Question

Aspirin is acetylsalicylic acid (o-acetoxybenzoic acid, \(\left.0-\mathrm{CH}_{3} \mathrm{COO}-\mathrm{C}_{6} \mathrm{H}_{4} \mathrm{COOH}\right)\); oil of wintergreen is the ester, methyl salicylate. Outline the synthesis of these two compounds from phenol.

Short answer

To synthesize acetylsalicylic acid (aspirin) and methyl salicylate (oil of wintergreen) from phenol, follow these steps: 1. Convert phenol to salicylic acid via the Kolbe-Schmitt reaction with NaOH and CO2, followed by acidification with HCl. 2. Synthesize aspirin by reacting salicylic acid with acetic anhydride in the presence of a strong acid catalyst. $$\text{C}_{6}\text{H}_{4}(\text{OH})\text{COOH} + (\text{CH}_{3}\text{CO})_{2}\text{O} \rightarrow \text{CH}_{3}\text{COOC}_{6}\text{H}_{4}\text{COOH} + \text{CH}_{3}\text{COOH}$$ 3. Synthesize oil of wintergreen by reacting salicylic acid with methanol in the presence of a strong acid catalyst. $$\text{C}_{6}\text{H}_{4}(\text{OH})\text{COOH} + \text{CH}_{3}\text{OH} \rightarrow \text{CH}_{3}\text{OC}_{6}\text{H}_{4}\text{COOH} + \text{H}_{2}\text{O}$$

Step-by-step solution

Convert phenol to salicylic acid

First, we need to convert phenol into salicylic acid. This can be done by the Kolbe-Schmitt reaction, in which phenol reacts with sodium hydroxide (NaOH) and carbon dioxide (CO2) to form sodium salicylate, followed by acidification to give salicylic acid. Reactions: 1. Phenol + NaOH -> Sodium phenoxide (NaOC6H5) 2. Sodium phenoxide + CO2 -> Sodium salicylate (NaOC6H4COO-) 3. Sodium salicylate + HCl -> Salicylic acid (C6H4(OH)COOH) + NaCl

Synthesis of Acetylsalicylic Acid (Aspirin)

To synthesize aspirin, we need to convert the salicylic acid obtained in step 1 into its acetyl derivative, acetylsalicylic acid. This can be done via an esterification reaction with acetic anhydride in the presence of or using a strong acid catalyst like sulfuric acid. Reaction: Salicylic acid (C6H4(OH)COOH) + Acetic anhydride ((CH3CO)2O) -> Acetylsalicylic acid (Aspirin) (CH3COOC6H4COOH) + Acetic acid (CH3COOH)

Synthesis of Methyl Salicylate (Oil of Wintergreen)

To synthesize methyl salicylate, we need to convert the salicylic acid obtained in step 1 into its methyl ester. This can be done by an esterification reaction with methanol in the presence of a strong acid catalyst like sulfuric acid or hydrochloric acid. Reaction: Salicylic acid (C6H4(OH)COOH) + Methanol (CH3OH) -> Methyl salicylate (Oil of Wintergreen) ( CH3OC6H4COOH) + Water (H2O) These steps outline the synthesis of both acetylsalicylic acid (aspirin) and methyl salicylate (oil of wintergreen) from phenol.

Key concepts

Acetylsalicylic Acid

Acetylsalicylic acid, commonly known as aspirin, is a widely used medication that alleviates pain and reduces inflammation. It has the chemical formula \( ext{CH}_3 ext{COOC}_6 ext{H}_4 ext{COOH}\). This compound is synthesized through a process known as esterification. This involves salicylic acid reacting with acetic anhydride in the presence of a catalyst.

Here's a closer look at how this happens:

• Salicylic acid acts as the substrate, while acetic anhydride provides the acetyl group that forms the ester linkage in aspirin.
• A strong acid catalyst, such as sulfuric acid, is used to enhance the reaction rate.
• The reaction produces acetylsalicylic acid and acetic acid as a byproduct.

Understanding this esterification step is crucial, as it connects the pain-relieving salicylic acid with its acetyl group to form aspirin.

Methyl Salicylate

Methyl salicylate, also known as oil of wintergreen, is another ester derived from salicylic acid. It possesses a distinctive minty aroma and is often used in muscle rubs for its soothing properties. The chemical formula is \( ext{CH}_3 ext{OC}_6 ext{H}_4 ext{COOH}\).

To produce methyl salicylate:

• Salicylic acid undergoes esterification with methanol.
• This reaction is often acid-catalyzed, using sulfuric or hydrochloric acid to speed up the process.
• The product formed is methyl salicylate along with water.

This synthesis highlights the versatility of salicylic acid, showcasing how its conversion into different esters results in products with varying applications like in pain relief or as flavor and fragrance agents.

Kolbe-Schmitt Reaction

The Kolbe-Schmitt reaction is an important step in synthesizing salicylic acid from phenol. This reaction capitalizes on the interaction of phenol with carbon dioxide under basic conditions to introduce a carboxylate group onto the phenol molecule.

Here's how the Kolbe-Schmitt reaction unfolds:

• Phenol reacts with sodium hydroxide to form sodium phenoxide, preparing it for carboxylation.
• The sodium phenoxide then encounters carbon dioxide, forming sodium salicylate.
• An acidification step, typically using hydrochloric acid, converts sodium salicylate into salicylic acid.

Understanding the Kolbe-Schmitt reaction is essential because it lays the foundational chemistry needed for further conversion of salicylic acid into valuable derivatives like acetylsalicylic acid and methyl salicylate. It demonstrates a clever use of carbon dioxide as a reactant to transform simple phenol into a key aromatic compound.