Hydrazines thiosemicarbazones

Recent studies have been directed towards the synthesis of heterocyclic hydrazones which have lower toxicities than thiosemicarbazones [44], It has been proposed that the hydrazinic N-H group is essential for activity since it might be involved in a crucial radical formation step important in the mechanism of RDR. This is supported by the loss of antileprotic activity for this series of compounds when the hydrazinic hydrogen is replaced by a methyl group [44]. The heterocyclic hydrazones, like thiosemicarbazones, behave as tridentate ligands. 

Indian workers described the synthesis of l,3,4-thiadiazolo[3,2-a]-5-triazine-5(//)-thiones (61) by a hetero Diels-Alder reaction between 2-(arylideneamino)-5-ethylthio-l,3,4-thiadiazoles (60) and aromatic isothiocyanates (Equation (2)) <94MI 410-0I>. Thiadiazoles can be reduced with sodium amalgam to the aldehyde thiosemicarbazone while lithium aluminum hydride will reduce mesoionic thiadiazoles all the way to the hydrazine <84CHEC-I(4)545>. 

Thiosemicarbazides (TSC) and thiosemicarbazones generally react with transition metal ions to form chelate complexes by bonding through both the sulfur and the hydrazinic nitrogen atoms. With silver(I) however, they appear to behave as monodentate ligands and bond through the sulfur atom only.436... 

Acetylation of benzaldehyde thiosemicarbazone (165) yields the thiadiazoline (166) and not the diacyl derivative (167) as previously suggested (Scheme 18). Structural proof rests on spectroscopic data and on oxidation to the thiadiazole (168) followed by deacetylation with hydrazine to (169). Mild acid or base hydrolysis of (166) furnishes the starting (165) while methylation gives (170), a product identical to that obtained from the acetylation of (171) (80JOC1473). 

Although some guanylhydrazone-thiosemicarbazones showed high antitubercular activity, 176 did not. 6-Acyl- and 6-aroyl-5i7-1 -pyrin-dine-5,7(6//)-diones also react with hydrazine.112... 

Addition to the Carbonyl Group — The internal, cyclic hemiacetal formation is one of the illustrations of such addition. The H2N-X nucleophiles, with X being NH2 (hydrazine), NHAr (arylhydrazines), OH (hydroxylamine), NHCONH2 (semi-carbazide), NHCSNH2 (thiosemicarbazide), or alkyl (primary amine), produce hydrazones, arylhydrazones, oximes, semicarbazones, thiosemicarbazones, and alkyl imines (Schiff bases), respectively, following the following path 5.4 + 5.15 — 5.16 ->. .. -> 5.21. 

The periodate oxidation of 165 and its derivatives gave 195, which could be transformed into a variety of derivatives (194 and 196) (80MI8) upon reaction with amines, hydrazines, semicarbazide, or thiosemicarbazide (Scheme 44). The thiosemicarbazones 196 were cyclized to the thiadiazoles 199 and thiadiazolines 198, which are of chemotherapeutic interest (80MI8). The aldehyde also affords the expected dimedone derivative 197. 

Starch dialdehyde condenses readily with amino amides2624 and diamines,2625 and forms oximes with hydroxylamine.2626 The reaction of starch dialdehyde with isoniazid, 4 -formacelanilide thiosemicarbazone, 4 - amin o b e n z a I de h y de thiosemicarbazone or thiosemicarbazone, produced the corresponding condensation products.613-615 617 2627-2629 Hydrazones were readily formed when hydrazine and its derivatives were blended with starch dialdehyde and acidified with acetic acid2543,2630 or simply on heating the reaction mixture.2631 Condensation of starch... 

A large number of glycosulose l-(2-substituted) hydrazones have been prepared by Henseke and coworkers from the osazones by action of nitrous acid. These products, such as (89), were then treated with other substituted hydrazines, to give mixed osazones," or with hydrazine and other carbonyl reagents, to obtain ketazines and azines" hydrazone thiosemicarbazones, and hydrazone oximes. ... 

A suspension of purine-6-carboxaldehyde thiosemicarbazone in aq. hydrazine hydrate refluxed 20 min. -> purine-6-carboxaldehyde hydrazone. Y 72%. A. Giner-Sorolla, I. Zimmerman, and A. Bendich, Am. Soc. 81, 2515 (1959). 

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