CN114702417A - Synthesis method for preparing difluoroethylene sulfide by nucleophilic substitution of beta site of gem-difluoroallene compound - Google Patents
Synthesis method for preparing difluoroethylene sulfide by nucleophilic substitution of beta site of gem-difluoroallene compound Download PDFInfo
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- CN114702417A CN114702417A CN202210103194.2A CN202210103194A CN114702417A CN 114702417 A CN114702417 A CN 114702417A CN 202210103194 A CN202210103194 A CN 202210103194A CN 114702417 A CN114702417 A CN 114702417A
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- difluoroallene
- difluoroethylene
- sulfide
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 39
- WHEHARLKIQJDDA-UHFFFAOYSA-N 2,3-difluorothiirane Chemical compound FC1C(S1)F WHEHARLKIQJDDA-UHFFFAOYSA-N 0.000 title claims abstract description 21
- 238000010534 nucleophilic substitution reaction Methods 0.000 title claims abstract description 21
- 238000001308 synthesis method Methods 0.000 title claims abstract description 9
- IXHBTMCLRNMKHZ-LBPRGKRZSA-N levobunolol Chemical class O=C1CCCC2=C1C=CC=C2OC[C@@H](O)CNC(C)(C)C IXHBTMCLRNMKHZ-LBPRGKRZSA-N 0.000 title claims abstract description 7
- -1 thiol compound Chemical class 0.000 claims abstract description 26
- 238000006243 chemical reaction Methods 0.000 claims abstract description 16
- 239000003054 catalyst Substances 0.000 claims abstract description 14
- 239000003446 ligand Substances 0.000 claims abstract description 13
- 238000000034 method Methods 0.000 claims abstract description 10
- 239000010948 rhodium Substances 0.000 claims abstract description 10
- 238000010189 synthetic method Methods 0.000 claims abstract description 8
- 229910052703 rhodium Inorganic materials 0.000 claims abstract description 7
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 claims abstract description 7
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 10
- 229940125904 compound 1 Drugs 0.000 claims description 10
- 125000001624 naphthyl group Chemical group 0.000 claims description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 9
- 239000002904 solvent Substances 0.000 claims description 9
- 125000002541 furyl group Chemical group 0.000 claims description 8
- 239000011541 reaction mixture Substances 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 7
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- 125000001041 indolyl group Chemical group 0.000 claims description 6
- 229930192474 thiophene Chemical group 0.000 claims description 6
- 229940125782 compound 2 Drugs 0.000 claims description 5
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 claims description 4
- TZIHFWKZFHZASV-UHFFFAOYSA-N methyl formate Chemical compound COC=O TZIHFWKZFHZASV-UHFFFAOYSA-N 0.000 claims description 4
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 claims description 3
- 229940126214 compound 3 Drugs 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 239000011737 fluorine Substances 0.000 claims description 3
- 239000011261 inert gas Substances 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 3
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims description 2
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 2
- 125000006711 (C2-C12) alkynyl group Chemical group 0.000 claims description 2
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 2
- BLRHMMGNCXNXJL-UHFFFAOYSA-N 1-methylindole Chemical compound C1=CC=C2N(C)C=CC2=C1 BLRHMMGNCXNXJL-UHFFFAOYSA-N 0.000 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 2
- CTYPJIUQROQJBG-DQEYMECFSA-N [(2s,4s)-4-diphenylphosphanylpentan-2-yl]-diphenylphosphane Chemical compound C=1C=CC=CC=1P([C@@H](C)C[C@H](C)P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 CTYPJIUQROQJBG-DQEYMECFSA-N 0.000 claims description 2
- 125000003342 alkenyl group Chemical group 0.000 claims description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Chemical group C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 2
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Chemical group CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 2
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Chemical group C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 2
- 229940095102 methyl benzoate Drugs 0.000 claims description 2
- 239000012046 mixed solvent Substances 0.000 claims description 2
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 claims description 2
- 125000005069 octynyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C#C* 0.000 claims description 2
- 229960005235 piperonyl butoxide Drugs 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 239000008096 xylene Substances 0.000 claims description 2
- 230000002194 synthesizing effect Effects 0.000 claims 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 1
- 230000003197 catalytic effect Effects 0.000 abstract description 3
- 238000005935 nucleophilic addition reaction Methods 0.000 abstract description 3
- 238000011161 development Methods 0.000 abstract description 2
- 239000002994 raw material Substances 0.000 abstract description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 42
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- 239000000243 solution Substances 0.000 description 17
