A real space picture of the role of steric effects inS_N2reactions

Abstract

Within substitution reactions, the Bimolecular Nucleophilic Substitution (SN2) reaction mechanism is one of the most frequently found and studied ones. Among other factors, the easiness of the SN2 pathway is classically considered to be determined by steric hindrance. However, the diffuse nature of the latter inevitably darkens these and other arguments holding the pillars of chemical intuition. In this work, we employ the steric energy (EST) descriptor, formulated within the Interacting Quantum Atoms approach, to offer insights regarding this problem. The steric demands of the substrate, nucleophile and leaving group were studied using the gas‐phase SN2 reaction with different organic skeletons (CH3, CH3CH2, (CH3)2CH, (CH3)3C, (CH3)3CCH2) and halogens (F, Cl, and Br) as test‐bed systems. Our results show that, according to EST, the SH experienced along these simple reactions fits, in the general case, the trends predicted by a meticulous and rigorous application of chemical intuition. However, steric clash alone should not be considered as the only argument used to explain the easiness of the SN2 reaction over different electrophiles.

Effects of Methyl Substitution and Leaving Group on E2/SN2 Competition for Reactions of F− with RY (R = CH3, C2H5, iC3H7, tC4H9; Y = Cl, I)

“…For each anion series, the trend that KIEs became increasingly more normal (k H /k D > 1) as the extent of substitution indicated that the E2 pathway became the predominant pathway and steric effects inhibited the S N 2 pathway. A method calculating "steric hindrance (SH)" was proposed by Pendás and co-workers [39,40], which was consistent with the chemical intuition that the SH of the complex methylated alkyl system S N 2 was greater than E2.…”

Hydrolysis of ester phosphates mediated by a copper complex

“…Mevinphos has two –O–CH 3 groups, which do not generate an important steric hindrance due to the relative bulkiness of these groups. 57 Therefore the phosphorane intermediate appears in a shorter Nu–P distance. As shown in Fig.…”

Solvent-induced dual nucleophiles and the α-effect in the SN2 versus E2 competition

“…Bimolecular nucleophilic substitution (S N 2) and elimination (E2) are ubiquitous, often mutually competing, reactions. For nearly 50 years, the mechanism of the S N 2 reaction has been extensively studied experimentally and theoretically, including its temperature dependence, 1–3 benchmark studies, 4–11 steric effects, 12–21 and solvent effects. 14,15,22–29 Solvation can have a tremendous effect on chemical reactions.…”