Question

\(p\) -Aminobenzoic acid (PABA) is widely used as a sunscreen agent. Propose a synthesis of PABA starting from toluene.

Short answer

Nitrate toluene, reduce nitro group to amine, then oxidize methyl to carboxyl.

Step-by-step solution

Nitration of Toluene

The first step is to introduce a nitro group to the benzene ring of toluene. This can be accomplished through a nitration reaction. React toluene with a mixture of concentrated nitric acid (HNO₃) and concentrated sulfuric acid (H₂SO₄) to obtain ortho and para-nitrotoluene, but primarily para-nitrotoluene due to steric and electronic effects.

Reduction of Nitro Group

Next, convert the nitro group to an amino group. Reduce the para-nitrotoluene using a reducing agent like tin (Sn) and hydrochloric acid (HCl), or iron (Fe) and HCl. This results in the formation of para-aminotoluene (p-toluidine).

Oxidation of Methyl Group

The final step is to oxidize the methyl group of para-aminotoluene to a carboxylic acid group, which will yield para-aminobenzoic acid (PABA). This can be achieved by using a strong oxidizing agent such as potassium permanganate (KMnO₄) under acidic or neutral conditions. This process converts the methyl group directly to a carboxyl group.

Key concepts

Nitration of Toluene

Nitration of toluene is the first step in synthesizing compounds such as para-aminobenzoic acid (PABA). In this reaction, a nitro group (\(\text{-NO}_2\)) is introduced into the benzene ring of toluene.
This is achieved by using a nitrating mixture of concentrated nitric acid (\(\text{HNO}_3\)) and sulfuric acid (\(\text{H}_2\text{SO}_4\)). The reaction is designed to add the nitro group primarily to the para position relative to the methyl group due to the electronic and steric effects.

• The methyl group in toluene directs the nitration to the ortho and para positions.
• Para-nitration is favored due to less steric hindrance compared to the ortho position.

By conducting this reaction, you obtain a mixture of ortho and para-nitrotoluene, with the para isomer being predominant.

Reduction of Nitro Group

Reducing the nitro group to an amino group is essential in transforming para-nitrotoluene to para-aminotoluene. This involves using reducing agents such as tin (Sn) with hydrochloric acid (HCl), or iron (Fe) with HCl.
These reagents help in breaking the strong N-O bonds in the nitro group.

• Reduction changes the nitro group (\(\text{-NO}_2\)) into an amino group (\(\text{-NH}_2\)).
• It's crucial to control the reaction conditions to avoid side reactions and achieve the desired amine product.

Successful reduction yields para-aminotoluene, a vital intermediate in the synthesis process.

Oxidation of Methyl Group

The final step in synthesizing PABA from para-aminotoluene involves converting the methyl group into a carboxylic acid group. This is accomplished through the oxidation process.
A strong oxidizing agent like potassium permanganate (\(\text{KMnO}_4\)) is typically used here.

• The oxidation happens under acidic or neutral conditions to ensure the complete transformation of the methyl group to a carboxyl group (\(\text{-COOH}\)).
• This step requires careful control of reaction conditions, as over-oxidation can lead to unwanted by-products.

Through this method, you transform para-aminotoluene into para-aminobenzoic acid (PABA), completing the synthesis.

Para-Nitrotoluene

Para-nitrotoluene is a key intermediate in the synthesis path from toluene to PABA. It is one of the main products of the nitration of toluene.
Due to the electronic nature of the methyl group in toluene, it directs nitration primarily to the para position, although some ortho product is formed.

• The para-nitro group is positioned opposite the methyl group on the benzene ring.
• It’s important due to its tendency to undergo reduction reactions effectively, which is the next step in synthetic transformations.

Understanding the formation and reactions of para-nitrotoluene is crucial for successful chemical synthesis.

Para-Aminotoluene

Para-aminotoluene is formed by reducing para-nitrotoluene and serves as a critical precursor to para-aminobenzoic acid. Transforming it involves reducing the nitro group (\(\text{-NO}_2\)) to an amino group (\(\text{-NH}_2\)).
This compound plays an essential role due to its reactivity and conversion potential.

• It sits ready for the final transformation to para-aminobenzoic acid through oxidation.
• This compound highlights the importance of understanding functional group transformations in organic chemistry, such as reductions and oxidations.

Knowing the behavior and preparation of para-aminotoluene helps in refining chemical synthesis techniques.