RU2019541C1 - Process for preparing benzamide - Google Patents

Abstract

FIELD: chemical industry. SUBSTANCE: the product is benzamide. Reagent 1: benzoic acid methyl ester prepared by reacting benzoic acid with CH₃OH in the presence of a strong cationite in H⁺-form, the reaction mixture is then kept till the equilibrium of the esterification-hydrolysis reaction is established on heating, followed by cooling and separation of the cationite. Reagent 2: a 25% aqueous solution. Reaction conditions: NH₃ is added to the resultant reaction mixture and the process is carried out in a homogeneous medium at a benzoic acid to CH₃OH to cationite to NH₃ weight ratio of 1: (5-10): (0.5-1):(4.7-7), followed by removal of NH₃ and CH₃OH from the reaction mixture and distillation of the unreacted benzoic acid methyl ester. EFFECT: improved properties of the title product. 3 cl, 1 tbl

Description

 The invention relates to chemistry, specifically to an improved method for producing benzamide.

 Known methods for the synthesis of benzamide based on benzonitrile (1-6). Despite the high yields, the applicability of these methods is limited by the relatively low availability of the starting benzonitrile.

 Classical methods for producing benzamide by fusion of benzoic acid or ammonium benzoate with carbonate (7) or ammonium chloride (8), as well as acid amides: acetamide (9), trichloroacetamide (10), urea (11), phosphoric amides (12) and sulfuric ( 13, 14) acids require the use of high temperatures, pressure, equipment for working in aggressive environments and are associated with difficulties in isolating the target product due to the formation of by-products - acids or salts. The described methods are complex in technological design and therefore have not found practical application in industry.

 The most comprehensive Comprehensive Organic Chemistry textbook emphasizes that “There are three methodological approaches for the synthesis of esters and amides: direct acid-catalyzed reaction of an alcohol with an acid, preliminary conversion of an acid to a reactive derivative, and activation of an alcohol or amine with respect to a nucleophilic attack of carboxyl ions "(15).

 As described in the most authoritative reference books, the industrial methods for producing benzamide are the hydrolysis of benzonitrile (16), which is described in more detail above, the interaction of benzoyl chloride with ammonium carbonate (17, 18) or ammonia (16, 18). The desired benzoyl chloride is prepared by reacting benzoic acid with inorganic acid chlorides.

 Thus, the closest to the proposed method is a method for producing benzamide from benzoic acid by converting it to benzoyl chloride with further ammonolysis of the latter with aqueous ammonia solution (19) (prototype).

 The disadvantage of the prototype method is the need to work with benzoyl chloride, which has a strong lacrimating effect, as well as the easy hydrolysis of benzoyl chloride and the formation of by-products: an equivalent amount of ammonium chloride, a significant amount of benzoic acid, etc. The conversion of benzoic acid to benzoyl chloride is particularly ecological danger. These shortcomings acquire even greater fundamental importance from an environmental point of view in the consolidation of the scale of benzamide production.

 The aim of the invention is to provide an environmentally friendly method for producing benzamide from benzoic acid.

This goal is achieved by the method of producing benzamide, which consists in the fact that a strong cation exchanger in H ⁺ form (preferably KU-2-8) is placed in a solution of benzoic acid in methanol and the reaction mixture is usually kept under heating, preferably until equilibrium of the esterification-hydrolysis reactions is established and after cooling and separation of the cation exchange resin, an aqueous solution of ammonia is added to the filtrate, and the resulting homogeneous reaction mixture containing benzoic acid methyl ester is usually kept at room temperature re, ammonia and methanol are removed, unreacted methylbenzonate is distilled off from the reaction mixture with water vapor, benzamide is isolated by conventional methods. The optimal ratio is the mass ratio of benzoic acid: methanol: cation exchange resin: aqueous ammonia 25%, equal to 1: (5-10) :( 0.5-1) :( 4.5-7).

 Thus, according to the proposed method, all unreacted reagents can be regenerated and used in subsequent cycles. Cation exchanger after separating it from the reaction mass can be further used repeatedly without further processing. Therefore, the proposed method is environmentally friendly.

