SN2/E2 Branching in Protic Solvents Bull. Korean Chem. Soc. 2009, Vol. 30, No. 7 1535 S N 2/E2 Branching in Protic Solvents: A Mechanistic Study Young-Ho Oh, Suk Im, Sung-Woo Park, Sungyul Lee, * and Dae Yoon Chi †,* Department of Applied Chemistry, Kyunghee University, Gyeonggi 446-701, Korea * E-mail: sylee@khu.ac.kr † Department of Chemistry, Sogang University, Seoul 121-742, Korea. * E-mail: dychi@sogang.ac.kr Received April 23, 2009, Accepted May 14, 2009 We present calculations for SN2/E2 reactions in protic solvents (t-butyl alcohol, ethylene glycol). We focus on the role of the hydroxyl (-OH) groups in determining the SN2/E2 rate constants. We predict that the ion pair E2 mechanism is more favorable than the naked ion E2 reaction in ethylene glycol. E2 barriers are calculated to be much larger (~ 9 kcal/mol) than SN2 reaction barriers in protic solvents, in agreement with the experimental observation [Kim, D. W. et al. J. Am. Chem. Soc. 2006, 128, 16394] of no E2 products in the reaction of CsF in t-butyl alcohol. Key Words: SN2/E2 branching, Protic solvent Introduction Although the bimolecular nucleophilic substitution (SN 2) 1-15 reaction has been known for very long, recent studies showed that the efficiency of the reaction may be significantly improved by careful and systematic investigation. The focus of these new developments in SN2 reaction was on the role of counterion (cation) and solvent. Chi and co-workers 9,11 de- monstrated that employing bulky protic solvents such as t-butyl alcohol and amyl alcohol leads to very efficient SN2 reactions, which is in direct contradiction with the conventional wisdom in SN2 community. The mechanism of this new type of SN2 reaction received a keen interest, and Lee and co-workers 9(a),12 proposed that the nucleophile reacts as a contact ion pair rather than as a solvent-separated ion pair, and that the protic solvents act as a Lewis base. This mechanism was in agreement with the observed features of the reaction, 9(b) such as the strong dependence on cation (Cs + , K + , Na + ) and the order of reactivity (F − > Cl − > Br − ). Small bifunctional protic solvent (ethylene glycol) was also predicted to give highly efficient SN2 reac- tions. The bimolecular elimination 16-26 (E2) rate constants are also of primary importance, because the E2 reactions usually compete with S N 2. It is well known that E2 reaction of a strong base such as F - may occur as readily as SN2. Detailed and sys- tematic investigation for the mechanism of competing SN2/E2 reactions at molecular level may yield invaluable information for elucidating the relative SN2/E2 rate constants as a function of interactions between the cation, solvent, and leaving group. In this work, we investigate the S N 2/E2 branching in protic solvent (t-butyl alcohol and ethylene glycol) by calculating and comparing the barriers of the SN2 [F − + n-C3H7-OMs → n-C3H7-F + OMs − ] and E2 [F − + n-C3H7-OMs → C3H6 + HF + OMs − ] reactions under the influence of the counterion Cs + and protic solvents. We focus on the role of the hydroxyl groups in protic solvent in determining the S N 2/E2 rate constants. Computational Methods Density functional theory method (MPW1K) 27,28 is em- ployed with the 6-311++G** basis set and the effective core potential for Cs (Hay-Wadt VDZ(n+1)), 29 as implemented in GAUSSIAN 03 set of programs. 30 Stationary structures are confirmed by ascertaining that all the harmonic frequencies are real. Structures of the transition state (TS) are obtained by verifying that one and only one of the harmonic frequencies is imaginary, and also by carrying out the intrinsic reaction coordinate (IRC) analysis along the reaction pathway. Zero point energies (ZPE) are taken into account, and default criteria are used for all optimizations. Results and Discussion Figure 1 presents the calculated E2 reactions of F ‒ in ethylene glycol. The most intriguing question concerning the mechanism of E2 reactions in protic solvents will be whether the nucleophile F − reacts as an ion pair as in S N 2 reactions discussed in previous works, 9,10,12 or as a naked ion. 11 The ion pair E2 reaction [Cs + F − ⋯C3H7-OMs] shown in Figure 1(a) proceeds from the lowest energy pre-reaction complex from which SN2 reaction also originate, 9(c) with the E2 barrier of 28.3 kcal/mol. On the other hand, the pre-reaction complexes for naked ion E2 reaction [F − + n-C 3 H 7 -OMs] depicted in Figure 1(b) are different from the lowest energy complex for naked ion SN2 reaction. 9(c) In the lowest energy complex for naked ion SN2 reaction, the two OH groups (each from the two ethylene glycol molecules) bind to the nucleophile F − (RH-F = 1.511, 1.539 Å), and the nucleophile F - also interacts with a hydrogen (R H-F = 1.882, 2.051 Å) of methyl group in the leaving group and α-hydrogen (RH-F = 1.882, 2.051 Å). In the naked ion E2 pre-reaction complexes, on the other hand, the two OH groups (each from the two ethylene glycol molecules) bind more strongly to the nucleophile F − (RH-F = 1.482, 1.449 Å), and the nucleophile F − (RH-F = 2.093 Å) interacts with the β-hydrogen. The energy of naked ion E2 complex presented in Figure 1 (b) is ~ 7.4 kcal/mol above the naked ion SN2 pre- reaction complex. Since the barrier from this E2 pre-reaction complex is calculated to be 23.6 kcal/mol, the overall barrier from the lowest energy naked ion complex is calculated to be