High yield preparation method of ligustrazine

Abstract

The invention discloses a high yield preparation method of ligustrazine. The method comprises the following steps: S1, adding 3-hydroxy-2-butanone, ammonium acetate, 28-33wt% hydrogen peroxide and water into a reaction vessel, rising the temperature of the mixture in the reaction vessel to 80-90 DEG C, insulating for 0.8-1.2 h, cooling to room temperature to obtain a mixed solution, and keeping stirring in the heating and heat preservation process; S2, adding 1.8-2.1mol / L sodium hydroxide solution the mixed solution from the S1 until the pH value reaches 9-10, then cooling to 10-15 DEG C, stirring for 10-20 min fir crystallization, filtering to obtain a filter cake, and washing the filter cake with water to obtain ligustrazine. The method greatly shortens reaction time, is more convenient , energy saving and environment-friendly in the purification processing, and the prepared ligustrazine is white needle crystal form with final yield is up to 91%, which is superior to the prior art.

Description

technical field [0001] The invention relates to the technical field of compound preparation, in particular to a high-yield preparation method of ligustrazine. Background technique [0002] Ligustrazine is an alkaloid isolated and purified from the rhizome of Ligusticum chuanxiong, a plant belonging to the genus Umbelliferae. The chemical name is 2,3,5,6-tetramethylpyrazine, referred to as tetramethylpyrazine. It has relatively good pharmacological effects such as dilating blood vessels, mildly lowering blood pressure, inhibiting platelet adhesion and aggregation and thrombus formation, and inhibiting the proliferation of smooth muscle cells and fibroblasts. Now it is mainly used clinically to treat occlusive vascular diseases, such as cerebral embolism, coronary heart disease, angina pectoris, vasculitis, chronic pulmonary heart disease, chronic renal failure, etc. [0003] Ligustrazine is a colorless needle crystal with a molecular weight of 138.20. The melting point is 8...

AI Technical Summary

Problems solved by technology

[0006] The disadvantage of the biological method is that the yield is low and the production process is complicated; while the extraction process of the separation and purification method is complicated, it needs to consume a large amount of organic solvents, and a large amount of organic solvents remain in the discharge, which is very polluting to the environment. Volatile characteristics, atmospheric distillation will distill with water vapor, resulting in high production costs and low yields

There are also many preparation methods in the chemical synthesis method, but often the reaction time is long, the energy consumption is large, and the yield is low. For example, the patent CN200610054510.2 provides a preparation method of ligustrazine, using 3-hydroxy-2-butanone, Ammonium acetate and ethanol are raw materials, N 2 Protection, using manganese dioxide or copper oxide as an oxidant, post-processing to obtain the product through two vacuum distillations, long reaction time, large energy consumption, and yield less than 72%

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