Method for selective alkylation of substituted thiophenol
By using a combination of quaternary ammonium salts and sodium borohydride, selective alkylation of substituted thiophenols was achieved, solving the problems of expensive reagents, toxicity, and disulfide formation in existing methods. This improved the yield and simplified the operation, making it suitable for industrial production.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- DALIAN UNIV OF TECH
- Filing Date
- 2026-01-29
- Publication Date
- 2026-05-12
AI Technical Summary
Existing alkylation methods for replacing thiophenols use expensive, toxic, and environmentally polluting methylating reagents, which are prone to forming disulfides under high-temperature conditions, leading to reduced synthesis yields.
Quaternary ammonium salts were used as alkylating agents, and sodium borohydride was used as a reducing polymerization inhibitor. Selective alkylation was carried out in the presence of alkali, with the reaction temperature controlled at 100-110℃ and the reaction time at 4-8 h. Solvents such as DMF and DMSO were used, and the products were separated by recrystallization or column chromatography.
This approach improves reaction selectivity and yield, reduces synthesis costs, simplifies operation and post-processing, reduces environmental hazards, and enables the preparation of environmentally friendly substituted phenyl sulfides.
Smart Images
Figure CN122010800A_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of natural compounds and pharmaceutical chemical intermediates and related chemical technologies, and relates to a method for the selective alkylation of thiophenol. Background Technology
[0002] Substituted phenyl sulfides are an important class of intermediates in organic synthesis, playing a vital role in chemical and pharmaceutical fields due to their unique properties. In the chemical industry, substituted phenyl sulfides can serve as raw materials for synthesizing other compounds, such as dyes and fragrances. In the pharmaceutical industry, substituted anisole is frequently used as an intermediate or active ingredient in drug synthesis. Furthermore, substituted anisole can be used to prepare pesticides, coatings, and other products, providing crucial support to the agricultural and construction industries. Therefore, substituted phenyl sulfides have a wide range of applications.
[0003] There are various methods for preparing substituted phenyl sulfides, mainly involving the direct alkylation of substituted thiophenols via mercaptoyl groups. For example, the methylation of thiophenols uses iodomethane, dimethyl sulfate, and methyl metal compounds as methylating agents; however, iodomethane is expensive, dimethyl sulfate is highly toxic, and methyl metal reagents cause significant environmental pollution. Furthermore, substituted thiophenols readily form disulfides under high temperatures, directly reducing the yield of substituted phenyl sulfides. Therefore, developing an environmentally friendly method for preparing substituted phenyl sulfides using inexpensive, low-toxicity reagents is of great importance. Summary of the Invention
[0004] This invention provides a method for preparing substituted phenyl sulfides. This method uses quaternary ammonium salts as alkylating agents and inhibits the formation of disulfides by adding sodium borohydride. It has the advantages of mild reaction conditions, inexpensive and readily available alkylating agents, and high reaction selectivity.
[0005] The technical solution of the present invention: A method for the selective alkylation of substituted thiophenols, using substituted thiophenols as raw materials, sodium borohydride as a reducing polymerization inhibitor, and a quaternary ammonium salt as an alkylating agent, selectively alkylates substituted phenyl sulfides in the presence of an alkali and in a solvent; the synthetic reaction formula is as follows: The reaction temperature is 100~110℃, and the reaction time is 4~8 h; R 1 It can be a hydroxyl, amino, carboxyl, aliphatic hydrocarbon, or aromatic hydrocarbon group; R 2 It is an aliphatic hydrocarbon group such as methyl, ethyl, propyl, or butyl; The quaternary ammonium salts mentioned are tetramethylammonium fluoride, tetramethylammonium chloride, tetramethylammonium bromide, tetraethylammonium chloride, tetrapropylammonium chloride, tetrabutylammonium chloride, tetrabutylammonium bromide, and other tetraalkylammonium halides. The alkali mentioned is an alkali metal alkali such as sodium hydroxide, potassium hydroxide, or lithium hydroxide; The solvent is DMF, DMSO, N One of the following: methylpyrrolidone, 1,3-dimethyl-2-imidazolinone, chlorobenzene, and toluene; The amount of sodium borohydride used is 0.1 to 1.0 equivalents of thiophenol.
