CN116535280A - Synthesis method of alkynyl thioether compound - Google Patents

Synthesis method of alkynyl thioether compound Download PDF

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CN116535280A
CN116535280A CN202310562755.XA CN202310562755A CN116535280A CN 116535280 A CN116535280 A CN 116535280A CN 202310562755 A CN202310562755 A CN 202310562755A CN 116535280 A CN116535280 A CN 116535280A
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alkynyl
alpha
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闻建
周俊岐
王子玉
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Jiangnan University
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Abstract

The invention belongs to the field of organic synthesis, and particularly relates to a synthesis method of alkynyl thioether compounds. The synthesis method takes alpha-bromostyrene sulfonium salt and nucleophilic reagent as raw materials, and the alkynyl thioether compound is obtained through heating reaction under the action of alkali. The invention has the advantages of cheap and easily obtained raw materials, no need of using a catalyst, environmental protection, no pollution, wide substrate range, high yield, simple operation, easy separation and purification of products and the like.

Description

Synthesis method of alkynyl thioether compound
Technical Field
The invention belongs to the field of organic synthesis, and particularly relates to a synthesis method of alkynyl thioether compounds.
Background
Alkynes play a very important role in organic synthesis, and their click reaction with azide is considered to be one of the best biorthogonal conjugation methods as modified biomolecules so far. Among the different classes of alkynes, heteroatom-substituted alkynes are particularly important. The hetero atoms are directly connected with the carbon-carbon triple bond, so that new physical, chemical and biological properties are endowed. Alkynyl sulfides play an important role in pharmaceutical, agricultural and fine chemical industries and are present in many synthetic molecules with various biological activities, such as mGlu5receptor antagonist (compound a), trichophytoisis (compound B), antimicrobial agent precursor (compound C). These are all within the scope of application of alkynyl thioether compounds. Although these compounds are important, the preparation of these high-value compounds remains very challenging, especially in the construction of alkynylsulfides containing active molecular components, and thus development of gentle and efficient synthetic methods remains of great interest.
The existing synthesis method of the alkynyl thioether compound mainly comprises the following four steps: (1) coupling with a sulfur nucleophile via an alkynyl electrophile; the method comprises the steps of pre-activating terminal alkyne, and reacting the terminal alkyne with a sulfur nucleophile to obtain an alkynyl thioether compound; (2) coupling with a sulfur-containing electrophile via a terminal alkyne; preparing a sulfur reagent into a sulfur electrophile, and then reacting with terminal alkyne under the catalysis of transition metal to obtain an alkynyl thioether compound; (3) By the oxidative coupling method of terminal alkyne and mercaptan and thiophenol; the method needs to control the oxidative cross coupling and the self-coupling of terminal alkyne; (4) Preparing an electrophile of alkynyl sulfur in advance, and synthesizing an alkynyl thioether compound through an alkynyl sulfur transfer strategy; however, the substrate range of the method is limited.
In addition, the patent with publication No. CN 115583902A provides a preparation method of alkynyl thioether compounds, which comprises dissolving silicon alkyne (D) and N-thiosuccinimide (F) in an organic solvent, heating and reacting to obtain a target product,
the method has limited substrate range (R 5 Is trifluoromethyl, alkyl and aryl substituent groups, does not contain other hetero atoms), and simultaneously needs to synthesize alkynyl silicon reagents and sulfur reagents, and has complex operation.
Disclosure of Invention
The invention aims to solve the problems that the existing synthesis method needs metal participation and has more byproducts, and provides a synthesis method of alkynyl thioether compounds, which is efficient, free of catalyst, wide in applicable substrate range, high in yield, simple in operation, easy in product separation and the like.
According to the technical scheme of the invention, the synthesis method of the alkynyl thioether compound takes alpha-bromostyrene sulfonium salt and nucleophilic reagent as raw materials, and the alkynyl thioether compound is obtained through heating reaction under the action of alkali;
the nucleophile is selected from morpholine, cyclohexylimine, N-methylaniline, diethylamine, N-allylbenzylamine, 2-thiophenemethylamine, alpha-methylbenzylamine, amantadine, propargylamine, 8-aminoquinoline, 4-methanesulfonylaniline, 3-amino-9-ethylcarbazole, imidazole, 4-methoxyacetanilide, 1-methylindole-2-carboxylic acid, N-methyl-L-proline, oxaprazine, 2- (6-methoxy-2-naphthyl) propionic acid, 4-dimethylaminobenzoic acid, aspirin or estrone.
Specifically, the structural formulas of the alpha-bromostyrene sulfonium salt and the nucleophile are respectively shown in a formula I and a formula II, and the general formula of the obtained alkynyl thioether compound is shown in a formula III:
wherein R in formula II or III is selected from
Further, the alpha-bromostyrene sulfonium salt is prepared from alpha-bromostyrene and tetramethylene sulfoxide in the presence of trifluoromethanesulfonic anhydride (Tf 2 And O) reacting.
Further, the alpha-bromostyrene, tetramethylene sulfoxide and Tf 2 The molar ratio of O is 1:1-1.3:1-1.3, for example, may be 1:1.1:1.1.
Further, the reaction is carried out under a protective atmosphere selected from argon, nitrogen, helium, etc., preferably helium.
Further, the reaction is carried out in methylene chloride; the reaction is carried out in two steps, wherein the reaction temperature in the first step is between-45 ℃ and-35 ℃ and the reaction time is between 12 and 20 minutes, preferably between-40 ℃ and 15 minutes; the second reaction temperature is-5 deg.c for 1.5-4 hr, and preferably 0 deg.c for 2min.
Further, the reaction includes a solvent removal and purification step after completion. Specifically, the solvent is removed under reduced pressure in vacuo, and the α -bromostyrol sulfonium salt is purified by recrystallization from methylene chloride and diethyl ether.
Further, the molar ratio of the alpha-bromostyryl sulfonium salt to the nucleophile is 1.0:2.0 to 3.0, for example, 1:2, 1:2.5, 1:3, etc.
Further, the alkali is a strong base selected from one or more of potassium hydroxide, sodium hydroxide, cesium carbonate and lithium tert-butoxide.
Further, the molar ratio of the base to the alpha-bromostyrene sulfonium salt is 2.0 to 5.0:1.0, for example, may be 2:1, 3:1, 4:1, 5:1, etc., preferably 3.0 to 4.0:1.0.
further, the temperature of the heating reaction is 80-100 ℃ and the time is 12-16 h.
