Synthesis method of cinnamyl piperazine

A technology of cinnamylpiperazine and synthesis method, applied in the direction of organic chemistry, etc., can solve the problems of increased pollution, high energy consumption, high production cost, etc., and achieve the effects of reducing production steps, reducing pollution problems, and reducing the amount of acid used

Inactive Publication Date: 2017-02-01
郑州瑞康制药有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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 ...

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] The synthetic method of the cinnamylpiperazine of the present embodiment, the steps are as follows:

[0025] (1) Put 100g of ethanol into a glass reaction bottle with a capacity of 500 mL, add 86g of piperazine under stirring, cool down to below 20°C, keep the temperature at 20~25°C, and drop 220g of hydrochloric acid with a mass fraction of 36% to make the reaction liquid pH = 2, react for 1 hour after the dropwise addition, cool to 20°C, collect piperazine dihydrochloride solid 141g by centrifugation, the mother liquor can be concentrated again, crystallize, and collect piperazine dihydrochloride by centrifugation;

[0026] (2) Put 69 grams of ethanol into a 500mL reaction flask, stir and put 30g of piperazine dihydrochloride and 15g of piperazine into it, heat up to 78°C and reflux for 1 hour;

[0027] (2) Cool down to 55°C and add 25.7g of cinnamyl chloride dropwise. After the dropwise addition, raise the temperature to 65°C and keep it warm for 2 hours;

[0028] (...

Embodiment 2

[0031] A kind of synthetic method of cinnamylpiperazine, the steps are as follows:

[0032] (1) Put isopropanol into the reaction kettle, add piperazine, stir to dissolve all piperazine, add hydrochloric acid dropwise at 24°C to make the reaction solution PH = 2 as the end point, and cool to 20°C after reacting for 1 hour. Centrifugal filtration to obtain piperazine dihydrochloride, and the mother liquor can be further concentrated to obtain piperazine dihydrochloride;

[0033] (2) Put propanol into the reaction kettle, add 28g of piperazine dihydrochloride and 14g of piperazine while stirring, and react at 75°C for 2 hours;

[0034] (3) Cool down to 50°C and add 24g of cinnamyl chloride dropwise. After the dropwise addition, raise the temperature to 70°C and keep it warm for 2 hours, then cool down to 20°C, centrifuge and recover the solid filter cake to obtain piperazine dihydrochloride for recycling. The mother liquor is pumped into the distillation reactor;

[0035] (4) ...

Embodiment 3

[0037] A kind of synthetic method of cinnamylpiperazine, the steps are as follows:

[0038] (1) Put the solvent ethanol into the reaction kettle, add piperazine, stir to dissolve all the piperazine, add hydrochloric acid dropwise at 20°C to make the reaction solution PH = 2 as the end point, react for 1 hour, cool to 20°C, and centrifuge Shake filtration to obtain piperazine dihydrochloride, and the mother liquor can continue to be concentrated to obtain piperazine dihydrochloride;

[0039] (2) Put ethanol into the reaction kettle, add 42g of piperazine dihydrochloride and 21g of piperazine while stirring, and react at 68°C for 3 hours;

[0040] (3) Cool down to 45°C and add 36g of cinnamyl chloride dropwise. After the dropwise addition, raise the temperature to 60°C and keep it warm for 4 hours, then cool down to 10°C, centrifuge and recover the solid filter cake to obtain piperazine dihydrochloride for recycling. The mother liquor is pumped into the distillation reactor;

...

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PUM

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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...

Claims

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Application Information

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IPC IPC(8): C07D295/03C07D295/023
CPCC07D295/03C07D295/023
Inventor 张杰张国用李明轩刘媛媛
Owner 郑州瑞康制药有限公司
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