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- 238000003786 synthesis reaction Methods 0.000 description 8
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 7
- 238000004293 19F NMR spectroscopy Methods 0.000 description 7
- 238000005160 1H NMR spectroscopy Methods 0.000 description 7
- 238000004483 ATR-FTIR spectroscopy Methods 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 6
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 6
- 229910052739 hydrogen Inorganic materials 0.000 description 6
- 239000001257 hydrogen Substances 0.000 description 6
- 238000010898 silica gel chromatography Methods 0.000 description 6
- 238000001228 spectrum Methods 0.000 description 6
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- 238000002955 isolation Methods 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 238000004321 preservation Methods 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- WLWNRAWQDZRXMB-YLFCFFPRSA-N (2r,3r,4r,5s)-n,3,4,5-tetrahydroxy-1-(4-phenoxyphenyl)sulfonylpiperidine-2-carboxamide Chemical compound ONC(=O)[C@H]1[C@@H](O)[C@H](O)[C@@H](O)CN1S(=O)(=O)C(C=C1)=CC=C1OC1=CC=CC=C1 WLWNRAWQDZRXMB-YLFCFFPRSA-N 0.000 description 3
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 3
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 3
- 229910052786 argon Inorganic materials 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
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- 229940126062 Compound A Drugs 0.000 description 2
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 2
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 229940043279 diisopropylamine Drugs 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- YLEIFZAVNWDOBM-ZTNXSLBXSA-N ac1l9hc7 Chemical compound C([C@H]12)C[C@@H](C([C@@H](O)CC3)(C)C)[C@@]43C[C@@]14CC[C@@]1(C)[C@@]2(C)C[C@@H]2O[C@]3(O)[C@H](O)C(C)(C)O[C@@H]3[C@@H](C)[C@H]12 YLEIFZAVNWDOBM-ZTNXSLBXSA-N 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 150000001361 allenes Chemical group 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000010504 bond cleavage reaction Methods 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000012295 chemical reaction liquid Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
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- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 239000012434 nucleophilic reagent Substances 0.000 description 1
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 238000009877 rendering Methods 0.000 description 1
- 229910000144 sodium(I) superoxide Inorganic materials 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
- C07C319/16—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides by addition of hydrogen sulfide or its salts to unsaturated compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
- C07F7/1872—Preparation; Treatments not provided for in C07F7/20
- C07F7/1892—Preparation; Treatments not provided for in C07F7/20 by reactions not provided for in C07F7/1876 - C07F7/1888
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a synthetic method for preparing difluoroethylene sulfide by nucleophilic substitution of beta site of a geminal difluoroallene compound. According to the method, gem-difluoroallene compounds are used as raw materials, and in a high-universality catalytic system formed by a rhodium catalyst and a bidentate ligand, a thiol compound performs high-selectivity nucleophilic addition on beta positions of the gem-difluoroallene compounds to prepare various difluoroethylene sulfides. The whole synthesis method has simple steps, mild reaction conditions, high selectivity and ideal yield, is suitable for quickly constructing the difluoroethylene sulfide in large quantity, and can further promote the development and application of the compound.
Description
Technical Field
The invention relates to the field of chemical industry, in particular to a synthetic method for preparing difluoroethylene sulfide by nucleophilic substitution of beta-position of gem-difluoroallene compound.
Background
Fluorine-containing compounds are important chemical intermediates and are widely applied to the fields of medicines, pesticides, materials and the like. In recent years, gem-difluoroallenes containing two fluorine atoms are receiving attention from various fields due to the huge application potential in the fields of new drug development, organic synthesis, material science and the like. However, compared to the non-fluorinated analogues, the gem-difluoroallenes have more reactive sites, not only in the alpha, beta, gamma positions of the allenes, but also in the terminal CF2Nucleophilic substitution of groups that also undergo C-F bond cleavage, thereby rendering regioselective nucleophilic substitution of such compounds challenging.
In addition, the dominant reaction sites of the geminal difluoroallene compound are alpha position and gamma position, in the prior art, nucleophilic reagents such as mercaptan and the like perform selective nucleophilic substitution on the geminal difluoroallene compound, only a few reports are found on the alpha position and the gamma position, and high-selective nucleophilic substitution on the beta position with low reaction activity is not realized yet for the beta position with low reaction activity, so that the difluoroethene sulfide is prepared.
