Q.Write steps to carry out the conversion of phenol to aspirin.

Concept: Electrophilic Aromatic Substitution (Kolbe-Schmitt reaction) followed by esterification.

Step 1: Treat phenol with sodium hydroxide to form sodium phenoxide, which is more nucleophilic.

Step 2: React sodium phenoxide with carbon dioxide under pressure (Kolbe-Schmitt reaction). This introduces a carboxyl group ortho to the hydroxyl group via electrophilic attack, yielding salicylic acid after acidification. …

The key to this conversion lies in understanding how the phenolic –OH group directs incoming electrophiles. Phenol is highly activated toward electrophilic aromatic substitution because the oxygen lone pairs donate electron density into the ring, making the ortho and para positions strongly nucleophilic. We exploit this twice: once to place a carboxyl group at the ortho position, and once to protect the –OH by acetylating it.

Let’s walk through the chemistry step by step.

1. Step 1: Kolbe-Schmitt carboxylation

   Phenol is first converted to sodium phenoxide by treatment with NaOH. The phenoxide ion is even more electron-rich than phenol itself, making it extremely reactive toward electrophiles.

   The reaction is carried out under pressure with CO₂ gas at 125–150 °C. CO₂ acts as a weak electrophile; the phenoxide attacks the carbon of CO₂, forming a carboxylate group at the ortho position.

   Why ortho? The negative charge on oxygen directs the incoming electrophile to the ortho position via a six-membered cyclic transition state. After acidification (with dilute HCl), the carboxylate is protonated to give salicylic acid (2-hydroxybenzoic acid).

   $\ce{C6H5OH ->[NaOH] C6H5O- Na+ ->[CO2, 125-150°C][then H3O+] o-HOC6H4COOH}$

2. Step 2: Acetylation of the phenolic –OH

   Salicylic acid has both a carboxylic acid group and a phenolic –OH. We want to acetylate only the –OH, leaving the –COOH untouched. This is done using acetic anhydride in the presence of a catalytic amount of concentrated H₂SO₄ or phosphoric acid.

   The mechanism is a classic esterification: the phenolic oxygen attacks one carbonyl carbon of acetic anhydride, displacing acetate as a leaving group. The product is acetylsalicylic acid — aspirin. …

Conversion of Phenol to Aspirin — Electrophilic Aromatic Substitution

Method: Kolbe–Schmitt Reaction followed by Acetylation

This is a two-step industrial route. The first step is an electrophilic aromatic substitution (Kolbe–Schmitt), and the second is an esterification (acetylation).

Step 1: Kolbe–Schmitt Reaction (Electrophilic Aromatic Substitution)

Goal: Convert phenol to salicylic acid.

Reagents & Conditions:

• Phenol + NaOH → sodium phenoxide
• Then, heat with CO₂ under pressure (125 °C, 4–7 atm)
• Finally, acidify with dilute HCl

Mechanism (brief):

1. Phenol is converted to the more nucleophilic phenoxide ion ($\ce{C6H5O-}$).
2. CO₂ acts as the electrophile (the carbon in CO₂ is electron-deficient).
3. The phenoxide ion attacks the electrophilic carbon of CO₂, forming an intermediate.
4. Rearrangement gives salicylic acid after acidification.

Key point: The –OH group is ortho/para-directing, so substitution occurs at the ortho position.

Equation:

Step 2: Acetylation (Esterification)

Goal: Convert salicylic acid to aspirin (acetylsalicylic acid).

Reagents & Conditions:

• Salicylic acid + acetic anhydride
• Catalytic amount of concentrated H₂SO₄ or H₃PO₄
• Warm at 50–60 °C for about 15–20 minutes

Mechanism (brief):

1. The –OH group of salicylic acid acts as a nucleophile.
2. Acetic anhydride provides the acetyl group ($\ce{CH3CO-}$).
3. Acid catalyst activates the anhydride, making it a better electrophile. …

Common Mistakes in Phenol → Aspirin Conversion (Electrophilic Aromatic Substitution)

🧪 The Correct Conversion Steps (Briefly)

Phenol → Aspirin (acetylsalicylic acid) requires:

1. Kolbe-Schmitt reaction: Phenol + NaOH → Sodium phenoxide → CO₂ (high pressure, 125°C) → Salicylic acid
2. Acetylation: Salicylic acid + Acetic anhydride (or acetyl chloride) + H₂SO₄ → Aspirin

✗ Mistake #1: Forgetting the Kolbe-Schmitt Mechanism

What students do wrong: They try to directly nitrate or halogenate phenol, then convert to carboxylic acid — missing the specific ortho-hydroxylation + carboxylation.

Why it's wrong: Electrophilic aromatic substitution on phenol gives ortho/para products, but the Kolbe-Schmitt reaction is a special case — it uses CO₂ as the electrophile, and only works because the phenoxide ion is strongly activating.

How to avoid: Memorise that phenol → salicylic acid is a named reaction (Kolbe-Schmitt). Write the mechanism:

• Phenoxide ion attacks CO₂ (electrophile)
• Rearrangement gives ortho-hydroxybenzoic acid

✗ Mistake #2: Using the Wrong Reagent for Acetylation

What students do wrong: Using acetic acid ($CH_3COOH$) directly to acetylate salicylic acid.

Why it's wrong: Acetic acid is a weak electrophile — it won't react with the phenolic -OH. You need a more reactive acylating agent.

How to avoid: Always use:

• Acetic anhydride $(CH_3CO)_2O$ (most common in exams)
• Or acetyl chloride $CH_3COCl$
• With a catalyst: conc. $H_2SO_4$ or pyridine

✗ Mistake #3: Forgetting to Protect the -OH Group

What students do wrong: Trying to directly acetylate the carboxylic acid group instead of the phenolic -OH.

Why it's wrong: Aspirin is acetylsalicylic acid — the acetyl group goes on the phenolic -OH, not the -COOH. The -COOH remains free.

How to avoid: Remember the structure:

• Salicylic acid: ortho-hydroxybenzoic acid (both -OH and -COOH)
• Aspirin: acetyl group on the phenolic oxygen, -COOH untouched

✗ Mistake #4: Skipping the Base Step in Kolbe-Schmitt

What students do wrong: Reacting phenol directly with CO₂ without first converting to sodium phenoxide.

Why it's wrong: Phenol itself is not nucleophilic enough to attack CO₂. The phenoxide ion ($C_6H_5O^-$) is a much stronger nucleophile.

How to avoid: Always write: …