Thiosemicarbazides

II. Thiazoies from a-Halocarbonyl Compounds and Derivatives 249 D. Thiosemicarbazides and Thiosemicarbazones... 

Thiosemicarbazides (141), Rj = H, yield the 2-hydrazinothiazoles (Scheme 68). Compound 142, R] = H, on reaction with o-halocarbonyl... 

Several sulfonamides (142), Rj = p-H2NS02CeH4, have been obtained by condensing the corresponding thiosemicarbazide (141), R, = p-H2NSO2C6H4, with a-halocarbonyl compounds (396, 466) in alcohol solution. 

TABI.R 11-21 2-HYDRAZINOTHIAZOLES FROM THIOSEMICARBAZIDES AND a-HALOCARBONYL COMPOUNDS... 

Condensation of thiosemicarbazides of nicotinic and isonicotinic acids (528) and their hydrochlorides, with a-halocarbonyl compounds gave the corresponding hydrazinylthiazoles (149), in which Rj = methyl, phenyl, or aryl and R2 = H (Scheme 74). 

The rates of reaction of phenacyl bromide with thiosemicarbazide and its phenylated derivative were determined by conductivity measurements in ethanol (517). The reaction is second order up to 85% completion. The activation energies are 10.5 to 11.3 kcal/mole with the phenyl thiosemicarbazide and 8.5 to 9.3 kcal/mole for the unsubstituted derivatives. 

Br , citrate, CE, CN , E, NH3, SCN , S20 , thiourea, thioglycolic acid, diethyldithiocarba-mate, thiosemicarbazide, bis(2-hydroxyethyl)dithiocarbamate Acetate, acetylacetone, BE4, citrate, C20 , EDTA, E , formate, 8-hydroxyquinoline-5-sul-fonic acid, mannitol, 2,3-mercaptopropanol, OH , salicylate, sulfosalicylate, tartrate, triethanolamine, tiron... 

Acetone, (reduction with) ascorbic acid, citrate, CE, CN , 2,3-dimercaptopropan-I-oI, EDTA, formate, E, 8CN , 80 , tartrate, thiosemicarbazide, thiourea, triethanolamine CE, EDTA, F , 8CN , tartrate, thiourea, triethanolamine Citrate, CN , 8CN , tartrate, thiourea Citrate, EDTA, F , oxalate, tartrate, tiron... 

Thiosemicarbazides are useful in forming 1,3,4-thiadiazoles, a class of compounds having herbicidal activity. 

When thiourea or thiosemicarbazide are used for substitution of a chlorine atom with a mercapto group, thiouronium salts are formed first, and they are hydrolysed by aqueous base. Other groups, such as alkoxy, alkyl, amino and cyano, if present, are usually not... 

A. l-Formyl-3-thiosemicarbazide. Four hundred milliliters of 90% formic acid contained in a 2-1. round-bottomed flask is heated on a steam bath for 15 minutes, and then 182 g. (2 moles) of colorless thiosemicarbazide (Note 1) is added. The mixture is swirled until the thiosemicarbazide dissolves. The heating is continued for 30 minutes, during which time crystalline 1-formyl-3-thiosemicarbazide usually separates. Boiling water (600 ml.) is added, and the milky solution that results is filtered through a fluted filter paper. After standing for 1 hour, the filtrate is cooled in an ice bath for 2 hours, and the l-formyl-3-thiosemicarbazide that separates is collected by suction filtration and air-dried overnight. It weighs 170 192 g. (71-81%) and melts at 177-178° with decomposition. 

The thiosemicarbazide must be of good quality or the yield and quality of l-formyl-3-thiosemicarbazide will suffer. The thiosemicarbazide supplied by Olin Mathieson Chemical Corporation, obtained as a colorless free-flowing powder, can be used without purification. 

Triazole-3(5)-thiol has been prepared by heating thio-semicarbazide and formic acid, by heating l-formyl-3-thiosemi-carbazide, and by heating 1,3,5-triazine and thiosemicarbazide. The ring closure of l-formyl-3-thiosemicarbazide using aqueous base was suggested by L. F. Audrieth and F. Hersman. 

The starting semicarbazones were most often prepared directly from the a-keto acids. Godfrin proceeded from a-alkyl acetoacetates, which were converted by oxidation with nitrosylsulfuric acid to a-keto-acid oximes and the latter transformed to semicarbazones or thioseraicarbazones by applying semicarbazide or thiosemicarbazide. For glyoxylic acid semicarbazone a very convenient procedure was employed, making use of the hydrolysis of nonisolated chloral semicarbazone. ... 

By reaction of thiosemicarbazide or its 4-alkyl derivatives with nitrous acid Freund and co-workers in 1896 prepared compounds which were formulated as amino or alkylamino derivatives of the ring system 1,2,3,4-thiatriazole (1). Oliveri-Mandala, however, argued that these compounds are actually thioazides (2), and this view seems to have been generally accepted (e.g. in Beilstein s Handbuch) until... 

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