General acid catalysis of the reversible addition of thiolate anions to cyanamide

Abstract

The addition of aromatic thiols (pK_a = 2.6–6.5) to cyanamide to give the isothiourea is subject to general-acid catalysis of the addition of thiolate anions by tertiary ammonium ions, with α = 0.26 and 0.31 (±0.07) for the addition of thiophenol and 4-nitrothiophenol, respectively. The Brønsted coefficients and a small solvent isotope effect of k_H2O/k_D2O = 1.6 for catalysis by 4-morpholinoethanesulfonic acid (MES) buffer and for the uncatalysed addition of thiophenol are consistent with significant movement of a hydron in the transition state. The conclusion that the reaction proceeds through a basic asymmetric intermediate in the absence of catalysis is supported by the similar rate constants for the addition of thiophenolate anion to cyanamide and to N,N-dimethylcyanamide, which cannot tautomerize to the carbodiimide. The reaction has a central transition state in which S–C bond formation takes place with β_nuc = 0.55. It is concluded that the mechanism of catalysis involves partial transfer of a hydron to the cyano nitrogen atom in the transition state.