CN114409515B - Preparation method of gem-difluoroolefin compound - Google Patents
Preparation method of gem-difluoroolefin compound Download PDFInfo
- Publication number
- CN114409515B CN114409515B CN202111497997.2A CN202111497997A CN114409515B CN 114409515 B CN114409515 B CN 114409515B CN 202111497997 A CN202111497997 A CN 202111497997A CN 114409515 B CN114409515 B CN 114409515B
- Authority
- CN
- China
- Prior art keywords
- compound
- preparation
- geminal
- reaction
- substituted phenyl
- 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.)
- Active
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 33
- 238000002360 preparation method Methods 0.000 title claims abstract description 22
- 238000006243 chemical reaction Methods 0.000 claims abstract description 30
- 238000000034 method Methods 0.000 claims abstract description 24
- -1 trifluoromethyl olefin compound Chemical class 0.000 claims abstract description 14
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims abstract description 12
- 229910000024 caesium carbonate Inorganic materials 0.000 claims abstract description 12
- YFPJFKYCVYXDJK-UHFFFAOYSA-N Diphenylphosphine oxide Chemical compound C=1C=CC=CC=1[P+](=O)C1=CC=CC=C1 YFPJFKYCVYXDJK-UHFFFAOYSA-N 0.000 claims abstract description 11
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 claims abstract description 10
- 238000006115 defluorination reaction Methods 0.000 claims abstract description 9
- 238000005984 hydrogenation reaction Methods 0.000 claims abstract description 9
- 239000002904 solvent Substances 0.000 claims abstract description 9
- 230000009471 action Effects 0.000 claims abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 50
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 18
- 230000008569 process Effects 0.000 claims description 17
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 5
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 4
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 2
- 239000004305 biphenyl Substances 0.000 claims description 2
- 235000010290 biphenyl Nutrition 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 150000002148 esters Chemical group 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 125000005504 styryl group Chemical group 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 239000002994 raw material Substances 0.000 claims 1
- 125000001544 thienyl group Chemical group 0.000 claims 1
- 125000000524 functional group Chemical group 0.000 abstract description 3
- 239000000047 product Substances 0.000 description 16
- 235000019439 ethyl acetate Nutrition 0.000 description 15
- 238000001228 spectrum Methods 0.000 description 9
- 239000000243 solution Substances 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- AFCRGWZRNWPLNA-UHFFFAOYSA-N FC(=C(CC(=O)C1=CC=CC=C1)C)F Chemical compound FC(=C(CC(=O)C1=CC=CC=C1)C)F AFCRGWZRNWPLNA-UHFFFAOYSA-N 0.000 description 6
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000003638 chemical reducing agent Substances 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- ZJZITTCDQOTBNY-UHFFFAOYSA-N 4,4-difluoro-1,3-diphenylbut-3-en-1-one Chemical compound FC(=C(CC(=O)C1=CC=CC=C1)C1=CC=CC=C1)F ZJZITTCDQOTBNY-UHFFFAOYSA-N 0.000 description 5
- WJFPHIQPHAFQGV-UHFFFAOYSA-N BrC1=CC=C(C=C1)C(CC(=C(F)F)C1=CC=CC=C1)=O Chemical compound BrC1=CC=C(C=C1)C(CC(=C(F)F)C1=CC=CC=C1)=O WJFPHIQPHAFQGV-UHFFFAOYSA-N 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 238000012512 characterization method Methods 0.000 description 5
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 5
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 239000000654 additive Substances 0.000 description 4
- 230000000996 additive effect Effects 0.000 description 4
- 229910052731 fluorine Inorganic materials 0.000 description 4
- 239000011737 fluorine Substances 0.000 description 4