 Although amylation of carboxylic acid esters is a common method for producing amides in organic chemistry and attempts have been made to apply it to benzoic acid esters, the low reaction rate and reversibility of the processes did not allow us to hope for its practical implementation for the synthesis of benzamide. This is illustrated by the work of Gordon et al. (20, 21) in studying the kinetics of ammonolysis of various esters. Unlike fatty acid esters, aromatic acid esters, in particular benzoic, are practically inert in ammonolysis reactions. Under the same conditions, the relative rate of ammonolysis of methylbenzonate is only 8% of the rate of ammonolysis of methyl acetate (21).

 A comparison of the rates of ammonolysis of benzoic acid esters shows that the alcohol residue has little effect on the reactivity in the ammonolysis of benzoic acid esters (21).

Emil Fischer (22) shows that many hours of heating with a large excess of ethyl benzoate saturated at ⁰ ° alcoholic ammonia at ¹²⁵ ° C leads to formation of the benzamide in a yield of 5% and at 17.5 ^{° C} - 17%. In view of the above, the achievement of a positive effect by the proposed method is unexpected, and the method of producing benzamide by ammonolysis of methylbenzonate in aqueous ammonia at room temperature could not be proposed a priori.

 The selection of optimal conditions for the process, the repeated reuse of regenerated catalysts unexpectedly made it possible to obtain benzamide in high yield and high quality in an environmentally friendly and essentially waste-free way.

 The reaction of benzoic acid with methanol in the presence of strong cation exchange resin is preferably carried out by boiling the reaction mixture, since this process takes a long time at room temperature. Naturally, the maximum yield of the target product will take place upon reaching equilibrium of the esterification reaction; however, in practice it is hardly advisable to achieve equilibrium and 25-35-hour boiling is sufficient. The mass ratio of benzoic acid: cation exchange resin, equal to 0.5-1, is chosen arbitrarily in the sense that the increase in the amount of cation exchange resin does not significantly affect the speed of the process.

 At the stage of ammonolysis, an increase in the temperature of the process certainly leads to an increase in the rate of ammonolysis, however, the rates of side reactions increase even more significantly and it is not possible to immediately obtain a pure target product, and additional operations are required to clean it.

 Distinctive features of the proposed method for the production of benzamide from benzoic acid is the interaction of benzoic acid with methanol in the presence of strong cation exchange resin and ammonolysis of the resulting methyl ester with concentrated aqueous ammonia in a homogeneous reaction medium, preferably at room temperature, removing excess amounts of ammonia, methanol and methylbenzonate, better at a mass ratio benzoic acid: methanol: cation exchange resin: aqueous ammonia 25%, equal to 1: (5-10) :( 0.5-1) :( 4.5-7).

PRI me R s 1-9. KU-2-8 resin is added to a solution of 30 g of benzoic acid in methanol and the reaction mixture is boiled for 25-35 hours (the formation of benzoic acid methyl ester can be controlled by titration of unreacted benzoic acid with an alkali solution). Then the reaction mixture is cooled, the resin is separated, and a 25% solution of ammonia in water is added to the solution. After aging for 240-300 hours at room temperature, the excess amount of ammonia and methanol is removed, unreacted methyl benzoate is distilled off with steam until the distillation becomes completely transparent. When cooled, benzamide crystallizes. Get benzamide with so pl. 127-129 ^about S.

 After recrystallization from water, benzamide is obtained with a basic substance content of 99.6-99.8% (titrimetrically after decomposition with alkali followed by distillation of ammonia), the content of benzoic acid is not higher than 0.1% (TLC, titrimetric). The data are given in the table.

Claims (3)

1. METHOD FOR PRODUCING BENZAMIDE by reacting an activated benzoic acid derivative and an aqueous ammonia solution, characterized in that benzoic acid methyl ester obtained by reacting benzoic acid with methanol in the presence of strong cation exchange resin in an H ⁺ form is used as an activated derivative, followed by exposure to the reaction mass until equilibrium of the reactions of esterification-hydrolysis upon heating and subsequent cooling and separation of cation exchanger, an aqueous solution of ammonia add to the resulting reaction mass and the process is carried out in a homogeneous medium with a mass ratio of benzoic acid: methanol: cation exchange resin: aqueous ammonia (25%) 1: 5 - 10: 0.5 - 1: 4.5 - 7, respectively, followed by removal from the reaction mass of ammonia and methanol; and distillation of the unreacted methyl benzoic acid ester with steam. 2. The method according to claim 1, characterized in that the KU-2 resin in the H ⁺ form is used as cation exchanger.  3. The method according to claims 1 and 2, characterized in that the process of ammonolysis is carried out at room temperature.

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