CN101880271A - Synthesis method of 2-thiophene acetylchloride - Google Patents
Synthesis method of 2-thiophene acetylchloride Download PDFInfo
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Abstract
The invention relates to a synthesis method of 2-thiophene acetylchloride. The method is characterized by using thiophene as a raw material and mainly comprising the following steps of: (1) acetylating the thiophene in the presence of a catalyst to obtain 2-acetyl thiophene; (2) acting the 2-acetyl thiophene with sodium nitrite and hydrochloric acid in the presence of a catalyst to obtain 2-thiophene glyoxylic acid; (3) reducing the 2-thiophene glyoxylic acid by using hydrazine hydrate to obtain 2-thiopheneacetic acid; and (4) acyl chloridizing the 2-thiopheneacetic acid to obtain the 2-thiophene acetylchloride. The synthesis method has the advantages of easy obtaining of raw materials, simple and convenient operation, high yield, high product purity, and the like and is suitable for industrial production.
Description
Technical field
The present invention relates to a kind of preparation method of 2-thiophen acetyl chloride, belong to medicine and chemical technology field.
Background technology
The 2-thiophen acetyl chloride is widely used at pharmaceutical industry, is the intermediate of broad spectrum antibiotic cefoxitin, Cephaloridine, cefoxitin, and (7 one ACA) carries out structural modification to cephalosporin mother nucleus 7 one amino-cephalo-alkanoic acids, can improve the anti-microbial activity of medicine.In recent years, develop many new cephalosporin antibiotics with 2 one thiophen acetyl chlorides again abroad, cefetrizole, nitrocefin and Menazone etc. are arranged.In addition, 2 one thiophen acetyl chlorides also have a wide range of applications in agricultural chemicals, other field of fine chemical of dye well.
Synthetic reported method about the 2-thiophen acetyl chloride is more, and these methods all are to be raw material with the thiophene, adopts the multistep synthesis technique, finally obtains target product.German Pat No.832755 is reported in that the thiophene acetylize gets the 2-acetyl thiophene under the various catalyzer conditions; under pressurized conditions, carry out the WILLGERODT reaction with ethanol, sulphur, ammoniacal liquor then and generate 2-thiophene ethanamide; hydrolysis obtains the 2-thiophene acetic acid again, and last and sulfur oxychloride effect obtains the 2-thiophen acetyl chloride.This technology prepares 2-thiophene ethanamide by the 2-acetyl thiophene need under high pressure carry out, and sulphur is excessive in a large number, and the target product yield is low.British Pat No.1122658 is reported in POCl
3Have thiophene and N down, the dinethylformamide reaction obtains 2 thiophene carboxaldehyde, with sodium cyanide and trichloromethane reaction, the products obtained therefrom hydrogenation is obtained 2 thiophene acetonitrile then, and hydrolysis gets the 2-thiophene acetic acid again, and last and sulfur oxychloride effect obtains the 2-thiophen acetyl chloride.This method route is long, needs to use the highly toxic substance sodium cyanide, and uses the high density platinum catalyst, considers on safety and economy, is not suitable for carrying out suitability for industrialized production.US Pat No.4287352 report obtains the 2-chloromethyl thiophene by thiophene through chloromethylation earlier, pressurize under the catalysis of cobalt salt with carbon monoxide, methyl alcohol, potassium hydroxide then and generate 2-thiophene acetic acid ester, get the 2-thiophene acetic acid through hydrolysis again, last and sulfur oxychloride effect obtains the 2-thiophen acetyl chloride.This method gained intermediate product 2-chloromethyl thiophene is a kind of lachrymator, and instability can not be long time stored, and the danger of blast is arranged when airtight.US Pat No.4196299 report thiophene obtains the 2-acetyl thiophene through acetylize; making corresponding imines with C4-C8 Armeen or cyclammonium catalysis below 120 ℃ then; corresponding imines and excessive sulphur react in not being higher than 100 ℃ organic solvent and obtain 2-thiophenic sulfur acid amides; obtain the 2-thiophene acetic acid through hydrolysis, acidifying, last and sulfur oxychloride effect obtains the 2-thiophen acetyl chloride.This method reactions steps is loaded down with trivial details, the intermediates separation difficulty, and the target compound productive rate is low, is not suitable for carrying out suitability for industrialized production.Chinese patent application 200510047449 discloses a kind of method by thiophene and oxoethanoic acid Synthetic 2-thiophene acetic acid, though this method technology is simple, used oxoethanoic acid need carry out processed, the cost height, and excessive red phosphorus is not described in this document.
