In the 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 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... 

Cyclotrithiazyl chloride is also a useful reagent in organic chemistry in the fusion of 1,2,5-thiadiazoles to quinones as well as the synthesis of (a) isothiazoles from 2,5-disubstituted furans and (b) bis-1,2,5-thiadiazoles from A-alkylpyrroles (Scheme 8.4). Alkenes and alkynes react readily with (NSC1)3 to give 1,2,5-thiadiazoles, while 1,4-diphenyl-1,3-butadiene gives a variety of heterocyclic products including a bis(l, 2,5-thiadiazole). ... 

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. 

The 1,2,3-thiadiazole literature was extensively reviewed in CHEC(1984) <1984CHEC(6)447> and CHEC-II(1996) <1996CHEC-II(4)289>. It covered the literature up to 1996 and cited many excellent references to 1,2,3-thiadiazoles. A further review on the chemistry of 1,2,3-thiadiazoles, which gives a critical review of methods of synthesis and is accompanied by experimental procedures, appeared in Science of Synthesis <2004HOU(13)253>. Another review of 1,2,3-thiadiazoles also appeared in 2004 . An annual review of the chemistry of 1,2,3-thiadiazoles appears in Progress in Heterocyclic Chemistry (Chapter 5.5). This review covers the 1,2,3-thiadiazole literature up to 2006. 

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). 

The chemistry of 1,2,3,5-thiatriazoles was covered previously in CHEC(1984) <1984CHEC(6)579> together with data on 1,2,3,4-oxa- and thiatriazoles, and in CHEC-II(1996) <1996CHEC-II(4)733>. Older reviews were cited in the introductions to these texts. Synthetic aspects of 1,2,3,5-thiadiazole derivatives and the isomeric 1,2,3,4-thiatri-azoles were recently reviewed by Begtrup <2004HOU833>. 

The ninth volume of Advances in Heterocyclic Chemistry includes surveys of the chemistry of the following groups of heterocyclic compounds 1,2,5-thiadiazoles (L. M. Weinstock and P. I. Pollack) 1,3,4-thiadiazoles (J. Sandstrom) pyridazines (M. Ti ler and B. Stanovnik) Reissert compounds (F. D. Popp) phenothiazines (C. Bodea and I. Silberg) and pyrrolopyridines (R. E. Willette). 

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