloromethane (50 mL × 3), the combined organic phases were back-extracted 5 times with saturated brine, and then dried over anhydrous sodium sulfate for 15min, and then filtered with a sand core funnel, the organic phases were combined, and the solvent was removed by rotary evaporation to obtain a crude product 2c.
Finally, a 100mL round bottom flask which is baked for 1.5 hours in an oven at 120 ℃ is taken, a magneton is placed after cooling,and (3) vacuumizing for three times under the atmosphere of nitrogen or argon, adding 10mmol of M-chloroperoxybenzoic acid into 0.1M dichloromethane, directly adding the crude product 2c after dissolution, and reacting for 16h at normal temperature. After the reaction was completed, an appropriate amount of saturated sodium carbonate solution was poured into the reaction solution, then the organic phase was extracted with dichloromethane (30 mL × 3), the combined organic phases were back-extracted with saturated brine for 3 times, and then dried over anhydrous sodium sulfate for 15min, and then filtered with a sand core funnel, and the organic phases were combined, and the solvent was removed by rotary evaporation to obtain a crude product 3c. Column chromatography of 3c gave purified 3c in 53.2% yield. 1 H NMR(400MHz，CDCl 3 )δ5.06(1H，m，J＝6.2Hz)，3.28–3.23(2H，m)，3.01–2.74(2H，m)，1.27(3H，s)，1.25(3H，s)。
Example 4 was prepared.
The method comprises the following specific operation steps: firstly, a 200mL round-bottom flask which is baked for 1 hour in an oven at 120 ℃ is cooled, then a magneton is placed, air is pumped out for three times under the atmosphere of nitrogen or argon, 20mmol of 4-toluene sodium thiosulfonate salt is added, 20mmol of tert-butyl 3-bromopropionate and 0.4M of ultra-dry N, N-dimethylformamide solvent are added, the reaction solution is stirred and reacted for 15 hours at normal temperature, the reaction solution is poured into 40mL of water, the organic phase is extracted by ethyl acetate (30 mL multiplied by 3), the combined organic phase is back-extracted by 3 times by water, then dried for 15 minutes by anhydrous sodium sulfate, then filtered by a sand core funnel, the combined organic phase is spin-evaporated to remove the solvent. The final crude product was subjected to silica gel column chromatography to give the objective product 1d as a colorless liquid in an isolated yield of 67.9%. 1 H NMR(400MHz，CDCl 3 )δ7.81(2H，d，J＝8.1Hz)，7.34(2H，d，J＝8.1Hz)，3.13(2H，t，J＝7.0Hz)，2.62(2H，t，J＝6.9Hz)，2.45(3H，s)，1.41(9H，s).
Then a 100mL round bottom flask with a branch opening which is baked for 1 hour in an oven at 120 ℃ is taken, after cooling, a magneton is put into the flask, the atmosphere of nitrogen or argon is pumped and exchanged for three times, 10mmol of 1d and 30mmol of NaOAc are mixed at-30 ℃ in a 1.0M volume ratio of 6: 5-redistilled dichloromethane and dimethyl sulfoxide, and 30mmol of trimethyltrifluoromethylsilicon was added dropwise thereto, after 12 hours of reaction, 50mL of a saline solution was poured into the reaction solution, the organic phase was extracted with dichloromethane (50 mL. Times.3), the combined organic phases were back-extracted 5 times with a saturated saline solution, and then dried over anhydrous sodium sulfate for 15 minutes, followed by filtration through a sand-core funnel, the organic phases were combined, and the solvent was removed by rotary evaporation to obtain a crude product 2d.
And finally, taking a 100mL round-bottom flask which is baked for 1 hour in an oven at the temperature of 120 ℃, cooling, then putting in magnetons, vacuumizing for three times under the atmosphere of nitrogen or argon, dissolving 10mmol of M-chloroperoxybenzoic acid in 1.0M dichloromethane, directly adding the crude product 2d, and reacting for 14 hours at normal temperature. After the reaction, an appropriate amount of saturated sodium carbonate solution was poured into the reaction solution, then the organic phase was extracted with dichloromethane (30 mL × 3), the combined organic phase was back-extracted with saturated brine for 3 times, and then dried with anhydrous sodium sulfate for 15min, and then filtered with a sand core funnel, the organic phases were combined, and the solvent was removed by rotary evaporation to obtain a crude product 3d. Column chromatography of 3d gave purified 3d in 65.9% yield. 1 H NMR(400MHz，CDCl 3 )δ3.29–3.16(2H，m)，2.94–2.71(2H，m)，1.47(9H，s)。
Example 5 was prepared.
The method comprises the following specific operation steps: firstly, a 200mL round-bottom flask which is baked for 2 hours in an oven at 120 ℃ is cooled, then magnetons are placed in the flask, the atmosphere of nitrogen or argon is pumped and exchanged for three times, 20mmol of 4-toluene sodium thiosulfonate salt is added, 20mmol of 3-bromopropionic propionitrile and 0.8M of ultra-dry N, N-dimethylacetamide are added, the mixture is stirred and reacted for 20 hours at normal temperature, the reaction solution is poured into 40mL of water, the organic phase is extracted by ethyl acetate (30 mL multiplied by 3), the combined organic phase is back-extracted by water for 3 times, then dried for 15 minutes by anhydrous sodium sulfate, then filtered by a sand core funnel, the combined organic phase is spin-evaporated to remove the solvent. Finally, the crude product was subjected to silica gel column chromatography to obtain the objective product 1e as a colorless liquid in an isolated yield of 42.2%. 1 H NMR(400MHz，CDCl 3 )δ7.82(2H，d，J＝8.3Hz)，7.38(2H，d，J＝8.0Hz)，3.18(2H，t，J＝7.2Hz)，2.81(2H，t，J＝7.2Hz)，2.47(3H，s).
Then a 100mL round bottom flask with a branch opening which is baked in an oven at 120 ℃ for 2 hours is taken, after cooling, magnetons are put into the flask, gas is pumped out for three times under the nitrogen atmosphere, and 8.4mmol of 1e and 25.2mmol of NaOAc are mixed at-25 ℃ in a 0.4M volume ratio of 3: 5-redistilled dichloromethane and dimethyl sulfoxide, and 25.2mmol of trimethyltrifluoromethylsilane was added dropwise thereto, after reaction for 15 hours, 50mL of brine was poured into the reaction solution, the organic phase was extracted with dichloromethane (30 mL. Times.3), the combined organic phases were back-extracted 5 times with saturated brine, and then dried over anhydrous sodium sulfate for 15min, and then filtered with a sand-core funnel, the organic phases were combined, and the solvent was removed by rotary evaporation to obtain a crude product 2e.
And finally, taking a 100mL round-bottom flask which is baked for 2 hours in an oven at 120 ℃, cooling, then adding magnetons, exhausting for three times in a nitrogen atmosphere, dissolving 8.4mmol of M-chloroperoxybenzoic acid in 0.8M dichloromethane, directly adding the crude product 2e, and reacting for 11 hours at normal temperature. After the reaction, an appropriate amount of saturated sodium carbonate solution was poured into the reaction solution, then the organic phase was extracted with dichloromethane (20 mL × 3), the combined organic phase was back-extracted with saturated brine for 3 times, and then dried with anhydrous sodium sulfate for 15min, and then filtered with a sand core funnel, the organic phases were combined, and the solvent was removed by rotary evaporation to obtain a crude product 3e. Column chromatography of 3e gave purified 3e in 36.7% yield. 1 H NMR(400MHz，CDCl 3 )δ3.40–3.20(2H，m)，3.08–2.84(2H，m)。
Use of the trifluoromethyl sulfoxides prepared according to the process of examples 1 to 5 as reagents for trifluoromethylsulfoxylating and trifluoromethylthionating, with the substrates diaryliodonium salt derivatives or 1, 1-diphenylethylene derivatives or electron-rich aromatics.
Example 1 was applied.
The method comprises the following specific operation steps: 25.0mL of a sealed tube which has been baked in an oven at 120 ℃ for 1.5 hours is placed in a magneton and cooled, the gas is evacuated three times under a nitrogen atmosphere, 0.550mmol of iodine diphenyltrifluoromethanesulfonate and 1.50mmol of cesium carbonate are added, the gas is evacuated three times under a nitrogen or argon atmosphere, 5.00mL of ultra-dry 1, 4-dioxane and 0.500mmol of a reagent are added, the reaction mixture is stirred at normal temperature for 12 hours, the reaction mixture is poured into 20mL of saturated saline solution, the aqueous phase is extracted with dichloromethane (20 mL. Times.3), the combined organic phase is back-extracted 5 times with saturated saline solution, and then dried with anhydrous sodium sulfate for 15 minutes, and then filtered with a sand core funnel, the combined organic phase is combined, and the solvent is removed by rotary evaporation. Finally, the crude product is added with 0.500mmol of trifluorotoluene internal standard, the fluorine spectrum yield proves that the reaction yield is 85 percent, and the GC-MS can prove that the product is obtained.
Example 2 was applied.
The method comprises the following specific operation steps: 25.0mL of a sealed tube which has been baked in an oven at 120 ℃ for 1 hour is cooled, a magneton is placed, gas is evacuated three times under a nitrogen atmosphere, 0.550mmol of iodonium p-chlorodiphenyltrifluoromethanesulfonate and 1.50mmol of cesium carbonate are added, gas is evacuated three times under a nitrogen or argon atmosphere, 5.00mL of ultra-dry 1, 4-dioxane and 0.500mmol of a reagent are added, the reaction is stirred at normal temperature for 12 hours, the reaction solution is poured into 20mL of saturated saline, the aqueous phase is extracted with dichloromethane (20 mL. Times.3), the combined organic phase is back-extracted 5 times with saturated saline, and then dried with anhydrous sodium sulfate for 15 minutes, and then filtered by a sand core of a funnel, the combined organic phase is subjected to rotary evaporation to remove the solvent, and finally the crude product can be subjected to silica gel column chromatography to obtain a colorless liquid target product with a separation yield of 81%. 1 H NMR(500MHz，CDCl 3 )δ7.73(2H，d，J＝8.2Hz)，7.59(2H，d，J＝8.6Hz)； 13 C NMR(101MHz，CDCl 3 )δ140.4，134.1，130.1，127.4，124.6(q，J C-F ＝336.5Hz)； 19 FNMR(471MHz，CDCl 3 )δ–74.9。
Example 3 was applied.
The method comprises the following specific operation steps: after cooling, a magneton was placed in a 25.0mL sealed tube which had been baked in an oven at 120 ℃ for 2 hours, and the tube was evacuated under nitrogen atmosphere three times, 0.550mmol of iodonium p-bromodiphenyltriflate and 1.50mmol of cesium carbonate were added, evacuation was carried out under nitrogen or argon atmosphere three times, 5.00mL of ultra-dry 1, 4-dioxane and 0.500mmol of a reagent were added, the reaction was stirred at room temperature for 12 hours, the reaction solution was poured into 20mL of saturated saline solution, the aqueous phase was extracted with dichloromethane (20 mL. Times.3), the combined organic phase was back-extracted with saturated saline solution 5 times, and after that, drying was carried out with anhydrous sodium sulfate for 15 minutes, and then filtering was carried out with a sand core funnel, the organic phases were combined, the solvent was removed by rotary evaporation, and finally the crude product was chromatographed on a silica gel column to give a colorless liquid as the objective product in 79% isolated yield. 1 H NMR(400MHz，CDCl 3 )δ7.75(2H，d，J＝8.6Hz)，7.65(2H，d，J＝8.4Hz)； 13 C NMR(101MHz，CDCl 3 )δ134.7，133.0，128.8，127.4，124.4(q，J C-F ＝336.5Hz)； 19 F NMR(471MHz，CDCl 3 )δ–74.4。
Example 4 was applied.
The method comprises the following specific operation steps: sealing 25.0mL of tube which has been dried in an oven at 100 ℃ for 2 hours, cooling, placing magneton, evacuating under nitrogen atmosphere for three times, adding 0.550mmol of iodonium o-methyldiphenyltrifluoromethanesulfonate and 1.50mmol of cesium carbonate, evacuating under nitrogen or argon atmosphere for three times, adding 5.00mL of ultra-dry 1, 4-dioxane and 0.500mmol of reagent, stirring at room temperature for 12 hours, pouring the reaction solution into 20mL of saturated saline solution, extracting the aqueous phase with dichloromethane (20 mL. Times.3), back-extracting the combined organic phase with saturated saline solution for 5 times, drying with anhydrous sodium sulfate for 15 minutes, and passing through a sand core funnelFiltration, combination of the organic phases, removal of the solvent by rotary evaporation and finally chromatography on silica gel column gave the desired product as a colorless liquid in 78% isolated yield. 1 H NMR(400MHz，CDCl 3 )δ8.00(1H，d，J＝7.7Hz)，7.54–7.42(2H，m)，7.29(1H，d，J＝7.5Hz)，2.45(3H，s)； 13 C NMR(101MHz，CDCl 3 )δ138.0，134.2，133.2，131.4，127.3，125.9，125.3(q，J C-F ＝337.1Hz)，18.3； 19 F NMR(471MHz，CDCl 3 )δ–73.6。
Example 5 was applied.
The method comprises the following specific operation steps: 25.0mL of a sealed tube which has been baked in an oven at 100 ℃ for 1 hour is cooled, a magneton is placed into the tube, the tube is evacuated three times under a nitrogen atmosphere, 0.550mmol of iodonium o-methoxydiphenyl trifluoromethanesulfonate and 1.50mmol of cesium carbonate are added, the tube is evacuated three times under a nitrogen or argon atmosphere, 5.00mL of ultra-dry 1, 4-dioxane and 0.500mmol of a reagent are added, the reaction solution is stirred at normal temperature for 12 hours, the reaction solution is poured into 20mL of saturated saline, the aqueous phase is extracted with dichloromethane (20 mL. Times.3), the combined organic phase is back-extracted 5 times with saturated saline, and then dried with anhydrous sodium sulfate for 15 minutes, and then filtered by a sand core funnel, the combined organic phase is combined, the solvent is removed by rotary evaporation, and finally the crude product can be subjected to silica gel column chromatography to obtain a colorless liquid target product with the separation yield of 85%. IR (thin film) 2874 (w), 2756 (w), 1590 (m), 1479(s), 1278(s), 1247 (m), 1173(s), 1130(s), 1075(s), 1049(s), 1016(s), 795 (m), 755(s); 1 H NMR(400MHz，CDCl 3 )δ7.89(1H，d，J＝9.1Hz)，7.19(1H，dd，J＝8.5，8.9Hz)，7.19(1H，dd，J＝7.8，7.4Hz)，6.99(1H，d，J＝8.3Hz)，3.88(3H，s)； 13 C NMR(101MHz，CDCl 3 )δ157.8，134.9，126.8，125.2(q，J C-F ＝340.2Hz)，123.5，121.8，111.5，56.1； 19 F NMR(471MHz，CDCl 3 )δ–74.0；H RMS(ESI+)[M+H]+calc’dforC 8 H 7 F 3 O 2 SNa:247.0011，found:247.0014。
example 6 was applied.
The method comprises the following specific operation steps: after cooling, a magneton is placed in a 25.0mL sealed tube which is baked in an oven at 100 ℃ for 1.5 hours, the tube is evacuated under nitrogen atmosphere for three times, 0.550mmol of iodonium p-methoxydiphenyl trifluoromethanesulfonate and 1.50mmol of cesium carbonate are added, the gas is evacuated under nitrogen or argon atmosphere for three times, 5.00mL of ultra-dry 1, 4-dioxane and 0.500mmol of reagents are added, the reaction is stirred at normal temperature for 12 hours, the reaction solution is poured into 20mL of saturated saline solution, the aqueous phase is extracted with dichloromethane (20 mL. Times.3), the combined organic phase is back extracted with saturated saline solution for 5 times, then dried with anhydrous sodium sulfate for 15 minutes, filtered by a sand core funnel, the organic phases are combined, the solvent is removed by rotary evaporation, and finally the crude product can be separated by silica gel column chromatography to obtain a colorless liquid target product at a separation yield of 95%. 1 H NMR(400MHz，CDCl 3 )δ7.68(2H，d，J＝8.7Hz)，7.04(2H，d，J＝8.9Hz)，3.82(3H，s)； 13 C NMR(101MHz，CDCl 3 )δ164.0，128.1，126.1，124.7(q，J C-F ＝336.0Hz)，115.2，55.6； 19 F NMR(471MHz，CDCl 3 )δ–75.4。
Example 7 was applied.
The method comprises the following specific operation steps: drying 25.0mL of the solution in an oven at 150 ℃ for 1 hour, sealing the tube, cooling, placing a magneton, exhausting gas for three times in a nitrogen atmosphere, adding 0.550mmol of iodonium o-chlorodiphenyltrifluoromethanesulfonate and 1.50mmol of cesium carbonate, exhausting gas for three times in a nitrogen or argon atmosphere, adding 5.00mL of ultra-dry 1, 4-dioxane and 0.500mmol of a reagent, stirring and reacting at normal temperature for 12 hours, pouring the reaction solution into 20mL of saturated saline solution, and extracting the aqueous phase with dichloromethane (2: 2)0 mL. Times.3), and the combined organic phases were back-extracted with saturated brine 5 times, then dried over anhydrous sodium sulfate for 15min, and then filtered through a sand-core funnel, and the organic phases were combined, and the solvent was removed by rotary evaporation, and finally the crude product was subjected to silica gel column chromatography to obtain the objective product as a colorless liquid in an isolated yield of 58%. 1 H NMR(400MHz，CDCl 3 )δ8.06–7.99(1H，m)，7.61–7.57(2H，m)，7.52–7.46(1H，m)； 13 C NMR(101MHz，CDCl 3 )δ134.7，134.6，133.4，130.5，128.2，127.9，125.2(q，J C - F ＝339.4Hz)； 19 F NMR(471MHz，CDCl 3 )δ–72.7。
Example 8 was applied.
