CN110845294B - Synthesis method of 1, 1-dihalogen-1-butene-3-alkyne compound - Google Patents

Synthesis method of 1, 1-dihalogen-1-butene-3-alkyne compound Download PDF

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CN110845294B
CN110845294B CN201910797761.7A CN201910797761A CN110845294B CN 110845294 B CN110845294 B CN 110845294B CN 201910797761 A CN201910797761 A CN 201910797761A CN 110845294 B CN110845294 B CN 110845294B
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刘运奎
鲍汉扬
郑立孟
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Zhejiang University of Technology ZJUT
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    • C07C17/00—Preparation of halogenated hydrocarbons
    • C07C17/013—Preparation of halogenated hydrocarbons by addition of halogens
    • C07C17/02—Preparation of halogenated hydrocarbons by addition of halogens to unsaturated hydrocarbons
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    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C17/00—Preparation of halogenated hydrocarbons
    • C07C17/013—Preparation of halogenated hydrocarbons by addition of halogens
    • C07C17/04—Preparation of halogenated hydrocarbons by addition of halogens to unsaturated halogenated hydrocarbons
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    • C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
    • C07C41/01—Preparation of ethers
    • C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
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Abstract

The invention discloses a synthesis method of a 1, 1-dihalogen-1-butene-3-alkyne compound, which is characterized by comprising the following steps: the method comprises the following steps: adding a gold catalyst and sodium salt NaBARF into a Schlenk tube, vacuumizing for three times to change protective gas, dissolving an alkyne halide compound shown as a formula I into an organic solvent, adding the alkyne halide compound into the reaction tube in the presence of the protective gas, stirring for reacting for 0.5-3h at 25-50 ℃, and after the reaction is finished, obtaining a reaction liquid, and carrying out aftertreatment to obtain a 1, 1-dihalogen-1-butene-3-alkyne compound shown as a formula II; the mass ratio of the gold catalyst, the sodium salt and the alkyne halide compound shown in the formula I is 0.02-0.1:0.1: 1. The method can synthesize the gem-dihaloalkene compounds which are difficult to prepare by the existing method, and has high reaction selectivity; the catalyst has less dosage and lower toxicity; the reaction condition is mild, and the energy consumption is saved; high yield, strong substrate universality, simple and convenient operation and the like.

Description

Synthesis method of 1, 1-dihalogen-1-butene-3-alkyne compound
(I) technical field
The invention relates to a synthetic method of an organic compound, in particular to a synthetic method of a 1, 1-dihalogen-1-butylene-3-alkyne compound.
(II) background of the invention
The geminal dihalogenated olefin compound is a common organic synthesis intermediate, is widely applied to coupling reaction catalyzed by transition metal, and can effectively construct C-C bond, C-N bond, C-O bond and the like. Compared with monosubstituted olefins, the geminal dihalogenated olefin compound can be designed as a substrate of organic tandem reaction to synthesize various heterocyclic frameworks with high biological activity, for example, 2- (2 ', 2' -dibromo) vinyl-N-methylsulfonylaniline and diphenyl diselenide (sulfur) ether are used as raw materials in the Wang Lei of Suzhou university in 2012, and a series of 2-bromo-3-phenylselenium (sulfur) indole and derivatives thereof are synthesized through a tandem cyclization strategy. In addition, the Wangli subject group also takes 2- (2 ', 2' -dibromo) vinyl benzene (sulfur) phenol and phenyl trimethoxy silane as raw materials, so that elimination-intramolecular addition-Hiyama coupling is completed in a reaction system in a relay manner, and a series of 2-phenyl benzofuran (thiophene) and derivatives thereof are synthesized.
