10.10 : Conversion of Alcohols to Alkyl Halides

Alcohols react with hydrogen halides to generate corresponding alkyl halides.

In the mechanism, the first step is the protonation of the hydroxyl group. Thereafter, while tertiary alcohols interact via the S_N1 mechanism, primary alcohols prefer an S_N2 route. Secondary alcohols can proceed via either mechanism, where the preference is dictated by the reaction conditions.

Recall that an S_N1 mechanism occurs sequentially: a loss of the leaving group, followed by the nucleophilic attack. Since this reaction proceeds via the carbocation intermediate, it is suitable for the tertiary carbocation, which is stabilized by hyperconjugation.

For primary alcohols, the protonation of the hydroxyl group leads to the S_N2 mechanism. However, while the S_N2 mechanism is straightforward with hydrogen bromide, hydrogen chloride needs an additional catalyst, zinc chloride.

Zinc chloride, being ionic, is limited to water-soluble alcohols. It converts their hydroxyl group into a better leaving group, enabling the subsequent S_N2 process.

A more common process for primary alcohols uses thionyl chloride. A primary alcohol interacts with thionyl chloride in the presence of pyridine or a tertiary amine, which forms the corresponding alkyl chlorosulfite intermediate.

As a result, the intermediate bears an excellent leaving group—chlorosulfite—rather than a poor leaving group like water. Subsequently, nucleophilic substitution by the chloride forms the corresponding alkyl halide. The bromination with phosphorus tribromide follows the same route.

Similarly, primary and secondary alcohols react with sulfonyls in the presence of pyridine to form the corresponding reactive products. Here, the sulfonate anion is a weak base, further stabilized by resonance extended to the substituted aromatic ring, making the tosylate anion an excellent leaving group for S_N2 reactions. Subsequently, reaction with the hydrogen halide yields the alkyl halides.

Interestingly, the choice of reagent defines stereochemistry. While thionyl chloride inverts the chiral configuration of the native alcohol, the tosyl chlorides retain the chiral configuration. In the latter, the alcohol first undergoes inversion while becoming the tosylate, and then undergoes another inversion with the S_N2 mechanism.