CN108863865B - Method for synthesizing butanedithiol - Google Patents
Method for synthesizing butanedithiol Download PDFInfo
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- CN108863865B CN108863865B CN201810947438.9A CN201810947438A CN108863865B CN 108863865 B CN108863865 B CN 108863865B CN 201810947438 A CN201810947438 A CN 201810947438A CN 108863865 B CN108863865 B CN 108863865B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/02—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of thiols
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/093—Preparation of halogenated hydrocarbons by replacement by halogens
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/093—Preparation of halogenated hydrocarbons by replacement by halogens
- C07C17/18—Preparation of halogenated hydrocarbons by replacement by halogens of oxygen atoms of carbonyl groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C335/00—Thioureas, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C335/30—Isothioureas
- C07C335/32—Isothioureas having sulfur atoms of isothiourea groups bound to acyclic carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/08—Preparation of carboxylic acid esters by reacting carboxylic acids or symmetrical anhydrides with the hydroxy or O-metal group of organic compounds
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Abstract
The invention discloses a method for synthesizing butanedithiol, which comprises the following steps: (1) esterifying 2, 3-butanediol with an esterifying agent to obtain an intermediate I (diester); (2) reacting the intermediate I (diester) with an acetic acid solution of hydrogen bromide to obtain an intermediate II (2, 3-dibromobutane); (3) condensing the intermediate II and thiourea to obtain an intermediate III; (4) the intermediate III is hydrolyzed by KOH and acidified to obtain the 2, 3-butanedithiol, the yield is more than 60.0 percent, the invention has the advantages that the 2, 3-butanediol is used as the initial raw material, the price is only 100 yuan/kg, the cost is lower than 800 yuan, the operation is normal pressure, the process is simple, the intermediate is easy to separate in each step, the final product only needs reduced pressure distillation, and the purity is high.
Description
Technical Field
The invention relates to the technical field of butanedithiol synthesis, in particular to a butanedithiol synthesis method.
Background
In the prior art, patent ZL00100889.7 of Beijing university of Industrial and commercial discloses a preparation method of 2, 3-butanedithiol, which comprises the steps of taking 2, 3-epoxybutane as a raw material, reacting with thiourea, and carrying out ring-opening addition on sodium hydrosulfide to obtain the 2, 3-butanedithiol, wherein the chemical reaction formula is as follows:
the reaction has the following problems:
1. the boiling point of the 2, 3-epoxybutane is 56-57 ℃, the reaction temperature is limited, the reaction is not thorough, the yield is lower and is below 65 percent, if the reaction yield is improved, a pressure reaction is needed, equipment requires a high-pressure kettle, and the 2, 3-epoxybutane is difficult to prepare, expensive and 800 yuan/kg, so the cost is seriously increased;
2. in the step of ring-opening addition of sodium hydrosulfide, the sodium hydrosulfide is a hydrate, the purity is about 70 percent, side reaction is caused in the ring-opening process, 2-hydroxy-3-mercaptobutane is generated, the separation is difficult, the reduced pressure rectification separation is needed, and the yield of the 2, 3-butanedithiol is 55 percent;
3. the total yield of the two steps is only about 40 percent, and the cost of the 2, 3-butanedithiol is 2000 yuan/kg.
Disclosure of Invention
The technical problem to be solved by the invention is to overcome the defects in the prior art, and provide a synthetic method of butanedithiol, which is simple to operate, high in product yield and low in cost, and can effectively solve the problems in the background art.
In order to achieve the purpose, the invention provides the following technical scheme: a method for synthesizing butanedithiol comprises the following reaction equation:
the method comprises the following steps:
(1) adding 2, 3-butanediol, an esterifying agent with the molar weight of 2.0-4.0 times of that of the alcohol and an acid-binding agent with the molar weight of 2.0-3.0 times of that of the alcohol, heating to 40.0-80.0 ℃, stirring to react until the 2, 3-butanediol completely reacts, washing with 5.0% of NaHCO3 water, drying, and concentrating to obtain an intermediate I (diester), wherein the yield is 95.0%;
(2) adding an acetic acid solution of 30.0% hydrogen bromide with the molar weight of 2.0-4.0 times that of the intermediate I (diester) into the intermediate I (diester), reacting at room temperature for 3.0-5.0 h, and removing the solvent under reduced pressure after the reaction is finished to obtain an intermediate II (2, 3-dibromobutane), wherein the yield is 85.0%;
(3) adding thiourea with the molar weight of 2.0-2.5 times and ethanol with the mass ratio of 2.0 times into the intermediate II, performing reflux reaction until the intermediate II completely reacts, and performing cooling crystallization to obtain an intermediate III with the yield of 92.0%;
(4) adding the intermediate III into 10.0-30.0% potassium hydroxide aqueous solution with the mass ratio of 2.0-4.0 times, refluxing and hydrolyzing for 2.0-5.0 hours, adjusting the pH value to 3.0 by using concentrated hydrochloric acid after the reaction is finished, adding ethyl acetate for extraction, layering, washing with water, and concentrating to obtain a crude product 2, 3-butanedithiol, wherein the yield is 85.0%;
(5) and (3) carrying out reduced pressure distillation, and collecting a fraction with a boiling point of 86.0-87.0 ℃ (50mmHg) to obtain the product 2, 3-butanedithiol, wherein the GC purity is more than 99.0%, and the total yield is more than 60.0%.
