CN107557401B - Preparation method of 2-thiophenecarboxylic acid - Google Patents
Preparation method of 2-thiophenecarboxylic acid Download PDFInfo
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Abstract
The invention relates to the field of biochemistry, and particularly relates to a preparation method of 2-thiophenecarboxylic acid. Adding 2-thiophenemethanol into the activated bacteria solution bottle, performing shaking table reaction, and tracking the reaction process by TLC; after the reaction is finished, the bacterial liquid is centrifuged and filtered, the supernatant is taken and alkalized by NaOH solution until the pH value is more than 10, extraction is carried out, an organic phase is separated, a hydrochloric acid solution is used for acidification of a water phase, centrifugation and ethyl acetate extraction are carried out, anhydrous magnesium sulfate is dried, the organic phase is concentrated, and the concentrated solution is recrystallized by petroleum ether to obtain the 2-thiophenecarboxylic acid. The method for preparing the 2-thiophenecarboxylic acid has mild reaction conditions, the reaction is carried out under normal pressure, and the reaction temperature is 30-40 ℃; the reaction operation is simple, the 2-thiophene methanol is mixed with the activating solution, and the reaction condition is constant; organic solvent, catalyst and the like are not used in the reaction, so that the cost is low; no pollutant is generated in the reaction raw materials and the reaction process, and the method is green and environment-friendly.
Description
Technical Field
The invention relates to the field of biochemistry, and particularly relates to a preparation method of 2-thiophenecarboxylic acid.
Background
The 2-thiophenecarboxylic acid is used in the fields of medicines, color developing agents, chemical industry, new materials and the like, can be used for synthesizing raltitrexed, an anti-inflammatory analgesic intermediate, a photovoltaic material and the like, and is an important intermediate material. However, the traditional process for preparing 2-thiophenecarboxylic acid has the defects of complex operation, high cost, low yield, large pollution and the like.
As in the chemical world, 1995, 36 (3): P283-286A process for the preparation of 2-thiophenecarboxylic acid: the method comprises the steps of acetylating thiophene serving as a raw material to obtain 2-acetylthiophene, and then heating and oxidizing by using chloroform or nitric acid to obtain 2-thiophenecarboxylic acid, wherein the yield is about 60%, and in the method, a large amount of acid and alkali are required for acetylating, chloroform reaction or oxidizing reaction, so that the pollution is great, and the yield is low; a chemical intermediate, 2007, (12) the method for preparing 2-thiophenecarboxylic acid disclosed in P13-14: thiophene is used as a raw material, pyridine bromide hydrobromate is used for brominating to obtain 2-bromothiophene, 2-methyltetrahydrofuran is used as a solvent to prepare a Grignard reagent, the Grignard reagent is added with triethyl orthoformate and hydrolyzed to prepare 2-thiophenecarboxaldehyde, and finally hydrogen peroxide is used for oxidizing to obtain the 2-thiophenecarboxylic acid, wherein the yield is about 60 percent, and the method for preparing the 2-thiophenecarboxylic acid has long reaction steps and serious bromination pollution.
Patent CN200910143971.0 discloses a preparation method of 2-thiophenecarboxylic acid: dissolving thiophene (II) by using halohydrocarbon and hydrobromic acid as solvents, adding perbromopyridine salt in batches, stirring at the temperature of below 0 ℃, extracting, washing and distilling to obtain 2-bromothiophene (III); reacting diethyl malonate and alkali metal at 90 ℃, heating to 100 ℃ to react to obtain salt, then cooling to room temperature, dropwise adding a toluene solution of 2-bromothiophene, heating to 100-120 ℃ after dropwise adding, reacting, extracting, and distilling to obtain 2- (2-thiophene) diethyl malonate (IV); and 2- (2-thiophene) diethyl malonate firstly heats up and refluxes in an alcohol solvent under an alkaline condition to carry out saponification reaction, the solvent is distilled off, acid is added to carry out heating up, refluxes and decarboxylation, and the 2-thiophene formic acid (I) is obtained by solvent extraction, washing, drying and recrystallization.
In view of the foregoing, there is a need for improvement in the deficiencies of the prior art.
