19. Reactions of Aromatics: EAS and Beyond

Tyramine is an alkaloid found in mistletoe and ripe cheese. Dopamine is a neurotransmitter involved in the regulation of the central nervous system.

d. How can b-phenylethylamine be prepared from benzyl chloride?

Ibuprofen is the active ingredient in pain relievers such as Advil, Motrin, and Nuprin. How can ibuprofen be synthesized from benzene?

Pyrrole undergoes electrophilic aromatic substitution more readily than benzene, and mild reagents and conditions are sufficient. These reactions normally occur at the 2-position rather than the 3-position, as shown in the following example.

a. Propose a mechanism for the acetylation of pyrrole just shown. You may begin with pyrrole and the acylium ion, CH3C≡O+. Be careful to draw all the resonance structures of the intermediate.

Suggest a synthesis of each of the molecules shown beginning with benzene.

(c)

Acetohexamide is used to treat type 2 diabetes that cannot be well controlled by diet alone. Fill in the blanks of the synthetic scheme used to synthesize acetohexamide. [Hints have been provided below each step.]

Predict the product(s) of each of the following multistep reactions.

(b)

Fluoxetine, an antidepressant, is better known as Prozac®. Suggest reagents that could be used to make the indicated C–O bond of fluoxetine. [Note that CF₃, an electron-withdrawing group, is para to where the new bond will be formed.]