Systems incorporating 1,2,5-Thiadiazole

Only relatively little recent work concerns the parent monocyclic system by far the greater part is devoted to fused ring systems incorporating 1,2,5-thiadiazole. 

Benzo[l,2-c 3,4-c 5,6-c ]tris[l,2,5]thiadiazole.—Four related condensed tetracyclic ring systems incorporating 1,2,5-thiadiazole (202 X = S, Se, CH, or CH=CH) are accessible from a common starting material, benzo[l,2-c 3,4-c ]-bis[l,2,5]thiadiazole (200), which is converted into the diamine (201) and variously cyclized to (202). The condensation of (201) and 9,10-phenanthrene-quinone in boiling acetic acid similarly yields the heptacyclic ring system dibenzo-[a,c]bis[l,2,5]thiadiazolo[3,4-/r.3, 4V]phenazine. 2... 

Condensed ring systems incorporating 1,2,4-thiadiazole are formed when a heterocyclic compound (178) functioning as the amidine is condensed with chlorothioformyl chloride (179) or ethyldithiocarbonyl chloride (180) the scope of this synthesis is very wide indeed. 

The condensation of sulphamide and diethyl oxalate produces 3,4-dihydroxy-1,2,5-thiadiazole 1,1-dioxide as the dipotassium salt in high yield. The free acid (177) is an excellent precursor for the preparation of other functional derivatives, and for building up fused ring systems incorporating the 1,2,5-thiadiazole 1,1-dioxide structure (see below). The two isomeric benzothiadiazole acetoximes (178) and (179) undergo the Beckmann reaction, resulting in the fission of their carbocyclic ring. This provides an effective synthesis of novel ajS-unsaturated 1,2,5-thiadiazoles (180 X = COaH, Y = CR=CHCN X =... 

The 1,2,3-thiadiazole ring system has been incorporated into a number of compounds which have antiviral activity. The thioamide 86 is a potent inhibitor of cytomegalovirus (CMV) <2004BML3401>. 

When thioxo (or thiol) derivatives (as part of a thiourea function incorporated into the heterocyclic system) are present, effective. Y-alkylation is observed. Thus, the 3-heteroaryl-substituted [l,2,4]triazolo[3,4-/)][l,3,4]thiadiazole-6(5//)-thiones 37 dissolved in sodium hydroxide solution react with alkyl halides to afford the corresponding 6-alkylthio derivatives 38 (Equation 4) <1992IJB167>. The mesoionic compounds 39, inner salts of anhydro-7-aryl-l-methyl-3-methylthio-6-sulfonyl-[l,2,4]triazolo[4,3-A [l,2,4]triazolium hydroxides, are methylated with methyl iodide to give the corresponding quaternary salts 40 (Equation 5) <1984TL5427, 1986T2121>. 

Numerous structures containing the thiocarbonyl ylide dipole are conceivable. Incorporation of the thiocarbonyl ylide dipole into a bicyclic heterocyclic system is possible by the conversion of the cyclic thione (203) into the ring-fused mesoionic system (204). The thiocarbonyl ylide dipole (205) undergoes cycloaddition with both alkenic and alkynic electron-poor dipolarophiles in refluxing benzene or xylene so that, after extrusion of hydrogen sulfide or sulfur, respectively, from the initial 1 1 cycloadducts (206) and (207), a ring-fused pyridinone is formed. The method has been used for the annelation of pyridinones to the imidazole, 1,2,4-triazole, thiazole and 1,3,4-thiadiazole systems... 

Synthesis.—The majority of 1,3,4-thiadiazole syntheses are based on cyclizations of thiosemicarbazidcs or compounds incorporating this basic structural pattern. Others involve ring-closures of dithiocarbazates, acyl hydrazines, or bithioureas, or interconversions of other ring systems, particularly oxadiazoles and dithiolethiones. Recent contributions to this subject have been numerous and are presented, as far as possible, in accordance with this classification. 

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