Synthesis method of 4-mercaptoethyl pyridine compound
By reacting 4-vinylpyridine with potassium sulfide under acidic conditions, combined with an acidic catalyst and optimized process, the problems of low yield and safety hazards in existing technologies have been solved, realizing the efficient and environmentally friendly synthesis of 4-mercaptoethylpyridine, which is suitable for industrial applications.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- DALIAN INSTITUTE OF CHEMICAL PHYSICS CHINESE ACADEMY OF SCIENCES
- Filing Date
- 2024-11-11
- Publication Date
- 2026-05-12
AI Technical Summary
Existing methods for synthesizing 4-mercaptoethylpyridine suffer from low yields, the use of hydrogen sulfide gas, and high costs, making them unsuitable for industrial applications.
4-Vinylpyridine was reacted with potassium sulfide under acidic conditions, with the addition of acidic catalysts such as p-toluenesulfonic acid and benzoic acid. The reaction temperature was controlled at 50℃-180℃, and the reaction time was 1-24 hours. Post-treatment included pH adjustment and distillation to optimize the reaction conditions and improve the yield.
It significantly improves the yield of 4-mercaptoethylpyridine, reduces reaction costs, is suitable for industrial production, and is environmentally friendly, non-toxic, and harmless.
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Figure CN122010823A_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of organic synthesis, specifically relating to a method for synthesizing a 4-mercaptoethylpyridine compound. Background Technology
[0002] 4-Mercaptoethylpyridine is a high-value-added chemical product that can be used to synthesize bisphenol A and many other fine organic chemical intermediates. It has wide applications in polymer materials, surfactants, pharmaceuticals, pesticides and other fields.
[0003] There are currently two main routes for the production of 4-mercaptoethylpyridine: The first route involves reacting 4-vinylpyridine with thiourea under acidic conditions, followed by neutralization with alkali to obtain the target product, 4-mercaptoethylpyridine.
[0004] [CN1206220C], this route achieves a yield of up to 80%. The second route involves the reaction of 4-vinylpyridine and hydrogen sulfide under alkaline catalysis to produce 4-mercaptoethylpyridine [CN1283627C]. This route achieves a yield of up to 95%. Although the yield is good, hydrogen sulfide gas has an unpleasant odor, and a pressure vessel is required during the reaction, increasing safety risks and indirectly raising the cost. To enrich the synthetic methods of 4-mercaptoethylpyridine, we present a method for synthesizing 4-mercaptoethylpyridine compounds under acidic conditions, which can significantly improve the yield of 4-mercaptoethylpyridine, increase production efficiency, and is environmentally friendly. Summary of the Invention
[0005] The purpose of this invention is to provide a method for synthesizing 4-mercaptoethylpyridine compounds. This method is simple to operate, uses readily available raw materials, and has high reactivity, which greatly improves production efficiency, reduces reaction costs, and has high industrial application value.
[0006] This invention provides a method for synthesizing 4-mercaptoethylpyridine, the specific steps of which are as follows: 4-vinylpyridine, potassium sulfide and reaction solvent are added to a reaction flask in a certain proportion, then acid is added, the temperature is raised to 50℃-180℃, the reaction is carried out for 1-24 hours, after cooling, the mixture is filtered, the pH of the filtrate is adjusted with alkaline water, the aqueous layer is removed, the solvent is removed from the organic layer under reduced pressure, and the product 4-mercaptoethylpyridine is obtained by further distillation under reduced pressure.
[0007]
[0008] The acid is selected from one or more of p-toluenesulfonic acid, benzenesulfonic acid, benzoic acid, acetic acid, oxalic acid, hydrochloric acid, sulfuric acid, and nitric acid, with benzoic acid and hydrochloric acid being preferred.
[0009] The reaction solvent is selected from at least one of water, toluene, benzene, methanol, ethanol, isopropanol, butanol, dichloromethane, dichloroethane, carbon tetrachloride, ethyl acetate, diethyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, dimethyl sulfoxide, or N,N-dimethylformamide. Alcohols are preferred, and methanol is more preferred.
[0010] The molar ratio of 4-vinylpyridine to potassium sulfide is 1-20:1, preferably 1-10:1, and more preferably 1-5:1;
[0011] The molar ratio of 4-vinylpyridine to acid is 1:1-10, preferably 1:1-8, and more preferably 1:1-5;
[0012] The reaction conditions are as follows:
[0013] The reaction temperature is 25℃-180℃, preferably 50℃-120℃, and more preferably 50℃-100℃;
[0014] The reaction time is 1-24 hours, preferably 5-15 hours, and more preferably 5-12 hours.
