Thiocarbamoyl azides

Phenyl-l,2,3,4-thiatriazole was prepared in this laboratory in 1952 and shown by its infrared spectrum not to be an azide. However, this observation was made in conjunction with rather extensive studies of thioacids and their derivatives and was not published until 1961, when sixteen 5-aryl- and 5-heterocyclyl-l,2,3,4-thiatriazoles were described. Independently, 5-phenyl-1,2,3,4-thiatriazole was also obtained by Bacchetti and Alemagna, Kirmse, and Smith and Kenny and shown by its infrared spectrum not to be an azide. The last two groups of investigators also prepared some other 5-sub-stituted-l,2,3,4-thiatriazoles. Finally, Scottcommented on the anomalous infrared spectra of thiocarbamoyl azides and concluded that they were actually thiatriazoles. 

Additions of hydrazoic acid to carbon-sulphur double bonds may conceivably be of the general type outlined in equation (88) but do not constitute a synthetic route to azides. Recent corrections to the earlier literature relating to this field are, however, noteworthy. It was originally suggested that thiocarbamoyl azides " (193) were obtained from organic isothiocyanates and hydrazoic acid. The spectroscopic studies of Lieber and co-workers " have now established that the products are in fact thiatriazoles (194). The reactions of sodium azide with isothiocyanates , and carbon disulphide , which were also previously considered to furnish organic azides, have now been shown to produce the heterocyclic compounds 195 and 196 respectively. 

Treatment of thionhydrazides, RC(==S)—NH—NH2 with nitrous acid should lead to thiocarbonyl azides, RC(=S)—N3, and it seems likely that these azides are indeed formed as short-lived intermediates. The isolated products are 1,2,3,4-thiatriazoles. When thiosemi-carbazides are nitrosated, 5-amino-l,2,3,4-thiatriazoles or/and 5-mercaptotetrazoles are obtained. Freundformulated his products as such in 1895, while Oliveri-Mandala considered them thiocarbamoyl azides on the basis of some chemical evidence. Lieber resolved this controversy by recording the infrared spectra of the compounds and demonstrating the absence of an azide band . He did the same for the 5-alkylmercapto-l,2,3,4-thiatriazoles , which had earlier been reported as azido-dithiocarbonates , and for the products from azide ion and thiophosgene and carbon disulphide , all of which possess thiatriazole structures. Lieber also demon-... 

It appears quite probable that this reaction occurs by the same mechanism as the reaction of nitrous acid with thiosemicarbazides and of sodium azide with isothiocyanates. The primary reaction product is a thiocarbamoyl azide (CCXIII) to which, however, the cyclic structure of a 5-amino-l,2,3,4-thiatriazole (CCXIV) is attributed. In alkaline medium these compounds rearrange to the corresponding 1 -substituted-Zla-tetrazoline-5-thiones (CCXII) 236, 237). A survey of these compounds, prepared from the dithiocarbamic acid esters, is given in Table 33. 

The reactivity of electrophilic isothiocyanates towards inorganic and organic azides is well known. The conversion of hydrazoic acid with aryl isothiocyanates 175 provides 5-amino-substituted 1,2,3,4-thiatriazoles 177 by addition of hydrazoic acid to the C=S bond of the isothiocyanate moiety, probably via unstable thiocarbamoyl azides 176 [132]. Benzoyl isothiocyanate (179, R = CeHs), for example, reacts with hydrazoic acid to benzoylcyanamide (180, R = CeHs). hi contrast, the reaction of sodium azide with isothiocyanates 175 occurs at the C=N bond of the isothiocyanate moiety and gives l-substituted-A -tetrazoHne-5-thiones, also known as l-substituted-5-mercaptotetrazoles 178 (Scheme 35) [133-135]. 

Thiazyl halides, aromaticity of, 357 Thienotropylium cation, salts of, 65 Thiocarbamoyl azides, 264 Thiohydrazides, 1,2,3,4-thiatriazoles firom, 265... 

These compounds exhibit no infrared absorption in the 2100-2200 cm range,and this definitely rules out the thiocarbamoyl azide structure. For the disubstituted derivatives of 5-amino-1,2,3,4-thiatriazole, therefore, only one structure is possible, i.e. structure 7. For the unsubstituted and monosubstituted compounds, however, it has been proposed that they exist as the tautomeric 5-imino-l,2,3,4-thiatriazolines (8). For 5-methylamino-l,2,3,4-thiatriazole this possibility is ruled out by an investigation of its n.m.r. spectrum,and this result is probably generally valid for the 5-alkylamino-l,2,3,4-thiatriazoles. The unsubstituted compound has infrared absorption bands at 3135, 3257, and 1621 cm , which may be assigned to two NH2 stretching bands and a NHg deformation band, respectively therefore it almost certainly exists as 5-amino-l,2,3,4-thiatriazole and not as 5-imino-l,2,3,4-thiatriazoline. 

It has been shown also that both thiocarbamoylimidazoles 147 and 148 can react with sodium azide. These compounds were successfully used to prepare heterocycle-peptide conjugates as peptidomimetics. A-Terminal aminothiatriazole modified amino acids have been synthesized using two methods (Scheme 35). To prepare monosubstituted aminothiatriazoles 151 the amino acid derivatives were converted into the thiocarbamoyl imidazoles of type 147 that can react with azide ion to form the thiatriazole ring. On the other hand, for the synthesis of disubstituted amino acid derivatives of 1,2,3,4-thiatriazoles 153 and 155 the activation of the thiocarbonyl group via a salt of type 148 was required. The reaction conditions and the yields of thiatriazoles 151, 153, and 154 prepared by this approach are shown in Scheme 35. 

Carboxy includes carboxy (carboxylic acids), alkoxycarbonyl (esters), carbamoyl (amides), thiocarbamoyl, hydrazinocarbamoyl (hydrazides), guanidinocarbonyl, azidocarbonyl (azides), chlorocarbonyl (acid chlorides), amidino, C-hydrazino-C-iminomethyl, C-alkoxy-C-iminomethyl (imino ethers), C-alkylthio-C-iminomethyl (iminothioethers), cyano (nitriles), C-formyl(aldehydes), dialkoxymethyl (acetals of aldehydes), C-acyl (ketones), isocyanato, and thiocyanato groups. 

From thiocarbonohy dr azide. Thiocarbonohydrazide (76) is converted into l-aminothiocarbamoyl-4-aroyl-3-thiosemicarbazides (77) or l,5-bis(aroyl-thiocarbamoyl)thiocarbonohydrazides (78) by the addition of one or two moles of aroyl isothiocyanate. The mono-adducts (77) are cyclized to... 

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