Acyl thiosemicarbazides, cyclization

The synthesis of 1,3,4-thiadiazoIes is discussed in terms of the number of bonds being formed and by ring transformation. Thiadiazole synthesis by one-bond formation is exemplified by the cyclization of an acylated thiosemicarbazide as shown in Scheme 16. The most common two bond formation takes place via 1,3-dipolar cycloadditions presented in Scheme 23. 

Acylation of thiosemicarbazide with propionyl chloride, interestingly, does not stop at the acylated product (124). Instead, this intermediate cyclizes to the thiadiazole, 125, under the reaction conditions. Hydrolysis then affords the heterocyclic amine, 126. Acylation by 88 followed by removal qf the acetyl group affords sulfaethidole (116) variation of thle acid chloride used in the preparation of the heterocycle leads to 117 and 118. 

Monothiodiacylhydrazines 127, derived from the acylation of thiosemicarbazides or as intermediates in the reactions of (1) thiohydrazides with carboxylic acids and their derivatives (see Section 5.10.9.2.2(i)) or (2) hydrazides with thiocarbonyl compounds (see Section 5.10.9.2.3(i)), cyclize in the presence of an acid catalyst to give 1,3,4-thiadiazoles 128 (Equation 39, Table 4). 

Acylation of thiosemicarbazides with acyl chloride 222, under standard basic conditions, gives 2-aryl-5-methyl-thia-zolo[3.2-// [ l, 2,4]triazolc-6-carbothiosemicarbazides 223, that on sodium hydroxide-promoted cyclization affords 2-aryl-5-methyl-thiazolo[3,2-4][l,2,4]triazol-6-yl)-l//-l,2,4-triazole-3-thiones224 (unreported yields) (Scheme 14) <2001FAR15>. 

The synthesis of numerous thiadiazoles substituted in the 5-position with carbamoyl or heteroaryl moieties and hydroxyl or amino groups in the 2-position (Scheme 20), was achieved by reacting dithioesters with semicarbazide or thiosemicarbazide and cyclizing the resulting acylated sem-... 

A versatile route to 2-aminooxadiazoles (92), which generally proceeds in higher yield than oxidation of thiosemicarbazides (82), is the cyclization in aqueous or alcoholic solution of l-acyl-2-cyanohydrazines (91) prepared from acylhydrazines and cyanogen bromide (Scheme 16). Alternatively, hydrazines (91) are obtained by acylation of cyanohydrazines (66EGP52668). 

---