The method comprises the following specific operation steps: after cooling, a magneton was placed in a 25.0mL sealed tube which had been baked in an oven at 150 ℃ for 2 hours, and the tube was evacuated under nitrogen atmosphere three times, 0.550mmol of iodonium salt of m-methyldiphenyltrifluoromethanesulfonate and 1.50mmol of cesium carbonate were added, evacuation was carried out three times under nitrogen or argon atmosphere, 5.00mL of ultra-dry 1, 4-dioxane and 0.500mmol of a reagent were added, the reaction was stirred at room temperature for 12 hours, the reaction solution was poured into 20mL of saturated saline solution, the aqueous phase was extracted with dichloromethane (20 mL. Times.3), the combined organic phase was back-extracted with saturated saline solution 5 times, and after that, drying was carried out with anhydrous sodium sulfate for 15 minutes, and then filtering was carried out with a sand core funnel, the organic phases were combined, the solvent was removed by rotary evaporation, and finally the crude product was chromatographed on a silica gel column to obtain a colorless liquid as a target product in 96% isolation yield. 1 H NMR(400MHz，CDCl 3 )δ7.60(1H，s)，7.56(1H，d，J＝7.0Hz)，7.56(2H，m)，2.44(3H，s)； 13 C NMR(101MHz，CDCl 3 )δ140.1，135.5，134.5，129.5，126.1，124.8(q，J C-F ＝336.3Hz)，123.2，21.4； 19 F NMR(471MHz，CDCl 3 )δ–74.。
Example 9 was applied.
The method comprises the following specific operation steps: 25.0mL of a sealed tube which has been baked in an oven at 150 ℃ for 1.5 hours is cooled, a magneton is placed, gas is evacuated three times under a nitrogen atmosphere, 0.550mmol of iodine 1-o-methyldiphenyl-1-phenyltrifluoromethanesulfonate and 1.50mmol of cesium carbonate are added, gas is evacuated three times under a nitrogen or argon atmosphere, 5.00mL of ultra-dry 1, 4-dioxane and 0.500mmol of a reagent are added, the reaction is stirred at normal temperature for 12 hours, the reaction solution is poured into 20mL of saturated saline, the aqueous phase is extracted with dichloromethane (20 mL. Times.3), the combined organic phase is back-extracted with saturated saline for 5 times, and then dried with anhydrous sodium sulfate for 15 minutes, and then filtered by a sand core funnel, the organic phases are combined, the solvent is removed by rotary evaporation, and finally the crude product can be separated by silica gel column chromatography to obtain a colorless liquid target product at a separation yield of 68.4%. 1 H NMR(500MHz，CDCl 3 )δ8.00(2H，d，J＝7.8Hz)，7.51(1H，dd，J＝6.2，7.4Hz)，7.46(1H，dd，J＝7.3，7.4Hz)，7.29(1H，d，J＝7.5Hz)，2.46(3H，s)； 13 C NMR(101MHz，CDCl 3 )δ138.0，134.2，133.3，131.4，127.4，125.9，125.3(q，J C-F ＝337.1Hz)，18.3； 19 F NMR(471MHz，CDCl 3 )δ–73.6。
Example 10 was applied.
The method comprises the following specific operation steps: sealing 25.0mL of the tube which is baked for 1 hour in an oven at 110 ℃, cooling, placing a magneton, exhausting gas for three times in a nitrogen atmosphere, adding 0.550mmol of 1-mesityl-1-phenyl trifluoromethanesulfonate iodide salt and 1.50mmol of cesium carbonate, exhausting gas for three times in a nitrogen or argon atmosphere, adding 5.00mL of super-dry 1, 4-dioxane and 0.500mmol of a reagent, stirring and reacting at normal temperature for 12 hours, pouring the reaction solution into 20mL of saturated saline solution, extracting the aqueous phase with dichloromethane (20 mL x 3), back-extracting the combined organic phase with saturated saline solution for 5 times, drying with anhydrous sodium sulfate for 15 minutes, and then leaking a sand coreBucket filtration, combination of organic phases, rotary evaporation to remove the solvent, and final silica gel column chromatography of the crude product can obtain the target product as colorless liquid with 91% separation yield. 1 H NMR(400MHz，CDCl 3 )δ6.92(2H，s)，2.54(6H，bs)，2.31(3H，s)； 13 C NMR(101MHz，CDCl 3 )δ143.7，131.6，128.3，126.2(q，J C-F ＝262.6Hz)，121.6，21.2，19.2； 19 F NMR(471MHz，CDCl 3 )δ–70.1。
Example 11 was applied.
The method comprises the following specific operation steps: a25.0 mL reaction tube with a branch opening which is baked for 2 hours in an oven at 110 ℃ is cooled, a magneton is placed into the reaction tube, gas is pumped out for three times under the nitrogen atmosphere, 2.50mL carbon tetrachloride, 0.500mmol 1, 1-stilbene and 0.750mmol reagent are added into the reaction tube under the nitrogen or argon atmosphere, 0.750mmol trifluoromethanesulfonic anhydride is added dropwise, the reaction is stirred for 1 hour at normal temperature, 1.50mmol cesium carbonate is added, and the reaction is carried out for 6 hours at normal temperature. After completion of the reaction, 20mL of saturated brine and 20mL of dichloromethane were added to the reaction solution, the aqueous phase was extracted with dichloromethane (20 mL. Times.3), and the combined organic phases were back-extracted with saturated brine 3 times, dried over anhydrous sodium sulfate for 15min, filtered through a sand core funnel, the organic phases were combined, and the solvent was removed by rotary evaporation. Finally, the crude product can be obtained by silica gel column chromatography with 83% separation yield to obtain a colorless liquid target product. 1 H NMR(400MHz，CDCl 3 )δ7.51–7.44(3H，m)，7.38(3H，d，J＝4.4Hz)，7.31(4H，dd，J＝7.1，6.8Hz)，6.79(1H，s). 13 C NMR(101MHz，CDCl 3 )δ146.5，140.4，138.2，130.0(q，J C-F ＝308.9Hz)，129.5，128.8，128.7，128.6，128.5，127.5，112.3(q，J C-F ＝3.3Hz). 19 F NMR(471MHz，CDCl 3 )δ–42.5。
Example 12 was applied.
The method comprises the following specific operation steps: a25.0 mL reaction tube which is baked for 1.5 hours in an oven at 110 ℃ is cooled, magnetons are placed in the reaction tube, gas is pumped out for three times in a nitrogen atmosphere, 2.50mL of carbon tetrachloride, 0.500mmol of 1, 1-p-chlorostyrene and 0.750mmol of reagent are added in the nitrogen or argon atmosphere, then 0.750mmol of trifluoromethanesulfonic anhydride is added dropwise, the mixture is stirred and reacted for 1 hour at normal temperature, then 1.50mmol of cesium carbonate is added, and the reaction is reacted for 6 hours at normal temperature. After completion of the reaction, 20mL of saturated brine and 20mL of dichloromethane were added to the reaction solution, the aqueous phase was extracted with dichloromethane (20 mL. Times.3), and the combined organic phases were back-extracted with saturated brine 3 times, followed by drying over anhydrous sodium sulfate for 15min, followed by filtration through a sand-core funnel, and the organic phases were combined and the solvent was removed by rotary evaporation. Finally, the crude product can be isolated by silica gel column chromatography in 78% yield to give the desired product as a colorless liquid. 1 H NMR(400MHz，CDCl 3 )δ7.42(2H，d，J＝8.4Hz)，7.31(2H，d，J＝8.5Hz)，7.18(4H，d，J＝8.4Hz)，6.73(1H，s). 13 C NMR(101MHz，CDCl 3 )δ144.1，138.5，136.1，134.9，134.7，130.8，129.7(q，J C-F ＝309.2Hz)，129.2，128.9，128.7，113.4(q，J C-F ＝113.4Hz). 19 F NMR(471MHz，CDCl 3 )δ–42.6。
Example 13 was applied.