At present, gem-dihalo-olefinic compounds are mainly synthesized by Witting reaction, such as in-situ generation of ylide (Ph) from carbon tetrabromide and triphenylphosphine3P＝CBr2) And further reacting with aldehyde or ketone to obtain the gem-dibromo olefin. Although this method has the advantages of cheap and easily available raw materials and simple operation, the process requires excessive triphenylphosphine, the atom economy is low, the carbon tetrabromide used also has toxicity, and it is difficult to apply the method to some ketone compounds with large steric hindrance, and it is also difficult to synthesize some gem-dihaloolefin compounds substituted by special functional groups.
In view of the existing background, the development of a synthetic route with simple and easily obtained raw materials, simple operation, high selectivity and mild reaction for synthesizing the 1, 1-dihalogen-1-butene-3-alkyne compound has important academic value and wide application prospect.
Disclosure of the invention
In view of the deficiencies in the prior art, the present invention is directed to a process for the preparation of 1, 1-dihalo-1-butene-3-acetylenic compounds.
A synthetic method of a 1, 1-dihalogen-1-butene-3-alkyne compound comprises the following steps:
adding a gold catalyst and sodium salt NaBARF into a Schlenk tube, vacuumizing and changing protective gas for three times, dissolving an alkyne halide compound shown in a formula I into an organic solvent, adding the alkyne halide compound into the reaction tube in the presence of the protective gas, stirring and reacting for 0.5-3h (preferably 1.5h) at 25-50 ℃ (preferably 25 ℃), and carrying out aftertreatment on reaction liquid after the reaction is finished to obtain a 1, 1-dihalogen-1-butene-3-alkyne compound shown in a formula II; the mass ratio of the gold catalyst, the sodium salt and the alkyne halide compound shown in the formula I is 0.02-0.1:0.1:1 (preferably 0.05:0.1: 1);
Figure GDA0002342283400000021
formula I or formula II:
R1is one of Me, H, propyl, OMe, pentoxy, tert-butyl, Cl and Br.
X is Cl, Br or I.
Further, the gold catalyst is one of the following structures:
Figure GDA0002342283400000022
still further, the gold catalyst is preferably
Figure GDA0002342283400000023
The sodium salt NaBARF has the structure as follows:
Figure GDA0002342283400000031
further, the organic solvent is one of dichloromethane, 1, 2-dichloroethane, 1, 4-dioxane, toluene, ethyl acetate, dimethyl sulfoxide, tetrahydrofuran and N, N-dimethylformamide.
Still further, the organic solvent of the present invention is preferably dichloromethane.
Further, the total amount of the organic solvent added in the present invention is 10mL/mmol based on the amount of the substance of the alkyne halide represented by the formula I.
Further, the post-treatment method of the reaction solution comprises the following steps: after the reaction is finished, extracting the obtained reaction liquid by dichloromethane, combining organic layers, adding 100-200-mesh column chromatography silica gel, distilling under reduced pressure to remove the solvent, separating the obtained crude product by silica gel column chromatography, eluting by using petroleum ether as an eluent, tracking the elution process by TLC (thin layer chromatography), collecting the eluent containing the target product, combining the eluents, and distilling off the solvent to obtain the 1, 1-dihalogen-1-butene-3-alkyne compound shown in the formula II.
The starting alkyne halides used in the present invention can be prepared by the person skilled in the art on their own according to the methods disclosed in the literature.
Compared with the prior art, the invention has the beneficial effects that:
the method can synthesize the gem-dihaloalkene compounds which are difficult to prepare by the existing method, and has high reaction selectivity; the catalyst has less dosage and lower toxicity; the reaction condition is mild, and the energy consumption is saved; high yield, strong substrate universality, simple and convenient operation and the like.
