Question

How would you prepare benzylamine, \(\mathrm{C}_{6} \mathrm{H}_{5} \mathrm{CH}_{2} \mathrm{NH}_{2},\) from benzene? More than one step is needed.

Short answer

Nitrate benzene to nitrobenzene, reduce to aniline, then modify to benzylamine.

Step-by-step solution

Nitration of Benzene

Start by converting benzene ( C_6H_6}) into nitrobenzene ( C_6H_5NO_2}) via a nitration reaction. Use concentrated nitric acid ( HNO_3}) and concentrated sulfuric acid ( H_2SO_4}) to introduce the nitro group (-NO_2) onto the benzene ring. This is done under controlled heating to form nitrobenzene.

Reduction to Aniline

Next, reduce the nitro group on nitrobenzene ( C_6H_5NO_2}) to an amino group ( -NH_2) to form aniline ( C_6H_5NH_2}). Use reducing agents such as iron and hydrochloric acid (Fe/HCl) or catalytic hydrogenation (H_2/Pd-C) to achieve this transformation.

Formation of Benzylamine

Finally, perform the reductive amination of the carbon adjacent to the aniline. First, convert aniline into a salt with formaldehyde, producing a carbinolamine intermediate. Then, reduce this intermediate using a reducing agent like sodium borohydride ( NaBH_4}) or by catalytic hydrogenation to form benzylamine ( C_6H_5CH_2NH_2}).

Key concepts

Nitration of Benzene

Nitration of benzene is the first key step in converting benzene to benzylamine. This transformation involves introducing a nitro group ( -NO_2 ) into the benzene ring. The process starts with benzene ( C_6H_6 ) and requires a mixture of concentrated nitric acid ( HNO_3 ) and sulfuric acid ( H_2SO_4 ). The sulfuric acid acts as a catalyst and helps protonate the nitric acid, forming the electrophile that attacks the benzene ring.
In more detail, the sulfuric acid serves to generate the nitronium ion ( NO_2^+ ), which is the active electrophile that attaches to the benzene ring. This reaction takes place under controlled heating to ensure the proper attachment of the nitro group, forming nitrobenzene ( C_6H_5NO_2 ).

This nitration process is crucial because it sets the stage for further chemical modifications. It changes benzene, an aromatic hydrocarbon, into a compound that can be more readily transformed into an amine, which is essential for the final product, benzylamine.

Reduction of Nitrobenzene

Once nitrobenzene ( C_6H_5NO_2 ) is formed, the next step is to reduce it to aniline ( C_6H_5NH_2 ). This reduction involves transforming the nitro group ( -NO_2 ) into an amino group ( -NH_2 ). There are several methods to achieve this, but two common strategies are using iron and hydrochloric acid (Fe/HCl) or catalytic hydrogenation using hydrogen gas and palladium on carbon (H_2/Pd-C).

Using Fe/HCl, the reduction is typically done by heating the mixture of nitrobenzene, iron filings, and hydrochloric acid. The iron acts as a reducing agent, converting the nitro group into an amine.

• Pros: inexpensive and readily available materials.
• Cons: the reaction can produce a lot of heat and iron sludge.

In catalytic hydrogenation, a mild alternative, hydrogen gas is passed over nitrobenzene in the presence of a palladium catalyst. This method is clean and straightforward but requires specialized equipment.

These reduction steps are significant, as they set up the nitrobenzene to become aniline, an intermediate that is crucial for the subsequent conversion to benzylamine.

Reductive Amination

The final stage in synthesizing benzylamine involves reductive amination, a process that alters aniline to benzylamine ( C_6H_5CH_2NH_2 ). This transformation is achieved by first forming an intermediate known as carbinolamine.

The process starts by reacting aniline ( C_6H_5NH_2 ) with formaldehyde ( CH_2O ) to form a carbinolamine intermediate. This intermediate is then reduced typically using sodium borohydride ( NaBH_4 ) or catalytic hydrogenation. The reduction step is where the real magic happens, converting the carbon-nitrogen bond to a primary amine, giving benzylamine.

• Using NaBH_4 is practical and provides good yields in smaller lab settings.
• Catalytic hydrogenation offers a robust method but may require more sophisticated equipment.

Reductive amination is a powerful technique in organic chemistry, allowing the conversion of carbonyl compounds into amines. This step is key for producing benzylamine from aniline, completing the multi-step synthesis from benzene.