Summary of the invention
Technical problem to be solved by this invention is at the deficiencies in the prior art, provides a kind of technology advantages of simple, cost low, is suitable for industrialized 2-thiophen acetyl chloride synthetic method.
The present invention is a raw material with the thiophene, mainly comprises the steps:
(1) thiophene acetylize in the presence of catalyzer obtains the 2-acetyl thiophene;
(2) the 2-acetyl thiophene obtains 2-thiophene oxoethanoic acid with Sodium Nitrite and hydrochloric acid effect in the presence of catalyzer;
(3) 2-thiophene oxoethanoic acid obtains the 2-thiophene acetic acid with hydrazine hydrate reduction;
(4) chloride of 2-thiophene acetic acid obtains the 2-thiophen acetyl chloride.
Concrete technical scheme of the present invention is as follows:
A kind of synthetic method of 2-thiophen acetyl chloride is characterized in, its step is as follows:
(1) preparation of 2-acetyl thiophene: catalyzer exists down, thiophene and acylating agent in organic solvent reacting by heating 3-10 hour, the mol ratio of thiophene and acylating agent is 1: 1.0-1.8, temperature of reaction is 65-95 ℃, precipitation (removing organic solvent), vacuum distilling is collected 102-105 ℃ of (15mmHg) cut and is promptly got the 2-acetyl thiophene; Described acylating agent is selected from acetate, Acetyl Chloride 98Min. or aceticanhydride; Catalyst system therefor is strong phosphoric acid, molecular sieve or fluoroform sulphonate; Described organic solvent is selected from ethylene dichloride, zellon or N, dinethylformamide;
(2) preparation of 2-thiophene oxoethanoic acid: in the presence of catalyzer, get the 2-acetyl thiophene and in the mixing solutions of Sodium Nitrite and hydrochloric acid, carry out reacting by heating, the weight ratio of 2-acetyl thiophene, Sodium Nitrite and hydrochloric acid is 1: 1.5-5.0: 10-15, temperature of reaction is 65-95 ℃, and reaction finishes postcooling, regulates pH to 2-3, organic solvent extraction is removed impurity, water is regulated the pH value and is lower than 1, press filtration, and the filter cake oven dry promptly gets 2-thiophene oxoethanoic acid; Described catalyzer is the aprotic acid catalyzer; The weight ratio of catalyzer and 2-acetyl thiophene is 0.01-0.1: 1; Extraction is selected from ethyl acetate, toluene, methylene dichloride or N, dinethylformamide with organic solvent;
(3) preparation of 2-thiophene acetic acid: under the alkaline condition, get 2-thiophene oxoethanoic acid and hydrazine hydrate insulation reaction, temperature of reaction is 55-98 ℃, and the reaction times is 6-12 hour, and reaction finishes the back and transfers pH=8, crystallisation by cooling, press filtration, and the filter cake oven dry obtains the 2-thiophene acetic acid; The mol ratio of 2-thiophene oxoethanoic acid and hydrazine hydrate is 1: 1-5;
(4) finished product preparation: get the 2-thiophene acetic acid with an amount of zellon heating for dissolving after dripping thionyl chloride react, temperature of reaction is 40-90 ℃, reaction finishes the back precipitation, 118-120 ℃ of (8mmHg) cut of vacuum distilling collection promptly gets 2-thiophen acetyl chloride finished product; The mol ratio of 2-thiophene acetic acid and sulfur oxychloride is 1: 1-3.