As a preferable technical scheme of the invention, the esterifying agent in the step (1) is one of acetic anhydride, propionic anhydride, p-toluenesulfonyl chloride and maleic anhydride, and the addition amount is 2.0-4.0 times of the molar amount of the alcohol.
As a preferable technical scheme of the invention, the acid-binding agent in the step (1) is pyridine, triethylamine, DIEA, DMAP, sodium acetate and the like, and the using amount of the acid-binding agent is 2.0-3.0 times of the molar weight of alcohol.
As a preferred technical scheme of the invention, in the step (2), the addition amount of the acetic acid solution of 30.0% hydrogen bromide is 2.0-4.0 times of that of the intermediate II, and the reaction lasts for 3.0-5.0 h.
As a preferable technical scheme of the invention, the adding amount of the thiourea in the step (3) is 2.0-2.5 times of the molar amount of the intermediate II.
As a preferred technical scheme of the invention, the mass concentration of the potassium hydroxide aqueous solution in the step (4) is 10.0-30.0%, the addition amount is 2.0-4.0 times of the mass of the intermediate III, and the reflux hydrolysis time is 2.0-5.0 hours.
Compared with the prior art, the invention has the beneficial effects that:
1. 2, 3-butanediol is used as a starting material, the price is only 100 yuan/kg, the total yield is 60 percent, and the cost is lower than 800 yuan;
2. the operation is normal pressure, and the process is simple;
3. the intermediates in each step are easy to separate, and the final product only needs reduced pressure distillation and has high purity.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail with reference to the following embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
Example one
A method for synthesizing butanedithiol comprises the following steps:
(1) adding 2, 3-butanediol, an esterifying agent with the molar weight of 2.0 times of that of the alcohol and an acid-binding agent with the molar weight of 2.0 times of that of the alcohol, wherein the esterifying agent is one of acetic anhydride, propionic anhydride, p-toluenesulfonyl chloride and maleic anhydride, the adding amount is 2.0 times of that of the alcohol, the acid-binding agent is pyridine, triethylamine, DIEA, DMAP, sodium acetate and the like, the using amount is 2.0 times of that of the alcohol, heating to 40.0 ℃, stirring and reacting until the 2, 3-butanediol completely reacts, and then carrying out 5.0% NaHCO reaction on the obtained product3Washing, drying and concentrating to obtain an intermediate I (diester), wherein the yield is 94.0%;
(2) adding an acetic acid solution of 30.0% hydrogen bromide with the molar weight 2.0 times that of the intermediate I (diester), adding an acetic acid solution of 30.0% hydrogen bromide with the molar weight 2.0 times that of the intermediate II, reacting at room temperature for 3.0h, and removing the solvent under reduced pressure after the reaction is finished to obtain an intermediate II (2, 3-dibromobutane), wherein the yield is 87.0%;
(3) adding thiourea of which the molar weight is 2.0 times that of the intermediate II into the intermediate II, wherein the addition amount of the thiourea is 2.0 times that of the intermediate II and the mass ratio of the thiourea to the ethanol is 2.0 times that of the intermediate II, performing reflux reaction until the intermediate II completely reacts, and performing cooling crystallization to obtain an intermediate III, wherein the yield is 92.0%;
(4) adding the intermediate III into a 10.0-30.0% potassium hydroxide aqueous solution with the mass ratio of 2.0 times, wherein the mass concentration of the potassium hydroxide aqueous solution is 10.0%, the addition amount of the potassium hydroxide aqueous solution is 2.0 times of the mass of the intermediate III, performing reflux hydrolysis for 2.0 hours, adjusting the pH value to 3.0 by using concentrated hydrochloric acid after the reaction is finished, adding ethyl acetate for extraction, layering, washing with water, and concentrating to obtain a crude product 2, 3-butanedithiol, wherein the yield is 88.0%;
(5) vacuum distilling, collecting the fraction with boiling point of 86.0 deg.C (50mmHg) to obtain 2, 3-butanedithiol product with GC purity of 99.2% and total yield of 66.2%.
