Q.55. - Organic Chemistry

Question

Question: Reaction of X and phenylacetic acid forms an intermediate Y, which undergoes an intramolecular reaction to yield rofecoxib. Rofecoxib is a nonsteroidal anti-inflammatory agent once marketed under the trade name Vioxx, now withdrawn from the market because of the increased risk of heart attacks from long-term use in some patients. Identify Y and draw a stepwise mechanism for its conversion to rofecoxib.

Step-by-Step Solution

Answer

Answer

The structure of Y is:

Mechanism of conversion of Y to rofecoxib

Step 1: Intramolecular Aldol Reactions

Intramolecular aldol condensation occurs in the case of dicarbonyl compound, in which one of the carbonyl groups forms a resonance stabilized enolate and acts as a nucleophile and the other acts as the electrophilic center. The condensation reaction yields five or six-membered ring structures.

Step 2: Formation of Y

In presence of triethylamine and DBU, the two compounds react to form an ester as given below:

Structure of Y

Step 3: Mechanism for the formation of rofecoxib

In presence of a base, the  $\alpha$-hydrogen is protonated and an enolate is formed. The nucleophile then attacks at the other carbonyl carbon enter to form a 5-membered lactone line structure, as shown below:

Enolate formation and nucleophilic attack

 

 The hydroxyl group formed is eliminated by E1cb mechanism, as shown below:

Deprotonation and elimination of hydroxyl group