Beta receptor blocker Acebutolol intermediate synthesized by photochemical Fries rearrangement

A photochemical and β-receptor technology, which is applied in the fields of organic photochemistry and medicinal chemistry, can solve problems such as high cost, high toxicity and pollution, and complex reaction operations, and achieve the effects of low pollution, simple and easy synthesis methods, and simple purification operations

Pending Publication Date: 2021-10-22
山东盛安贝新材料有限公司
View PDF3 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The purpose of the present invention is to provide an environmentally friendly and green chemical synthesis method to synthesize beta receptor blockers in order to overcome the existing problems in the prior art, such as high toxicity and pollution of reagents used, high cost, and complicated reaction operations. Acebutolol intermediate 2-acetyl-4-n-butyrylaminophenol

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Beta receptor blocker Acebutolol intermediate synthesized by photochemical Fries rearrangement
  • Beta receptor blocker Acebutolol intermediate synthesized by photochemical Fries rearrangement

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] 1.1. Put 2.64g of n-butyric anhydride, 1.09g of p-aminophenol, and 3.40g of toluene into the reaction flask, heat up and reflux for dehydration. Reflux for about 9 hours, (moisture content is about 1.45g) carry out atmospheric distillation and reclaim toluene. After recovering about 80% of the amount of toluene, carry out vacuum distillation to evaporate the toluene. Cool to T<35°C, add 10 g of water, stir and dropwise add 6.00 g of sodium hydroxide, and then dropwise add 2.20 g of acetic anhydride. Stir for 3.5 hours and filter. Recrystallized from acetone. Activated carbon decolorization, hot filtration. The crystalline product was dried and weighed to obtain 1.43 g of N-(4-acetoxyphenyl)butyramide, with a yield of 65.1%.

[0027] 1.2. Put 1.1 g of the intermediate product N-(4-acetoxyphenyl) butyramide in the above step 1.1 into a photoreaction container and add 5.5 g of tetrahydrofuran, and after fully dissolving, use ultraviolet-visible light to irradiate the p...

Embodiment 2

[0029] 2.1. Put 2.85g of n-butyric anhydride, 1.09g of p-aminophenol, and 3.40g of toluene into the reaction flask, heat up and reflux for dehydration. Reflux for about 8 hours, (moisture content is about 1.45g) carry out atmospheric distillation and reclaim toluene. After recovering about 80% of the amount of toluene, carry out vacuum distillation to evaporate the toluene. Cool to T<35°C, add 20g of water, stir and dropwise add 6.00g of potassium hydroxide, and then dropwise add 2.30g of acetic anhydride. Stir for 3.5 hours and filter. Recrystallized from acetone. Activated carbon decolorization, hot filtration. The crystalline product was dried and weighed to obtain 1.23 g of N-(4-acetoxyphenyl)butyramide, with a yield of 61.3%.

[0030] 2.2. Put 1.1 g of the intermediate product N-(4-acetoxyphenyl) butyramide in the above step 2.1 into a photoreaction container and add 5.5 g of tetrahydrofuran, fully dissolve and irradiate the photoreaction container with ultraviolet-vi...

Embodiment 3

[0032] 3.1. Put 3.15g of n-butyric anhydride, 1.09g of p-aminophenol, and 3.40g of toluene into the reaction bottle, and heat up and reflux for dehydration. Reflux for about 10 hours, (moisture content is about 1.45g) carry out atmospheric distillation and reclaim toluene. After recovering about 81% of the amount of toluene, carry out vacuum distillation to evaporate the toluene. Cool to T<35°C, add 20 g of water, stir and add 6.00 g of potassium hydroxide dropwise, and then add dropwise 2.70 g of acetic anhydride. Stir for 4.5 hours and filter. Recrystallized from acetone. Activated carbon decolorization, hot filtration. The crystalline product was dried and weighed to obtain 1.47 g of N-(4-acetoxyphenyl)butyramide, with a yield of 73.2%.

[0033] 3.2. Put 1.1 g of the intermediate product N-(4-acetoxyphenyl) butyramide in the above step 3.1 into the photoreaction container and add 6.6 g of tetrahydrofuran, and after fully dissolving, use ultraviolet-visible light to irra...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

The invention belongs to the field of organic photochemistry and medicinal chemistry, and particularly relates to a beta receptor blocker Acebutolol intermediate synthesized by photochemical Fries rearrangement. An efficient continuous acetylation synthesis method is adopted, raw materials including p-aminophenol and n-butyric anhydride are mixed and subjected to a water diversion reaction with a water-carrying agent, then the water-carrying agent is removed through distillation, reactants are cooled, water is added as a dispersing agent, then liquid caustic soda is added for a reaction, phenate is generated, acetic anhydride is dropwise added, the mixture is stirred for a reaction, ester is generated, recrystallizing is carried out to generate a first-step product N-(4-acetoxyphenyl) butyrylamide; and in the step 2 photochemical Fries liquid phase rearrangement reaction is adopted, the product in the first step is dissolved in an organic solvent, then Fries rearrangement is carried out by irradiation of ultraviolet-visible light with a specific wavelength, the solvent is heated and evaporated after the reaction is completed, and the important intermediate 2-acetyl-4-n-butyryl aminophenol of Acebutolol is obtained after recrystallization. The method is simple and easy to implement, and low-toxicity, efficient and cheap green chemical reagents are used in the synthesis process.

Description

technical field [0001] The invention belongs to the fields of organic photochemistry and medicinal chemistry, and particularly relates to a photochemical Fries rearrangement synthesis of a beta receptor blocker Acebutolol intermediate. Background technique [0002] The description of the background technology of the present invention and the relevant technologies related to the present invention are only used for illustration and to facilitate the understanding of the content of the present invention, and should not be understood as the applicant's definite or inferred that the applicant believes that the present invention is the application for the first application day's prior art. [0003] Acebutolol is a beta 1 - Adrenergic receptor-selective commonly used cardiovascular drugs (beta-receptor blockers), which can be used to treat high blood pressure, and can also be used to treat arrhythmia, myocardial infarction and other diseases. 2-Acetyl-4-n-butyrylaminophenol is an...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Applications(China)
IPC IPC(8): C07C231/02C07C231/12C07C231/24C07C233/25C07C233/33
CPCC07C231/02C07C231/12C07C231/24C07C233/25C07C233/33
Inventor 姜珍华赵嘉邵昌尧高然许延想周法政闫浩磊王魁
Owner 山东盛安贝新材料有限公司
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap