CN-122010800-A - A kind of substituted thiophenol is a process for the selective alkylation of

Abstract

The invention belongs to the technical fields of natural compounds, pharmaceutical chemical intermediates and related chemistry, and discloses a method for selectively alkylating substituted thiophenol, the substituted thiophenol is used as a raw material, sodium borohydride is used as a reduction polymerization inhibitor, quaternary ammonium salt is used as an alkylating reagent, and the substituted thiophenol is prepared by selective alkylation in a solvent in the presence of alkali. The method has high product selectivity and simple operation and post-treatment. The addition of sodium borohydride reduces polymerization inhibition raw materials, greatly improves the conversion rate and yield of the reaction, reduces the synthesis cost and provides possibility for realizing industrialization. Meanwhile, the use of high-activity and high-toxicity methylating agents is avoided, and the environmental hazard is reduced.

Inventors

• BAO MING
• LI TAO
• WANG YONGCAN

Assignees

• 大连理工大学

Dates

Publication Date

20260512

Application Date

20260129

Claims (8)

1. 1. A method for selectively alkylating substituted thiophenol is characterized in that the substituted thiophenol is taken as a raw material, sodium borohydride is taken as a reduction polymerization inhibitor, quaternary ammonium salt is taken as an alkylating agent, and the substituted thiophenol is prepared by selectively alkylating in a solvent in the presence of alkali, wherein the synthesis reaction formula is as follows: ; The reaction temperature is 100-110 ℃, and the reaction time is 4-8 h; R 1 is hydroxy, amino, carboxyl, aliphatic or aromatic hydrocarbon; R 2 is aliphatic hydrocarbon group such as methyl, ethyl, propyl or butyl.
2. 2. The process for the selective alkylation of a substituted thiophenol according to claim 1, wherein said quaternary ammonium salt is tetramethyl ammonium fluoride, tetramethyl ammonium chloride, tetramethyl ammonium bromide, tetraethyl ammonium chloride, tetrapropyl ammonium chloride, tetrabutyl ammonium bromide.
3. 3. The process for the selective alkylation of substituted thiophenols according to claim 1, wherein said base is sodium hydroxide, potassium hydroxide, lithium hydroxide.
4. 4. The method for selective alkylation of substituted thiophenols according to claim 1, wherein said solvent is one of DMF, DMSO, N-methylpyrrolidone, 1, 3-dimethyl-2-imidazolidinone, chlorobenzene, toluene.
5. 5. The method for selective alkylation of substituted thiophenols according to claim 1, wherein said sodium borohydride is used in an amount of 0.1 to 1.0 equivalent of substituted thiophenols.
6. 6. The method for selective alkylation of a substituted thiophenol according to claim 1, wherein the amount of the base used is 1.0 to 3.0 equivalents of the substituted thiophenol.
7. 7. The method for the selective alkylation of a substituted thiophenol according to claim 1, wherein the quaternary ammonium salt is used in an amount of 1.0 to 2.0 equivalents of the substituted thiophenol.
8. 8. The method for selective alkylation of a substituted thiophenol according to claim 1, wherein the molar concentration of said substituted thiophenol in the reaction system is 1 to 5 mol/L.

Description

A kind of substituted thiophenol is a process for the selective alkylation of Technical Field The invention belongs to the technical fields of natural compounds, pharmaceutical chemical intermediates and related chemistry, and relates to a method for selectively alkylating substituted thiophenols. Background Substituted phenyl sulfide is an important intermediate in organic synthesis, and has important position in the fields of chemical industry, medicine and the like because of the special property. In the chemical industry, substituted phenyl sulfides can be used as raw materials for synthesizing other compounds, such as dyes, fragrances and the like. In the pharmaceutical field, substituted phenylthioethers are often used as intermediates or active ingredients in pharmaceutical synthesis. In addition, the substituted phenyl sulfide can also be used for preparing products such as pesticides, coatings and the like, and provides important support for agriculture and building industry. Therefore, the substituted phenyl sulfide has wide application fields. The preparation method of the substituted phenyl sulfide is various, and is mainly prepared by taking substituted thiophenol as a raw material and directly alkylating sulfhydryl. For example, methyl thiophenol is methylated by using methyl iodide, dimethyl sulfate, methyl metal compound, etc. as methylating agent, however, methyl iodide is expensive, dimethyl sulfate is toxic and the environmental pollution of methyl metal agent is serious. In addition, the substituted thiophenol is easy to form disulfide under the high temperature condition, and the synthesis yield of the substituted thiophenol is directly reduced. Therefore, the preparation method has important significance in selecting cheap and low-toxicity reagents and developing an environment-friendly method for preparing the substituted phenyl sulfide. Disclosure of Invention The invention provides a preparation method of substituted phenyl sulfide, which adopts quaternary ammonium salt as an alkylating reagent, inhibits disulfide generation by adding sodium borohydride, and has the advantages of mild reaction conditions, low price and easy obtainment of the alkylating reagent, high reaction selectivity and the like. The technical scheme of the invention is as follows: A method for selectively alkylating substituted thiophenol, which takes substituted thiophenol as raw material, sodium borohydride as reduction polymerization inhibitor and quaternary ammonium salt as alkylating agent, prepares substituted thiophenol by selective alkylation in solvent in the presence of alkali, the synthetic reaction formula is as follows: The reaction temperature is 100-110 ℃, and the reaction time is 4-8 h; R 1 is hydroxy, amino, carboxyl, aliphatic or aromatic hydrocarbon; r 2 is aliphatic hydrocarbon group such as methyl, ethyl, propyl or butyl; the quaternary ammonium salt is tetraalkyl ammonium halides such as tetramethyl ammonium fluoride, tetramethyl ammonium chloride, tetramethyl ammonium bromide, tetraethyl ammonium chloride, tetrapropyl ammonium chloride, tetrabutyl ammonium bromide and the like; the alkali is alkali metal alkali such as sodium hydroxide, potassium hydroxide, lithium hydroxide and the like; The solvent is one of DMF, DMSO, N-methylpyrrolidone, 1, 3-dimethyl-2-imidazolidinone, chlorobenzene and toluene; The usage amount of the sodium borohydride is 0.1-1.0 equivalent of the substituted thiophenol. The usage amount of the alkali is 1.0-3.0 equivalent of the substituted thiophenol. The usage amount of the quaternary ammonium salt is 1.0-2.0 equivalent of the substituted thiophenol. The molar concentration of the substituted thiophenol in the reaction system is 1-5 mol/L. The separation method comprises recrystallization, column chromatography and the like. The solvent used in the recrystallization method is water, and silica gel or basic alumina can be used as stationary phase by column chromatography method, and the developing agent is generally mixed solvent of polarity and nonpolar, such as ethyl acetate-petroleum ether, ethyl acetate-n-heptane, and petroleum ether. The method has the beneficial effects that the product selectivity of the method is high, and the operation and the post-treatment are simple. The addition of sodium borohydride reduces polymerization inhibition raw materials, greatly improves the conversion rate and yield of the reaction, reduces the synthesis cost and provides possibility for realizing industrialization. Meanwhile, the use of high-activity and high-toxicity methylating agents is avoided, and the environmental hazard is reduced. Drawings FIG. 1 is a 1 H nuclear magnetic spectrum of 3-methylthiobenzoic acid in example 1. FIG. 2 is a 1 H nuclear magnetic spectrum of 2-methylthiobenzoic acid in example 2. FIG. 3 is a 1 H nuclear magnetic spectrum of 4-methylthiobenzoic acid in example 3. FIG. 4 is a 1 H nuclear magnetic spectrum of 3-aminoanisole in example 4. FIG