The electrochemical oxidation of hematoxylin in acidic solutions has been studied using cyclic voltammetry, differential pulse voltammetry, controlled potential coulometry and digital simulation methods. The results revealed that hematoxylin shows two oxidation-reduction peaks (EE mechanism). In the first step hematoxylin is converted to hematein via a two-electron process. Five possible structures were designed for the first oxidation step and optimized at the B3LYP/6-311 + G** level of theory. Also, the electrochemical oxidation of hematoxylin has been studied in the presence of p-toluenesulfinic acid as a nucleophile. The results showed that the electrochemically generated hematein participates in Michael addition reaction with p-toluenesulfinic acid via a novel "E-Tautomerization-C" mechanism and is converted to an unexpected isomer of tolylsulfonylhematoxylin. In this work, an electrochemical method for the synthesis of a new hematoxylin derivative is also reported. (C) 2012 Elsevier B.V. All rights reserved.