Disclosure of Invention
Aiming at the defects in the prior art, the invention provides a synthetic method for preparing difluoroethylene sulfides by nucleophilic substitution of a geminal difluoroallene compound beta site. The method adopts a rhodium catalyst and a bidentate ligand to form a high-universality catalytic system, promotes the mercaptan to carry out high-selectivity nucleophilic addition on the beta position of the geminal difluoroallene compound, and prepares a plurality of difluoroethylene sulfides. The method has the advantages of simple steps, mild reaction conditions and high selectivity, and is suitable for quickly and massively constructing the compounds.
In order to achieve the technical purpose, the invention provides a synthetic method for preparing difluoroethylene sulfide by nucleophilic substitution of a beta-position of a geminal difluoroallene compound, which is characterized in that the synthetic route is as follows:
wherein
R1 is C1-C12 alkyl, C2-C12 rare group or C2-C12 alkynyl;
r2 is phenyl or naphthyl or furyl or benzyl or C1-C4 alkyl;
r1 can be substituted by one or more, the same or different, R3;
r3 is phenyl or naphthyl or thiophene or indolyl or furyl or tert-butyldimethylsilyloxy or C3-C12 cycloalkyl or C4-C12 poly-alkenyl, and one of phenyl or naphthyl or thiophene or indole substituted by benzyloxy or C1-C4 alkyl or C1-C4 alkoxycarbonyl;
r2 can be substituted by one or more, the same or different, R4;
r4 is one of C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, halogen, C1-C4 alkoxycarbonyl or phenyl.
Further, said R1 is preferably ethyl or undecyl or octynyl; r3 is one of phenyl, naphthyl, thiophene, furyl, indolyl, tert-butyldimethylsilyloxy, cyclohexyl, p-benzyloxyphenyl, methyl benzoate, N-methylindole and 2-methylfuryl; r2 is one of phenyl, naphthyl, furyl, benzyl, ethyl or n-hexyl; and R4 is one of methyl, methoxy, tert-butyl, trifluoromethyl, fluorine, chlorine, bromine or methyl formate.
Further, the preparation method comprises the following steps:
(1) under the protection of inert gas, dissolving a catalyst and a ligand in a first solvent, then adding a compound 1 and a compound 2, and uniformly mixing;
(2) controlling the temperature of the system to be-20-150 ℃, reacting for 0.5-96h, concentrating and desolventizing the reaction mixture, and purifying the obtained residue to obtain the compound 3.
Further, in the step (1), the catalyst is a rhodium catalyst.
Further, the rhodium catalyst is (R, R) -2, 3-bis (2, 5-dimethyl-thien-1-yl) benzo [ B]Thiophene cyclooctadiene rhodium (I) tetrafluoroborate ([ Rh (cod))]BF4)。
Further, in the step (1), the ligand is a bidentate ligand.
Further, the bidentate ligand is one or more of 1, 10-phenanthroline or 5, 5-bis (diphenylphosphino) -4, 4-di-1, 3-piperonyl or (2S,4S) - (-) -2, 4-bis (diphenylphosphino) pentane.
Further, in the step (1), the first solvent is one or more of dichloromethane, dichloroethane, methanol, ethanol, toluene, xylene or acetonitrile; when more than two mixed solvents are adopted, the solvents are mixed according to any ratio; the ratio of the first solvent to the compound 1 is 5-40 mL/g.
Further, in the step (1), trifluoroacetic acid is adopted to promote the reaction; the molar ratio of compound 1 to trifluoroacetic acid is 1: (0.1 to 1).
In the step (1), the molar ratio of the compound 1 to the catalyst, the ligand and the compound 2 is 1 (0.003-0.1): (0.003-0.1): (1-4).
Advantageous effects
The invention provides a synthetic method for preparing difluoroethylene sulfide by nucleophilic substitution of beta site of a geminal difluoroallene compound. According to the method, a geminal difluoroallene compound is used as a raw material, and in a high-universality catalytic system formed by a rhodium catalyst and a bidentate ligand, mercaptan is used for carrying out high-selectivity nucleophilic addition on the beta position of the geminal difluoroallene compound to prepare various difluoroethene sulfur compounds. The method has the advantages of simple steps, mild reaction conditions, high selectivity and ideal yield, and provides a new way for development and application of the geminal difluoroallene compounds.
It should be understood that all combinations of the foregoing concepts and additional concepts described in greater detail below are contemplated as being part of the inventive subject matter of this disclosure unless such concepts are mutually inconsistent.
