Computational study of S_N2 reactions promoted by crown ether: Contact ion pair versus solvent‐separated ion pair mechanism

Abstract

We examined by quantum chemical methods the mechanism of SN2 reaction using metal bromide MBr (M = Na, K, Cs) and KX (X= F, Cl) in CH3CN promoted by crown ether (18‐crown‐6). We focus on whether the metal salts react as a contact ion pair (CIP; M+ and X– in close contact) or as a solvent‐separated ion pair (SSIP; M+ and X– at large distance). In SSIP mechanism, X– is removed far enough from M+ for the metal salt to be considered as “separated” by the effects of the crown ether and the solvent. In the CIP picture, conversely, the coordination of 18‐crown‐6 to M+ is not sufficient to overcome the powerful Coulombic interactions between M+ and X–. We find that the CIP route is favored for SN2 bromination processes using MBr (M = Na, K, Cs). For SN2 reaction using KF, the feasibility of the two pathways is essentially equal, whereas for SN2 chlorination by KCl the SSIP route is predicted to be favored.

Inter- and Intra-Molecular Organocatalysis of SN2 Fluorination by Crown Ether: Kinetics and Quantum Chemical Analysis

“…It seems that the latter structure formed between 2 and 3 for intermolecular S N 2 fluorination of 2 strongly resembles the TS for intramolecular S N 2 fluorination of 1 shown in Figure 3 . From this, the role of 18-crown-6 is clear: the metal salt Cs + F − coordinates to 3 , just as in S N 2 fluorination of 1 , and the O atoms in 18-crown-6 are acting as a Lewis base alleviating the Coulombic influence of the counter-cation Cs + to enhance the nucleophilicity of F − , as previously elucidated for other promoters [ 17 , 18 , 19 , 20 , 21 , 22 , 23 ] (bulky alcohols, oligoethylene glycols, and ionic liquids).…”

“…In this regard, some useful wisdom has been frequently invoked concerning the role of counter-cation and solvent for S N 2 reactions: alkali metal cations are considered to be inefficient as counter-cation, and protic solvents (water, alcohols) are to be avoided because of the harmful hydrogen bonding through –OH with the nucleophile. In a series of investigations, however, we have demonstrated [ 17 , 18 , 19 , 20 , 21 , 22 , 23 ] that these well-known concepts are not always true, showing that using alkali metal salts (such as CsF or KBr) in combination with Lewis base promoter/solvent (bulky alcohols, oligoethylene glycols, ionic liquids and derivatives et al) may lead to excellent S N 2 reactions without many side-products (usually with >90% S N 2 yield within several hours).…”

“…Here, we present the S N 2 fluorination promoted by crown ether [ 23 , 24 , 25 , 26 , 27 , 28 ] using the alkali metal salt CsF to estimate the efficacy of the promoter and to elucidate the mechanism - . We employ different types of substrates ( 1 vs. 2 ) for comparison.…”

Coordination Sites for Sodium and Potassium Ions in Nucleophilic Adeninate Contact ion-Pairs: A Molecular-Wide and Electron Density-Based (MOWED) Perspective

“…As the formation of a CIP results in the rearrangement of the electron density throughout a molecular system, it becomes apparent that adeninate anions in CIPs must exhibit different nucleophilic properties compared to that of the free anion [25]. Hence, to understand the chemical behavior of the reaction system of a CIP, it is imperative to establish the coordination site for the metal cation.…”