10.1021/jp900576x.s001 Suk Im Suk Im Sung-Woo Jang Sung-Woo Jang Hye-Rim Kim Hye-Rim Kim Young-Ho Oh Young-Ho Oh Sung-Woo Park Sung-Woo Park Sungyul Lee Sungyul Lee Dae Yoon Chi Dae Yoon Chi A Mechanistic Study of S<sub>N</sub>2 Reaction in a Diol Solvent American Chemical Society 2009 protic cation SN 2 Reaction hydroxyl groups act ethylene glycol 353K SN 2 reactions nucleophile OH Lewis ethylene glycol manifests 2009-04-16 00:00:00 Journal contribution https://acs.figshare.com/articles/journal_contribution/A_Mechanistic_Study_of_S_sub_N_sub_2_Reaction_in_a_Diol_Solvent/2863453 We present calculations for the mechanism of S<sub>N</sub>2 reactions in ethylene glycol, focusing on the role of two protic functional groups (−OH) in the solvent molecule. We find that some hydroxyl groups act as Lewis base to interact with the cation, whereas others affect the reaction as Lewis acid to the nucleophile. We predict that the nucleophile (F<sup>−</sup>) reacts as an ion pair rather than as a solvent-separated ion when metal cation (Cs<sup>+</sup>) is used as a counterion. The overall influence of ethylene glycol manifests itself as the reaction barrier (<i>E</i><sup>⧧</sup> = 20.0, <i>G</i><sub>353K</sub><sup>⧧</sup> = 21.5 kcal/mol) that is a bit smaller than that in <i>tert</i>-butyl alcohol, which proved to be a very efficient solvent for S<sub>N</sub>2 reactions [Kim, D. W., et al. J. Am. Chem. Soc. 2006, 128, 16394]. We therefore show that a small protic solvent such as ethylene glycol may be as efficient as a bulky alcohol for S<sub>N</sub>2 reactions.