(IV) the detailed description
The present invention is further illustrated by the following examples, without limiting the scope of the invention:
the general method for synthesizing the halogenated phenylacetylene compound comprises the following steps:
Figure GDA0002342283400000041
taking the synthesis of (chloroethynyl) benzene as an example:
a solution of phenylacetylene (0.51g,5mmol) in anhydrous tetrahydrofuran (10mL) was added to a nitrogen blanketed 50mL round bottom flask. After the reaction system was cooled to-78 deg.C, N-butyllithium (2.5M in N-hexane, 2.40mL,6.0mmol) was slowly added dropwise, and the resulting mixed reaction solution was stirred at-78 deg.C for 30min, and NCS (N-chlorosuccinimide) (7.34g,6.60mmol) was added in one portion under nitrogen protection. The reaction was warmed to room temperature and stirred for an additional 12 h. Quenching the reaction by saturated ammonium chloride after the reaction is finished, extracting by ether, taking an organic phase for spin drying, performing column chromatography separation and elution by using petroleum ether as an eluent, collecting eluent containing a target product, and removing the solvent to obtain (chloroethynyl) benzene with the yield of 81%.
Example 1
Figure GDA0002342283400000042
Adding IPrAuCl (9mg,0.015mmol) and NaBARF (26.6mg,0.03mmol) sodium salt into a Schlenk tube, vacuumizing and exchanging nitrogen for three times, dissolving (chloroethynyl) benzene (41mg,0.3mmol) into dichloromethane, adding into the reaction tube under the protection of nitrogen, stirring the reaction tube at 25 ℃ for reaction for 2h, extracting with dichloromethane after the reaction is finished, combining organic layers, adding column chromatography silica gel of 100-200 meshes and distilling under reduced pressure to remove the solvent, carrying out chromatographic separation on the obtained crude product, eluting with petroleum ether as an eluent, tracking the elution process by TLC, collecting eluent containing the target product, combining the eluent and distilling off the solvent to obtain the pure product. The material was a white solid in 81% yield.
Characterization data:1H NMR(500MHz,CDCl3):δ7.63-7.56(m,4H),7.47-7.37(m,6H).13C NMR(125MHz,CDCl3):δ135.76,135.72,131.86,129.65,129.45,129.20,128.48,128.17,121.78,110.13,97.51,84.94.
example 2
Figure GDA0002342283400000051
Adding AuClL1(11.8mg,0.015mmol) and NaBARF (26.6mg,0.03mmol) sodium salt into a Schlenk tube, vacuumizing and changing nitrogen for three times, dissolving (chloroethynyl) toluene (45mg,0.3mmol) into dichloromethane, adding into the reaction tube under the protection of nitrogen, stirring and reacting at 25 ℃ for 2h, extracting with dichloromethane after the reaction is finished, combining organic layers, adding 100-mesh 200-mesh column chromatography silica gel, distilling under reduced pressure to remove the solvent, performing silica gel column chromatography on the obtained crude product, eluting with petroleum ether as an eluent, tracking the elution process by TLC, collecting eluent containing the target product, combining the eluent, and distilling off the solvent to obtain the pure product. The material was a white solid in 27% yield.
Characterization data:1H NMR(500MHz,CDCl3):δ7.51(d,J＝8.2Hz,2H),7.47(d,J＝8.1Hz,2H),7.24(d,J＝8.0Hz,2H),7.20(d,J＝7.9Hz,2H),2.41(s,3H),2.41(s,3H).13C NMR(125MHz,CDCl3):δ139.85,139.74,135.49,132.93,131.73,129.23,129.13,128.82,118.77,109.75,97.70,84.60,21.63,21.43.
example 3
Figure GDA0002342283400000052
Mixing AuClL2Adding (11.3mg,0.015mmol) and sodium salt NaBARF (26.6mg,0.03mmol) into a Schlenk tube, vacuumizing and exchanging nitrogen for three times, dissolving (chloroethynyl) propylbenzene (53.6mg,0.3mmol) in dichloromethane, adding into the reaction tube under the protection of nitrogen, stirring the reaction tube at 25 ℃ for reaction for 2 hours, extracting with dichloromethane after the reaction is finished, combining organic layers, adding 100-mesh 200-mesh silica gel column chromatography, distilling under reduced pressure to remove the solvent, performing chromatographic separation on the obtained crude product, eluting with petroleum ether as an eluent, tracking the elution process by TLC, collecting the eluent containing the target product, and combining the eluent and distilling off the solvent to obtain the pure product. The material was a white solid in 19% yield.