Example two
A method for synthesizing butanedithiol comprises the following steps:
(1) adding 2, 3-butanediol and alcohol with the molar weight of 30 time of esterifying agent and 2.5 times of acid-binding agent of alcohol molar weight, wherein the esterifying agent is one of acetic anhydride, propionic anhydride, p-toluenesulfonyl chloride and maleic anhydride, the adding amount is 3.0 times of the alcohol molar weight, the acid-binding agent is pyridine, triethylamine, DIEA, DMAP, sodium acetate and the like, the using amount is 2.5 times of the alcohol molar weight, the temperature is raised to 60.0 ℃, the stirring reaction is carried out until the 2, 3-butanediol reaction is complete, and then 5.0 percent of NaHCO is added3Washing, drying and concentrating to obtain an intermediate I (diester), wherein the yield is 93.0%;
(2) adding an acetic acid solution of 30.0% hydrogen bromide with the molar weight 3.0 times that of the intermediate I (diester), adding an acetic acid solution of 30.0% hydrogen bromide with the molar weight 3.0 times that of the intermediate II, reacting at room temperature for 4.0h, and removing the solvent under reduced pressure after the reaction is finished to obtain an intermediate II (2, 3-dibromobutane), wherein the yield is 84.0%;
(3) adding thiourea of which the molar weight is 2.2 times that of the intermediate II into the intermediate II, wherein the addition amount of the thiourea is 2.3 times that of the intermediate II, and the mass ratio of the thiourea to the ethanol is 2.0 times that of the intermediate II, performing reflux reaction until the intermediate II completely reacts, and performing cooling crystallization to obtain an intermediate III, wherein the yield is 93.0%;
(4) adding the intermediate III into a potassium hydroxide aqueous solution with the mass ratio of 20.0-30.0% which is 3.0 times that of the intermediate III, adjusting the pH value to 3.0 by using concentrated hydrochloric acid after the reaction is finished, adding ethyl acetate for extraction, layering, washing with water, and concentrating to obtain a crude product 2, 3-butanedithiol, wherein the mass concentration of the potassium hydroxide aqueous solution is 15.0%, and the addition amount of the potassium hydroxide aqueous solution is 3.0 times that of the intermediate III, refluxing and hydrolyzing for 3.0 hours, and the yield is 83.0%;
(5) vacuum distilling, collecting the fraction with boiling point of 86.5 deg.C (50mmHg) to obtain 2, 3-butanedithiol product with GC purity of 99.1% and total yield of 60.3%.
EXAMPLE III
A method for synthesizing butanedithiol comprises the following steps:
(1) adding 2, 3-butanediol, an esterifying agent with the molar weight of 4.0 times of that of the alcohol and an acid-binding agent with the molar weight of 3.0 times of that of the alcohol, wherein the esterifying agent is one of acetic anhydride, propionic anhydride, p-toluenesulfonyl chloride and maleic anhydride, the adding amount is 4.0 times of that of the alcohol, the acid-binding agent is pyridine, triethylamine, DIEA, DMAP, sodium acetate and the like, the using amount is 3.0 times of that of the alcohol, heating to 80.0 ℃, stirring and reacting until the temperature reaches 2, 3 DEG CThe butanediol reaction was complete, followed by 5.0% NaHCO3Washing, drying and concentrating to obtain an intermediate I (diester), wherein the yield is 92.0%;
(2) adding an acetic acid solution of 30.0% hydrogen bromide with the molar weight of 4.0 times that of the intermediate I (diester), adding an acetic acid solution of 30.0% hydrogen bromide with the molar weight of 4.0 times that of the intermediate II, reacting at room temperature for 5.0h, and removing the solvent under reduced pressure after the reaction is finished to obtain an intermediate II (2, 3-dibromobutane), wherein the yield is 85.0%;
(3) adding thiourea of which the molar weight is 2.0-2.5 times that of the intermediate II into the intermediate II, wherein the addition amount of the thiourea is 2.5 times that of the intermediate II and the mass ratio of the thiourea to ethanol is 2.0 times that of the intermediate II, performing reflux reaction until the intermediate II completely reacts, and performing cooling crystallization to obtain an intermediate III, wherein the yield is 92.4%;
(4) adding the intermediate III into a 30.0% potassium hydroxide aqueous solution with the mass ratio of 4.0 times, wherein the mass concentration of the potassium hydroxide aqueous solution is 30.0%, the addition amount of the potassium hydroxide aqueous solution is 4.0 times of the mass of the intermediate III, refluxing and hydrolyzing for 5.0 hours, adjusting the pH value to 3.0 by using concentrated hydrochloric acid after the reaction is finished, adding ethyl acetate for extracting, layering, washing and concentrating to obtain a crude product 2, 3-butanedithiol, and the yield is 84.2%;
(5) vacuum distilling, collecting the fraction with boiling point of 87.0 deg.C (50mmHg) to obtain 2, 3-butanedithiol product with GC purity of 99.3% and total yield of 60.8%.
