Multi-level Quantum Mechanics And Molecular Mechanics Study Of The F^-+NH₂Cl In Aqueous Solution

In recent years,there has been a lot of research into the mechanism of bimolecular nucleophilic substitution reactions,also known as S_N2 reactions.In 2016,a paper published in Science described eight mechanisms of S_N2 reactions in detail.According to the types of reactions,the eight reaction mechanisms are divided into two types,direct reaction mechanisms and indirect reaction mechanisms.Including a new indirect mechanism called the double-inversion mechanism.The double-inversion reaction mechanism was discovered in the F^-+CH₃Cl reaction in the gas phase in 2015.In this reaction mechanism,two inversion processes including induced abstraction-induced inversion and Walden-inversion were included.It also undergoes two transition states:the abstraction-induced inversion transition state and the Walden inversion transition state.The two inversion processes are connected by the intermediate complex.The intermediate complex is not only the product complex of the abstraction-induced inversion process but also the reaction complex of the Walden inversion process.And then,in the gas phase,in the X^-+CH₃Y?Y^-+CH₃X?X,Y=F,Cl,Br,I?reaction,they also found the double inversion mechanism.The same mechanism was also found in F^-+CH₃Cl and F^-+CH₃I reactions in the liquid phase.Therefore,it is believed that the double-inversion mechanism is universal in S_N2 reactions centered on C atom.In 2018,in the gas phase,the double-inversion reaction mechanism was discovered for the first time in the F^-+NH₂Cl reaction.The new mechanism involves the rotation of NHCl with one proton of NH₂Cl abstracted by the nucleophile,followed by a classical,backside-attack process.Thus,N atoms centered S_N2 reaction mechanisms still need further research.We employ a multi-level quantum mechanics and molecular mechanics method to investigate the double inversion mechanism of the nucleophilic substitution reaction atcenter:the F^-+NH₂Cl reaction in aqueous solution.We find that the structures of the stationary points along the reaction path are quite different from the ones in gas phase owing to the hydrogen-bond interactions between the solute and the surrounding water molecules.In the gas phase and the liquid phase,the difference of upside-down proton inversion transition state structure is particularly obvious.In gas phase,the N-H₁ bond is increased from 1.13?to 1.42?from reactant complex to TS1;at the same time,the F-H₁ bond is decreased from 1.36?to 1.03?.In other words,the nucleophile pulls H₁ out of the substrate at TS1.However,in the liquid phase,from the reactant complex to TS1,the corresponding two bond lengths change much less,especially the N-H₁ bond,only by 0.02?.The atomic-level evolutions of the structures and charge transfer along the reaction path show that this double-inversion mechanism consists of an upside-down proton inversion process and a Walden-inversion process.This is consistent with previous findings.The computed potential of mean force at the CCSD?T?/MM level of theory has the two-inversion barrier heights,and reaction free energy at 11.7,29.6,and 12.6kcal/mol,agreeing well with the predicted ones at 12.6,32.5,and 12.2 kcal/mol obtained based on the gas-phase reaction path and the solvation free energies of the stationary points.We also compare the double-flip mechanism of F^-+NH₂Cl reaction and F^-+CH₃Cl reaction in the liquid phase.For the first inversion mechanism,the barrier heights of TS1 in gas phase is-23.7 kcal/mol and 16.4 kcal/mol for F^-+NH₂Cl and F^-+CH₃Cl,while the barrier heights of TS1 in water are 11.7 kcal/mol and 75.1kcal/mol respectively.For the second inversion,the barrier height of F^-+NH₂Cl reaction is 29.6 kcal/mol,which is bigger than the one of F^-+CH₃Cl at 28.3 kcal/mol.The main reason for the difference is that N atom is more electronegative than C atom.In this article,we mainly introduce the development of quantum chemistry and basic concept in chapter 1;show the method in theory in chapter 2;study the characteristics of F^-+NH₂Cl reaction in chapter 3.The fourth chapter is summary and outlook.