The α-effect exhibited in gas-phase S_N2@N and S_N2@C reactions

Abstract

In order to explore the existence of α-effect in gas-phase S(N)2@N reactions, and to compare its similarity and difference with its counterpart in S(N)2@C reactions, we have carried out a theoretical study on the reactivity of six α-oxy-Nus (FO(-), ClO(-), BrO(-), HOO(-), HSO(-), H2NO(-)) in the S(N)2 reactions toward NR2Cl (R = H, Me) and RCl (R = Me, i-Pr) using the G2(+)M theory. An enhanced reactivity induced by the α-atom is found in all examined systems. The magnitude of the α-effect in the reactions of NR2Cl (R = H, Me) is generally smaller than that in the corresponding S(N)2 reaction, but their variation trend with the identity of α-atom is very similar. The origin of the α-effect of the S(N)2@N reactions is discussed in terms of activation strain analysis and thermodynamic analysis, indicating that the α-effect in the S(N)2@N reactions largely arises from transition state stabilization, and the "hyper-reactivity" of these α-Nus is also accompanied by an enhanced thermodynamic stability of products from the n(N) → σ*(O-Y) negative hyperconjugation. Meanwhile, it is found that the reactivity of oxy-Nus in the S(N)2 reactions toward NMe2Cl is lower than toward i-PrCl, which is different from previous experiments, that is, the S(N)2 reactions of NH2Cl is more facile than MeCl.

Probing the reactivity of microhydrated α‐nucleophile in the anionic gas‐phase SN2 reaction

“… HO − versus HOO − : This pair of reagents is usually used as a typical example for showing the α‐effect of HOO − . Our previously computed Δ G ≠ (HOO − ) is higher than Δ G ≠ (HO − ) by 5.3 kJ/mol, that is, k HOO− / k HO− = 0.118. This result reveals that no α‐effect can be detected for the unhydrated HOO − compared with HO − in the gas‐phase reactions with CH 3 Cl.…”

“…Table lists the computed magnitude of the α‐effect, denoted as ΔΔ G ≠ α , for monohydrated and dihydrated α‐oxy‐nucleophiles, also including unhydrated ones for comparison. Several interesting points can be extracted from these studies: As unsolvated nucleophiles, the α‐effect of monohydrated and dihydrated α‐nucleophiles still becomes weaker when the position of α‐atom moves from the top to the bottom or from right to left in the periodic table, that is, ΔΔ G ≠ α value is larger for α‐nucleophile with a more electro‐negative α‐atom. The magnitude of α‐effects generally increases from monohydrated to dihydrated nucleophiles, implying that dihydration of nucleophiles might be a good model for observing the α‐effect in the case of microsolvation. The ΔΔ G ≠ α values of unhydrated α‐Nus are generally larger than those of microhydrated α‐Nus, revealing that the reactivity of α‐Nu will be weaken instead of being enhanced with the microhydration, which is in contrast to the conclusion by the comparison of α‐Nu with specific normal nucleophile, for example, ROO − versus RO − (R = H, Me). …”

“…HO 2 versus HOO 2 : This pair of reagents is usually used as a typical example for showing the a-effect of HOO 2 . Our previously computed DG 6 ¼ (HOO 2 ) is higher than DG 6 ¼ (HO 2 ) by 5.3 kJ/mol, [46] that is, k HOO2 /k HO2 We can draw some conclusion from above findings. There are different microsolvation effects on the relative reactivity in the comparisons of a-nucleophile with specific normal nucleophile.…”

“…1. As unsolvated nucleophiles, [46] the a-effect of monohydrated and dihydrated a-nucleophiles still becomes weaker when the position of a-atom moves from the top to the bottom or from right to left in the periodic table, that is, DDG 6 ¼ a value is larger for a-nucleophile with a more electro-negative a-atom. 2.…”

“…The mechanism on α‐effect had been explored for more than 50 years, but the definitive answer for its origin has not been found. There are usually four explanations put forward for the origin of α‐effect, and one of them suggests that the α‐effect is induced by external solvent, and can not be observed in the gas phase, whereas the existence of α‐effect in gas phase was predicted by recent theoretical studies, and validated by the experiments …”