4- Amino-5-substituted-1,2,4-triazole-3-thiones

The Schiff base derivatives 73 of the 3-hetaryl-substituted 4-amino-3-thiol-l,2,4-triazoles, on treatment with acetic anhydride, undergo cyclization to give the corresponding 3-substituted-5-acetyl-5,6-dihydro-6-phenyl[l,2,4]triazolo[3,4-7][l,3,4]thiadiazoles 76 (Equation 16) <1990IJB135>. Similar treatment of 4-(A-bcnzoylamino)-4,5-dihydro-l-methyl-3-mcthylthio-1 //-[ 1,2,4 triazolc-5-thione 77 leads to the [l,2,4]triazolo[3,4-4][l,3,4]thiadiazolium trifluoromethanesulfonate 78 (Equation 17) <1986LA1540>. 

The most widely used method for the preparation of [l,2,4]triazolo[3,4-A][l,3,4]thiadiazoles 85 employs 4-amino-5-thio-4/7-[l,2,4]triazoles 83 or 4-amino[l,2,4]-triazole-5(47T)-thiones 84 as starting materials. The reaction of the triazoles 83 or 84 with carbonic acid derivatives furnishes [l,2,4]triazolo[3,4-4][l,3,4]thiadiazoles with a heteroatom substituent (N, O, S) at position 6 the O- and S-functions are formulated as 6-hydroxy and 6-thio derivatives 85a or as thiadiazol-(5/7)6-ones and -thiadiazole-(577)6-thiones 85b, respectively reaction with carboxylic acid derivatives provides the 6-substituted-[l,2,4]triazolo[3,4-4][l,3,4]-thiadiazoles 85c (Equation 20 Table 3). 

Contrasting with the reported formation of fused [l,3,4]thiadiazole rings in the course of the reaction of 3-substituted-4-amino-5-thio-47/-[l,2,4]triazoles 83 with various isothiocyanates (cf. Section 11.07.8.3, Table 3), the reactions with methyl isothiocyanate and with phenylisocyanate afford 3,7-disubstituted-6,7-dihydro-57/-[l,2,4]triazolo[4,3-f] [l,2,4]triazole-6-thiones 110 and -triazole-6-ones 111, respectively (Equation 29) <1986MI607, 1992IJB167>.The same reaction of 4-amino-l-methyl-3,5-bis(methylthio)[l,2,4]triazolium iodide 112 with aryl isothiocyanates yields the mesoionic compounds 113 (Equation 30) <1984TL5427, 1986T2121>. 

The reactions of 7-chloro-pyrimido[5,4-/][l,2,4]triazolo[3,4- ]l,3,4] thiadiazepines 81a-c with different nucleophiles were described in order to obtain new derivatives with possible antitumor activity <2003MI46>. The substituted 81a-c were prepared by cyclocondensation of 4,6-dichloro-2-methylthiopyrimidine-5-carbaldehyde 82 with the corresponding 3-substituted 4-amino-l,2,4-triazole-5-thiones 83. The different reactions as well as the corresponding yields are described in Scheme 8. Interestingly, hydrolysis occurred even during 111 NMR experiments in DMSO at 80 °C. 

Several papers have dealt with 1,2,4-triazolo[3,4-fc][ 1,3,4]thiadiazines including synthesis of new derivatives and tautomeric studies <02SC3455 02ZN(B)552 02PS487> and a one-pot synthesis starting from 4-amino-5-substituted-l,2,4-triazole-3-thiones involving a solid acid-induced cyclocondensation <02PS2403>. 

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