The method comprises the following specific operation steps: a25.0 mL reaction tube which is baked for 2 hours in an oven at the temperature of 130 ℃ is cooled, magnetons are placed into the reaction tube, gas is pumped out for three times in a nitrogen atmosphere, 2.50mL of carbon tetrachloride, 0.500mmol of 1, 1-p-methylstyrene and 0.750mmol of reagent are added into the reaction tube in a nitrogen or argon atmosphere, then 0.750mmol of trifluoromethanesulfonic anhydride is added dropwise, the mixture is stirred and reacted for 1 hour at normal temperature, then 1.50mmol of cesium carbonate is added, and the reaction tube is reacted for 6 hours at normal temperature. After completion of the reaction, 20mL of saturated saline and 20mL of methylene chloride were added to the reaction mixture,the aqueous phase was extracted with dichloromethane (20 mL. Times.3) and the combined organic phases were back-extracted 3 times with saturated brine, then dried over anhydrous sodium sulfate for 15min, then filtered through a sand-core funnel, the organic phases were combined and the solvent was removed by rotary evaporation. Finally, the crude product can be separated by silica gel column chromatography to obtain the target product in colorless liquid with the separation yield of 90%. 1 H NMR(500MHz，CDCl 3 )δ7.28(2H，d，J＝7.8Hz)，7.24–7.13(6H，m)，6.69(1H，s)，2.46(3H，s)，2.41(3H，s). 13 C NMR(101MHz，CDCl 3 )δ146.8，138.6，138.4，137.9，135.4，130.0(q，J C-F ＝309.0Hz)，129.4，129.3，127.5，110.7(q，J C-F ＝3.3Hz)，21.5，21.3. 19 F NMR(471MHz，CDCl 3 )δ–42.7。
Example 14 was applied.
The method comprises the following specific operation steps: a25.0 mL reaction tube which is baked for 1 hour in an oven at 130 ℃ is cooled, magnetons are placed into the reaction tube, gas is pumped out for three times in a nitrogen atmosphere, 2.50mL of carbon tetrachloride, 0.500mmol of 1, 1-p-bromostilbene and 0.750mmol of reagent are added into the reaction tube in a nitrogen or argon atmosphere, then 0.750mmol of trifluoromethanesulfonic anhydride is added dropwise, the mixture is stirred and reacted for 1 hour at normal temperature, then 1.50mmol of cesium carbonate is added, and the reaction tube is reacted for 6 hours at normal temperature. After completion of the reaction, 20mL of saturated brine and 20mL of dichloromethane were added to the reaction solution, the aqueous phase was extracted with dichloromethane (20 mL. Times.3), and the combined organic phases were back-extracted with saturated brine 3 times, followed by drying over anhydrous sodium sulfate for 15min, followed by filtration through a sand-core funnel, and the organic phases were combined and the solvent was removed by rotary evaporation. Finally, the crude product was purified by silica gel column chromatography to give the desired product as a colorless liquid in an isolated yield of 76%. 1 H NMR(400MHz，CDCl 3 )δ7.58(2H，d，J＝8.4Hz)，7.46(2H，d，J＝8.5Hz)，7.11(4H，d，J＝8.3Hz)，6.73(1H，s). 13 C NMR(101MHz，CDCl 3 )δ144.1，138.8，136.4，132.2，131.9，131.1，129.6(q，J C - F ＝309.3Hz)，129.0，123.2，123.0，113.5(q，J C-F ＝3.4Hz). 19 F NMR(471MHz，CDCl 3 )δ–42.3。
Example 15 was applied.
The method comprises the following specific operation steps: a25.0 mL reaction tube which is baked for 1.5 hours in an oven at 130 ℃ is cooled, magnetons are placed in the reaction tube, gas is pumped out for three times in a nitrogen atmosphere, 2.50mL of carbon tetrachloride, 0.500mmol of 1, 1-p-fluorostilbene and 0.750mmol of reagent are added in the nitrogen or argon atmosphere, then 0.750mmol of trifluoromethanesulfonic anhydride is added dropwise, stirring reaction is carried out for 1 hour at normal temperature, 1.50mmol of cesium carbonate is added, and reaction is carried out for 6 hours at normal temperature. After completion of the reaction, 20mL of saturated brine and 20mL of dichloromethane were added to the reaction solution, the aqueous phase was extracted with dichloromethane (20 mL. Times.3), and the combined organic phases were back-extracted with saturated brine 3 times, followed by drying over anhydrous sodium sulfate for 15min, followed by filtration through a sand-core funnel, and the organic phases were combined and the solvent was removed by rotary evaporation. Finally, the crude product can be separated by silica gel column chromatography to obtain the target product in colorless liquid with the separation yield of 90%. 1 H NMR(400MHz，CDCl 3 )δ7.21–7.17(4H，m)，7.10(2H，dd，J＝8.6，8.7Hz)，7.00(2H，dd，J＝8.5，8.7Hz)，6.64(1H，s). 13 C NMR(101MHz，CDCl 3 )δ164.2(d，J C-F ＝14.5Hz)，161.7(d，J C-F ＝14.4Hz)，144.8，136.5(d，J C-F ＝3.2Hz)，134.0(d，J C-F ＝3.5Hz)，131.4(d，J C-F ＝8.2Hz)，129.8(q，J C-F ＝309.1Hz)，129.3(d，J C-F ＝8.4Hz)，115.9(d，J C-F ＝31.6Hz)，115.7(d，J C-F ＝31.6Hz)，112.4. 19 F NMR(471MHz，CDCl 3 )δ–42.6，–112.1，–112.9。
Example 16 was applied.
The method comprises the following specific operation steps: a25.0 mL reaction tube with a branch opening which is baked for 1 hour in an oven at the temperature of 140 ℃ is cooled, a magneton is placed into the reaction tube, gas is pumped and exhausted for three times under the nitrogen atmosphere, 2.50mL carbon tetrachloride, 0.500mmol 1, 1-p-methoxystilbene and 0.750mmol reagent are added into the reaction tube under the nitrogen or argon atmosphere, then 0.750mmol trifluoromethanesulfonic anhydride is added dropwise, the reaction tube is stirred for 1 hour at normal temperature, 1.50mmol cesium carbonate is added into the reaction tube, and the reaction tube is reacted for 6 hours at normal temperature. After completion of the reaction, 20mL of saturated brine and 20mL of dichloromethane were added to the reaction solution, the aqueous phase was extracted with dichloromethane (20 mL. Times.3), and the combined organic phases were back-extracted with saturated brine 3 times, followed by drying over anhydrous sodium sulfate for 15min, followed by filtration through a sand-core funnel, and the organic phases were combined and the solvent was removed by rotary evaporation. Finally, the crude product can be obtained by silica gel column chromatography in 89% isolated yield as a colorless liquid target product. 1 H NMR(400MHz，CDCl 3 )δ7.24–7.18(4H，m)，6.98(2H，d，J＝8.5Hz)，6.88(2H，d，J＝8.7Hz)，6.57(1H，s)，3.87(3H，s)，3.84(3H，s). 13 C NMR(101MHz，CDCl 3 )δ160.0，159.8，146.8，133.4，130.9，130.6，130.0(q，J C-F ＝308.8Hz)，129.0，114.0，113.9，109.1(q，J C-F ＝3.1Hz)，55.3，55.3. 19 F NMR(471MHz，CDCl 3 )δ–43.9。
Example 17 was applied.
The method comprises the following specific operation steps: a25.0 mL reaction tube with a branch opening which is baked for 2 hours in an oven at the temperature of 140 ℃ is cooled, a magneton is placed into the reaction tube, gas is pumped and discharged for three times under the nitrogen atmosphere, 2.50mL carbon tetrachloride, 0.500mmol 1-p-chlorophenyl-1-phenylethylene and 0.750mmol reagent are added into the reaction tube under the nitrogen or argon atmosphere, then 0.750mmol trifluoromethanesulfonic anhydride is added dropwise, the reaction tube is stirred for 1 hour at the normal temperature, 1.50mmol cesium carbonate is added, and the reaction tube is reacted for 6 hours at the normal temperature. After completion of the reaction, 20mL of saturated brine and 20mL of methylene chloride were added to the reaction mixture, the aqueous phase was extracted with methylene chloride (20 mL. Times.3), and the mixture was combinedAnd the organic phase is back extracted for 3 times by saturated salt solution, then dried by anhydrous sodium sulfate for 15min, then filtered by a sand core funnel, the organic phase is combined, and the solvent is removed by rotary evaporation. Finally, the crude product can be obtained by silica gel column chromatography with the separation yield of 85 percent as a colorless liquid target product. 1 H NMR(400MHz，CDCl 3 )δ7.41–7.36(2H，m)，7.31–7.25(2H，m)，7.22–7.14(5H，m)，6.68(1H，s). 13 C NMR(101MHz，CDCl 3 )δ145.1，140.1，137.8，134.7，134.5，129.9(q，J C-F ＝309.2Hz)，129.4，128.9，128.8，127.5，112.9(q，J C-F ＝3.2Hz). 19 F NMR(471MHz，CDCl 3 )δ–42.5。
Example 18 was applied.
