Hydrazides and Thiohydrazides

Alkoxycarbonylimidazoles or alkoxythiocarbonylimidazoles, easily prepared from alcohols and CDI or ImCSIm, are treated with hydrazines to give alkoxycarbonic acid hydrazides and thiohydrazides, respectively 12261,12271... 

A few hydrazides and thiohydrazides prepared with the aid of alkoxycarbonyl-imidazoles or thiocarbonylimidazoles are shown below 12261,12271... 

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>. 

The hydrazides or thiohydrazides 35, formed as intermediates in the aforementioned reaction, have frequently been isolated, which could then be cyclized to 33 and/or 34 [57JCS727 59JOC793 60YZ1542 86JCS(P1)711 87JHC1605 95MI2] (Scheme 15). 

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). 

Functional group substituents on N-l of 2-pyrazolin-5-ones (Table XXXVII) are acyl, sulfonyl and various carboxyl derivatives, such as carbalkoxy, amides, thioamides, hydrazides, thiohydrazides and amidines. The usual synthesis of these compounds is by the classical 2-pyrazolin-5-one synthesis, reaction of a /J-ketoester with a hydrazine. In these cases the hydrazines are special types such as hydrazide,... 

Phenyl- and 5-aryl-2-benzyl-6//-l,3,4-thiadiazincs 8 (R3 = Ph, Bn) are prepared by condensation of thiobenzohydrazide or phenylthioacetic acid hydrazide with a-halocarbonyl compounds.10, 50 Under appropriate conditions it is also possible to isolate the primarily formed 4,5-dihydro-6//-1,3,4-thiadiazin-5-ol intermediates 7a-h. For this purpose, the thiohydrazide is added to an equimolar amount of sodium ethoxide solution, then at — 25 °C an ethanolic solution of the respective phenacyl bromide, 2-bromo-l,2-diphenylethan-l-one, 2-bromo-l-phenylpropan-l-one, or 2-bromo-l-phenylbutan-l-one is added. The 4,5-dihydro-6//-l,3,4-thiadiazin-5-ols 7 separate as colorless precipitates. They undergo partial dehydration at room temperature to the 2-phenyl- or 2-benzyl-6//-l, 3,4-thiadiazines 8 on heating for about 5-7 minutes in ethanol or chloroform, the dehydration is complete. 

A frequently used method for the synthesis of l,4-dihydro-l,2,4,5-tetrazines 17 and, hence, for the preparation of 1,2,4,5-tetrazines 18 is the dimerization of activated hydrazidic acid derivatives, such as hydrazinoyl chlorides 1, thiohydrazides 4, amidrazones 10, selenohydrazides 12, hydrazonic esters 15, hydrazidines 16 or thiohydrazonic esters 13. This corresponds to a synthesis by a (3 + 3) fragment method. 

---