RU2231522C2 - Method for preparing 3-(4-hydroxy-3,5-di-tertiary-butylphenyl)-propionic acid methyl ester - Google Patents

Abstract

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to the improved method for preparing 3-(4-hydoxy-di-tert.-butylphenyl)-propionic acid methyl ester used in manufacturing stabilizing agents for polymeric materials, in agriculture as a fodder supplement and in medicine as a component of medicinal preparations. Method involves interaction of 2,6-di-tert.-butylphenol with methyl acrylate in the presence of alkaline metal 2,6-di-tert.-butylphenolate as an alkaline catalyst prepared by interaction of 2,6-di-tret.-butylphenol with alkaline metal hydroxide at enhanced temperature under inert atmosphere and involving removal of water from the reaction medium. Method involves using a catalyst prepared at temperature 151-240 C in the presence of water-absorbing substance. Method provides preparing the high-quality end product with the yield above 99%.

EFFECT: improved preparing method, enhanced yield.

2 cl, 4 ex

Description

The invention relates to organic synthesis, and in particular, to a method for producing 3- (4-hydroxy-3,5-di-tert-butylphenyl) propionic acid methyl ester used in the production of stabilizers of polymeric materials in agriculture as a feed additive, and also in medicine as a component of drugs.

A known group of methods for producing 3- (4-hydroxy-3,5-di-tert-butylphenyl) propionic acid methyl ester by reacting methyl acrylate with 2,6-di-tert-butylphenol at elevated temperatures with alkaline catalysts such as tert- potassium butylate, alkali metal phenolates, lithium metal in the presence of solvents such as tert-butyl alcohol, dimethyl sulfoxide, dimethylformamide, dimethoxybenzene. [US Patent 3247240 (1966); Journal of Organic Chemistry, 1984, v. 20, No. 9, p. 1899; Russian Chemical Journal, 2000, vol. 44, No. 2, p. 81; US patent 5264612 (1994)].

The disadvantage of these methods is the need to use large quantities of catalysts, since their activity decreases in the presence of organic solvents. For example, when conducting a reaction in a solution of dimethoxybenzene at 130-140 ° C to obtain a 94% yield of the target product, the potassium tert-butylate catalyst is used at a concentration comparable to the concentration of 2,6-di-tert-butylphenol. [US Patent 3247240 (1966)]. There is a need to separate the target product from the solvent and catalyst residues.

A known method of producing methyl ester of 3- (4-hydroxy-3,5-di-tert-butylphenyl) propionic acid by the interaction of 2,6-di-tert-butylphenol with 50% aqueous solutions of potassium and sodium hydroxides at 100 ° C for 1 hour with the removal of water by vacuum, followed by the addition of methyl acrylate dropwise over 2 hours at a temperature of 115 ° C and maintaining the reaction mass until a clear solution is formed, followed by neutralization of the alkaline catalyst with formic acid. [US Patent 5,177,247 (1993)]. The disadvantage of this method is the decrease in catalyst efficiency at the stage of evacuation, which leads to a decrease in the yield of the product, as well as the fact that evacuation leads to the release of 2,6-di-tert-butylphenol vapor into the atmosphere and crystallization of 2,6-di-tert-butylphenol in vacuum system, which complicates and complicates the practical use of this method.

A known method of producing methyl ester of 3- (4-hydroxy-3,5-di-tert-butylphenyl) propionic acid by the interaction of 2,6-di-tert-butylphenol with methyl acrylate in a molar ratio of 1: 1.1 in the presence of 2 mol.% Catalyst with at a temperature of 115 ° С in a nitrogen atmosphere by dropping methyl acrylate to a mixture of 2,6-di-tert-butylphenol-catalyst for 2 hours, followed by holding the reaction mass for 2 hours, separating the catalyst by filtration and fractional distillation of the residue in vacuum at a temperature of 124-126 ° С and a vacuum of 10 mm RT. Art. An alkylation catalyst is obtained by heating a compound containing calcium oxide at 1100 ° C. followed by hydration, mixing with potassium fluoride, additional mixing with or without potassium hydroxide, calcining and using the resulting alkaline product in a reaction with 2,6-di-tert- butylphenol at a temperature of 115-120 ° C for 1 hour under conditions of separation of water by vacuum [US 5206414A, publ. 04/27/93]. The disadvantage of this method is the difficulty of obtaining the catalyst, the duration of obtaining the target product, the need to separate excess catalyst by filtration, and the possibility of the release of phenol-containing products into the atmosphere during the vacuum process.

The closest technical solution, selected as a prototype, is a method for producing methyl ester of 3- (4-hydroxy-3,5-di-tert-butyl-phenyl) propionic acid by reacting 2,6-di-tert-butylphenol with methyl acrylate at molar 1: 1-1.3 ratio in the presence of a catalyst containing, along with potassium or sodium hydroxide, potassium or sodium 2,6-di-tert-butylphenolate in an amount of 2-20 mol.% of 2,6-di-tert- butylphenol in terms of the amount of alkali metal hydroxide and 2,6-di-tert-butylphenol alkali metal. The catalyst is obtained by heating 2,6-di-tert-butylphenol with potassium or sodium hydroxide in an inert gas atmosphere (argon or nitrogen) at a temperature of 50-150 ° C with separation of water by azeotropic distillation with 2,6-di-tert-butylphenol . The reaction proceeds within 1.5-3.5 hours. The content of the products in the solid melt (mp. 64-65 ° C) obtained after processing the reaction mixture with 5% sulfuric acid is 86% [a.s. USSR 1001649 (1980), Bull. fig. and open 1986, (23), 258]. To obtain a cleaner product, additional fractionation with subsequent crystallization is required.

