A novel facile solid-phase strategy for the synthesis of N,N′,N-substituted guanidines

A new facile solid-phase synthesis of N,N',N-substituted guanidines from an immobilised amine component is described. The resin-bound amine was reacted with di-(2-pyridyl)thionocarbonate to generate the isothiocyanate which was treated with aryl/alkyl amines to yield the corresponding resin-bound thiourea. Desulfurisation of the thiourea was readily achieved by treatment with triphenylphosphine dichloride, and further reaction with aryl/alkyl amines followed by acidic cleavage with trifluoroacetic acid yielded N,N',N-substituted guanidines of excellent purity and in good yield. (C) 2002 Elsevier Science Ltd. All rights reserved.