15.7:
Acid-Catalyzed α-Halogenation of Aldehydes and Ketones
Aldehydes or ketones undergo α-halogenation in an acid-catalyzed condition to yield a monohalogenated product.
Here, the C=O oxygen is first protonated by the acid to form a resonance-stabilized cation. The cation intermediate then undergoes deprotonation at the α carbon to yield the enol tautomer.
As the electron-releasing –OH group renders the C=C bond highly nucleophilic, the double bond rapidly attacks an electrophilic halogen molecule to form a monohalogenated carbocation.
Finally, deprotonation of the carbocation yields the α-halo aldehydes or ketones.
The presence of an electron-withdrawing halogen atom reduces the reactivity of the C=O oxygen atom, thus preventing multiple halogenation.
Further, the acid formed as a byproduct can catalyze the first step of enolization, thus making the reaction autocatalytic.
The acid-catalyzed α-halogenation reaction is useful to convert ketones into α,β-unsaturated ketones via E2 elimination reactions, generating a new π bond.
15.7:
Acid-Catalyzed α-Halogenation of Aldehydes and Ketones
By replacing an α-hydrogen with a halogen, acid-catalyzed α-halogenation of aldehydes or ketones yields a monohalogenated product
In the first step of the mechanism, the acid protonates the carbonyl oxygen resulting in a resonance-stabilized cation, which subsequently loses an α-hydrogen to form an enol tautomer. The C=C bond in an enol is highly nucleophilic because of the electron-donating nature of the –OH group. Consequently, the double bond attacks an electrophilic halogen to form a monohalogenated carbocation. In the final step, deprotonation of the carbocation yields the α-halo aldehydes or ketones.
Note that the enol formation is the rate-determining step of the reaction, and the halogen is not involved in the rate-limiting step. Therefore, the initial rates of the α-halogenation are independent of the type and concentration of halogen. Overall, the reaction follows second-order kinetics, wherein the rates depend on the concentration of the carbonyl and the acid.
The addition of a second halogen is unfavorable as the carbocation intermediate formed by the reaction of a monohalogenated enol with halogens is highly destabilized by the electron-withdrawing polar effect of two halogen atoms. Interestingly, the acid formed as a by-product of this reaction can ultimately catalyze the first step of enolization, thus turning the reaction autocatalytic. The unsymmetrical ketones undergo α-halogenation at the more substituted carbon by the preferential formation of a thermodynamic enol. As shown below, the acid-catalyzed α-halogenation reaction also works well to convert ketones to α,β‒unsaturated ketones via E2 elimination reactions forming a new π bond.