[0006] The amount of alkali used is 1.0 to 3.0 equivalents of the thiophenol substitute.
[0007] The amount of the quaternary ammonium salt used is 1.0 to 2.0 equivalents of the thiophenol substitute.
[0008] The molar concentration of the substituted thiophenol in the reaction system is 1~5 mol / L.
[0009] Separation methods include recrystallization and column chromatography. Recrystallization uses water as the solvent; column chromatography can use silica gel or basic alumina as the stationary phase, and the developing solvent is generally a mixture of polar and nonpolar solvents, such as ethyl acetate-petroleum ether, ethyl acetate-n-heptane, n-heptane, or petroleum ether.
[0010] The beneficial effects of this invention are: the method exhibits high product selectivity and is simple to operate and process. The addition of sodium borohydride reduces and inhibits the polymerization of the raw materials, significantly improving the conversion rate and yield of the reaction, reducing synthesis costs, and making its industrialization possible. Simultaneously, it avoids the use of highly reactive and toxic methylating agents, reducing environmental harm. Attached Figure Description
[0011] Figure 1 It is the 3-methylthiobenzoic acid in Example 1 1 H NMR spectrum.
[0012] Figure 2 It is 2-methylthiobenzoic acid in Example 2 1 H NMR spectrum.
[0013] Figure 3 It is the 4-methylthiobenzoic acid in Example 3 1 H NMR spectrum.
[0014] Figure 4 It is the 3-aminoanisidine in Example 4. 1 H NMR spectrum.
[0015] Figure 5It is the 4-aminoanisidine in Example 5. 1 H NMR spectrum.
[0016] Figure 6 It is 3-methylthiophenol in Example 6 1 H NMR spectrum.
[0017] Figure 7 It is 3-ethylthiobenzoic acid in Example 7. 1 H NMR spectrum.
[0018] Figure 8 It is 3-propanethiobenzoic acid in Example 8. 1 H NMR spectrum.
[0019] Figure 9 It is 3-butyrobenzoic acid in Example 9. 1 H NMR spectrum. Detailed Implementation
[0020] The specific embodiments of the present invention will be further described below with reference to the accompanying drawings and technical solutions.
[0021] The method for preparing substituted phenyl sulfides described in this invention achieves selectivity and reaction yield of up to 100% and 95%, respectively, and is simple to operate and process, providing favorable conditions for its industrial production.
[0022] The present invention will be further described below with reference to specific embodiments. Any simple substitutions or modifications made to the present invention by those skilled in the art are within the scope of the technical solutions protected by the present invention.
[0023] Example 1: 3-Methylthiobenzoic acid 12 Add 3-mercaptobenzoic acid (1.0 g, 6.49 mmol, 1.0 eq.), KOH (0.76 g, 13.6 mmol, 2.1 eq.), and DMF (3.0 mL) to a 100 mL four-necked flask. Heat the reaction solution to 70-75 °C. The reaction solution gradually becomes clear. Tetramethylammonium chloride (0.85 g, 7.78 mmol, 1.2 eq.) was added to the reaction solution, and the mixture was stirred for 30 min. The temperature was slowly increased to 100-110 °C. Sodium borohydride (98 mg, 2.59 mmol, 0.4 eq.) was added to the reaction solution in portions. Gas was generated during the addition process. After the addition was completed, the mixture was kept warm and stirred for 1.0 h. Three