6.20 : Predicting Products: Substitution vs. Elimination

When a nucleophile and an alkyl halide react, a competition between the nucleophilic substitution and β-elimination takes place, dictating the reaction outcome.

An alkyl halide has two reactive sites. An attack on the electrophilic α-carbon results in a substitution reaction via an S_N1 or an S_N2 mechanism.

Alternatively, the nucleophile acts as a base and deprotonates the β-hydrogen, leading to an elimination reaction via an E1 or an E2 mechanism.

The reaction outcome is influenced by parameters like the relative steric hindrance of the substrate, the nucleophile’s size and basicity, temperature, and the type of solvent.

Depending upon the relative rate of the unimolecular or bimolecular reactions, a mixture of products is generally obtained. To predict the major and minor products, consider the following.

In general, β-eliminations are favored over substitution reactions with increased temperature, more basic and hindered nucleophiles, and increased substitution of the substrate.

Primary halides, being the least sterically hindered, exclusively undergo bimolecular reactions. Higher concentrations of strong nucleophiles or bases further accelerate the S_N2 or E2 reaction, irrespective of the solvent.

A strong unhindered nucleophile attacks the α-carbon faster, favoring an S_N2 product. Conversely, a strong hindered base has less access to the α-carbon, thus favoring an E2 product.

Primary halides, however, disfavor unimolecular reactions, as primary carbocations are relatively unstable.

In secondary halides, as increased branching hinders S_N2 reactions, E2 products are favored, especially with strong bases. Conversely, the use of weak bases increases the likelihood of S_N2 products.

Unimolecular reactions are rarely observed with secondary halides. However, they may proceed at a moderate pace in the presence of a weak nucleophile or base in polar protic solvents.

In tertiary halides, increased steric hindrance disfavors the S_N2 mechanism.  With strong bases, the E2 reaction is favored, while both unimolecular reactions are predominant in the presence of weak bases or nucleophiles.

However, with increased temperature and the possibility of generating highly substituted alkenes, the E1 mechanism dominates over S_N1.