Abstract:
As some hydrazides and diacylhydrazines of isonicotinic acid were known to possess high tuberculostatic activity, but some of them were also relatively highly toxic or easily excreted. In this study
N-N'-diacylhydrazines and polyhydrazide containing other nucleus,such as benzene ring and furan ring were prepared for the purpose of finding some most active and least toxic antituberculosis compounds.
N,N'-diacylhydrazine was prepared by the action of the appropriate acid chloride on acyl hydrazine in presence of anhydrous pyridine or acetonitrile.One hydrazide and six
N,N'-diacylhydrazines prepared are listed in table 1.Three of them have been tested for tuberculostatic activity,but none of those compounds was active. Poly-hydrazide was prepared by the action of the corresponding ester with hydrazine hydrate.The thiosemicarbazide was prepared by the action of acid chloride on thiosemicarbazide in anhydrous pyridine or acetonitrile.Six compounds of poly-hydrazide and corresponding thiosemicarbazide prepared are listed in table 1.Four of them have been tested for tuberculostatic ac tivity,none of the compounds was found active. In this study,the following phenomena had been observed: 1. The reaction product between
o-amino-benzoylhydrazide and p-acetaminobenzoyl chloride is
N-(
o-amino-benzoyl)-
N'-(
p-acetamino-benzoyl)-hydrazine.This compound is different from the reaction product between
o-(
p-acetamino-benzoylamino)-ethyl-benzoate and hydrazine hydrate. 2. Reaction between
o-acetamino-benzoyl chloride and
p-acetamino-benzoyl hydrazide forms
N-(
o-acetamino-benzoyl)-
N'-(p-acetamino-benzoyl)-hydrazine.The acetyl compound of
N-(
o-amino-benzoyl)-
N'-(
p-acetamino-benzoyl)-hydrazine is difficult to obtain as it is dehydrated easily and cyclized to yield 2-methyl-3-(
p-acetamino-benzoyl)-amino-quinazolene-4.This was also obtained by condensation of 2-methyl-3-amino-quinazolene-4 and
p-acetamino-benzoyl-chloride. 3. Diethyl phthalate was reacted with hydrazine hydrate on during heating.The product was cyclized to form phthalazine.If the reaction is carried out at room temperature,cyclization can be avoided and phthalyl hydrazide is produced. 4. Let one mole of phthaloyl chloride react with two moles of thiosemicarbazide,the product obtained is
o-carbothiosemicarbazido-benzoic acid instead of phthalyl-thiosemicarbazide.This may be due to steric hindrance and orthosffect.