The disadvantages of this method are the complexity of the process for producing a catalyst associated with the need for water distillation, low catalyst activity, which determines the duration of the alkylation process (1.5-3.5 hours), and does not allow to obtain the target product with a high degree of purity, as a result of which additional purification of the target product by fractional distillation.

The objective of the present invention is to develop a method for producing methyl ester of 3- (4-hydroxy-3,5-di-tert-butylphenyl) propionic acid, which allows to simplify and intensify the process while improving the quality of the target product, as well as to eliminate environmental pollution during the emission waste phenol-containing products into the atmosphere.

The essence of the proposed method consists in the fact that methyl 3- (4-hydroxy-3,5-di-tert-butylphenyl) propionic acid is obtained in an inert atmosphere by reacting 2,6-di-tert-butylphenol with methyl acrylate in the presence of a catalyst, obtained at elevated temperature from 2,6-di-tert-butylphenol and potassium and (or) sodium hydroxides in the presence of a water-absorbing substance, for example lithium hydride, calcium oxide, silica gel or combinations thereof, located, depending on the form of the method and the properties of the water-absorbing substance wa, in the reaction system directly in the reaction mixture or outside it. The alkali metal 2,6-di-tert-butylphenolate catalyst is prepared at a temperature of 151-240 ° C. and used in the reaction in an amount of 1-4 mol% of 2,6-di-tert-butylphenol and 2,6-di tert-butylphenol and methyl acrylate are reacted at a molar ratio of 1: 1-1.3, respectively, and the alkylation reaction is carried out at a temperature of 80-140 ° C for 15-60 minutes.

Obtaining a catalyst at elevated temperature in the presence of a water-absorbing substance allows you to quickly (in 2-30 minutes) to obtain the most active form of the catalyst in the form of monomers of potassium and (or) sodium 2,6-di-tert-butylphenolate, which, in turn, can reduce the required amount of catalyst to 1-4 mol.%, and also reduce the alkylation time to 15-60 minutes. The content of the target product in the reaction mass reaches 94-98%, and after crystallization - more than 99%. The proposed method does not contain water distillation operations at the stage of preparation of the catalyst, and does not require fractional distillation at the stage of separation of the target product, which excludes the emission of phenol-containing products into the atmosphere. Of great importance for the possibility of industrial application of the proposed method is that it can be used in a continuous process.

The proposed method is as follows: heated to a predetermined temperature 2,6-di-tert-butylphenol in an inert gas atmosphere (argon or nitrogen) add the calculated amounts of alkali metal hydroxide in the form of a solid or aqueous solution, and use as a water-absorbing substance, for example, lithium hydride, silica gel or calcium oxide. The preparation of the catalyst proceeds in the temperature range 151-240 ° C. Methyl acrylate is added to a mixture of 2,6-di-tert-butylphenol and a catalyst at a temperature of 80-140 ° C. At the end of the reaction, the reaction mass is neutralized or the target product is isolated in the form of a melt, and, if necessary, crystallized, for example, from isopropyl alcohol or heptane.

The possibility of practical implementation of the proposed method is illustrated by the following examples.

Example 1

In a flask equipped with a reflux condenser and an inert gas inlet, 20.6 g (0.1 g-mol) of 2,6-di-tert-butylphenol with a 50% aqueous solution of 0.22 g (0.004) are heated under argon atmosphere. g-mol) of potassium hydroxide and 0.8 g of lithium hydride at a temperature of 151-165 ° С for 30 minutes, after which the reaction mass is cooled to a temperature of 120 ° С and 9.5 g are added to the flask for 1 minute (0, 11 gmol) methyl acrylate. The temperature drops to 85 ° C, and then spontaneously rises to 110 ° C. After 15 minutes, according to liquid chromatography (LC), the conversion of 2,6-di-tert-butylphenol is 94%. 30 minutes after the completion of the addition of methyl acrylate, the reaction mass is separated from lithium hydride and neutralized with acetic acid. Upon cooling, 29.0 g of a colorless crystalline product are formed, which, according to LC, contains 98.5% of the target product. After crystallization from aqueous isopropyl alcohol, the content of 3- (4-hydroxy-3,5-di-tert-butylphenyl) propionic acid methyl ester in the target product is 99.6%, melting point 68 ° C. The reaction of the prototype method under comparable conditions provides the yield of the target product in an amount of 32%.

