Reaction of Amines with Isothiocyanates

A comparatively large selection of thioureas can be formed from the reaction of amines with isothiocyanates, hence they are attractive starting materials for formation of guanidines. A common solution-phase approach to this reaction involves abstraction of the sulfur via a thiophillic metal salt, like mercuric chloride.10 For solid-phase syntheses, however, formation of insoluble heavy-metal sulfides can have undesirable effects on resin properties and on biological assays that may be performed on the product. A more relevant strategy, with respect to this chapter, is S-alkylation of thioureas and then reaction of the methyl carbamimidothioates formed (e.g., 5, Scheme 6) with amines. This type of process has been used extensively in solution-phase syntheses.1 Ul4 Two examples are shown in Scheme 6 11 the second is an intramolecular variant, which involves concomitant detrity-lation.15... 

Synthesis.—Diarylthioureas have been made from arylamines and either bis-(alkoxythiocarbonyl) disulphides or CSj and an alumina catalyst. The standard reaction of amines with isothiocyanates was used in the preparation of adamantyl- and glycosyl- thioureas. Benzoyl isothiocyanate, when treated with sterically hindered amines, e.g. Pr jNH or dicyclohexylamine, gives... 

---