The method comprises the following specific operation steps: a25.0 mL reaction tube with a branch opening which is baked for 1.5 hours in an oven at the temperature of 140 ℃ is cooled, a magneton is placed in the reaction tube, gas is pumped and discharged for three times under the nitrogen atmosphere, 2.50mL carbon tetrachloride, 0.500mmol 1-p-methoxyphenyl-1-phenylethylene and 0.750mmol reagent are added under the nitrogen or argon atmosphere, then 0.750mmol trifluoromethanesulfonic anhydride is added dropwise, the reaction is stirred for 1 hour at the normal temperature, 1.50mmol cesium carbonate is added, and the reaction is carried out for 6 hours at the normal temperature. After completion of the reaction, 20mL of saturated brine and 20mL of dichloromethane were added to the reaction solution, the aqueous phase was extracted with dichloromethane (20 mL. Times.3), and the combined organic phases were back-extracted with saturated brine 3 times, dried over anhydrous sodium sulfate for 15min, filtered through a sand core funnel, the organic phases were combined, and the solvent was removed by rotary evaporation. Finally, the crude product can be obtained by silica gel column chromatography with the separation yield of 91 percent as a colorless liquid target product. 1 H NMR(400MHz，CDCl 3 )δ7.40–7.33(2H，m)，7.29–7.13(4H，m)，6.82(2H，d，J＝8.7Hz)，6.59(1H，s)，3.76(3H，s). 13 C NMR(101MHz，CDCl 3 )δ160.0，147.0，138.4，133.1，130.9，130.0(q，J C-F ＝308.8Hz)，129.5，128.8，128.7，113.9，109.8(q，J C-F ＝3.1Hz)，55.3. 19 FNMR(471MHz，CDCl 3 )δ–42.7。
Example 19 was used.
The method comprises the following specific operation steps: a25.0 mL branched reaction tube which is dried for 80 minutes in an oven at 120 ℃ is cooled, a magneton is placed into the tube, gas is pumped out for three times under the nitrogen atmosphere, 2.50mL of carbon tetrachloride, 0.500mmol of 1-biphenyl-1-phenylethene and 0.750mmol of reagent are added into the tube under the nitrogen or argon atmosphere, then 0.750mmol of trifluoromethanesulfonic anhydride is added dropwise, the mixture is stirred and reacted for 1 hour at normal temperature, then 1.50mmol of cesium carbonate is added, and the reaction is carried out for 6 hours at normal temperature. After completion of the reaction, 20mL of saturated brine and 20mL of dichloromethane were added to the reaction solution, the aqueous phase was extracted with dichloromethane (20 mL. Times.3), and the combined organic phases were back-extracted with saturated brine 3 times, followed by drying over anhydrous sodium sulfate for 15min, followed by filtration through a sand-core funnel, and the organic phases were combined and the solvent was removed by rotary evaporation. Finally, the crude product was purified by silica gel column chromatography to obtain the desired product as a white solid in an isolated yield of 73%. M.p. =75.7-76.4 ℃; IR (thin film) 3003 (w), 3000 (w), 1598 (w), 1497 (w), 1432 (w), 1107(s), 758(s), 690(s). 1 H NMR(400MHz，CDCl 3 )δ7.75–7.59(4H，m)，7.56–7.31(10H，m)，6.85(1H，s). 13 C NMR(101MHz，CDCl 3 )δ146.1，142.3，140.4，139.2，138.1，130.0(q，J C-F ＝309.1Hz)，129.5，129.0，128.7，128.6，127.9，127.7，127.7，127.4，127.3，127.1，112.2(q，J C-F ＝3.4Hz). 19 F NMR(471MHz，CDCl 3 )δ–42.5。
Example 20 was applied.
The method comprises the following specific operation steps: drying a 25.0mL reaction tube with a branch opening in an oven at 120 ℃ for 100 minutes, cooling, adding magnetons, and pumping in nitrogen atmosphereAnd (3) introducing the mixture three times, adding 2.50mL of carbon tetrachloride, 0.500mmol of 1-biphenyl-1-phenylethene and 0.750mmol of reagent under the atmosphere of nitrogen or argon, then dropwise adding 0.750mmol of trifluoromethanesulfonic anhydride, stirring and reacting for 1h at normal temperature, then adding 1.50mmol of cesium carbonate, and reacting for 6h at normal temperature. After completion of the reaction, 20mL of saturated brine and 20mL of dichloromethane were added to the reaction solution, the aqueous phase was extracted with dichloromethane (20 mL. Times.3), and the combined organic phases were back-extracted with saturated brine 3 times, followed by drying over anhydrous sodium sulfate for 15min, followed by filtration through a sand-core funnel, and the organic phases were combined and the solvent was removed by rotary evaporation. Finally, the crude product was purified by silica gel column chromatography to give the desired product as a white solid in 73% isolated yield. IR (thin film) 3026 (w), 2925 (w), 1504 (m), 1444 (m), 1159 (m), 1103(s), 755(s), 697(s). 1 H NMR(400MHz，CDCl 3 )δ7.49–7.42(5H，m)，7.36–7.31(3H，m)，6.72(1H，s)，2.32(3H，s)，2.29(3H，s). 13 C NMR(101MHz，CDCl 3 )δ147.1，140.7，138.5，137.3，136.8，130.0(q，J C-F ＝308.8Hz)，130.0，129.5，128.7，128.5，127.6，125.1，111.0(q，J C-F ＝3.1Hz)，19.9，19.6. 19 F NMR(471MHz，CDCl 3 )δ–42.6.HRMS(APCI)[M+H]+calc’dforC17H16F3S:309.0919，found:309.0921。
Example 21 was applied.
The method comprises the following specific operation steps: a25.0 mL reaction tube with a branch opening which is dried for 110 minutes in an oven at 120 ℃ is cooled, a magneton is placed into the reaction tube, gas is pumped out for three times under the nitrogen atmosphere, 2.50mL carbon tetrachloride, 0.500mmol 1-m-chlorophenyl-1-phenylethylene and 0.750mmol reagent are added into the reaction tube under the nitrogen or argon atmosphere, then 0.750mmol trifluoromethanesulfonic anhydride is added dropwise, the reaction tube is stirred for 1 hour at normal temperature, 1.50mmol cesium carbonate is added into the reaction tube, and the reaction tube is reacted for 6 hours at normal temperature. After completion of the reaction, 20mL of saturated brine and 20mL of methylene chloride were added to the reaction mixture, the aqueous phase was extracted with methylene chloride (20 mL. Times.3), and the combined organic phases were saturated with saturated brineThe brine was back extracted 3 times, then dried over anhydrous sodium sulfate for 15min, then filtered through a sand-core funnel, the organic phases were combined and the solvent was removed by rotary evaporation. Finally, the crude product was purified by silica gel column chromatography to give the desired product as a colorless liquid in an isolated yield of 69%. IR (thin film) 3203 (w), 1587 (w), 1103(s), 773 (m), 753 (m), 694 (m). 1 H NMR(400MHz，CDCl 3 )δ7.48–7.33(5H，m)，7.28–7.24(3H，m)，7.18–7.15(1H，m)，6.77(1H，s). 13 C NMR(101MHz，CDCl 3 )δ145.2，142.2，139.8，134.8，130.1，129.8(q，J C-F ＝309.1Hz)，129.4，129.0，128.8，127.7，127.5，125.7，113.2(q，J C-F ＝3.1Hz). 19 F NMR(471MHz，CDCl 3 )δ–42.2.
Example 22 was applied.
The method comprises the following specific operation steps: a25.0 mL reaction tube which is baked for 70 minutes in an oven at 120 ℃ is cooled, magnetons are placed into the reaction tube, gas is pumped out for three times in a nitrogen atmosphere, 2.50mL of carbon tetrachloride, 0.500mmol of 1-o-methylphenyl-1-phenylethylene and 0.750mmol of reagent are added into the reaction tube in a nitrogen or argon atmosphere, then 0.750mmol of trifluoromethanesulfonic anhydride is added dropwise, the mixture is stirred and reacted for 1 hour at normal temperature, then 1.50mmol of cesium carbonate is added, and the reaction is carried out for 6 hours at normal temperature. After completion of the reaction, 20mL of saturated brine and 20mL of dichloromethane were added to the reaction solution, the aqueous phase was extracted with dichloromethane (20 mL. Times.3), and the combined organic phases were back-extracted with saturated brine 3 times, dried over anhydrous sodium sulfate for 15min, filtered through a sand core funnel, the organic phases were combined, and the solvent was removed by rotary evaporation. Finally, the crude product was purified by silica gel column chromatography to give the desired product as a colorless liquid in an isolated yield of 62%. IR (thin film) 2923 (m), 2802 (m), 1572 (w), 1465 (w), 1112(s), 751 (m), 731 (m), 694 (m). 1 H NMR(400MHz，CDCl 3 )δ7.43–7.17(9H，m)，6.94(1H，s)，2.17(3H，s). 13 C NMR(101MHz，CDCl 3 )δ145.3，138.7，137.3，136.3，130.8，130.0(q，J C-F ＝309.0Hz)，129.6，128.8，128.5，128.4，126.4，126.2，113.0(q，J C-F ＝3.3Hz)； 19 F NMR(471MHz，CDCl 3 )δ–42.2.
Example 23 was applied.