Example 2

In a ball refrigerator, 50 g of silica gel is fixed. From 51.6 g (0.25 g mol) of 2,6-di-tert-butylphenol, 0.1 g (0.0025 g mol) of sodium hydroxide, taken dry, at a temperature of 240 ° C in the atmosphere argon for 2 minutes get the catalyst. The reaction mass is cooled to 135 ° C. and 21.5 g (0.25 g mol) of methyl acrylate are added. The reaction mixture is maintained at a temperature of 100-125 ° C for 60 minutes. According to LC, the content of 3- (4-hydroxy-3,5-di-tert-butylphenyl) propionic acid methyl ester in the colorless transparent reaction mass is 94%. After recrystallization from heptane, the content of the basic substance is 99.6%, the melting point is 68 ° C.

Example 3

In a ball refrigerator, 20 g of calcium oxide are fixed. Of 51.6 g (0.25 g mol) of 2,6-di-tert-butylphenol, 0.1 g (0.00179 g mol) of potassium hydroxide and 0.13 g (0.00325 g mol) sodium hydroxide in a nitrogen atmosphere at a temperature of 180-200 ° C for 12 minutes to obtain a catalyst. The reaction mass is cooled to 100 ° C. and 27.95 g (0.325 g mol) of methyl acrylate are added. The reaction is carried out at a temperature of 100-120 ° C. According to LC, after 45 minutes, the content of 3- (4-hydroxy-3,5-di-tert-butylphenyl) propionic acid methyl ester in the reaction mass was 98%. After crystallization from hexane, the content of the target product increases to 99.7%. Melting point 68 ° C.

The possibility of using the proposed method in a continuous process is illustrated by the following example.

Example 4

The production of 3- (4-hydroxy-3,5-di-tert-butyl-phenyl) propionic acid methyl ester is carried out in a steel reactor in the form of a column consisting of three sections interconnected by valves to transfer the reaction mixture from one section to another and equipped with devices for introducing reaction components — potassium and (or) sodium hydroxides, melt of 2,6-di-tert-butylphenol, methyl acrylate, inert gas, and for withdrawing reaction products. The upper unheated part of the upper section contains a grid on which a mixture of calcium oxide and silica gel is placed in a mass ratio of 1: 1. The lower, heated part of the upper section, in which the actual production of the catalyst occurs, contains a grid on which lithium hydride is placed. The upper section of the reaction column together with a heated vessel for 2,6-di-tert-butylphenol form a closed system. The process is carried out as follows: the system is filled with argon, after which 20.6 g (0.1 mol) of 2,6-di-tert-butylphenol heated to 200 ° C and 0.12 g (0.0021) are fed into the upper section through a dispenser mol) potassium hydroxide. The interaction occurs in the heated zone of the upper section at a temperature of 200 ° C for 5 minutes, while lithium hydride is on the surface of the melt. The water formed during the reaction is captured by lithium hydride, and the excess in the form of steam carried away by an argon flow is absorbed by a mixture of silica gel and calcium oxide located in an unheated zone. The connecting valve between the upper and middle sections is opened, and the resulting suspension of 2,6-di-tert-butylphenolate of potassium in 2,6-di-tert-butylphenol enters the middle section, heated to a temperature of 100 ° C, where it interacts with 10.3 g (0.12 mol) of methyl acrylate fed through a dispenser. Three minutes later, a valve is opened connecting the middle and lower sections, and the reaction mixture enters the lower section, in which the mixture is kept at a temperature of 100-120 ° C for 1 hour. According to LC, the purity of the product is 98%. Simultaneously with transferring the reaction mixture to the lower section, 2,6-di-tre-butylphenol and potassium hydroxide are fed to the upper section.

Thus, the use of the proposed method for the preparation of 3- (4-hydroxy-3,5-di-tert-butylphenyl) propionic acid methyl ester by alkylation of 2,6-di-tert-butylphenol with methyl acrylate in the presence of a catalyst obtained by heating 2,6- di-tert-butylphenol with potassium hydroxide and (or) sodium at a temperature of 151-240 ° C under conditions of water absorption by a water-absorbing substance, for example lithium hydride, silica gel or calcium oxide, it allows to reduce the process time, increase the selectivity of alkylation with a decrease in the amount of kata lyser, resulting in a higher quality target product with a yield exceeding 99%, and also to eliminate the release of phenol-containing products into the atmosphere.

The proposed method can be used to carry out a continuous process for the preparation of 3- (4-hydroxy-3,5-di-tert-butylphenyl) propionic acid methyl ester, in which it is possible to simultaneously introduce the starting components into the reaction medium and remove the target product from the reaction sphere.

Claims (2)

1. The method of obtaining methyl ester of 3- (4-hydroxy-3,5-di-tert-butylphenyl) propionic acid by the interaction of 2,6-di-tert-butylphenol with methyl acrylate in the presence of an alkaline catalyst - 2,6-di-tert- alkali metal butylphenolate obtained by reacting 2,6-di-tert-butylphenol with an alkali metal hydroxide at an elevated temperature in an inert atmosphere, including removing water from the reaction medium, characterized in that a catalyst obtained at a temperature of 151-240 ° C in the presence of water-absorbing substance. 2. The method according to claim 1, characterized in that, for example, lithium hydride, calcium oxide, silica gel are used as the water-absorbing substance.