Further, the heating reaction is performed under an air atmosphere.
Further, the heating reaction is performed in an organic solvent selected from one or more of 1, 4-dioxane, acetonitrile, DMSO (dimethyl sulfoxide) and tetrahydrofuran.
Further, the amount of the organic solvent added is 1.5 to 3mL/mmol in terms of the amount of the substance of the alpha-bromostyrene sulfonium salt, i.e., 1.5 to 3mL of the organic solvent is added per 1mmol of the alpha-bromostyrene sulfonium salt.
Further, the heating reaction further comprises the operation of purifying the product.
Further, the product was purified by column chromatography on silica gel.
Specifically, after the heating reaction is finished, column chromatography silica gel is added, the solvent is removed by reduced pressure distillation, the silica gel is dried by spin until the silica gel adsorption product is in powder form, then the powder is loaded into a chromatographic column, and the mixture of petroleum ether and ethyl acetate is used for eluting, collecting, evaporating and concentrating to obtain the alkynyl thioether compound.
Compared with the prior art, the technical scheme of the invention has the following advantages:
the method does not need a catalyst or metal, has easily obtained raw materials, and is environment-friendly and pollution-free;
the alkynyl thioether has wide product range, high yield, simple operation and easy separation and purification; has important significance in the synthesis of alkynyl thioether compounds.
Detailed Description
The present invention will be further described with reference to specific examples, which are not intended to be limiting, so that those skilled in the art will better understand the present invention and practice it.
The α -bromostyryl sulfonium salts of the invention can be prepared by themselves using either exo-products or according to existing literature, for example, literature C.Wang, B.Liu, Z.Shao, J.Zhou, A.Shao, l. -H.Zou, J.Wen, org.Lett.2022,24,6455-6459. The invention provides a synthesis method which comprises the following steps:
alpha-bromostyrene (10.0 mmol,1.82 g), tetramethylene sulfoxide (11.0 mmol,1.14 g), and trifluoromethanesulfonic anhydride (11.0 mmol,3.1 g) were added to a 100mL reaction tube under argon, and finally methylene chloride (50 mL) was added, and the reaction was carried out at-40℃for 15 minutes, then at 0℃for 2 hours, and the reaction was completed, and the solvent was removed under reduced pressure. Recrystallizing with dichloromethane and diethyl ether to obtain white solid, which is the corresponding sulfonium salt.
The gram-grade synthesis route is as follows:
all of the starting materials used in the present invention are commercially available.
The synthesis route of the target product is as follows:
example 1
The structural formula of the alkynyl thioether compound prepared in the embodiment is as follows:
the preparation method comprises the following steps: a10 mL reaction tube was charged with alpha-bromostyryl sulfonium salt (0.3 mmol,125.7 mg), morpholine (0.9 mmol,78.4 mg), sodium hydroxide (0.9 mmol,36.0 mg) and then tetrahydrofuran (2.0 mL) under air conditions, followed by stirring at 80℃for 12 hours. After the reaction, the reaction solution is cooled to room temperature, the solvent is removed by reduced pressure distillation, the crude product is subjected to silica gel column chromatography separation, petroleum ether and ethyl acetate (petroleum ether: ethyl acetate=2:1) are eluted with mixed solution, TLC (thin layer chromatography) plates are used for tracking and detecting, the eluent containing the target product is collected, the eluent containing the target product is combined, and the target product is evaporated and concentrated to obtain the compound with the yield of 93%. The material was a colorless oily liquid.
Characterization data: 1 H NMR(500MHz,Chloroform-d)δ7.42–7.38(m,2H),7.31–7.27(m,3H),3.71–3.69(m,4H),2.82(t,J＝7.1Hz,2H),2.44–2.42(m,4H),2.39–2.36(m,2H),1.88–1.82(m,2H),1.69–1.65(m,2H). 13 C NMR(126MHz,Chloroform-d)δ131.4,128.3,128.0,123.5,93.0,79.3,67.0,58.6,53.7,35.6,27.1,25.0.HRMS m/z(ESI)calcd for C 16 H 22 NOS(M+H) + 276.1417,found 276.1414.
example 2
The structural formula of the alkynyl thioether compound prepared in the embodiment is as follows:
the preparation method comprises the following steps: a10 mL reaction tube was charged with alpha-bromostyryl sulfonium salt (0.3 mmol,125.7 mg), cyclohexylimine (0.9 mmol,89.3 mg), sodium hydroxide (0.9 mmol,36.0 mg) and tetrahydrofuran (2.0 mL) under air conditions, followed by stirring at 80℃for 12 hours. After the reaction is finished, the reaction solution is cooled to room temperature, the solvent is removed by reduced pressure distillation, the crude product is subjected to silica gel column chromatography separation, the mixture of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate=2:1) is used for eluting, a TLC (thin layer chromatography) plate is used for tracking and detecting, the eluent containing the target product is collected, the eluent containing the target product is combined, and the target product is evaporated and concentrated to obtain the compound with the yield of 65%. The material was a pale yellow oily liquid.
Characterization data: 1 H NMR(400MHz,Chloroform-d)δ7.41–7.38(m,2H),7.30–7.27(m,3H),2.82(t,J＝7.2Hz,2H),2.62–2.60(m,4H),2.52–2.48(m,2H),1.85–1.78(m,1H),1.66–1.54(m,10H). 13 C NMR(101MHz,Chloroform-d)δ131.4,128.2,127.9,123.5,92.9,79.6,57.6,55.5,35.8,28.1,27.4,27.0,26.2.HRMS m/z(ESI)calcd for C 18 H 26 NS(M+H) + 288.1780,found 288.1781.
example 3
The structural formula of the alkynyl thioether compound prepared in the embodiment is as follows:
the preparation method comprises the following steps: alpha-bromostyrenesulfonium salt (0.3 mmol,125.7 mg), N-methylaniline (0.9 mmol,96.4 mg), sodium hydroxide (0.9 mmol,36.0 mg) were added to a 10mL reaction tube under air, followed by tetrahydrofuran (2.0 mL) and stirred at 80℃for 12 hours. After the reaction, the reaction solution is cooled to room temperature, the solvent is removed by reduced pressure distillation, the crude product is subjected to silica gel column chromatography separation, the crude product is eluted by a mixed solution of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate=3:1), the TLC is used for tracking and detecting, the eluent containing the target product is collected, the eluent containing the target product is combined, and the target product is evaporated and concentrated to obtain the compound with the yield of 63%. The material was a pale yellow oily liquid.
Characterization data: 1 H NMR(400MHz,Chloroform-d)δ7.39–7.36(m,2H),7.28–7.26(m,3H),7.22–7.18(m,2H),6.70–6.65(m,3H),3.34(t,J＝7.1Hz,2H),2.91(s,3H),2.79(t,J＝7.0Hz,2H),1.86–1.79(m,2H),1.76–1.69(m,2H). 13 C NMR(101MHz,Chloroform-d)δ149.2,131.4,129.1,128.2,123.4,116.2,112.2,93.2,79.3,52.2,38.3,35.6,27.0,25.5.HRMS m/z(ESI)calcd for C 19 H 22 NS(M+H) + 296.1467,found 296.1463.
example 4
The structural formula of the alkynyl thioether compound prepared in the embodiment is as follows:
the preparation method comprises the following steps: a10 mL reaction tube was charged with an alpha-bromostyryl sulfonium salt (0.3 mmol,125.7 mg), diethylamine (0.9 mmol,65.8 mg), sodium hydroxide (0.9 mmol,36.0 mg) under air, followed by tetrahydrofuran (2.0 mL) and stirring at 80℃for 12 hours. After the reaction is finished, the reaction solution is cooled to room temperature, the solvent is removed by reduced pressure distillation, the crude product is subjected to silica gel column chromatography separation, the mixture of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate=5:1) is used for eluting, a TLC (thin layer chromatography) plate is used for tracking and detecting, the eluent containing the target product is collected, the eluent containing the target product is combined, and the target product is evaporated and concentrated to obtain the compound with the yield of 64%. The material was a pale yellow oily liquid.
Characterization data: 1 H NMR(400MHz,Chloroform-d)δ7.41–7.37(m,2H),7.30–7.27(m,3H),2.82(t,J＝7.2Hz,2H),2.56(q,J＝7.2Hz,4H),2.52–2.48(m,2H),1.85–1.78(m,2H),1.67–1.60(m,2H),1.04(t,J＝7.2Hz,6H). 13 C NMR(101MHz,Chloroform-d)δ131.4,128.2,127.9,123.5,93.0,79.5,52.3,46.8,35.7,27.4,25.5,11.5.HRMS m/z(ESI)calcd for C 16 H 24 NS(M+H) + 262.1624,found 262.1620.
example 5
The structural formula of the alkynyl thioether compound prepared in the embodiment is as follows:
the preparation method comprises the following steps: a10 mL reaction tube was charged with alpha-bromostyryl sulfonium salt (0.3 mmol,125.7 mg), N-allylbenzylamine (0.9 mmol,132.5 mg), sodium hydroxide (0.9 mmol,36.0 mg) and tetrahydrofuran (2.0 mL) under air conditions, followed by stirring at 80℃for 12 hours. After the reaction, the reaction solution is cooled to room temperature, the solvent is removed by reduced pressure distillation, the crude product is subjected to silica gel column chromatography separation, the crude product is eluted by a mixed solution of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate=5:1), TLC (thin layer chromatography) plates are used for tracking and detecting, the eluent containing the target product is collected, the eluent containing the target product is combined, and the target product is evaporated and concentrated to obtain the compound with the yield of 79%. The material was a colorless oily liquid.
Characterization data: 1 H NMR(400MHz,Chloroform-d)δ7.41–7.36(m,2H),7.32–7.25(m,7H),7.22–7.19(m,1H),5.92–5.82(m,1H),5.20–5.10(m,2H),3.55(s,2H),3.06(d,J＝6.3Hz,2H),2.74(t,J＝7.2Hz,2H),2.46(t,J＝7.0Hz,2H),1.85–1.78(m,2H),1.67–1.60(m,2H). 13 C NMR(101MHz,Chloroform-d)δ139.7,136.0,131.4,128.8,128.2,128.1,127.9,126.7,123.6,117.1,92.9,79.6,58.2,56.7,52.5,35.6,27.0,25.6.HRMS m/z(ESI)calcd for C 22 H 26 NS(M+H) + 336.1780,found 336.1783.
example 6
The structural formula of the alkynyl thioether compound prepared in the embodiment is as follows:
the preparation method comprises the following steps: alpha-bromostyryl sulfonium salt (0.3 mmol,125.7 mg), 2-thiophenemethylamine (0.9 mmol,101.9 mg), sodium hydroxide (0.9 mmol,36.0 mg) were added to a 10mL reaction tube under air, followed by tetrahydrofuran (2.0 mL) and stirred at 80℃for 12 hours. After the reaction is finished, the reaction solution is cooled to room temperature, the solvent is removed by reduced pressure distillation, the crude product is subjected to silica gel column chromatography separation, the mixture of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate=10:1) is used for eluting, a TLC (thin layer chromatography) plate is used for tracking and detecting, the eluent containing the target product is collected, the eluent containing the target product is combined, and the target product is evaporated and concentrated to obtain the compound with the yield of 56%. The material was a yellow oily liquid.
Characterization data: 1 H NMR(400MHz,Chloroform-d)δ7.42–7.38(m,2H),7.30–7.28(m,3H),7.20(d,J＝5.0Hz,1H),6.95–6.91(m,2H),4.00(s,2H),2.82(t,J＝7.2Hz,2H),2.72(t,J＝7.1Hz,2H),1.91–1.84(m,2H),1.72–1.65(m,2H),1.45(brs,1H). 13 C NMR(101MHz,Chloroform-d)δ144.3,131.4,128.2,127.9,126.6,124.7,124.2,123.5,93.0,79.4,48.5,48.4,35.7,28.5,27.1.HRMS m/z(ESI)calcd for C 17 H 20 NS 2 (M+H) + 302.1032,found 302.1031.
example 7
The structural formula of the alkynyl thioether compound prepared in the embodiment is as follows:
the preparation method comprises the following steps: alpha-bromostyrenesulfonium salt (0.3 mmol,125.7 mg), alpha-methylbenzylamine (0.9 mmol,109.6 mg), sodium hydroxide (0.9 mmol,36.0 mg) were added to a 10mL reaction tube under air, followed by tetrahydrofuran (2.0 mL) and stirred at 80℃for 12 hours. After the reaction, the reaction solution is cooled to room temperature, the solvent is removed by reduced pressure distillation, the crude product is subjected to silica gel column chromatography separation, the crude product is eluted by a mixed solution of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate=3:1), the TLC is used for tracking and detecting, the eluent containing the target product is collected, the eluent containing the target product is combined, and the target product is evaporated and concentrated to obtain the compound with the yield of 63%. The material was a colorless oily liquid.
