Nucleophilic Aliphatic Substitution Preparation of Alkyl Halides

Nucleophiles have the property in common of bearing at least one pair of nonbonding electrons and being either neutral or negatively charged. During a substitution reaction, the nonbonding pair of electrons of the nucleophile is donated to an electrophilic, Lewis acidic carbon atom with concomitant formation of a new covalent 

The first step of an Sj jl reaction is much slower than the second because it involves breaking the C-L bond to generate an unstable carbocation, an endothermic process. The second step is a fast, exothermic process involving bond formation. Thus, the first step of an Sj jl reaction is the rate-determining step (rds) of the reaction, and the rate of the reaction depends only upon the concentration of the substrate, R-L. Such a reaction is termed unimolecular. This is expressed mathematically in Equation 14.4, where is the first-order rate constant. 

When substitution occurs by an Sn2 mechanism, the nucleophile directly attacks the substrate, with the angle of approach being 180 to the C-L bond. This is called backside attack, and the reaction proceeds with inversion of stereochemistry, the so-called Walden inversion. The C-L bond is being broken concurrently with the formation of the C-Nu bond, so both the substrate, R-L, and the nucleophile are involved in the transition state of the rate-determining step. Reactions in which two reactants are involved in the transition state of the rate-determining step are termed bimolecular, and the rate of such processes depends on the concentration of the substrate and the nucleophile, as shown in Equation 14.5, where k2 is the second-order rate constant. 

We can summarize some of the important factors that dictate whether a particular substrate undergoes substitution preferentially by an Sj l or mechanism as follows. 

As more alkyl groups are attached to the carbon atom C-L imdergoing substitution, it becomes sterically more difficult for the nucleophile to attack from the backside because of the bulk of these groups, thereby decreasing the ease with which the Sj j2 process can occur. 

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