title: Phase-transfer-catalyzed alkylation of guanidines by alkyl halides under biphasic conditions: a convenient protocol for the synthesis of highly functionalized guanidines.
abstract: An operationally straightforward and efficient method for the alkylation of carbamate-protected guanidines with various alkyl halides and mesylates is described. This protocol proceeds via deprotonation of the acidic N-carbamate hydrogen of the guanidine under biphasic conditions using a catalytic amount of a tetrabutylammonium salt as a phase-transfer catalyst. In this manner, highly functionalized guanidines can be obtained. The reaction is tolerant of a wide range of functional groups on both the alkyl halide and guanidine component. In addition, the reaction is sufficiently mild such that simple aqueous workup and filtration through a short silica gel column yields the substituted guanidines in high purity. In conjunction with the EDCI-mediated guanylation of disubstituted thioureas with amines, phase-transfer catalyzed alkylation of guanidines via a one-pot, three-component synthesis of substituted guanidines was achieved.
authors.affiliation: Davenport Research Laboratories, Department of Chemistry, University of Toronto, Ontario M5S 3H6, Canada.
authors.forename: David A
authors.initials: DA
authors.lastname: Powell
authors.forename: Philip D
authors.initials: PD
authors.lastname: Ramsden
authors.forename: Robert A
authors.initials: RA
authors.lastname: Batey