Question

Draw a stepwise mechanism for the following reaction, a key step in the synthesis of the anti-inflammatory drug celecoxib (trade name Celebrex).

Short answer

The abstraction of a proton by the substrate from the reacting medium to form the corresponding cation is known as protonation.

4,4,4-Trifluoro-1-(p-tolyl) butane-1,3-dione is protonated in the presence of hydrochloric acid. The lone pair of electrons on the nitrogen atom of 4-sulfamoylaphenylhydrazine attack the carbonyl carbon forming a C-N bond.

Protonation of 4,4,4-Trifluoro-1-(p-tolyl) butane-1,3-dione

Step-by-step solution

Protonation

The abstraction of a proton by the substrate from the reacting medium to form the corresponding cation is known as protonation.

4,4,4-Trifluoro-1-(p-tolyl) butane-1,3-dione is protonated in the presence of hydrochloric acid. The lone pair of electrons on the nitrogen atom of 4-sulfamoylaphenylhydrazine attack the carbonyl carbon forming a C-N bond.

Protonation of 4,4,4-Trifluoro-1-(p-tolyl) butane-1,3-dione

Intramolecular proton transfer (IMPT)

A proton from the nitrogen atom shifts towards the more electronegative oxygen atom, thereby forming an imine bond, followed by dehydration.

Intramolecular proton transfer

Nucleophilic attack

The O atom of the other carbonyl group would abstract a proton. This is followed by the nucleophilic attack of the hydrazine group’s other nitrogen atom and intramolecular proton transfer to form the ring.

Nucleophilic attack followed by IMPT

Deprotonation

The proton would donate a pair of electrons to form a new C=C, followed by the stabilization of the charge on the nitrogen atom to form the required product.

Formation of the product