The method comprises the following specific operation steps: a25.0 mL branched reaction tube which is dried for 80 minutes in an oven at the temperature of 130 ℃ is cooled, magnetons are placed in the tube, gas is pumped out for three times in the nitrogen atmosphere, 2.50mL of carbon tetrachloride, 0.500mmol of anisole and 0.750mmol of reagent are added in the nitrogen or argon atmosphere, then 0.750mmol of trifluoromethanesulfonic anhydride is added in the tube, the mixture is stirred and reacted for 1 hour at the normal temperature, and then 1.50mmol of triethylamine is added in the tube, and the reaction is carried out for 6 hours at the normal temperature. After the reaction, the solvent was removed from the reaction mixture by rotary evaporation. Finally, the crude product can be separated by silica gel column chromatography to obtain a colorless liquid target product with the separation yield of 82 percent. 1 H NMR(400MHz，CDCl 3 )δ7.58(2H，d，J＝8.7Hz)，6.93(2H，d，J＝8.9Hz)，3.84(3H，s). 13 C NMR(101MHz，CDCl 3 )δ162.0，138.4，129.8(q，J C-F ＝309.3Hz)，115.1，114.9(q，J C-F ＝2.0Hz)，55.5. 19 F NMR(471MHz，CDCl 3 )δ–44.0。
Example 24 was applied.
The method comprises the following specific operation steps: a25.0 mL branched reaction tube which is baked for 70 minutes in an oven at the temperature of 130 ℃ is cooled, magnetons are placed in the tube, gas is pumped out for three times in a nitrogen atmosphere, 2.50mL of carbon tetrachloride, 0.500mmol of o-bromoanisole and 0.750mmol of reagent are added in the nitrogen or argon atmosphere, then 0.750mmol of trifluoromethanesulfonic anhydride is added dropwise, stirring reaction is carried out for 1 hour at normal temperature, 1.50mmol of triethylamine is added, and reaction is carried out for 6 hours at normal temperature. After the reaction, the solvent was removed from the reaction mixture by rotary evaporation. Finally passing the crude product through siliconThe gel column chromatography gave the desired product as a colorless liquid in an isolated yield of 63%. 1 H NMR(400MHz，CDCl 3 )δ7.83(1H，s)，7.56(1H，d，J＝8.6Hz)，6.90(1H，d，J＝8.6Hz)，3.91(3H，s). 13 C NMR(101MHz，CDCl 3 )δ158.3，141.0，137.4，129.5(q，J C-F ＝309.5Hz)，116.1(d，J C-F ＝2.1Hz)，112.3，56.4. 19 F NMR(471MHz，CDCl 3 )δ–43.6。
Example 25 was applied.
The method comprises the following specific operation steps: a25.0 mL reaction tube with a branch opening which is dried for 100 minutes in an oven at 130 ℃ is cooled, magnetons are placed in the reaction tube, gas is pumped out for three times under the nitrogen atmosphere, 2.50mL carbon tetrachloride, 0.500mmol o-anisole and 0.750mmol reagent are added under the nitrogen or argon atmosphere, then 0.750mmol trifluoromethanesulfonic anhydride is added dropwise, the reaction is stirred for 1 hour at normal temperature, 1.50mmol triethylamine is added, and the reaction is carried out for 6 hours at normal temperature. After the reaction, the solvent was removed from the reaction mixture by rotary evaporation. Finally, the crude product can be separated by silica gel column chromatography to obtain a colorless liquid target product with the separation yield of 98 percent. 1 H NMR(400MHz，CDCl 3 )δ7.22(1H，dd，J＝8.3，2.0Hz)，7.09(1H，d，J＝1.9Hz)，6.85(1H，d，J＝8.4Hz)，3.87(3H，s)，3.87(3H，s). 13 C NMR(101MHz，CDCl 3 )δ151.6，149.3，130.2，129.7(q，J C-F ＝309.4Hz)，118.9，114.9(q，J C-F ＝2.0Hz)，111.5，56.1，55.9. 19 F NMR(471MHz，CDCl 3 )δ–43.8。
Example 26 was applied.
The method comprises the following specific operation steps: a 25.0mL reaction tube which had been baked in an oven at 130 ℃ for 110 minutes was cooled, then magnetons were placed in the tube, and a nitrogen atmosphere was appliedAnd (2) vacuumizing for three times, adding 2.50mL of carbon tetrachloride, 0.500mmol of piperonyl and 0.750mmol of reagent under the atmosphere of nitrogen or argon, then dropwise adding 0.750mmol of trifluoromethanesulfonic anhydride, stirring and reacting for 1h at normal temperature, then adding 1.50mmol of triethylamine, and reacting for 6h at normal temperature. After the reaction, the solvent was removed from the reaction mixture by rotary evaporation. Finally, the crude product can be isolated by silica gel column chromatography in a yield of 70% to give the desired product as a colorless liquid. 1 H NMR(400MHz，CDCl 3 )δ7.17(1H，d，J＝9.2Hz)，7.09(1H，s)，6.83(1H，d，J＝8.1Hz)，6.04(2H，s). 13 C NMR(101MHz，CDCl 3 )δ150.5，148.4，131.7，129.7(q，J C-F ＝309.4Hz)，116.4，116.1(q，J C-F ＝2.0Hz)，109.2，102.1. 19 F NMR(471MHz，CDCl 3 )δ–43.9。
Example 27 was applied.
The method comprises the following specific operation steps: a25.0 mL reaction tube with a branch opening which is dried for 80 minutes in an oven at the temperature of 140 ℃ is cooled, magnetons are placed in the reaction tube, gas is pumped and exhausted for three times under the nitrogen atmosphere, 2.50mL carbon tetrachloride, 0.500mmol sym-trimethoxy benzene and 0.750mmol reagent are added under the nitrogen or argon atmosphere, then 0.750mmol trifluoromethanesulfonic anhydride is added dropwise, stirring reaction is carried out for 1 hour at normal temperature, 1.50mmol triethylamine is added, and reaction is carried out for 6 hours at normal temperature. After the reaction, the solvent was removed from the reaction mixture by rotary evaporation. Finally, the crude product was purified by silica gel column chromatography to give the desired product as a white solid in an isolated yield of 94%. 1 H NMR(400MHz，CDCl 3 )δ6.13(2H，s)，3.84(3H，s)，3.81(3H，s). 13 C NMR(101MHz，CDCl 3 )δ164.6，163.5，129.6(q，J C-F ＝311.7Hz)，91.4(q，J C-F ＝1.8Hz)，91.0，56.2，55.4. 19 F NMR(471MHz，CDCl 3 )δ–43.5。
Example 28 was applied.
The method comprises the following specific operation steps: a25.0 mL reaction tube with a branch opening which is baked for 70 minutes in an oven at the temperature of 140 ℃ is cooled, magnetons are placed in the reaction tube, gas is pumped and exhausted for three times under the nitrogen atmosphere, 2.50mL carbon tetrachloride, 0.500mmol mesitylene and 0.750mmol reagent are added under the nitrogen or argon atmosphere, then 0.750mmol trifluoromethanesulfonic anhydride is added dropwise, stirring reaction is carried out for 1 hour at normal temperature, 1.50mmol triethylamine is added, and reaction is carried out for 6 hours at normal temperature. After the reaction, the solvent was removed from the reaction mixture by rotary evaporation. Finally, the crude product can be separated by silica gel column chromatography to obtain the target product in colorless liquid with the separation yield of 48 percent. 1 H NMR(400MHz，CDCl 3 )δ7.03(2H，s)，2.56(6H，s)，2.32(3H，s). 13 C NMR(101MHz，CDCl 3 )δ145.4，141.5，130.3(q，J C-F ＝310.4Hz)，129.7，120.2(d，J C-F ＝1.3Hz)，22.2，21.3. 19 F NMR(471MHz，CDCl 3 )δ–41.9。
Example 29 was used.
The method comprises the following specific operation steps: a25.0 mL reaction tube with a branch opening which is dried for 100 minutes in an oven at the temperature of 140 ℃ is cooled, a magneton is placed into the reaction tube, gas is pumped and discharged for three times under the nitrogen atmosphere, 2.50mL carbon tetrachloride, 0.500mmol 1, 3-diphenylmethyl ether and 0.750mmol reagent are added into the reaction tube under the nitrogen or argon atmosphere, then 0.750mmol trifluoromethanesulfonic anhydride is added dropwise, the reaction tube is stirred for 1 hour at the normal temperature, 1.50mmol triethylamine is added, and the reaction tube is reacted for 6 hours at the normal temperature. After the reaction, the solvent was removed from the reaction mixture by rotary evaporation. Finally, the crude product can be separated by silica gel column chromatography to obtain a colorless liquid target product with the separation yield of 98 percent. 1 H NMR(400MHz，CDCl 3 )δ7.52(1H，d，J＝9.2Hz)，6.52–6.50(2H，m)，3.87(3H，s)，3.82(3H，s). 13 C NMR(101MHz，CDCl 3 )δ164.1，162.2，140.3，129.7(q，J C-F ＝310.3Hz)，105.7，103.1(d，J C-F ＝1.3Hz)，99.3，56.0，55.5. 19 F NMR(471MHz，CDCl 3 )δ–43.7。
Example 30 was applied.
The method comprises the following specific operation steps: a25.0 mL branched reaction tube which is dried in an oven at the temperature of 140 ℃ for 110 minutes is cooled, magnetons are placed in the tube, gas is pumped out for three times in the nitrogen atmosphere, 2.50mL of carbon tetrachloride, 0.500mmol of 1-methoxynaphthalene and 0.750mmol of reagent are added in the nitrogen or argon atmosphere, then 0.750mmol of trifluoromethanesulfonic anhydride is added dropwise, the mixture is stirred and reacted for 1 hour at the normal temperature, and then 1.50mmol of triethylamine is added and the reaction is carried out for 6 hours at the normal temperature. After the reaction, the solvent was removed from the reaction mixture by rotary evaporation. Finally, the crude product can be isolated by silica gel column chromatography in 78% yield to give the desired product as a colorless liquid. 1 H NMR(400MHz，CDCl 3 )δ8.46(1H，d，J＝8.5Hz)，8.29(1H，d，J＝8.4Hz)，7.85(1H，d，J＝8.1Hz)，7.62(1H，dd，J＝7.1，7.2Hz)，7.52(1H，dd，J＝8.1，7.1Hz)，6.76(1H，d，J＝8.1Hz)，3.96(3H，s). 13 C NMR(101MHz，CDCl 3 )δ158.8，139.1，136.3，129.9(q，J C-F ＝310.8Hz)，128.2，126.5，126.1，125.8，122.7，112.3(d，J C-F ＝1.5Hz)，104.0，55.8. 19 F NMR(471MHz，CDCl 3 )δ–43.2。
Example 31 was used.
The method comprises the following specific operation steps: drying a 25.0mL reaction tube with a branch opening in an oven at 110 ℃ for 80 minutes, cooling, placing magnetons, exhausting for three times in a nitrogen atmosphere, adding 2.50mL carbon tetrachloride, 0.500mmol 2-methoxynaphthalene and 0.750mmol reagent in the nitrogen or argon atmosphere, then dropwise adding 0.750mmol trifluoromethanesulfonic anhydride, stirring and reacting at normal temperatureAfter 1 hour, 1.50mmol of triethylamine was added and the reaction was carried out at room temperature for 6 hours. After the reaction, the solvent was removed from the reaction mixture by rotary evaporation. Finally, the crude product was purified by silica gel column chromatography to give the desired product as a white solid in an isolated yield of 54%. 1 H NMR(400MHz，CDCl 3 )δ8.56(1H，d，J＝8.6Hz)，8.00(1H，d，J＝9.1Hz)，7.81(1H，d，J＝8.1Hz)，7.64(1H，dd，J＝8.2，8.2Hz)，7.44(1H，dd，J＝7.8，7.1Hz)，7.31(1H，d，J＝9.1Hz)，4.04(3H，s). 13 C NMR(101MHz，CDCl 3 )δ160.8，137.0，134.3，129.8(q，J C-F ＝311.7Hz)，128.4，128.3，125.1，124.4，113.1，105.2(d，J C-F ＝1.2Hz)，56.9. 19 F NMR(471MHz，CDCl 3 )δ–41.8。
Example 32 was applied.
The method comprises the following specific operation steps: a25.0 mL reaction tube with a branch opening which is baked for 70 minutes in an oven at 110 ℃ is cooled, magnetons are placed in the reaction tube, gas is pumped out for three times under the nitrogen atmosphere, 2.50mL of carbon tetrachloride, 0.500mmol of naphthalene and 0.750mmol of reagent are added under the nitrogen or argon atmosphere, then 0.750mmol of trifluoromethanesulfonic anhydride is added dropwise, the reaction is stirred for 1 hour at normal temperature, 1.50mmol of triethylamine is added, and the reaction is carried out for 6 hours at normal temperature. After the reaction, the solvent was removed from the reaction mixture by rotary evaporation. Finally, the crude product was purified by silica gel column chromatography to give the desired product as a colorless liquid in an isolated yield of 64%. 1 H NMR(400MHz，CDCl 3 )δ8.58(1H，d，J＝8.5Hz)，8.01(2H，dd，J＝9.4，8.3Hz)，7.91(1H，d，J＝8.2Hz)，7.68(1H，dd，J＝8.1，7.3Hz)，7.59(1H，dd，J＝7.1，7.1Hz)，7.52(1H，dd，J＝7.6，7.9Hz). 13 C NMR(101MHz，CDCl 3 )δ138.0，135.5，134.4，132.5，130.4(q，J C-F ＝311.7Hz)，128.7，126.9，126.0，125.7，121.7(d，J C-F ＝1.6Hz). 19 F NMR(471MHz，CDCl 3 )δ–42.2。
Example 33 was used.
The method comprises the following specific operation steps: a25.0 mL reaction tube with a branch opening which is dried for 100 minutes in an oven at 110 ℃ is cooled, then magnetons are put in, gas is pumped out for three times under the nitrogen atmosphere, 2.50mL carbon tetrachloride, 0.500mmol 1,2, 3-trimethoxybenzene and 0.750mmol reagent are added under the nitrogen or argon atmosphere, then 0.750mmol trifluoromethanesulfonic anhydride is added dropwise, the mixture is stirred and reacted for 1 hour at normal temperature, and then 1.50mmol triethylamine is added, and the reaction is carried out for 6 hours at normal temperature. After the reaction, the solvent was removed from the reaction mixture by rotary evaporation. Finally, the crude product can be separated by silica gel column chromatography to obtain the target product in colorless liquid with the separation yield of 90%. 1 H NMR(400MHz，CDCl 3 )δ7.33(1H，d，J＝8.8Hz)，6.69(1H，d，J＝8.8Hz)，3.94(3H，s)，3.87(3H，s)，3.85(3H，s). 13 C NMR(101MHz，CDCl 3 )δ156.9，156.0，142.9，133.4，129.6(q，J C-F ＝309.9Hz)，109.3(d，J C-F ＝1.5Hz)，107.7，61.5，60.9，56.1. 19 F NMR(471MHz，CDCl 3 )δ–43.3。
Example 34 was applied.
The method comprises the following specific operation steps: a25.0 mL branched reaction tube which is dried in an oven at 110 ℃ for 110 minutes is cooled, magnetons are placed into the tube, gas is pumped out for three times in a nitrogen atmosphere, 2.50mL of carbon tetrachloride, 0.500mmol of o-chloroanisole and 0.750mmol of reagent are added into the tube in a nitrogen or argon atmosphere, 0.750mmol of trifluoromethanesulfonic anhydride is added dropwise, the tube is stirred and reacted for 1 hour at normal temperature, 1.50mmol of triethylamine is added, and the reaction is carried out for 6 hours at normal temperature. After the reaction, the solvent was removed from the reaction mixture by rotary evaporation. Finally, the crude product can be separated by silica gel column chromatography to obtain the target product in a colorless liquid with 79% separation yield. 1 H NMR(400MHz，CDCl 3 )δ7.67(1H，d，J＝2.1Hz)，7.53(1H，dd，J＝8.6，2.1Hz)，6.95(1H，d，J＝8.6Hz)，3.94(3H，s). 13 C NMR(101MHz，CDCl 3 )δ157.5，138.1，136.7，129.5(q，J C-F ＝309.8Hz)，123.4，115.7(d，J C-F ＝2.1Hz)，112.5，56.4. 19 F NMR(471MHz，CDCl 3 )δ–43.6。
Claims (10)
1. The synthesis method of the trifluoromethyl sulfoxide reagent is characterized by comprising the following steps:
adding sodium p-toluenesulfonate into the container in the step (1), adding bromide and a first organic solvent, and reacting at normal temperature for 12-24 hours under the protection of nitrogen or argon to obtain a sulfonic acid ester compound; in a reaction system, the molar ratio of sodium p-toluenesulfonate to sodium benzenesulfonate is 1;
the structural formula of the sodium p-toluenesulfonate is as follows
The structural formula of the bromide is
The reaction formula is as follows:
adding a sulfonic acid ester compound into the container in the step (2), and then adding sodium acetate and trifluoromethyl trimethylsilane TMSCF 3 Reacting with a second organic solvent for 6 to 18 hours at the temperature of between 10 ℃ below zero and 30 ℃ below zero under the protection of nitrogen or argon to obtain a trifluoro-methyl sulfide substance; in the reaction system, sulfonate compound, sodium acetate and trifluoromethyl trimethylsilane TMSCF 3 1 to 10 liters of a second organic solvent with the concentration of 0.1 to 1.0M is added to each mole of the sulfonic acid ester compound, wherein the molar ratio of (1); the reaction formula is as follows:
adding a trifluoromethyl sulfide substance, m-chloroperoxybenzoic acid and a third organic solvent into the container in the step (3), and reacting for 10 to 16 hours at normal temperature under the protection of nitrogen or argon to obtain a trifluoromethyl sulfoxide reagent with the structure of
In the reaction system, the mol ratio of M-chloroperoxybenzoic acid to the trifluoro-methyl sulfide substances is 1; the reaction formula is as follows:
2. the method of synthesizing a trifluoromethyl sulfoxide reagent of claim 1, wherein: in the step (1), the bromide is 3-bromomethyl propionate with a structural formula
Or 3-bromopropionic acid ethyl ester with the structural formula
Or 3-bromopropionic acid tert-butyl ester with the structural formula
Or 3-bromoisopropyl propionate with the structural formula
Or 3-bromopropionitrile, the structural formula is
3. The method of synthesizing a trifluoromethyl sulfoxide reagent of claim 1, wherein: in the step (1), the first organic solvent is N, N-dimethylformamide solvent DMF or N, N-dimethylacetamide solvent DMAc.