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- 230000005526 G1 to G0 transition Effects 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical group O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 239000007795 chemical reaction product Substances 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 239000012299 nitrogen atmosphere Substances 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 238000010898 silica gel chromatography Methods 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000007810 chemical reaction solvent Substances 0.000 description 2
- OIKHZBFJHONJJB-UHFFFAOYSA-N dimethyl(phenyl)silicon Chemical compound C[Si](C)C1=CC=CC=C1 OIKHZBFJHONJJB-UHFFFAOYSA-N 0.000 description 2
- GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 description 2
- MWQBWSPPTQGZII-UHFFFAOYSA-N ethoxy(phenyl)phosphinic acid Chemical compound CCOP(O)(=O)C1=CC=CC=C1 MWQBWSPPTQGZII-UHFFFAOYSA-N 0.000 description 2
- 150000002367 halogens Chemical group 0.000 description 2
- 239000012280 lithium aluminium hydride Substances 0.000 description 2
- PARWUHTVGZSQPD-UHFFFAOYSA-N phenylsilane Chemical compound [SiH3]C1=CC=CC=C1 PARWUHTVGZSQPD-UHFFFAOYSA-N 0.000 description 2
- 229910000160 potassium phosphate Inorganic materials 0.000 description 2
- 235000011009 potassium phosphates Nutrition 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- DQOJPESMCGTLIH-SDNWHVSQSA-N (e)-4,4,4-trifluoro-1,3-diphenylbut-2-en-1-one Chemical compound C=1C=CC=CC=1/C(C(F)(F)F)=C\C(=O)C1=CC=CC=C1 DQOJPESMCGTLIH-SDNWHVSQSA-N 0.000 description 1
- DNXUQMXQCJPJCC-BQYQJAHWSA-N (e)-4,4,4-trifluoro-3-methyl-1-phenylbut-2-en-1-one Chemical compound FC(F)(F)C(/C)=C/C(=O)C1=CC=CC=C1 DNXUQMXQCJPJCC-BQYQJAHWSA-N 0.000 description 1
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 1
- 238000006130 Horner-Wadsworth-Emmons olefination reaction Methods 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 125000004799 bromophenyl group Chemical group 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 239000012973 diazabicyclooctane Substances 0.000 description 1
- LXCYSACZTOKNNS-UHFFFAOYSA-N diethoxy(oxo)phosphanium Chemical compound CCO[P+](=O)OCC LXCYSACZTOKNNS-UHFFFAOYSA-N 0.000 description 1
- SULWMEGSVQCTSK-UHFFFAOYSA-N diethyl hydrogen phosphite Chemical compound CCOP(O)OCC SULWMEGSVQCTSK-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 125000001207 fluorophenyl group Chemical group 0.000 description 1
- 125000006303 iodophenyl group Chemical group 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a preparation method of a gem-difluoroolefin compound, which comprises the step of carrying out hydrogenation defluorination reaction on a trifluoromethyl olefin compound in a solvent under the action of diphenyl phosphine oxide and cesium carbonate to obtain the gem-difluoroolefin compound. The method has the advantages of mild reaction conditions, good functional group tolerance and good regioselectivity.
Description
Technical Field
The invention belongs to the technical field of organic compound synthesis, and particularly relates to a preparation method of a geminal difluoroalkene compound.
Background
The geminal difluoroolefin has important function in the fields of medicines, agrochemicals and material science, has the reaction performance similar to that of carbonyl, and can improve the biological activity, metabolic stability and lipophilicity of organic molecules. Moreover, gem-difluoroalkenyl groups can be conveniently converted to monofluoroalkenyl, difluoroalkyl, trifluoromethyl and a variety of other fluorine-containing structures. Therefore, in recent years, efficient synthesis of geminal difluoroolefins has received much attention.
In general, the compounds can be prepared from carbonyl compounds via classical reactions including Wittig, horner-Wadsworth-Emmons, and the like. However, these methods generally need to be performed under strongly alkaline conditions and the substrate range is relatively limited. Therefore, it is a problem to be further sought to develop a reaction system having mild reaction conditions and a wide substrate tolerance.
