| N-alkylation has been widely studied since its important role in chemistry,medicine,pesticide and functional materials.Amines react with alcohol under transition metal catalysts using borrowing hydrogen strategy to synthesize higher amines can not only provide high yield,but also theoretically generates water as the only byproduct.Traditional transition metal catalysts such as palladium complexes can cause environmental problems,despite the high catalytic efficiency.With more attention paid to environmental problems,the demand of environmental-friendly catalysts is increasing.With the properties of availability and low cost in mind,iron-catalysts have started to become popular recently.However,the difficulty of iron complexes as N-alkylation catalysts is that Fe(III)tends to carry out single electron transfer,while double electrons transfer is required in hydrogen borrowing mechanism.Meanwhile,although the N-alkylation of primary amine with alcohol has been deeply studied,the alkylation of secondary amine is still being explored.In 2011,Saito and colleagues published N-alkylation of secondary amines and alcohols under a Fe(III)catalyst opened an era for Fe(III)catalyst.Based on Satio and his colleagues’ experiment,we studied the mechanism of N-alkylation between secondary amines and alcohols under iron-based catalyst using density functional theory(DFT)method and the SMD solvation model in the Gaussian09 program.By comparing the Gibbs free energy barrier of each transition state,we obtained the most favorable pathway.According to the calculation performed at M06-2x level,there’re three sequential steps: Fe(III)catalyst takes one hydrogen from alcohol methyl to generate benzyl radical;the benzyl radical on alcohol attacks the nitrogen on the secondary amine to form a single carbon-nitrogen bond and dehydrate;hydrogen reduction to form the final advanced amine product,and the catalyst completes a catalytic cycle.According to the optimized structure of the Fe(III)catalyst,there are two possible pathways for the hydrogen borrowing process: the oxygen attached to the nitrogen ring on the catalyst takes the hydrogen from alcohol methyl group;The oxygen directly connects to the Fe takes the alcohol of benzyl hydrogen.Therefore,there are also two pathways in hydrogen reduction.Meanwhile,we discussed four possible pathways to form a nitrogen-carbon bond:(1)the radical on methyl group attacks the secondary amine followed by direct dehydration;(2)the radical on methyl group attacks the secondary amines,leading to a multi-step dehydration;(3)a primary amine and aldehyde are formed first.Then,it follows the traditional N-alkylation of primary amine with alcohol without water or transition-metal catalyst.The initial steps of(4)and(3)are the same,except for after the primary amine and aldehyde are generated,the extra amount of ligand in the solvent participates in the reaction as a hydrogen bridge.Considering the solvation effect of 1,2,4-TMB,we calculated the free energy barriers.As a result,the free energy barrier of the oxygen connected to nitrogen ring taking hydrogen is lower in terms of hydrogen borrowing and hydrogen reduction,which means it is easier to carry out.Also,we found that the direct dehydration has the lowest free energy barrier and contains only one transition state,indicating it’s more favorable.Ligand participation in the reaction as a hydrogen bridge can greatly reduce the free energy barrier.However,forming a primary amine from the secondary amine requires a high free energy barrier.Thus,this path is difficult to proceed.The rate-determine steps are the transition states in borrowing hydrogen and the dehydration step.The research shows that the Fe(III)complex can play a catalytic role on the N-alkylation of secondary amine with alcohol.It helps the hydrogen radical transfer and generates the radical on alcohol to attack the secondary amine.This study provides theoretical information for N-alkylation with alcohol study and develops a new idea on the hydrogen borrowing strategy. |
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