The invention uses 2, 3-butanediol as starting material, the price is only 100 yuan/kg, the total yield is 60%, the cost is lower than 800 yuan, the operation is normal pressure, the process is simple, the intermediates in each step are easy to separate, the final product only needs reduced pressure distillation, and the purity is high.
Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that changes, modifications, substitutions and alterations can be made in these embodiments without departing from the principles and spirit of the invention, the scope of which is defined in the appended claims and their equivalents.
Claims (1)
1. A method for synthesizing butanedithiol is characterized by comprising the following steps: the method comprises the following steps:
(1) adding 2, 3-butanediol, an esterifying agent with the molar weight of 2.0-4.0 times of that of the alcohol and an acid-binding agent with the molar weight of 2.0-3.0 times of that of the alcohol, heating to 40.0-80.0 ℃, stirring to react until the 2, 3-butanediol completely reacts, washing with 5.0% of NaHCO3, drying, and concentrating to obtain intermediate I diester with the yield of 95.0%;
(2) adding an acetic acid solution of 30.0% hydrogen bromide with the molar weight of 2.0-4.0 times of that of the intermediate I diester, reacting at room temperature for 3.0-5.0 h, and removing the solvent under reduced pressure after the reaction is finished to obtain an intermediate II2, 3-dibromobutane with the yield of 85.0%;
(3) adding thiourea with the molar weight of 2.0-2.5 times and ethanol with the mass ratio of 2.0 times into the intermediate II, performing reflux reaction until the intermediate II completely reacts, and performing cooling crystallization to obtain an intermediate III with the yield of 92.0%;
(4) adding the intermediate III into 10.0-30.0% potassium hydroxide aqueous solution with the mass ratio of 2.0-4.0 times, refluxing and hydrolyzing for 2.0-5.0 hours, adjusting the pH value to be =3.0 by using concentrated hydrochloric acid after the reaction is finished, adding ethyl acetate for extraction, layering, washing and concentrating to obtain a crude product 2, 3-butanedithiol, wherein the yield is 85.0%;
(5) carrying out reduced pressure distillation, and collecting fractions with boiling points of 86.0-87.0 ℃ to obtain a product 2, 3-butanedithiol, wherein the GC purity is over 99.0 percent, and the total yield is over 60.0 percent;
the esterifying agent in the step (1) is one of acetic anhydride, propionic anhydride, p-toluenesulfonyl chloride and maleic anhydride;
the acid-binding agent in the step (1) is pyridine, triethylamine, DIEA, DMAP and sodium acetate.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1834100A (en) * | 2005-11-11 | 2006-09-20 | 浙江大学 | Bisilane coupler contg. sulfur and nitrogen element and prepn. thereof |
| CN1896053A (en) * | 2005-12-02 | 2007-01-17 | 中国医学科学院放射医学研究所 | Improved production of 1, 2-ethanedithiol |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1834100A (en) * | 2005-11-11 | 2006-09-20 | 浙江大学 | Bisilane coupler contg. sulfur and nitrogen element and prepn. thereof |
| CN1896053A (en) * | 2005-12-02 | 2007-01-17 | 中国医学科学院放射医学研究所 | Improved production of 1, 2-ethanedithiol |
Non-Patent Citations (3)
| Title |
|---|
| Absolute configuration of (+)-tartaric acid;Buding,Hartmuth等;《Angewandte Chemie》;19851231;第97卷(第6期);第503页 * |
| Adrenaline profiling of lipases and esterases with 1,2-diol and carbohydrate acetates;Denis Wahler等;《Tetrahedron》;20041231;第60卷;P703-710 * |
| Synthesis by substitution of oxygen functionalities;Braun, M.;《Science of Synthesis》;20071231;第35卷;第323页 Scheme1 * |
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