A kind of preparation method of troxerutin

Abstract

The invention discloses a method for preparing troxerutin, belongs to the field of chemical pharmaceutical technology, and mainly solves the problem that the troxerutin reaction selectivity of the prior art is not high and the yield is low. Rutin is placed in a beaker, methanol, diethylamine, ethylene oxide and 4-dimethylaminopyridine are added for heating reaction, pH is adjusted, crystallization is filtered, and washing is dried. A method for preparing troxerutin provided by the present invention does not need to be refined, and the obtained troxerutin content is ≥95%. The method for preparing troxerutin provided by the present invention controls the pH value of the solution through the reaction of rutin and ethylene oxide, reduces the reaction temperature, avoids troxerutin from over-reacting to generate a tetrasubstituted product, and simultaneously adds a catalyst 4-dimethylaminopyridine to promote rutin, a monosubstituted product and a disubstituted product to be converted into troxerutin, improves the reaction selectivity, thereby improving the yield.

Description

Technical Field

[0001] The invention relates to the technical field of chemical pharmacy, and more specifically, to a method for preparing troxerutin. Background Art

[0002] Troxerutin is also known as vitamin P4, hydroxyethyl rutin, vinorutin, toxerutin, etc. Its chemical formula is C 33 H 42 O 19 It can be used as an anticoagulant and has the effect of preventing thrombosis. It is suitable for hemiplegia, aphasia, myocardial infarction, arteriosclerosis, etc. caused by cerebral thrombosis and cerebral embolism.

[0003] This product is a semi-synthetic flavonoid compound made from rutin by hydroxyethylation. It has the function of inhibiting the aggregation of red blood cells and platelets, preventing thrombosis, and at the same time increasing the oxygen content in the blood, improving microcirculation, and promoting the formation of new blood vessels to enhance collateral circulation. It has a protective effect on endothelial cells, can resist vascular damage caused by 5-hydroxytryptamine and bradykinin, increase the resistance of capillaries, reduce the permeability of capillaries, and prevent edema caused by increased vascular permeability. It also has the functions of resisting radiation damage, inflammation, allergy, and ulcer.

[0004] At present, the methods for producing troxerutin basically use rutin and ethylene chloride as raw materials, react in an alcohol solution, add an alkaline catalyst to cause a substitution reaction, and then undergo hydroxyethylation to obtain a hydroxyethyl rutin mixture mainly composed of trihydroxyethyl rutin. However, when a strong base is used as a catalyst, side reactions such as hydrolysis and oxidation are prone to occur in the later stage, which increases the difficulty of purification. The yield is only 62%, and the industrialization cost is high. Therefore, it is very necessary to explore new catalysts to improve the production of the active ingredient trihydroxyethyl rutin. Summary of the invention

[0005] The invention aims to provide a method for preparing troxerutin. The method comprises the following steps: controlling the pH value of a solution and lowering the reaction temperature through the reaction of rutin and ethylene oxide to avoid excessive reaction of troxerutin to generate a tetrasubstituted product; and adding a catalyst 4-dimethylaminopyridine to promote the conversion of rutin, a monosubstituted product and a disubstituted product into troxerutin, thereby improving the reaction selectivity and thus improving the yield.

[0006] The technical scheme of the object of the present invention is: a preparation method of troxerutin, which comprises placing rutin in a beaker, adding methanol, diethylamine, ethylene oxide and 4-dimethylaminopyridine to carry out heating reaction, adjusting pH, crystallizing and filtering, washing and drying.

[0007] Preferably, in g / mL, the mass volume ratio of rutin to methanol solution is 1:2-5, the weight ratio of diethylamine to rutin is 1-4%, the weight ratio of ethylene oxide to rutin is 30-50%, and the weight ratio of 4-dimethylaminopyridine to rutin is 0.1-1%.

[0008] Preferably, the heating temperature is 40-60° C. and the heating time is 8-16 hours.

[0009] Preferably, hydrochloric acid is used to adjust the solution pH to 4-6.

[0010] Preferably, the crystallization temperature is 10-30°C and the crystallization time is 2-6h.

[0011] Preferably, the washing is a methanol washing.

[0012] Beneficial Effects

[0013] Compared with the prior art, the present invention has the following advantages:

[0014] 1. In the reaction of rutin and ethylene oxide, the pH value of the solution is controlled and the reaction temperature is lowered to avoid excessive reaction of troxerutin to generate a tetrasubstituted product. At the same time, the catalyst 4-dimethylaminopyridine is added to promote the conversion of rutin, a monosubstituted product and a disubstituted product into troxerutin, thereby improving the reaction selectivity and thus the yield.

[0015] 2. Methanol is both a reaction solvent and a recrystallization solvent. After the reaction is completed, it can be directly recrystallized and purified to obtain qualified troxerutin finished products. DETAILED DESCRIPTION

[0016] The present invention will be further described below in conjunction with specific embodiments.

[0017] Example 1

[0018] 100g of rutin was placed in a flask, and 200ml of methanol, 30g of ethylene oxide, 1ml of diethylamine, and 0.1g of 4-dimethylaminopyridine were added. The mixture was stirred and heated to 40°C for 16h. After the reaction, the pH was adjusted to 5, cooled to 10°C for crystallization for 2h, filtered, washed with methanol, and dried to obtain 96g of troxerutin with a content of 96%.

[0019] Example 2

[0020] 100g of rutin was placed in a flask, and 300ml of methanol, 40g of ethylene oxide, 2ml of diethylamine, and 0.5g of 4-dimethylaminopyridine were added. The mixture was stirred and heated to 50°C for 12h. After the reaction, the pH was adjusted to 5, cooled to 20°C for crystallization for 4h, filtered, washed with methanol, and dried to obtain 95g of troxerutin with a content of 95%.

[0021] Example 3

[0022] 100g of rutin was placed in a flask, and 500ml of methanol, 50g of ethylene oxide, 4ml of diethylamine, and 1g of 4-dimethylaminopyridine were added, and the mixture was stirred and heated to 60°C for 8h. After the reaction, the pH was adjusted to 5, and the mixture was cooled to 30°C for crystallization for 6h, filtered, washed with methanol, and dried to obtain 96g of troxerutin with a content of 96%.

[0023] The above are only preferred embodiments of the present invention. It should be pointed out that for those skilled in the art, several modifications and improvements can be made without departing from the structure of the present invention, which will not affect the effect and practicality of the implementation of the present invention.

Claims

1. A method for preparing troxerutin, characterized in that: Put rutin in a beaker, add methanol, diethylamine, ethylene oxide and 4-dimethylaminopyridine to heat and react, adjust pH, crystallize and filter, wash and dry; In g / mL, the mass volume ratio of rutin and methanol solution is 1:2-5, the weight ratio of diethylamine to rutin is 1-4%, the weight ratio of ethylene oxide to rutin is 30-50%, and the weight ratio of 4-dimethylaminopyridine to rutin is 0.1-1%.

2. The method for preparing troxerutin according to claim 1, wherein The heating temperature is 40-60° C., and the heating time is 8-16 hours.

3. The method for preparing troxerutin according to claim 1, wherein The solution pH was adjusted to 4-6 with hydrochloric acid.

4. The method for preparing troxerutin according to claim 1, wherein The crystallization temperature is 10-30°C, and the crystallization time is 2-6h.

5. The method for preparing troxerutin according to claim 1, wherein The washing is methanol washing.