The foregoing and other aspects, embodiments and features of the present teachings will be more fully understood from the following description taken in conjunction with the accompanying drawings. Additional aspects of the present invention, such as features and/or advantages of exemplary embodiments, will be apparent from the description which follows, or may be learned by practice of specific embodiments in accordance with the teachings of the present invention.
Drawings
The drawings are not intended to be drawn to scale. In the drawings, each identical or nearly identical component that is illustrated in various figures may be represented by a like numeral. For purposes of clarity, not every component may be labeled in every drawing. Embodiments of various aspects of the present invention will now be described, by way of example, with reference to the accompanying drawings, in which:
FIG. 1 is a nuclear magnetic hydrogen spectrum of compound 3aa in example 1 of the present invention.
FIG. 2 is a nuclear magnetic hydrogen spectrum of Compound 3ab in example 1 of the present invention.
FIG. 3 is a nuclear magnetic hydrogen spectrum of compound 3ak in example 1 of the present invention.
FIG. 4 is a nuclear magnetic hydrogen spectrum of Compound 3ap in example 1 of the present invention.
FIG. 5 is a nuclear magnetic hydrogen spectrum of Compound 3ia in example 1 of the present invention.
FIG. 6 is a nuclear magnetic hydrogen spectrum of Compound 3ja in example 1 of the present invention.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the drawings of the embodiments of the present invention. It is to be understood that the described embodiments are only a few, and not all, embodiments of the present invention. All other embodiments, which can be derived by a person skilled in the art from the described embodiments of the invention without any inventive step, are within the scope of protection of the invention. Unless defined otherwise, technical or scientific terms used herein shall have the ordinary meaning as understood by one of ordinary skill in the art to which this invention belongs.
A synthetic method of a difluoroethylene compound comprises the following steps:
firstly, under the protection of inert gas, dissolving a catalyst and a ligand in a first solvent, then adding a compound 1 and a compound 2, and uniformly mixing.
And secondly, controlling the temperature of the system to be-20-150 ℃, reacting for 0.5-96h, concentrating the reaction mixture, desolventizing, and purifying the obtained residue to obtain a compound 3.
In the step (1), trifluoroacetic acid is adopted to promote the reaction;
compound 1 can be synthesized using the following general procedure I:
the synthesis process comprises the following steps of dissolving diisopropylamine in tetrahydrofuran solution at 0 ℃ within 5-60 min, adding n-butyllithium, and stirring for 5-60 min under heat preservation after the addition is finished. Controlling the temperature to be-100-50 ℃ within 5-60 min, and adding CF3CH2And (I) dripping the solution dissolved in THF into the mixture, and stirring for 5-60 min at the constant temperature. Adding a solution of the compound A dissolved in THF, keeping the temperature of the mixture, stirring for 5-60 min, and heating the reaction mixture to-30-50 ℃ within 30-120 min. Acetic anhydride was added and the reaction mixture was then raised to-5-50 ℃ over 2 h. Washing the reaction solution with ammonium chloride aqueous solution, extracting with ethyl acetate, combining organic phases, washing with saturated saline solution, drying, desolventizing, and purifying by column chromatography to obtain the compound B.
And (3) putting zinc powder into N, N-dimethylformamide at room temperature under the protection of argon, adding the obtained mixed solution into a solution of the compound B dissolved in the N, N-dimethylformamide, and stirring for 1-6 hours under the condition of heat preservation. Filtering, diluting the filtrate with ethyl acetate and brine, extracting with ethyl acetate, combining the organic phases, washing with saturated brine, drying, desolventizing, and purifying by column chromatography to obtain compound 1.
The present invention is described in detail below by way of specific examples, but is not limited thereto.
Example 1
Compound 1a was prepared according to general procedure I:
at 0 ℃, n-BuLi (20.0mmol) is added into a solution of diisopropylamine (20.0mmol) dissolved in tetrahydrofuran (10mL) within 10min, after the addition is finished, the temperature is kept and stirred for 15min, and then the temperature of the system is reduced to-93 ℃. Within 10min, CF3CH2A solution of I (10.0mmol) in THF (5mL) was added dropwise thereto, and the mixture was stirred for 20min with heat preservation. A solution of Compound A (10.0mmol) in THF (5mL) was added over 5 min. The mixture was stirred for 30min at room temperature and the reaction mixture was brought to-30 ℃ over 90 min. Acetic anhydride (12.0mmol) was added and the reaction mixture was raised to 0 ℃ over 2 h. Then, the reaction solution was washed with an aqueous ammonium chloride solution, extracted with ethyl acetate, the organic phases were combined, washed with saturated brine, dried, desolventized, and purified by column chromatography to obtain compound Ba.