Disclosure of Invention
In order to overcome the defects in the prior art, the invention provides the preparation method of the 2-thiophenecarboxylic acid, which has the advantages of mild reaction conditions, simple operation, higher yield, low cost, greenness and environmental protection. Acetobacter is an aerobic microorganism commonly used in the vinegar industry to oxidize ethanol to acetic acid. The invention uses acetobacter to oxidize 2-thiophenemethanol into 2-thiophenecarboxylic acid.
In order to solve the technical problems, the technical scheme adopted by the invention is as follows:
a preparation method of 2-thiophenecarboxylic acid comprises the following steps:
s1, adding 2-thiophene methanol into the activated bacteria solution bottle, carrying out shaking table reaction, and tracking the reaction process by TLC;
s2, after the reaction is finished, the bacterial liquid is centrifuged and filtered, the supernatant is taken and alkalized by NaOH solution until the pH value is more than 10, the organic phase is extracted and separated, the aqueous phase is acidified by hydrochloric acid solution, the centrifugation and the ethyl acetate extraction are carried out, the anhydrous magnesium sulfate is dried, the organic phase is concentrated, and the concentrated solution is recrystallized by petroleum ether to obtain the 2-thiophenecarboxylic acid.
The activated bacteria liquid is as follows: placing distilled water and glucose into a bottle, sterilizing at high temperature, cooling to room temperature, adding Acetobacter into the sterilized bottle, activating for 2h at 30 ℃ of a shaking table, and activating to obtain a bacterial liquid. The mass ratio of the distilled water to the glucose to the acetobacter is 25:1: 4.
The mass ratio of the 2-thiophenemethanol to the activated bacteria liquid is 1: 120.
Compared with the prior art, the invention has the beneficial effects that:
the preparation method of the 2-thiophenecarboxylic acid has the advantages of reaction temperature of 30-40 ℃, normal pressure and mild reaction conditions; the reaction only needs to mix the 2-thiophene methanol with the activating solution, the reaction condition is constant, the operation is simple, and the method is suitable for an industrial production mode; the reaction does not contain organic solvent, catalyst and the like, and the cost is low, so the method is easy to popularize; no pollutant is generated in the reaction raw materials and the reaction process, and the method is green and environment-friendly.
Detailed Description
The technical solutions in the embodiments of the present invention are clearly and completely described below, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
A preparation method of 2-thiophenecarboxylic acid comprises the steps of putting distilled water and glucose into a triangular flask according to the mass ratio of W: W =25:1, sterilizing at high temperature, cooling to room temperature, adding the distilled water, the glucose and acetobacter aceti into the sterilized triangular flask according to the mass ratio of W: W: W =25:1:4, activating for 2h by a shaking table at 30 ℃, and completing activation.
Adding 2-thiophene methanol and the activated bacillus aceticus liquid into an activated bacteria liquid triangular flask according to the mass ratio of W: W =1:120, carrying out shake-bed reaction at 30-40 ℃, and tracking the reaction process by TLC. After the reaction is finished, the bacterial liquid is centrifuged and filtered, the supernatant is taken and alkalized by NaOH solution until the pH value is more than 10, extraction is carried out, an organic phase is separated, a water phase is acidified by hydrochloric acid solution, centrifugation, ethyl acetate extraction, anhydrous magnesium sulfate drying and concentration are carried out, and the concentrated solution is recrystallized by petroleum ether to obtain the 2-thiophenecarboxylic acid.
Wherein W represents the mass of the material and the unit is g.
Activation of bacterial liquid: adding 50mL of distilled water and 2g of glucose into a 100mL triangular flask, stirring for dissolving, sterilizing at high temperature (121 ℃, 15 min), cooling to room temperature, adding 8g of bacillus aceticus, and activating for 2h by a shaker (30 ℃, 160 rpm), thereby completing activation.
Example 1
Adding 0.5g of 2-thiophenemethanol into the activated bacterial liquid, placing the triangular flask into a shaking table for reaction at 37 ℃, and tracking the reaction process by TLC. After the reaction is finished, the bacterial liquid is centrifuged, the supernatant is filtered, the filtrate is alkalized by 5% by mass of NaOH solution until the pH value is more than 10, ethyl acetate is used for extraction, an organic phase is separated, a water phase is acidified by 5% by mass of HCl solution until the pH value is less than 2, the organic phase is concentrated by centrifugation, ethyl acetate is used for extraction, anhydrous magnesium sulfate is used for drying, the organic phase is concentrated, and the concentrated solution is recrystallized by petroleum ether to obtain the 2-thiophenecarboxylic acid with the yield of 70%.
