Question

Question:Propranolol, an antihypertensive agent used in the treatment of high blood pressure, canbe prepared from 1-naphthol, epichlorohydrin, and isopropyl amine using two successivenucleophilic substitution reactions. Devise a stepwise synthesis of propranolol from thesestarting materials.

Short answer

Answer

Step-by-step solution

Step-by-Step Solution Step 1: Nucleophilic substitution reaction

A nucleophilic substitution reaction is when an electron-rich group (nucleophile) displaces the leaving group from the electrophilic center of a compound and takes its place.

A general reaction scheme is given below:

Nucleophilic substitution reaction

Stepwise mechanism

• First, 1-napthol is treated with a strong base to convert it into an alkoxide ion, as shown below:

Proton abstraction of 1-napthol

• The alkoxide ion hence formed, acts as a nucleophile, and attacks at the electrophilic alkyl halide center of epichlorohydrin. The reaction is shown below:

Attack of the nucleophile at the alkyl halide center

• The isopropyl amine group contains a lone pair over nitrogen, which donates its lone pair to the epoxide carbon center, thus opening the ring. After further proton transfer, propranolol is formed.

Attack of isopropyl amine and formation of propanolol