Under the protection of argon, zinc powder (17.0mmol) is placed in N, N-dimethylformamide (26mL) at room temperature to prepare a mixed solution, the obtained mixed solution is added into a solution of a compound B (8.5mmol) dissolved in N, N-dimethylformamide (17mL), and the mixture is stirred for 3 hours under the condition of heat preservation. Filtration, dilution of the filtrate with ethyl acetate and brine, extraction with ethyl acetate, combination of the organic phases, washing with saturated brine, drying, desolventizing, purification by column chromatography gave 2.01g of compound 1a, yield 71%.
1H NMR(500MHz,CDCl3)δ7.47(d,J＝7.3Hz,2H),7.43(dd,J＝10.1,4.8Hz, 2H),7.39–7.34(m,1H),7.14(d,J＝8.6Hz,2H),6.96(d,J＝8.6Hz,2H),6.54– 6.43(m,1H),5.08(s,2H),2.79(t,J＝7.7Hz,2H),2.65–2.50(m,2H).
13C NMR(126MHz,CDCl3)δ170.1(t,J＝36.1Hz),157.2,152.7(t,J＝261.1Hz), 137.1,133.0,129.3,128.5,127.9,127.4,121.5(t,J＝5.5Hz),114.8,70.0,34.0(t,J ＝1.6Hz),32.9(t,J＝1.3Hz).
19F NMR(471MHz,CDCl3)δ-101.7.
ATR-FTIR(cm-1):2357,1275,750.
HRMS(ESI+)Calcd for C18H16F2ONa[M+Na]+:309.1061,found:309.1057
Synthesis of (Z) - (5- (4- (benzyloxy) phenyl) -1, 1-difluoropent-2-en-2-yl) (4-methoxyphenyl) sulfonamide (3aa) as shown in FIG. 1:
25mL of Schlenk tube was purged with argon 3 times, and then [ Rh (cod) ]was added]BF4(3.2mg,0.04eq), 1, 10-phenanthroline (1.7mg, 0.048eq) and 1mL acetonitrile/toluene (v/v ═ 1: 1). Then compound 1a (57.2mg, 0.2mmol, 1.0eq) and compound 2a (64.0mg, 0.4mmol, 2.0eq) were added. The reaction mixture was stirred at 60 ℃ for 12 hours, GC detected that the ratio of Z-3aa to E-3aa was 85:15, the reaction was concentrated in vacuo and purified by silica gel column chromatography to give 68.0mg of Z/E-3aa, 80% yield.
Further isolated as a white solid, Z-3aa, characterized as follows:
mp:57-59℃.
1H NMR(500MHz,CDCl3)δ7.45(d,J＝7.4Hz,2H),7.40(t,J＝7.4Hz,2H), 7.34(t,J＝7.2Hz,1H),7.23–7.13(m,2H),7.10(d,J＝8.5Hz,2H),6.93(t,J＝5.6 Hz,2H),6.84–6.74(m,2H),6.54(t,J＝6.9Hz,1H),5.92(t,J＝56.3Hz,1H),5.06 (s,2H),3.77(s,3H),2.82–2.61(m,4H).13C NMR(126MHz,CDCl3)δ159.1, 157.3,141.9(t,J＝7.1Hz),137.1,133.0,132.5,129.4,129.1(t,J＝21.3Hz),128.5, 127.9,127.4,123.9,114.8,114.7,113.9(t,J＝241.7Hz),70.0,55.3,33.7(t,J＝1.5 Hz),31.2.
19F NMR(471MHz,CDCl3)δ-112.4(d,J＝2.3Hz).
ATR-FTIR(cm-1):2361,2338,1275,750,671.
HRMS(ESI+)Calcd for C25H25F2O2S[M+H]+:427.1538,found:427.1536.
example 2
Synthesis of (Z) - (5- (4- (benzyloxy) phenyl) -1, 1-difluoropent-2-en-2-yl) (phenyl) sulfanilamide (3ab) as shown in FIG. 2
The preparation was carried out according to example one.
GC-MS detects that the ratio of Z-3ab to E-3ab is 83:17, the reaction solution is subjected to vacuum concentration and silica gel column chromatography purification, and 56.0mg of Z/E-3ab is obtained, wherein the yield is 71%.
