Efficiency of Bulky Protic Solvent for S_N2 Reaction

Abstract

We calculate and compare the effects of aprotic vs protic solvent on the rate of SN2 reaction [F- + C3H7OMs--> C3H7F + OMs-]. We find that aprotic solvent acetonitrile is more efficient than a small protic solvent such as methanol. Bulky protic solvent (tert-butyl alcohol) is predicted to be quite efficient, giving the rate constant that is similar to that in CH3CN. Our calculated relative activation barriers of the SN2 reaction in methanol, tert-butyl alcohol, and CH3CN are in good agreement with experimental observations.

Bis‐Terminal Hydroxy Polyethers as All‐Purpose, Multifunctional Organic Promoters: A Mechanistic Investigation and Applications

“…The other OH group interacts with the mesylate leaving group, thus helping it to detach from the reactant. The calculated energy barrier (E°= 18.6 kcal mol À1 , G°(100 8C) = 19.9 kcal mol À1 ) for the reaction with KF in tetraethylene glycol is much lower than even those calculated by similar methods for the same reaction with cesium and tetra-n-butylammonium fluoride in tert-butyl alcohol and ethylene glycol; [11] [Cs + F À + C 3 H 7 OMs!Cs + OMs À + C 3 H 7 F] in tert-butyl alcohol (E°= 23.5 kcal mol À1 , G°(80 8C) = 23.1 kcal mol À1 ), [nBu 4 N + F À + C 3 H 7 OMs!nBu 4 N + OMs À + C 3 H 7 F] in tert-butyl alcohol (E°= 25.3 kcal mol À1 , G°(80 8C) = 22.3 kcal mol À1 ), [12] and [Cs + F À + C 3 H 7 OMs!Cs + OMs À + C 3 H 7 F] in ethylene glycol (E°= 20.0 kcal mol À1 , G°(80 8C) = 21.5 kcal mol À1 ). [13] Replacing one hydroxy group of tetraethylene glycol by a methoxy group (see Figure S2) is calculated to increase the activation barrier significantly (E°and G°by 1.2 and 1.7 kcal mol À1 , respectively): this increase is due to the much lower acidity and tenuous interactions of OCH 3 with the leaving group compared with OH, which is in agreement with the experimental observation of a corresponding decrease in the reaction rate (see Scheme 2).…”

Bis‐Terminal Hydroxy Polyethers as All‐Purpose, Multifunctional Organic Promoters: A Mechanistic Investigation and Applications

“…The other OH group interacts with the mesylate leaving group, thus helping it to detach from the reactant. The calculated energy barrier ( E ≠ =18.6 kcal mol −1 , G ≠ (100 °C)=19.9 kcal mol −1 ) for the reaction with KF in tetraethylene glycol is much lower than even those calculated by similar methods for the same reaction with cesium and tetra‐ n ‐butylammonium fluoride in tert ‐butyl alcohol and ethylene glycol;11 [Cs + F − + C 3 H 7 OMs→Cs + OMs − + C 3 H 7 F] in tert ‐butyl alcohol ( E ≠ =23.5 kcal mol −1 , G ≠ (80 °C)=23.1 kcal mol −1 ), [ n Bu 4 N + F − + C 3 H 7 OMs→ n Bu 4 N + OMs − + C 3 H 7 F] in tert ‐butyl alcohol ( E ≠ =25.3 kcal mol −1 , G ≠ (80 °C)=22.3 kcal mol −1 ),12 and [Cs + F − + C 3 H 7 OMs→Cs + OMs − + C 3 H 7 F] in ethylene glycol ( E ≠ =20.0 kcal mol −1 , G ≠ (80 °C)=21.5 kcal mol −1 ) 13. Replacing one hydroxy group of tetraethylene glycol by a methoxy group (see Figure S2) is calculated to increase the activation barrier significantly ( E ≠ and G ≠ by 1.2 and 1.7 kcal mol −1 , respectively): this increase is due to the much lower acidity and tenuous interactions of OCH 3 with the leaving group compared with OH, which is in agreement with the experimental observation of a corresponding decrease in the reaction rate (see Scheme ).…”

Origin of Enhanced Reactivity of a Microsolvated Nucleophile in Ion Pair SN2 Reactions: The Cases of Sodium p-Nitrophenoxide with Halomethanes in Acetone

“…In this case, the dominant nucleophilic species will be ion pairs instead of free ions . Actually, many important organic reactions as well as biological processes usually involve neutral ion pairs as nucleophiles. − In recent years, the ion pair reaction has received increasing attention since its application has been discovered in the field of phase-transfer catalysis …”