Thiohydrazides, formation

Reaction of the malononitrile-derived diazene 275 with active methylene compounds proceeds via addition to a cyano group followed by intramolecular hydrazide or thiohydrazide formation, pyridazin-3(2//)-ones and thio analogs 276 are respectively produced (Equation 70) <1999JCM8>. 

This approach is suitable for the formation of mesoionic 1,3,4-thiadiazoles. The thiohydrazide (427) with phosgene, thiophosgene or an isocyanide dichloride leads to ready ring closure and formation of the mesoionic 1,3,4-thiadiazoles (428 X = 0, S, NR, respectively) (b-79MI40300). 

Activated hydrazine derivatives of carboxylic acids (337, 338) can dimerize to afford dihydro-1,2,4,5-tetrazines (89) which can be oxidized to the tetrazines (39) but which can also rearrange to 4-amino-1,2,4-triazoles (339). In many cases where the isolated products have been formulated as dihydro-1,2,4,5-tetrazines (89) it has either been shown, or it can be assumed, that in fact 4-amino-l,2,4-triazoles (339) were obtained. Very often the formation of dihydro-1,2,4,5-tetrazines (89) is a side-reaction in the synthesis of activated hydrazine derivatives of carboxylic acids, such as amidrazones (337 Y = NH2), hydrazidines (337 Y = NHNH2), thiohydrazides (338 X = S) and so on and not the attempted reaction. Therefore the number of effective synthetic processes for dihydrotetrazines (89) or tetrazines (39) by this synthetic principle is not very high. 

When the imidazoline-4-thione (347) was treated with hydrazine the 1,2,4,5-tetrazine (348) was obtained, probably via the intermediate thiohydrazide (349) (72LA(76l)95). Reaction of the alkynic thioacetate (350) with hydrazine affords 3,6-dipentyl- 1,4-dihydro-1,2,4,5-tetrazine (351), the formation of which can be rationalized by the intermediate formation of (352) (67RTC907). 

Treatment of thiohydrazides with nitrous acid leads to formation of thiatriazoles. 5-Amino-l,2,3,4-selenatriazoles may be prepared in the same manner from the corresponding selenosemicarbazides (83 R1 = R -Et, ca. 60%) but the reaction is accompanied by the formation of elemental selenium. A comparable yield is achieved by use of an aza transfer reagent (55-70%) (equation 54). The best yield and purest material are obtained from the... 

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>. 

A. Jensen, H. R. Baccaro, O. Buchardt, G. E. Olsen, C. Pedersen, and J. Toft, Studies of thioacids and their derivatives. V. A-substituted thiohydrazides, Acta Chem. Scand., 15 (1961) 1109-1123. A. Jensen and C. Pedersen, Studies of thioacids and their derivatives. VI. Formation of thiadiazoles and tetrazines in the preparation of thiohydrazides, Acta Chem. Scand., 15 (1961) 1124-1129. 

Bis nucleophilic molecules can also add to triple bonds Michael-fashion, followed by various modes of cyclization. Thiohydrazides and acetylenic esters have been shown to produce thiadiazolines. Kubota et al ° have explained the formation of A -l,3,4-thiadiazolines (374) from thiosemicarbazones (373) on the basis of the hard and soft acid and base principle. Hard acylating agents... 

Evidence for the intermediate formation of an aminosulphene during the oxidative elimination of sulphur from thioamides is provided by the production of imidates on oxidation of thioamide 5-oxides in the presence of alcohols. (See Section 2, p. 138.) Oxidation of thiohydrazides gave the disulphides (111 X = S2, Ar = Ar = = R = Ph), which on further oxidation with... 

Among the several papers reporting on the applicability of thioamides " and thiohydrazides in the synthesis of heterocyclic compounds, the most interesting paper is perhaps that of Ofitserov and his co-workers, desc bing the formation of (275) by the action of aqueous ammonia on the meso-ionic thioamide (273) the formation of (275) was explained on the basis of a mechanism involving (274) as a spontaneously rearranging intermediate. ... 

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