[0015] This reaction method uses inexpensive and readily available starting materials, yields high purity, is highly efficient, and is simple, making it highly valuable for industrial applications.
[0016] The present invention has the following advantages:
[0017] 1. Starting materials are readily available and inexpensive.
[0018] 2. The reaction conditions are mild, resulting in high yield and high efficiency.
[0019] 3. This method greatly reduces reaction costs, is environmentally friendly and green, and the entire process is suitable for industrial production. Attached Figure Description
[0020] Figure 1 The 1H NMR spectrum of 4-mercaptoethylpyridine prepared in Example 1;
[0021] Figure 2 The carbon NMR spectrum of 4-mercaptoethylpyridine prepared in Example 1. Detailed Implementation
[0022] The following examples will further illustrate the present invention, but are not intended to limit the invention. Nuclear magnetic resonance (NMR) measurements were performed using a Bruker 400 NMR spectrometer, and gas chromatography was performed using an Agilent 7820A.
[0023] Example 1
[0024] 10.5 g (0.1 mol) of 4-vinylpyridine, 11.26 g (0.1 mol) of potassium sulfide, and 100 mL of dichloromethane were added to a reaction flask, followed by 17.2 g (0.1 mol) of p-toluenesulfonic acid. The mixture was heated to 50 °C and reacted for 5 hours. After cooling to room temperature, the solid residue was removed by filtration. The pH of the filtrate was adjusted to 9-10 with 2 mol / L NaOH aqueous solution. The mixture was then separated, and the aqueous layer was extracted again with 20 mL x 3 dichloromethane. The dichloromethane layers were combined, and the dichloromethane was removed by distillation under reduced pressure. The fraction with a boiling range of 70-80 °C was collected and analyzed by NMR to be the product 4-mercaptoethylpyridine, weighing 8.35 g (0.06 mol), with a yield of 60%.
[0025] 1 H NMR (400MHz, CDCl3) δ8.54(dd,J=4.5,1.5Hz,2H),7.19–7.12(m,1H),2.93(t,J=7.2Hz,2H),2.85–2.76(m,2H),1.40(t,J=7.9Hz,1H).
[0026] 13 C NMR (101MHz, CDCl3) δ149.9,148.5,124.0,39.2,24.8.
[0027] Example 2
[0028] 10.5 g (0.1 mol) of 4-vinylpyridine, 11.26 g (0.1 mol) of potassium sulfide, and 100 mL of methanol were added to a reaction flask, followed by 17.2 g (0.1 mol) of p-toluenesulfonic acid. The mixture was heated to 60 °C and reacted for 10 hours. After cooling to room temperature, the solid residue was removed by filtration. The pH of the filtrate was adjusted to 9-10 with 2 mol / L NaOH aqueous solution, and methanol was removed by rotary evaporation. The aqueous layer was then extracted with 30 mL of dichloromethane three times. The dichloromethane layers were combined, and the dichloromethane was removed by evaporation. The residue was collected by vacuum distillation, and the fraction with a boiling range of 70-80 °C was collected. NMR analysis showed that the product was 4-mercaptoethylpyridine, weighing 11.83 g (0.085 mol), with a yield of 85%.
[0029] Example 3
[0030] 10.5 g (0.1 mol) of 4-vinylpyridine, 11.26 g (0.1 mol) of potassium sulfide, and 100 mL of ethanol were added to a reaction flask, followed by 17.2 g (0.1 mol) of p-toluenesulfonic acid. The mixture was heated to 70 °C and reacted for 10 hours. After cooling to room temperature, the solid residue was removed by filtration. The pH of the filtrate was adjusted to 9-10 with 2 mol / L NaOH aqueous solution, and the ethanol was removed by rotary evaporation. The aqueous layer was then extracted with 30 mL of dichloromethane three times. The dichloromethane layers were combined, and the dichloromethane was removed by evaporation. The residue was collected by vacuum distillation, and the fraction with a boiling range of 70-80 °C was collected. NMR analysis showed that the product was 4-mercaptoethylpyridine, weighing 11.55 g (0.083 mol), with a yield of 83%.
