Categories: C-N Bond Formation >
Synthesis of thioureas
A simple condensation between amines and carbon disulfide in aqueous medium allows an efficient synthesis of symmetrical and unsymmetrical substituted thiourea derivatives. This protocol works smoothly with aliphatic primary amines to afford various di- and trisubstituted thiourea derivatives.
M. R. Maddani, K. R. Prabhu, J. Org. Chem., 2010, 75, 2327-2332.
A completely atom-economic reaction of isocyanides with aliphatic amines in the presence of elemental sulfur proceeds efficiently at (nearly) ambient temperature to produce thioureas in excellent yields.
T. B. Nguyen, L. Ermolenko, A. Al-Mourabit, Synthesis, 2014, 46, 3172-3179.
An "on-water" reaction of (thio)isocyanates with amines enables a facile, sustainable, and chemoselective synthesis of unsymmetrical (thio)ureas. The physical nature and solubility of reagents in water are responsible for the observed reaction rate and selectivity. The process offers simple product isolation through filtration and the recycling of the water effluent and avoids the use of toxic VOCs.
A. D. Karche, P. Kamalakannan, R. Powar, G. G. Shenoy, K. J. Padiya, Org. Process Res. Dev.., 2022, 26, 3141-3152.
The combination of sulfur and chloroform enables an efficient and practical synthesis of a thiocarbonyl surrogate. Various thiocarbamides and oxazolidinethiones have been synthesized, including chiral thiourea catalysts and chiral oxazolidinethione auxiliaries with high selectivity.
W. Tan, J. Wei, X. Jiang, Org. Lett., 2017, 19, 2166-2169.
Carbamoyl isothiocyanates are ideal starting materials for the synthesis of multisubstituted guanidines. The nature of these carbamoyl thioureas permits creation of disubstituted and trisubstituted guanidines, as well as aromatic guanidines.
B. R. Linton, A. J. Carr, B. P. Orner, A. D. Hamilton, J. Org. Chem., 2000, 65, 1566-1568.
Various thioureas derived from primary amines and carbamoyl-protected isothiocyanates react with the Burgess reagent to give the corresponding guanidines via either a stepwise or one-pot procedure. A selective deprotection of the N,N′-diprotected guanidines affords N-monoprotected guanidines.
T. Maki, T. Tsuritani, T. Yasukata, Org. Lett., 2014, 16, 1868-1871.
Stable and readily available N,N'-di-Boc-substituted thiourea can be used as a mild thioacylating agent when activated with trifluoroacetic acid anhydride. Through thioacylation of nucleophiles, such as amines, alcohols, thiols, sodium benzenethiolate, and sodium malonates, a series of thiocarbonyl compounds were prepared with good chemical selectivity and functional group tolerance.
B.-L. Yin, Z.-G. Liu, J.-C. Zhang, Z.-R. Li, Synthesis, 2010, 991-999.