The reaction equation of the synthetic method of 2-thiophen acetyl chloride of the present invention is:
In the synthetic method technology of above-described 2-thiophen acetyl chloride:
1, in the step (1), the preferred tin protoxide of described catalyzer, tetrabutyl titanate, iron(ic) chloride or zinc chloride, further preferred zinc chloride.
2, in the step (1), the mol ratio of thiophene and acylating agent is preferably 1: 1.2, and temperature of reaction is preferably 85 ℃.
3, in the step (2), the weight ratio of catalyzer and 2-acetyl thiophene is preferably 0.025-0.05: 1.
4, in the step (2), the weight ratio of 2-acetyl thiophene, Sodium Nitrite and hydrochloric acid is preferably 1: 3.0: 13, and temperature of reaction is preferably 85 ℃; Described hydrochloric acid can be technical hydrochloric acid.
5, in the step (2), reaction finishes postcooling, preferably regulates pH to 3, and organic solvent extraction is removed impurity, and water is preferably regulated pH to 0.5; Regulating pH can regulate with the acid of routine, preferred hydrochloric acid.
6, in the step (3), the mol ratio of 2-thiophene oxoethanoic acid and hydrazine hydrate (concentration can be 100%) is preferably 1: 1.5-2.
7, in the step (3), the reaction times is preferably 8-9 hour.
8, in the step (4), the mol ratio of 2-thiophene acetic acid and sulfur oxychloride is preferably 1: 1.5-1.8.
9, in the step (4), temperature of reaction is preferably 55-75 ℃.
Compared with prior art, the present invention is a kind of novel method of Synthetic 2-thiophen acetyl chloride, it have raw material be easy to get, easy and simple to handle, yield is high, the product purity advantages of higher is fit to suitability for industrialized production.
Embodiment
Provide specific embodiment to come the present invention is further set forth below, but embodiment does not limit protection scope of the present invention.
Embodiment 1.A kind of synthetic method of 2-thiophen acetyl chloride, its step is as follows:
(1) preparation of 2-acetyl thiophene: catalyzer exists down, thiophene and acylating agent reacting by heating 3 hours in organic solvent, the mol ratio of thiophene and acylating agent is 1: 1.0, temperature of reaction is 65 ℃, precipitation, vacuum distilling is collected 102 ℃ of (15mmHg) cuts and is promptly got the 2-acetyl thiophene; Described acylating agent is an acetate; Catalyst system therefor is a strong phosphoric acid; Described organic solvent is an ethylene dichloride;
(2) preparation of 2-thiophene oxoethanoic acid: in the presence of catalyzer, get the 2-acetyl thiophene and in the mixing solutions of Sodium Nitrite and hydrochloric acid, carry out reacting by heating, the weight ratio of 2-acetyl thiophene, Sodium Nitrite and hydrochloric acid is 1: 1.5: 10, temperature of reaction is 65 ℃, and reaction finishes postcooling, regulates pH to 2, organic solvent extraction is removed impurity, water is regulated the pH value and is lower than 1, press filtration, and the filter cake oven dry promptly gets 2-thiophene oxoethanoic acid; Described catalyzer is the aprotic acid catalyzer; The weight ratio of catalyzer and 2-acetyl thiophene is 0.01: 1; Extraction is an ethyl acetate with organic solvent;
(3) preparation of 2-thiophene acetic acid: under the alkaline condition, get 2-thiophene oxoethanoic acid and hydrazine hydrate insulation reaction, temperature of reaction is 55 ℃, and the reaction times is 6 hours, and reaction finishes the back and transfers pH=8, crystallisation by cooling, press filtration, and the filter cake oven dry obtains the 2-thiophene acetic acid; The mol ratio of 2-thiophene oxoethanoic acid and hydrazine hydrate is 1: 1;
(4) finished product preparation: get the 2-thiophene acetic acid with an amount of zellon heating for dissolving after dripping thionyl chloride react, temperature of reaction is 40 ℃, reaction finishes the back precipitation, 118 ℃ of (8mmHg) cuts of vacuum distilling collection promptly get 2-thiophen acetyl chloride finished product; The mol ratio of 2-thiophene acetic acid and sulfur oxychloride is 1: 1.
Embodiment 2.A kind of synthetic method of 2-thiophen acetyl chloride, its step is as follows:
(1) preparation of 2-acetyl thiophene: catalyzer exists down, thiophene and acylating agent reacting by heating 10 hours in organic solvent, the mol ratio of thiophene and acylating agent is 1: 1.8, temperature of reaction is 95 ℃, precipitation, vacuum distilling is collected 105 ℃ of (15mmHg) cuts and is promptly got the 2-acetyl thiophene; Described acylating agent is an Acetyl Chloride 98Min.; Catalyst system therefor is a molecular sieve; Described organic solvent is a zellon;
(2) preparation of 2-thiophene oxoethanoic acid: in the presence of catalyzer, get the 2-acetyl thiophene and in the mixing solutions of Sodium Nitrite and hydrochloric acid, carry out reacting by heating, the weight ratio of 2-acetyl thiophene, Sodium Nitrite and hydrochloric acid is 1: 5.0: 15, temperature of reaction is 95 ℃, and reaction finishes postcooling, regulates pH to 3, organic solvent extraction is removed impurity, water is regulated the pH value and was lower than for 1 (containing), press filtration, and the filter cake oven dry promptly gets 2-thiophene oxoethanoic acid; Described catalyzer is the aprotic acid catalyzer; The weight ratio of catalyzer and 2-acetyl thiophene is 0.1: 1; Extraction is a methylene dichloride with organic solvent;
(3) preparation of 2-thiophene acetic acid: under the alkaline condition, get 2-thiophene oxoethanoic acid and hydrazine hydrate insulation reaction, temperature of reaction is 98 ℃, and the reaction times is 12 hours, and reaction finishes the back and transfers pH=8, crystallisation by cooling, press filtration, and the filter cake oven dry obtains the 2-thiophene acetic acid; The mol ratio of 2-thiophene oxoethanoic acid and hydrazine hydrate is 1: 5;
(4) finished product preparation: get the 2-thiophene acetic acid with an amount of zellon heating for dissolving after dripping thionyl chloride react, temperature of reaction is 90 ℃, reaction finishes the back precipitation, 120 ℃ of (8mmHg) cuts of vacuum distilling collection promptly get 2-thiophen acetyl chloride finished product; The mol ratio of 2-thiophene acetic acid and sulfur oxychloride is 1: 3.
