Question

Question:Coumarin, a naturally occurring compound isolated from lavender, sweet clover, and tonka bean, is made in the laboratory fromo-hydroxybenzaldehyde by the reaction depicted below. Draw a stepwise mechanism for this reaction. Coumarin derivatives are useful syntheticanticoagulants.

Short answer

Answer

Step 1:

Step 2:

Step 3:

Step-by-step solution

Coumarin

Coumarin is a natural product derived from plants and is known to have antiviral, anti-inflammatory, anti-cancer, and anti-coagulant properties. It is of great importance in the treatment of cancer.

Deprotonation of alcohol

The hydroxyl group of o-hydroxybenzaldehyde is deprotonated using the sodium acetate present, as shown below:

Deprotonation of alcohol

Attack at the carbonyl carbon center

The negative charge on oxygen acts as a nucleophile and attacks the carbonyl carbon center of acetic anhydride. The acetate group acts as a leaving group and is eliminated. The sodium acetate further deprotonates the $\mathit{\alpha }$-hydrogen present. The mechanism is shown below:

The nucleophilic attack followed by removal of acetate and deprotonation

Ring formation and removal of the hydroxyl group

The negative charge attacks at the electrophilic carbon center of the aldehyde group. This step is followed by deprotonation of acidic hydrogen which leads to the elimination of the hydroxyl group. The coumarin is formed upon removal of hydroxyl group, as shown below:

Ring formation followed by the removal of alcohol