Disclosure of Invention
This section is for the purpose of summarizing some aspects of embodiments of the invention and to briefly introduce some preferred embodiments. In this section, as well as in the abstract and the title of the invention of this application, simplifications or omissions may be made to avoid obscuring the purpose of the section, the abstract and the title, and such simplifications or omissions are not intended to limit the scope of the invention.
The present invention has been made keeping in mind the above problems and/or problems occurring in the prior art.
One of the objectives of the present invention is to provide a novel method for promoting the hydrogenation and defluorination of trifluoromethyl olefin by diphenyl phosphine oxide and water, wherein the chemical formula of the reaction is as follows:
in order to solve the technical problems, the invention provides the following technical scheme: a preparation method of a geminal difluoroalkene compound comprises the following steps,
carrying out hydrogenation defluorination reaction on a trifluoromethyl olefin compound shown in a formula I in a solvent under the action of diphenyl phosphine oxide and cesium carbonate to obtain a compound shown in a formula II;
wherein R is 1 、R 2 One selected from halogen substituted phenyl, methyl substituted phenyl, methoxy substituted phenyl, cyano substituted phenyl, nitro substituted phenyl, trifluoromethyl substituted phenyl, ester substituted phenyl, naphthyl, thiophene, methyl, biphenyl and styryl. Wherein, the halogen substituted phenyl comprises one of fluorophenyl, chlorphenyl, bromophenyl and iodophenyl.
As a preferred embodiment of the process for the preparation of the geminal difluoroolefin compound of the invention, wherein: the molar ratio of the trifluoromethyl olefin compound to the diphenyl phosphine oxide is 1:2 to 3.
As a preferred embodiment of the process for the preparation of the geminal difluoroolefin compound of the invention, wherein: the molar ratio of the trifluoromethyl olefin compound to the cesium carbonate is 1:2 to 3.
As a preferred embodiment of the process for the preparation of the geminal difluoroolefin compound of the invention, wherein: the solvent comprises one of dichloroethane, ethyl acetate, nitromethane, N-methylpyrrolidone and N, N-dimethylacetamide.
As a preferred embodiment of the process for the preparation of the geminal difluoroolefin compound of the invention, wherein: the solvent is ethyl acetate.
As a preferred embodiment of the process for the preparation of the geminal difluoroolefin compound of the invention, wherein: the method also comprises the step of adding a reaction promoter, wherein the reaction promoter is water.
As a preferred embodiment of the process for the preparation of the geminal difluoroolefin compound of the invention, wherein: the equivalent weight of water is less than 20.
As a preferred embodiment of the process for the preparation of the geminal difluoroolefin compound of the invention, wherein: the equivalent weight of water is 5.
As a preferred embodiment of the process for the preparation of the geminal difluoroolefin compound of the invention, wherein: the hydrogenation defluorination reaction is carried out, and the reaction temperature is 70 ℃.
As a preferred embodiment of the process for the preparation of the geminal difluoroolefin compound of the invention, wherein: the hydrogenation defluorination reaction is carried out for 25-360 min.
