CN102977073B - Method for synthesizing 2-thiophene acetic acid through 2-thiophene alcohol - Google Patents
Method for synthesizing 2-thiophene acetic acid through 2-thiophene alcohol Download PDFInfo
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- CN102977073B CN102977073B CN201210492466.9A CN201210492466A CN102977073B CN 102977073 B CN102977073 B CN 102977073B CN 201210492466 A CN201210492466 A CN 201210492466A CN 102977073 B CN102977073 B CN 102977073B
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Abstract
The invention discloses a method for synthesizing 2-thiophene acetic acid through 2-thiophene alcohol, which comprises the following steps of: directly oxidizing 2-thiophene alcohol serving as an initial raw material into 2-thiophene acetic acid by using an oxidizing agent; and recrystallizing to obtain high-purity 2-thiophene acetic acid. The new synthetic method disclosed by the invention has the beneficial effects that 1) the reaction is completed by directly generating 2-thiophene acetic acid from 2-thiophene alcohol through one-step oxygenation; 2) an obtained product has high yield of 55%-65% and high product purity of 99.0%; and 3) the method disclosed by the invention has the advantages that operation is simple, reaction conditions are easy to control, yield is high, product purity is high and cost is low, and is suitable for industrialized production.
Description
Technical field
The present invention relates to a kind of method by the synthetic 2-thiophene acetic acid of 2-thiophene ethanol, belong to fine chemical technology field.
Background technology
2-thiophene acetic acid is a kind of important organic synthesis intermediate, is widely used in the synthetic of medicine and agricultural chemicals, as synthetic broad spectrum antibiotic cefoxitin, Cephaloridine, cefoxitin.Cephalosporin mother nucleus 7-amino-cephalosporanic acid is carried out to structural modification, can improve the anti-microbial activity of medicine.
About synthesizing of 2-thiophene acetic acid, have more report.For example:
German Pat No.832755 is reported under various catalyzer conditions, and thiophene obtains 2-acetyl thiophene through acetylize, then under pressurized conditions, carry out WILLGERODT with ethanol, sulphur, ammoniacal liquor and react generation 2-thiophene ethanamide, then hydrolysis obtains 2-thiophene acetic acid.This technique is prepared in 2-thiophene ethanamide process and is needed under high pressure to carry out by 2-acetyl thiophene, and sulphur is greatly excessive, product yield only 20.9%.
British Pat No.1122658 is reported in POCl
3exist lower thiophene to react with DMF and obtain 2 thiophene carboxaldehyde, then react with sodium cyanide and trichloromethane, products obtained therefrom hydrogenation is obtained to 2 thiophene acetonitrile, then hydrolysis obtains 2-thiophene acetic acid.This method route is longer, need to use highly toxic substance sodium cyanide, and uses high density platinum catalyst, in security and economy, considers, is not suitable for suitability for industrialized production.
US Pat No.4287352 report thiophene obtains 2-chloromethyl thiophene through chloromethylation, then pressurizes under cobalt salt catalysis with carbon monoxide, methyl alcohol, potassium hydroxide and generates 2-thiophene acetic acid ester, then generate 2-thiophene acetic acid through hydrolysis.This method gained intermediate 2-chloromethyl thiophene is a kind of lachrymator, unstable, can not store for a long time, when airtight by the danger of exploding.
US Pat No.4196299 report thiophene first obtains 2-acetyl thiophene through acetylize; and then make corresponding imines with C4-C8 Armeen or Cyclamine catalyst under 120 ℃; reflect and obtain 2-thiophenic sulfur acid amides in not higher than the organic solvent of 100 ℃ with sulphur again, obtain 2-thiophene acetic acid finally by acidication.This method reactions steps is loaded down with trivial details, intermediate separation difficulty, and target compound productive rate is low, is not suitable for suitability for industrialized production.
Chinese patent application CN 101880271 discloses a kind of elder generation and has obtained 2-acetyl thiophene by thiophene through acetylize, then reacts generation thiophene oxoethanoic acid with Sodium Nitrite with hydrochloric acid, then reacts the method that generates 2-thiophene acetic acid with hydrazine hydrate.But through repeating experiment, result shows that the method primary product is thiophenic acid.
Generate thiophenic acid because thiophene ethanol is easy to over oxidation, through retrieval, do not find that direct oxidation thiophene ethanol prepares the bibliographical information data of thiophene acetic acid.
Summary of the invention
The object of the invention is for the deficiencies in the prior art, provide a kind of new technique simple, cost is low, is applicable to the synthetic method of the 2-thiophene acetic acid of suitability for industrialized production.
For achieving the above object, the present invention adopts following technical proposals:
By the method for the synthetic 2-thiophene acetic acid of 2-thiophene ethanol, take 2-thiophene ethanol as starting raw material, with oxygenant direct oxidation be 2-thiophene acetic acid, obtain highly purified 2-thiophene acetic acid through recrystallization.
The method specifically comprises the following steps:
1. 2-thiophene ethanol is dissolved in organic solvent, adds oxygenant, reaction 0.5 ~ 24h, temperature of reaction is-20 ~ 80 ℃;
2. after having reacted, add quencher cancellation reaction, obtain crude product through aftertreatment, obtain high purity 2-thiophene acetic acid by solvent recrystallization.
Organic solvent described in above-mentioned steps 1 is acetone, methylethylketone, methylene dichloride, ethylene dichloride, the one in chloroform, preferably acetone; Described oxygenant is Jones reagent, PDC, RuO
4, NaClO, NaClO
2in one, preferably Jones reagent; Temperature of reaction is-20 ~ 80 ℃, preferably 0～-10 ℃; Reaction times is 0.5 ~ 24h, preferably 0.5 ~ 3h.
In above-mentioned steps 2, described quencher is Virahol, methyl alcohol, ethanol, the one in the alcoholic solvents such as n-propyl alcohol, preferably Virahol; The solvent that described recrystallization adopts is water, sherwood oil, water/ethanol, in one, be preferably sherwood oil.
The method that in step 2, " aftertreatment " is conventional aftertreatment, comprises that concentrated, extraction, crystallization, filtering separation etc. comprise.Such as being: after cancellation reaction, stir after 30 minutes and be evaporated to cutout (being concentrated into dry), the hydro-oxidation sodium adjusting ph10 extraction that adds diethyl ether, organic layer is removed in layering, water layer is adjusted to ph1 with concentrated hydrochloric acid, ice bath stirring and crystallizing, filters to obtain tawny solid, is the crude product after aftertreatment.
Novel synthesis provided by the present invention possesses following beneficial effect:
1) reaction directly generates 2-thiophene acetic acid by 2-thiophene ethanol oxidation step;
2) present method products obtained therefrom yield is high by 55 ~ 65%, the high >99.0% of product purity;
3) present method possess simple to operate, easy control of reaction conditions, yield is high, the expensive low advantage of product purity, be applicable to suitability for industrialized production.
Embodiment
Below by example, processing step of the present invention is described, but not limited by embodiment.
Embodiment 1:
By after 26.7g (0.267mol) chromium trioxide, 23ml vitriol oil stirring and dissolving, be diluted with water to 100ml and make Jones reagent.In 250ml there-necked flask, add 12.8g(0.1mol) 2-thiophene ethanol, 60ml acetone, stirring and dissolving cooling, keep 0 ~-5 ℃ and drip Jones reagent 53.4ml(0.2mol), drip off follow-up continuous insulated and stirred finishes to reacting for 0.5 hour, add Virahol 20ml to stir after 30 minutes and be evaporated to cutout (being concentrated into dry), hydro-oxidation sodium regulates the ph10 extraction that adds diethyl ether, organic layer is removed in layering, water layer is adjusted to ph1 with concentrated hydrochloric acid, ice bath stirring and crystallizing, filter to obtain tawny solid, recrystallization obtains 2-thiophene acetic acid 7.9g(HPLC purity 99.2%), yield 55.6%.
Embodiment 2:
By after 26.7g (0.267mol) chromium trioxide, 23ml vitriol oil stirring and dissolving, be diluted with water to 100ml and make Jones reagent.In 250ml there-necked flask, add 12.8g(0.1mol) 2-thiophene ethanol, 60ml acetone, stirring and dissolving cooling, keep 0 ~-5 ℃ and drip Jones reagent 80ml(0.3mol), drip off follow-up continuous insulated and stirred finishes to reacting for 1 hour, add Virahol 30ml to stir after 30 minutes and be evaporated to cutout, hydro-oxidation sodium regulates ph10 to add toluene extraction, organic layer is removed in layering, water layer is adjusted to ph1 with concentrated hydrochloric acid, and ice bath stirring and crystallizing, filters to obtain tawny solid, recrystallization obtains 2-thiophene acetic acid 8.5g(HPLC purity 99.4%), yield 59.8%.
Embodiment 3:
By after 53.4g (0.534mol) chromium trioxide, 46ml vitriol oil stirring and dissolving, be diluted with water to 200ml and make Jones reagent.In 250ml there-necked flask, add 12.8g(0.1mol) 2-thiophene ethanol, 60ml acetone, stirring and dissolving cooling, keep-5～-10 ℃ and drip Jones reagent 106.8ml(0.4mol), drip off follow-up continuous insulated and stirred 3 hours, add Virahol 50ml to stir after 30 minutes and be evaporated to cutout, add sodium carbonate and regulate the ph10 extraction that adds diethyl ether, organic layer is removed in layering, water layer is adjusted to ph0.5 with concentrated hydrochloric acid, and ice bath stirring and crystallizing, filters to obtain tawny solid, recrystallization obtains 2-thiophene acetic acid 9.2g(HPLC purity 99.3%), yield 64.8%.
Embodiment 4:
By after 53.4g (0.534mol) chromium trioxide, 46ml vitriol oil stirring and dissolving, be diluted with water to 200ml and make Jones reagent.In 250ml there-necked flask, add 12.8g(0.1mol) 2-thiophene ethanol, 60ml acetone, stirring and dissolving cooling, keep-5～-10 ℃ and drip Jones reagent 80ml(0.3mol), drip off follow-up continuous insulated and stirred and finish to reacting for 3 hours, add Virahol 40ml to stir after 30 minutes and be evaporated to cutout, extraction adds methylene chloride, dried over mgso evaporate to dryness, recrystallization 2-thiophene acetic acid 9.0g(HPLC purity 99.5%), yield 63.4%.
Claims (3)
1. by the method for the synthetic 2-thiophene acetic acid of 2-thiophene ethanol, it is characterized in that, take 2-thiophene ethanol as starting raw material, with oxygenant direct oxidation be 2-thiophene acetic acid, obtain highly purified 2-thiophene acetic acid through recrystallization; Specifically comprise the following steps:
(1) 2-thiophene ethanol is dissolved in acetone, adds Jones reagent, under-5--10 ℃ of temperature condition, react 3h, or react 0.5h or 1h under 0--5 ℃ of condition;
(2) after having reacted, add quencher cancellation reaction, obtain crude product through aftertreatment, obtain high purity 2-thiophene acetic acid by solvent recrystallization.
2. the method as described in claim 1, is characterized in that, described quencher is Virahol, methyl alcohol, ethanol, the one in n-propyl alcohol alcoholic solvent.
3. the method as described in claim 1, is characterized in that, the solvent that described recrystallization adopts is water, sherwood oil, the one in water/ethanol.
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| CN201210492466.9A CN102977073B (en) | 2012-11-27 | 2012-11-27 | Method for synthesizing 2-thiophene acetic acid through 2-thiophene alcohol |
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| 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 |
| CN104725345B (en) * | 2015-03-06 | 2017-06-20 | 黄河三角洲京博化工研究院有限公司 | A kind of process for cleanly preparing of 2 thiophene acetic acid |
| CN104844446A (en) * | 2015-04-24 | 2015-08-19 | 巨化集团技术中心 | Preparation method for perfluorohexyl acetate |
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| US4287352A (en) * | 1978-03-20 | 1981-09-01 | Montedison, S.P.A. | Process for preparing alpha-thienylacetic acid, esters and salts thereof |
| CN101880271B (en) * | 2010-07-16 | 2012-11-28 | 连云港宏业化工有限公司 | Synthesis method of 2-thiophene acetylchloride |
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