drops of the reaction solution were added dropwise to 1 mL of 5% hydrochloric acid. The reaction was detected by HPLC. After the reaction was complete, the reaction solution was cooled to 10-15 °C. 10 mL of saturated saline solution was added to the reaction solution to quench the reaction. The reaction solution gradually became clear. Concentrated hydrochloric acid was then added dropwise to the reaction solution until the pH = 1. During the dropwise addition, a large amount of solid precipitated out. The mixture was cooled to 0 °C, stirred for 1 h, filtered, and dried to obtain a white solid 3-methylthiobenzoic acid (1.01 g, 93%). 1 H NMR (400 MHz, DMSO- d 6): δ 13.08 (bs, 1H), 7.76 (s, 1H), 7.71 (d, J = 7.6 Hz, 1H), 7.52 (d, J = 6.8 Hz, 1H), 7.44 (dd, J = 8.0, 8.0 Hz, 1H), 2.52 (s, 3H). Example 2: Synthesis of 2-methylthiobenzoic acid Add 2-mercaptobenzoic acid (1.0 g, 6.49 mmol, 1.0 eq.), KOH (0.76 g, 13.6 mmol, 2.1 eq.), and DMF (3.0 mL) to a 100 mL four-necked flask. Heat the reaction solution to 70-75 °C. The reaction solution gradually becomes clear. Tetramethylammonium chloride (0.85 g, 7.78 mmol, 1.2 eq.) was added to the reaction solution, and the mixture was stirred for 30 min. The temperature was slowly increased to 100-110 °C. Sodium borohydride (98 mg, 2.59 mmol, 0.4 eq.) was added to the reaction solution in portions. Gas was generated during the addition process. After the addition was complete, the mixture was kept at this temperature and stirred for 1.0 h. Three drops of the reaction solution were added dropwise to 1 mL of 5% hydrochloric acid, and the reaction was detected by HPLC. After the reaction was complete, the reaction solution was cooled to 10-15 °C. 10 mL of saturated saline solution was added to the reaction solution to quench the reaction. The reaction solution gradually became clear. Concentrated hydrochloric acid was then added dropwise to the reaction solution until the pH = 1. During the addition, a large amount of solid precipitated out. The mixture was cooled to 0 °C, stirred for 1 h, filtered, and dried to obtain 2-methylthiobenzoic acid (1.03 g, 95%), a white solid. 1 H NMR (400 MHz, DMSO- d 6): δ 12.98 (bs, 1H), 7.92 (d, J = 1.6 Hz, 1H), 7.90-7.53 (m, 1H), 7.36 (d, J = 8.0 Hz, 1H), 7.23-7.19 (m, 1H), 2.40 (s, 3H). Example 3: Synthesis of 4-methylthiobenzoic acid Add 4-mercaptobenzoic acid (1.0 g, 6.49 mmol, 1.0 eq.), KOH (0.76 g, 13.6 mmol, 2.1 eq.), and DMF (3.0 mL) to a 100 mL four-necked flask. Heat the reaction solution to 70-75 °C. The reaction solution gradually becomes clear. Tetramethylammonium chloride (0.85 g, 7.78 mmol, 1.2 eq.) was added to the reaction solution, and the mixture was stirred for 30 min. The temperature was slowly increased to 100-110 °C, and sodium borohydride (98 mg, 2.59 mmol, 0.4 eq.) was added in portions. Gas was generated during the addition process. After the addition was complete, the mixture was kept at this temperature and stirred for 1.0 h. Three drops of the reaction solution were added dropwise to 1 mL of 5% hydrochloric acid, and the reaction was detected by HPLC. After the reaction was complete, the reaction solution was cooled to 10-15 °C, and 10 mL of saturated saline solution was added dropwise to quench the reaction solution. The reaction solution gradually became clear. Concentrated hydrochloric acid was then added dropwise to the reaction solution until the pH = 1. During the addition process, a large amount of solid precipitated out. The mixture was cooled to 0 °C, stirred for 1 h, filtered, and dried to obtain 4-methylthiobenzoic acid (1.02 g, 94%). 