Addition of cyanates and thiocyanates

The principle of Wohler s method provides a method of very wide and varied applicability for the preparation of urea derivatives. Alkali cyanates and isocyanic and isothiocyanic esters on the one hand and ammonia, amines, amides, hydrazines, etc., on the other, undergo the reaction. When an alkali cyanate is used it is usually possible to work in aqueous solution and add the amine as a salt alternatively, the free amine can be used in dilute acetic acid room temperature or moderate temperatures usually suffice. A series of examples for the preparation of monoarylureas by this method is to be found in Organic Syntheses.64 

Isocyanic esters and primary amines in indifferent solvents at room temperature give exothermally almost quantitative yields of the corresponding mixed ureas secondary amines react more slowly, aromatic secondary amines in fact poorly. Water-soluble amines can often be used in aqueous solution since isocyanates react faster with amines than with water. 

Thioureas are obtained analogously by boiling an amine hydrochloride and an alkali thiocyanate in aqueous solution66 or an amine and a thioiso-cyanate in alcohol 67 aromatic thioisocyanates generally react even in the cold. Further, aqueous ammonia solutions are converted smoothly into mono-alkylthioureas by isothiocyanates.68 Isothiocyanates can be converted directly into symmetrical thioureas by boiling them in aqueous dimethylformamide or dimethyl sulfoxide the thiocarbamic acids formed as intermediates by partial hydrolysis add to unchanged isothiocyanate with loss of COS.69 

The following directions have proved valuable for the preparation of thio-semicarbazide 70 

Preparation of acylureas from amides and isocyanic esters requires more critical conditions but generally gives good yields. 

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