# Preparation of Procaine and Procaine Monohydrochloride from p-Aminobenzoic Acid ## Step 1: Synthesis of Procaine from p-Aminobenzoic Acid **Equation:** 1. **Esterification:** - p-Aminobenzoic acid is first converted to p-aminobenzoyl chloride using SOCl₂. - Then, it reacts with 2-diethylaminoethanol (an alcohol) to form the ester (procaine). \[ \text{p-Aminobenzoic acid} + \text{SOCl}_2 \rightarrow \text{p-Aminobenzoyl chloride} + \text{SO}_2 + \text{HCl} \] \[ \text{p-Aminobenzoyl chloride} + \text{2-diethylaminoethanol} \rightarrow \text{Procaine} + \text{HCl} \] **Explanation:** The carboxylic acid group of p-aminobenzoic acid is converted to an acid chloride, which is more reactive for esterification. This acid chloride reacts with 2-diethylaminoethanol to give procaine (an ester with a diethylamino side chain). --- ## Step 2: Formation of Procaine Monohydrochloride **Equation:** \[ \text{Procaine} + \text{HCl} \rightarrow \text{Procaine monohydrochloride} \] **Explanation:** Procaine is treated with hydrochloric acid to form the monohydrochloride salt. The basic diethylamino group is protonated, creating a water-soluble salt suitable for pharmaceutical use. --- ## Which Amino Group is Protonated First in Procaine? **Procaine contains:** - An aromatic amine (aniline-type, at the para position on the benzene ring) - A tertiary aliphatic amine (diethylamino group on the side chain) **Answer:** The **tertiary aliphatic amine** (the diethylamino group) will be protonated first. **Defense:** - Aliphatic amines are **more basic** than aromatic amines. - The lone pair on the nitrogen of the aromatic amine is delocalized into the benzene ring, reducing its basicity. - The lone pair on the diethylamino group is localized and more available for protonation. --- ## Final Answers 1. **Preparation:** - p-Aminobenzoic acid → (acid chloride) → reacts with 2-diethylaminoethanol → procaine - Procaine + HCl → procaine monohydrochloride 2. **Protonation:** The tertiary aliphatic (diethylamino) group is protonated first due to its higher basicity compared to the aromatic amine.