Theoretical Study On Palladium-Catalyzed Carbonylation Reaction Of Benzohydrazide

1,3,4-Oxadiazole-2(3H)-ones are widely applied to produce herbicide and insecticide in agriculture.It has been found that 1,3,4-Oxadiazole-2(3H)-ones can significantly improve pharmacological activities in medical field.And they are also excellent in anti-tumor,anti-virus,and other aspects.Therefore,synthesis of 1,3,4-Oxadiazole-2(3H)-ones have important theoretical and practical significance.In this paper,we employ density functional theory(DFT)M06 method to investigate the reaction mechanism of palladium catalyzed carbonylation of benzohydrazide to obtain 1,3,4-Oxadiazole-2(3H)-ones.The major research contents are presented as follows:I.The research progress of experimental and theoretical studies on palladium catalyzed carbonylation,and synthetic methods of 1,3,4-Oxadiazole-2(3H)-ones in recent years are introduced in the first part.II.We briefly introduce the basic theoretical knowledge of reaction mechanism,including density functional theory,transition state theory,and calculation software.III.The mechanism of palladium catalyzed carbonylation of benzohydrazide is studied in detail by density functional theory.This catalytic reaction mainly includes two possible mechanisms: Mechanism A and Mechanism B.In Mechanism A,four steps are mainly included: N1-H activation,N2-H activation,CO insertion,and reductive elimination.The activation of N1-H bond is accomplished by the classical CMD mechanism,which involves a six-membered ring transition state TS(1/2)-1.Then we find that the seven-membered ring transition state TS(3/6)can activate N2-H bond by one-step reaction,which greatly simplify the reaction.The energy barrier of directly N2-H activation is only 15.3 kcal/mol.In the process of carbonyl insertion,there are two possible pathways: CO insert into Pd-N bond(Path A-I)and CO insert into Pd-O bond(Path A-II).Finally,Path A-I and Path A-II of reductive elimination form the C-O bond and C-N bond,respectively.Two paths both can obtain 1,3,4-Oxadiazole-2(3H)-ones product.The results show that Path A-I is superior to Path A-II.In Mechanism B,four sequential steps are mainly included: N1-H activation,CO insertion,N2-H activation,and reductive elimination.CMD mechanism activate N1-H bond to get intermediate 3.Next,according to the position of CO insertion,the carbonyl insertion is divided into Path B-I and Path B-II to get 5-1? and 5-2?,respectively.Through the directly N2-H activation,the intermediate 10-2 and 10-5 are generated.Finally,reductive elimination occurs to obtain the target product.The results indicate that the CO insert into Pd-N bond(Path B-I)has the lower energy barrier,and it is more favorable when acetonitrile used as a ligand.Comparing with the favorable paths of Mechanism A and B,Path B-I is the most probable reaction pathway.CO insert into Pd-N bond(4-1??TS(4/5)-1??5-1?)needs to overcome the highest energy barrier,which is the rate-determining step in this carbonylation reaction.In addition,we research the influence of ligand effect and substituent effect on this reaction.Studies of ligand effect demonstrate that acetonitrile play two-fold roles in this reaction.It is not only used as a solvent,but also as a ligand to activate the Pd atom to significantly reduce the activation energy.Different N-aryl substituted derivatives have been examined for the rate-determining step and the results show that this reaction is generality with different substituents,which are consistent with the experimental conclusions.