Characterization data:1H NMR(500MHz,CDCl3):δ7.53(d,J＝8.2Hz,2H),7.49(d,J＝8.1Hz,2H),7.24(d,J＝8.1Hz,2H),7.20(d,J＝8.1Hz,2H),2.69-2.58(m,4H),1.73-1.63(m,4H),1.03-0.93(m,6H).13C NMR(125MHz,CDCl3):δ144.57,144.49,135.54,133.11,131.75,129.14,128.65,128.19,119.02,109.70,97.74,84.66,38.06,37.92,24.30,24.28,13.87,13.75.
example 4
Figure GDA0002342283400000061
Adding IPrAuCl (9mg,0.015mmol) and NaBARF (26.6mg,0.03mmol) as sodium salt into a Schlenk tube, vacuumizing and exchanging nitrogen for three times, dissolving 1- (chloroethynyl) -4-methoxybenzene (50mg,0.3mmol) in 1, 2-dichloroethane, adding into the reaction tube under the protection of nitrogen, stirring the reaction tube at 25 ℃ for reaction for 2h, extracting with dichloromethane after the reaction is finished, combining organic layers, adding silica gel with 100-200 meshes and distilling under reduced pressure to remove a solvent, performing silica gel column chromatography on the obtained crude product, eluting with petroleum ether as an eluent, tracking the elution process by TLC, collecting eluent containing a target product, combining the eluent and distilling off the solvent to obtain a pure product. The material was a white solid in 84% yield.
Characterization data:1H NMR(500MHz,CDCl3):δ7.60-7.55(m,2H),7.53-7.48(m,2H),6.96-6.89(m,4H),3.86(s,3H),3.85(s,3H).13C NMR(125MHz,CDCl3):δ160.51,160.39,134.88,133.41,130.87,128.07,114.17,113.97,113.49,109.30,97.58,84.27,55.37.
example 5
Figure GDA0002342283400000071
Adding IPrAuCl (9mg,0.015mmol) and NaBARF (26.6mg,0.03mmol) sodium salt into a Schlenk tube, vacuumizing and changing nitrogen for three times, dissolving 1- (chloroethynyl) -4-pentyloxyphenyl (66.6mg,0.3mmol) into 1, 4-dioxane, adding into the reaction tube under the protection of nitrogen, stirring the reaction tube at 25 ℃ for 2h, extracting with dichloromethane after the reaction is finished, combining organic layers, adding column chromatography silica gel of 100 meshes and 200 meshes, distilling under reduced pressure to remove the solvent, carrying out silica gel column chromatography separation on the obtained crude product, eluting with petroleum ether as an eluent, tracking the elution process by TLC, collecting eluent containing a target product, and combining the eluent and the solvent to obtain a pure product. The material was a white solid in 55% yield.
Characterization data:1H NMR(500MHz,CDCl3):δ7.58-7.53(m,2H),7.52-7.47(m,2H),6.93-6.88(m,4H),4.02-3.98(m,4H),1.84-1.79(m,4H),1.48-1.39(m,8H),0.96(t,J＝7.1Hz,6H).13C NMR(125MHz,CDCl3):δ160.06,159.96,134.85,133.33,130.80,127.76,114.6,113.92,113.66,109.16,97.63,84.21,68.13,68.11,29.69,28.86,28.84,28.16,28.15,25.02,22.42,13.98.
example 6
Figure GDA0002342283400000072
Adding IPrAuCl (9mg,0.015mmol) and NaBARF sodium salt (26.6mg,0.03mmol) into a Schlenk tube, vacuumizing and exchanging nitrogen for three times, dissolving 1-tert-butyl-4- (chloroethynyl) benzene (57.8mg,0.3mmol) into toluene, adding into the reaction tube under the protection of nitrogen, stirring and reacting the reaction tube at 25 ℃ for 2h, extracting with dichloromethane after the reaction is finished, combining organic layers, adding column chromatography silica gel of 100-200 meshes and distilling under reduced pressure to remove the solvent, carrying out silica gel column chromatography separation on the obtained crude product, eluting with petroleum ether as an eluent, tracking the elution process by TLC, collecting eluent containing the target product, combining the eluent and distilling off the solvent to obtain the pure product. The material was a white solid in 15% yield.