Characterization data: 1 H NMR(400MHz,Chloroform-d)δ7.41–7.36(m,2H),7.31–7.22(m,8H),3.76(q,J＝6.6Hz,1H),2.75(t,J＝7.2Hz,2H),2.58–2.52(m,1H),2.49–2.43(m,1H),1.88–1.72(m,2H),1.70–1.56(m,2H),1.35(d,J＝6.6Hz,3H). 13 C NMR(101MHz,Chloroform-d)δ145.4,131.4,128.4,128.2,127.9,126.9,126.5,123.5,93.0,79.4,58.3,47.0,35.6,28.7,27.1,24.2.HRMS m/z(ESI)calcd for C 20 H 24 NS(M+H) + 310.1624,found 310.1625.
example 8
The structural formula of the alkynyl thioether compound prepared in the embodiment is as follows:
the preparation method comprises the following steps: a10 mL reaction tube was charged with α -bromostyryl sulfonium salt (0.3 mmol,125.7 mg), amantadine (0.9 mmol,136.1 mg), sodium hydroxide (0.9 mmol,36.0 mg) and tetrahydrofuran (2.0 mL) under air, followed by stirring at 80℃for 12 hours. After the reaction is finished, the reaction solution is cooled to room temperature, the solvent is removed by reduced pressure distillation, the crude product is subjected to silica gel column chromatography separation, the mixture of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate=3:1) is used for eluting, a TLC (thin layer chromatography) plate is used for tracking and detecting, the eluent containing the target product is collected, the eluent containing the target product is combined, and the target product is evaporated and concentrated to obtain the compound with the yield of 68%. The material was a white solid.
Characterization data: 1 H NMR(400MHz,Chloroform-d)δ7.42–7.40(m,2H),7.30–7.27(m,3H),6.65(brs,1H),2.94–2.91(m,2H),2.79(t,J＝6.5Hz,2H),2.17(s,3H),1.95–1.85(m,10H),1.71–1.63(m,6H). 13 C NMR(101MHz,Chloroform-d)δ131.5,128.2,128.1,123.3,93.4,78.6,57.8,39.8,38.5,35.5,34.8,29.0,26.5,25.4.HRMS m/z(ESI)calcd for C 22 H 30 NS(M+H) + 340.2093,found 340.2095.
example 9
The structural formula of the alkynyl thioether compound prepared in the embodiment is as follows:
the preparation method comprises the following steps: alpha-bromostyryl sulfonium salt (0.3 mmol,125.7 mg), propargylamine (0.9 mmol,49.6 mg), sodium hydroxide (0.9 mmol,36.0 mg) were added to a 10mL reaction tube under air, followed by tetrahydrofuran (2.0 mL) and stirring at 80℃for 12h. After the reaction is finished, the reaction solution is cooled to room temperature, the solvent is removed by reduced pressure distillation, the crude product is subjected to silica gel column chromatography separation, the mixture of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate=5:1) is used for eluting, a TLC (thin layer chromatography) plate is used for tracking and detecting, the eluent containing the target product is collected, the eluent containing the target product is combined, and the target product is evaporated and concentrated to obtain the compound with the yield of 60%. The material was a yellow oily liquid.
Characterization data: 1 H NMR(400MHz,Chloroform-d)δ7.41–7.37(m,2H),7.30–7.26(m,3H),3.44(d,J＝2.4Hz,2H),2.82(t,J＝7.2Hz,2H),2.75(t,J＝7.2Hz,2H),2.22(t,J＝2.4Hz,1H),2.02(brs,1H),2.02–1.83(m,2H),1.71–1.63(m,2H). 13 C NMR(101MHz,Chloroform-d)δ131.4,128.2,127.9,123.4,93.0,81.8,79.3,71.5,47.8,38.0,35.5,28.1,27.0.HRMS m/z(ESI)calcd for C 15 H 18 NS(M+H) + 244.1154,found 244.1159.
example 10
The structural formula of the alkynyl thioether compound prepared in the embodiment is as follows:
the preparation method comprises the following steps: a10 mL reaction tube was charged with an alpha-bromostyryl sulfonium salt (0.3 mmol,125.7 mg), 8-aminoquinoline (0.9 mmol,129.8 mg), sodium hydroxide (0.9 mmol,36.0 mg) and tetrahydrofuran (2.0 mL) under air conditions, followed by stirring at 80℃for 12 hours. After the reaction, the reaction solution is cooled to room temperature, the solvent is removed by reduced pressure distillation, the crude product is subjected to silica gel column chromatography separation, the crude product is eluted by a mixed solution of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate=2:1), TLC (thin layer chromatography) plates are used for tracking and detecting, the eluent containing the target product is collected, the eluent containing the target product is combined, and the target product is evaporated and concentrated to obtain the compound with the yield of 63%. The material was a colorless oily liquid.
Characterization data: 1 H NMR(400MHz,Chloroform-d)δ8.69(dd,J＝4.2,1.7Hz,1H),8.06(dd,J＝8.3,1.7Hz,1H),7.43–7.34(m,4H),7.31–7.25(m,3H),7.05(dd,J＝8.2,1.2Hz,1H),6.68(dd,J＝7.7,1.2Hz,1H),6.18(brs,1H),3.39(dt,J＝9.6,4.5Hz,2H),2.88(t,J＝6.8Hz,2H),2.07–1.93(m,4H). 13 C NMR(101MHz,Chloroform-d)δ146.8,144.7,138.1,136.0,131.4,128.6,128.2,127.9,127.8,123.4,121.3,113.7,104.5,93.2,79.2,42.8,35.5,27.8,27.0.HRMS m/z(ESI)calcd for C 21 H 21 N 2 S(M+H) + 333.1420,found 333.1421.
example 11
The structural formula of the alkynyl thioether compound prepared in the embodiment is as follows:
the preparation method comprises the following steps: a10 mL reaction tube was charged with alpha-bromostyryl sulfonium salt (0.3 mmol,125.7 mg), 4-methanesulfonylaniline (0.9 mmol,154.1 mg), sodium hydroxide (0.9 mmol,36.0 mg) and then tetrahydrofuran (2.0 mL) under air conditions, followed by stirring at 80℃for 12 hours. After the reaction is finished, the reaction solution is cooled to room temperature, the solvent is removed by reduced pressure distillation, the crude product is subjected to silica gel column chromatography separation, the mixture of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate=5:1) is used for eluting, a TLC (thin layer chromatography) plate is used for tracking and detecting, the eluent containing the target product is collected, the eluent containing the target product is combined, and the target product is evaporated and concentrated to obtain the compound with the yield of 52%. The material was a white solid.
