Question

Isoniazid, a drug used to treat tuberculosis, is prepared from pyridine-4-carboxylic acid. How might this synthesis be carried out?

Short answer

Question: Outline the synthetic route for the preparation of Isoniazid from pyridine-4-carboxylic acid. Answer: The synthesis of Isoniazid from pyridine-4-carboxylic acid can be carried out in two steps: 1. Convert pyridine-4-carboxylic acid to its corresponding acid chloride using thionyl chloride (SOCl2). 2. React the acid chloride with hydrazine (NH2NH2), forming Isoniazid through nucleophilic attack and releasing a hydrochloric acid molecule.

Step-by-step solution

Converting Pyridine-4-carboxylic acid to its Acid Chloride

First, we convert pyridine-4-carboxylic acid (1) to its acid chloride (2) by treating it with thionyl chloride (SOCl_2). This is a common reaction used to convert carboxylic acids to their corresponding acid chlorides. Pyridine-4-carboxylic acid (1) + SOCl_2 -> Pyridine-4-carbonyl chloride (2) + SO_2 + HCl

Formation of Isoniazid by amination of the acid chloride

Next, we treat the pyridine-4-carbonyl chloride (2) with hydrazine (NH_2NH_2) to form the isoniazid (3). This is done by nucleophilic attack of the nitrogen atom in hydrazine to the carbonyl carbon of the acid chloride, resulting in the formation of the desired product and the release of a hydrochloric acid molecule. Pyridine-4-carbonyl chloride (2) + NH_2NH_2 -> Isoniazid (3) + HCl By following these two steps, the synthesis of Isoniazid (3) from pyridine-4-carboxylic acid (1) can be carried out.