Further isolation gave Z-3ab as a white solid, characterized as follows:
1H NMR(500MHz,CDCl3)δ7.47(d,J＝7.3Hz,2H),7.43(dd,J＝10.1,4.7Hz, 2H),7.39–7.34(m,1H),7.30–7.24(m,2H),7.24–7.17(m,3H),7.10(d,J＝8.6 Hz,2H),6.93(d,J＝8.6Hz,2H),6.73(t,J＝6.8Hz,1H),6.01(t,J＝56.2Hz,1H), 5.08(s,2H),2.81–2.68(m,4H).
13C NMR(126MHz,CDCl3)δ157.3,144.7(t,J＝7.4Hz),137.1,134.2,132.9, 129.4,129.0,128.7,128.6,127.9,127.8(t,J＝21.2Hz),127.4,126.5,114.8,114.0(t, J＝242.2Hz),70.0,33.6(t,J＝1.5Hz),31.3.
19F NMR(471MHz,CDCl3)δ-112.1.
ATR-FTIR(cm-1):2361,2339,1275,750.
HRMS(ESI+)Calcd for C24H23F2OS[M+H]+:397.1432,found:397.1434.
example 3
Synthesis of (Z) - (5- (4- (benzyloxy) phenyl) -1, 1-difluoropent-2-en-2-yl) (naphthalen-2-yl) sulfanilamide (3ak) as shown in FIG. 3
The preparation is carried out with reference to example one.
GC-MS detects that the ratio of Z-3ak to E-3ak is 65:35, the reaction solution is concentrated in vacuum and purified by silica gel column chromatography to obtain 46.0mg of Z/E-3ak, and the yield is 52%.
Further isolation gave a white solid, Z-3ak, characterized as follows:
1H NMR(400MHz,CDCl3)δ7.80–7.74(m,1H),7.74–7.67(m,2H),7.65(d,J＝ 1.5Hz,1H),7.51–7.29(m,7H),7.27–7.20(m,1H),7.04(d,J＝8.6Hz,2H),6.87 (d,J＝8.6Hz,2H),6.78–6.68(m,1H),6.01(t,J＝56.2Hz,1H),5.01(s,2H),2.84 –2.61(m,4H).
13C NMR(101MHz,CDCl3)δ157.3,144.9(t,J＝6.9Hz),137.1,133.7,132.8, 132.0,131.6,129.4,128.7,128.6,127.9,127.7,127.6,127.4,127.2,127.2,126.7, 126.6,126.0,114.9,114.0(t,J＝241.8Hz),70.0,33.6(t,J＝1.7Hz),31.3.
19F NMR(377MHz,CDCl3)δ-112.0.
ATR-FTIR(cm-1):2361,2338,1275,1261,750,670,435.
HRMS(ESI+)Calcd for C28H24F2NaOS[M+Na]+:469.1408,found:469.1404.
example 4
Synthesis of (Z) -methyl 3- ((5- (4- (benzyloxy) phenyl) -1, 1-difluoropent-2-en-2-yl) thio) propanoate (3ap) as shown in FIG. 4
The preparation was carried out according to example one.
GC-MS detects that the ratio of Z-3ap to E-3ap is 89:11, the reaction solution is concentrated in vacuum and purified by silica gel column chromatography to obtain 55.9mg of Z/E-3ap, and the yield is 71%.
Further isolation gave Z-3ap as a white solid, which was characterized as follows:
1H NMR(400MHz,CDCl3)δ7.52–7.29(m,5H),7.16–7.06(m,2H),6.96–6.86 (m,2H),6.44(t,J＝4.5Hz,1H),6.06(t,J＝56.3Hz,1H),5.05(s,2H),3.67(s,3H), 2.92(t,J＝7.3Hz,2H),2.69(s,4H),2.54(t,J＝7.3Hz,2H).
13C NMR(101MHz,CDCl3)δ172.1,157.4,144.2(t,J＝8.0Hz),137.2,133.0, 129.4,128.6,128.0,127.5,116.1(t,J＝239.9Hz),114.9,70.1,51.9,34.6,33.7(t,J ＝1.8Hz),31.2,29.8,28.8.19F NMR(377MHz,CDCl3)δ-110.0.
ATR-FTIR(cm-1):2362,2339,1275,1261,750,671,490,420.
HRMS(ESI+)Calcd for C22H24F2NaO3S[M+Na]+:429.1306,found:429.1305.
example 5
Synthesis of methyl (Z) -2- (5, 5-difluoro-4- ((4-methoxyphenyl) thio) pent-3-en-1-yl) benzoate (3ia) as illustrated in FIG. 5
The preparation was carried out according to example one.
