G10 Journal of The Electrochemical Society, 164 (2) G10-G16 (2017) 0013-4651/2017/164(2)/G10/7/$33.00 © The Electrochemical Society Electrochemical Synthesis of Some 6-Amino-5-hydroquinone- 1,3-dimethyluracil Derivatives: A Green, Simple and Efficient Strategy Mehdi Shabani-Nooshabadi, a, z Mohsen Moradian, b and Samira Dadkhah-Tehrani a a Department of Analytical Chemistry, Faculty of Chemistry, University of Kashan, Kashan, Iran b Department of Organic Chemistry, Faculty of Chemistry, University of Kashan, Kashan, Iran In order to synthesize some of new 6-amino-5-hydroquinone-1,3-dimethyluracil derivatives, the electrochemical oxidation of hy- droquinones (1a-c) was carried out in the presence of 6-amino-1,3-dimethyluracil as a nucleophile in an aqueous phosphate buffer solution. The results show that electrogenerated p-benzoquinone moieties (1a ′ -c ′ ) participate in the reaction with 6-amino-1,3- dimethyluracil via the EC mechanism to form the corresponding uracil derivatives (3a-c). The electrosynthesis of these compounds (3a-c) was performed successfully in an aqueous solution at carbon rod electrodes, without using any toxic reagents, catalyst or solvents and the products were finally produced in high yield and purity. The proposed method has a novel viewpoint in the synthesis of potential anticancer/antiviral uracil-base drugs. © 2016 The Electrochemical Society. [DOI: 10.1149/2.0321702jes] All rights reserved. Manuscript submitted September 7, 2016; revised manuscript received November 28, 2016. Published December 8, 2016. Dearomatization reactions have been widely recognized as a pow- erful tactic for the synthesis of complex molecules from simple aro- matic substrates. 1–5 In this way, the controlled oxidation of arenes is very important for a substitution of different nucleophiles on the oxi- dized component. 6 This tactic can perform in organic synthesis with an electrochemical method like constant potential coulometry. The main benefits of using electrochemistry include high atom economy (conversion efficiency of the process) and reduction of waste gener- ated by the several chemical processes as well as of the time and work required to carry them out. In recent years, organic electrosynthesis has been known as a green methodology in organic chemistry. 7–10 Since electrons can be used as clean reduction reactants, it is possible to replace toxic and dangerous reagents 11–29 such as hypervalent iodine (exmp. PhI(OAc) 2 , PhI(TFA) 2 , F-PhI(TFA) 2 ), 30–32 Pb(OAc) 4 , 33 oxone as the source of sin- glet oxygen, 34 [{(-)-sparteine} 2 Cu 2 O 2 ] complex 35 and other reagents with an electric current. Essential reactions such as carbon-carbon, carbon-nitrogen, carbon-sulfur and carbon-oxygen bond formation and functional group interconversions 36 can be obtained from electron transfer. 37 These reactions in the electroorganic synthesis technique can be carried out at high selectivity, can reduce energy consumption, and can be carried at room temperature and without using of cata- lyst and toxic reagents. 38 Classical procedures of organic synthesis take place in organic solvents with low volatility, but electrochemical synthesis reactions can be performed in an aqueous medium with- out organic solvents 7 moreover, hydroalcoholic mixtures also are an excellent media to carry out electrosynthesis reactions. 39,40 Due to the biological and environmental significance of hydro- quinone such as application as antioxidant, production of dyes, phar- maceutical, cosmetics and photographic industries, the synthesis of hydroquinone derivatives is very important 41–43 and their redox system has been extensively studied. 44–47 Uracil is one of the four nucleobases in the nucleic acid of RNA (ribonucleic acid) building block. Uracil derivatives are used as anticancer and antiviral drugs, pesticides and anti-photosynthetic herbicides. 48–54 In the present study, we investigated a simple electrochemi- cal method for the synthesis of new 6-amino-5-hydroquinone-1,3- dimethyluracil derivatives by the electrochemical oxidation of some hydroquinone moieties in the presence of 6-amino-1,3-dimethyluracil. The reaction was performed in an aqueous media and the target prod- ucts were produced in excellent yield and purity that enables multiple transformations in the one-pot reaction sequence. Moreover, the re- action was carried out at room temperature and using any organic solvents and catalysts under green conditions. The other novelties of z E-mail: m.shabani@kashanu.ac.ir this work are the in situ production of quinone in the electrode in- terface area as an unsoluble reagent in the buffer solution media and replacing toxic and dangerous oxidizing reagents with electrons and reduce energy consumption of the reaction. Experimental Apparatus and reagents.—Cyclic voltammetry (CV), preparative electrolysis and controlled-potential coulometry were performed us- ing a μ-AUTOLAB potentiostat/galvanostat model μIII AUTO 71174 connected to a Pentium IV personal computer through a USB electro- chemical interface. The pH of the buffer solutions was adjusted using a pH-meter (Corning, Model 140) with a double junction glass elec- trode. The working and counter electrodes used in the voltammetry experiments were a glassy carbon disc electrode (0.031 cm 2 area) and a platinum wire electrode respectively. The working electrode used in controlled-potential coulometry and macroscale electrolysis was an assembly of tree ordinary carbon rods (9 mm diameter and 6 cm length). A large platinum gauze cylinder (10 cm 2 area) constituted the counter electrode. The potential of working electrode was mea- sured versus Ag/AgCl (3.0 M KCl) electrode (all electrodes were from Azar Electrode Company). The glassy carbon electrode was polished with a polishing cloth before each measurement. The electrolysis was performed under a constant-potential condition in a cell with two com- partments separated by an ordinary porous fritted glass diaphragm (a tube with 4 cm diameter). During electrolysis, a magnetic stirrer was used. The final products characterized using 1 H NMR, 13 C NMR, FT-IR spectroscopic techniques and CHNS analyzer. Fourier trans- form infrared (FT-IR) spectra were obtained using a Perkin-Elmer 781 spectrophotometer. The NMR spectra were recorded on a Bruker Avance DPX 400 MHz instrument spectrometer at 400 and 100 MHz in DMSO as a solvent in the presence of tetramethylsilane as internal standard. The hydroquinones (hydroquinone, 2-methylhydroquinone and 2,3-dimethylhydroquinone) and 6-amino-1,3-dimethyluracil were reagent grade material and purchased from Merck chemical com- pany. The NaH 2 PO 4 , Na 2 HPO 4 and other acids and bases were of pro-analysis grade from Merck chemical company. These chemicals and solvents were used without further purification. All experiments were carried out at room temperature. General procedure for the electroorganic synthesis of 6-amino- 5-hydroquinone-1,3-dimethyluracil.—In a general procedure, phos- phate buffer solution (pH 7.0, 0.1 M) containing of the 0.25 mmol of hydroquinones (1a-c) and 0.25 mmol of 6-amino-1,3-dimethyluracil (2) was electrolyzed at suitable potential (0.40, 0.39 and 0.37 V vs Ag/AgCl electrode for the 1a, 1b and 1c respectively) in a divided cell. The progress of the reaction was monitored by the method of ) unless CC License in place (see abstract). ecsdl.org/site/terms_use address. Redistribution subject to ECS terms of use (see 139.80.123.50 Downloaded on 2016-12-09 to IP