1 H NMR (400 MHz, DMSO- d 6): δ 12.84 (bs, 1H), 7.86 (d, J = 8.4 Hz, 2H), 7.34 (d, J = 8.4 Hz, 2H,), 2.52 (s, 3H). Example 4: Synthesis of 3-aminoanisidine Add 3-aminothiophenol (1.0 g, 7.99 mmol, 1.0 eq.), KOH (0.49 g, 8.79 mmol, 1.1 eq.), and DMF (3.0 mL) to a 100 mL four-necked flask. Heat the reaction solution to 70-75 °C. The reaction solution gradually becomes clear. Tetramethylammonium chloride (1.05 g, 9.59 mmol, 1.2 eq.) was added to the reaction solution, and the mixture was stirred for 30 min. The temperature was slowly increased to 100-110 °C. Sodium borohydride (120.8 mg, 3.20 mmol, 0.4 eq.) was added to the reaction solution in portions. Gas was generated during the addition process. After the addition was completed, the mixture was kept at this temperature and stirred for 4.0 h. Three drops of the reaction solution were added dropwise to 5% hydrochloric acid and detected by HPLC. After the reaction was complete, the reaction solution was cooled to 10-15 °C. 2 mL of 5% hydrochloric acid was added dropwise to quench the reaction solution, and the pH was adjusted to 10. The reaction solution gradually became clear. 5.0 mL of dichloromethane was added to extract the reaction solution twice, and the solution was washed once with saturated brine. The organic phase was dried, and column chromatography (ethyl acetate / petroleum ether 1:10) was performed to obtain 3-aminoanisidine sulfide (0.98 g, 88%). 1 H NMR (300 MHz, CDCl3): δ 7.10 (dd, J = 7.6, 7.6 Hz, 1H), 6.68 (d, J = 7.6 Hz 1H), 6.60 (s, 1H), 6.47 (dd, J = 8.0, 1.6 Hz, 1H), 3.49 (brs, 2H), 2.48 (s, 3H).
[0024] Example 5: Synthesis of 4-aminoanisidine Add 4-aminothiophenol (1.0 g, 7.99 mmol, 1.0 eq.), KOH (0.49 g, 8.79 mmol, 1.1 eq.), and DMF (3.0 mL) to a 100 mL four-necked flask. Heat the reaction solution to 70-75 °C. The reaction solution gradually becomes clear. Tetramethylammonium chloride (1.05 g, 9.59 mmol, 1.2 eq.) was added to the reaction solution, and the mixture was stirred for 30 min. The temperature was slowly increased to 100-110 °C. Sodium borohydride (120.8 mg, 3.20 mmol, 0.4 eq.) was added to the reaction solution in portions. Gas was generated during the addition process. After the addition was completed, the mixture was kept at this temperature and stirred for 4.0 h. Three drops of the reaction solution were added dropwise to 5% hydrochloric acid and detected by HPLC. After the reaction was complete, the reaction solution was cooled to 10-15 °C. 2 mL of 5% hydrochloric acid was added dropwise to quench the reaction solution, and the pH was adjusted to 10. The reaction solution gradually became clear. 5.0 mL of dichloromethane was added to extract the reaction solution twice, and the solution was washed once with saturated brine. The organic phase was dried, and column chromatography (ethyl acetate / petroleum ether 1:10) was performed to obtain 4-aminoanisidine sulfide (0.96 g, 86%). 1 H (400 MHz, CDCl3): δ7.20(d, J = 8.4 Hz, 2 H), 6.65 (d, J = 8.4 Hz, 2H), 3.54 (s, 2H), 2.44 (s, 3H).
