Facile S(N)2 reaction in protic solvent: quantum chemical analysis.
We study the effects of protic solvent (water, methanol, ethanol, and tert-butyl alcohol) and cation (Na+, K+, Cs+) on the unsymmetrical SN2 reaction X- + RY --> RX + Y- (X = F, Br; R = CH3,C3H7;Y = Cl, OMs). We describe a series of calculations for the S(N)2 reaction mechanism under the influence of cation and protic solvent, presenting the structures of pre- and postreaction complexes and transition states and the magnitude of the activation barrier. An interesting mechanism is proposed, in which the protic solvent molecules that are shielded from the nucleophile by the intervening cation act as a Lewis base to reduce the unfavorable Coulombic influence of the cation on the nucleophile. We predict that the reaction barrier for the S(N)2 reaction is significantly lowered by the cooperative effects of cation and protic solvent. We show that the cation and protic solvent, each of which has been considered to retard the SN2 reactivity of the nucleophile, can accelerate the reaction tremendously when they interact with the fluoride ion in an intricate, combined fashion. This alternative S(N)2 mechanism is discussed in relation to the recently observed phenomenal efficiency of fluorination in tert-alcohol media [Kim, D. W.; et al. J. Am. Chem. Soc. 2006, 128, 16394].
Oh
Young-Ho
YH
College of Environmental Science and Applied Chemistry (BK 21), Kyunghee University, Kyungki 449-701, Korea.
Ahn
Doo-Sik
DS
Chung
Sang-Yoon
SY
Jeon
Jeong-Hwan
JH
Park
Sung-Woo
SW
Oh
Seung Jun
SJ
Kim
Dong Wook
DW
Kil
Hee Seup
HS
Chi
Dae Yoon
DY
Lee
Sungyul
S
D002412:Cations; D002586:Cesium / Q000737:chemistry; D002621:Chemistry / Q000379:methods; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D004364:Pharmaceutical Preparations / Q000737:chemistry; D011789:Quantum Theory; D012969:Sodium Fluoride / Q000737:chemistry; D012984:Software; D012997:Solvents / Q000737:chemistry*; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
D002412:Cations; D004364:Pharmaceutical Preparations; D012997:Solvents; D014867:Water; D002586:Cesium; D012969:Sodium Fluoride