Marcus theory nucleophilic substitution

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. 

In the section on nucleophilic substitution processes we saw that the SN2 process is simply a single electron shift coupled with bond reorganization. The question we wish to consider in this section is how the CM model treats standard electron transfer reactions such as (89) and how the model relates to the Marcus theory, now universally accepted for treating such processes (Marcus, 1964, 1977). 

A large number of radical reactions proceed by redox mechanisms. These all require electron transfer (ET), often termed single electron transfer (SET), between two species and electrochemical methods are very useful to determine details of the reactions (see Chapter 6). We shall consider two examples here - reduction with samarium di-iodide (Sml2) and SRN1 (substitution, radical-nucleophilic, unimolecular) reactions. The SET steps can proceed by inner-sphere or outer-sphere mechanisms as defined in Marcus theory [19,20]. 

Picosecond absorption spectroscopy studies of the contact ion pairs formed in the photo-initiated, S N 1 reaction of three substituted benzhydryl acetates (18) provided the rate constants for the k and k2 steps of the reaction (Scheme 10), in acetonitrile and DMSO.83 The activation parameters for the k and k2 steps were obtained from the temperature dependence of these steps and the transition state energies were calculated from the rate constants. This allowed the energy surfaces for three substituted substrates to be calculated in each solvent. The effect of solvent reorganization on the reactions of the unsubstituted and methyl-substituted benzhydryl contact ion pairs (CIP) was significant, causing a breakdown of transition state theory for these reactions. The results indicated that it will be very difficult to develop a simple theory of nucleophilicity in, S N1 reactions and that Marcus theory cannot be applied to SnI processes. 

As Bunnett has noted (4), the kinetic barrier to nucleophilic attack is affected by the thermodynamics of the reaction. If this thermodynamic contribution could be removed, then intrinsic nucleophilicities for substitution reactions could be obtained that would be independent of the leaving group. Pioneering work by Albery and Kreevoy (7), Pellerite and Brauman (8), and Lewis et al. (9) has shown that Marcus theory can be applied to methyl-transfer reactions to separate thermodynamic and kinetic contributions and provide intrinsic barriers to nucleophilic attack. One expression of Marcus theory is given in equation 1, where AE is the activation energy, AE° is the heat of reaction, and AE0 is the intrinsic activation energy or the barrier to reaction in the absence of any thermodynamic driving force. 

Standard electrode potentials of alkyl halides and nucleophiles have been used to pi edict die rates of SKT alternatives to Ss2 substitution mechanisms 134.49.50.08.601. A reaction much faster than predicted on the basis of Marcus theory is a likelv S 2 process, while similarity between prediction and rate, favors SET. Despite some disagreement as to the proper treatment rtf a dissociative electron transfer 48.7(). this approach has proven useful in helping to classify reactions as probably SN2 or SET in mechanism (most successfully with large, delocalized nucleophiles). 

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