Question

Beginning with nitrobenzene, how would you synthesize the following compounds? (a) Bromobenzene (b) Benzonitrile

Short answer

(a) To synthesize bromobenzene from nitrobenzene, first reduce the nitro group to an amino group using Sn and HCl, forming aniline. Next, treat aniline with Br2 and H2O to yield bromobenzene through electrophilic aromatic substitution. (b) To synthesize benzonitrile from nitrobenzene, first reduce the nitro group to an amino group using Sn and HCl, forming aniline. Then, diazotize the amino group with HNO2 at 0-5°C to form benzene diazonium chloride. Finally, treat the diazonium salt with CuCN to yield benzonitrile through the Sandmeyer reaction.

Step-by-step solution

Reduction of the nitro group to an amino group

Treat nitrobenzene with a strong reducing agent like tin (Sn) and hydrochloric acid (HCl) to convert the nitro group to an amino group. This reaction is called nitro-to-amine reduction, and the product is aniline. The reaction is as follows: \[ \text{Nitrobenzene} + \text{Sn} + \, 6\text{HCl} \rightarrow \text{Aniline} + \, 2\text{H}_{2}\text{O} + \, 4\text{NaCl} \]

Substitution of the amino group with a bromine atom

Now that we have aniline, treat it with bromine (Br2) in the presence of water (H2O) to yield bromobenzene. This reaction is called electrophilic aromatic substitution (specifically, bromination). The resulting product is bromobenzene. The reaction is as follows: \[ \text{Aniline} + \text{Br}_{2} + \text{H}_{2}\text{O} \rightarrow \text{Bromobenzene} + \, 2\text{HBr} \] (b) Synthesizing benzonitrile from nitrobenzene

Reduction of the nitro group to an amino group

As in the previous synthesis, we first reduce the nitro group to an amino group using tin (Sn) and hydrochloric acid (HCl) to obtain aniline. The reaction is as follows: \[ \text{Nitrobenzene} + \text{Sn} + \, 6\text{HCl} \rightarrow \text{Aniline} + \, 2\text{H}_{2}\text{O} + \, 4\text{NaCl} \]

Diazotization of the amino group to form a diazonium salt

Next, we need to convert aniline to a diazonium salt. Treat aniline with nitrous acid (HNO2) at 0-5°C (generated in situ using sodium nitrite (NaNO2) and hydrochloric acid (HCl)) to form the benzene diazonium chloride. The reaction is as follows: \[ \text{Aniline} + \text{HNO}_{2} \rightarrow \text{Benzene Diazonium Chloride} + \, 2\text{H}_{2}\text{O} \]

Substitution of the diazonium salt with a cyano group

To obtain benzonitrile, we need to substitute the diazonium salt with a cyano group. Treat benzene diazonium chloride with copper(I) cyanide (CuCN) to yield benzonitrile. This reaction is called the Sandmeyer reaction. The reaction is as follows: \[ \text{Benzene Diazonium Chloride} + \text{CuCN} \rightarrow \text{Benzonitrile} + \, 2\text{HCl} + \text{CuCl} \]

Key concepts

Electrophilic Aromatic Substitution

Let's begin by understanding how an electrophilic aromatic substitution (EAS) is crucial in the synthesis of various aromatic compounds. This chemical reaction is a cornerstone of organic chemistry, where an atom attached to an aromatic system, such as benzene, is replaced by an electrophile, which is an electron-deficient atom or molecule. In the context of transforming aniline into bromobenzene, the electrophile is a bromine atom.During the process, the aromatic ring of aniline acts as a rich source of electrons and forms a temporary complex with bromine. Subsequently, hydrogen is substituted by a bromine atom to produce bromobenzene and hydrogen bromide. This mechanism preserves the stability of the benzene ring, a priority in EAS reactions.

Illustration of Bromination

Aniline, possessing an amino group, is highly reactive towards bromine due to the ring's electron rich nature induced by the amino substituent. This makes the bromination proceed without the need for a strong Lewis acid catalyst, a requirement in other EAS reactions. The simplicity of this process allows students to readily appreciate the fundamentals of EAS through this transformation.

Nitro-to-Amine Reduction

Nitro-to-amine reduction is a valuable transformation in organic synthesis. This reduction process involves converting a nitro group, which is a functional group with the notation NO2, to an amine group (NH2). Nitro compounds, like nitrobenzene, can be reduced using various reagents; tin (Sn) and hydrochloric acid (HCl) is a classic combination.In the given textbook exercise, nitrobenzene undergoes reduction to form aniline. The tin and hydrochloric acid work together to donate electrons to the nitrobenzene, systematically replacing the oxygen atoms with hydrogen atoms to form the amine group.

Understanding the Mechanism

The reduction occurs in multiple steps, with the nitro group being progressively hydrogenated. The HCl provides the acidic conditions and the necessary protons, while Sn acts as the reducing agent. This reaction not only is pivotal in industrial applications but also offers a hands-on application of redox chemistry that students can relate to real-world chemical processes.

Sandmeyer Reaction

The Sandmeyer reaction is a powerful tool in aromatic chemistry that enables the conversion of aromatic amines into a variety of other functional groups. This reaction specifically involves replacing the amino group of an aromatic diazonium salt with a nucleophile, facilitated by a copper(I) salt, such as copper(I) chloride (CuCl) or copper(I) cyanide (CuCN).In the solution provided in the exercise, benzene diazonium chloride reacts with CuCN to yield benzonitrile, alongside the formation of copper(I) chloride and hydrogen chloride as byproducts. The magic of the Sandmeyer reaction lies in its ability to introduce groups that would otherwise be difficult to attach to an aromatic ring, thereby expanding the synthetic possibilities.

Application in Benzonitrile Synthesis

The ability to synthesize benzonitrile from aniline showcases the use of the Sandmeyer reaction. The choice of CuCN as the copper salt is driven by the desire to introduce a cyano group into the aromatic ring, illustrating the flexibility of this reaction to accommodate various nucleophiles for diverse aromatic substitutions.

Diazotization

Diazotization is an essential reaction in organic chemistry where primary aromatic amines are treated with nitrous acid to form diazonium salts. This reaction occurs under cold conditions, usually between 0-5°C, to maintain the stability of the diazonium salt, which is prone to decomposition at higher temperatures.The process begins with the generation of nitrous acid in situ from sodium nitrite (NaNO2) and hydrochloric acid (HCl). When aniline comes into contact with nitrous acid, it swiftly transforms into benzene diazonium chloride, a key intermediate in synthesizing many aromatic compounds, including halogenated aromatics and cyano aromatics.

Strategic Use in Syntheses

The diazonium group has a unique ability to be replaced by various nucleophiles, making diazotization an invaluable step in creating a plethora of derivatives from a single starting material. When teaching the concept of diazotization, emphasizing its role as a gateway reaction can help students appreciate its strategic importance in organic synthesis.