Thiosemicarbazides acid esters

Derivatives of 1,3,4-thiadiazolylacetic and -propionic acids are also known, but they seem to have normal stability. They have been prepared by reaction between thiosemicarbazide and dicarboxylic acid ester chlorides (30). 

The hydrazones of thiocarbohydrazides also react in this manner (304). The 5-amino-.d4-1,3,4-thiadiazoline-2-thiones, which may be prepared from thiosemicarbazides and carbon disulfide, are listed in Table 19-The preparation of these compounds from dithiocarbazic acid esters and isothiocyanates in basic medium is discussed in Section VII.7. It must be pointed out that the numbering of the substituents in Guha s paper (146) is not always very clear so that, for the last three substances in Table 19, there is some doubt about the position of the substituents. 

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 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). 

The N—C—N—N fragment can also be supplied by thiosemicarbazides (NH2N(R)CSNH2) which react with malonic acid derivatives or j8-keto esters to give l,2,4-triazepine-3-thiones (78JHC71, 80RTC301). 

Condensation reactions can be grouped into two categories. The first category involves pyrazol-3-ones with formyl, acyl, nitroso, a,jS-unsaturated oxo, 3-oxo-2-azobutyric acid ethyl ester or acetonitrile substituents at position 4 or formyl substituents at position 5 and their reaction with carbanions, heterocyclic methylcarbenium salts, primary and secondary amines, diamines, heterocyclic perchlorates, hydroxylamine, hydrazines, urea or thiosemicarbazide. The second category involves pyrazol-3-ones with amino, hydrazino, heteroaromatic amino, acetyl or acetonitiilo groups at position 4 and their reaction with aryl or heteroaromatic aldehydes or cyclic ketones. 

The ester 5 reacts with thiosemicarbazide to yield the thiazole 6, the thiadiazine 8, or the corresponding carboxylic acids, depending on the acidity of the medium, but no triazine is obtained. The covalent hydrate 7 is an intermediate in the formation of 8. Acetylation of the thiazole 6 leads to unidentified thiadiazines or pyrazoles <96KGS1266 97CA(126)89345>. 

These include carbamates and thiosemicarbazides of Si, with Sn deiivadves of phosphate, RO2CCH2, mercapto, and dithiocarbonate and carbazate, Schiff base, N-heterocycles including pyrazoles, azobenzene, aminophenyl sulphides, and N-macrocycles, pyridine carboxylates and N-subsdtuted phenols, aminobenzoates, alkoxides, esters and salicylates, sulphur and nitrogoi subsdmted carboxylic acids, amino acids, steroids and lead-soine complexes. ... 

The successful synthesis of stable 4-hydroxy-3-thiosemicarbazides (90)" has opened the way to novel, substituted, 2-hydroxyamino-l,3,4-thiadiazoles (91), by their conventional condensation with imino-esters" or with acid halides R COCl and subsequent dehydrative cyclization. ... 

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