Chemistry of 1.3.4-thiadiazoles

The chemistry of 1,3,4-thiadiazole and its derivatives has been previously covered in both CHEC(1984) <1984CHEC(6)545> and CHEC-II(1996) <1996CHEC-II(4)379>. A major review which covers the synthetic chemistry of the ring system up to 2002 has also appeared <2004HOU(13)349>. Since 1991 advances in the chemistry of 1,3,4-thiadiazole have been annually reviewed in Progress in Heterocyclic Chemistry <1991PHC149>. 

The chemistry of 1,3,4-thiadiazole has been recently reviewed <04MI405>. The 2-substituted 1,3,4-thiadiazoles 258 are formed by the reactions of thiohydrazides 257 with DMF and diethyl chlorophosphate. This cyclodehydrating agent is superior to several commonly used ones such as ethyl orthoformate, ethyl formate or even phosphorus oxychloride for this type of cyclization <04817>. Reaction of/ -tolualdehyde hydrazone 259 with disulfur dichloride in the presence of DBU gives 2,5-di(p-tolyl)-1,3,4-thiadiazole 260 <04S1929>. 

The purpose of this chapter is to review the organic and physical chemistry of monocyclic 1,2,5-thiadiazoles up to the early part of 1967. Reference is made to the 2,1,3-benzothiadiazoles and related compounds only as they contribute to the chemistry of the basic ring system. The four isomeric thiadiazoles, including their benzo derivatives, were previously reviewed by Bambas, Grignard, and Sherman and the chemistry of 1,2,4-thiadiazoles was reviewed by Kurzer. ... 

The development of 1,3,4-thiadiazole chemistry is linked to the discovery of phenylhydrazine by Emil Fischer and of hydrazine by Th. Curtins in the late nineteenth century. The first 1,3,4-thiadiazole was described by Fischer in 1882, but the true nature of the ring system was demonstrated first in 1890 by Freund and Kuh. From 1894 Busch and his school took up work in this field, and they came to play a leading part in the rapid expansion during the first decades of the twentieth century. After a period of relatively low activity between the wars, interest was renewed due to the discovery of sulfa drugs... 

The chemistry of 1,2,5-thiadiazole systems (RC)2N2S has been extensively investigated. " In addition to the condensation reactions of sulfur halides with 1,2-diaminobenzenes, this ring system is obtained in high yields by the reaction of S4N4 with acetylenes (Section 5.2.6). For example, the reaction of S4N4 with diphenylacetylene produces 3,4-diphenyl-1,2,5-thiadiazole in 87% yield. 

Proton, C, N, and N NMR values for 1,3,4-thiadiazoles were discussed in the first edition of Comprehensive Heterocyclic Chemistry (CHEC-I) and some representative chemical shifts are summarized in Figure 1 <84CHEC-I(4)549). 

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