Example 2
Adding 0.5g of 2-thiophenemethanol into the activated bacterial liquid, placing the triangular flask into a shaking table for reaction at 40 ℃, and tracking the reaction process by TLC. After the reaction is finished, the bacterial liquid is centrifuged, the supernatant is filtered, the filtrate is alkalized by 5% NaOH solution by mass fraction until the pH value is more than 10, ethyl acetate is used for extraction, an organic phase is separated, a water phase is acidified by 5% HCl solution by mass fraction until the pH value is less than 2, the organic phase is concentrated by centrifugation, ethyl acetate is used for extraction, anhydrous magnesium sulfate is used for drying, the organic phase is concentrated, and the concentrated solution is recrystallized by petroleum ether to obtain 2-thiophenecarboxylic acid with the yield of 68%.
Although only the preferred embodiments of the present invention have been described in detail, the present invention is not limited to the above embodiments, and various changes can be made without departing from the spirit of the present invention within the knowledge of those skilled in the art, and all changes are encompassed in the scope of the present invention.
Claims (4)
1. The preparation method of the 2-thiophenecarboxylic acid is characterized by comprising the following steps:
s1, adding 2-thiophene methanol into the activated bacteria solution bottle, carrying out shaking table reaction, and tracking the reaction process by TLC;
s2, after the reaction is finished, centrifuging and filtering the bacterial liquid, taking supernate, alkalifying the supernate with NaOH solution to pH of more than 10, extracting, separating an organic phase, acidifying a water phase with hydrochloric acid solution, centrifuging, extracting with ethyl acetate, drying with anhydrous magnesium sulfate, concentrating the organic phase, and recrystallizing the concentrated solution with petroleum ether to obtain 2-thiophenecarboxylic acid;
the activated bacteria liquid is as follows: placing distilled water and glucose into a bottle, sterilizing at high temperature, cooling to room temperature, adding Acetobacter into the sterilized bottle, activating by a shaking table, and activating to obtain a bacterium solution.
2. The method for preparing 2-thiophenecarboxylic acid according to claim 1, wherein the mass ratio of distilled water, glucose and acetobacter is 25:1: 4.
3. The method of claim 1, wherein the acetobacter aceti is added to the sterilized bottle and then activated by shaking at 30 ℃ for 2 hours.
4. The method for preparing 2-thiophenecarboxylic acid according to claim 1, wherein the mass ratio of the 2-thiophenemethanol to the activated bacteria solution is 1: 120.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101906092A (en) * | 2009-06-04 | 2010-12-08 | 浙江医药股份有限公司新昌制药厂 | Preparation method of 2-thiophenecarboxylic acid |
| CN106496184A (en) * | 2016-11-07 | 2017-03-15 | 王志训 | A kind of preparation method of 2 thiophenic acid |
| CN106947795A (en) * | 2017-05-13 | 2017-07-14 | 太原理工大学 | A kind of method that living things catalysis synthesizes 2 thiophene ethamines |
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| IL114114A (en) * | 1995-06-12 | 2000-02-29 | Yanirsch Technologies Ltd | Foamed magnesite cement and articles made therewith |
| US7262269B2 (en) * | 2001-10-26 | 2007-08-28 | The Regents Of University Of California | Method for screening combinational bead library; ligands for cancer cells |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101906092A (en) * | 2009-06-04 | 2010-12-08 | 浙江医药股份有限公司新昌制药厂 | Preparation method of 2-thiophenecarboxylic acid |
| CN106496184A (en) * | 2016-11-07 | 2017-03-15 | 王志训 | A kind of preparation method of 2 thiophenic acid |
| CN106947795A (en) * | 2017-05-13 | 2017-07-14 | 太原理工大学 | A kind of method that living things catalysis synthesizes 2 thiophene ethamines |
Non-Patent Citations (1)
| Title |
|---|
| 醋酸菌的分类进展;王斌等;《中国酿造》;CNKI;20141215;第33卷(第12期);摘要，第6页左栏第2段 * |
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