Efficient Routes for the Synthesis of Novel Bis(s-triazolo[3,4-b][1,3,4]thiadiazines)

Bis(triazolo[3,4-b]thiadiazine) 4 in which the fused system is linked directly to the benzene core can be synthesized in 75% yield by, firstly, preparation of bis(s-triazole) 2 followed by reaction with phenacyl bromide 3 in refluxing EtOH/DMF mixture containing piperidine. Bis(s-triazolo[3,4-b][1,3,4]thiadiazines) 8 and 11 in which the triazolothiadiazines are linked to benzene core via alkyl or ether linkage were synthesized in 70 and 72% yields, respectively, starting from dicarboxylic acids 5 and 9 upon treatment with two moles of thiocarbohydrazide 6 to give the corresponding bis(4-amino-5-mercapto-s-triazolo-3-y1) derivatives 7 and 10 and subsequent reaction with twoequivalents of phenacyl bromide. Bis(6-phenyl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines) 15a, 15b, 15c, 15d, 15e, 15f, which are linked to arene cores via sulfanylmethylene spacers, were prepared by the reaction of 4-amino-4H-1,2,4-triazole-3,5-dithiol 12 with the appropriate bis(bromomethyl)benzenes 13a, 13b, 13c, 13d, 13e, 13f to give bis(4-amino-5-mercapto-4H-3-sulfanylmethyl)arenes 14a, 14b, 14c, 14d, 14e, 14f and subsequent reaction with phenacyl bromide. Compounds 15a, 15b, 15c, 15d, 15e, 15f were alternatively obtained in 60-70% yields by twofold substitution of 13a, 13b, 13c, 13d, 13e, 13f with twoequivalents of 6-phenyl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine-3-thiol 16 in refluxing EtOH/DMF mixture containing KOH. Bis(triazolothiadiazine) 22 attached to the benzene core through the thiadiazine ring via an amine linkage was prepared in 70% yield starting from p-phenylenediamine 19 by, firstly, acylation with chloroacetyl chloride 18 followed by bis-alkylation with 1,2,4-triazole 20 and subsequent intramolecular ring closure upon treatment with phosphorus oxychloride.