Studies on Chemotherapeutics for Mycobacterium tuberculosis. X.

Synthesis and Antibacterial Activity of 2-o-Hydroxybenzylidene-hydrazono-4-thiazolidone and Its Related Compounds. (5)

Abstract

It has already been shown that o-hydroxybenzylidenehydrazono-4-thiazolidone (I) is a powerful growth inhibitor of tubercle bacilli. 2-Salicyloylhydrazono-4-thiazolidone (II), with a very similar structure with a hydroxyl group in the ortho-position of the benzene ring bonded to -CONH-N=group, lacks the antibacterial functional group, -CH=N-N-, present in (I) so that its antibacterial action is very weak. Ten kinds of 2-acylhydrazono-4-thiazolidones possessing -CO-NH-N=structure as in (II) were prepared and were submitted to antibacterial tests. The actions were found to be very weak with the exception of 2-isonicotinoylhydrazono-4-thiazolidone (VIII), whose comparatively high antibacterial action was assumed to be due to the isonicotinoyl residue.
The syntheses of these compounds followed two methods. The one started with the heating of carboxylic acid hydrazide hydrochlorides with ammonium thiocyanate in chlorobenzene as a solvent, the thiocyanate was submitted to rearrangement to form the acylthiosemicarbazide, which was condensed with ethyl chloroacetate to obtain the desired 2-acylhydrazono-4-thiazolidones. The other was a new method devised by the writers in which 2-thio-4-thiazolidone and carboxylic acid hydrazide were reacted in methanol solution, in weakly alkaline state, with hydrogen peroxide which effected concurrent desulfurization and the desired reaction to the objective substance. This method is recommended because of a good yield of the products.