Studies in sulphanilamides

Abstract

The present thesis consists of three parts (each part being divided into further sub-sections) preceded by a General introductory article on “Sulphonamides”. Under the heading of “Sulphonamides” various aspects of problems of sulpha-drugs have been considered in good detail. History of development of these drugs has been traced up-to-date and their mode of action, drawbacks and correlation of physiological activity with chemical structure has been discussed thoroughly. The article concluded with general remarks as to the future of these chemotherapeuticals.

Part I deals with the preparation of alkylene-bis-N?-sulphanilamide and their azo, acyl and Schiff derivatives. In section A of this part various alkylene-bis-N?-sulphanilamides have been prepared by reacting potassium salt of acetyl sulphanilamide with various alkylene dibromides (from C? to C? alkylene dibromides), and hydrolysing the N-acetyl group later on. This method has not been hitherto used for such condensations. In the case of ethylene dibromide product a pressure reaction was successfully conducted. Total number of compounds reported is five. In section B of this part, one of the compounds prepared in section A, i.e., ethylene-bis-N?-sulphanilamide, was reacted with various aromatic aldehydes to give the Schiff’s bases of this compound, since anils have been reported in this section. Section C deals with the preparation of aromatic hydroxy azo-dyes and aromatic amine azo-dyes of ethylene-bis-N?-sulphanilamide. Ten azo-dyes and ten hydroxy azo-dyes of ethylene-bis-N?-sulphanilamide have been reported. Section D deals with aliphatic monocarboxylic acyl derivatives of ethylene-bis-N?-sulphanilamide. Acids from acetic to heptoic have been used for the purpose, and out of these a few had to be specially prepared for this purpose.

Part II of this thesis deals with the synthesis of various alkylene-bis-N?-sulphanilamides and acyl derivatives of one of the compounds in this group. Section A deals with the preparation of various alkylene-bis-N?-sulphanilamides by condensing sulphanilamide with various alkylene dibromides (same as in the case of Part I, Section A). In this case also sulphanilamide condensation with ethylene dibromide was conducted in a pressure bottle. Section B of this part deals with preparation of ethylene-bis-N?-di-N?-acyl-sulphanilamides by reacting various aliphatic monocarboxylic acid chlorides with ethylene-bis-N?-sulphanilamide. The acids used in this case are the same as in Part I, Section D. A proof to the fact that acylations in this case go only at N?-position and not at N¹ has also been furnished by experimental evidence.

Part III of this thesis deals with various N-sulphanilamide-aliphatic esters and acids. N-sulphanilamide-aliphatic esters have been prepared by reacting sulphanilamide with various bromo-substituted aliphatic esters. Various bromo-esters used were: bromoacetic ester, ?-bromo-propionic ester, ?-bromo-butyric ester, ?-bromo-malic ester and ?-bromo-phenyl-acetic ester. The ester products were hydrolysed (saponified) to give the free acid derivatives. In all the above sections of the various parts, detailed discussion in the light of literature available has been done in the introductory parts for the reasons which led to undertaking of the present work. The compounds mentioned in this thesis are awaiting pharmacological examination.