CS267461B1 - Method of 2-/4-hydroxybenzoyl/ benzoic acid's methyl ester production - Google Patents

Abstract

The present invention relates to a process for the preparation of ethyl ester 2- (4-Hydroxybenzoyl) behzoic acid which is an intermediate of the known synthesis spasmolytics of pitophonone hydrochloride. Esterifikaco has so far been carried out with a large surplus methyl alcohol by catalysing a large excess sulfuric acid and the reaction product isolated by pouring the reaction mixture into saturated aqueous sodium carbonate solution. The process is used in the esterification process with half the amount of methanol sulfuric acids. Reaction reaction isolation The product is subjected to neutralization of the reaction medium adding an aqueous bicarbonate solution alkali metal, bicarbonate ammonium or alkali metal carbonate, event. ammonium carbonate with value control drank the reaction mixture.

Description

The invention relates to a process for the preparation of 2- (N-hydroxybonzoyl) bonzoic acid methyl ester of the formula I

Which is an intermediate of the synthesis of the known spasmolytic pitophenone hydrochloride.

According to available literature / Meyer H .: Monatsh.Cheo. 25, 1188, 90 ^: (1 Orndorf WR,

Kelley L.: J. Amor, Chem. A4, 1518, 1922 / s, the compound of formula I is prepared by esterifying 2- (a-hydroxybenzoyl) benzoic acid in the presence of a large excess of sulfuric acid catalyst as a large excess of methanol, and the resulting ester is isolated by pouring the reaction mixture into sodium carbonate solution. When reproducing the process described in the literature, it has been found that half the amount of both sulfuric acid and methanol is sufficient for good esterification. It has also been shown that, when the ester is isolated (neutralization of the sulfuric acid) with sodium carbonate, there is a greater risk of conversion of the phonolic group of the methyl ester to the salt and hence the possibility of greater losses. A more preferred neutralizing agent has therefore been gnawed. According to the literature, the crude ester is purified by crystallization from water or methanol and yields are not given.

These disadvantages have been overcome by the development of a process for the preparation of notylostere acid 2- ^; 1-hydroxybenzoyl / benzoic acid of the formula I, prepared up to now by esterifying 2- (N-hydroxybenzoyl) benzoic acid in an amount of 25 to 35 moles, in the presence of ^; 1 to 5 moles conc. Sulfuric acid catalyst, boiling the reaction mixture and isolating the resulting ester of formula I by pouring the reaction mixture into a saturated aqueous sodium carbonate solution according to the invention, characterized in that 30 uses 1.8-2 moles per mole of acid for estorification conc. sulfuric acid and a maximum of L ^R t moles of methanol. After the reaction mixture was neutralized with roakčni adding an aqueous solution of alkali metal bicarbonate, ammonium bicarbonate or alkali metal carbonates ovont. ammonium carbonate provided that the pH of the reaction mixture does not exceed 8.5. The ester of formula (I) is obtained in a yield of 90% to 92% and used without purification for the next step.

The process according to the invention represents a technical and economical advantage of the process described in the literature and leads to high yields of the desired product in a purity which is sufficient for further use.

Further details of the method according to the invention can be seen from the following example which illustrates but does not limit this method.

To a solution of 1000 g of 2- (N-hydroxybenzoyl) benzoic acid in 2350 ml of methanol was added dropwise AAO ml of concentrated sulfuric acid while boiling, and the mixture was maintained at boiling point. After cooling to 25 to 3θ ³⁰ ° C solution of 900 g of sodium hydrogonuhličitanu in 8200 ml of water and stirring and cooling to 10-15 ° C with continued for 2 hours. The crystals of methyl excluded are aspirated and washed with water until neutral. 1020 g of ester containing 98 to 99% are obtained, which is used as is in the next stage.

Claims (1)

SUBJECT OF THE INVENTION A process for preparing 2- (4-hydroxybenzoyl) benzoic acid methyl ester of formula I cooch ₃ The esterification of 2- (a-hydroxybenzoyl) benzoic acid in an amount of 25 to 35 moles in the presence of 4 to 5 moles of cono. sulfuric acid catalyst, at a reflux temperature of the reaction mixture and isolating the resulting ester of formula I by pouring the reaction mixture into a saturated aqueous solution of sodium carbonate, characterized in that 1.8 to 2 moles of concentrated sulfuric acid are used for esterification and 1 mole of methyl alcohol, after completion of the reaction, the reaction mixture is neutralized by the addition of an aqueous solution of alkali metal bicarbonates, ammonium bicarbonate, alkali metal carbonates, or ammonium carbonate provided that the pH of the reaction mixture does not exceed 8.5.