Question

The base-promoted rearrangement of an \(\alpha\)-haloketone to a carboxylic acid, known as the Favorskii rearrangement, is illustrated by the conversion of 2-chlorocyclohexanone to cyclopentanecarboxylic acid.

Short answer

Question: Explain the Favorskii rearrangement of 2-chlorocyclohexanone to cyclopentanecarboxylic acid, including the step-by-step mechanism. Answer: The Favorskii rearrangement involves the following steps: 1. Base-promoted deprotonation of α-haloketone to form an enolate anion. 2. Nucleophilic attack on the halogen atom by the enolate anion to form a cyclic inorganic ester. 3. Intramolecular cyclization of the cyclic inorganic ester, leading to the formation of a six-membered ring intermediate with a carboxylate anion and a halide anion. 4. Hydrolysis of the intermediate to yield the carboxylic acid. In the case of 2-chlorocyclohexanone, this rearrangement results in the formation of cyclopentanecarboxylic acid.

Step-by-step solution

Introduction to Favorskii rearrangement

Favorskii rearrangement is a reaction in which an α-haloketone is treated with base to produce carboxylic acid. The reaction proceeds through the formation of an inorganic ester, followed by intramolecular cyclization and finally hydrolysis to yield the carboxylic acid.

Formation of the enolate intermediate

In the first step of the Favorskii rearrangement, the base-promoted deprotonation of the α-haloketone occurs to form an enolate anion. For example, if the base is \(\ce{OH-}\), the reaction is as follows: \(\ce{2-Cl-cyclohexanone ->[OH-] enolate}\)

Nucleophilic attack on the halogen atom

The formed enolate anion acts as a nucleophile and attacks the electrophilic carbon atom of the halide group, forming a five-membered cyclic intermediate known as an inorganic ester. The reaction can be represented as: \(\ce{enolate -> cyclic\ inorganic\ ester}\)

Intramolecular cyclization

The cyclic inorganic ester then undergoes ring-opening (intramolecular cyclization), leading to the formation of a six-membered ring intermediate with a carboxylate anion and a halide anion. For our example with 2-chlorocyclohexanone: \(\ce{cyclic\ inorganic\ ester -> six\ membered\ cyclic\ intermediate}\)

Hydrolysis and formation of carboxylic acid

Finally, the reaction mixture is treated with water (hydrolysis), leading to the formation of a carboxylic acid through the elimination of the halide anion. In our example, the final product is cyclopentanecarboxylic acid: \(\ce{six\ membered\ cyclic\ intermediate ->[H2O] cyclopentanecarboxylic\ acid}\) In conclusion, the Favorskii rearrangement involves base-promoted deprotonation of α-haloketone, nucleophilic attack to form a cyclic inorganic ester, intramolecular cyclization, and hydrolysis to yield the corresponding carboxylic acid. In our given example, the reaction transforms 2-chlorocyclohexanone to cyclopentanecarboxylic acid.