GC-MS detects that the ratio of Z-3ia to E-3ia is 90:10, the reaction solution is concentrated in vacuum and purified by silica gel column chromatography to obtain 63.5mg of Z/E-3ia, and the yield is 84%.
A bright yellow oil, Z-3ia, was further isolated and characterized as follows:
1H NMR(400MHz,CDCl3)δ7.91(dd,J＝7.8,1.3Hz,1H),7.44(td,J＝7.5,1.4 Hz,1H),7.32–7.24(m,1H),7.25–7.15(m,3H),6.82–6.73(m,2H),6.59(tt,J＝ 7.3,1.8Hz,1H),5.91(t,J＝56.3Hz,1H),3.89(s,3H),3.78(s,3H),3.12(t,J＝7.6 Hz,2H),2.90–2.64(m,2H).
13C NMR(101MHz,CDCl3)δ167.8,159.1,142.6,141.9(t,J＝7.1Hz),132.5, 132.1,131.1,130.9,129.4,129.0(t,J＝21.3Hz),126.3,124.0,114.7,114.0(t,J＝ 241.7Hz),55.3,52.0,33.0,(t,J＝1.5Hz)31.0.
19F NMR(377MHz,CDCl3)δ-112.4.
ATR-FTIR(cm-1):2361,2339,1275,1261,750,671,490,420.
HRMS(ESI+)Calcd for C20H20F2NaO3S[M+Na]+:401.0993,found:401.0986.
example 6
Synthesis of (Z) -tert-butyl ((8, 8-difluoro-7- ((4-methoxyphenyl) thio) oct-6-en-1-yl) oxy) dimethylsilane (3ja) as shown in FIG. 6
The preparation is carried out with reference to example one.
GC-MS detects that the ratio of Z-3ja to E-3ja is 86:14, reaction liquid is subjected to vacuum concentration and silica gel column chromatography purification, 61.1mg of Z/E-3ja is obtained, and the yield is 74%.
Further isolation gave Z-3ja as a bright yellow oil, characterized as follows:
1H NMR(400MHz,CDCl3)δ7.25(d,J＝8.9Hz,2H),6.84–6.66(m,2H),6.55– 6.41(m,1H),5.90(t,J＝56.3Hz,1H),3.74(s,3H),3.55(t,J＝6.5Hz,2H),2.48– 2.31(m,2H),1.47(dd,J＝14.2,6.8Hz,2H),1.39(dd,J＝14.6,7.5Hz,2H),1.36– 1.26(m,2H),0.85(s,9H),0.00(s,6H).
13C NMR(101MHz,CDCl3)δ159.1,143.2(t,J＝7.1Hz),132.4,128.4(t,J＝21.5 Hz),124.2,114.7,114.2(t,J＝241.5Hz),63.0,55.3,32.6,29.2,28.3(t,J＝1.5Hz), 26.0,25.5,18.4,-5.3.
19F NMR(377MHz,CDCl3)δ-112.1.
ATR-FTIR(cm-1):2361,2339,1275,1261,750,671,490,420.
HRMS(ESI+)Calcd for C21H34F2NaO2SSi[M+Na]+:439.1909,found:439.1905.
although the present invention has been described with reference to the preferred embodiments, it is not intended to be limited thereto. Those skilled in the art to which the invention pertains will appreciate that various modifications and adaptations can be made without departing from the spirit and scope of the invention. Therefore, the protection scope of the present invention should be determined by the appended claims.
Claims (10)
1. A synthetic method for preparing difluoroethylene sulfide by nucleophilic substitution of beta site of gem-difluoroallene compound is characterized in that the synthetic route is as follows:
wherein
R1 is C1-C12 alkyl, C2-C12 rare group or C2-C12 alkynyl;
r2 is phenyl or naphthyl or furyl or benzyl or C1-C4 alkyl;
r1 can be substituted by one or more, the same or different, R3;
r3 is phenyl or naphthyl or thiophene or indolyl or furyl or tert-butyldimethylsilyloxy or C3-C12 cycloalkyl or C4-C12 poly-alkenyl, and one of phenyl or naphthyl or thiophene or indole substituted by benzyloxy or C1-C4 alkyl or C1-C4 alkoxycarbonyl;
r2 can be substituted by one or more, the same or different, R4;
r4 is one of C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, halogen, C1-C4 alkoxycarbonyl or phenyl.