Compared with the prior art, the invention has the following beneficial effects:
the invention provides a method for generating a series of gem-difluoroolefin compounds by a hydrogenation defluorination reaction of trifluoromethyl olefin compounds in ethyl acetate under a metal-free condition by using diphenyl phosphine oxide as a reducing agent, cesium carbonate as a base and water as an additive; the reaction condition is mild, the functional group tolerance is good, and the regioselectivity is good.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings required to be used in the description of the embodiments are briefly introduced below, and it is obvious that the drawings in the description below are only some embodiments of the present invention, and it is obvious for those skilled in the art that other drawings can be obtained according to the drawings without inventive labor. Wherein:
FIG. 1 is a hydrogen spectrum of the target product 4,4-difluoro-1,3-diphenyl-3-buten-1-one of example 1 of the present invention;
FIG. 2 is a fluorine spectrum of the target product 4,4-difluoro-1,3-diphenyl-3-buten-1-one of example 1 of the present invention;
FIG. 3 is a carbon spectrum of the target product 4,4-difluoro-1,3-diphenyl-3-buten-1-one of example 1 of the present invention;
FIG. 4 is a hydrogen spectrum of the desired product, 1- (4-bromophenyl) -4,4-difluoro-3-phenyl-3-buten-1-one, of example 2 of the present invention;
FIG. 5 is a plot of the fluorine spectrum of the desired product, 1- (4-bromophenyl) -4,4-difluoro-3-phenyl-3-buten-1-one, of example 2 of this invention;
FIG. 6 is a carbon spectrum of the desired product, 1- (4-bromophenyl) -4,4-difluoro-3-phenyl-3-buten-1-one, of example 2 of the present invention;
FIG. 7 is a hydrogen spectrum of the target product 4,4-difluoro-3-methyl-1-phenyl-3-buten-1-one of example 3 of the present invention;
FIG. 8 is a fluorine spectrum of the target product 4,4-difluoro-3-methyl-1-phenyl-3-buten-1-one of example 3 of the present invention;
FIG. 9 is a carbon spectrum of the target product 4,4-difluoro-3-methyl-1-phenyl-3-buten-1-one of example 3 of this invention.
Detailed Description
In order to make the aforementioned objects, features and advantages of the present invention more comprehensible, specific embodiments thereof are described in detail below with reference to examples of the specification.
In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present invention, but the present invention may be practiced in other ways than those specifically described and will be readily apparent to those of ordinary skill in the art without departing from the spirit of the present invention, and therefore the present invention is not limited to the specific embodiments disclosed below.
Furthermore, the references herein to "one embodiment" or "an embodiment" refer to a particular feature, structure, or characteristic that may be included in at least one implementation of the present invention. The appearances of the phrase "in one embodiment" in various places in the specification are not necessarily all referring to the same embodiment, nor are separate or alternative embodiments mutually exclusive of other embodiments.
Example 1
(1) To a 10mL Schlenk tube were added in sequence (E) -4,4,4-trifluoro-1,3-diphenyl-2-buten-1-one (82.9mg, 0.3mmol, 1.0equiv.), ethyl acetate (3.5 mL), water (27.0mg, 1.5mmol, 5.0equiv.), diphenyl phosphine oxide (151.6mg, 0.75mmol, 2.5equiv.), cesium carbonate (195.5mg, 0.6mmol, 2.5equiv.), and the reaction mixture was stirred at 70 ℃ for 3 hours under a nitrogen atmosphere.
(2) After the reaction in the step (1) is finished, saturated NH is used 4 The Cl solution was quenched and extracted with ethyl acetate (20 mL. Times.3); the combined organic phases were washed successively with saturated brine (20 mL) and driedDrying over sodium sulfate and concentrating in vacuo to obtain the crude product; the crude product is purified by a silica gel column chromatography, and the column chromatography separation conditions are as follows: the stationary phase is silica gel powder with 300-400 meshes, the mobile phase is ethyl acetate (A) and petroleum ether (B), and the mobile phase change program (A: B) is 0:1 → 1:100 to finally obtain 67.5mg of a target product 4,4-difluoro-1,3-diphenyl-3-butene-1-ketone, wherein the structural formula of the compound is as follows:
the above 4,4-difluoro-1,3-diphenyl-3-buten-1-one was characterized as shown in figures 1,2 and 3 with the results: a white solid; 1 H NMR(400MHz,CDCl 3 ):δ8.02-7.05(m,2H),7.63-7.56(m,1H),7.52-7.45(m,2H),7.37-7.31(m,4H),7.30-7.22(m,1H),4.08(t,J=2.2Hz,2H)ppm. 19 F NMR(376MHz,CDCl 3 ):δ-87.93(d,J=37.2Hz,1F),-89.08(d,J=37.3Hz,1F)ppm. 13 C NMR(100MHz,CDCl 3 ):δ195.3(t,J C-F =2.7Hz),154.7(dd,J C-F =292.4,288.0Hz),136.2,133.4,128.7,128.5,128.1,128.0(t,J C-F =3.6Hz),127.4,87.1(dd,J C-F =21.7,17.3Hz),38.3(d,J C-F =2.4Hz)ppm.HRMS(m/z):calcd for C 16 H 13 F 2 O[M+H] + 259.0929,found:259.0934.
according to the characterization data, the obtained reaction product 4,4-difluoro-1,3-diphenyl-3-butene-1-ketone (purity is more than 98%); the product yield was calculated to be 87%.
Example 2
(1) To a 10mL Schlenk tube were added in this order (E) -1- (4-bromophenyl) -4,4,4-trifluoro-3-phenyl-2-buten-1-one (106.5mg, 0.3mmol, 1.0equv.), ethyl acetate (3.5 mL), water (27.0mg, 1.5mmol, 5.0equv.), diphenylphosphine (151.6mg, 0.75mmol, 2.5equv.), cesium carbonate (195.5mg, 0.6mmol, 2.0equv.), and the reaction mixture was stirred at 70 ℃ for 3 hours under a nitrogen atmosphere.
(2) After the reaction in the step (1) is finished, saturated NH is used 4 The Cl solution was quenched and extracted with ethyl acetate (20 mL. Times.3); mergingThe organic phase was washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, and concentrated in vacuo to give the crude product; the crude product is purified by a silica gel column chromatography, and the column chromatography separation conditions are as follows: the stationary phase is silica gel powder with 300-400 meshes, the mobile phase is ethyl acetate (A) and petroleum ether (B), and the mobile phase change program (A: B) is 0:1 → 1:100, and finally obtaining 85.2mg of a target product 1- (4-bromophenyl) -4,4-difluoro-3-phenyl-3-butene-1-ketone, wherein the structural formula of the compound is as follows:
characterization of the above 1- (4-bromophenyl) -4,4-difluoro-3-phenyl-3-buten-1-one, as shown in figures 4,5 and 6, resulted in: a white solid; 1 H NMR(400MHz,CDCl 3 ):δ7.84-7.78(m,2H),7.63-7.56(m,2H),7.36-7.27(m,4H),7.26-7.21(m,1H)4.01(t,J=2.2Hz,2H)ppm. 19 F NMR(376MHz,CDCl 3 ):δ-87.71(d,J=35.9Hz,1F),-88.74(d,J=36.0Hz,1F)ppm. 13 C NMR(100MHz,CDCl 3 ):δ194.4(t,J C-F =2.7Hz),154.7(dd,J C-F =292.6,288.3Hz),134.9,133.2(t,J C-F =4.1Hz),132.0,129.6,128.6,128.5,127.9(t,J C-F =3.4Hz),127.5,87.0(dd,J C-F =21.7,17.8Hz),38.3(d,J C-F =2.4Hz)ppm.HRMS(m/z):calcd for C 16 H 12 BrF 2 O[M+H] + 337.0034,found:337.0036.
according to characterization data, the reaction product 1- (4-bromophenyl) -4,4-difluoro-3-phenyl-3-buten-1-one (purity > 98%) is obtained; the product yield was calculated to be 84%.
Example 3
(1) To a 10mL Schlenk tube were added in this order (E) -4,4,4-trifluoro-3-methyl-1-phenyl-2-buten-1-one (64.3mg, 0.3mmol, 1.0equ.), ethyl acetate (3.5 mL), water (27.0mg, 1.5mmol, 5.0equ.), diphenylphosphine (151.6mg, 0.75mmol, 2.5equ.), cesium carbonate (195.5mg, 0.6mmol, 2.0equ.), and the reaction mixture was stirred at 70 ℃ for 3 hours under a nitrogen atmosphere.