[0031] Example 4
[0032] 10.5 g (0.1 mol) of 4-vinylpyridine, 11.26 g (0.1 mol) of potassium sulfide, and 100 mL of methanol were added to a reaction flask, followed by 12.2 g (0.1 mol) of benzoic acid. The mixture was heated to 60 °C and reacted for 10 hours. After cooling to room temperature, the solid residue was removed by filtration. The pH of the filtrate was adjusted to 9-10 with 2 mol / L NaOH aqueous solution, and methanol was removed by rotary evaporation. The aqueous layer was then extracted with 30 mL of dichloromethane three times. The dichloromethane layers were combined, and the dichloromethane was removed by evaporation. The residue was collected by vacuum distillation, and the fraction with a boiling range of 70-80 °C was collected. NMR analysis showed that the product was 4-mercaptoethylpyridine, weighing 12.39 g (0.089 mol), with a yield of 89%.
[0033] Example 5
[0034] 10.5 g (0.1 mol) of 4-vinylpyridine, 22.52 g (0.2 mol) of potassium sulfide, and 100 mL of methanol were added to a reaction flask, followed by 12.2 g (0.1 mol) of benzoic acid. The mixture was heated to 60 °C and reacted for 10 hours. After cooling to room temperature, the solid residue was removed by filtration. The pH of the filtrate was adjusted to 9-10 with 2 mol / L NaOH aqueous solution, and methanol was removed by rotary evaporation. The aqueous layer was then extracted with 30 mL of dichloromethane three times. The dichloromethane layers were combined, and the dichloromethane was removed by evaporation. The residue was collected by vacuum distillation, and the fraction with a boiling range of 70-80 °C was collected. NMR analysis showed that the product was 4-mercaptoethylpyridine, weighing 12.67 g (0.091 mol), with a yield of 91%.
[0035] Example 6
[0036] 10.5 g (0.1 mol) of 4-vinylpyridine, 22.52 g (0.2 mol) of potassium sulfide, and 100 mL of methanol were added to a reaction flask, followed by 18.3 g (0.15 mol) of benzoic acid. The mixture was heated to 60 °C and reacted for 10 hours. After cooling to room temperature, the solid residue was removed by filtration. The pH of the filtrate was adjusted to 9-10 with 2 mol / L NaOH aqueous solution, and methanol was removed by rotary evaporation. The aqueous layer was then extracted with 30 mL of dichloromethane three times. The dichloromethane layers were combined, and the dichloromethane was removed by evaporation. The residue was collected by vacuum distillation, and the fraction with a boiling range of 70-80 °C was collected. NMR analysis showed that the product was 4-mercaptoethylpyridine, weighing 12.81 g (0.092 mol), with a yield of 92%.
[0037] Example 7
[0038] 10.5 g (0.1 mol) of 4-vinylpyridine, 22.52 g (0.2 mol) of potassium sulfide, and 100 mL of methanol were added to a reaction flask, followed by 5.5 g (0.15 mol) of hydrochloric acid. The mixture was heated to 60 °C and reacted for 10 hours. After cooling to room temperature, the solid residue was removed by filtration. The pH of the filtrate was adjusted to 9-10 with 2 mol / L NaOH aqueous solution, and methanol was removed by rotary evaporation. The aqueous layer was then extracted with 30 mL of dichloromethane three times. The dichloromethane layers were combined, and the dichloromethane was removed by evaporation. The residue was collected by vacuum distillation, and the fraction with a boiling range of 70-80 °C was collected. NMR analysis showed that the product was 4-mercaptoethylpyridine, weighing 12.81 g (0.092 mol), with a yield of 92%.
[0039] Example 8
[0040] 10.5 g (0.1 mol) of 4-vinylpyridine, 22.52 g (0.2 mol) of potassium sulfide, and 100 mL of toluene were added to a reaction flask. Then, 5.5 g (0.15 mol) of hydrochloric acid was added, and the mixture was heated to 110 °C and reacted for 12 hours. After cooling to room temperature, the solid residue was removed by filtration. The pH of the filtrate was adjusted to 9-10 with 2 mol / L NaOH aqueous solution. The mixture was then separated, and the aqueous layer was extracted with 30 mL of toluene three times. The organic layers were combined, and the toluene was removed by distillation. The fraction with a boiling range of 70-80 °C was collected by vacuum distillation. The fraction was identified as 4-mercaptoethylpyridine by NMR analysis. The product weighed 10.0 g (0.072 mol), with a yield of 72%.
