10.11: Conversion of Alcohols to Alkyl Halides
This lesson delves into the conversion of alcohols to corresponding alkyl halides and the mechanism of action for different reagents. Typically, the hydroxyl group is first protonated to convert it to a stable leaving group. Consequently, based on the starting alcohol, the mechanism undergoes either of the nucleophilic substitution routes, SN1 or SN2. Tertiary alkyl halides are made using the two-step SN1 mechanism that occurs via a carbocation intermediate, which is stabilized by hyperconjugation. However, for primary alcohols, the protonation of the hydroxyl group leads to the concerted SN2 route. Secondary alcohols can proceed via either mechanism based on the reaction conditions.
The popular reagents used for converting alcohols to corresponding alkyl halides include the hydrogen halides like hydrogen bromide and hydrogen chloride. However, while it is straightforward with the former, the latter needs an additional catalyst like zinc chloride. This catalyzes the hydroxyl group into a better leaving group enabling the subsequent SN2 process. Other reagents of choice are thionyl chloride and phosphorus tribromide with a similar mechanism. In the presence of relatively weak bases like pyridine/tertiary amine, they generate an excellent leaving group compared to the original leaving group of water.
The most exciting class of reagents is sulfonyls. They react with the alcohols to form corresponding mesylates, tosylates, or triflates to improve their reactivity in an SN2 reaction. In these species, resonance stabilization is inherent to the sulfonyl group. Additional resonance stabilization is contributed by the benzene ring of the tosyl group, and further stability is provided by the strongly electron-withdrawing trifluoromethyl in the triflate.
Most importantly, the choice of reagent influences the stereochemistry of the product formed. The use of thionyl chloride leads to an inversion of configuration, while tosyl chlorides retain the chiral configuration in the native alcohol.