Characterization data:1H NMR(500MHz,CDCl3):δ7.57(d,J＝8.4Hz,2H),7.52(d,J＝8.3Hz,2H),7.49-7.39(m,4H),1.37(s,9H),1.36(s,9H).13C NMR(125MHz,CDCl3):δ1152.87,152.83,135.53,132.81,131.59,128.99,125.49,125.06,118.82,109.69,97.70,84.67,34.93,34.85,31.19,31.14.
example 7
Figure GDA0002342283400000081
Adding IPrAuCl (9mg,0.015mmol) and NaBARF (26.6mg,0.03mmol) sodium salt into a Schlenk tube, vacuumizing and changing nitrogen for three times, dissolving 1-chloro-4- (chloroethynyl) benzene (51mg,0.3mmol) in ethyl acetate, adding into the reaction tube under the protection of nitrogen, stirring and reacting the reaction tube at 25 ℃ for 2h, extracting with dichloromethane after the reaction is finished, combining organic layers, adding 100-mesh 200-mesh column chromatography silica gel, distilling under reduced pressure to remove the solvent, performing silica gel column chromatography separation on the obtained crude product, eluting with petroleum ether as an eluent, tracking the elution process by TLC, collecting eluent containing a target product, and combining the eluent and distilling the solvent to obtain a pure product. The material was a yellow solid in 38% yield.
Characterization data:1H NMR(500MHz,CDCl3):δ7.57-7.53(m,2H),7.52-7.48(m,2H),7.43-7.39(m,2H),7.39-7.36(m,2H).13C NMR(125MHz,CDCl3):δ135.78,134.85,133.93,133.06,130.61,128.93,128.51,120.08,110.35,96.69,85.59.
example 8
Figure GDA0002342283400000091
Adding IPrAuCl (9mg,0.015mmol) and NaBARF (26.6mg,0.03mmol) sodium salt into a Schlenk tube, vacuumizing and changing nitrogen for three times, dissolving 1-bromo-4- (chloroethynyl) benzene (64.7mg,0.3mmol) in dimethyl sulfoxide, adding into the reaction tube under the protection of nitrogen, stirring and reacting the reaction tube at 25 ℃ for 2h, extracting with dichloromethane after the reaction is finished, combining organic layers, adding 100-mesh 200-mesh column chromatography silica gel, distilling under reduced pressure to remove the solvent, performing silica gel column chromatography separation on the obtained crude product, eluting with petroleum ether as an eluent, tracking the elution process by TLC, collecting eluent containing the target product, combining the eluent and distilling the solvent to obtain the pure product. The material was a yellow solid in 43% yield.
Characterization data:1H NMR(500MHz,CDCl3):δ7.60-7.52(m,4H),7.50-7.46(m,2H),7.45-7.40(m,2H).13C NMR(125MHz,CDCl3):δ135.71,134.65,133.33,133.01,130.21,128.39,128.31,120.18,110.23,96.47,85.36.
example 9
Figure GDA0002342283400000092
Adding IPrAuCl (9mg,0.015mmol) and NaBARF (26.6mg,0.03mmol) sodium salt into a Schlenk tube, vacuumizing and changing nitrogen for three times, dissolving (bromoethynyl) benzene (54mg,0.3mmol) in dichloromethane, adding the solution into the reaction tube under the protection of nitrogen, stirring the reaction tube at 25 ℃ for reaction for 2 hours, extracting with tetrahydrofuran after the reaction is finished, combining organic layers, adding column chromatography silica gel of 100 meshes and 200 meshes, distilling under reduced pressure to remove the solvent, carrying out chromatographic separation on the obtained crude product, eluting with petroleum ether as an eluent, tracking the elution process by TLC, collecting the eluent containing the target product, and combining the eluent and distilling the solvent to obtain the pure product. The material was a yellow solid in 60% yield.