[0041] Example 9
[0042] 10.5 g (0.1 mol) of 4-vinylpyridine, 22.52 g (0.2 mol) of potassium sulfide, and 200 mL of methanol were added to a reaction flask, followed by 5.5 g (0.15 mol) of hydrochloric acid. The mixture was heated to 60 °C and reacted for 12 hours. After cooling to room temperature, the solid residue was removed by filtration. The pH of the filtrate was adjusted to 9-10 with 2 mol / L NaOH aqueous solution, and methanol was removed by rotary evaporation. The aqueous layer was then extracted with 30 mL of dichloromethane three times. The dichloromethane layers were combined, and the dichloromethane was removed by evaporation. The residue was collected by vacuum distillation, and the fraction with a boiling range of 70-80 °C was collected. NMR analysis showed that the product was 4-mercaptoethylpyridine, weighing 12.67 g (0.091 mol), with a yield of 91%.
[0043] Comparative Example
[0044] 10.5 g (0.1 mol) of 4-vinylpyridine, 15.61 g (0.2 mol) of sodium sulfide, and 200 mL of methanol were added to a reaction flask, followed by 5.5 g (0.15 mol) of hydrochloric acid. The mixture was heated to 60 °C and reacted for 12 hours. After cooling to room temperature, the solid residue was removed by filtration. The pH of the filtrate was adjusted to 9-10 with 2 mol / L NaOH aqueous solution, and methanol was removed by rotary evaporation. The aqueous layer was then extracted with 30 mL of dichloromethane. The dichloromethane layers were combined, and the dichloromethane was removed by evaporation. The residue was collected by vacuum distillation, and the fraction with a boiling range of 70-80 °C was collected. NMR analysis confirmed that the product was 4-mercaptoethylpyridine, weighing 7.24 g (0.052 mol), with a yield of 52%. The above-described embodiments are merely examples illustrating the implementation of the present invention and should not be construed as limiting the scope of the present invention. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these modifications and improvements are all within the scope of protection of the present invention.
Claims
1. A method for synthesizing 4-mercaptoethylpyridine, characterized in that: Using 4-vinylpyridine and potassium sulfide as raw materials, a reaction is carried out under acidic conditions. After the reaction is completed, the pH value is adjusted with alkali (adjusted to pH 7-14, preferably 8-12, more preferably 9-10), and then distilled to obtain the compound 4-mercaptoethylpyridine.
2. The synthesis method according to claim 1, characterized in that: The 4-mercaptoethylpyridine compound has the following structure:
3. The synthesis method according to claim 1 or 2, characterized in that, The reaction equation is shown below:
4. The synthesis method according to claim 1, characterized in that: The reaction is carried out in a solvent, which is selected from at least one or more of the following: water, toluene, benzene, methanol, ethanol, isopropanol, butanol, dichloromethane, dichloroethane, carbon tetrachloride, ethyl acetate, diethyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, dimethyl sulfoxide, or N,N-dimethylformamide. Preferably, it is one or more of the above-mentioned alcohol compounds, and more preferably methanol.
5. The synthesis method according to claim 1, characterized in that: The acid is selected from one or more of p-toluenesulfonic acid, benzenesulfonic acid, benzoic acid, acetic acid, oxalic acid, hydrochloric acid, sulfuric acid, and nitric acid, preferably one or two of benzoic acid and hydrochloric acid.
6. The synthesis method according to claim 1, 4, or 5, characterized in that: The molar ratio of 4-vinylpyridine to potassium sulfide is 1:1-20, preferably 1:1-10, and more preferably 1:1-5; The molar ratio of 4-vinylpyridine to acid is 1:1-10, preferably 1:1-8, and more preferably 1:1-5; The amount of the reaction solvent used is 1-50 mL per millimole of 4-vinylpyridine, preferably 1-10 mL.
7. The synthesis method according to claim 1, characterized in that: The reaction temperature is 25℃-180℃, preferably 50℃-120℃, and more preferably 50℃-100℃; The reaction time is 1-24 hours, preferably 5-15 hours, and more preferably 5-12 hours.
8. The synthesis method according to any one of claims 1-7, characterized in that: The method is as follows: 4-Vinylpyridine, potassium sulfide, and reaction solvent are added to a reaction flask in proportion. Then acid is added, and the temperature is raised to 50°C-180°C. The reaction is carried out for 1-24 hours. After cooling, the mixture is filtered. The pH of the filtrate is adjusted with alkaline water (adjusted to pH 7-14, preferably 8-12, more preferably 9-10). The aqueous layer is removed, and the solvent in the organic layer is removed by vacuum distillation. The product 4-mercaptoethylpyridine is obtained by further vacuum distillation.