3- 1,2,5-thiadiazole 5,5-dioxide

Although unsubstituted 1,2,5-thiadiazole is stable on heating at 220 °C, 3,4-diphenyl-1,2,5-thiadiazole 1,1-dioxide (26) decomposes into benzonitrile and sulfur dioxide at 250 °C (68AHC(9)107). 

In contrast to thiazoles, certain isothiazoles and benzisothiazoles have been directly oxidized to sulfoxides and sulfones. 4,5-Diphenyl-l,2,3-thiadiazole is converted by peracid into the trioxide (146). Although 1,2,5-thiadiazole 1,1-dioxides are known, they cannot be prepared in good yield by direct oxidation, which usually gives sulfate ion analogous to the results obtained with 1,2,4- and 1,3,4-thiadiazoles (68AHC 9)107). 

Furthermore, a series of single crystal X-ray diffraction studies were reported for several thiadiazole 1-monoxides and 1,1-dioxides, allowing a direct comparison in bond lengths and angles for an identical 3,4-substitution pattern (Table 4). The related fused phenanthro[9,10-r-]-l,2,5-thiadiazole 1,1-dioxide 51 and acenaphtho[l,2-f]-l,2,5-thiadiazole 1,1-dioxide 53 have similar bond lengths to 3,4-diphenyl-1,2,5-thiadiazole 1,1-dioxide 10 <2001JST157>. 

While 1,2,5-thiadiazole 1,1-dioxide has not yet been prepared, extrapolation of data on the known 3,4-dimethyl-l,2,5-thiadiazole 1,1-dioxide 23 <1998JP091> indicated that the nonaromatic or antiaromatic 1,2,5-thiadiazole 1,1-dioxide has a more delocalized structure than its isomeric thiadiazole 1,1-dioxide anologues <1997JMT119, 2001JMT285>. 

Thiophene-1-oxide and 1 -substituted thiophenium salts present reduced aromaticity.144 A variety of aromaticity criteria were used in order to assess which of the 1,1-dioxide isomers of thiophene, thiazole, isothiazole, and thiadiazole was the most delocalized (Scheme 46).145 The relative aromaticity of those molecules is determined by the proximity of the nitrogen atoms to the sulfur, which actually accounts for its ability to participate in a push-pull system with the oxygen atoms of the sulfone moiety. The relative aromaticity decreases in the series isothiazole-1,1-dioxide (97) > thiazole-1,1 -dioxide (98) > thiophene-1-dioxide (99) then, one has the series 1,2,5 -thiadiazole-1,1 -dioxide (100) > 1, 2,4-thiadiaz-ole-1,1-dioxide (101) > 1,2,3-thiadiazole-1,1 -dioxide (102) > 1,3,4-thiadiazole-l,1-dioxide (103) in the order of decreasing aromaticity. As 1,2,5-thiadiazole-1,1-dioxide (100) was not synthesized, the approximations used extrapolations of data obtained for its 3,4-dimethyl-substituted analogue 104 (Scheme 46). 

When the 1,2,5-thiadiazole-1,1-dioxide is fused to an aromatic ring, the nucleophilic addition occurs at sulfur not carbon. In these cases, the reduced thiadiazole behaves as a classic sulfamide, readily undergoing amine exchange (Scheme 8) <82JCR(S)84>. 

Azole approach. 3,4-Diamino-l,2,5-thiadiazole reacts with 1,2-dicarbonyl compounds to form pyrazines (747) (76JHC13). From the reaction of 1,2,5-thiadiazole 1,1-oxides such as (748) with o-phenylenediamine, the l,3-dihydro[l,2,5]thiadiazolo[3,4-Z>]quinoxaline 2,2-dioxide (749) is formed. To understand this reaction it is pointed out that the 1,2,5-thiadiazole 1,1-dioxide ring is to be regarded as alicyclic rather than aromatic and is strongly 7r-electron deficient. Substituents with leaving properties in the 3,4-positions are therefore readily displaced as in the reaction of (748) (75JOC2743). 

In the study of novel fluoroionophores as receptors for transition metal cations, 1,2,5-thiadiazole-1,1-dioxide 322 is used as an intermediate to produce the 4,5-dicyano analog 323. Upon treatment of compound 321 wth sulfamide and HCl in anhydrous ethanol, 1,2,5-thiadiazole-1,1-dioxide 322 is obtained. Vacuum pyrolysis of compound 322 yields 1-nitro-4,5-dicyanonaphthalene 323 <03TL2087>. 

Section III deals with 1,2,5-thiadiazole 1,1-dioxides and fused systems. Other six-membered rings, such as thiatriazines and oxathiadiazines are gathered in Section IV, and Section V deals with miscellaneous compounds. Finally, in Section VI, the biological properties and other applications are described. 

The reactivity of 1,2,5-thiadiazole 1,1-dioxide derivatives, as many other aspects of their chemistry, has not been fully explored, and only a heterogeneous series of generally unrelated reactions is known. Nevertheless, the discovery of the potential of thiadiazole 1,1-dioxides as urea equivalent fragments (82JMC207,82JMC210) in the development of new histamine Hj-receptor antagonists (Section VI) may perhaps increase the interest in this field. 

The most important reactions of substituted 1,2,5-thiadiazole 1,1-dioxides are, without doubt, nucleophilic displacements of heteroatom-containing groups at positions 3 and 4, The behavior of chloro, alkoxy, and amino derivatives has been compared with that of acid chlorides, esters, and amides, respectively. The enhanced reactivity of these compounds has been explained by taking account of the electron-withdrawing power of the SO 2 group, which also justifies the strong acidic character of compound 95a (Section III,B,3) (75JOC2743). 

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