GB850394A - Process for the preparation of acetanilide derivatives - Google Patents

Abstract

Dichloroacet-4-hydroxy-N-methylanilide and its carboxylic esters <FORM:0850394/IV(b)/1> where R1 is a hydrogen atom or an acyl radical are prepared by methylating a compound of the general formula: <FORM:0850394/IV(b)/2> where R3O- may be identical with the ester group above or R3 may be a group readily removable by hydrolysis, e.g. a tetrahydropyranyl group, and -N=Y represents the group -NHR4 wherein R4 is a formyl, acetyl or a dichloracetyl group, or -N=Y represents -N=CHR5 wherein R5 represents a phenyl radical or a substituted phenyl radical, the methylated product is then hydrolysed, except in the case where -N=Y represents -NHCOCl2, whereby there is obtained R3O PhNMeH from which the desired compound is obtained if necessary, by dichloracetylation and/or hydrolysis. Example 1 describes the preparation of 4-(dichloroacet-N-methylamido) phenyl benzoate. The starting-material is p-aminophenol which is treated with chloral cyanohydrin or with dichloroacetyl chloride to produce p-dichloro-acetamidophenol, this is then converted by means of benzoyl chloride into 4-dichloro acetamido phenyl benzoate, which is converted into the desired product by methylation with methyl iodide in the presence of potassium hydroxide or with dimethyl sulphate in the presence of potassium carbonate. In example 2, the product of example 1 is hydrolysed, by two methods, to give dichloroacet-4-hydroxy-N-methylanilide. In example 6, dichloroacet-4-hydroxy-N-methylanilide is obtained by a similar series of reactions except that, in the second step, p-dichloroacetamidiophenol, instead of being converted into the benzoate, is reacted with dihydropyran to give dichloroacet-4-(21-tetrahydro-pyranyloxy)-anilide. In example 5, p-aminophenol is condensed with benzaldehyde to obtain 4-benzylidene-aminophenol, which is then acetylated with acetic anhydride. The 4-benzylideneaminophenyl acetate so obtained is heated with dimethyl sulphate, and the cooled product is treated with water and allowed to decompose overnight. The solution is next treated with excess of sodium bicarbonate whereupon 4-methylaminophenyl acetate separates as an oil, which is extracted with benzene. Finally, the 4-methylaminophenyl acetate is reacted with dichloroacetyl chloride to obtain 4-(dichloroacet-N-methylamido) phenyl acetate. In example 7, p-aminophenol is reacted with formic acid to obtain p-hydroxyformanilide, which is treated with benzoyl chloride to give 4-formamidophenyl benzoate. Methylation of the latter yields 4-(formo-N-methylamido) phenylbenzoate, which is hydrolysed with N-HCl to give 4-methylaminophenyl benzoate. In example 8, the product of example 7 is treated with dichloro acetyl chloride to obtain 4-(dichloroacet-N-methylamido) phenyl benzoate. In example 9, 4-methylaminophenyl benzoate is hydrolysed with 5 N-H2SO4 to obtain 4-methylaminophenol sulphate, which is dichloroacetylated to yield dichloroacet-4-hydroxy-N-methylanilide. Specifications 767,148, 788,806, and 794,762 are referred to.