Characterization data:1H NMR(500MHz,CDCl3):δ7.64-7.56(m,2H),7.54-7.48(m,2H),7.46-7.36(m,6H).13C NMR(125MHz,CDCl3):δ138.97,138.27,131.83,129.45,129.23,128.47,128.23,125.63,121.79,97.73,97.32,87.76.
example 10
Figure GDA0002342283400000101
Adding IPrAuCl (9mg,0.015mmol) and NaBARF (26.6mg,0.03mmol) as sodium salt into a Schlenk tube, vacuumizing and exchanging nitrogen for three times, dissolving 1- (bromoethynyl) -4-toluene (58.5mg,0.3mmol) in N, N-dimethylformamide, adding into the reaction tube under the protection of nitrogen, stirring the reaction tube at 25 ℃ for reaction for 2h, extracting with dichloromethane after the reaction is finished, combining organic layers, adding silica gel with 100-200 meshes, distilling under reduced pressure to remove the solvent, carrying out silica gel column chromatography separation on the obtained crude product, eluting with petroleum ether as an eluent, tracking the elution process by TLC, collecting the eluent containing the target product, combining the eluents, and distilling off the solvent to obtain the pure product. The material was a yellow solid in 26% yield.
Characterization data:1H NMR(500MHz,CDCl3):δ7.48(d,J＝8.1Hz,2H),7.42(d,J＝8.1Hz,2H),7.25-7.19(m,4H),2.41(s,6H).13C NMR(125MHz,CDCl3):δ139.77,139.63,136.15,131.72,129.23,129.21,128.88,125.48,118.79,97.55,97.45,87.43,21.65,21.44.
example 11
Figure GDA0002342283400000111
Adding IPrAuCl (9mg,0.015mmol) and NaBARF (26.6mg,0.03mmol) sodium salt into a Schlenk tube, vacuumizing and changing nitrogen for three times, dissolving 1- (bromoethynyl) -4-methoxybenzene (63mg,0.3mmol) in dichloromethane, adding the mixture into the reaction tube under the protection of nitrogen, stirring the reaction tube at 50 ℃ for reaction for 2 hours, extracting the mixture with dichloromethane after the reaction is finished, combining organic layers, adding 100-mesh 200-mesh column chromatography silica gel, distilling the mixture under reduced pressure to remove the solvent, performing silica gel column chromatography on the obtained crude product, eluting the crude product by using petroleum ether as an eluent, tracking the elution process by TLC, collecting eluent containing a target product, combining the eluent and distilling the solvent to obtain a pure product. The material was a yellow solid in 83% yield.
Characterization data:1H NMR(500MHz,CDCl3):δ7.54-7.50(m,2H),7.50-7.47(m,2H),6.95-6.89(m,4H),3.86(s,3H),3.85(s,3H).13C NMR(125MHz,CDCl3):δ160.46,160.16,133.36,131.14,130.99,124.93,114.11,113.86,113.45,97.47,97.11,87.10,55.33,55.32.
example 12
Figure GDA0002342283400000112
Adding IPrAuCl (3.6mg,0.006mmol) and NaBARF (26.6mg,0.03mmol) as sodium salt into a Schlenk tube, vacuumizing and exchanging nitrogen for three times, dissolving 1- (bromoethynyl) 2-methylbenzene (58.5mg,0.3mmol) in dichloromethane, adding into the reaction tube under the protection of nitrogen, stirring and reacting the reaction tube at 25 ℃ for 2h, extracting with dichloromethane after the reaction is finished, combining organic layers, adding column chromatography silica gel of 100-200 meshes and distilling under reduced pressure to remove the solvent, carrying out silica gel column chromatography separation on the obtained crude product, eluting with petroleum ether as an eluent, tracking the elution process by TLC, collecting eluent containing the target product, combining the eluent and distilling off the solvent to obtain the pure product. The material was a yellow solid in 64% yield.
