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CN-121976208-A - Method for preparing albendazole sulfoxide through electrochemical micro-channel

CN121976208ACN 121976208 ACN121976208 ACN 121976208ACN-121976208-A

Abstract

The invention provides a green and efficient preparation method of an insect repellent albendazole sulfoxide, which takes water as a green oxygen source, drives anodic oxidation reaction through electric energy at room temperature, synthesizes albendazole sulfoxide with high selectivity, and effectively avoids excessive oxidation to generate sulfone byproducts. The method is that albendazole, cheap electrolyte sodium bromide, dimethyl sulfoxide and water are mixed into homogeneous reaction liquid, and the homogeneous reaction liquid is introduced into an electrochemical microchannel continuous reactor without inert gas protection to realize oxidation. Compared with the traditional hydrogen peroxide oxidation and low-temperature chemical oxidation method, the method does not need to use stoichiometric oxidant, has mild reaction conditions, effectively avoids related safety and environmental risks, meets the requirement of green sustainable development, and has good industrial application prospect.

Inventors

  • HUANG DA
  • YANG LIU
  • WANG CHANGSHENG
  • SHEN LEI
  • LI YUGUANG

Assignees

  • 南京先进生物材料与过程装备研究院有限公司

Dates

Publication Date
20260505
Application Date
20260211

Claims (6)

  1. 1. The research reports a new method for preparing the insect repellent albendazole sulfoxide by continuous flow oxidation of a green electrochemical microchannel. The method is characterized in that albendazole and water are subjected to electrochemical oxidation reaction in an electrochemical microchannel continuous reaction device to prepare albendazole sulfoxide products; the structures of the albendazole, the water and the albendazole sulfoxide are shown in the following formulas I, II and III respectively:
  2. 2. the method of claim 1, wherein the electrical reaction is performed in an electrochemical microchannel continuous flow reaction apparatus.
  3. 3. The method of claim 2, wherein the albendazole is mixed with dimethyl sulfoxide, water and electrolyte to obtain a reaction solution, and the reaction solution is pumped into an electrochemical microchannel continuous flow reactor for electrochemical anodic oxidation reaction to obtain the albendazole sulfoxide product.
  4. 4. The method according to claim 3, wherein the volume ratio of the solvent dimethyl sulfoxide to water is 9:1, the concentration of albendazole in the reaction solution is 0.05 mmol/mL, the flow rate of the reaction solution pumped into the electrochemical micro-channel continuous flow reactor is 0.05-0.5 mL/min, the reaction temperature is room temperature, and the constant current of the electric reaction is 140-300 mA.
  5. 5. The method of claim 3, wherein the electrolyte is any one of tetraethylammonium chloride, tetrabutylammonium hexafluorophosphate, tetrabutylammonium acetate, tetrabutylammonium fluoride, sodium chloride, lithium perchlorate, tetraethylammonium chloride, and sodium bromide.
  6. 6. The method of claim 3, wherein the electrochemical micro-channel continuous flow reaction device comprises an injection pump, an electrochemical micro-channel continuous flow reactor, an electric box and a receiving bottle, wherein the injection pump, the electrochemical micro-channel continuous flow reactor and the receiving bottle are sequentially connected in series through a polytetrafluoroethylene connecting pipeline, the anode of the electrochemical micro-channel continuous flow reactor is a platinum sheet plate, the cathode of the electrochemical micro-channel continuous flow reactor is a graphite plate, the electric box is used for applying current at two ends of the electrochemical micro-channel continuous flow reactor, the positive electrode of the electric box is connected with the anode end of the electrochemical micro-channel continuous flow reactor, the negative electrode of the electric box is connected with the cathode end of the electrochemical micro-channel continuous flow reactor, and the reaction volume of the electrochemical micro-channel continuous flow reactor is 5 mL.

Description

Method for preparing albendazole sulfoxide through electrochemical micro-channel Technical Field The invention belongs to the technical field of electromechanical chemical oxidation, and relates to a method for preparing an insect repellent albendazole sulfoxide in a continuous flow mode of an electrochemical micro-channel. Background Albendazole sulfoxide is a high-efficiency broad-spectrum benzimidazole anthelmintic and has extremely important application in the fields of human medicine and veterinary medicine. The prodrug is a primary active metabolite of albendazole in vivo, sulfoxide groups and other key pharmacophores in the molecular structure form the basis ,（J. Biochem. Biophys. Methods, 2002, 54, 339-345., J. Pharm. Biomed. Anal. 2002, 27, 555-567., ACS Catal. 2017, 7, 7587-7592., Antimicrob. Agents Chemother. 2019, 63, e0248918.）. of pharmacological activity, the albendazole sulfoxide has stable chemical property, and the prodrug can effectively act on tubulin of parasites and inhibit energy metabolism of the parasites, thereby exerting a strong insect repellent effect. In addition, as a substance which directly exerts the efficacy in vivo, albendazole sulfoxide has better bioavailability and tissue permeability than albendazole, can be more efficiently distributed in target tissues, and ensures the full exertion of the curative effect. Due to the excellent insect repellent activity and pharmacokinetics, albendazole sulfoxide has become one of the main stream products in the current antiparasitic drug market, and has huge market demand and broad development prospect. Currently, the industrial production of albendazole sulfoxide is almost entirely achieved by the process route of selective oxidation of albendazole. Therefore, how to develop a green, economical and high-selectivity synthesis process to realize the high-efficiency preparation of albendazole sulfoxide has great industrial significance. At present, the industrial synthesis of albendazole sulfoxide mainly depends on an equivalent chemical oxidation method, and a batch kettle type batch production mode is generally adopted. The traditional production mode has obvious limitations, and the core challenge is that the product selectivity of the oxidation process is controlled, namely, due to the structural characteristics of thioether in the albendazole molecules, if the control is improper in the oxidation process, peroxidation is easy to occur, and inactive albendazole sulfone byproducts are generated, so that the yield of the target product is low, the purity of the product is low and the purification is difficult. Currently, the oxidation process is commonly carried out industrially by using an oxidation system such as m-chloroperoxybenzoic acid (m-CPBA) or a hydrogen peroxide-metal catalyst (RSC adv. 2014, 4, 46545-46554, J. Chem. Duc. 2008, 85, 1652). The former is costly and the post-treatment produces a large amount of chlorine-containing wastewater and organic acid, while the latter has metal residues and is demanding in terms of reaction conditions. The methods can generate excessive harmful three wastes, cause larger pressure on the environment and have high post-treatment cost. Meanwhile, the academic world has explored other novel routes, but the method still faces great challenges in the aspects of reaction efficiency, catalyst cost and scale, and industrial application has not been realized. In summary, the defects of the existing chemical oxidation process in efficiency, selectivity and environmental protection seriously restrict the high-quality, low-cost and green preparation of albendazole sulfoxide. Disclosure of Invention The invention aims to solve the problems of poor reaction selectivity, easy peroxidation, need of using equivalent oxidant and the like in the prior art of albendazole sulfoxide synthesis method, and provides a method for preparing albendazole sulfoxide by using an electrochemical micro-channel continuous flow reactor. The invention takes albendazole as a raw material, and adopts an electrochemical catalytic oxidation strategy in a microchannel reactor to directly and highly selectively convert the albendazole into albendazole sulfoxide. The method can accurately control the oxidation process by regulating and controlling electrochemical parameters such as current, flow speed, electrolyte and the like without adding chemical oxidant or metal catalyst, and effectively inhibit the generation of sulfone peroxidation byproducts. The method has the outstanding advantages of high reaction selectivity, high product yield and purity, simple and convenient reaction operation and environmental protection. In order to achieve the above purpose, the invention provides a method for continuously preparing albendazole sulfoxide by using an electrochemical micro-channel reaction device, which comprises the following specific steps: (1) Dissolving raw materials albendazole and electrolyte in a proper solvent to obtain