CN102020631B - Synthetic method of 2-thiophene ethylamine - Google Patents
Synthetic method of 2-thiophene ethylamine Download PDFInfo
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Abstract
The invention relates to a synthetic method of 2-thiophene ethylamine prepared by using thiofuran and N,N-dimethyl formamide as raw materials through five chemical reactions in a synthetic line of thiofuran->2-thiophene carboxaldehyde->2-thiophenic acid->2-thiophene acetic acid-> thiophene acid->2-thiophene ethylamine. The invention provides a new path for preparing the 2-thiophene ethylamine, has mild reaction conditions, and the steps (3) and (4) have extremely similar chemical reaction processes and principles so as to simplify the design of the production operation and process condition. The method provided by the invention has the advantages of low production cost, simple and convenient operation steps, less equipment investment, and the like, is suitable for industrial production and can be used as a new theoretical research path for preparing 2-thiophene ethylamine.
Description
Technical field
The present invention relates to a kind of 2 thiophene ethyl amine synthetic method.
Background technology
The synthetic route of bibliographical information 2 thiophene ethyl amine is more, wherein industrialization or have following three routes of mainly containing of industrial application value.
1) Nitromethane 99Min. method: this method is by thiophene and N, under phosphorus oxychloride exists, there is cationoid reaction and obtain 2 thiophene carboxaldehyde in dinethylformamide (DMF), under the condition that 2 thiophene carboxaldehyde and Nitromethane 99Min. exist at sodium hydroxide, prepare 2-(nitro) thiofuran ethylene, the diborane that the diethyl ether solution of sodium borohydride and boron trifluoride of take generates is reductive agent, and reductase 12-(nitro) thiofuran ethylene is 2 thiophene ethyl amine.The subject matter that this route exists is that sodium borohydride is expensive, and large usage quantity in reaction.2) isopropyl chloracetate method: this method is that reaction in the presence of phosphorus oxychloride obtains 2 thiophene carboxaldehyde with DMF and thiophene, Mono Chloro Acetic Acid and Virahol esterification obtain isopropyl chloracetate, 2 thiophene carboxaldehyde reacts and obtains 2-thiophene acetaldehyde with isopropyl chloracetate generation Darzens, react with oxammonium hydrochloride and obtain 2-thiophene ethylidenehydroxylamine again, the reduction of 2-thiophene ethylidenehydroxylamine obtains 2 thiophene ethyl amine.2-thiophene ethylidenehydroxylamine is reduced into 2 thiophene ethyl amine, need under high pressure adopt hydrogenating reduction under RaneyNi catalysis, and reaction conditions is harsher.3) 2 thiophene acetonitrile method: this method is to take thiophene as the synthetic 2-chloromethyl thiophene of raw material, then reacts and obtains 2 thiophene acetonitrile with sodium cyanide, restores and prepares 2 thiophene ethyl amine.This method synthesis step is few, and reaction conditions is gentle, and product yield is higher, but shortcoming is: used severe poisonous chemicals sodium cyanide, and produced a certain amount of cyanide wastewater, environmental pollution is comparatively serious.
There is respectively the shortcomings such as raw materials cost is high, chemical reaction condition is harsh, environmental pollution is more serious in above method.
Goal of the invention
The features such as its object of the present invention is just to provide a kind of 2 thiophene ethyl amine synthetic method, has production cost low, easy and simple to handle, and facility investment is few, are applicable to suitability for industrialized production, also can be used as a kind of theoretical investigation new way of preparing 2 thiophene ethyl amine.
The technical scheme that realizes above-mentioned purpose and take, take thiophene and DMF as raw material, and through the synthetic 2 thiophene ethyl amine of five kinds of chemical reactions, synthetic route is:
Thiophene → 2 thiophene carboxaldehyde → 2-thiophenic acid → 2-thiophene acetic acid → 2-thiophene propionic acid 2 thiophene ethyl amine;
1) preparation of 2 thiophene carboxaldehyde
By 130 milliliters of N, dinethylformamide and 100 milliliters of thiophene add in the reaction flask of 1 liter, stir, mix, splash into again 152 milliliters of phosphorus oxychloride, after dripping off, rise to 94 ℃, stir 5 hours, then stop heating, be cooled to room temperature, trash ice is added in reaction flask, very exothermic is cooling with cold water, with 25% sodium hydroxide solution, being neutralized to pH value is afterwards 5, by extracted with diethyl ether 3 times, each 250 milliliters of ether, merge three times extraction liquid, wash with water after ether layer, add anhydrous sodium sulfate drying, then elimination sodium sulfate, redistillation material, first normal pressure boils off ether, underpressure distillation after evaporate to dryness ether, obtain 2 thiophene carboxaldehyde,
2) preparation of 2-thiophenic acid
40 grams of 2 thiophene carboxaldehyde liquid are added in the reaction flask of 500 milliliters, splash into after 3 of the vitriol oils heating in water bath to 78 ℃, vigorous stirring, drip 50 grams, 30% hydrogen peroxide again, within 2.5 hours, drip and finish, insulation continues reaction 3 hours, crystallisation by cooling, filter, and use a small amount of water washing, afterwards, at 106 ℃, dry, obtain 2-thiophenic acid;
3) preparation of 2-thiophene acetic acid, Arndt-Eistert reaction
2-thiophenic acid is through acyl chlorides or thionyl chloride SOCl
2with excessive diazomethane effect, gained diazo-ketones (RCOCHN
2) further react and generate ketenes (RCH=C=O), ketenes is hydrolyzed the 2-thiophene acetic acid obtaining than the many carbon atoms of 2-thiophenic acid again,
Wherein, R is:
4) preparation of 2-thiophene propionic acid, Arndt-Eistert reaction
2-thiophene acetic acid is through acyl chlorides or thionyl chloride SOCl
2with excessive diazomethane effect, gained diazo-ketones (RCH
2cOCHN
2) further reaction generation ketenes RCH
2cH=C=O, ketenes is hydrolyzed the 2-thiophene propionic acid obtaining than the many carbon atoms of 2-thiophene acetic acid again,
Wherein, R is:
5) preparation of 2 thiophene ethyl amine, Schmidt rearrangement reaction
Under sulfuric acid exists, hydrazoic acid (HN
3) or sodiumazide (Na N
3) and the effect of 2-thiophene propionic acid, generate than the 2 thiophene ethyl amine of the few carbon atom of 2-thiophene propionic acid.
Beneficial effect
The invention provides a kind of new way of preparing 2 thiophene ethyl amine, reaction conditions is gentle, and the 3rd, the 4th liang of step chemical reaction process is all closely similar close with mechanism, thereby has simplified the design of production operation and processing condition.The features such as method provided by the present invention, has production cost low, easy and simple to handle, and facility investment is few, are applicable to suitability for industrialized production.Also can be used as a kind of theoretical investigation new way of preparing 2 thiophene ethyl amine.
Embodiment
Take thiophene and DMF as raw material, and through the synthetic 2 thiophene ethyl amine of five kinds of chemical reactions, synthetic route is:
Thiophene → 2 thiophene carboxaldehyde → 2-thiophenic acid → 2-thiophene acetic acid → 2-thiophene propionic acid → 2 thiophene ethyl amine;
1) preparation of 2 thiophene carboxaldehyde
By 130 milliliters of N, dinethylformamide and 100 milliliters of thiophene add in the reaction flask of 1 liter, stir, mix, splash into again 152 milliliters of phosphorus oxychloride, after dripping off, rise to 94 ℃, stir 5 hours, then stop heating, be cooled to room temperature, trash ice is added in reaction flask, very exothermic is cooling with cold water, with 25% sodium hydroxide solution, being neutralized to pH value is afterwards 5, by extracted with diethyl ether 3 times, each 250 milliliters of ether, merge three times extraction liquid, wash with water after ether layer, add anhydrous sodium sulfate drying, then elimination sodium sulfate, redistillation material, first normal pressure boils off ether, underpressure distillation after evaporate to dryness ether, obtain 2 thiophene carboxaldehyde,
2) preparation of 2-thiophenic acid
40 grams of 2 thiophene carboxaldehyde liquid are added in the reaction flask of 500 milliliters, splash into after 3 of the vitriol oils heating in water bath to 78 ℃, vigorous stirring, drip 50 grams, 30% hydrogen peroxide again, within 2.5 hours, drip and finish, insulation continues reaction 3 hours, crystallisation by cooling, filter, and use a small amount of water washing, afterwards, at 106 ℃, dry, obtain 2-thiophenic acid;
3) preparation of 2-thiophene acetic acid, Arndt-Eistert reaction
2-thiophenic acid is through acyl chlorides or thionyl chloride SOCl
2with excessive diazomethane effect, gained diazo-ketones (RCOCHN
2) further react and generate ketenes (RCH=C=O), ketenes is hydrolyzed the 2-thiophene acetic acid obtaining than the many carbon atoms of 2-thiophenic acid again,
Wherein R is:
4) preparation of 2-thiophene propionic acid, Arndt-Eistert reaction
2-thiophene acetic acid is through acyl chlorides or thionyl chloride SOCl
2with excessive diazomethane effect, gained diazo-ketones (RCH
2cOCHN
2) further reaction generation ketenes RCH
2cH=C=O, ketenes is hydrolyzed the 2-thiophene propionic acid obtaining than the many carbon atoms of 2-thiophene acetic acid again,
Wherein R is:
5) preparation of 2 thiophene ethyl amine, Schmidt rearrangement reaction
Under sulfuric acid exists, hydrazoic acid (HN
3) or sodiumazide (Na N
3) and the effect of 2-thiophene propionic acid, generate than the 2 thiophene ethyl amine of the few carbon atom of 2-thiophene propionic acid.
Chemical equation summary
Illustrate:
--------------------------------------thiophene
HCON (CH
3)
2--------------------------------------DMF
POCL
3-------------------------------------phosphorus oxychloride
NaOH--------------------------------------sodium hydroxide
(2)
Illustrate:
Illustrate:
------------------------------2-thiophene acetic acid
(4)
Illustrate:
(5)
Illustrate:
Embodiment
1) preparation of 2 thiophene carboxaldehyde
By 130 milliliters of N, dinethylformamide and 100 milliliters of thiophene add in the reaction flask of 1 liter, stir, mix, splash into again 152 milliliters of phosphorus oxychloride, along with the carrying out splashing into, temperature rising now, after dripping off, rise to 94 ℃, stir 5 hours, then stop heating, be cooled to room temperature, trash ice is added in reaction flask, very exothermic is cooling with cold water, with 25% sodium hydroxide solution, being neutralized to pH value is afterwards 5, by extracted with diethyl ether 3 times, each 250 milliliters of ether, merge three times extraction liquid, wash with water after ether layer, add anhydrous sodium sulfate drying, then elimination sodium sulfate, redistillation material, first normal pressure boils off ether, underpressure distillation after evaporate to dryness ether, obtain 2 thiophene carboxaldehyde, productive rate 61%,
2) preparation of 2-thiophenic acid
40 grams of 2 thiophene carboxaldehyde liquid are added in the reaction flask of 500 milliliters, splash into after 3 of the vitriol oils heating in water bath to 78 ℃, vigorous stirring, then drip 50 grams, 30% hydrogen peroxide, within 2.5 hours, drip and finish, insulation continues reaction 3 hours, crystallisation by cooling, filters, and uses a small amount of water washing, afterwards, at 106 ℃, dry, obtain 2-thiophenic acid, yield 79%;
3) preparation of 2-thiophene acetic acid (Arndt-Eistert reaction)
2-thiophenic acid is through acyl chlorides (thionyl chloride SOCl
2) and excessive diazomethane effect, gained diazo-ketones (RCOCHN
2) further react and generate ketenes (RCH=C=O), ketenes is hydrolyzed the 2-thiophene acetic acid obtaining than the many carbon atoms of 2-thiophenic acid again;
(wherein, R is:
)
4) preparation of 2-thiophene propionic acid (Arndt-Eistert reaction)
2-thiophene acetic acid is through acyl chlorides (thionyl chloride SOCl
2) and excessive diazomethane effect, gained diazo-ketones (RCH
2cOCHN
2) further reaction generation ketenes RCH
2cH=C=O, ketenes is hydrolyzed the 2-thiophene propionic acid obtaining than the many carbon atoms of 2-thiophene acetic acid again;
(wherein, R is:
)
5) preparation of 2 thiophene ethyl amine (Schmidt rearrangement reaction)
Under sulfuric acid exists, hydrazoic acid (HN
3) or sodiumazide (Na N
3) and the effect of 2-thiophene propionic acid, generate than the 2 thiophene ethyl amine of the few carbon atom of 2-thiophene propionic acid.
Claims (1)
1. a 2 thiophene ethyl amine synthetic method, is characterized in that, take thiophene and DMF as raw material, and through the synthetic 2 thiophene ethyl amine of five kinds of chemical reactions, synthetic route is:
Thiophene → 2 thiophene carboxaldehyde → 2-thiophenic acid → 2-thiophene acetic acid → 2-thiophene propionic acid → 2 thiophene ethyl amine;
(1) preparation of 2 thiophene carboxaldehyde
By 130 milliliters of N, dinethylformamide and 100 milliliters of thiophene add in the reaction flask of 1 liter, stir, mix, splash into again 152 milliliters of phosphorus oxychloride, after dripping off, rise to 94 ℃, stir 5 hours, then stop heating, be cooled to room temperature, trash ice is added in reaction flask, very exothermic is cooling with cold water, with 25% sodium hydroxide solution, being neutralized to pH value is afterwards 5, by extracted with diethyl ether 3 times, each 250 milliliters of ether, merge three times extraction liquid, wash with water after ether layer, add anhydrous sodium sulfate drying, then elimination sodium sulfate, redistillation material, first normal pressure boils off ether, underpressure distillation after evaporate to dryness ether, obtain 2 thiophene carboxaldehyde,
(2) preparation of 2-thiophenic acid
40 grams of 2 thiophene carboxaldehyde liquid are added in the reaction flask of 500 milliliters, splash into after 3 of the vitriol oils heating in water bath to 78 ℃, vigorous stirring, drip 50 grams, 30% hydrogen peroxide again, within 2.5 hours, drip and finish, insulation continues reaction 3 hours, crystallisation by cooling, filter, and use a small amount of water washing, afterwards, at 106 ℃, dry, obtain 2-thiophenic acid;
(3) preparation of 2-thiophene acetic acid, Arndt-Eistert reaction
2-thiophenic acid is through thionyl chloride SOCl
2with excessive diazomethane effect, gained diazo-ketones RCOCHN
2further reaction generates ketenes RCH=C=O, and ketenes is hydrolyzed the 2-thiophene acetic acid obtaining than the many carbon atoms of 2-thiophenic acid again,
Wherein, R is:
4) preparation of 2-thiophene propionic acid, Arndt-Eistert reaction
2-thiophene acetic acid is through thionyl chloride SOCl
2with excessive diazomethane effect, gained diazo-ketones RCH
2cOCHN
2further reaction generates ketenes RCH
2cH=C=O, ketenes is hydrolyzed the 2-thiophene propionic acid obtaining than the many carbon atoms of 2-thiophene acetic acid again,
Wherein, R is:
5) preparation of 2 thiophene ethyl amine, Schmidt rearrangement reaction
Under sulfuric acid exists, hydrazoic acid (HN
3) or sodiumazide (Na N
3) and the effect of 2-thiophene propionic acid, generate than the 2 thiophene ethyl amine of the few carbon atom of 2-thiophene propionic acid.
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| CN102993165A (en) * | 2012-12-05 | 2013-03-27 | 青岛前线生物工程有限公司 | Synthesis method of 5-chlorothiophene-2-formic acid |
| CN103351376B (en) * | 2013-07-02 | 2015-05-27 | 浙江燎原药业股份有限公司 | Synthetic method of 2-thiophene ethylamine |
| CN103467441B (en) * | 2013-09-23 | 2015-04-01 | 连云港宏业化工有限公司 | Synthetic method of 2-thiopheneacetic acid |
| CN103980265A (en) * | 2014-05-14 | 2014-08-13 | 武汉工程大学 | Synthetic technology for 3-phenyl-5-(thiophene-2-yl)-1,2,4-oxadiazole |
| CN107382959A (en) * | 2017-06-28 | 2017-11-24 | 湖南理工学院 | A kind of technique that 2 thiophenic acids are synthesized using hydrogen peroxide green catalysis oxidation system |
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| JPS5419964A (en) * | 1977-07-11 | 1979-02-15 | Seitetsu Kagaku Co Ltd | Preparation of thiophene-substituted fatty acid halode |
| JPS5422363A (en) * | 1977-07-19 | 1979-02-20 | Seitetsu Kagaku Co Ltd | Preparation of thiophene-substituted fatty acid halide |
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| CN1341598A (en) * | 2000-09-07 | 2002-03-27 | 刁凤森 | Preparation method of 2-thiophene ethamine |
| CN101885720A (en) * | 2010-07-19 | 2010-11-17 | 连云港宏业化工有限公司 | Method for synthesizing 2-thiophene ethylamine |
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