Question

Propose a synthesis of the topical anesthetic cyclomethycaine from 4-hydroxybenzoic acid, 2-methylpiperidine, and any other necessary reagents.

Short answer

Based on the step-by-step solution provided, briefly describe the synthesis of cyclomethycaine from 4-hydroxybenzoic acid and 2-methylpiperidine.

Step-by-step solution

Esterification of 4-hydroxybenzoic acid with methanol

First, we will convert the carboxylic acid group of 4-hydroxybenzoic acid into a methyl ester. This can be done through an esterification reaction by treating 4-hydroxybenzoic acid with methanol and a catalytic amount of sulfuric acid. The equation for this reaction is: 4-hydroxybenzoic acid + CH3OH -> methyl 4-hydroxybenzoate + H2O

Acylation of 2-methylpiperidine with methyl 4-hydroxybenzoate

Next, we will react 2-methylpiperidine with the ester group of methyl 4-hydroxybenzoate. This process is known as an acylation reaction. To carry out this reaction, we will use 2-methylpiperidine (a secondary amine) and methyl 4-hydroxybenzoate from step 1 as our starting materials. The equation for this reaction is: 2-methylpiperidine + methyl 4-hydroxybenzoate -> N-(2-methylpiperidin-1-yl)-4-hydroxybenzamide

Cyclization with 1-bromo-3-chloropropane

Finally, we will carry out a cyclization reaction to form the final cyclomethycaine product. To do this, we will treat the N-(2-methylpiperidin-1-yl)-4-hydroxybenzamide with 1-bromo-3-chloropropane and an appropriate base, such as potassium carbonate or sodium hydride. The reaction equation is as follows: N-(2-methylpiperidin-1-yl)-4-hydroxybenzamide + 1-bromo-3-chloropropane -> cyclomethycaine

Summary

To synthesize cyclomethycaine from 4-hydroxybenzoic acid, 2-methylpiperidine, and other necessary reagents, we carried out the following sequence of reactions: esterification, acylation, and cyclization. This synthetic route involves various reagents and conditions, and allows for the successful generation of the desired final product: cyclomethycaine.