Question

Draw a stepwise mechanism for the following reaction that forms ether D. D can be converted to the antidepressant fluoxetine (trade name Prozac) in a single step.

Short answer

Stepwise mechanism

Step 1.

Step 2.

Step 3.

Step-by-step solution

Reaction of aryl halides

Aryl halides having strong electron-withdrawing groups on the ortho or para positions react with nucleophiles to give substitution products.

They are inert for ${\text{S}}_{\text{N}}\text{1}$and ${\text{S}}_{\text{N}}2$mechanism and hence follow ${\text{S}}_{\text{N}}\text{Ar}$(addition-elimination) mechanism.

Mechanism

• Tertiary butoxide ion acts as a base.

Proton is abstracted from an alcoholic group of 3-(dimethylamino)-1-phenylpropan-1-ol to form its conjugate base.

• The conjugate base of 3-(dimethylamino)-1-phenylpropan-1-ol reacts with 1-chloro-4-(trifluoromethyl) benzene to form more stable resonance contributors.

• The resonance stabilized carbanion undergoes an elimination reaction and forms the required compound D.