RU2298548C1 - Method for preparing arylchlorosulfonyl benzamides from benzoic acids - Google Patents

Abstract

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to a method for synthesis of arylchlorosulfonyl benzamides used in synthesis of different derivatives of sulfoacids. Invention describes a method for synthesis of different arylchlorosulfonyl benzamides wherein benzoic acids are sulfochlorinated with chlorosulfonic acid, amidated with ammonia or other amine successively and prepared sulfamides are subjected for interaction with chlorosulfonic acid by the reaction of intramolecular re-amidation. Proposed method provides synthesis of arylchlorosulfonyl benzamides with aliphatic amine fragments and electron-acceptor substitutes in aromatic ring by the simplified technology.

EFFECT: improved and simplified method of synthesis.

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Description

The invention relates to the field of organic chemistry, specifically to a new method for producing arylchlorosulfonylbenzamides.

These compounds are widely used in the synthesis of various derivatives of sulfonic acids, mainly sulfamides, which are used in the preparation of dyes, various types of polycondensation polymer materials, paint-forming components in film photography, medicinal and biologically active substances with a wide spectrum of action: diuretics, natriuretics, anticonvulsants, prophylactic and therapeutic agents for treating disorders of the cardiovascular system and the like.

A method based on the different reactivity of the acid chloride and sulfonyl chloride groups in dichlorohydrides of aromatic sulfobenzoic acids / Barr C.R., Salminen I.F., Weissberger A. // The Reaction of 3-Chlorosulfonylbenzoyl Chloride with Amines. - J. Am. Chem. Soc., 1951. - Vol. 73. - P.4131-4133 /. Synthesize such acid chlorides from benzoic acid or its substituted, sequentially carrying out sulfochlorination with chlorosulfonic acid (HSC) and dehydroxylation with thionyl chloride.

The resulting compounds can selectively react on the acid chloride group with various amines - aromatic / Pat. Brit No. 912060, 05.12.62 / or heterocyclic / Pat. Switzerland No. 436288, 11/15/1967 /.

The disadvantage of this method is the inability to selectively carry out the reaction in the case of the most reactive, aliphatic amines. Thus, it is possible to obtain only a limited number of derivatives.

In some cases, when a strong electron-donating substituent is present in the aromatic fragment of benzamide, direct sulfochlorination without decomposition of the amide bond is also possible / Pat. USA No. 3055905, 09/25/1962 /, which slightly increases the number of products obtained.

However, arylchlorosulfonylbenzamides containing other substituents in the aromatic nucleus, in particular halogens, cannot be obtained by this method.

Closest to the proposed method is the method / Pat. Brit No. 909751, 11/07/1962 /, in which the target products are obtained in several stages: 1) nitration of aryl-substituted benzoic acids with a concentrated solution of nitric acid in 100% sulfuric acid; 2) dehydroxylation of benzoic acid with thionyl chloride to give an acid chloride; 3) obtaining an amide by acylation of ammonia or an aliphatic amine; 4) reduction of the nitro group to amine in an aqueous solution of ethanol acidified with hydrochloric acid in the presence of iron powder or hydrogenation on a catalyst (palladium, platinum, Raney nickel); 5) a diazotization reaction of the obtained compound with an aqueous solution of sodium nitrite, followed by treatment of the diazocompound with a concentrated solution of sulfur dioxide in acetic acid with the addition of copper chloride.

It is multi-stage that is the disadvantage of this method, because losses at each stage may not allow to achieve a significant yield of the target substance. This is indirectly confirmed by the absence of the yields of products and intermediates described in this patent.

The objective of the invention is to simplify the process, obtaining arylchlorosulfonylbenzamides with aliphatic amine fragments and various, including electron-withdrawing, substituents in the aromatic ring.

The proposed method is based on the detected intramolecular transamidation reaction, which occurs when chlorosulfonic acid acts on aromatic compounds in the molecule of which there are simultaneously carboxyl and sulfamide substituents.

where R ₁ and R ₂ are H, Alk;

R is H, Alk, Hal.

The reaction is carried out in a medium of chlorosulfonic acid with its 2- and 3-fold excess. Such conditions are due to the fact that HSC acts simultaneously as a solvent and a reagent, as well as the poor solubility of sulfamic acid and its derivatives (supposed intermediate compounds) in it. The reaction is carried out at a temperature of 70-120 ° C for 1-4 hours, depending on the structure of the starting compound.

The process consists of the following stages: 1) sulfochlorination of benzoic acid or its substituted 2- and 3-fold excess of chlorosulfonic acid at 100-150 ° C for 1.0-2.5 hours; 2) amidation of sulfonyl chloride with ammonia or an aliphatic amine in an aqueous medium at a reduced temperature; 3) intramolecular transamidation under the action of chlorosulfonic acid.

Thus, the advantage of the proposed method over the prototype is to reduce the number of stages from 5 to 3 using the same starting compounds. The yields of sulfochlorination and amidation products are 80-90%; in the transamidation reaction, the yield is 65-85%. In addition, the process is greatly simplified, the number of solvents and reagents used is significantly reduced: chlorosulfonic acid performs both of these functions in the first and last stages, and in the second stage the reaction proceeds in an aqueous solution.

