Theoretical Studies on F^– + NH₂Cl Reaction: Nucleophilic Substitution at Neutral Nitrogen

Abstract

The SN2 reactions at N center, denoted as SN2@N, has been recognized to play a significant role in carcinogenesis, although they are less studied and less understood. The potential energy profile for the model reaction of SN2@N, chloramine (NH2Cl) with fluorine anion (F(-)), has been characterized by extensive electronic structure calculations. The back-side SN2 channel dominates the reaction with the front-side SN2 channel becoming feasible at higher energies. The minimum energy pathway shows a resemblance to the well-known double-well potential model for SN2 reactions at carbon. However, the complexes involving nitrogen on both sides of the reaction barrier are characterized by NH---X (X = F or Cl) hydrogen bond and possess C1 symmetry, in contrast to the more symmetric ion-dipole carbon analogues. In the F(-) + NH2Cl system, the proton transfer pathway is found to become more competitive with the SN2 pathway than in the F(-) + CH3Cl system. The calculations reported here indicate that stationary point properties on the F(-) + NH2Cl potential energy surface are slightly perturbed by the theories employed. The MP2 and CAM-B3LYP, as well as M06-2X and MPW1K functionals give overall best agreement with the benchmark CCSD(T)/CBS energies for the major SN2 reaction channel, and are recommended as the preferred methods for the direct dynamics simulations to uncover the dynamic behaviors of the title reaction.

Facilitated inversion complicates the stereodynamics of an SN2 reaction at nitrogen center

“…New geometries, carefully selected and added to improve the PES, are generated in quasi-classical trajectory (QCT) simulations and by the Holebuster subprogram. 40 ROBOSURFER iterations are performed at the following collision energies (kcal mol À1 ) used in the dynamics computations with the maximal values of the b impact parameter (the distance between the velocity vectors of the reactants in bohr) in parentheses: 64, 27,13,11,13,27,17,62,36 Quasi-classical trajectory simulations are performed at seven collision energies: 0.9, 6.9, 10.0, 20.0, 30.0, 40.0, and 46.1 kcal mol À1 to investigate the dynamics of the F À + NH 2 Cl reaction. The spatial orientation of the reactants is randomly sampled, and the initial distance between the F À ion and the center of mass of the NH 2 Cl molecule is set to ffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi x 2 þ b 2 p bohr, where x ¼ 30.0 bohr and the b impact parameter is varied between 0 and b max , the distance where the reaction probability becomes zero, with a step size of 1.0 bohr.…”

“…20 Theoretical investigations of the S N 2 reactions at N center began with the characterization of the potential energy surfaces (PESs) of X À + NH 2 Y and N(CH 3 ) 2 Y [X, Y ¼ F, Cl, Br, I] using lower-level ab initio [21][22][23][24] and density functional theory (DFT) methods. [25][26][27] Later, Bickelhaupt and co-workers studied the impact of replacing the central carbon atom in S N 2 reactions with several other atoms by performing an activation strain analysis. 28,29 In 2018 one of the present authors reported benchmark classical and adiabatic CCSD(T)-F12b/complete-basis-set-quality stationary-point energies and geometries taking also into account the correlation of core electrons both for identity and non-identity X À + NH 2 Y [X, Y ¼ F, Cl, Br, I] reactions.…”

Theoretical Investigation of the Gas-Phase SN2 Reactions of Anionic and Neutral Nucleophiles with Chloramines

“…The intrinsic reaction coordinate (IRC) 44 calculation was performed to confirm that every transition state connects with the corresponding reactant and product through the minimized-energy pathway. Previous results 25,27 reported that basis set effects on the energy barriers of the S N 2@N reactions are small. As CCSD(T) energies for F − + NH 2 Cl stationary points reported by Zhang et al, 27 regarding the augcc-pVXZ (X = D, T, Q, and 5) basis sets enlarged from X = D to 5, the CCSD(T) reference data are converged fast for the minima with the deviations within 2 kcal/mol, whereas those for the transition states are converged slightly slower with the deviations around 2−5 kcal/mol.…”

“…Recently, Wang et al 26 employed a multilevel quantum mechanics and molecular mechanics approach to study the reaction HO − + NH 2 Cl in aqueous solution, and also found that S N 2@N reaction is a faster reaction than the corresponding S N 2@C reaction. Zhang and Yang et al 27 explored the potential energy profile for the model S N 2 reaction of F − with NH 2 Cl by extensive electronic structure calculations and found that the backside channel dominates the reaction, and the proton transfer pathway is more competitive for S N 2@N reaction compared with the corresponding S N 2@C reaction. Very recently, they 28 also studied the atomistic dynamics of the above reaction by using direct dynamics simulations and found strikingly distinct features from those determined for a S N 2@C congener F − + CH 3 Cl.…”

Multilevel Quantum Mechanics and Molecular Mechanics Study of the Double-Inversion Mechanism at Nitrogen: F– + NH2Cl in Aqueous Solution

“…However, the above studies are mostly done for the S N 2 reaction at the carbon center; nitrogen-centered S N 2 reactions have been less studied. − For the title reaction, F – + NH 2 Cl , in gas phase, Buhl and Schaefer performed ab initio DZP/SCF calculations and obtained the barrier height of the Walden-inversion pathway at −6.9 kcal/mol. Liu et al studied the reaction profiles of this reaction for the indirect hydrogen-bond complex, proton transfer, and front side mechanism with the coupled-cluster singles and doubles with perturbative triples (CCSD­(T))/CBS theory.…”