Embodiment 3.A kind of synthetic method of 2-thiophen acetyl chloride, its step is as follows:
(1) preparation of 2-acetyl thiophene: catalyzer exists down, thiophene and acylating agent reacting by heating 6 hours in organic solvent, the mol ratio of thiophene and acylating agent is 1: 1.2, temperature of reaction is 85 ℃, precipitation, vacuum distilling is collected 103 ℃ of (15mmHg) cuts and is promptly got the 2-acetyl thiophene; Described acylating agent is an aceticanhydride; Catalyst system therefor is a fluoroform sulphonate; Described organic solvent is N, dinethylformamide;
(2) preparation of 2-thiophene oxoethanoic acid: in the presence of catalyzer, get the 2-acetyl thiophene and in the mixing solutions of Sodium Nitrite and hydrochloric acid, carry out reacting by heating, the weight ratio of 2-acetyl thiophene, Sodium Nitrite and hydrochloric acid is 1: 3: 13, temperature of reaction is 85 ℃, and reaction finishes postcooling, regulates pH to 3, organic solvent extraction is removed impurity, water is regulated pH value 0.5, press filtration, and the filter cake oven dry promptly gets 2-thiophene oxoethanoic acid; Described catalyzer is the aprotic acid catalyzer; The weight ratio of catalyzer and 2-acetyl thiophene is 0.025: 1; Extraction is N with organic solvent, dinethylformamide;
(3) preparation of 2-thiophene acetic acid: under the alkaline condition, get 2-thiophene oxoethanoic acid and hydrazine hydrate insulation reaction, temperature of reaction is 75 ℃, and the reaction times is 8 hours, and reaction finishes the back and transfers pH=8, crystallisation by cooling, press filtration, and the filter cake oven dry obtains the 2-thiophene acetic acid; The mol ratio of 2-thiophene oxoethanoic acid and hydrazine hydrate is 1: 1.5;
(4) finished product preparation: get the 2-thiophene acetic acid with an amount of zellon heating for dissolving after dripping thionyl chloride react, temperature of reaction is 55 ℃, reaction finishes the back precipitation, 190 ℃ of (8mmHg) cuts of vacuum distilling collection promptly get 2-thiophen acetyl chloride finished product; The mol ratio of 2-thiophene acetic acid and sulfur oxychloride is 1: 1.5.
Embodiment 4.A kind of synthetic method of 2-thiophen acetyl chloride, its step is as follows:
(1) preparation of 2-acetyl thiophene: catalyzer exists down, thiophene and acylating agent reacting by heating 8 hours in organic solvent, the mol ratio of thiophene and acylating agent is 1: 1.6, temperature of reaction is 75 ℃, precipitation, vacuum distilling is collected 104 ℃ of (15mmHg) cuts and is promptly got the 2-acetyl thiophene; Described acylating agent is selected from acetate, Acetyl Chloride 98Min. or aceticanhydride; Catalyst system therefor is strong phosphoric acid, molecular sieve or fluoroform sulphonate; Described organic solvent is selected from ethylene dichloride, zellon or N, dinethylformamide;
(2) preparation of 2-thiophene oxoethanoic acid: in the presence of catalyzer, get the 2-acetyl thiophene and in the mixing solutions of Sodium Nitrite and hydrochloric acid, carry out reacting by heating, the weight ratio of 2-acetyl thiophene, Sodium Nitrite and hydrochloric acid is 1: 2.0: 12, temperature of reaction is 75 ℃, and reaction finishes postcooling, regulates pH to 2.5, organic solvent extraction is removed impurity, water is regulated pH value 0.2, press filtration, and the filter cake oven dry promptly gets 2-thiophene oxoethanoic acid; Described catalyzer is the aprotic acid catalyzer; The weight ratio of catalyzer and 2-acetyl thiophene is 0.05: 1; Extraction is selected from ethyl acetate, toluene, methylene dichloride or N, dinethylformamide with organic solvent;
(3) preparation of 2-thiophene acetic acid: under the alkaline condition, get 2-thiophene oxoethanoic acid and hydrazine hydrate insulation reaction, temperature of reaction is 85 ℃, and the reaction times is 9 hours, and reaction finishes the back and transfers pH=8, crystallisation by cooling, press filtration, and the filter cake oven dry obtains the 2-thiophene acetic acid; The mol ratio of 2-thiophene oxoethanoic acid and hydrazine hydrate is 1: 2;
(4) finished product preparation: get the 2-thiophene acetic acid with an amount of zellon heating for dissolving after dripping thionyl chloride react, temperature of reaction is 55 ℃, reaction finishes the back precipitation, 118-120 ℃ of (8mmHg) cut of vacuum distilling collection promptly gets 2-thiophen acetyl chloride finished product; The mol ratio of 2-thiophene acetic acid and sulfur oxychloride is 1: 1.8.
Embodiment 5.A kind of synthetic method of 2-thiophen acetyl chloride, its step is as follows:
(1) preparation of 2-acetyl thiophene: catalyzer exists down, thiophene and acylating agent reacting by heating 4 hours in organic solvent, the mol ratio of thiophene and acylating agent is 1: 1.4, temperature of reaction is 80 ℃, precipitation, vacuum distilling is collected 102-105 ℃ of (15mmHg) cut and is promptly got the 2-acetyl thiophene; Described acylating agent is selected from acetate, Acetyl Chloride 98Min. or aceticanhydride; Catalyst system therefor is strong phosphoric acid, molecular sieve or fluoroform sulphonate; Described organic solvent is selected from ethylene dichloride, zellon or N, dinethylformamide;
(2) preparation of 2-thiophene oxoethanoic acid: in the presence of catalyzer, get the 2-acetyl thiophene and in the mixing solutions of Sodium Nitrite and hydrochloric acid, carry out reacting by heating, the weight ratio of 2-acetyl thiophene, Sodium Nitrite and hydrochloric acid is 1: 3.5: 14, temperature of reaction is 80 ℃, and reaction finishes postcooling, regulates pH to 2.8, organic solvent extraction is removed impurity, water is regulated pH value 0.8, press filtration, and the filter cake oven dry promptly gets 2-thiophene oxoethanoic acid; Described catalyzer is the aprotic acid catalyzer; The weight ratio of catalyzer and 2-acetyl thiophene is 0.07: 1; Extraction is selected from ethyl acetate, toluene, methylene dichloride or N, dinethylformamide with organic solvent;
(3) preparation of 2-thiophene acetic acid: under the alkaline condition, get 2-thiophene oxoethanoic acid and hydrazine hydrate insulation reaction, temperature of reaction is 80 ℃, and the reaction times is 10 hours, and reaction finishes the back and transfers pH=8, crystallisation by cooling, press filtration, and the filter cake oven dry obtains the 2-thiophene acetic acid; The mol ratio of 2-thiophene oxoethanoic acid and hydrazine hydrate is 1: 3;
(4) finished product preparation: get the 2-thiophene acetic acid with an amount of zellon heating for dissolving after dripping thionyl chloride react, temperature of reaction is 75 ℃, reaction finishes the back precipitation, 118-120 ℃ of (8mmHg) cut of vacuum distilling collection promptly gets 2-thiophen acetyl chloride finished product; The mol ratio of 2-thiophene acetic acid and sulfur oxychloride is 1: 1.5.
Embodiment 6.In the step (1) of any one described synthetic method of embodiment 1-5, described catalyzer can be tin protoxide, tetrabutyl titanate, iron(ic) chloride or zinc chloride.
Embodiment 7.The preparation experiment of 2-acetyl thiophene.
In the there-necked flask of band mechanical stirring, thermometer, add 60g thiophene, 92g aceticanhydride, 10g strong phosphoric acid and 350ml zellon, slowly be heated to 65-68 ℃, insulation reaction 5 hours, decompression steams zellon, and reclaim under reduced pressure thiophene and by-product acetic acid are collected 102-105 ℃ of (15mmHg) cut and got 2-acetyl thiophene 82.8g again, yield 92%, content 99.4%.
Embodiment 8.The preparation experiment of 2-thiophene oxoethanoic acid.
In the there-necked flask of band mechanical stirring, thermometer, add 2-acetyl thiophene, 3.5g zinc chloride, 273g Sodium Nitrite and the 250ml water of 90g embodiment 7 preparations, be warming up to 80 ℃ of Dropwise 5 52g concentrated hydrochloric acids, dripped back 85 ℃ of insulation reaction 1 hour.Reaction finishes, and regulates Ph=3, ethyl acetate extraction, the water cooling down with acid adjusting Ph＜0.5 to no longer separating out solid, suction filtration, filter cake dry light yellow 2-thiophene oxoethanoic acid 96.4g, yield 86.5%, content 98.8% (HPLC).
