KR820000075B1 - New process for the preparation of 2,5-disubstituted benzamides - Google Patents

Abstract

Benzamides. (I; A = low molecular wt. mono- or dialkyl-amino; R = low molecular wt. alkyl or alkenyl; m <4; B = low molecular wt. alkyl or alkenyl; n = 1 or 2; X = amino, mono- or dialkylamino, alkyl or alkenyl) were prepd. by the reaction of 2,5-disubstituted benzoic acid(II) and H2N(CH2)n-A in the presence of anhydrous phosphoric acid. Thus, 2-methoxy 5-sulfamidobenzoic acid and N-ethyl 2-aminomethylpyrrolidine were reacted with anhydrous phosphoric acid in 150≰C to give N-(1-ethyl 2-pyrrolidylmethyl) 2-methoxy 5-sulfamidobenzamide in 67-9% yield.

Description

Method for producing 2,5-disubstituted benzamide

The present invention relates to a novel process for producing 2,5-disubstituted benzamide having the following general formula (1).

Wherein [A is a low molecular weight mono- or dialkylamino group, the alkyl group can be combined with nitrogen, oxygen or oil port or singly to form a ring (when the ring contains a nitrogen atom, the nitrogen atom is low Or a ring in this case, for example, pyrrolidinyl, piperidinyl, imidazolidinyl, piperazino, morpholino and thiazolidinyl, or the like. And heterocycle groups.

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

The present invention also includes acid addition salts and quaternary ammonium salts with pharmacologically acceptable inorganic or organic acids of benzamide having the general formula (1).

The method of the present invention is to prepare desired benzamide of formula (1) by reacting 2,5-disubstituted benzoic acid of formula (2) with an amine of formula (3) in the presence of anhydrous phosphoric acid: Consists of.

In the formula, B, X, n and A are as described above. The present invention will be described in detail based on the following examples.

Example 1

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

6.9 g (0.03 mol) of 2-methoxy 5-sulfamidobenzoic acid and 7.7 g (0.06 mol) of N-ethyl 2-amino methylpyrrolidine were injected into a 250 ml volumetric flask equipped with a stirrer and a thermometer. The mixture was raised to a temperature of 100 ° C. and 6.9 g (0.045 moles) of anhydrous phosphoric acid was added, followed by continued heating and raising to 165 ° C. in a few seconds when reaching a temperature of about 110 ° C. The mixture was stirred at about 150 ° C. for 20 minutes and then cooled to 100 ° C. 70 ml of water was added thereto, the reaction mixture was heated to boiling temperature, filtered, the hot filtrate was alkalinized with ammonia to PH9, cooled, and the resulting suspension was extracted three times with 200 ml of chloroform. The organic phase was dried over magnesium sulfate, the solution was filtered, the solvent was evaporated, and the residue was recrystallized from ethanol. 65%) was obtained. Melting Point: 179 ℃

Example 2

N- (diethylaminoethyl) 2-methoxy 5-methylsulfonylbenzamide

6.9 g (0.03 mol) of 2-methoxy 5-methylsulfonylbenzoic acid and 7 g (0.06 mol) of N, N-diethylethylenediamine were injected into a 250 ml spherical flask equipped with a stirrer and a thermometer. The mixture was raised to 100 ° C., after adding 6.5 g (0.045 mol) of phosphoric anhydride to the temperature of 135 ° C., heating was continued, and the reaction was continued at 150 ° C. for 20 minutes. The reaction mixture was cooled to about 100 ° C. and 80 ml of water was added to dissolve the mixture. The solution was then left to cool by alkaline with 20 ml of sodium hydroxide and extracted three times with 50 ml of methylene chloride. The organic phase was dried over magnesium sulfate, filtered and the solvent was evaporated in vacuo. The residue was dissolved in 20 ml of water and 2 ml of sodium hydroxide, and the solution was filtered to wash the raw document and dried in a drier at 50 ° C. N- (diethylaminoethyl) 2-methoxy 5-methylsulfonylbenzamide 6.6 g (Yield 67%) was obtained. Melting Point: 118 ℃

Example 3

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

7.3 g (0.03 mol) of 2-methoxy 5-ethylsulfonylbenzoic acid and 6.8 g (0.053 mol) of N-ethyl 2-aminomethylpyrrolidine were injected into a 250 ml spherical flask equipped with a stirrer and a thermometer. The mixture is heated to 100 ° C. and 6.3 g (0.044 mol) of phosphoric anhydride is added to produce an exothermic reaction. When the heating was continued to reach a temperature of 160 ° C., the reaction mixture was allowed to react for about 15 minutes, cooled to 100 ° C., 50 ml of water was added, and the solution was alkaline with sodium hydroxide. The aqueous solution was left to cool to normal temperature and extracted three times with 50 ml of methylene chloride. The organic phase was dried over magnesium sulfate, filtered, evaporated to dryness, the residue dissolved in ethanol and the solution acidified with hydrochloric alcohol. The solution was crystallized in a cooler, filtered and the product was washed with a small amount of alcohol and dried in a drier at 50 ° C .. N- (1-ethyl-2-pyrrolidylmethyl) 2-methoxy 5-ethyl sulfonylbenzamide (Yield 69%) was obtained. Melting Point: 186 ℃

Claims (1)

As described above in the text, the 2,5-disubstituted benzoic acid of the following general formula (2) is reacted with the amine of the following general formula (3) in the presence of phosphoric anhydride to give the 2,5-disubstituted general formula (1) Method for producing benzamides.

Wherein [A is a low molecular weight mono- or dialkylamino group, in which the alkyl group is combined with nitrogen, oxygen or sulfur or alone to form a ring (when the ring contains a nitrogen atom, the nitrogen atom has a low molecular weight Ring in this case, for example, pyrrolidinyl, piperidinyl, imidazolidinyl, piperazino, morpholino and thiazolidinyl, etc.) or a hetero having the following general formula It includes a cycle group.

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