Characterization data: 1 H NMR(400MHz,Chloroform-d)δ7.65(d,J＝8.8Hz,2H),7.38(dd,J＝6.6,3.0Hz,2H),7.30–7.27(m,3H),6.58(d,J＝8.8Hz,2H),4.42(brs,1H),3.24–3.20(m,2H),2.98(s,3H),2.83(t,J＝6.8Hz,2H),1.94–1.89(m,2H),1.85–1.78(m,2H). 13 C NMR(101MHz,Chloroform-d)δ152.2,131.3,129.3,128.3,128.1,127.1,123.2,111.7,93.3,78.9,45.0,42.7,35.2,27.5,26.5.HRMS m/z(ESI)calcd for C 19 H 22 NO 2 S 2 (M+H) + 360.1086,found 360.1087.
example 12
The structural formula of the alkynyl thioether compound prepared in the embodiment is as follows:
the preparation method comprises the following steps: a10 mL reaction tube was charged with alpha-bromostyrenesulfonium salt (0.3 mmol,125.7 mg), 3-amino-9-ethylcarbazole (0.9 mmol,189.2 mg), sodium hydroxide (0.9 mmol,36.0 mg) and then tetrahydrofuran (2.0 mL) under air, followed by stirring at 80℃for 12 hours. After the reaction, the reaction solution is cooled to room temperature, the solvent is removed by reduced pressure distillation, the crude product is subjected to silica gel column chromatography separation, the crude product is eluted by a mixed solution of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate=5:1), TLC (thin layer chromatography) plates are used for tracking and detecting, the eluent containing the target product is collected, the eluent containing the target product is combined, and the target product is evaporated and concentrated to obtain the compound with the yield of 63%. The material was a dark yellow oily liquid.
Characterization data: 1 H NMR(400MHz,Chloroform-d)δ8.06(d,J＝7.8Hz,1H),7.49–7.44(m,3H),7.37(dd,J＝5.2,2.9Hz,2H),7.34–7.32(m,3H),7.26(d,J＝8.6Hz,1H),7.22–7.18(m,1H),6.89(dd,J＝8.6,2.3Hz,1H),4.32(q,J＝7.2Hz,2H),3.31(t,J＝7.0Hz,2H),2.90(t,J＝7.1Hz,2H),2.05–1.99(m,2H),1.92–1.86(m,2H),1.42(t,J＝7.2Hz,2H). 13 C NMR(126MHz,Chloroform-d)δ141.6,140.2,134.0,131.4,128.3,128.0,125.2,123.6,123.4,122.6,120.3,117.8,114.5,109.1,108.3,103.3,93.2,79.3,45.0,37.4,35.4,28.2,26.9,13.8.HRMS m/z(ESI)calcd for C 26 H 27 N 2 S(M+H) + 399.1889,found 399.1887.
example 13
The structural formula of the alkynyl thioether compound prepared in the embodiment is as follows:
the preparation method comprises the following steps: a10 mL reaction tube was charged with alpha-bromostyryl sulfonium salt (0.3 mmol,125.7 mg), imidazole (0.6 mmol,40.9 mg), sodium hydroxide (0.9 mmol,36.0 mg) and tetrahydrofuran (2.0 mL) under air, followed by stirring at 80℃for 12 hours. After the reaction is finished, the reaction solution is cooled to room temperature, the solvent is removed by reduced pressure distillation, the crude product is subjected to silica gel column chromatography separation, the mixture of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate=2:1) is used for eluting, a TLC (thin layer chromatography) plate is used for tracking and detecting, the eluent containing the target product is collected, the eluent containing the target product is combined, and the target product is evaporated and concentrated to obtain the compound with the yield of 65%. The material was a pale yellow oily liquid.
Characterization data: 1 H NMR(400MHz,Chloroform-d)δ7.47(s,1H),7.38–7.36(m,2H),7.30–7.26(m,3H),7.03(s,1H),6.90(s,1H),3.97(t,J＝7.0Hz,2H),2.76(t,J＝6.9Hz,2H),1.98–1.91(m,2H),1.82–1.75(m,2H). 13 C NMR(101MHz,Chloroform-d)δ136.9,131.3,129.4,128.2,128.1,123.1,118.6,93.3,78.6,46.4,34.9,29.4,26.1.HRMS m/z(ESI)calcd for C 15 H 17 N 2 S(M+H) + 257.1107,found257.1104.
example 14
The structural formula of the alkynyl thioether compound prepared in the embodiment is as follows:
the preparation method comprises the following steps: a10 mL reaction tube was charged with alpha-bromostyrenesulfonium salt (0.3 mmol,125.7 mg), 4-methoxyacetanilide (0.9 mmol,148.8 mg), sodium hydroxide (0.9 mmol,36.0 mg) and tetrahydrofuran (2.0 mL) under air, followed by stirring at 80℃for 12 hours. After the reaction is finished, the reaction solution is cooled to room temperature, the solvent is removed by reduced pressure distillation, the crude product is subjected to silica gel column chromatography separation, the mixture of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate=3:1) is used for eluting, a TLC (thin layer chromatography) plate is used for tracking and detecting, the eluent containing the target product is collected, the eluent containing the target product is combined, and the target product is evaporated and concentrated to obtain the compound with the yield of 72%. The material was a pale yellow oily liquid.
