Synthesis method of cinnamyl piperazine

Abstract

The invention discloses a synthesis method of cinnamyl piperazine. The method includes the steps of: a) adding a solvent into a reaction kettle and adding piperazine to uniformly dissolve the piperazine, dropwisely adding hydrochloric acid at 20-25 DEG C until the pH of the reaction solution is 2, which is the terminal, and after the reaction is performed for 1 h, cooling the reaction solution to 20 DEG C, and centrifugally spin-filtering the reaction solution to obtain piperazine dihydrochloride; b) adding the solvent into the reaction kettle, adding the piperazine dihydrochloride and the piperazine with stirring at the same time, and performing a reaction at 68-85 DEG C for 0.5-3 h; c) reducing the temperature to 45-55 DEG C, dropwisely adding cinnamyl chloride, and then increasing the temperature to 60-75 DEG C to perform a temperature maintained reaction for 1-4 h, and reducing the temperature to 10-35 DEG C, performing centrifugal separation, sucking a mother liquid into a distillation reaction kettle, heating the distillation mother liquid to recycle the solvent, adding pure water, and dropwisely adding an alkali liquid to regulate the pH to 9-12, and adding chloroform to perform extraction, drying the mixture, and evaporate-drying the chloroform to obtain the cinnamyl piperazine. The synthesis method reduces production steps and pollutant emission, and is more suitable for modern industrial production.

Description

technical field [0001] The invention belongs to the field of organic chemical synthesis, and in particular relates to a synthesis method of cinnamyl piperazine. Background technique [0002] Cinnamylpiperazine is a synthetic intermediate of flunarizine hydrochloride, which is a calcium channel blocker that can prevent cell damage caused by intracellular pathological calcium overload caused by ischemia and other reasons. The effects of flunarizine hydrochloride are as follows: 1. It can relieve vasospasm, and has a lasting inhibitory effect on the persistent vasospasm caused by vasoconstrictor substances, especially on the basilar artery and internal carotid artery, and its effect is stronger than that of naoyizine by 15 2. The vestibular inhibitory effect can increase the blood flow of cochlear arterioles and improve the vestibular organ circulation; 3. Anti-epileptic effect, this product can block the pathological calcium overload of nerve cells and prevent paroxysmal depol...

AI Technical Summary

Problems solved by technology

[0006] In the first issue of "Fine Petrochemical Industry" in 2001, the paper on the synthesis of cinnamylpiperazine from piperazine dihydrochloride used potassium hydroxide as an acid scavenger. Hydrochloric acid becomes cinnamylpiperazine hydrochloride, and then neutralized and extracted, which obviously increases pollution and costs, which is not conducive to large-scale production

[0007] In the paper on the improvement of the synthesis process of flunarizine hydrochloride in the fourth issue of "Chemical Progress" in volume 34 in 2015, the piperazine used is 4.3 times that of cinnamyl chloride, which greatly increases the production cost, and the final treatment is to use hydrochloric acid to form a salt first , and then use lye to neutralize, which not only increases the cost, but also increases the pollution

[0008] In summary, the existing intermediate cinnamylpiperazine preparation process has various defects such as complex reaction process, serious pollution, or high energy consumption and high production cost.