KR800000225B1 - Process for the preparation of 2,5-disubstituted benzamides - Google Patents

Abstract

Title compds. [I; A =low mol. wt. mono-or dialkylamino or heterocyclic group (IV; R =low mol. wt.alkyl or alkylene, m<=4), B = low mol. wt. alkyl or alkylene, n= 1,2, x= amino, mono-or dialkylamino, alkyl or aklylene were prepd. by treating 2,5-disubstituted benzoic acid(II) with amino(III)in the presence of tetraethylpyrophosphite. Thus, 1.15 g 2-methoxy-5-sulfamide benzoic acid and 0.64 g N-ethy1-2-aminomethylpyrrolidine were reacted for 2 hr in dioxane in the presence of 1.4 g tetraethylpyrophosphite to give I.

Description

Method for producing 2,5-disubstituted benzamides

The present invention relates to a method for producing 2,5-disubstituted benzamides of the following general formula (1).

Food,

A may be a low molecular weight mono- or dialkylamino group.

Here, the alkyl group may be bonded together with or without nitrogen oxygen or sulfur to form a ring.

When the ring contains a nitrogen atom, the nitrogen atom can be bound to a low molecular weight alkyl group.

The ring so formed may, for example, be pyrrolidinyl, piperidinyl, imidazolidinyl, piperazino, morpholino or thiazolidinyl.

Alternatively, A may be a heterocycle group of the form:

Food,

R is a low molecular weight alkyl group,

Or an alkylene group,

m is an integer of 4 or less.

B may be a low molecular weight alkyl group or alkylene group,

n is 1 or 2,

X may be an amino, mono- or dialkylamino, alkyl or alkylene group.

According to the present invention, as well as benzamides of the general formula (1) described above, inorganic or organic acid addition salts thereof and quaternary ammonium salts thereof are provided.

In the process of the present invention, 2,5-disubstituted benzoic acid of the following general formula (2) is used as a starting material and is treated with an amine of the general formula (3) in the presence of tetraethyl pyrophosphite of the following general formula (4) It is comprised by obtaining the benzamide of General formula (1).

Food,

A, B, X and n are as described above.

Tetraethylpyrophosphite is prepared by the method described in [Methoden der Organischen Chemie (Houben Weyl), page 123, X II / 2].

The method will be described in detail with reference to Examples.

Example 1

N- (1-ethyl-2-pyrrolidylmethyl) -2-methoxy-5-sulfamido benzamide

1.15 g (0.005 mol) of 2-methoxy-5-sulfamidobenzoic acid 0.64 g (0.005 mol) N-ethyl-2-aminomethylpyrrolidine, 30 ml di Oxane and 1.4 g (0.005 mole) of tetraethyl pyrophosphite were injected.

After heating the contents of the flask under reflux for 2 hours and cooling, the dioxane was evaporated under vacuum.

30 ml of water was added to the residue, acidified with hydrochloric acid, then boiled and filtered. Ammonia was added to the hot filtrate.

The filtrate was cooled, extracted three times with 30 ml of chloroform, and the organic solution was dried over magnesium sulfate.

The solution was filtered, the solvent was evaporated under vacuum to crystallize the residue with isopropanol, and then filtered and dried in an oven at 50 ° C., 0.35 g of N- (1-ethyl-2-pyrrolidylmethyl) -2-mer Toxy-5-sulfamidobenzamide was obtained. Melting Point: 179 ℃

Example 2

N- (diethylaminoethyl) -2-methoxy-5-methylsulfonyl benzamide

In a 100 ml flask equipped with a stirrer and a cooler, 1.15 g (1.005 mole) of 2-methoxy-5-methylsulfonylbenzoic acid, 0.58 g (0.005 mole) of N, N-diethylethyleneamine, 30 ml of dioxane, and 1.4 g (0.005 mole) of tetraethylpyrophosphite was injected.

The contents of the flask were heated at reflux for 24 hours, then cooled and the solvent was evaporated under vacuum.

The residue was dissolved in 15 ml of water and 2 ml of hydrochloric acid, then filtered, and left to be alkaline by addition of soda to harden. The product was filtered, washed with water and dried in an oven at 50 ° C. to give N- (diethylaminoethyl) -2-methoxy-5-methylsulfonylbenzamide of 1.1. Melting point 120 ℃

Example 3

N- (1-ethyl-2-pyrrolidylmethyl) -2-methoxy-5-ethylsulfonylbenzamide

In a 100 ml flask equipped with a stirrer and a cooler, 1.2 g (0.049 mol) of 2-methoxy-5-ethylsulfonylbenzoic acid, 0.65 g (0.005 mol) of N-ethyl-2-aminomethylpyrrolidine, 50 ml Dioxane and 1.4 g (0.005 mole) of tetraethylpyrophosphite were injected.

The contents of the flask were heated to reflux for 2 hours 30 minutes to cool, and then the solvent was evaporated under vacuum. The residue was dissolved in 30 ml of water and acidified with hydrochloric acid. Subsequently, the filtrate was made alkaline by adding soda and extracted twice with 30 ml of methylene chloride.

The organic solution was dried over magnesium sulfate. After filtration, the solvent was evaporated under vacuum to dissolve the residue in isopropanol, and then hydrochloric ethanol was added to pH 1. The product was left to crystallize, filtered and dried in an oven at 50 ° C., and 1.3 g of N- (1-ethyl-pyrrolidylmethyl) -2-methoxy-5-ethylsulfonyl benzamide was obtained. Melting Point: 186 ℃

Claims (1)

As described above in the text, 2,5-disubstituted benzoic acid of the following general formula (2) is used as a starting material and is treated with an amine of the following general formula (3) in the presence of tetraethyl pyrophosphite. The manufacturing method of benzamide of following General formula (1).

Food, A may be a low molecular weight mono- or dialkyl amino group. Here, the alkyl group may be combined with or without nitrogen, oxygen or sulfur to form a ring. When the ring contains a nitrogen atom, the nitrogen atom can be bound to a low molecular weight alkyl group. The ring so formed can be, for example, pyrrolidinyl, piperidinyl, imidazolinyl, piperazino, morpholino or thiazolidinyl. Alternatively, A may be a heterocycle group of the following form.

Food, R is a low molecular weight alkyl group or alkylene group, m is an integer of 4 or less. B may be a low molecular weight alkyl group or alkylene group, n is 1 or 2, X may be an amino, mono- or dialkylamino, alkyl or alkylene group.