2. The synthesis method for preparing difluoroethylene sulfide by nucleophilic substitution at beta position of gem-difluoroallene compound according to claim 1, wherein R1 is preferably ethyl or undecyl or octynyl; r3 is one of phenyl, naphthyl, thiophene, furyl, indolyl, tert-butyldimethylsilyloxy, cyclohexyl, p-benzyloxyphenyl, methyl benzoate, N-methylindole and 2-methylfuryl; r2 is one of phenyl, naphthyl, furyl, benzyl, ethyl or n-hexyl; and R4 is one of methyl, methoxy, tert-butyl, trifluoromethyl, fluorine, chlorine, bromine or methyl formate.
3. The synthesis method for preparing difluoroethylene sulfide by nucleophilic substitution at beta position of gem-difluoroallene compound according to claim 1, wherein the preparation method comprises the following steps:
(1) under the protection of inert gas, dissolving a catalyst and a ligand in a first solvent, then adding a compound 1 and a compound 2, and uniformly mixing;
(2) controlling the temperature of the system to be-20-150 ℃, reacting for 0.5-96h, concentrating and desolventizing the reaction mixture, and purifying the obtained residue to obtain the compound 3.
4. The synthesis method for preparing difluoroethylene sulfide by nucleophilic substitution at beta position of gem-difluoroallene compound according to claim 3, wherein in the step (1), the catalyst is rhodium catalyst.
5. The method for synthesizing difluoroethene sulfide with β -position nucleophilic substitution of gem-difluoroallene compound as claimed in claim 4, wherein the rhodium catalyst is (R, R) -2, 3-bis (2, 5-dimethyl-thienylphos-1-yl) benzo [ B]Thiophene cyclooctadiene rhodium (I) tetrafluoroborate ([ Rh (cod))]BF4)。
6. The synthesis method for preparing difluoroethylene sulfide by nucleophilic substitution at beta position of gem-difluoroallene compound according to claim 3, wherein in the step (1), the ligand is bidentate.
7. The synthetic method for preparing difluoroethylene sulfide by nucleophilic substitution at beta position of gem-difluoroallene compound according to claim 6, wherein in the step (1), the bidentate ligand is one or more of 1, 10-phenanthroline or 5, 5-bis (diphenylphosphino) -4, 4-di-1, 3-piperonyl or (2S,4S) - (-) -2, 4-bis (diphenylphosphino) pentane.
8. The synthesis method for preparing difluoroethylene sulfide by nucleophilic substitution at beta position of gem-difluoroallene compound according to claim 3, wherein in the step (1), the solvent is one or more of dichloromethane, dichloroethane, methanol, ethanol, toluene, xylene or acetonitrile; when two or more mixed solvents are used, the solvents are mixed in an arbitrary ratio; the ratio of the first solvent to the compound 1 is 5-40 mL/g.
9. The synthesis method for preparing difluoroethylene sulfide by nucleophilic substitution at beta-position of gem-difluoroallene compound according to claim 3, characterized in that in the step (1), trifluoroacetic acid is adopted to promote the reaction; the molar ratio of compound 1 to trifluoroacetic acid is 1: (0.1-1).
10. The method for synthesizing difluoroethylene sulfide by nucleophilic substitution of the beta site of the gem-difluoroallene compound according to claim 3, wherein in the step (1), the molar ratio of the compound 1 to the catalyst, the ligand and the compound 2 is 1 (0.003-0.1): (0.003-0.1): (1-4).
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| JPH0710840A (en) * | 1993-06-23 | 1995-01-13 | Mitsubishi Chem Corp | Sulfide derivative, bactericidal agent using the same as effective component and intermediate therefor |
| JPH0717944A (en) * | 1993-07-06 | 1995-01-20 | Mitsubishi Chem Corp | Trifluorobutenone derivative and fungicide containing the same as active ingredient |
| CN111517954A (en) * | 2020-06-08 | 2020-08-11 | 浙江师范大学 | (Z) -5-fluoro-2-difluoromethylene olefin derivative and preparation method thereof |
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| JPH0710840A (en) * | 1993-06-23 | 1995-01-13 | Mitsubishi Chem Corp | Sulfide derivative, bactericidal agent using the same as effective component and intermediate therefor |
| JPH0717944A (en) * | 1993-07-06 | 1995-01-20 | Mitsubishi Chem Corp | Trifluorobutenone derivative and fungicide containing the same as active ingredient |
| CN111517954A (en) * | 2020-06-08 | 2020-08-11 | 浙江师范大学 | (Z) -5-fluoro-2-difluoromethylene olefin derivative and preparation method thereof |
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