Verfahren zur Herstellung von antimykotisch wirksamen 4-Halogensalicylsaeureamiden

The invention comprises compounds of the formula : (wherein Hal is chlorine, bromine or iodine, R1 is an alkyl, alkenyl, phenyl-alkyl, cycloalkyl or cycloalkyl-alkyl group, the alkyl and alkenyl groups of which contain at most 10 carbon atoms, and R2 is a hydrogen atom or an alkyl group of at most 3 carbon atoms) and alkali metal and alkaline earth metal salts thereof ; and the preparation thereof by reacting a reactive derivative of the appropriate 4-halogen-2-hydroxy-benzoic acid with the appropriate amine. In examples (1) 4-chloro-2-hydroxy-benzoic acid n-butylamide is prepared from the n-butyl ester and n-butylamine, and is also converted into the sodium salt and into a complex with n-butylamine containing 2 mols of amide per mol of amine ; (2) to (4) the corresponding n-hexylamide, n-and iso-propylamides, n-pentylamide, benzylamide, iso-amylamide, allylamide and betaphenylethylamide are prepared similarly ; (5) 4-chloro-2-hydroxy-benzoic acid and oxalyl chloride give 4-chloro-2-hydroxy-benzoic acid chloride, and this with n-butylamine gives the product of (1) ; (6) 4-bromo-2-hydroxybenzoic acid and ethanol in presence of H2SO4 give ethyl 4-bromo-2-hydroxy-benzoate and this with n-butylamine gives the n-butylamide ; (7) methyl 4-iodo-2-hydroxybenzoate and hydrazine hydrate give 4-iodo-2-hydroxy-benzoic acid hydrazide, this on diazotisation gives 4-iodo-2-hydroxybenzoic acid azide, and this with n-butylamine gives the n-butylamide ; (8) 4-chloro-2-hydroxy-benzoic acid azide is prepared by diazotisation of the corresponding hydrazide, and is then reacted with N-allyl-N-ethylamine to give the (N-ethyl-N-allyl)-amide ; (9) 4-chloro-2- hydroxy-benzoic acid cyclohexylamide and cyclopentylamide are prepared by a method similar to (1) ; and (10) 4-chloro-2-hydroxy-benzoic acid hydrazide, prepared from the methyl ester and hydrazine hydrate, is converted to the azide and this is reacted with hexahydrobenzylamine to give the corresponding (N-hexahydrobenzyl)-amide. Other amine reactants are also referred to. Specification 757,999 is referred to.ALSO:Pharmaceutical compositions comprise compounds of the formula: (wherein Hal is chlorine, bromine or iodine, R1 is an alkyl, alkenyl, phenyl-alkyl, cycloalkyl or cycloalkyl-alkyl group, the alkyl and alkenyl groups of which contain at most 10 carbon atoms, and R2 is a hydrogen atom or an alkyl group of at most 3 carbon atoms) or alkali metal or alkaline earth metal salts ther