SN2 Reactions in the Gas Phase

The first su estion of the double niinimum potential well energy model for the gas-phase Sn2 reaction resulted from Olmstead and Brauman s work on the reaction of chloride ion with methyl chloride (Eqn (1.14)). °° 

McMahon and coworkers considered the study of reaction (Eqn (1.14)) with isotopically labeled reactants, Cl and CH Cl, which would have given very valuable information, but were unable to do so because the cost of reagents was prohibitive. They did carry out an excellent high-pressure mass spectrometric study that provided thermochemical data for reaction (Eqn (1.14)) and related Sn2 reactions. For identity reactions they found that an increase in the well depth increases with increasing size 

A non-identity reaction system on which computation studies have been carried out is illustrated in Eqn (1.15). This reaction has attracted considerable attention, while a more general study of reactions of the Eqn (1.10) type has not. 

Perhaps the most extensive computations were those of Press and Radom. C2(+) theory was used and it was pointed out that this level of theory is equivalent to the high level QCTSD(T)/6-311+G(3df,2p). The main goals of the study were to obtain more accurate energy data for the double potential energy wells and the transition states and to assess the role of thermodynamics in governing barrier heights and to test the 

It should be pointed out that the indirect pathway is expected to result from conventional ab initio computations. 

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Other measures of nucleophilicity have been proposed. Brauman et al. studied Sn2 reactions in the gas phase and applied Marcus theory to obtain the intrinsic barriers of identity reactions. These quantities were interpreted as intrinsic nucleo-philicities. Streitwieser has shown that the reactivity of anionic nucleophiles toward methyl iodide in dimethylformamide (DMF) is correlated with the overall heat of reaction in the gas phase he concludes that bond strength and electron affinity are the important factors controlling nucleophilicity. The dominant role of the solvent in controlling nucleophilicity was shown by Parker, who found solvent effects on nucleophilic reactivity of many orders of magnitude. For example, most anions are more nucleophilic in DMF than in methanol by factors as large as 10, because they are less effectively shielded by solvation in the aprotic solvent. Liotta et al. have measured rates of substitution by anionic nucleophiles in acetonitrile solution containing a crown ether, which forms an inclusion complex with the cation (K ) of the nucleophile. These rates correlate with gas phase rates of the same nucleophiles, which, in this crown ether-acetonitrile system, are considered to be naked anions. The solvation of anionic nucleophiles is treated in Section 8.3. 

There is evidence, both experimental and theoretical, that there are intermediates in at least some Sn2 reactions in the gas phase, in charge type I reactions, where a negative ion nucleophile attacks a neutral substrate. Two energy minima, one before and one after the transition state, appear in the reaction coordinate (Fig. 10.1). The energy surface for the Sn2 Menshutkin reaction (p. 499) has been examined and it was shown that charge separation was promoted by the solvent.An ab initio study of the Sn2 reaction at primary and secondary carbon centers has looked at the energy barrier (at the transition state) to the reaction. These minima correspond to unsymmetrical ion-dipole complexes. Theoretical calculations also show such minima in certain solvents, (e.g., DMF), but not in water. "... 

The exothermicities of SN2 reactions in the gas phase tend to be in excess of 20 kcal mol-1. For the prototype reactions (19) the enthalpy change can be... 

An important question regarding SN2 reactions in the gas phase concerns the stereochemistry and the extent to which a Walden inversion occurs at the reaction site. Since the experimental techniques monitor exclusively ion concentration, the actual nature of the neutrals produced in the reaction is subject to some doubt. An indirect method to ascertain the nature of the products is to assess the thermochemistry of other possible reaction channels. In the case of methyl derivatives, the alternatives are few and result in highly endothermic reactions, as exemplified in (22) and (23). For more complicated systems, this argument may not be satisfactory or may not yield an unequivocal answer. 

From these examples, one can conclude that anionic and cationic SN2 reactions in the gas phase display similar stereochemistry. 

