Electrochemically Mediated Synthesis Of Hydroxyalkylquinoxalines And N-(α-Alkoxyalkyl) Azoles

The construction of C-C,C-O and C-N bonds has received extensive attention from chemists because of their important role in natural products,drugs,pesticides and materials.Therefore,the development of green and sustainable synthesis methods has profound implications for the chemistry community.Over the past decade,organic electrosynthesis has emerged as a powerful green and sustainable method for the construction of chemical bonds.Herein,we focus on the reduction of aldehydes to hydroxyalkyl radicals at the cathode,followed by the construction of C-C,C-O and C-N bonds via radical cross-coupling to synthesize nitrogen-containing compounds.The details of the study are as follows:（1）Quinoxalin-2（1H）-ones are an important class of heterocyclic compounds widely used in synthetic chemistry,materials,natural products and pharmaceuticals.Among them,functionalized quinoxalin-2（1H）-one derivatives at the C3 position have been reported in recent years for therapeutic applications in the pharmaceutical field,such as antibacterial,antitumor,anti-inflammatory,aldose reductase inhibitors and muscle relaxants for biological activities.Therefore,it has caused a wide range of chemists to investigate the functionalized quinoxalin-2（1H）-ones at the C3 position.We designed a method in which the reduction of aldehydes occurs at the cathode under constant current conditions to generate hydroxyalkyl radicals,which subsequently combine with quinoxalin-2（1H）-ones to obtain nitrogen radicals;at the anode,Cp₂Fe is oxidized to Cp₂Fe⁺,which promotes the further indirect oxidation of nitrogen radicals to nitrogen cations and finally deprotonates to give 3-hydroxyalkylquinoxalin-2（1H）-one analogues.This method dispenses with the use of heavy metal catalysts,stoichiometric oxidants and reducing agents,providing an environmentally friendly and organic electrosynthesis method under mild conditions.In addition,the gram products were obtained in electrochemical continuous flow reactors,which demonstrated its application potential.（2）Benzotriazoles are a useful structural motif associated with functionalized materials,drugs and ligands.In addition,benzotriazoles are versatile precursors for organic synthesis,and N¹ alkylated benzotriazoles often exhibit unique biological activities and are used as analgesics,antidepressants,anxiolytics and antagonists.Currently,selective N¹ alkylation in benzotriazoles remains challenging.We designed a method for the synthesis of a series of N-（α-alkoxyalkyl）azole derivatives under electrochemical conditions using inexpensive azoles,aldehydes,and alcohols as substrates.In this reaction,benzotriazoles were oxidized to nitrogen radicals at the anode and aldehydes were reduced to hydroxyalkyl radicals at the cathode,followed by the formation of hydroxyalkyl azole intermediates by radical coupling reactions and finally the reaction with alcohols to remove one molecule of water to obtain N-（α-alkoxyalkyl）azoles.The reaction was carried out under mild conditions without the addition of additional oxidation and reduction catalysts and metal catalysts,which is characterized by simple operation,atomic economy and green environment protection,providing a promising synthetic strategy for the structure modification of benzotriazoles.Further scale-up studies show its potential application value.