Question

The Favorskii reaction involves treatment of an \(\alpha\) -bromo ketone with base to yield a ring-contracted product. For example, reaction of 2 -bromocyclohexanone with aqueous NaOH yields cyclopentanecarboxylic acid. Propose a mechanism.

Short answer

The mechanism involves carbanion formation, nucleophilic substitution, ring contraction, and acidic workup.

Step-by-step solution

Formation of Carbanion

Under basic conditions, NaOH deprotonates the \(\alpha\) -carbon adjacent to the carbonyl group of 2-bromocyclohexanone, forming a carbanion. This step is vital as it initiates the rearrangement process by making the carbanion a good nucleophile.

Nucleophilic Substitution

The carbanion attacks the carbon bearing the bromine atom, resulting in the displacement of the bromide ion. This leads to the formation of an intermediate cyclopropane derivative by closing the ring with the nucleophilic attack.

Ring Contraction via Migration

The intermediate cyclopropane ring undergoes a rearrangement called a ring contraction. This involves the migration of the alkyl group from one carbon of the cyclopropane to the next, leading to a five-membered ring structure.

Acidic Workup

In an aqueous environment, the basic conditions allow the intermediate molecule to hydrolyze, forming cyclopentanecarboxylic acid as the final product. The carboxylate ion is protonated to give the acid.

Key concepts

alpha-bromo ketone

An \( \alpha \)-bromo ketone is a type of organic compound characterized by the presence of a bromine atom attached to the carbon that is adjacent to a carbonyl group. This specific positioning of bromine is crucial because it plays a significant role in facilitating various chemical reactions:

• The carbonyl group, with its strong electronegativity, pulls electron density away from the \( \alpha \)-carbon, making it more prone to reactions.
• The presence of the bromine makes this position ripe for nucleophilic attacks, given bromine's ability to leave as a bromide ion.

In a Favorskii reaction, these properties help set the stage for the subsequent steps where specific rearrangements and reactions take place. The bromine atom acts as a leaving group, allowing transformation into other compounds.

carbanion formation

Carbanion formation is a critical step in many organic reactions, including the Favorskii reaction. A carbanion is a negatively charged carbon species. This happens when the \( \alpha \)-bromo ketone interacts with a base such as NaOH:

• The base deprotonates the \( \alpha \)-hydrogen adjacent to the carbonyl group, leading to a negative charge on the carbon atom.
• This negative charge makes the carbanion highly nucleophilic, meaning it is eager to donate its electron pair and form a new bond.

This carbanion is the driving force in the Favorskii reaction, setting off a chain of transformations that ultimately leads to the creation of a ring-contracted product.

nucleophilic substitution

In the context of the Favorskii reaction, nucleophilic substitution is a pivotal process where a nucleophile (like the carbanion) attacks an electrophilic center. Here's how it unfolds in this reaction:

• The carbanion formed previously uses its negative charge to attack the carbon that holds the bromine atom (an electrophilic center).
• This attack results in the substitution of the bromine atom by the carbanion, leading to the formation of a cyclopropane ring derivative.
• Such a substitution is essential and paves the way for the subsequent ring contraction step.

This entire process showcases how nucleophilic substitution helps to transform the structure of the original molecule, enabling further interesting chemical rearrangements.

ring contraction

Ring contraction in the Favorskii reaction is a fascinating transformation where a larger ring structure is converted into a smaller one. This is mainly due to the inherent instability of the intermediate structure:

• The cyclopropane intermediate formed during nucleophilic substitution is strained, making it prone to further rearrangement.
• This strain leads to the migration of an alkyl group from one of the ring's carbon atoms to another, effectively shrinking the ring size.
• The final product from this step is a five-membered ring, such as cyclopentanecarboxylic acid when starting with a cyclohexanone derivative.

This ring contraction is an excellent example of how chemical processes can fine-tune molecular structures, making them more stable or more suitable for subsequent reactions.