Carboxylic acids thiohydrazides

Sodium hydroxide Carboxylic acid thiohydrazides from dithiocarboxylic acid esters... 

Carboxylic acids from formazans via carboxylic acid thiohydrazides... 

Monothiodiacylhydrazines 127, derived from the acylation of thiosemicarbazides or as intermediates in the reactions of (1) thiohydrazides with carboxylic acids and their derivatives (see Section 5.10.9.2.2(i)) or (2) hydrazides with thiocarbonyl compounds (see Section 5.10.9.2.3(i)), cyclize in the presence of an acid catalyst to give 1,3,4-thiadiazoles 128 (Equation 39, Table 4). 

Fragments S-C-N-N and C Thiohydrazide derivatives with a carbon source 5.10.9.2.2 From carboxylic acid derivatives... 

Table 6 Preparation of 1,3,4-thiadiazoles from thiohydrazide 138 and carboxylic acids...

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. 

Dihydrotetrazines (340), which can easily be oxidized to 1,2,4,5-tetrazines, can be formed by dimerization of thiohydrazides (337) or amidrazones (338). The ring closure of hydrazidines (339) in a [5 + 1] fashion proceeds well with activated carboxylic acid derivatives such as imidates (341), orthocarboxylates (342) or dithiocarboxylates (343). The [4 + 2] procedure is found in the transformation of 1,3,4-oxadiazoles (346) or 1,4-dichloroazines (345) with hydrazine. Finally diazoalkanes (344) can be dimerized in a [3 - - 3] manner under the influence of a base the dimerization of diazoacetic ester is an early example, leading to 3,6-tetrazinedicarboxylate (48), which is frequently used in (4 -I- 2) cycloaddition reactions with inverse electron demand. Nitrile imines, reactive intermediates which are formed from many precursors, can dimerize in a [3 -I- 3] fashion to form 1,3,4,6-tetrasubstituted 1,4-dihydrotetrazines. These reactions are summarized in Scheme 57. 

Thiadiazines are prepared best by cyclocondensation of thiohydrazides with a-halo ketones (Section 9.08.8.2.2). Pharmacologically interesting 2,3-dihydro-l,3,4-thiadiazin-2-ones are obtained by cyclocondensation of 0-alkyl thiocarbazates (Section 9.08.8.2.2). By the reactions of a-halo carboxylic acids or a-halo carbonic esters, 1,3,4-thiadiazin-5-ones are formed (Section 9.08.8.2.2). Hydrazonyl chlorides react with ethyl sulfanylacetate to afford... 

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