CN114989133A - Environment-friendly preparation method of 2-thiopheneacetyl chloride - Google Patents
Environment-friendly preparation method of 2-thiopheneacetyl chloride Download PDFInfo
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- CN114989133A CN114989133A CN202210679125.6A CN202210679125A CN114989133A CN 114989133 A CN114989133 A CN 114989133A CN 202210679125 A CN202210679125 A CN 202210679125A CN 114989133 A CN114989133 A CN 114989133A
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- thiopheneacetyl 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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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/584—Recycling of catalysts
Abstract
The invention provides an environment-friendly preparation method of 2-thiophene acetyl chloride, belonging to the technical field of preparation of acyl chloride compounds, and the preparation method comprises the steps of dissolving triphosgene in an organic solvent, stirring at low temperature, adding a catalyst at low temperature after full dissolution, stirring at low temperature for reaction, then adding 2-thiophene acetic acid, continuing to react at low temperature, after the reaction is finished, adding water for washing, separating liquid, discarding a water phase, retaining an organic phase, and distilling the organic phase under reduced pressure to obtain the 2-thiophene acetyl chloride. The solvent can be recovered, the product is easy to separate and purify, the purity of the 2-thiophene acetyl chloride product reaches more than 99 percent, the reaction yield reaches more than 90 percent, and no other three wastes are discharged except the waste water containing the hydrogen chloride in the whole process; the preparation method has the advantages of simple preparation process, short production period, high product purity, high yield, economy and environmental protection; the raw materials are economical and easily obtained, safe and stable, have good economic value and are suitable for industrial production.
Description
Technical Field
The invention relates to the technical field of preparation of acyl chloride compounds, and particularly relates to an environment-friendly preparation method of 2-thiophene acetyl chloride.
Background
Thiophene heterocyclic compounds are widely used in medicine, agriculture, industry, and the like, and thus have received great attention from researchers in a variety of fields including organic synthetic chemistry, biochemistry, and pharmacology. The compound is more derivatives of the compound, wherein the dosage and variety of alpha-position thiophene derivatives are larger and more than those of beta-position thiophene derivatives.
2-thiophene acetyl chloride is an important intermediate of cephalo-drugs of cephalo-thiophene, cefoxitin and cefalonium, and has better effect than 2-thiophene acetic acid as an acylating agent. For the research of 2-thiophene acetyl chloride, thionyl chloride is used as an acyl chlorinating agent in the current literature and patent reports, the thionyl chloride is used as a solvent and participates in the reaction, the yield of the method is low, and the input amount of the thionyl chloride is too small under the condition of serving as the solvent and the reactant, so that the raw material is not completely converted. Since the reaction process is fast, it is difficult to control and impurities are easily generated. The method has the advantages of large consumption of thionyl chloride, difficult treatment of waste gas, difficult purification of products, more impurities, serious corrosion of equipment and high production cost.
Therefore, it is desirable to provide an environmentally friendly method for preparing 2-thiopheneacetyl chloride, which solves the above existing problems.
Disclosure of Invention
In view of the above, the invention provides an environment-friendly preparation method of 2-thiopheneacetyl chloride, which has the advantages of simple process, mild reaction conditions, short production period, high product purity and high yield, and meanwhile, the method has the advantages of economic and easily obtained raw materials, safety and stability, good economic value and suitability for industrial production.
Dissolving triphosgene in an organic solvent, stirring at low temperature, adding a catalyst at low temperature after full dissolution, stirring at low temperature for reaction, then adding 2-thiopheneacetic acid, continuing to react at low temperature, after the reaction is finished, adding water for washing, separating liquid, removing a water phase, keeping an organic phase, and distilling the organic phase under reduced pressure to obtain the 2-thiopheneacetyl chloride.
Further, the concentration of triphosgene dissolved in the organic solvent is 0.10-0.40 g/ml.
Further, the molar ratio of the catalyst to the triphosgene is 0.5-2.0.
Furthermore, the molar ratio of the 2-thiopheneacetic acid to the triphosgene is 0.6-1.1.
Further, the organic solvent comprises one or more of esters, alcohols, hydrocarbons and ketones.
Further, after the catalyst is added at a low temperature, stirring at the low temperature for reaction for 30-120 min.
Further, adding 2-thiopheneacetic acid, continuously reacting at low temperature for 60-120 min, detecting the 2-thiopheneacetic acid by using HPLC, and finishing the reaction when the residual percentage of the 2-thiopheneacetic acid on an HPLC chromatogram is less than 0.5%.
Furthermore, the catalyst is one or more of N, N-dimethylformamide, N-dimethylacetamide, imidazole, pyridine and triethylamine.
Further, the low temperature is required to be-30 ℃ to 0 ℃.
The technical scheme of the invention at least comprises the following beneficial effects:
1. the preparation method of the 2-thiophene acetyl chloride of the invention replaces the carbon tetrachloride and the tetrachloroethylene of the original process with common organic solvents, adopts triphosgene to replace thionyl chloride, and has mild conditions;
2. in the whole preparation reaction process, except the waste water containing the hydrogen chloride, no other three wastes are discharged, so that the method is more environment-friendly;
3. the triphosgene is used for preparing the 2-thiophene acetyl chloride, the reaction is thorough, the purity is high, the organic solvent is easy to recover, the product is easy to separate and purify, the yield is high, and the economic benefit is high;
4. the raw materials are economical and easily obtained, safe and stable, have good economic value and are suitable for industrial production.
Detailed Description
The following examples illustrate the present invention in detail, but are not intended to limit the invention thereto. The described embodiments are only some, but not all embodiments of the invention. All other embodiments, which can be derived by a person skilled in the art from the described embodiments of the invention, are within the scope of the invention.
Dissolving triphosgene in organic solvent, stirring at low temperature, adding catalyst at low temperature after full dissolution, stirring at low temperature for reaction, adding 2-thiopheneacetic acid, continuing to react at low temperature, adding water for washing after the reaction is finished, separating liquid, discarding water phase, retaining organic phase, and distilling organic phase under reduced pressure to obtain 2-thiopheneacetyl chloride.
Further, the concentration of triphosgene dissolved in the organic solvent is 0.10-0.40 g/ml.
Further, the molar ratio of the catalyst to the triphosgene is 0.5-2.0.
Further, the molar ratio of the 2-thiopheneacetic acid to the triphosgene is 0.6-1.1.
Further, the organic solvent comprises one or more of esters, alcohols, hydrocarbons and ketones.
Further, after the catalyst is added at a low temperature, stirring at the low temperature for reaction for 30-120 min.
Further, adding 2-thiopheneacetic acid, continuously reacting at low temperature for 60-120 min, detecting the 2-thiopheneacetic acid by using HPLC, and finishing the reaction when the residual percentage of the 2-thiopheneacetic acid on an HPLC chromatogram is less than 0.5%.
Furthermore, the catalyst is one or more of N, N-dimethylformamide, N-dimethylacetamide, imidazole, pyridine and triethylamine.
Further, the low temperature is required to be-30 ℃ to 0 ℃.
Example 1
Dissolving 24g of triphosgene in 200ml of dichloromethane, controlling the temperature to be minus 30 to minus 20 ℃ under stirring, adding 13g of DMAC after clearing, controlling the temperature to be minus 25 ℃, and stirring for reacting for 45 min. Adding 25g of 2-thiopheneacetic acid, controlling the temperature to be minus 30 to minus 15 ℃, reacting for 60min, detecting by HPLC, and ending the reaction when the 2-thiopheneacetic acid residue is less than 0.5 percent. 100ml of ice water is added for washing twice, liquid separation is carried out, the water phase is discarded, and the organic phase is reserved. The organic phase is distilled and dripped out under reduced pressure to obtain the 2-thiophene acetyl chloride. The purity was 99.3% and the yield was 91.5%.
The production table for this example is as follows:
example 2
Dissolving 42g of triphosgene in 200ml of chloroform, controlling the temperature to be minus 20 to minus 10 ℃ under stirring, adding 20g of DMF after dissolving, controlling the temperature to be minus 15 ℃, and stirring for reaction for 30 min. Adding 25g of 2-thiopheneacetic acid, controlling the temperature to be minus 15 to minus 10 ℃, reacting for 90min, detecting by HPLC, and ending the reaction when the 2-thiopheneacetic acid residue is less than 0.5%. 100ml of ice water is added for washing twice, liquid separation is carried out, the water phase is discarded, and the organic phase is reserved. The organic phase is distilled and dripped out under reduced pressure to obtain the 2-thiophene acetyl chloride. The purity is 99.2 percent, and the yield is 92.8 percent.
The production table for this example is as follows:
example 3
Dissolving 45g of triphosgene in 200ml of dichloromethane, controlling the temperature to be 15 ℃ below zero to 0 ℃ under stirring, adding 12g of DMAC after the triphosgene is dissolved, controlling the temperature to be 5 ℃ below zero, and stirring for reacting for 80 min. Adding 25g of 2-thiopheneacetic acid, controlling the temperature to be-10-0 ℃, reacting for 30min, detecting by HPLC, and ending the reaction when the 2-thiopheneacetic acid residue is less than 0.5%. 100ml of ice water is added for washing twice, liquid separation is carried out, the water phase is discarded, and the organic phase is reserved. The organic phase is distilled and dripped out under reduced pressure to obtain the 2-thiophene acetyl chloride. The purity was 99.5% and the yield was 93.6%.
The production table for this example is as follows:
the foregoing is a preferred embodiment of the present invention, and it should be noted that it would be apparent to those skilled in the art that various modifications and enhancements can be made without departing from the principles of the invention, and such modifications and enhancements are also considered to be within the scope of the invention.
Claims (9)
1. An environment-friendly preparation method of 2-thiopheneacetyl chloride, which is characterized in that: dissolving triphosgene in an organic solvent, stirring at low temperature, adding a catalyst at low temperature after full dissolution, stirring at low temperature for reaction, then adding 2-thiopheneacetic acid, continuing to react at low temperature, adding water for washing after the reaction is finished, separating liquid, removing a water phase, retaining an organic phase, and distilling the organic phase under reduced pressure to obtain the 2-thiopheneacetyl chloride.
2. The environmentally friendly process of preparing 2-thiopheneacetyl chloride of claim 1, wherein: the concentration of triphosgene dissolved in the organic solvent is 0.10-0.40 g/ml.
3. The environment-friendly preparation method of 2-thiopheneacetyl chloride of claim 1, characterized in that: the molar ratio of the catalyst to the triphosgene is 0.5-2.0.
4. The environmentally friendly process of preparing 2-thiopheneacetyl chloride of claim 1, wherein: the molar ratio of the 2-thiopheneacetic acid to the triphosgene is 0.6-1.1.
5. The environmentally friendly process of preparing 2-thiopheneacetyl chloride of claim 1, wherein: the organic solvent comprises one or more of esters, alcohols, hydrocarbons and ketones.
6. The environmentally friendly process of preparing 2-thiopheneacetyl chloride of claim 1, wherein: after the catalyst is added at a low temperature, stirring and reacting at the low temperature for 30-120 min.
7. The environmentally friendly process of preparing 2-thiopheneacetyl chloride of claim 1, wherein: adding 2-thiopheneacetic acid, continuously reacting at low temperature for 60-120 min, detecting the 2-thiopheneacetic acid by using HPLC, and finishing the reaction when the residual percentage of the 2-thiopheneacetic acid on an HPLC graph is less than 0.5%.
8. The environment-friendly preparation method of 2-thiopheneacetyl chloride of claim 1, characterized in that: the catalyst is one or more of N, N-dimethylformamide, N-dimethylacetamide, imidazole, pyridine and triethylamine.
9. The environmentally friendly process of preparing 2-thiopheneacetyl chloride of claim 1, wherein: the requirement for low temperature is-30 ℃ to 0 ℃.
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20120277217A1 (en) * | 2009-10-28 | 2012-11-01 | Newlink Genetics Corporation | Imidazole Derivatives as IDO Inhibitors |
| CN103833724A (en) * | 2012-11-20 | 2014-06-04 | 上海医药工业研究院 | Preparation method of 5-penphene-2-formyl chloride |
| 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 |
| CN107011319A (en) * | 2017-04-24 | 2017-08-04 | 鲁东大学 | A kind of preparation method of 2 thiophen acetyl chloride |
| CN108947960A (en) * | 2018-10-27 | 2018-12-07 | 阜新孚隆宝医药科技有限公司 | A kind of synthetic method of 2- thiophen acetyl chloride |
| CN112851632A (en) * | 2020-12-29 | 2021-05-28 | 徐州砥研医药科技有限公司 | Method for efficiently preparing thiophene medical intermediate |
-
2022
- 2022-06-16 CN CN202210679125.6A patent/CN114989133A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20120277217A1 (en) * | 2009-10-28 | 2012-11-01 | Newlink Genetics Corporation | Imidazole Derivatives as IDO Inhibitors |
| CN103833724A (en) * | 2012-11-20 | 2014-06-04 | 上海医药工业研究院 | Preparation method of 5-penphene-2-formyl chloride |
| 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 |
| CN107011319A (en) * | 2017-04-24 | 2017-08-04 | 鲁东大学 | A kind of preparation method of 2 thiophen acetyl chloride |
| CN108947960A (en) * | 2018-10-27 | 2018-12-07 | 阜新孚隆宝医药科技有限公司 | A kind of synthetic method of 2- thiophen acetyl chloride |
| CN112851632A (en) * | 2020-12-29 | 2021-05-28 | 徐州砥研医药科技有限公司 | Method for efficiently preparing thiophene medical intermediate |
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