Origin of the S_N2 Benzylic Effect

Abstract

The S N2 identity exchange reactions of the fluoride ion with benzyl fluoride and 10 para-substituted derivatives (RC6H 4CH 2F, R = CH3, OH, OCH 3, NH2, F, Cl, CCH, CN, COF, and NO2) have been investigated by both rigorous ab initio methods and carefully calibrated density functional theory. Groundbreaking focal-point computations were executed for the C6H5CH 2F + F (-) and C 6H 5CH2Cl + Cl (-) SN2 reactions at the highest possible levels of electronic structure theory, employing complete basis set (CBS) extrapolations of aug-cc-pV XZ (X = 2-5) Hartree-Fock and MP2 energies, and including higher-order electron correlation via CCSD/aug-cc-pVQZ and CCSD(T)/aug-cc-pVTZ coupled cluster wave functions. Strong linear dependences are found between the computed electrostatic potential at the reaction-center carbon atom and the effective SN2 activation energies within the series of para-substituted benzyl fluorides. An activation strain energy decomposition indicates that the SN2 reactivity of these benzylic compounds is governed by the intrinsic electrostatic interaction between the reacting fragments. The delocalization of nucleophilic charge into the aromatic ring in the SN2 transition states is quite limited and should not be considered the origin of benzylic acceleration of SN2 reactions. Our rigorous focal-point computations validate the benzylic effect by establishing SN2 barriers for (F (-), Cl (-)) identity exchange in (C6H5CH2F, C6H 5CH2Cl) that are lower than those of (CH3F, CH3Cl) by (3.8, 1.6) kcal mol (-1), in order.

d10-ML2 Complexes: Structure, Bonding, and Catalytic Activity

“…Due to its fragment-based nature, the model is most often applied to bimolecular processes, such as oxidative additions [24] as in this work, but also S N 2-reactions [16,25,26], pericyclic reactions [27], and even barrier-free bond formations, such as hydrogen or halogen bonds [28]. However, also unimolecular processes are successfully studied using the activation strain [29][30][31].…”

Effects of structural variations on the hydrogen bond pairing between adenine derivatives and thymine

“…Since the atoms in the vicinity of N1 and N6 atoms in adenine remain the same throughout the investigated series (Scheme 1), it can be considered that the shifts of V Y (Y = N1, H6) upon the distant structural variations (at position C8) are dominated by electron density variations near atoms Y. Numerous successful application of EPN as a reactivity index for hydrogen bonding and chemical reactivity confirm the credibility of this hypothesis [53][54][55][56][57][58][59][60][61][62][63][64][65]. Figure 1 illustrates key geometrical parameters of some optimized complexes.…”

“…Z A is the charge of nucleus A at position R A , and ρ(r) is the electron density func-tion. Following the original findings [53][54][55][56][57] that EPN values define quantitatively the ability of molecules to form hydrogen bonds, the EPN index was extensively applied in describing both hydrogen bonding and chemical reactivity of various molecular systems [58][59][60][61][62][63][64][65]. In a recent review, we surveyed the application of EPN in quantifying various molecular properties of aromatic systems [62].…”

Theoretical vs. Experimental Ir Frequency Shifts Upon Π- Hydrogen Bonding: Complexes of Substituted Phenols With Hexamethylbenzene

“…EPN was first introduced by Wilson in 1962 [41]. In a number of studies from our laboratory, we have established that EPN is a remarkably accurate descriptor of the abilities of specific atomic centers in molecules to form hydrogen bonds [42][43][44][45][46][47] and also in quantifying chemical reactivity [48][49][50][51]. In later years, EPN values have been successfully employed by other authors in examining reactivity trends [52][53][54][55][56][57][58][59][60].…”