Characterization data: 1 H NMR(500MHz,Chloroform-d)δ7.40–7.38(m,2H),7.30–7.27(m,3H),7.10–7.06(m,2H),6.91–6.88(m,2H),3.81(s,3H),3.72(t,J＝7.3Hz,2H),2.80(t,J＝7.0Hz,2H),1.87–1.80(m,5H),1.71–1.63(m,2H). 13 C NMR(101MHz,Chloroform-d)δ170.6,158.9,135.6,131.3,129.0,128.2,127.9,123.4,114.8,93.0,79.4,55.4,48.1,35.4,26.5,26.3,22.6.HRMS m/z(ESI)calcd for C 21 H 24 NO 2 S(M+H) + 354.1522,found 354.1520.
example 15
The structural formula of the alkynyl thioether compound prepared in the embodiment is as follows:
the preparation method comprises the following steps: a10 mL reaction tube was charged with alpha-bromostyryl sulfonium salt (0.3 mmol,125.7 mg), 1-methylindole-2-carboxylic acid (0.9 mmol,157.7 mg), cesium carbonate (0.9 mmol,293.2 mg) and tetrahydrofuran (2.0 mL) under air conditions, followed by stirring at 80℃for 12 hours. After the reaction is finished, the reaction solution is cooled to room temperature, the solvent is removed by reduced pressure distillation, the crude product is subjected to silica gel column chromatography separation, the mixture of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate=1:1) is used for eluting, a TLC (thin layer chromatography) plate is used for tracking and detecting, the eluent containing the target product is collected, the eluent containing the target product is combined, and the target product is evaporated and concentrated to obtain the compound with the yield of 55%. The material was a colorless oily liquid.
Characterization data: 1 H NMR(400MHz,Chloroform-d)δ7.60(d,J＝8.1Hz,1H),7.37–7.32(m,4H),7.28(s,1H),7.24–7.17(m,3H),7.14–7.10(m,1H),4.36(t,J＝5.9Hz,2H),4.03(s,3H),2.85(t,J＝6.7Hz,2H),2.04–1.91(m,4H). 13 C NMR(101MHz,Chloroform-d)δ162.1,139.6,131.3,128.2,128.0,127.7,125.8,124.9,123.3,122.5,120.5,110.2,93.3,79.0,63.7,35.2,31.5,27.3,25.9.HRMS m/z(ESI)calcd for C 22 H 22 NO 2 S(M+H) + 364.1366,found 364.1364.
example 16
The structural formula of the alkynyl thioether compound prepared in the embodiment is as follows:
the preparation method comprises the following steps: alpha-bromostyrenesulfonium salt (0.3 mmol,125.7 mg), N-methyl L-proline (0.9 mmol,116.2 mg), cesium carbonate (0.9 mmol,293.2 mg) were added to a 10mL reaction tube under air, followed by tetrahydrofuran (2.0 mL) and stirred at 80℃for 12 hours. After the reaction is finished, the reaction solution is cooled to room temperature, the solvent is removed by reduced pressure distillation, the crude product is subjected to silica gel column chromatography separation, the mixture of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate=1:1) is used for eluting, a TLC (thin layer chromatography) plate is used for tracking and detecting, the eluent containing the target product is collected, the eluent containing the target product is combined, and the target product is evaporated and concentrated to obtain the compound with the yield of 56%. The material was a colorless oily liquid.
Characterization data: 1 H NMR(400MHz,Chloroform-d)δ7.40–7.38(m,2H),7.29–7.27(m,3H),4.21–4.17(m,2H),3.13–3.08(m,1H),2.97–2.93(m,1H),2.81(t,J＝6.7Hz,2H),2.39(s,3H),2.32–2.26(m,1H),2.15–2.05(m,1H),1.98–1.81(m,6H),1.77–1.69(m,1H). 13 C NMR(101MHz,Chloroform-d)δ173.5,131.3,128.2,127.9,123.3,93.1,79.0,67.4,63.8,56.2,40.8,35.1,29.6,27.2,25.8,23.0.HRMS m/z(ESI)calcd for C18H24NO2S(M+H)+318.1522,found 318.1523.
example 17
The structural formula of the alkynyl thioether compound prepared in the embodiment is as follows:
the preparation method comprises the following steps: alpha-bromostyrenesulfonium salt (0.3 mmol,125.7 mg), oxaprozin (0.9 mmol,263.8 mg), cesium carbonate (0.9 mmol,293.2 mg) were added to a 10mL reaction tube under air, followed by tetrahydrofuran (2.0 mL) and stirred at 80℃for 12h. After the reaction, the reaction solution is cooled to room temperature, the solvent is removed by reduced pressure distillation, the crude product is subjected to silica gel column chromatography separation, the crude product is eluted by a mixed solution of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate=10:1), TLC (thin layer chromatography) plates are used for tracking and detecting, the eluent containing the target product is collected, the eluent containing the target product is combined, and the target product is evaporated and concentrated to obtain the compound with the yield of 53%. The material was a pale yellow oily liquid.
Characterization data: 1 H NMR(500MHz,Chloroform-d)δ7.64–7.62(m,2H),7.57–7.55(m,2H),7.40–7.30(m,8H),7.29–7.25(m,3H),4.18(t,J＝6.2Hz,2H),3.17(t,J＝7.5Hz,2H),2.90(t,J＝7.5Hz,2H),2.76(t,J＝6.8Hz,2H),1.87–1.82(m,4H). 13 C NMR(126MHz,Chloroform-d)δ171.9,161.6,145.4,135.1,132.4,131.4,128.9,128.6,128.5,128.4,128.2,128.0,128.0,127.8,126.4,123.3,93.2,79.0,64.1,35.1,31.1,27.1,25.7,23.5.HRMS m/z(ESI)calcd for C 30 H 28 NO 3 S(M+H) + 482.1784,found 482.1787.
example 18
The structural formula of the alkynyl thioether compound prepared in the embodiment is as follows:
the preparation method comprises the following steps: alpha-bromostyrenesulfonium salt (0.3 mmol,125.7 mg), 2- (6-methoxy-2-naphthyl) propionic acid (0.9 mmol,207.2 mg), cesium carbonate (0.9 mmol,293.2 mg) were added to a 10mL reaction tube under air, followed by tetrahydrofuran (2.0 mL) and stirred at 80℃for 12 hours. After the reaction, the reaction solution is cooled to room temperature, the solvent is removed by reduced pressure distillation, the crude product is subjected to silica gel column chromatography separation, the crude product is eluted by a mixed solution of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate=5:1), TLC (thin layer chromatography) plates are used for tracking and detecting, the eluent containing the target product is collected, the eluent containing the target product is combined, and the target product is evaporated and concentrated to obtain the compound with the yield of 71%. The material was a colorless liquid.