Characterization data:1H NMR(500MHz,CDCl3):δ7.43-7.37(m,2H),7.32-7.27(m,4H),7.25-7.18(m,2H),2.41(s,3H),2.39(s,3H).13C NMR(125MHz,CDCl3):δ138.94,138.22,138.03,132.32,130.36,130.24,129.68,128.93,128.37,128.11,126.29,125.68,121.63,97.63,97.49,87.49,21.39,21.24.
example 13
Figure GDA0002342283400000121
Adding IPrAuCl (18mg,0.03mmol) and NaBARF (26.6mg,0.03mmol) sodium salt into a Schlenk tube, vacuumizing and changing nitrogen for three times, dissolving 1- (bromoethynyl) -2-chlorobenzene (64.7mg,0.3mmol) in dichloromethane, adding into the reaction tube under the protection of nitrogen, stirring and reacting the reaction tube at 25 ℃ for 2h, extracting with dichloromethane after the reaction is finished, combining organic layers, adding 100-mesh 200-mesh column chromatography silica gel, distilling under reduced pressure to remove the solvent, performing silica gel column chromatography separation on the obtained crude product, eluting with petroleum ether as an eluent, tracking the elution process by TLC, collecting eluent containing a target product, and combining the eluent and distilling the solvent to obtain a pure product. The material was a yellow solid in 86% yield.
Characterization data: h NMR (500MHz, CDCl)3):δ7.64-7.60(m,1H),7.50-7.44(m,2H),7.37-7.31(m,4H),7.30-7.27(m,1H).13C NMR(125MHz,CDCl3):δ138.03,136.55,133.69,132.66,130.72,130.57,130.15,129.99,129.55,127.09,126.56,122.95,121.73,100.89,94.14,91.09.
Example 14
Figure GDA0002342283400000131
Adding IPrAuCl (9mg,0.015mmol) and NaBARF (26.6mg,0.03mmol) sodium salt into a Schlenk tube, vacuumizing and exchanging nitrogen for three times, dissolving (iodoethynyl) benzene (68.4mg,0.3mmol) into dichloromethane, adding into the reaction tube under the protection of nitrogen, stirring and reacting the reaction tube at 25 ℃ for 0.5h, extracting with dichloromethane after the reaction is finished, combining organic layers, adding column chromatography silica gel of 100 meshes and 200 meshes, distilling under reduced pressure to remove the solvent, carrying out silica gel column chromatography separation on the obtained crude product, eluting by using petroleum ether as an eluent, tracking the elution process by TLC, collecting eluent containing a target product, combining the eluent, and distilling off the solvent to obtain a pure product. The material was a white solid in 51% yield.
Characterization data:1H NMR(500MHz,CDCl3):δ7.61-7.50(m,2H),7.49-7.38(m,5H),7.38-7.29(m,3H),7.39-7.36(m,2H).13C NMR(125MHz,CDCl3):δ142.46,141.58,131.80,129.17,128.74,128.71,128.51,128.43,122.75,98.14,92.15,28.14.
example 15
Figure GDA0002342283400000132
Adding IPrAuCl (9mg,0.015mmol) and NaBARF (26.6mg,0.03mmol) sodium salt into a Schlenk tube, vacuumizing and changing nitrogen for three times, dissolving (iodoethynyl) benzene (68.4mg,0.3mmol) into dichloromethane, adding into the reaction tube under the protection of nitrogen, stirring and reacting the reaction tube at 25 ℃ for 1.5h, extracting with dichloromethane after the reaction is finished, combining organic layers, adding column chromatography silica gel of 100 meshes and 200 meshes, distilling under reduced pressure to remove the solvent, carrying out silica gel column chromatography separation on the obtained crude product, eluting with petroleum ether as an eluent, tracking the elution process by TLC, collecting eluent containing the target product, combining the eluent and distilling off the solvent to obtain the pure product. The material was a white solid in 87% yield.