(2) In step (1)After the reaction is finished, saturated NH is used 4 The Cl solution was quenched and extracted with ethyl acetate (20 mL. Times.3); the combined organic phases were washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, and concentrated in vacuo to give the crude product; the crude product is purified by a silica gel column chromatography, and the column chromatography separation conditions are as follows: the stationary phase is silica gel powder with 300-400 meshes, the mobile phase is ethyl acetate (A) and petroleum ether (B), and the mobile phase change program (A: B) is 0:1 → 1:100 to finally obtain 14.7mg of a target product 4,4-difluoro-3-methyl-1-phenyl-3-buten-1-one, wherein the structural formula of the compound is as follows:
characterization of 4,4-difluoro-3-methyl-1-phenyl-3-buten-1-one as described above, as shown in figures 7,8 and 9, resulted in: a colorless oily liquid; 1 H NMR(400MHz,CDCl 3 ):δ7.99-7.94(m,2H),7.62-7.56(m,1H),7.52-7.45(m,2H),3.64(t,J=1.9Hz,2H),1.65(t,J=3.2Hz,3H)ppm. 19 F NMR(376MHz,CDCl 3 ):δ-94.06(d,J=55.2Hz,1F),-94.41(d,J=53.7Hz,1F)ppm. 13 C NMR(100MHz,CDCl 3 ):δ196.3(t,J C-F =2.7Hz),153.7(dd,J C-F =281.6,280.2Hz),136.3,133.4,128.1,128.1,80.5(dd,J C-F =22.9,19.0Hz),38.3(d,J C-F =2.9Hz),12.6ppm.HRMS(m/z):calcd for C 18 H 14 F 2 NO 2 [M+H] + 197.0772,found:197.0778.
according to the characterization data, the reaction product 4,4-difluoro-3-methyl-1-phenyl-3-butene-1-one (purity > 98%) is obtained; the product yield was calculated to be 25%.
Example 4
Example 4 is essentially the same as example 1, except that in step (1), the reducing agent is different and no reaction promoter water is used, as shown in table 1 below:
TABLE 1
Reducing agent | Yield (%) |
Diphenylphosphine oxide | 62 |
Phenylphosphonic |
0 |
Phosphorous |
0 |
|
0 |
|
0 |
|
0 |
As can be seen from table 1, under the same reaction conditions, reducing agents were used, such as: synthesizing 4,4-difluoro-1,3-diphenyl-3-butene-1-one by ethyl phenylphosphonate, diethyl phosphite, phenylsilane, dimethylphenylsilane or lithium aluminum hydride, wherein the yield is lower; when diphenylphosphineoxide was used as the reducing agent, the reaction yield was 62%.
Example 5
Example 5 is essentially the same as example 1, except that in step (1), the base is different and no reaction promoter water is used, as shown in table 2 below:
TABLE 2
Alkali | Yield (%) |
Cesium carbonate | 62 |
|
0 |
|
0 |
|
0 |
|
0 |
|
0 |
|
0 |
|
0 |
|
0 |
As can be seen from table 2, under the same reaction conditions, a base is used, such as: lithium hydroxide, potassium phosphate, sodium hydroxide, sodium carbonate, triethylamine, sodium bicarbonate, sodium acetate, triethylene Diamine (DABCO), the yield is low; when cesium carbonate was used as a base, the reaction yield was 62%.
Example 6
Example 6 is essentially the same as example 1, except that in step (1), the equivalent amount of reaction promoter water added is different, as shown in table 3 below:
TABLE 3
As can be seen from table 3, under the same reaction conditions, the equivalent of additive water is used, such as: 0. 10 and 20 equivalents, the yield is low; when 5 equivalents of water were used as an additive, the reaction yield was 87%.
Example 7
Example 7 is essentially the same as example 1, except that in step (1), the reaction solvent is different and no reaction promoter water is used, as shown in table 4 below:
TABLE 4
Reaction solvent | Yield (%) |
DCE | 56 |
MeCN | 4 |
|
0 |
|
0 |
|
0 |
EtOAc | 62 |
|
25 |
|
10 |
|
10 |
As can be seen from table 4, under the same reaction conditions, solvents were used, such as: 1,2-dichloroethane, acetonitrile, dimethyl sulfoxide, N-dimethylformamide, ethanol, nitromethane, N-methylpyrrolidone, N-dimethylacetamide, in low yields; the reaction yield was 62% when ethyl acetate was used as the solvent.
