Synthesis from Oxadiazolium Salts

Synthesis from Oxadiazolium Salts. JV-Aryl-l,3,4-oxadiazolium salts (125) may serve as starting materials for the preparation of the corresponding 1,3,4-thiadiazoles. Their reaction with sodium sulphide yields 

Maguet, Y. Poirier, and J. Teste, Bull. Soc. chim. France, 1970, 1503. 

The same sequence of reactions furnishes 2,5,7-trisubstituted 8-cyano-l,3,4-thiadiazolo[3,2-fl]pyridinium salts (129), by way of intermediate substituted acylaminopyridine thiones (128).  

Numerous 1,3,4-thiadiazoles have been produced by known routes, mostly in the course of biological screening programmes. They are listed in Table 1, as are derivatives obtained by simple methods from the preformed heterocyclic system. 

Existing syntheses of 2-amino-5-(l-methyl-5-nitro-2-imidazoIyl)-l,3,4-thiadiazole (140), an outstandingly powerful antimicrobial and antiprotozoal agent, have been supplemented by a route in which the imidazole ring is built upon a preformed thiadiazole nucleus. 

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Amino-1,2,4-triazoles (50) or their derivatives are usually starting material for the synthesis. They are readily available and already contain the exocyclic N-N bond required for heteroaromatic A-imines. 4-Amino-1,2,4-triazoles can be quaternized by alkyl halides or tosylates at the N-l atom to give the salt 52.79-82 (Scheme 5) The orientation of quatemization is proved by the reactions in Scheme 6 for the example of the quaternary acylamino salts 52. Quaternary salts of the type 52 can also be prepared by reaction of 1,3,4-oxadiazolium salts (51)83 with aryl hydrazines84 and from aryl hydrazine hydrohalides and orthoesters.86 With alkali, the 1-alkyl-s-triazole-4-imines8(7-82 86 can be obtained in the normal manner from these salts (Scheme 5). The free A-imines are all stable except the A-unsubstituted compound itself.87 Recently, other structures were tentatively reported 88 for the deprotonation products of analogous quaternary salts (52) with hydrazine. 

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