Characterization data: 1 H NMR(500MHz,Chloroform-d)δ7.68(d,J＝8.6Hz,2H),7.64(d,J＝1.8Hz,1H),7.42–7.36(m,3H),7.31–7.25(m,3H),7.12(dd,J＝8.9,2.5Hz,1H),7.09(d,J＝2.5Hz,1H),4.14–4.10(m,2H).3.88(s,3H),3.83(q,J＝7.1Hz,1H),2.69(t,J＝7.6,5.6Hz,2H),1.80–1.72(m,4H),1.56(d,J＝7.2Hz,3H). 13 C NMR(126MHz,Chloroform-d)δ174.6,157.6,135.6,133.6,131.3,129.2,128.8,128.2,128.0,127.1,126.1,125.8,123.3,105.5,93.1,79.1,64.0,55.2,45.4,35.1,27.0,25.7,18.4.HRMS m/z(ESI)calcd for C 26 H 27 O 3 S(M+H) + 419.1675,found 419.1676.
example 19
The structural formula of the alkynyl thioether compound prepared in the embodiment is as follows:
the preparation method comprises the following steps: a10 mL reaction tube was charged with alpha-bromostyryl sulfonium salt (0.3 mmol,125.7 mg), 4-dimethylaminobenzoic acid (0.9 mmol,148.7 mg), cesium carbonate (0.9 mmol,293.2 mg) and tetrahydrofuran (2.0 mL) under air conditions, followed by stirring at 80℃for 12h. After the reaction, the reaction solution is cooled to room temperature, the solvent is removed by reduced pressure distillation, the crude product is subjected to silica gel column chromatography separation, the crude product is eluted by a mixed solution of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate=10:1), TLC (thin layer chromatography) plates are used for tracking and detecting, the eluent containing the target product is collected, the eluent containing the target product is combined, and the target product is evaporated and concentrated to obtain the compound with the yield of 62%. The material was a colorless oily liquid.
Characterization data: 1 H NMR(500MHz,Chloroform-d)δ7.92–7.89(m,2H),7.41–7.39(m,2H),7.29–7.26(m,3H),6.61–6.58(m,2H),4.32(t,J＝6.1Hz,2H),3.00(s,6H),2.86(t,J＝7.0Hz,2H),2.07–1.93(m,4H). 13 C NMR(126MHz,Chloroform-d)δ166.9,153.2,131.4,131.2,128.2,127.9,123.4,116.9,110.6,93.1,79.1,63.4,40.0,35.2,27.4,26.0.HRMS m/z(ESI)calcd for C 21 H 24 NO 2 S(M+H) + 354.1522,found 354.1520.
example 20
The structural formula of the alkynyl thioether compound prepared in the embodiment is as follows:
the preparation method comprises the following steps: alpha-bromostyryl sulfonium salt (0.3 mmol,125.7 mg), aspirin (0.9 mmol,162.14 mg), cesium carbonate (0.9 mmol,293.2 mg) were added to a 10mL reaction tube under air, followed by tetrahydrofuran (2.0 mL) and stirred at 80℃for 12h. After the reaction is finished, the reaction solution is cooled to room temperature, the solvent is removed by reduced pressure distillation, the crude product is subjected to silica gel column chromatography separation, the mixture of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate=3:1) is used for eluting, a TLC (thin layer chromatography) plate is used for tracking and detecting, the eluent containing the target product is collected, the eluent containing the target product is combined, and the target product is evaporated and concentrated to obtain the compound with the yield of 58%. The material was a colorless oily liquid.
Characterization data: 1 H NMR(500MHz,Chloroform-d)δ10.79(brs,1H),7.83(dd,J＝8.0,1.7Hz,1H),7.46–7.42(m,1H),7.40–7.38(m,2H),7.30–7.27(m,3H),6.98(dd,J＝8.4,1.1Hz,1H),6.83–6.79(m,1H),4.43–4.40(m,2H),2.89–2.86(m,2H),2.02–1.99(m,4H). 13 C NMR(126MHz,Chloroform-d)δ170.1,161.7,135.7,131.4,129.8,128.3,128.1,123.3,119.1,117.6,112.4,93.3,78.8,64.6,35.1,27.1,25.8.HRMS m/z(ESI)calcd for C 19 H 19 O 3 S(M+H) + 327.1049,found 327.1052.
example 21
The structural formula of the alkynyl thioether compound prepared in the embodiment is as follows:
the preparation method comprises the following steps: a10 mL reaction tube was charged with alpha-bromostyryl sulfonium salt (0.3 mmol,125.7 mg), estrone (0.6 mmol,162.2 mg), sodium hydroxide (0.9 mmol,36.0 mg) and then tetrahydrofuran (2.0 mL) under air conditions, followed by stirring at 100℃for 12 hours. After the reaction is finished, the reaction solution is cooled to room temperature, the solvent is removed by reduced pressure distillation, the crude product is subjected to silica gel column chromatography separation, the mixture of petroleum ether and ethyl acetate (petroleum ether: ethyl acetate=5:1) is used for eluting, a TLC (thin layer chromatography) plate is used for tracking and detecting, the eluent containing the target product is collected, the eluent containing the target product is combined, and the target product is evaporated and concentrated to obtain the compound with the yield of 52%. The material was a white solid.
Characterization data: 1 H NMR(500MHz,Chloroform-d)δ7.43–7.40(m,2H),7.31–7.28(m,3H),7.19(d,J＝8.6Hz,1H),6.72(dd,J＝8.6,2.7Hz,1H),6.65(d,J＝2.6Hz,1H),4.00(t,J＝6.0Hz,2H),2.90–2.86(m,4H),2.53(dd,J＝19.0,8.6Hz,1H),2.45–2.37(m,1H),2.27(dt,J＝10.6,5.7Hz,1H),2.21–2.12(m,1H),2.11–1.95(m,7H),1.63–1.48(m,6H),0.91(s,3H). 13 C NMR(126MHz,Chloroform-d)δ156.9,137.7,132.0,131.4,128.2,127.9,126.3,123.5,114.5,112.1,93.1,79.3,67.1,50.4,47.9,43.9,38.3,35.8,35.4,31.6,29.6,27.8,26.5,26.0,25.9,21.5,13.8.HRMS m/z(ESI)calcd for C 30 H 35 O 2 S(M+H) + 459.2352,found459.2352.
example 21: influence of alkali
Referring to example 1, only sodium hydroxide and the amount thereof were replaced with other bases or amounts shown in table 2, and the results of the corresponding reactions were shown in table 1, with the others unchanged.
