Question

organic chemistry ii
electrophilic aromatic substitution (synthesis
of substituted benzenes)
the problem:
starting from benzene, propose a multi-
step synthesis to create 4 - nitrobenzoic acid.
explain why the order of reagents matters

Explanation:

Step1: Benzene to Toluene (Alkylation)

Benzene undergoes Friedel-Crafts alkylation with methyl chloride ($CH_3Cl$) and a Lewis acid catalyst ($AlCl_3$) to form toluene.
$$\ce{C6H6 + CH3Cl ->[AlCl3] C6H5CH3 + HCl}$$

Step2: Toluene to p-Nitrotoluene (Nitration)

Toluene reacts with a nitrating mixture ($HNO_3/H_2SO_4$). The methyl group is an ortho/para-directing activator, so para-nitrotoluene is the major product.
$$\ce{C6H5CH3 + HNO3 ->[H2SO4] O2N-C6H4-CH3 (major) + H2O}$$

Step3: p-Nitrotoluene to 4-Nitrobenzoic Acid (Oxidation)

The methyl group on p-nitrotoluene is oxidized to a carboxylic acid using a strong oxidizing agent like potassium permanganate ($KMnO_4$) in basic conditions, followed by acidification.
$$\ce{O2N-C6H4-CH3 ->[KMnO4, OH-; H3O+] O2N-C6H4-COOH}$$

Step4: Explain Reagent Order

If nitration is done first: nitro group is a meta-directing deactivator. Friedel-Crafts alkylation cannot occur on nitrobenzene (deactivated ring), and any substitution would target meta positions, failing to form the desired para product.
If oxidation is done first: benzene cannot be oxidized to benzoic acid directly, and benzoic acid's carboxyl group is meta-directing, so nitration would give meta-nitrobenzoic acid instead of the para isomer.

Answer:

The multi-step synthesis of 4-nitrobenzoic acid from benzene is:

1. Friedel-Crafts alkylation of benzene to toluene
2. Nitration of toluene to p-nitrotoluene
3. Oxidation of p-nitrotoluene to 4-nitrobenzoic acid

The reagent order matters because:

• The methyl group (from alkylation) is an activating, ortho/para-directing group, which directs nitration to the desired para position.
• Nitrobenzene (if nitration is done first) is too deactivated for Friedel-Crafts alkylation, and the nitro group directs substitution to meta positions.
• Benzoic acid (if oxidation is done early) has a meta-directing carboxyl group, leading to the wrong isomer upon nitration.

The final product is 4-nitrobenzoic acid ($\ce{O2N-C6H4-COOH}$).