CS252337B1 - Process for preparing novel 2- (4-tert-aminophenylthiomethyl) benzoic acids - Google Patents

Abstract

The solution relates to the field of drug synthesis. Its subject is a method for preparing new 2-/4-tert.aminophenylthiomethyl/benzoic acids of the general formula I, /-CH2S-Á R COOH in which R denotes a dimethylamino, pyrrolidino, piperidino or morpholino residue. The substances of formula I are intermediates in the synthesis of neurotropically active drugs. The method of preparation consists in the reactions of phthalide with sodium salts of the corresponding 4-/tert.amino/thiophenols in boiling ethanol.

Description

The present invention relates to a process for the preparation of novel 2- (4) tertiaminophenylthiomethyl (benzoic acids) of the formula

COOH wherein R represents a dimethylamino, pyrrolidino, piperidino or morpholino radical

The compounds of the invention of formula I are intermediates in the synthesis of neurotrophic drugs. The process for the preparation of the compounds of the formula I according to the invention consists in reacting the phthalide with the sodium salts of the 4- (tert.amino) thiophenols of the formula II,

HS

(11) wherein R is the same as in Formula I, in boiling ethanol.

The starting 4- (tert.amino) thiophenols have been described in the literature in general: 4- (dimethylamino) thiophenol] see Banfield J.E., J.Chem.Soc. 1960, 456) and others, i.e., 4-pyrrolidinothiophenol, 4-piperidinothiophenol and 4-morpholinothiophenol in the work of Kmoníček V. et al., Collect. Czech. Chem. Commun. 51, 937 (1986). Details of this method of preparation are given in the examples, which are intended to illustrate the possibilities of the invention, but not all of these possibilities are exhaustively described. The compounds of formula I according to the invention are novel. Its identity was ensured both by analyzes and by usual spectral methods. They are mostly crystalline substances, which are very poorly soluble in water, but dissolve in solutions of alkali hydroxides and carbonates into solutions of the corresponding alkali salts.

Example 1

2 - {[1- (Dimethylamino) phenylthiomethyl] benzoic acid (1, R = dimethylamino)

Dissolve 4.1 g of sodium in 200 ml of ethanol to prepare a sodium ethoxide solution, add 27.4 g of 4- (dimethylamino) thiophenol / lithium citrate and 23.0 g of phthalide, and reflux for 3 h. . Ethanol is evaporated! in vacuo, the residue was dissolved in 100 ml of water, the solution was filtered, and the filtrate was neutralized with acetic acid to pH 6. Standing overnight and filtration gave 33.2 g (65%) of the crude product, m.p. Mp 140-145 ° C. An analytical sample was prepared by recrystallization from aqueous ethanol, m.p. Mp 151-153 ° C.

Example 2

2- (4-Pyrrolidinophenylthiomethyl) benzoic acid (1, R-pyrrolidino)

Prepared in analogy to Example 1 from 12.0 g of 4-pyrrolidinothiophenol (lithium citrate), 8.7 g of phthalide and sodium ethoxide (1,6 1.62 g of sodium) in 100 ml of ethanol; 10.2 g (50%), m.p. 193 DEG-195 DEG C. (ethanol).

Example 1 and d 3

2- (4-Piperidinophenylthiomethyl) benzoic acid (1, R-piperidino)

Prepared in analogy to the previous two products from 19.2 g of 4-piperidinothlophenol (lithium cited), 13.0 g of phthalide and sodium ethoxide (from 2.3 g of sodium) in 80 ml of ethanol; 14.5 g (45%), m.p. 146-148 ° C (aqueous ethanol).

Example 4

2- (4-Morpholinophenylthiomethyl) benzoic acid (1, R = morpholino)

Prepared in analogy to the previous procedure from 11.7 g of 4-morpholinothiophenol (lithium cited), 7.5 g of phthalide and sodium ethoxide (from 1.38 g of sodium) in 50 ml of ethanol; 11.6 g (60%), m.p. 123 DEG-124 DEG C. (aqueous methanol).

Claims (1)

SUBJECT OF THE INVENTION A process for the preparation of the novel 2- (4-tertiaminophenylthiomethyl) benzoic acids of the formula I COOH wherein R is a dimethylamino, pyrrolidino, piperidino or morpholino radical, characterized in that the phthalide is reacted with the sodium salts of the 4- (tert.amino) thiophenols XI HS (11), wherein R is the same as in Formula I, in boiling ethanol.