Synthesis method of diosmin raw medicine meeting EP7 version quality standards

Abstract

The invention discloses a synthesis method of diosmin. A microwave-assisted heating method is adopted, I2 and NaI are used as catalysts, the ethanol solution of K2CO3 and NaOH and a pyridine mixed solvent are used as reaction solvents for establishing a reaction system, hesperidin is dehydrogenized to prepare diosmin in one step, and the dehydrogenation process avoids high temperature and avoids use of a large amount of high-boiling-point toxic solvents such as pyridine, dimethyl sulfoxide and the like in the reaction solvent system. Through the invention, the total synthesis yield of the diosmin is more than 80%, and the product quality meets the EP7.0 standards. The method disclosed by the invention has the technical characteristics of easiness in acquisition of raw materials, mild reaction conditions, short reaction time, simplicity and convenience in operation, low production cost, good product quality and the like, and is suitable for industrialized production.

Description

[0001] technical field [0001] Biomedicine, chemical synthesis. Background technique Diosmin: alias 7-rutinoside, diosmin, English name Diosmin, chemical name 3',5,7-trihydroxy-4'-methoxyflavone, molecular formula C 28 h 32 o 15 , molecular weight 608.54, CAS number: 520-27-4, EINECS number: 208-289-7. Off-white or light yellow microcrystalline powder, almost insoluble in water, soluble in dimethyl sulfoxide, almost insoluble in ethanol, soluble in dilute alkaline solution. 1. It has a vitamin P-like effect, can reduce vascular fragility and abnormal permeability, and is also used as an adjuvant treatment for the prevention and treatment of hypertension and arteriosclerosis. The effect of treating capillary fragility is stronger than that of rutin and hesperidin, and has Features of low toxicity. 2. After orthopedic surgery, the change of lower extremity pain was basically the same as the change of swelling subsided. Compared with the control group, the micronized...

AI Technical Summary

Problems solved by technology

X is to use high-boiling point DMF as the reaction solvent, the reaction temperature is above 120 ℃, and the reaction time is 8-12 hours.

High reaction temperature, long reaction time, high energy consumption and high cost

Literature "Luo Meng. Synthesis and research of diosmin [J] Chemical Intermediates, 2004, 6: 29-30. 》reported that the preparation of diomin is mostly prepared by one-step iodine dehydrogenation of hesperidin. This method uses pyridine as a solvent, and if it is scaled up to industrialization, it will seriously pollute the environment

The Journal of Fourth Military Medical University (J Fourth Mil Med—Univ) 2008, 29— (21) reported "The Improvement of Diosmin Synthetic Process Exactly Feng Xuan, Zhu Xingmei, Li Xiaoye" utilizes the physical characteristics of Diosmin soluble in dilute alkali, Alkaline-added ethanol solvent is used as the reaction solvent, which solves the problem of solvent residue, but the reaction temperature is above 150°C, and it is difficult to control the conventional heating method in production, requiring high temperature and high pressure equipment

In conclusion, according to market research and analysis, China's diosmin industry currently has high energy consumption, serious environmental pollution, low yield, difficult solvent residues, and weak technological innovation capabilities.

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