Influence of Cu(II) Ions on the Mechanism of the Ring Transformation of S-(2-Oxotetrahydrofuran-3-yl)-N-(4-methoxyphenyl)isothiouronium Bromide


  • Dedicated to Professor Jaromír Kaválek on the occasion of his 75th birthday.

  • Contract grant sponsor: Ministry of Education, Youth and Sports of the Czech Republic

  • Contract grant sponsor: European Social Fund for “Enhancement of R&D Pools of Excellence at the University of Pardubice.”

  • Contract grant number: CZ.1.07./2.3.00/30.0021.

Correspondence to: Jiří Hanusek; e-mail:


The effect of additional Cu(II) ions on the rate of transformation of S-(2-oxotetrahydrofuran-3-yl)-N-(4-methoxyphenyl)isothiouronium bromide (1) into 5-(2-hydroxyethyl)-2-[(4-methoxyphenyl)imino]-1,3-thiazolidin-4-one (2) has been studied in aqueous buffer solutions. The reaction acceleration in acetate buffers is caused by the formation of a relatively weakly bonded complex (Kc = 600 L·mol−1) of substrate with copper(II) acetate in which the Cu(II) ion acts as a Lewis acid coordinating the carbonyl oxygen and facilitating the intramolecular attack, leading to the formation of intermediate T±. The formation of the complex of copper(II) acetate with free isothiourea in the fast preequilibrium (Kc) is followed by the rate-limiting transformation (kCu) of this complex. At the high concentrations of the acetate anions, the reaction is retarded by the competitive reaction of these ions with copper(II) acetate to give an unreactive complex [Cu(OAc)4]2−. The influence of Cu(II) ions on the stability of reaction intermediates and the leaving group ability of the alkoxide-leaving group compared to the Cu(II)-uncatalyzed reaction is also discussed.