Electrochemical Reduction Of Phthalimides And Its Application In Drug Synthesis

Hydrogenation of carbonyl group into alcohol is one of the most fundamental organic transformations,which has been widely used in industrial production and drug synthesis.The reducing products of phthalimides are valuable building blocks in synthesis of various pharmaceuticals such as sedatives,hypnotics and muscle-relaxing drugs,which have drawn much attention from researchers.Hydrogen is usually used as the hydrogen-atom source in traditional hydrogenation reaction.The carbonyl group can be smoothly reduced into the corresponding hydroxyl group via this method catalyzed by platinum,palladium,nickel or other metals.Alternatively,some hydride donors such as lithium aluminum tetrahydride and sodium borohydride can also reduce the carbonyl group.However,the traditional methods have some limitations.For example,Raney nickel,the most commonly used metal catalyst,has the potential of explosion as well as ultra-high catalytic activity.It can spontaneously ignite when exposed to air.Lithium aluminum tetrahydride and sodium borohydride are highly sensitive to moisture,oxidant and acid,which enhance the requirement of operation and equipment.In order to develop a more greener,safer,simpler and efficient hydrogenation reduction method,we carried out the research work of this thesis.Through the unremitting efforts,we have developed an electrochemical method to reduce phthalimide derivatives by utilizing acid as the hydrogen source.It is divided into the following three parts.In the first chapter,is the author reviewed the advances in carbonyl hydroreduction and electrochemical reduction.The merits and demerits of these methods were discussed.We also analyzed the reaction mechanism involved in these processes.In the second chapter,we detailed the novel electrochemical method for reduction of phthalimide derivatives.A large number of experiments and data showed that this approach possesses the features as high yield,excellent selectivity,mild condition and simple operation.In addition,good functional group tolerance,scalability and late-stage functionalization made it valuable to drug synthesis.Finally,we carried out a series of mechanistic studies on this system and proposed the possible mechanism.In the last chapter,the author summarized this electrochemical reduction.Furthermore,the possible application of this method in synthesis of pharmaceuticals was outlined.