A considerable number of 1,3,4-oxadiazole derivatives were found to have bactericidal, analgesic, muscle relaxant and tranquilizing properties'-5) . 5-Aryl-2-thiono-l,3,4-oxadiazoles have analgesic, antipyretic, antidescribes the synthesis and reactions of some 1,3,4-oxadiazoles.N -NH S phlogistic properties6"' and show antitubercular activity'). This manuscript
R S H RThus, 2-cyan0 (or phenyl) ethanoic acid hydrazides la, b were condensed with selected carbonyl compounds to give the hydrazones 2a, f, which upon treatment with acetic anhydride afforded the corresponding 5-benzyl-(or cyanomethyl)-3-acetyl-2,2-disubstituted-1,3,4-0xadizolines 3a, e.Interaction of the hydrazide l a or b with aliphatic or aromatic acid chlorides in pyridine yielded the corresponding N,"-diacylhydrazines as unisolated intermediates, which upon reflux with P0C139) or acetic anhydride gave the expected 2,5-disubstituted-l,3,4-oxadiazoles 4a, b. Prolonged heating of 4a with the appropriate aliphatic primary amine in xylene yielded the corresponding triazole derivatives 6a, b.Refluxing of equimolar amounts of l a or b and ClCOOC2Hs produced 2-hydroxy-5-(benzyl or cyanomethyl)-l,3,4-oxadiazoles 5a, b. 5a reacted with S0C1210) to give 5-chloro-2-benzyl-1,3,4oxadiazole (7).When N-nucleophiles") such as aniline, p-toluidene, hydrazine hydrate, and phenylhydrazine were reacted with 7, 2-arylamino, hydrazino, or phenylhydrazino-5-benzyl-1,3,4-oxadiazoles 8a-d were readily obtained. On the other hand when 7 was reacted wlrh NaN3 in boiling acetic acid, the 2-azido derivative 9 was obtained.Condensation of hydrazide l a or b with KOH and CS2 in ethanol' ') gave the corresponding 2-(benzyl or cyanomethyl)-l,3,4-oxadiazol-5-thiols 10a, b. Evidently"), these compounds exist as thiol-thione equilibrium:Thus, compound 10a reacted with piperidine or morpholine in the presence of formaldehyde to give the expected Mannich based3) lla, b. On the other hand 2-(benzyl or cyanomethyl)-5-carboxymethylthio-1,3,4-oxadiazoles 12a, b and their esters 13a, b were obtained by condensation of 10a and b wlth chloroacetic acid in alkaline medium or with ethyl bromoacetate in the presence of NaOH14), respectively.The ester 13a reacted readily with prim. aromatic amines and hydrazines, namely: aniline, p-toluidene, hydrazine hydrate, and phenylhydrazine giving the corresponding amides, hydrazide, and phenylhydrazide derivatives 14a-d, respectively.
Experimental PartMelting points: uncorrected. -IR spectra (KBr): Pye-Unicam SP lo00
N-Arylidene-N'-(cyanoacetylorphenylacetyl)-hydrazine 2a-fThe appropriate carbonyl compound (0.01 mol) was added to a hot solution of l a o r b (0.01 mol) in 50 ml ethanol and the mixture was refluxed for 1 h. The solid which separated on cooling was washed with ethanol and recrystallized from the proper solvent (Table 1)
