Question

$4-$Amino salicylic acid, called PAS, is an anti-tuberculosis drug. The proper method for its preparation involves a reaction of:

• A. $3-$aminophenol with chloroform in an alkaline medium
• B. $3-$aminophenol with carbon dioxide in an alkaline medium under pressure
• C. $conc.HN{O}_3$ and $conc.H_{2}S{O}_4$ on salicylic acid followed by catalytic reduction using $H_2/Ni$
• D. chlorine (limited amount) with $4-$aminobenzoic acid in the pressure of $FeC{l}_3$, followed by boiling the product in aq. alkali

Answer 1

Answer: (B)

$3-$aminophenol with carbon dioxide in an alkaline medium under pressure

The reaction is known as Kolbe's reaction.
Phenolic $-OH$ reacts with $NaOH/KOH$ to form phenoxide ion which is more reactive than parent phenol towards electrophilic aromatic substitution. Carbon dioxide is weak electrophile. Both $-OH$ and $-N{H}_2$ groups are ortho, para directing groups.