4. The method of synthesizing a trifluoromethyl sulfoxide reagent of claim 1, wherein: in the step (2), the second organic solvent is a mixture of a first organic solvent and a second organic solvent, wherein the volume ratio of the second organic solvent to the second organic solvent is 0.5-1.2: 1, a mixed solvent of redistilled dichloromethane DCM and redistilled dimethylsulfoxide DMSO.
5. The method of synthesizing a trifluoromethyl sulfoxide reagent of claim 1, wherein: in the step (3), the third organic solvent is redistilled dichloromethane DCM.
6. The method of synthesizing a trifluoromethyl sulfoxide reagent of claim 1, wherein: in the step (3), EWG is COOMe, COOEt, COO i Pr、COO t Bu or CN.
7. Use of the trifluoromethyl sulfoxide reagent prepared by the process of claim 1,2,3, 4, 5 or 6 as a trifluoromethyl sulfoxylating agent and a trifluormethionating agent, using a diaryl iodonium salt derivative, a 1, 1-stilbene derivative or an electron-rich aromatic hydrocarbon as a substrate.
8. Use of the trifluoromethyl sulfoxide reagent of claim 7 as a trifluoromethyl sulfoxylating and trifluoromethylating agent, wherein: the diaryl iodonium salt derivative is diphenyl trifluoromethanesulfonate iodonium salt derivative with the structural formula
Substituent R 1 And R 2 When the same, the compound is one of hydrogen, para-bromine, para-chlorine, para-methoxy, ortho-methyl, ortho-chlorine and meta-methyl; substituent R 1 And R 2 When not identical, R 1 Is hydrogen, R 2 Is mesitylOr an ortho-methyl group.
9. Use of the trifluoromethyl sulfoxide reagent of claim 7 as a trifluoromethyl sulfoxylating and trifluoromethylating agent, wherein: the 1, 1-stilbene derivative has the structure of
Substituent R 3 And R 4 When the same, the compound is one of p-fluorine, p-bromine, p-chlorine, p-methoxyl and p-methyl; substituent R 3 And R 4 When not identical, R 3 Is hydrogen, R 4 Is one of p-methoxy, p-phenyl, 3, 4-dimethyl, p-chlorine, m-chlorine and o-methyl.
10. Use of the trifluoromethyl sulfoxide reagent of claim 7 as a trifluoromethyl sulfoxylating and trifluoromethylating agent, wherein: the electron-rich aromatic hydrocarbon structure is
The substituent R is one of methoxyl, o-dimethoxy, m-dimethoxy, mesityl, sym-trimethoxy, 1-chloro-2-methoxyl, 1-bromo-2-methoxyl, 1,2, 3-trimethoxy and 1, 2-methylenedioxy; the main structure of the aromatic hydrocarbon is benzene or naphthalene.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211550947.0A CN115710206B (en) | 2022-12-05 | 2022-12-05 | Synthesis method and application of trifluoromethyl sulfoxide reagent |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211550947.0A CN115710206B (en) | 2022-12-05 | 2022-12-05 | Synthesis method and application of trifluoromethyl sulfoxide reagent |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN115710206A true CN115710206A (en) | 2023-02-24 |
| CN115710206B CN115710206B (en) | 2024-04-12 |
Family
ID=85235581
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202211550947.0A Active CN115710206B (en) | 2022-12-05 | 2022-12-05 | Synthesis method and application of trifluoromethyl sulfoxide reagent |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115710206B (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105985280A (en) * | 2015-01-30 | 2016-10-05 | 中国科学院上海有机化学研究所 | Difluoromethylthiolation reagent, and preparation method and application thereof |
| CN108569942A (en) * | 2018-05-30 | 2018-09-25 | 丽水学院 | A kind of preparation method of α-trifluoromethylthio substituted acetophenone class compound |
| CN113527158A (en) * | 2021-04-21 | 2021-10-22 | 华东师范大学 | Method for constructing fluorine-containing methyl sulfone compound by multi-component coupling |
| CN114957086A (en) * | 2022-06-30 | 2022-08-30 | 杭州师范大学 | Synthesis method and application of N-trifluoromethylsulfonyl phthalimide |
-
2022
- 2022-12-05 CN CN202211550947.0A patent/CN115710206B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105985280A (en) * | 2015-01-30 | 2016-10-05 | 中国科学院上海有机化学研究所 | Difluoromethylthiolation reagent, and preparation method and application thereof |
| CN108569942A (en) * | 2018-05-30 | 2018-09-25 | 丽水学院 | A kind of preparation method of α-trifluoromethylthio substituted acetophenone class compound |
| CN113527158A (en) * | 2021-04-21 | 2021-10-22 | 华东师范大学 | Method for constructing fluorine-containing methyl sulfone compound by multi-component coupling |
| CN114957086A (en) * | 2022-06-30 | 2022-08-30 | 杭州师范大学 | Synthesis method and application of N-trifluoromethylsulfonyl phthalimide |
Non-Patent Citations (3)
| Title |
|---|
| DONG WANG, C. GRACE CARLTON等: "Trifluoromethyl Sulfoxides: Reagents for Metal-Free C-H Trifluoromethylthiolation", ANGEW. CHEM., vol. 132, pages 16052 * |
| SOKOLENKO, LIUBOV V.: "General, practical and selective oxidation protocol for CF3S into CF3S(O) group", MOLECULES, vol. 24, no. 7, pages 1249 * |
| ZIWEI LUO等: "Perfluoroalkylation of Thiosulfonates: Synthesis of Per fluoroalkyl Sulfides", ORG. LETT., vol. 22, pages 6155 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN115710206B (en) | 2024-04-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN110627693B (en) | Allyl sulfone compound and preparation method and application thereof | |
| ES2701808T3 (en) | Method of preparation of vitamin K2 of type MK-7 | |
| CN109336860B (en) | Preparation method of 3-methylsulfonyl-2-substituted benzothiophene compound | |
| CN109761862A (en) | A kind of synthetic method of β-carbonyl sulfone compound | |
| EP3133061A1 (en) | Florfenicol synthesizing method | |
| CN111269074A (en) | Preparation method of α -halogenated trifluoromethyl substituted alkane | |
| CN107540598B (en) | Method for preparing N-difluoromethylthio phthalimide compound | |
| Liu et al. | β-Trifluorosulfinylesters: tuneable reagents for switchable trifluoromethylsulfinylation and C–H trifluoromethylthiolation | |
| CN115710206A (en) | Synthesis method and application of trifluoromethyl sulfoxide reagent | |
| Hu et al. | Defluorinative Multi‐Functionalization of Fluoroaryl Sulfoxides Enabled by Fluorine‐Assisted Temporary Dearomatization | |
| CN111155142B (en) | Method for synthesizing beta-trifluoromethyl substituted alcohol organic molecule | |
| Netscher et al. | Formation of sulfinate esters in the synthesis of triflates | |
| CN114957086B (en) | Synthesis method and application of N-trifluoromethyl sulfonyl phthalimide | |
| CN113880737B (en) | Application of novel persulfate reagent in synthesis of asymmetric polysulfide | |
| JP2018043952A (en) | Antitumor agent and composition containing the same | |
| CN113214124B (en) | Monofluoromethylselenated reagent and preparation method and application thereof | |
| KR20160026720A (en) | Method for producing ether compound | |
| EP1506958B1 (en) | Process for producing shogaol and intermediates for the synthesis thereof | |
| CN106631926A (en) | Method for selectively compounding aryl methyl sulphone and belta-hydroxy sulphone derivative | |
| CN112457340A (en) | Tri/difluoroethylation reagent and preparation method and application thereof | |
| CA2140610C (en) | Method of selective fluorination | |
| BR112018014326B1 (en) | PROCESS FOR PREPARATION OF SUBSTITUTED 2-ARYL ETHANOLS | |
| Iaroshenko et al. | Synthesis of trifluoromethyl-substituted salicylates by cyclocondensation of 1, 3-bis (silyloxy)-1, 3-butadienes with 4, 4-dimethylthio-1, 1, 1-trifluorobut-3-en-2-one | |
| CN115057803B (en) | S- (methyl-d) 3 ) Synthesis method and application of phenyl sulfide substance | |
| CN110590621A (en) | Method for synthesizing 1, 2-bis (arylsulfonyl) ethylene derivative by copper-catalyzed terminal alkyne |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |