Method for continuously producing prothioconazole by utilizing micro-channel reactor and micro-channel system

Abstract

The invention relates to a method for continuously producing prothioconazole by utilizing a micro-channel reactor and a micro-channel system and belongs to the technical field of organic synthesis processes. The method comprises the following steps: taking 2-(1-chloro-cyclopropyl)-1-(2-chlorphenyl)-3-hydrazino-propyl-2-ol as a raw material, carrying out a cyclization and oxidization two-step reaction in the micro-channel reactor so as to continuously complete a preparation process of prothioconazole, introducing the material into the micro-channel reactor by a metering pump, performing preheating, mixed reaction and quenching crystallization separation so as to obtain the product prothioconazole. According to the method, mass transfer and heat transfer in the reaction process can be enhanced, the reaction temperature and reaction time are accurately controlled, side reactions and a reactant auto-polymerization phenomenon caused by material enrichment in the cyclization process are avoided, and conditions that the side reactions are increased due to 'temperature runaway' and reactive oxygen species overflow in the oxidization process and the like are also avoided. The reaction timeis finally reduced, the atom utilization ratio is improved, the reaction conversion rate is greatly improved, and production of solid wastes and side reactions is reduced.

Description

technical field [0001] The present invention belongs to the production method of prothioconazole, relates to a kind of preparation method of triadimefon bactericide prothioconazole, more specifically in microchannel reactor with 2-(1-chlorocyclopropane Base)-1-(2-chlorophenyl)-3-hydrazinopropan-2-ol is a method for producing prothioconazole through a two-step reaction of cyclization and oxidation. Background technique [0002] Prothioconazole is a demethylation inhibitor (DMIs) developed by Bayer. Its mechanism of action is to inhibit the 14-position demethylation of lanosterol, the precursor of sterols in fungi. It has a bactericidal spectrum Wide range, good systemic activity, high protection, treatment and eradication activity, long effective period and so on. Through a large number of field efficacy tests, the results show that prothioconazole not only has good safety for crops, but also has obvious effects in disease prevention and treatment, and has a good effect in i...

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Problems solved by technology

[0003] The preparation method of prothioconazole mainly contains two kinds at present, and one is to react (US4913727) with hydroxytriazole and sulfur, with sulfur as the source of sulfur atom of prothioconazole compound, and U.S. Patent US5789430 discloses this type of method, It includes using N-methylpyrrolidone as a solvent to react at 200°C for 44 hours to obtain prothioconazole, with a yield of 20%, and first using n-butyllithium to extract hydrogen under ultra-low temperature conditions in a tetrahydrofuran solvent, and then reacting with sulfur, with a yield of 93%, U.S. Patent US2013005985 further improved this method, using Grignard reagents such as isopropylmagnesium chloride instead of n-butyllithium for hydrogen extraction and resulfurization to prepare prothioconazole, this method solved the problem of ultra-low temperature reaction and n-butyllithium reagent danger problem, but requires more than two equivalents of expensive format reagents, and the yield is reduced to 68%

There are two major defects in this type of method. One of the key intermediates is prepared by reacting triazole with chloride (US4913727) or epoxy compound (US5146001) as the starting material. This type of substitution reaction inevitably exists selective isomerization The by-products need to be further refined and removed, resulting in a decrease in yield; secondly, when sulfur is used for thiolation, it is inevitable to use expensive dangerous compounds under high temperature or ultra-low temperature conditions, which makes this technical solution costly and poor in operability. Not conducive to industrial production

[0004] Another kind is to be starting raw material with 2-chloro-1-(1-chlorocyclopropyl) ethyl ketone, first hydrazine and formaldehyde again, thiocyanate ring closure reoxidation (US6201128, US6559317, CT Ivnt.Appl .2001046158, etc.), this type of method can not only avoid the generation of isomer solid waste from the source, but also avoid the use of a series of reaction conditions that are not suitable for industrial production such as high temperature, ultra-low temperature, and dangerous chemicals. The ring reaction process is not easy to control, and there are many solid wastes that are not conducive to industrial production.

[0005] For example, in US6559317, in the preparation of compound V, 2-chloro-1-(1-chlorocyclopropyl)ethanone is first prepared into hydrazine and then passed through hydrogen chloride to form a salt for extraction, and then neutralized with alkali in the subsequent reaction. Formaldehyde, sodium thiocyanate, sodium bisulfate reaction, not only the reaction steps are cumbersome, but also lead to a large amount of solid waste

[0006] The reactors of the prothioconazole preparation process reported in the above-mentioned patent publications are all reaction bottles with stirring or stirred reactors, and the reaction methods are all intermittent operations. A large amount of solvent needs to be added to the reaction system to make the system homogeneous, and There are often problems such as low heat exchange capacity and serious liquid-liquid mass transfer barriers, which make the process control in intermittent fluctuations, low reaction efficiency, many side reactions, high material consumption, and large discharge of three wastes

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