Electrochemical late-stage modification of hydralazine an antihypertensive drug. A green strategy for the synthesis of nano-structured new sulfonylhydrazine derivatives

This work is focused on the electrochemical late-stage modification of hydralazine (1-hydrazinylphthalazine) ( HYD ), a common antihypertensive drug, and the synthesis of its new sulfonylhydrazine derivatives. The synthesis of HYD derivatives has been easily accomplished in one-pot via electrochemical oxidation of HYD in the presence of arylsulfinic acid derivatives ( ASA ) in a water/ethanol mixture at constant current conditions. The electrochemical results show that anodically generated 1-diazenylphthalazine ( HYD ox ) reacts with arylsulfinic acids and converts into the corresponding sulfonylhydrazine derivatives ( SHD ) with high yield and purity in an undivided cell equipped with graphite anode and stainless steel cathode. The main feature of this work is the synthesis of some new HYD derivatives in water/ethanol mixture as a “ Green ” reaction medium, using electrodes instead of toxic oxidants, having a high atom economy, having good energy efficiency and working at room temperature. These features are in accordance with the principles of green chemistry. Another advantage of this approach is that this method has led to the synthesis of sulfonylhydrazine derivatives in nano dimensions. Also, in this work, the electrochemical behavior of HYD and synthesized compounds ( SHD ) by different electrochemical methods were fully investigated and the results were reported. Furthermore, docking studies suggest that the products interact well with arylamine N -acetyltransferase ( NAT ) and show promising activity. The synthesis of hydralazine derivatives has been easily accomplished in one-pot via electrochemical oxidation of hydralazine in the presence of arylsulfinic acid derivatives in a water/ethanol mixture at constant current conditions. • Late-stage modification of drugs. • Electrochemical synthesis of new hydralazine derivatives. • Comprehensive electrochemical studies. • Green synthesis. • Molecular docking studies.