[0025] Example 6: Synthesis of 3-Methylthiophenol Add 3-hydroxyphenol (1.0 g, 7.92 mmol, 1.0 eq.), KOH (0.49 g, 8.71 mmol, 1.1 eq.), and DMF (3.0 mL) to a 100 mL four-necked flask. Heat the reaction solution to 70-75 °C. The reaction solution gradually becomes clear. Tetramethylammonium chloride (1.04 g, 7.51 mmol, 1.2 eq.) was added to the reaction solution, and the mixture was stirred for 30 min. The temperature was slowly increased to 100-110 °C. Sodium borohydride (120.8 mg, 3.20 mmol, 0.4 eq.) was added to the reaction solution in portions. Gas was generated during the addition process. After the addition was completed, the mixture was kept at this temperature and stirred for 4.0 h. Three drops of the reaction solution were added dropwise to 5% hydrochloric acid and detected by HPLC. After the reaction was complete, the reaction solution was cooled to 10-15 °C. 4 mL of 5% hydrochloric acid was added dropwise to quench the reaction solution, and the pH was adjusted to 4. The reaction solution gradually became clear. 5.0 mL of dichloromethane was added to extract the reaction solution twice, and the solution was washed once with saturated brine. The organic phase was dried, and column chromatography (ethyl acetate / petroleum ether 1:15) was performed to obtain 3-methylthiophenol (0.99 g, 89%). 1 H NMR (400 MHz, DMSO- d 6): δ 9.51 (s, 1H), 7.10 (dd, J = 8.0, 8.0 Hz, 1 H,), 6.68-6.64 (m, 2H), 6.56-6.53 (m,1H), 2.42 (s, 3H). Example 7: Synthesis of 3-Ethylthiobenzoic acid Add 3-mercaptobenzoic acid (1.0 g, 6.49 mmol, 1.0 eq.), KOH (0.76 g, 13.6 mmol, 2.1 eq.), and DMF (3.0 mL) to a 100 mL four-necked flask. Heat the reaction solution to 70-75 °C. The reaction solution gradually becomes clear. Tetraethylammonium chloride (1.29 g, 7.78 mmol, 1.2 eq.) was added to the reaction solution, and the mixture was stirred for 30 min. The temperature was slowly increased to 100-110 °C, and sodium borohydride (98 mg, 2.59 mmol, 0.4 eq.) was added in batches. Gas was generated during the addition process. After the addition was completed, the mixture was kept warm and stirred for 1.0 h. Three drops of the reaction solution were added dropwise to 1 mL of 5% hydrochloric acid, and the reaction was detected by HPLC. After the reaction was complete, the reaction solution was cooled to 10-15 °C, and 10 mL of saturated saline solution was added to quench the reaction solution. The reaction solution gradually became clear. Concentrated hydrochloric acid was then added dropwise to the reaction solution until the pH = 1. During the dropwise addition, a large amount of solid precipitated out. The mixture was cooled to 0 °C, stirred for 1 h, filtered, and dried to obtain 3-ethylthiobenzoic acid (1.06 g, 90%). 1 H NMR (400 MHz, DMSO- d 6) δ 11.90 (bs, 1H), 8.07 (d, J = 1.6 Hz, 1H), 7.93 (d, J = 7.6 Hz, 1H), 7.57 (d, J = 8.4 Hz, 1H), 7.41(dd, J = 8.0, 8.0 Hz, 1H), 3.04 (q, J = 7.2 Hz, 2H), 1.37 (t, J = 7.2 Hz, 3H). Example 8: Synthesis of 3-propylthiobenzoic acid Add 3-mercaptobenzoic acid (1.0 g, 6.49 mmol, 1.0 eq.), KOH (0.76 g, 13.6 mmol, 2.1 eq.), and DMF (3.0 mL) to a 100 mL four-necked flask. Heat the reaction solution to 70-75 °C. The reaction solution gradually becomes clear. Tetrapropylammonium chloride (1.73 g, 7.78 mmol, 1.2 eq.) was added to the reaction solution, and the mixture was stirred for 30 min. The temperature was slowly increased to 100-110 °C, and sodium borohydride (98 mg, 2.59 mmol, 0.4 eq.) was added in batches. Gas was generated during the addition process. After the addition was completed, the mixture was kept at this temperature and stirred for 1.0 h. Three drops of the reaction solution were added dropwise to 1 mL of 5% hydrochloric acid, and the reaction was detected by HPLC. After the reaction was complete, the reaction solution was cooled to 10-15 °C, and 10 mL of saturated saline solution was added to quench the reaction solution. The reaction solution gradually became clear. Concentrated hydrochloric acid was then added dropwise to the reaction solution until the pH = 1. During the addition process, a large amount of solid precipitated out. The mixture was cooled to 0 °C, stirred for 1 h, filtered, and dried to obtain 3-propylthiobenzoic acid (1.21 g, 95%). 1 H NMR (400 MHz, DMSO- d 6) : δ 13.10 (bs, 1H), 7.81 (d, J = 1.6 Hz, 1H), 7.73 (d, J = 7.6 Hz, 1H), 7.55 (d, J = 8.4 Hz, 1H), 7.44 (dd, J = 8.0, 8.0 Hz, 1H), 2.98 (t, J = 7.2 Hz, 2H), 1.60 (q, J = 7.6 Hz, 2H), 0.98 (t, J = 7.2 Hz, 3H).
