Electrochemical N-acylation Synthesis Of Amide From Aldehydes And Alcohols

As the basic structural unit of biological polypeptides and proteins,amide bond is the basis of all life processes and is ubiquitous in nature.Both the biological and chemical activities,as well as its structural characteristics,have a large demand market,which has inspired the interest and confidence of researchers,and a large number of good research has also achieved.The traditional methods have been gradually forgotten by researchers because of their inherent defects,such as low atom utilization rate,expensive catalyst,unstable and easy to pollute the environment,and replaced by novel,efficient,convenient,green,sustainable and easy to operate methods.In this respect,aldehydes and alcohols,due to their inherent advantages of low availability and toxicity,can be used as an important carrier for the synthesis of amide compounds,and a variety of strategies for the synthesis of amide have been explored.A large number of metal catalysts,such as various strong oxidants,various complex photocatalysts,iodine catalysts,N-heterocyclic carbene,nano materials,etc.have been developed,but most of these methods require extra strong bases,organic bases,harsh reaction conditions,long reaction time,etc.In view of the defects mentioned above,it is not a small challenge to develop an effective way to give full play to the advantages of various schemes and effectively avoid the inherent disadvantages.In recent years,researchers have begun to explore the method of high-efficiency synthesis of amides by electrochemical.Although researchers have achieved synthesis of amides by electrochemical,the disadvantages were by high reaction temperature and using expensive catalyst.Therefore,we have developed a green,sustainable and equivalent alternative oxidant,which can effectively synthesize amides from series of aldehydes and alcohols and series of amines by combining the very popular electrochemical synthesis in recent years with the iodine catalyst.It is also a very promising substitute of metal catalyst by using the oxidation-reduction cycle of iodine on the electrode surface to synthesize amide from series of aldehydes and alcohols.In order to select the best reaction conditions,benzaldehyde,benzylalcohol and morphorphine were selected as substrates.Firstly,the electrolyte type,electrode material,solvent,catalyst type and base/acid type were studied qualitatively.Then,the effects of reactant equivalent,catalyst dosage,voltage and current,reaction time and reaction atmosphere on the yield were investigated through quantitative analysis.The optimal reaction conditions were selected by comprehensive comparison of all the conditions.It is found that N-benzoylmorphorphine can be obtained by reaction of benzaldehyde and morphorphine with the equivalent of 1:10,without specific electrolyte,KI as catalyst and electrolyte,1:3 as equivalent,Pt as anode,Cu as cathode,6 V as constant pressure,Me OH as solvent,without any base,in undivided cell for 12 hours,with the highest yield of 91%.On the basis of aldehydes,the highest yield of N-benzoylmorphorphine obtained by HPLC is far lower than91%of aldehydes,only 52%.Through the optimization of a series of influence conditions,it is found that:under the condition of KI as catalyst and electrolyte,the equivalent is 550%,Pt as anode,Cu as cathode,Me OH as solvent,the equivalent of benzylalcohol and morpholine is1:20,and using air balloon to close the reaction system,and the reaction can be carried out in undivided cell at 8 V for 20 h without any base or extra electrolyte can increase the yield up to83%.In order to further verify the general applicability of the functional groups,different aldehydes,alcohols and amines were expanded respectively.Most of them have high yields under this condition,which shows that the scheme has a good application range.Finally,the structure of the purified product was characterized by ¹H NMR and ¹³C NMR.