TABLE 1 Effect of base on preparation of alkynyl thioethers
Alkali Dosage of Yield of alkynyl thioether compounds
Sodium hydroxide (example 1) 0.9mmol 93％
Potassium hydroxide 0.9mmol 90％
Lithium tert-butoxide 0.9mmol 81％
Cs 2 CO 3 0.9mmol 82％
Sodium hydroxide 0.3mmol 52％
Sodium hydroxide 0.6mmol 79％
Sodium hydroxide 1.2mmol 89％
Sodium hydroxide 1.5mmol 81％
Example 22: influence of solvent
Referring to example 1, only tetrahydrofuran was replaced with other solvents shown in table 3, and the other solvents were unchanged, and the results of the corresponding reactions are shown in table 2.
TABLE 2 Effect of solvent selection on preparation of alkynyl thioethers
Solvent(s) Yield of alkynyl thioether compounds
Tetrahydrofuran (example 1) 93％
1, 4-Dioxahexacyclic ring 45％
Acetonitrile 68％
DMSO 68％
Example 23: expansion of reaction atmosphere
Referring to example 1, the atmosphere was replaced with oxygen and nitrogen, respectively, and the results of the corresponding reactions were shown in table 3.
TABLE 3 influence of the reaction atmosphere on alkynyl thioethers
Example 24: amplification reaction
Referring to example 1, an α -bromostyrene sulfate (3.0 mmol,1.26 g), sodium hydroxide (9.0 mmol,360.0 mg) and morpholine (9.0 mmol,964.0 mg) were charged into a 50mL reaction tube under air, tetrahydrofuran (20.0 mL) was added, and reacted at 100℃for 12 hours. After the reaction, the solvent is removed by reduced pressure distillation, the crude product is subjected to silica gel column chromatography separation, petroleum ether is used for eluting, TLC (thin layer chromatography) point plate tracking detection is carried out, eluent containing the target product is collected, the eluent containing the target product is combined, and the compound shown in the example 1 is obtained by evaporation and concentration, and the yield is 85%. The material was a colorless oily liquid.
Example 25: one pot reaction
Alpha-bromostyrene (1.0 mmol,183.0 mg), tetramethylene sulfoxide (1.1 mmol,114.6 mg), and trifluoromethanesulfonic anhydride (1.1 mmol,301.0 mg) were charged into a 10mL Schlenk tube under argon atmosphere, methylene chloride (5.0 mL) was added, and the mixture was reacted at-40℃for 15 minutes and then transferred to 0℃for 2 hours. After the completion of the reaction, the solvent was distilled off under reduced pressure. Morpholine (3.0 mmol,261.3 mg), sodium hydroxide (5.0 mmol,200.0 mg) and tetrahydrofuran (5.0 mL) were added in this order and stirred at 100℃for 12 hours. After the reaction, the reaction solution is cooled to room temperature, the solvent is removed by reduced pressure distillation, the crude product is subjected to silica gel column chromatography separation, petroleum ether and ethyl acetate (petroleum ether: ethyl acetate=2:1) are eluted with mixed solution, TLC (thin layer chromatography) plates are used for tracking and detecting, the eluent containing the target product is collected, the eluent containing the target product is combined, and the target product is evaporated and concentrated to obtain the compound with the yield of 84%. The material was a colorless oily liquid.
It is apparent that the above examples are given by way of illustration only and are not limiting of the embodiments. Other variations or modifications of the above teachings will be apparent to those of ordinary skill in the art. It is not necessary here nor is it exhaustive of all embodiments. And obvious variations or modifications thereof are contemplated as falling within the scope of the present invention.

Claims (10)

1. The synthesis method of the alkynyl thioether compound is characterized in that alpha-bromostyrene sulfonium salt and a nucleophilic reagent are used as raw materials, and the alkynyl thioether compound is obtained through heating reaction under the action of alkali;
the nucleophile is selected from morpholine, cyclohexylimine, N-methylaniline, diethylamine, N-allylbenzylamine, 2-thiophenemethylamine, alpha-methylbenzylamine, amantadine, propargylamine, 8-aminoquinoline, 4-methanesulfonylaniline, 3-amino-9-ethylcarbazole, imidazole, 4-methoxyacetanilide, 1-methylindole-2-carboxylic acid, N-methyl-L-proline, oxaprazine, 2- (6-methoxy-2-naphthyl) propionic acid, 4-dimethylaminobenzoic acid, aspirin or estrone.
2. The synthesis method according to claim 1, wherein the molar ratio of the α -bromostyrenesulfonium salt to the nucleophile is 1.0:2.0 to 3.0.
3. The method of synthesis according to claim 1, wherein the base is a strong base selected from one or more of potassium hydroxide, sodium hydroxide, cesium carbonate and lithium t-butoxide.
4. A method of synthesis according to claim 1 or claim 3, wherein the molar ratio of base to the α -bromostyrenesulfonium salt is from 2.0 to 5.0:1.0.
5. the method according to claim 1, wherein the heating reaction is carried out at a temperature of 80 to 100 ℃ for a period of 12 to 16 hours.
6. The synthesis according to claim 1, wherein the heating reaction is carried out under atmospheric conditions.
7. The synthetic method of claim 1 wherein the heating reaction is performed in an organic solvent selected from one or more of 1, 4-dioxane, acetonitrile, DMSO, and tetrahydrofuran.
8. The synthesis method according to claim 7, wherein the amount of the organic solvent added is 1.5 to 3mL/mmol based on the amount of the substance of the α -bromostyrenesulfonium salt.
9. The method of claim 1, wherein the heating reaction is followed by purifying the product.
10. The synthetic method of claim 9 wherein the product is purified using silica gel column chromatography.
CN202310562755.XA 2023-05-18 2023-05-18 Synthesis method of alkynyl thioether compound Pending CN116535280A (en)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115819301A (en) * 2022-11-23 2023-03-21 湖南大学 Method for preparing alkynyl sulfur (selenium) ether by coupling zinc-promoted disulfide (selenium) ether with alkynyl bromide

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115819301A (en) * 2022-11-23 2023-03-21 湖南大学 Method for preparing alkynyl sulfur (selenium) ether by coupling zinc-promoted disulfide (selenium) ether with alkynyl bromide

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