Convergent paired electrochemical synthesis of symmetric dispiro and spiropyrimidine derivatives based on reduction of para-nitrophenol

Abstract

• Electrochemical study of para -nitrophenol. • Electrochemical synthesis of dispiro and spiropyrimidine derivatives. • Evaluation of antibacterial susceptibility of synthesized compounds. • Detailed mechanistic study of synthesized compounds. • Optimization of effective parameters on the yield of synthesized compounds. A green electrochemical method was developed for the synthesis of new types of spiro and dispiro pyrimidine derivatives. The electrochemical generation of reactive intermediates from para -nitrophenol ( PNP ) and their reactions with barbituric acids ( BA1-BA3 ) is a key step in the formation of target products ( P 1- P 3 ). Our data show that the reactivity of the nucleophile (barbituric acids) plays an important role in the type of product. Accordingly, when barbituric acid ( BA1 ) or thiobarbituric acid ( BA2 ) is used as a nucleophile, dispiro product ( P 1 or P 2 ) is formed in a convergent paired electrochemical reaction. However, when 1,3-dimethylbarbituric acid ( BA3 ) is used as a nucleophile, due to its higher reactivity than BA1 , the final product is an spiro compound that results from the reaction of BA3 with cathodically generated para -nitrosophenol. The highly symmetric dispiro and spiro compounds ( P 1- P 3 ) have been successfully synthesized in a water/ethanol mixture at the carbon electrode in an undivided cell using the constant current electrolysis method. Also, the antibacterial tests indicated that the products P 1- P 3 showed good antibacterial performance against gram-positive bacteria ( Bacillus cereus and Staphylococcus aureus ). In this work, we synthesized a number of new spiro and dispiro pyrimidine compounds ( P 1- P 3 ) using a convergent paired electrochemical method, by electrolysis of PNP in the presence of barbituric acids ( BA1-BA3 ), under mild and green conditions for the first time.