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

Start with nitration of benzene, reduce it to aniline, acetylate, brominate, remove acetyl group, and use Gabriel synthesis to obtain benzylamine.

Step-by-step solution

Nitration of Benzene

The first step involves the nitration of benzene to form nitrobenzene. This is done by treating benzene with a mixture of concentrated nitric acid (HNO3) and concentrated sulfuric acid (H2SO4) at a temperature of about 50°C. The equation for this reaction is: \[\mathrm{C}_{6} \mathrm{H}_{6} + \mathrm{HNO}_{3} \xrightarrow{\mathrm{H}_2\mathrm{SO}_4} \mathrm{C}_{6} \mathrm{H}_{5} \mathrm{NO}_{2} + \mathrm{H}_{2}\mathrm{O}\]

Reduction of Nitrobenzene

Next, reduce nitrobenzene to aniline (phenylamine) using a reducing agent such as iron filings and hydrochloric acid or a catalytic hydrogenation process. The balanced equation for this reaction is: \[\mathrm{C}_{6} \mathrm{H}_{5} \mathrm{NO}_{2} + 6\mathrm{[H]} \rightarrow \mathrm{C}_{6} \mathrm{H}_{5} \mathrm{NH}_{2} + 2\mathrm{H}_{2}\mathrm{O}\]

Acetylation of Aniline

To prevent oxidation of aniline during further reactions, acetylate aniline by reacting it with acetic anhydride to form acetanilide. This step helps to protect the amino group. The equation is:\[\mathrm{C}_{6} \mathrm{H}_{5} \mathrm{NH}_{2} + \mathrm{(CH}_{3}\mathrm{CO})_2\mathrm{O} \rightarrow \mathrm{C}_{6} \mathrm{H}_{5} \mathrm{NHCOCH}_{3} + \mathrm{CH}_{3}\mathrm{COOH}\]

Bromination of Acetanilide

Next, perform the bromination of acetanilide. This ensures a clean bromination at the para position which helps in easy removal of acetyl group later. This step is done by treating acetanilide with bromine in the presence of a solvent like acetic acid:\[\mathrm{C}_{6} \mathrm{H}_{5} \mathrm{NHCOCH}_{3} + \mathrm{Br}_{2} \xrightarrow{\mathrm{AcOH}} \mathrm{C}_{6} \mathrm{H}_{4} \mathrm{NHCOCH}_{3}\mathrm{Br}+ \mathrm{HBr}\]

Hydrolysis to Remove Acetyl Group

After bromination, hydrolyze the product to remove the acetyl group using an acid or base hydrolysis, which yields p-bromoaniline. By using water and heat, you can achieve:\[\mathrm{C}_{6} \mathrm{H}_{4} \mathrm{NHCOCH}_{3}\mathrm{Br} + \mathrm{H_2O} \rightarrow \mathrm{C}_{6} \mathrm{H}_{4} \mathrm{NH}_{2}\mathrm{Br} + \mathrm{CH}_3\mathrm{COOH}\]

Gabriel Synthesis Method Substitution

Finally, use the Gabriel synthesis method to convert p-bromoaniline to benzylamine. Through a series of steps involving potassium phthalimide and hydrazine, benzylamine ( C_{6}H_{5}CH_{2}NH_{2}) can be synthesized. This transformation requires substitution of the bromine with the amine group:\[\mathrm{C}_{6} \mathrm{H}_{4} \mathrm{NH}\mathrm{Br} + \mathrm{Phthalimide} + \mathrm{KOH} \rightarrow \mathrm{C}_{6} \mathrm{H}_{5} \mathrm{CH}_{2} \mathrm{NH}_{2} + \mathrm{Phthalamide} \]

Key concepts

Nitration of Benzene

Nitration is the introduction of a nitro group (-NO₂) into benzene. Typically, this reaction involves mixing concentrated nitric acid (HNO₃) and concentrated sulfuric acid (H₂SO₄) with benzene.
This mixture forms a powerful electrophilic species known as the nitronium ion (NO₂⁺). The reaction is conducted at moderate temperatures around 50°C to avoid any unwanted side reactions.

Nitration is highly valuable in industrial chemistry due to its application in synthesizing nitro compounds. These compounds are pivotal in producing dyes, pharmaceuticals, and explosives.

• Benzene, being aromatic, undergoes electrophilic aromatic substitution to yield nitrobenzene.
• The chemical equation is: \[ C_{6}H_{6} + HNO_{3} \xrightarrow{H₂SO₄} C_{6}H_{5}NO_{2} + H_{2}O \]

Understanding the mechanism of this reaction helps in optimizing the conditions to achieve maximum yield and purity.

Reduction of Nitrobenzene

Reduction of nitrobenzene aims to convert the nitro group (-NO₂) into an amine group (-NH₂). This step involves using reducing agents such as iron filings with hydrochloric acid, or catalytic hydrogenation.
Iron and hydrochloric acid work collectively to generate hydrogen gas, which acts as the reducing agent for the nitro group.

The reduction is essential in organic synthesis as it transforms nitrobenzene to aniline. Aniline is an important building block for dyes, pharmaceuticals, and polymers.

• The chemical equation for this process is: \[ C_{6}H_{5}NO_{2} + 6[H] \rightarrow C_{6}H_{5}NH_{2} + 2H_{2}O \]
• Aniline can undergo further reactions, thanks to its primary amine group.

Being proficient with reduction processes is crucial for efficient synthetic transformations.

Acetylation of Aniline

Acetylation is the process of introducing an acetyl group (CH₃CO-) into a compound. In the context of aniline, acetylation serves as a protective strategy.
Aniline can be quite reactive, especially towards oxidation, and acetylation helps stabilize it for subsequent reactions.

Reacting aniline with acetic anhydride yields acetanilide.

• The role of the acetyl group is to safeguard the amino group, allowing for selective reactions, such as bromination, without affecting the amine.
• The reaction formula: \[ C_{6}H_{5}NH_{2} + (CH₃CO)₂O \rightarrow C_{6}H_{5}NHCOCH₃ + CH₃COOH \]

Acetanilide is a useful intermediate, demonstrating the importance of protecting groups in organic synthesis.

Bromination

Bromination involves the introduction of a bromine atom into an organic compound. In the case of acetanilide, it ensures bromination occurs at the para position relative to the acetyl-protected amine group.
The reaction typically requires a source of bromine and a solvent like acetic acid.

Having a desired bromination position is crucial for synthesizing specific derivatives. It provides direction for further transformations and purification.

• The reaction equation is: \[ C_{6}H_{5}NHCOCH_{3} + Br_{2} \xrightarrow{AcOH} C_{6}H_{4}NHCOCH_{3}Br + HBr \]
• The bromination must be controlled to prevent multi-substituted products.

This step showcases how strategic reaction planning in organic chemistry achieves desired outcomes efficiently.

Gabriel Synthesis

Gabriel synthesis is a method for synthesizing primary amines from alkyl halides, using potassium phthalimide as the key reactant. In our synthesis pathway, it allows the transformation of brominated compounds into benzylamine.
The basic principle involves the substitution of a halogen with an amine group.

This synthesis is especially useful for preparing primary amines because it avoids side products that can occur with direct amination approaches.

• The general reaction steps include: reacting an alkyl halide with potassium phthalimide, followed by hydrolysis or hydrazinolysis to liberate the amine.
• For producing benzylamine, the bromine is replaced with an amine, forming the desired product without any undesired overreaction.

Gabriel synthesis exemplifies a reliable route in organic synthesis for creating amines with precision and efficiency.