Example 8
Example 8 is essentially the same as example 1, except that in step (1), the trifluoromethylolefin compound is different and the target product is specifically obtained as shown in table 5 below:
TABLE 5
The invention provides a method for generating a series of gem-difluoroolefin compounds by a hydrogenation defluorination reaction of trifluoromethyl olefin compounds in ethyl acetate under a metal-free condition by using diphenyl phosphine oxide as a reducing agent, cesium carbonate as a base and water as an additive; the reaction condition is mild, the functional group tolerance is good, and the regioselectivity is good.
It should be noted that the above-mentioned embodiments are only for illustrating the technical solutions of the present invention and not for limiting, and although the present invention has been described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that modifications or equivalent substitutions may be made on the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention, which should be covered by the claims of the present invention.
Claims (9)
1. A process for the preparation of a geminal difluoroalkene compound, characterized in that: comprises the steps of (a) preparing a mixture of a plurality of raw materials,
carrying out hydrogenation defluorination on a trifluoromethyl olefin compound shown in a formula I in a solvent under the action of diphenyl phosphine oxide and cesium carbonate to obtain a compound shown in a formula II;
wherein R is 1 、R 2 One selected from halogen substituted phenyl, methyl substituted phenyl, methoxy substituted phenyl, cyano substituted phenyl, nitro substituted phenyl, trifluoromethyl substituted phenyl, ester substituted phenyl, naphthyl, thienyl, methyl, biphenyl and styryl;
the solvent is one selected from dichloroethane, ethyl acetate, nitromethane, N-methylpyrrolidone and N, N-dimethylacetamide.
2. A process for the preparation of a geminal difluoroalkene compound according to claim 1, wherein: the molar ratio of the trifluoromethyl olefin compound to the diphenyl phosphine oxide is 1:2~3.
3. A process for the preparation of a geminal difluoroalkene compound according to claim 1, wherein: the molar ratio of the trifluoromethyl olefin compound to the cesium carbonate is 1:2~3.
4. A process for the preparation of a geminal difluoroalkene compound according to claim 1, wherein: the solvent is ethyl acetate.
5. The process for preparing a geminal difluoroolefin compound of any of claim 1~4, wherein: the method also comprises the step of adding a reaction promoter, wherein the reaction promoter is water.
6. A process for the preparation of a geminal difluoroalkene compound according to claim 5, wherein: the equivalent weight of water is less than 20.
7. A process for the preparation of a geminal difluoroalkene compound according to claim 6, wherein: the equivalent weight of water is 5.
8. The process for the preparation of a geminal difluoroolefin compound according to any one of claims 1~4, 6 or 7, wherein: the hydrogenation defluorination reaction is carried out, and the reaction temperature is 70 ℃.
