Electrochemical oxidation of 4-(piperazin-1-yl)phenols in the presence of indole derivatives: The unique regioselectivity in the synthesis of highly conjugated bisindolyl-p-quinone derivatives Amene Amani, Sadegh Khazalpour, Davood Nematollahi ⇑ Faculty of Chemistry, Bu-Ali Sina University, Hamedan 65178-38683, Iran article info Article history: Received 5 September 2011 Received in revised form 24 November 2011 Accepted 1 February 2012 Available online 10 February 2012 Keywords: Electrochemical synthesis 4-(Piperazin-1-yl)phenols Bisindolyl-p-quinones Michael type reaction Cyclic voltammetry abstract The electrochemical oxidation of 4-(piperazin-1-yl)phenols have been studied in the presence of indole derivatives as nucleophiles in water/acetonitrile mixture by means of cyclic voltammetry and controlled- potential coulometry. The reaction mechanism is believed to be oxidation of 4-(piperazin-1-yl)phenols, Michael addition reaction, oxidation of the formed adduct, another Michael addition reaction, oxidation of new adduct and hydrolysis (ECECEC). The results revealed that bisindolyl-p-quinones were synthesized through the regioselective addition of indoles to electrochemically generated quinone imines in good yields at carbon electrode in a divided cell. Ó 2012 Elsevier B.V. All rights reserved. 1. Introduction Facile access to substituted indoles is of general interest because indoles are building blocks of many natural products and have applications as pharmaceuticals, as agrochemicals, and in materials science [1]. Consequently, indoles or molecules containing the in- dole moiety have efficiently been synthesized for more than 100 years in solution. It is recognized that, the 3-indolylbenzoqui- none fragment is a core structure in a number of biologically active natural products such as asterriquinones [2]. Asterriquinone A1 (Fig. 1), has been shown to arrest the cell cycle in G1 (the major per- iod of cell growth during its lifespan) and promote apoptotic cell death [3]. Bisindolylquinones exhibit a range of biological activities against cancer and diabetes [4]. All these properties apparently stem from the ability of asterriq- uinones to either promote or prevent protein–protein interactions. The importance of these compounds has motivated many workers and us to synthesize a number of indolylquinones via different methods [5–10]. In this context, as a part of our program to electro- chemical synthesis of organic compound based on the in situ gener- ation of Michael acceptor [11–13], we thought that synthesis of new derivatives of bisindolylquinones would be useful from the point of view of pharmaceutical researches. This idea prompted us to inves- tigate electrochemical oxidation of 4-(piperazin-1-yl)phenols in the presence of indole derivatives as nucleophiles and report a facile and regioselective electrochemical method for the synthesis of some new bisindolylquinone compounds. 2. Experimental 2.1. Apparatus and reagents Cyclic voltammetry, controlled-potential coulometry and pre- parative electrolysis were performed using an Autolab model PGSTAT 20 potentiostat/galvanostat. The working electrode used in the voltammetry experiments was a glassy carbon disk (1.8 mm diameter) and a platinum wire was used as the counter electrode. The working electrode used in controlled-potential coulometry and macroscale electrolysis was an assembly of four ordinary car- bon rods (31 cm 2 from KIGCO, Mashhad, Iran), placed as single rods in the edges of a square with a distance of 3 cm. and a large platinum gauze cylinder (25 cm 2 area) constituted the counter electrode. The electrochemical oxidations were performed under controlled-po- tential conditions in a cell with two compartments separated by an ordinary porous fritted-glass diaphragm closed with a glass frit and equipped with a magnetic stirrer. All experiment was carried out at a temperature of 25 ± 1 °C. Melting points of all synthesized compounds were determined in open capillary tubes and are uncor- rected. More details are described in our previous paper [9]. 1-(4-(4-Hydroxyphenyl)piperazin-1-yl)ethanone (1a), 4-(pip- erazin-1-yl)phenol (1b), 1,2-dimethyl-1H-indol (3a), 2-dimethyl- 1H-indol (3b), 5-bromoindole (3c), were reagent-grade from 1572-6657/$ - see front matter Ó 2012 Elsevier B.V. All rights reserved. doi:10.1016/j.jelechem.2012.02.003 ⇑ Corresponding author. Tel.: +98 811 8282807; fax: +98 811 8257407. E-mail address: nemat@basu.ac.ir (D. Nematollahi). Journal of Electroanalytical Chemistry 670 (2012) 36–41 Contents lists available at SciVerse ScienceDirect Journal of Electroanalytical Chemistry journal homepage: www.elsevier.com/locate/jelechem