Embodiment 9.The preparation experiment of 2-thiophene acetic acid.
In the there-necked flask of band mechanical stirring, thermometer, add 420g water and 72g sodium hydroxide, stirring is warmed up to 55 ℃ of 2-thiophene oxoethanoic acids that add 96.4g embodiment 8 preparations, drip the 40.5g hydrazine hydrate in 30 minutes, be warming up to 98 ℃ after dripping off, continued insulation reaction 8 hours.When being cooled to 60 ℃, regulate PH=8, filter, filtrate is transferred PH＜0.5 with hydrochloric acid, is cooled to 0 ℃, suction filtration, filter cake dry light yellow 2-thiophene acetic acid 81.4g, yield 94.1%, content 993% (HPLC).
Embodiment 10.The preparation experiment of 2-thiophen acetyl chloride.
The 2-thiophene acetic acid 81.4g that in the there-necked flask of band mechanical stirring, thermometer, adds 180g zellon and embodiment 9 preparations, stirring is warming up to 50 ℃ and begins to drip the 130g sulfur oxychloride, drip off in 3 hours, continued 55 ℃ of insulation reaction 1 hour, be warming up to 75 ℃ again and wore out 1 hour, decompression steams tetracol phenixin, collects 118-120 ℃ of (8mmHg) cut and gets 2-thiophen acetyl chloride 78.5g, yield 92.2%, content 99.1%.
Claims (10)
1. the synthetic method of a 2-thiophen acetyl chloride is characterized in that, its step is as follows:
(1) preparation of 2-acetyl thiophene: catalyzer exists down, thiophene and acylating agent in organic solvent reacting by heating 3-10 hour, the mol ratio of thiophene and acylating agent is 1: 1.0-1.8, temperature of reaction is 65-95 ℃, precipitation, vacuum distilling is collected 102-105 ℃/15mmHg cut and is promptly got the 2-acetyl thiophene; Described acylating agent is selected from acetate, Acetyl Chloride 98Min. or aceticanhydride; Catalyst system therefor is strong phosphoric acid, molecular sieve or fluoroform sulphonate; Described organic solvent is selected from ethylene dichloride, zellon or N, dinethylformamide;
(2) preparation of 2-thiophene oxoethanoic acid: in the presence of catalyzer, get the 2-acetyl thiophene and in the mixing solutions of Sodium Nitrite and hydrochloric acid, carry out reacting by heating, the weight ratio of 2-acetyl thiophene, Sodium Nitrite and hydrochloric acid is 1: 1.5-5.0: 10-15, temperature of reaction is 65-95 ℃, and reaction finishes postcooling, regulates pH to 2-3, organic solvent extraction is removed impurity, water is regulated the pH value and is lower than 1, press filtration, and the filter cake oven dry promptly gets 2-thiophene oxoethanoic acid; Described catalyzer is the aprotic acid catalyzer; The weight ratio of catalyzer and 2-acetyl thiophene is 0.01-0.1: 1; Extraction is selected from ethyl acetate, toluene, methylene dichloride or N, dinethylformamide with organic solvent;
(3) preparation of 2-thiophene acetic acid: under the alkaline condition, get 2-thiophene oxoethanoic acid and hydrazine hydrate insulation reaction, temperature of reaction is 55-98 ℃, and the reaction times is 6-12 hour, and reaction finishes the back and transfers pH=8, crystallisation by cooling, press filtration, and the filter cake oven dry obtains the 2-thiophene acetic acid; The mol ratio of 2-thiophene oxoethanoic acid and hydrazine hydrate is 1: 1-5;
(4) finished product preparation: get the 2-thiophene acetic acid with an amount of zellon heating for dissolving after dripping thionyl chloride react, temperature of reaction is 40-90 ℃, reaction finishes the back precipitation, 118-120 ℃/8mmHg of vacuum distilling collection cut promptly gets 2-thiophen acetyl chloride finished product; The mol ratio of 2-thiophene acetic acid and sulfur oxychloride is 1: 1-3.
