Thiohydrazide

Reaction of a hydrazide (128) with phosgeneiminium chloride (115) led to the 2-dimethylamino-l,3,4-oxadiazole (129) in 90% yield (75AG(E)806). The 1,3,4-thiadiazole system was also obtained in an analogous reaction in which the dithioimidate (130) underwent reaction with the thiohydrazide (131). Depending on the nature of X in (131), the 2-substituent in the resultant 1,3,4-thiadiazole (132) may be varied (80ZC413). Although (130)... 

The most general route to 1,2,3,4-thiatriazoles involves treatment of a thiohydrazide with nitrous acid [Eq. (1)]. Thus, 5-amino-... 

From thiohydrazides, R CS NHNHg, in which R is an aromatic or a heterocyclic group, 1,2,3,4-thiatriazoles may in general be obtained in good yield by treatment with nitrous acid. ... 

Thiohydrazides can be prepared from alkyl- and aryl-substituted hydrazines and various 7V-thiobenzoylazoles,11651 as the following examples illustrate 11651,11661... 

The synthesis of hydrazono derivatives of thiohydrazides is described in reference... 

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... 

Fragments S-C-N-N and C Thiohydrazide derivatives with a carbon source 592... 

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). 

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

Acid chlorides react with thiohydrazide derivatives in polar solvents to give the corresponding thiadiazoles in a one-pot reaction (e.g., Equation 49) <2003BML4193, 2003RJ01133, 2000JCM544>. 

A charge-transfer complex of diethyl chlorophosphate with DMF as the one-carbon source effects the cyclization of thiohydrazides into thiadiazoles 142 (Equation 50) <2004S17>. 

Alkyl and aryl thiohydrazide derivatives react with orthoesters and trihalomethyls to afford 1,3,4-thiadiazoles. The reactions proceed via a thiosemicarbazone intermediate which cyclizes to eliminate either alcohol or hydrogen chloride. Treatment of the iV-thiohydrazide pyrazole 143 with triethyl orthoformate in acetic acid at reflux gave the 5-acetamido-l,3,4-thiadiazol-2-ylpyrazole 144 (Equation 51), and in the absence of acetic acid the 5-amino-l,3,4-thiadiazol-2-ylpyrazole 145 in 76% yield <2000JCM544>. 

The reaction of imines with thiohydrazides gives 1,3,4-thiadiazole via a thioacylimidohydrazine intermediate. The imidoyl chloride 148 when treated with the IV-phenyl thiosemicarbazide 149 gave the 1,3,4-thiadiazole hydrochloride 150 (Equation 53) <2002MI1241>. 

Thiohydrazides react with isothiocyanates to afford 1,3,4-thiadiazoles. The reaction proceeds via a dithioacylhy-drazine intermediate which under the reaction conditions cyclizes with loss of H2S. When the Ar-thiohydrazide pyrazole 143 is refluxed in DMF in the presence of phenyl isothiocyanate the 5-phenylamino-l,3,4-thiadiazol-2-yl pyrazole 144 is formed (Equation 54) <2000JCM544>. 

Thiohydrazides, 13 575 colorant for plastics, 7 374t Thioindigo pigments, 19 444 Thioindoxyl... 

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). 

Condensation of a-halo ketones with thiohydrazides (Scheme 53) is a general route to 1,3,4-thiadiazines (76JPR(3i8)97i). 

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). 

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). 

Condensations involving a two-carbon 1,2-dielectrophile, such as an a-halocarbonyl compound or a 1,2-dihaloalkane, are fairly common. Thus reaction of dichloroacetyl chloride with N-phenyl-N -benzoylhydrazine gives the 1,3,4-oxadiazine (168) (78JPR452). Condensation of a-halo ketones with thiohydrazides (Scheme 15) is a useful general route to 1,3,4-thiadiazines and many examples are known (69ZC111,70LA(74l)45,76JPR971). 

Thiohydrazides 136 react with nitrous acid or aryldiazonium salts to give 5-substituted 1,2,3,4-thiatriazoles 9... 

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