A kind of synthetic method of medicinal citrate

Abstract

The invention discloses a method for synthesizing medicinal citrate, in particular to a method for preparing a mesoporous molecular sieve-supported heteropolyacid catalyst by an in-situ synthesis method, and catalyzing the reaction of citric acid, ethanol and n-butanol to synthesize a citric acid The crude mixed ester is refined and purified to obtain the finished product of mixed ester of citric acid. The method has mild reaction conditions, short reaction time, recyclable catalyst and is suitable for industrial production. In addition, the product has a high esterification rate, and the mixed ester combines the advantages of the two citric acid esters while making up for the shortcomings of the single citric acid ester product, and has better performance than the single citric acid ester.

Description

Technical field [0001] The invention belongs to the field of organic synthesis, and relates to a method for synthesizing citrate esters, in particular to a method for catalyzing the synthesis of citrate esters by a mesoporous molecular sieve supported heteropoly acid. Background technique [0002] Citrate ester plasticizer is an environmentally friendly plasticizer produced from non-petroleum raw materials. It has already been industrialized in developed countries such as Europe, America and Japan. my country, as the second largest producer of citric acid, also started a small amount of industrial production at the end of the last century and entered the market at the beginning of this century. [0003] Citrate plasticizers are considered to be the most ideal environmentally friendly plasticizers that can replace phthalate plasticizers. Not only are they non-toxic, no special odor, but also have a very good plasticizing effect on PVC. , The speed-increasing effect is equivalent to...

AI Technical Summary

Problems solved by technology

The traditional esterification reaction uses concentrated sulfuric acid as a catalyst. Although the catalytic effect is good, concentrated sulfuric acid has strong acidity and strong oxidizing properties, which is highly corrosive to equipment and requires high requirements. At the same time, side reactions are prone to occur, such as carbonization of organic matter by concentrated sulfuric acid , ethanol itself condenses into ether, etc., resulting in low product yield and product quality problems: low product purity, poor color, easy acidification, and short validity period

However, the use of concentrated sulfuric acid as a catalyst still has the disadvantages of low selectivity, many by-products, unsatisfactory product yield, great corrosion to equipment, and high requirements for the treatment of three wastes.

[0010] CN102659591A discloses a method for preparing triethyl citrate by continuous catalysis. In view of problems such as easy loss of catalyst and complex post-treatment process in the above-mentioned scheme, it is proposed to use a fixed-bed continuous catalytic reaction device to produce triethyl citrate. The styrene-based cation exchange resin loaded with Lewis acid is used as a catalyst, and it is packed into a series fixed bed. The reactant enters from the top of the reactor, passes through the middle catalyst layer, and undergoes esterification reaction under heat preservation conditions, and the reaction product is discharged from the bottom of the reactor. And enter the gas-liquid separation device, the upper part of the gas-liquid separation device discharges unreacted ethanol, and the lower part discharges the crude triethyl citrate, which is purified to obtain pure product

However, because the catalyst is loaded on the resin, it is difficult to clean and regenerate the resin, and it is easy to breed microorganisms, so it is impossible to guarantee that the microbial limit and other quality regulations of the product can meet the pharmaceutical requirements

[0011] CN1762969A discloses a method for mesoporous materials to catalyze tributyl citrate. The HAl-MCM-41 mesoporous molecular sieve used in the patent has the following disadvantages: 1. The acid center is obtained by roasting ammonium nitrate, and does not form a chemical bond with the carrier , easy to be lost in the reaction; 2. The active center obtained by roasting ammonium nitrate is H + , less acid strength, lower conversion of citric acid

[0021] In fact, since the interaction between the heteropolyacid and the surface of the carrier is basically an acid-base reaction, the acid-base strength of the hydroxyl group on the surface of the carrier and the strength of the heteropolyacid are different, and the result of the interaction between the two forms the acid strength and loading. Different active bodies affect the activity and elution amount of the supported heteropolyacid catalyst in the reaction

Images