Dithiocarbazic 1,3,4-thiadiazoles

Tliiocarbohydrazide with two equivalents of carbon disulfide in boiling pyridine gives some 40% yield of 4-amino-l,2,4-triazolidine-3,5-dithione (LIV). Simultaneously some 40% of 2,3.5,d-tetrah5 dro-l,2,4-triazolo[3,4-b]-l,3,4-thiadiazole-3,6-dithione (LV) is obtained. This product is formed through cyclization (of the type mentioned in Section 1.7) of the intermediate N-(2-thioxo-z]4-1,3,4-thiadiazolin-5-yl)-dithiocarbazate. 

The reaction of dithiocarbazic acid esters (CCXXXVI) with isothiocyanates is more complicated in that the intermediate of the reaction, the ester of 1-(dithiocarboxy) thiosemicarbazide (CCXXXVII), can undergo ring closure to three kinds of substituted f,3,4-thiadiazole rings (62, JSO). 

Synthesis.—The majority of 1,3,4-thiadiazole syntheses are based on cyclizations of thiosemicarbazidcs or compounds incorporating this basic structural pattern. Others involve ring-closures of dithiocarbazates, acyl hydrazines, or bithioureas, or interconversions of other ring systems, particularly oxadiazoles and dithiolethiones. Recent contributions to this subject have been numerous and are presented, as far as possible, in accordance with this classification. 

Syntheses from Dithiocarbazates. A novel variant of the general synthesis of 2-aryl-5-mercapto-l,3,4-thiadiazoles from dithiocarbazates (107) derived from carbon disulphide and (thio)benzhydrazides (106 X = S or or benzhydrazoximes (106 X = NOH) involves the use of benzimidrazones... 

The interaction of dithiocarbazic esters and bromocyanogen in aqueous potassium bicarbonate produces good yields of 2-amino-5-alkylthio-1,3,4-thiadiazoles. The reaction is an extension of the known synthesis of the 5-alkoxy-analogues from alkoxythiocarbonylhydrazines and bromocyanogen. ... 

Phosgene passed with vigorous stirring first at 15-25 then with gradual warming to final reflux into a mixture of methyl dithiocarbazate and anhydrous benzene -> 5-methylthio-l,3,4-thiadiazol-2(3H)-one. Y 85%. F. e. s. K. Riifenacht, Helv. 55, 1178 (1972) 56, 162 (1973) the chemistry of phosgene, review, s. H. Babad and A. G. Zeiler, Chem. Rev. 73, 15 (1973). 

In a recent investigation (described below), we expanded the utility of the carbazate resin by applying it to the efficient solid-phase syntheses of 1,3,4-oxadiazole derivatives 11 and 1,3,4-thiadiazole derivatives 12 via selective, reagent-based cydization of an acyl-dithiocarbazate." The process employs an acyidithiocarbazate resin, from which the respective targets are generated by cyclodesulfurization (Figure 10.2, route a) or cyclo-dehydration (Figure 10.2, route b). 

As a member of the thiadiazole family, which is a privileged structure for the generation of drug-like libraries, 1,2,4-thiadiazoles have been used as the basic framework for substances of interest in numerous therapeutic areas Recently, we reported the results of a study that led to the development of a solution-phase parallel synthesis of various drug-like 5-amino-1,2,4-thiadiazoles via a three-component nucleophiUc substitution reaction between carbon disulhde, benzamidine, and benzyl chloride, using a key cyclization reaction of a carboxamidine dithiocarbazate induced by TsCl. We also developed a simple and efficient solid-phase parallel synthetic method capable of facilitating the... 

Alkylthio-l,3,4-thiadiazoles from dithiocarbazic acid esters and carboxylic acid dilorides... 

Several papers report on the nucleophilic reactivity of dithiocarbamate ions towards alkyl halides, 1,2-dibromoalkyl compounds, alkyl and aryl chloroformates, chloroacetic acid, chloroacetates, 3-halo-genophthalides, sulphenyl chlorides, sultones, and trialkylam-monium compounds. Examples of a similar reactivity of dithiocarbazate anions have also appeared. " A series of papers deal with addition or addition-elimination reactions of dithiocarbamate - or dithiocarbazate anions with w-nitrostyrene, 2-thioxo-, 2-oxo-, and 2-imino-5-methoxycarbonylmethylidene-4-thiazolidones, dimethyl acetylenedicar-boxylate, and NN -dialkyl phenylpropiolamidines. S-Monoalkylated N-cyanodithioimidocarbonates (492) underwent oxidative ring-closure to give 3-halogeno-l,2,4-thiadiazole sulphides (493) on treatment with halogenating agents. ... 

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