9. A process for the preparation of a geminal difluoroalkene compound according to claim 8, wherein: and carrying out the hydrodefluorination reaction for 25 to 360min.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202111497997.2A CN114409515B (en) | 2021-12-09 | 2021-12-09 | Preparation method of gem-difluoroolefin compound |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202111497997.2A CN114409515B (en) | 2021-12-09 | 2021-12-09 | Preparation method of gem-difluoroolefin compound |
Publications (2)
Publication Number | Publication Date |
---|---|
CN114409515A CN114409515A (en) | 2022-04-29 |
CN114409515B true CN114409515B (en) | 2023-03-21 |
Family
ID=81266319
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202111497997.2A Active CN114409515B (en) | 2021-12-09 | 2021-12-09 | Preparation method of gem-difluoroolefin compound |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN114409515B (en) |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN113149882B (en) * | 2021-02-05 | 2023-04-07 | 西南医科大学 | Gem-difluoroolefin-pyrroline compound and preparation method and application thereof |
CN115010753A (en) * | 2022-07-27 | 2022-09-06 | 南京工业大学 | Method for preparing phosphorylated gem-difluorodiene compound in aqueous phase |
CN115448816B (en) * | 2022-09-16 | 2024-04-12 | 中国石油大学(华东) | Synthesis method of beta-fluoro alkenyl alcohol |
CN116284126A (en) * | 2023-02-17 | 2023-06-23 | 南京工业大学 | Diaryl phosphono-4-fluoro-3-butene-1-one compound and preparation method thereof |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103922977A (en) * | 2014-05-07 | 2014-07-16 | 江南大学 | Novel method for preparing sulfonyl quinones |
CN104163798A (en) * | 2014-07-29 | 2014-11-26 | 苏州康润医药有限公司 | Synthesis method of 3-amino-8-trifluoromethyl quinoline |
CN104592281B (en) * | 2014-12-19 | 2018-05-04 | 河南师范大学 | Difunctional 4-TMS-5-I-1,2,3- triazole compounds and its preparation method and application |
-
2021
- 2021-12-09 CN CN202111497997.2A patent/CN114409515B/en active Active
Also Published As
Publication number | Publication date |
---|---|
CN114409515A (en) | 2022-04-29 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN114409515B (en) | Preparation method of gem-difluoroolefin compound | |
CN114685251B (en) | Direct cross-coupling reaction method of diaryl sulfoxide and aryl bromide | |
CN111205279A (en) | Polysubstituted benzodihydrofuran heterocyclic compound and preparation method and application thereof | |
CN113943252A (en) | Pyrazolidinesulfonyl fluoride compounds and preparation method thereof | |
CN111925356B (en) | Synthesis method and application of chiral quinoline-imidazoline ligand | |
CN115010753A (en) | Method for preparing phosphorylated gem-difluorodiene compound in aqueous phase | |
CN115043788B (en) | Trifluoromethyl oxazol-2-one compound and preparation method and application thereof | |
CN110790689A (en) | Synthetic method of 1, 1-difluoro-2-isonitrile-ethyl phenyl sulfone compound | |
CN107382910B (en) | Difluoromethyl aldehyde hydrazone compound and preparation method thereof | |
CN114605361A (en) | Method for synthesizing gamma-hydroxy-gamma-perfluoromethylbutenolide compound | |
CN111732552A (en) | Method for synthesizing 1, 3-oxazole-2-thioketone by palladium catalysis | |
CN112645841A (en) | 2-fluorobenzonitrile derivative and preparation method and application thereof | |
CN115466158B (en) | 1, 3-triaryl-1, 3-butadiene derivative and synthesis method thereof | |
CN113248418B (en) | 3-alkynyl-2, 4-diester-based pyrrole compound and preparation method thereof | |
CN115260103B (en) | Preparation method of 4,5-dihalogen-1- (difluoromethyl) -1H-imidazole | |
CN116284126A (en) | Diaryl phosphono-4-fluoro-3-butene-1-one compound and preparation method thereof | |
CN110372718B (en) | Difluoromethane thiochromanonthiophene compound and preparation method thereof | |
CN113387799B (en) | Preparation method of gamma, gamma-diaryl ester or gamma, gamma-triaryl ester compound and product thereof | |
CN115353457B (en) | Asymmetric carbonate and preparation method thereof | |
CN118047707A (en) | Direct cross coupling method of sulfoxide ylide and aryl fluorosulfonate | |
CN111777582B (en) | 2-fluoroalkyl-3-alkynyl substituted naphthofuran compound and preparation method thereof | |
CN111196786B (en) | Trifluoromethanesulfonyl substituted isoxazole compound and synthesis method thereof | |
JP4243683B2 (en) | Method for producing 1-tetralone | |
CN115925583A (en) | Preparation method of beta-fluoroalkyl-beta-aminovinyl ketone compound | |
CN116396328A (en) | Diaryl phosphono-4-fluoro-1, 3-butadiene phosphate compound and preparation method thereof |
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 |