The invention is illustrated by the following examples:

Example 1

a) A three-necked flask equipped with a mechanical stirrer, a thermometer and a reflux condenser is charged with 12.1 g (0.1 mol) of benzoic acid, then 20 ml (0.3 mol) of freshly distilled chlorosulfonic acid are added. The reaction mixture was heated to 100 ° C and maintained at this temperature with stirring for 1.5 hours. The mixture which had cooled to room temperature was poured onto ice with vigorous stirring. The precipitated product is filtered off and washed with water, and dried. Obtain 18.9 g of 3-chlorosulfobenzoic acid.

b) The resulting substance is poured into 20 ml of ice water and 25 ml of a 20% aqueous ammonia solution (0.27 mol) is added to the resulting mixture. Within a few minutes, a slight heating of the reaction mass and complete dissolution of the acid are observed. After 10 min, the pH of the medium is gradually added dropwise with a concentrated aqueous solution of hydrochloric or sulfuric acid to slightly acidic. The precipitate formed is filtered off, washed with a small amount of cold water. 13.5 g (0.067 mol) of 3-sulfamoylbenzoic acid are obtained. The melting point after recrystallization from acetic acid 234-236 ° C.

c) The setup for the experiment is similar to that described in paragraph (a). Download the resulting benzoic acid sulfamide, pour 9 ml (0.134 mol) of freshly distilled HSC. The reaction mixture is heated to 120 ° C and maintained at this temperature with stirring for 60 minutes. The mixture cooled to room temperature was poured onto ice with vigorous stirring. The precipitated product is filtered off and washed with water, and dried. 10.2 g of 3-chlorosulfobenzamide are obtained. The melting point after recrystallization from toluene is 89-91 ° C.

Example 2

20 g of p-methylbenzoic acid are sulfochlorinated according to the procedure described in paragraph (a) of example 1 at 120 ° C. The dried precipitate (28.9 g) obtained is amidated with ammonia as described in paragraph (b) of example 1. Dried and recrystallized from vinegar 3-sulfamoyl-4-methylbenzoic acid (23.3 g, mp 244-247 ° C) with stirring is heated with 21.5 ml of HSC in a flask under reflux at 90 ° C. After 2 hours, the reaction mixture cooled to 40 ° C was poured onto ice, the precipitate formed was filtered, washed with water, and dried. 18.6 g of 3-chlorosulfo-4-methylbenzamide are obtained. The melting point after recrystallization from toluene is 75-77.5 ° C.

Example 3

5 g of o-chlorobenzoic acid are sulfochlorinated according to procedure 1 (a). The temperature of the experiment 130 ° C, the time 2 hours. The product precipitated after pouring the reaction mixture onto ice is filtered off and washed with cold water, and dried. 6.7 g of 3-chlorosulfo-2-chlorobenzoic acid are obtained, which is treated with a 40% aqueous solution of dimethylamine according to procedure 1 (b). 6 g of 3-carboxy-4-chloro-N, N-dimethylsulfanilamide are obtained. The melting point after recrystallization from acetic acid is 169-172 ° C. According to method 1 (c), the obtained HSC compound is treated at 90 ° C for 3 hours. The precipitate formed in ice water is filtered off and dried. 4.6 g of 2-chloro-5-chlorosulfo-N, N-dimethylbenzamide are obtained. The melting point after recrystallization from toluene is 111-113 ° C.

Example 4

6 g of 2,4-dichlorobenzoic acid are added to a flat-bottomed flask, 10 ml of distilled HSC are added, and the flask with the reflux condenser installed is placed in a sand bath and the reaction is carried out at the boiling of chlorosulfonic acid (~ 150 ° C) for 2.5 hours. Then the reaction mixture is cooled and poured onto ice with vigorous stirring, the precipitate formed is filtered off and dried. The resulting sulfonyl chloride (8.3 g) is amidated with a 30% methylamine solution as described in 1 (b). Dried and recrystallized from vinegar 5-carboxy-2,4-dichloro-N-methylsulfanilamide (6.5 g) with stirring is heated with HSC for 2.5 hours in a flask under reflux at a temperature of 100 ° C. Then the reaction mixture cooled down to 40 ° С was poured onto the ice with vigorous stirring, the precipitated product was filtered off and dried. 5.6 g of 2,4-dichloro-5-chlorosulfo-N-methylbenzamide are obtained. The melting point after crystallization from toluene is 167-169 ° C.

Claims (1)

A method of producing arylchlorosulfonylbenzamides using benzoic acid or its substituted, characterized in that the benzoic acid or its substituted is reacted with a 2-3-fold excess of chlorosulfonic acid at 100-150 ° C for 1.0-2.5 hours, followed by amidation the resulting chlorosulfobenzoic acid with ammonia or an aliphatic amine in an aqueous medium at a reduced temperature and the treatment of the resulting sulfamide with a 2-3-fold excess of chlorosulfonic acid at 70-120 ° C for 1-4 hours with a flow of reactions of intramolecular transamidation.