[0026] Example 9: Synthesis of 3-Butylthiobenzoic acid Add 3-mercaptobenzoic acid (1.0 g, 6.49 mmol, 1.0 eq.), KOH (0.76 g, 13.6 mmol, 2.1 eq.), and DMF (3.0 mL) to a 100 mL four-necked flask. Heat the reaction solution to 70-75 °C. The reaction solution gradually becomes clear. Tetrabutylammonium chloride (2.16 g, 7.78 mmol, 1.2 eq.) was added to the reaction solution, and the mixture was stirred for 30 min. The temperature was slowly increased to 100-110 °C, and sodium borohydride (98 mg, 2.59 mmol, 0.4 eq.) was added in batches. Gas was generated during the addition process. After the addition was completed, the mixture was kept at this temperature and stirred for 1.0 h. Three drops of the reaction solution were added dropwise to 1 mL of 5% hydrochloric acid, and the reaction was detected by HPLC. After the reaction was complete, the temperature of the reaction solution was lowered to 10-15 °C, and 10 mL of saturated saline solution was added dropwise to quench the reaction solution. The reaction solution gradually became clear. Concentrated hydrochloric acid was then added dropwise to the reaction solution until the pH = 1. During the addition process, a large amount of solid precipitated out. The temperature was lowered to 0 °C, and the mixture was stirred for 1 h. The mixture was filtered and dried to obtain 3-butylthiobenzoic acid (1.27 g, 93%). 1 H NMR (400 MHz, DMSO- d 6): δ 8.07 (dd, J =1.6, 1.6 Hz, 1H),7.93-7.91 (m, 1H), 7.58-7.55 (m, 1H), 7.41 (dd, J = 8.0, 8.0Hz, 1H), 3.01 (t, J = 7.2 Hz, 2H), 1.73-1.65 (m, 2H), 1.50 (q, J = 7.2 Hz, 2H), 0.97 (t, J = 7.6 Hz, 3H). Example 10: 3-Methylthiobenzoic acid Add 3-mercaptobenzoic acid (1.0 g, 6.49 mmol, 1.0 eq.), KOH (0.76 g, 13.6 mmol, 2.1 eq.), and DMF (3.0 mL) to a 100 mL four-necked flask. Heat the reaction solution to 70-75 °C, and the solution gradually becomes clear. Add tetramethylammonium chloride (0.85 g, 7.78 mmol, 1.2 eq.) to the reaction solution, stir for 30 min, and slowly heat to 100-110 °C. Gas is generated during the addition process. After the addition is complete, maintain the temperature and stir for 1.0 h. Take 3 drops of the reaction solution and add them dropwise to 1 mL of 5% hydrochloric acid. HPLC analysis shows that the reaction is complete, producing 20% 3-methylthiobenzoic acid and 80% disulfide. In this comparative example, since the reducing inhibitor sodium borohydride was not added, it was observed that most of the product was a disulfide, with only a small amount of the target product formed. Furthermore, the two were difficult to separate, making it challenging to obtain a high-purity product. Related literature reports also corroborate that disulfides are formed under these conditions.
[0027] Example 11: Synthesis of 3-methylthiobenzoic acid In a 100 mL four-necked flask, 3-mercaptobenzoic acid (1.0 g, 6.49 mmol, 1.0 eq.), potassium carbonate (4.5 g, 32.5 mmol, 5.0 eq.), and DMF (15.0 mL) were added. The mixture was incubated at 0–5 °C. Iodimethane (2.76 g, 19.5 mmol, 3.0 eq.) was added dropwise. The mixture was stirred for 1.0 h. After the reaction was complete, 30 mL of ethyl acetate and 60 mL of water were added to the reaction mixture. The mixture was stirred for 30 min, and the layers were separated. The organic phase was washed twice with 60 mL of water and concentrated to dryness to obtain the intermediate. The intermediate was added to 10 mL of 1 N sodium hydroxide solution, followed by 10 mL of methanol and 10 mL of tetrahydrofuran. The mixture was stirred at 70 °C for 1.0 h. After the reaction was complete, the methanol and tetrahydrofuran were concentrated under reduced pressure to dryness. Concentrated hydrochloric acid was added to the reaction solution to bring the pH to 1. The temperature was lowered to 0-5 °C, and the mixture was stirred for 1.0 h. The mixture was filtered and dried to obtain a white solid, 3-methylthiobenzoic acid (1.01 g, 93%). This comparative example represents the mainstream synthetic route for 3-methylthiobenzoic acid reported in the literature. Methylation with iodomethane would lead to carboxylation, requiring hydrolysis to obtain the target product. Furthermore, the process is cumbersome, requires a large amount of organic solvent, and iodomethane is expensive.
[0028] In summary, when quaternary ammonium salts are used as methylating agents, the reaction system exhibits high chemoselectivity, selectively alkylating thiophenols to obtain the corresponding alkylated products, while other substituents, such as hydroxyl, amino, and carboxyl groups, are retained. The addition of sodium borohydride inhibits the formation of disulfides, resulting in almost no byproducts. Mainstream synthetic routes, however, often suffer from poor selectivity. Therefore, this invention has broad application prospects.
Claims
1. A method for the selective alkylation of substituted thiophenol, characterized in that, Using substituted thiophenol as a raw material, sodium borohydride as a reducing polymerization inhibitor, and quaternary ammonium salt as an alkylating agent, substituted phenyl sulfides were prepared by selective alkylation in the presence of an alkali and in a solvent; the synthetic reaction formula is as follows: ； The reaction temperature is 100~110℃, and the reaction time is 4~8 h; R 1 It can be a hydroxyl, amino, carboxyl, aliphatic hydrocarbon, or aromatic hydrocarbon group; R 2 It can be an aliphatic hydrocarbon group such as methyl, ethyl, propyl or butyl.
2. The method for selective alkylation of substituted thiophenol according to claim 1, characterized in that, The quaternary ammonium salt is tetramethylammonium fluoride, tetramethylammonium chloride, tetramethylammonium bromide, tetraethylammonium chloride, tetrapropylammonium chloride, tetrabutylammonium chloride, or tetrabutylammonium bromide.
3. The method for selective alkylation of substituted thiophenol according to claim 1, characterized in that, The alkali mentioned is sodium hydroxide, potassium hydroxide, or lithium hydroxide.
4. The method for selective alkylation of substituted thiophenol according to claim 1, characterized in that, The solvent is DMF, DMSO, N One of the following: 1,3-methylpyrrolidone, 1,3-dimethyl-2-imidazolinone, chlorobenzene, and toluene.
5. The method for selective alkylation of substituted thiophenol according to claim 1, characterized in that, The amount of sodium borohydride used is 0.1 to 1.0 equivalents of thiophenol.
6. The method for selective alkylation of substituted thiophenol according to claim 1, characterized in that, The amount of alkali used is 1.0 to 3.0 equivalents of the thiophenol substitute.
7. The method for selective alkylation of substituted thiophenol according to claim 1, characterized in that, The amount of the quaternary ammonium salt used is 1.0 to 2.0 equivalents of the thiophenol substitute.
8. The method for selective alkylation of substituted thiophenol according to claim 1, characterized in that, The molar concentration of the substituted thiophenol in the reaction system is 1~5 mol / L.