Question

Devise a synthesis of each compound from the given starting material(s). Albuterol is a bronchodilator and proparacaine is a local anesthetic.

(a)

(b)

Short answer

(a)

(b)

Step-by-step solution

Friedel–Craft acylation

Friedel–Craft acylation reaction is used to prepare ketone, alcohol, and amine via the nucleophilic substitution or nucleophilic addition reaction.

The acyl group contains the ketone group, which can be reduced by a reducing group such as sodium borohydride.

Protection of diols

Acetonide is the protecting group of diol. It forms a cyclic ketal when it reacts with the diol. Therefore, the diol is protected from the attack of other groups.

The cyclic ketal or the protection is easily removed in the acidic medium.

Explanation

a. The given reaction proceeds via the Friedel–Craft acylation process, where the acyl group is substituted para to one of the ether groups of the cyclic ketal. Further in the reaction, bromination occurs in the presence of an oxidizing agent.

In the next step, the amine group is substituted followed by the reduction of the ketone group from the sodium borohydride. At the end of the reaction, the cyclic ketal is deprotected in the acidic medium which gives diol.

The reaction scheme is shown as:

Reduction mechanism of a.

b. The given product is formed by several processes as shown in the diagram below:

Reduction mechanism of b.