These results are in accord with the long-accepted mechanism for the SN2 reaction in the gas phase experiments using ion cyclotron resonance were interpreted in the way shown for the calculations of Fig. 2 It is not possible to explain the observed rates on the basis of a single-well potential [38] the profile in Fig. 2 is called a double-well potential. Quantitative information comes from benchmark calculations by Bento et al., who even checked for relativistic effects, which were found to be negligible [39]. CCSD(T)/aug-cc-PVQZ (Sections 5.4.3 and 5.3.3 ) gave relative energies of 44 and +10.5 kJ mol-1, compared to —39 and —2.1 kJ mol-1 at out modest computational level. That the transition state lies slightly... 

Fig. 5-5. Schematic one-dimensional relative enthalpy diagram for the exothermic bimolecular displacement reaction HO + CH3—Br —> HO—CH3 + Br in the gas phase and at various degrees of hydration of the hydroxide ion [485]. Ordinate standard molar enthalpies of (a) the reactants, (b, d) loose ion-molecule clusters held together by ion-dipole and ion-induced dipole forces, (c) the activated complex, and (e) the products. Abscissa not defined, expresses only the sequence of (a). .. (e) as they occur in the chemical reaction. The barrier heights ascribed to the activated complex at intermediate degrees of hydration were chosen to be qualitatively consistent with the experimental rate measurements cf. Table 5-3 [485]. Possible hydration of the neutral reactant and product molecules, CH3—Br and HO—CH3, is ignored. The barrier height ascribed to the activated complex in aqueous solution corresponds to the measured Arrhenius activation energy. A somewhat different picture of this Sn2 reaction in the gas phase, which calls into question the simultaneous solvent-transfer from HO to Br , is given in reference [487].

The universality of the double-well energy surface for Sn2 reactions in the gas phase has also been addressed by further ab initio calculations. In particular, substantial exothermicity could be anticipated to reduce the vi-... 

In fact, why some reactions are fast and others slow is often difficult to explain in simple terms, and prediction of the rates of reactions is essentially impossible without either an elaborate quantum calculation or the use of a complex set of empirical parameters. Our work in studying simple SN2 reactions in the gas phase has been aimed at developing a view of these reactions that can be understood in relatively elementary terms. By removing the effects of solvation, we hope to discern the important factors involved in determining reaction rates. Although our efforts are far from complete, we believe that the reactions can now be understood, at least in the first approximation (1-8). 

Figure 2.8. Energy profile of Sn2 reaction in the gas phase (dotted line) and in aqueous solution (solid line)...

Sn2 reactions in the gas phase are generally believed to take place as illustrated in Eqns (1.10)-(1.13) where is an ionic nucleophile and R—X is an alkyl halide. In step 1 (Eqn (1.10)), the dissociated reactants combine to form the noncovalendy bonded ion-dipole complex. This complex has a linear or near-linear geometry with Y RX equal or near 180°. 

Ab inito direct dynamics trajectory calculations that include ab initio structure calculations on the Sn2 reaction in the gas phase have been carried out. A particularly interesting application is described in Scheme 1.10, in which hydroxide ion displaces fluoride ion in an Sn2 reaction... 

As shown in the drawing, the barrier to the Sn2 reaction in the gas phase can be comparable to, or even below, the energy of the separated nucleophile and electrophile. For example, the transition state enthalpy for reaction of chloride with methylbromide in the gas phase is actually 2.5 kcal / mol lower than the separated reactants (AE = 2.5). The reason that the rate constants can be very small, even though the enthalpy barrier is low relative to the reactants, is entropy control. The change in entropy going from the loose complex to the transition state is very large and negative. 

Figure 2.7 Monte Carlo reaction profile for an Sn2 reaction in the gas phase, dimethylformamide, and water. Reproduced with permission from Jorgensen (1989).Copyright 1989 American Chemical Society.

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