CN104016962A - Process for synthetizing 2-thiopheneacetyl chloride - Google Patents
Process for synthetizing 2-thiopheneacetyl chloride Download PDFInfo
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- CN104016962A CN104016962A CN201410266505.2A CN201410266505A CN104016962A CN 104016962 A CN104016962 A CN 104016962A CN 201410266505 A CN201410266505 A CN 201410266505A CN 104016962 A CN104016962 A CN 104016962A
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- reaction
- dichloromethane
- chloride
- acetic acid
- acetyl chloride
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The invention relates to a process for synthetizing 2-thiopheneacetyl chloride. The method comprises the following steps: dissolving 2-thiopheneacetic acid in dichloromethane, heating in the presence of nitrogen, dropping thionyl chloride in the state of keeping the system slightly boiling and holding the temperature for 2-3 hours after the dropping is completed; finally, carrying out suction filtration, desolvation and reduced pressure distillation to obtain the product 2-thiopheneacetyl chloride. The process disclosed by the invention has the positive effects that the dichloromethane low in boiling point is adopted as the solvent, so that the desolvation is easy and the product content is not influenced; SO2 and HCl produced in the reaction can be volatilized along with the dichloromethane through keeping a proper reaction temperature, so that the reaction can be fully carried out and the reaction yield is increased; the volatilized dichloromethane is cooled through cold saline and can be recycled after being washed by water; the process is mild in reaction condition, little in catalyst amount and simple; compared with an existing synthesis process, the process disclosed by the invention has obvious economic benefit and environmental benefit and is beneficial to industrial production.
Description
Technical field
The present invention relates to the synthesis technique of 2-thiophen acetyl chloride, belong to fine chemical technology field.
Background technology
2-thiophen acetyl chloride is a kind of important organic synthesis intermediate, is widely used in particularly synthesizing of cephalo medicine of medicine, as synthetic spectrum antimicrobial drug cefoxitin, Cephaloridine, cefoxitin.Cephalosporin mother nucleus 7-amino-cephalosporanic acid is carried out to structural modification, can improve the anti-microbial activity of medicine.
The method of preparing at present 2-thiophen acetyl chloride mainly contains following several: (1) adds 2-thiophene acetic acid and sulfur oxychloride in flask, be heated to 40-50 DEG C of insulation reaction 4h. then reaction solution carry out underpressure distillation, remove after superfluous sulfur oxychloride and low-boiling-point substance, continue distillation and be 2-thiophen acetyl chloride.During due to chloride, reaction system is acid, can make the thiphene ring oxidation in 2-thiophene acetic acid and 2-thiophen acetyl chloride, in vacuum distillation process, has a large amount of product carbonizations like this, thereby product yield is reduced; (2) Chinese patent application 201010227870.4 has reported that 2-thiophene acetic acid is under the existence of tetrachloroethylene solvent, reacts generate 2-thiophen acetyl chloride with sulfur oxychloride.This method product in the time of underpressure distillation is difficult to all slough solvent, causes product content undesirable; (3) Chinese patent application 200910046880.5 has reported that 2-thiophene acetic acid is solvent at tetracol phenixin, under reductive agent sodium sulphite anhydrous 99.3 exists, reacts generate 2-thiophen acetyl chloride, yield 85% with sulfur oxychloride.This method product in the time of underpressure distillation is not only difficult to all slough solvent, and reaction yield is also undesirable.
Summary of the invention
The object of the present invention is to provide a kind of technique advantages of simple, reduce product carbonization, improve reaction yield, be conducive to the synthesis technique of the 2-thiophen acetyl chloride of suitability for industrialized production.
Realizing the technical scheme that the object of the invention takes is: 2-thiophene acetic acid is dissolved among methylene dichloride, under the protection of nitrogen, while being heated to 35-38 DEG C, under the micro-state boiling of maintenance system, drips sulfur oxychloride, be incubated 2-3h after dropwising; Last suction filtration, precipitation, underpressure distillation obtains product 2-thiophen acetyl chloride.Wherein the material mass ratio that feeds intake is 2-thiophene acetic acid: sulfur oxychloride=1:2-3, the consumption of methylene chloride be 2-thiophene acetic acid quality 3-4 doubly.
Positively effect of the present invention is: adopt methylene dichloride as solvent, its boiling point is lower, and precipitation is easy, can not affect product content; Maintenance temperature of reaction is 35-38 DEG C, the SO that can make reaction produce
2and HCl volatilizees with methylene dichloride, thereby can react fully, improve reaction yield; Cooling through cool brine after methylene dichloride volatilization, after washing, can reuse; This reaction conditions gentleness, catalyst levels is few, and technique is simple; Compared with existing synthesis technique, the present invention has obvious economic benefit and environmental benefit, is conducive to technology and produces.
Embodiment
It is further to set forth of the present invention that concrete embodiment is provided below, but embodiment does not limit the scope of the invention.
Embodiment 1
In the four-hole boiling flask with mechanical stirring, thermometer, air guide outlet, add 100g 2-thiophene acetic acid; 300g methylene dichloride, stirs and is warming up to 35 DEG C, starts to drip 200g sulfur oxychloride under the protection of nitrogen; within 1.5 hours, drip off insulation reaction 2 hours at this temperature.The methylene dichloride of underpressure distillation remnants, continues 90-95 DEG C of (7mmHg) cuts of distillation collection and obtains 2-thiophen acetyl chloride 99.3g, and yield reaches 88.7%.
Embodiment 2
In the four-hole boiling flask with mechanical stirring, thermometer, air guide outlet, add 100g 2-thiophene acetic acid; 350g methylene dichloride, stirs and is warming up to 37 DEG C, starts to drip 250g sulfur oxychloride under the protection of nitrogen; within 1.5 hours, drip off insulation reaction 2.5 hours at this temperature.The methylene dichloride of underpressure distillation remnants, continues to distill obtaining 2-thiophen acetyl chloride 102.5g, and yield reaches 91.5%.
Embodiment 3
In the four-hole boiling flask with mechanical stirring, thermometer, air guide outlet, add 100g 2-thiophene acetic acid; 400g methylene dichloride, stirs and is warming up to 39 DEG C, starts to drip 300g sulfur oxychloride under the protection of nitrogen; within 1.5 hours, drip off insulation reaction 3 hours at this temperature.The methylene dichloride of underpressure distillation remnants, continues to distill obtaining 2-thiophen acetyl chloride 106.3g, and yield reaches 94.9%.
Claims (1)
1. a synthesis technique for 2-thiophen acetyl chloride, is characterized in that: 2-thiophene acetic acid is dissolved among methylene dichloride, under the protection of nitrogen, while being heated to 35-38 DEG C, under the micro-state boiling of maintenance system, drips sulfur oxychloride, be incubated 2-3h after dropwising; Last suction filtration, precipitation, underpressure distillation obtains product 2-thiophen acetyl chloride; Wherein the material mass ratio that feeds intake is 2-thiophene acetic acid: sulfur oxychloride=1:2-3, the consumption of methylene chloride be 2-thiophene acetic acid quality 3-4 doubly.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410266505.2A CN104016962A (en) | 2014-06-16 | 2014-06-16 | Process for synthetizing 2-thiopheneacetyl chloride |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410266505.2A CN104016962A (en) | 2014-06-16 | 2014-06-16 | Process for synthetizing 2-thiopheneacetyl chloride |
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| Publication Number | Publication Date |
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| CN104016962A true CN104016962A (en) | 2014-09-03 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN201410266505.2A Pending CN104016962A (en) | 2014-06-16 | 2014-06-16 | Process for synthetizing 2-thiopheneacetyl chloride |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111560005A (en) * | 2020-05-29 | 2020-08-21 | 安达市海纳贝尔化工有限公司 | Preparation method of 2-thiopheneacetyl chloride |
| CN112225720A (en) * | 2020-11-10 | 2021-01-15 | 吴仁涛 | Production method of thiophene-2-acetyl chloride |
| CN114989133A (en) * | 2022-06-16 | 2022-09-02 | 河南立诺制药有限公司 | Environment-friendly preparation method of 2-thiopheneacetyl chloride |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1324356A (en) * | 1998-10-23 | 2001-11-28 | 道农业科学公司 | Process for preparing 3-(substituted phenyl)-5-thienyl or fully)-1,2,4-triazoles and nove. intermediates utilized therein |
| CN101880271A (en) * | 2010-07-16 | 2010-11-10 | 连云港宏业化工有限公司 | Synthesis method of 2-thiophene acetylchloride |
| CN103113318A (en) * | 2013-02-26 | 2013-05-22 | 南京工业大学 | New etoxazole compounds, and preparation method and acarid killing activities thereof |
-
2014
- 2014-06-16 CN CN201410266505.2A patent/CN104016962A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1324356A (en) * | 1998-10-23 | 2001-11-28 | 道农业科学公司 | Process for preparing 3-(substituted phenyl)-5-thienyl or fully)-1,2,4-triazoles and nove. intermediates utilized therein |
| CN101880271A (en) * | 2010-07-16 | 2010-11-10 | 连云港宏业化工有限公司 | Synthesis method of 2-thiophene acetylchloride |
| CN103113318A (en) * | 2013-02-26 | 2013-05-22 | 南京工业大学 | New etoxazole compounds, and preparation method and acarid killing activities thereof |
Non-Patent Citations (1)
| Title |
|---|
| MROZEK THOMAS等: "Multimode-photochromism based on strongly coupled dihydroazulene and diarylethene", 《CHEMISTRY EUROPEAN JOURNAL》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111560005A (en) * | 2020-05-29 | 2020-08-21 | 安达市海纳贝尔化工有限公司 | Preparation method of 2-thiopheneacetyl chloride |
| CN112225720A (en) * | 2020-11-10 | 2021-01-15 | 吴仁涛 | Production method of thiophene-2-acetyl chloride |
| CN114989133A (en) * | 2022-06-16 | 2022-09-02 | 河南立诺制药有限公司 | Environment-friendly preparation method of 2-thiopheneacetyl chloride |
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Application publication date: 20140903 |