[62-56-6]  · CH4N2S  · Thiourea  · (MW 76.14)

(reduction of endoperoxides and ozonides; nucleophilic H2S equivalents; aminothiazole, pyrimidine, and episulfide synthesis; precursor of formamidinesulfinic acid)

Physical Data: mp 182 °C; d 1.405 g cm-3.

Solubility: sol water, alcohol.

Form Supplied in: solid; commercially available.

Handling, Storage, and Precautions: liable to hydrolysis with generation of hydrogen sulfide. Powder is therefore toxic as well as malodorous. Should be used only with adequate ventilation. Use in a fume hood.

Reduction of Peroxides.

One of the more common uses of thiourea is in the reduction of peroxides to the alcohols. Examples include the reduction of cyclopentadiene endoperoxide1 to form the corresponding diol (eq 1) and the reduction of ozonides2 to the corresponding carbonyl compounds (eq 2) with a minimum of expense or odor.

Isothiuronium Salts.

Another use of thiourea is related to its synthetic equivalence to Hydrogen Sulfide. Reaction with an alkyl halide or sulfonate via the sulfur of thiourea provides the isothiuronium salt (eq 3). This alternative provides an advantage over the use of hydrogen sulfide in that it avoids formation of dialkyl sulfides. Alkaline hydrolysis of the isothiuronium salt provides the thiol;3 aqueous chlorination can provide the sulfonyl chloride.4 Alternatively, the sulfur fragment may be easily displaced with an amine in a synthesis of substituted guanidines (eq 4).5

Heterocycle Synthesis.

A major use of thiourea is in the construction of heterocycles. Aminothiazoles can be synthesized by the Hantzsch synthesis wherein an a-halo carbonyl compound is treated with thiourea.6a,b The reaction of the carbonyl with one of the thiourea nitrogens to form the imine is the first step of the synthesis. Upon further heating, the sulfur displaces the halide with cyclization (eq 5). Pyrimidines are made by reaction of thiourea with b-dicarbonyl compounds7a,b via an initial attack by a thiourea nitrogen on a carbonyl, followed by cyclization and tautomerization (eq 6). Thiourea is the key reagent for the synthesis of episulfides8a,b from the corresponding epoxides, in one step and in synthetically useful yield (eq 7).

Lastly, thiourea and Hydrogen Peroxide are the starting materials for synthesis of Thiourea Dioxide (eq 8)9 a mild reducing agent commonly used in the reduction of ketones to secondary alcohols.10

1. Kaneko, C.; Sugimoto, A.; Tanaka, S. S 1974, 876.
2. Gupta, D.; Soman, G.; Dev, S. T 1982, 38, 3013.
3. Speziale, A. J. OSC 1963, 4, 401.
4. King, J. F.; Aslam, M. S 1980, 285, and references therein.
5. Brand, E.; Brand, F. C. OSC 1955, 3, 440.
6. (a) Dodson, R. M.; King, L. C. JACS 1945, 67, 2242. (b) Dahiya, R.; Pujari, H. K. IJC(B) 1986, 25, 966.
7. (a) Foster, H. M.; Snyder, H. R. OSC 1963, 4, 638. (b) Taylor, E. C.; Cheng, C. C. JOC 1960, 25, 148.
8. (a) Gao, Y.; Sharpless, K. B. JOC 1988, 53, 4114. (b) Bouda, H.; Borredon, M. E.; Delmas, M.; Gaset, A. SC 1989, 19, 491.
9. Barnett, E. D. B. JCS 1910, 97, 63.
10. Nakagawa, K.; Minami, K. TL 1972, 13, 343.

Onorato Campopiano

DuPont Agricultural Products, Wilmington, DE, USA

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