2. synthetic method according to claim 1 is characterized in that: in the step (1), described catalyzer is selected from tin protoxide, tetrabutyl titanate, iron(ic) chloride or zinc chloride.
3. synthetic method according to claim 1 is characterized in that: in the step (1), the mol ratio of thiophene and acylating agent is 1: 1.2, and temperature of reaction is 85 ℃.
4. synthetic method according to claim 1 is characterized in that: in the step (2), the weight ratio of catalyzer and 2-acetyl thiophene is 0.025-0.05: 1.
5. synthetic method according to claim 1 is characterized in that: in the step (2), the weight ratio of 2-acetyl thiophene, Sodium Nitrite and hydrochloric acid is 1: 3.0: 13, and temperature of reaction is 85 ℃.
6. synthetic method according to claim 1 is characterized in that: in the step (2), reaction finishes postcooling, regulates pH to 3, and organic solvent extraction is removed impurity, and water is regulated pH to 0.5.
7. synthetic method according to claim 1 is characterized in that: in the step (3), the mol ratio of 2-thiophene oxoethanoic acid and hydrazine hydrate is 1: 1.5-2.
8. synthetic method according to claim 1 is characterized in that: in the step (3), the reaction times is 8-9 hour.
9. synthetic method according to claim 1 is characterized in that: in the step (4), the mol ratio of 2-thiophene acetic acid and sulfur oxychloride is 1: 1.5-1.8.
10. synthetic method according to claim 1 is characterized in that: in the step (4), temperature of reaction is 55-75 ℃.
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| CN102977073A (en) * | 2012-11-27 | 2013-03-20 | 山东师范大学 | Method for synthesizing 2-thiophene acetic acid through 2-thiophene alcohol |
| CN104016962A (en) * | 2014-06-16 | 2014-09-03 | 商丘凯瑞达化工有限公司 | Process for synthetizing 2-thiopheneacetyl chloride |
| CN106831702A (en) * | 2016-12-05 | 2017-06-13 | 浙江燎原药业股份有限公司 | A kind of preparation method of the thiophenic acid of 5 substitution 2 |
| CN110590736A (en) * | 2019-10-09 | 2019-12-20 | 山东师范大学 | Synthesis method of 2-thiophene glyoxylic acid |
| CN112225720A (en) * | 2020-11-10 | 2021-01-15 | 吴仁涛 | Production method of thiophene-2-acetyl chloride |
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| HU203774B (en) * | 1984-04-26 | 1991-09-30 | Sumitomo Chemical Co | Process for producing catalyst-systhem for producing olefine polymeres and process for polymerizing olefines |
| CN101497598A (en) * | 2009-03-02 | 2009-08-05 | 上海应用技术学院 | Preparation of 2-thiophen acetyl chloride |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102977073A (en) * | 2012-11-27 | 2013-03-20 | 山东师范大学 | Method for synthesizing 2-thiophene acetic acid through 2-thiophene alcohol |
| CN104016962A (en) * | 2014-06-16 | 2014-09-03 | 商丘凯瑞达化工有限公司 | Process for synthetizing 2-thiopheneacetyl chloride |
| CN106831702A (en) * | 2016-12-05 | 2017-06-13 | 浙江燎原药业股份有限公司 | A kind of preparation method of the thiophenic acid of 5 substitution 2 |
| CN110590736A (en) * | 2019-10-09 | 2019-12-20 | 山东师范大学 | Synthesis method of 2-thiophene glyoxylic acid |
| CN112225720A (en) * | 2020-11-10 | 2021-01-15 | 吴仁涛 | Production method of thiophene-2-acetyl chloride |
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| Publication number | Publication date |
|---|---|
| CN101880271B (en) | 2012-11-28 |
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