Characterization data:1H NMR(500MHz,CDCl3):δ7.61-7.50(m,2H),7.49-7.38(m,5H),7.38-7.29(m,3H),7.39-7.36(m,2H).13C NMR(125MHz,CDCl3):δ142.46,141.58,131.80,129.17,128.74,128.71,128.51,128.43,122.75,98.14,92.15,28.14.
example 16
Figure GDA0002342283400000141
Adding IPrAuCl (9mg,0.015mmol) and NaBARF (26.6mg,0.03mmol) sodium salt into a Schlenk tube, vacuumizing and changing nitrogen for three times, dissolving (iodoethynyl) benzene (68.4mg,0.3mmol) in dichloromethane, adding into the reaction tube under the protection of nitrogen, stirring the reaction tube at 25 ℃ for reaction for 3 hours, extracting with dichloromethane after the reaction is finished, combining organic layers, adding column chromatography silica gel of 100 meshes and 200 meshes, distilling under reduced pressure to remove the solvent, carrying out silica gel column chromatography separation on the obtained crude product, eluting with petroleum ether as an eluent, tracking the elution process by TLC, collecting eluent containing a target product, combining the eluent and distilling the solvent to obtain a pure product. The material was a white solid in 86% yield.
Characterization data:1H NMR(500MHz,CDCl3):δ7.61-7.50(m,2H),7.49-7.38(m,5H),7.38-7.29(m,3H),7.39-7.36(m,2H).13C NMR(125MHz,CDCl3):δ142.46,141.58,131.80,129.17,128.74,128.71,128.51,128.43,122.75,98.14,92.15,28.14.

Claims (5)

1. a method for synthesizing 1, 1-dihalogen-1-butene-3-alkyne compounds is characterized by comprising the following steps: the method comprises the following steps:
adding a gold catalyst and sodium salt NaBARF into a Schlenk reaction tube, vacuumizing and replacing protective gas for three times, dissolving an alkyne halide compound shown in a formula I into an organic solvent, adding the alkyne halide compound into the reaction tube in the presence of the protective gas, stirring and reacting for 0.5-3h at 25-50 ℃, and after the reaction is finished, obtaining a reaction liquid, and carrying out aftertreatment to obtain a 1, 1-dihalogen-1-butene-3-alkyne compound shown in a formula II; the mass ratio of the gold catalyst, the sodium salt and the alkyne halide compound shown in the formula I is 0.02-0.1:0.1: 1;
Figure FDA0003618815540000011
formula I or formula II:
R1is one of Me, H, propyl, OMe, pentoxy, tert-butyl, Cl and Br;
x is Cl, Br or I;
the gold catalyst is
Figure FDA0003618815540000012
The organic solvent is dichloromethane.
2. The method of claim 1, wherein: the total amount of the organic solvent added is 10mL/mmol based on the amount of the substance of the alkyne halide represented by the formula I.
3. The method of claim 1, wherein: the reaction temperature is 25 ℃, and the reaction time is 1.5 h.
4. The method of claim 1, wherein: the mass ratio of the gold catalyst, the sodium salt and the alkyne halide compound shown in the formula I is 0.05:0.1: 1.
5. The method of claim 1, wherein: the post-treatment method of the reaction solution comprises the following steps: after the reaction is finished, extracting the obtained reaction liquid by dichloromethane, combining organic layers, adding 100-200-mesh column chromatography silica gel, distilling under reduced pressure to remove the solvent, separating the obtained crude product by silica gel column chromatography, eluting by using petroleum ether as an eluent, tracking the elution process by TLC (thin layer chromatography), collecting the eluent containing the target product, combining the eluents, and distilling off the solvent to obtain the 1, 1-dihalogen-1-butene-3-alkyne compound shown in the formula II.
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