Question

How could you prepare benzyl phenyl ether from benzene and phenol? More than one step is required.

Short answer

Use Friedel-Crafts alkylation to make benzyl chloride, then convert phenol to sodium phenoxide and use Williamson ether synthesis.

Step-by-step solution

Friedel-Crafts Alkylation

To form benzyl chloride, perform a Friedel-Crafts alkylation reaction. React benzene with chloromethyl methyl ether \(( ext{ClCH}_2 ext{OCH}_3)\) in the presence of a Lewis acid catalyst such as aluminum chloride \(( ext{AlCl}_3)\). This step introduces a chloromethyl group to benzene, forming benzyl chloride \(( ext{C}_6 ext{H}_5 ext{CH}_2 ext{Cl})\).

Preparation of Sodium Phenoxide

To create sodium phenoxide, react phenol \(( ext{C}_6 ext{H}_5 ext{OH})\) with sodium hydroxide \(( ext{NaOH})\) in aqueous solution. This deprotonates phenol, forming sodium phenoxide \(( ext{C}_6 ext{H}_5 ext{ONa})\), which is a more reactive form of phenol for the next step.

Williamson Ether Synthesis

Perform a Williamson ether synthesis by reacting benzyl chloride \(( ext{C}_6 ext{H}_5 ext{CH}_2 ext{Cl})\) with sodium phenoxide \(( ext{C}_6 ext{H}_5 ext{ONa})\). The nucleophilic sodium phenoxide attacks the electrophilic carbon of the benzyl chloride, forming benzyl phenyl ether \(( ext{C}_6 ext{H}_5 ext{OCH}_2 ext{C}_6 ext{H}_5})\) and releasing sodium chloride \(( ext{NaCl})\) as a byproduct.

Key concepts

Friedel-Crafts Alkylation

Friedel-Crafts Alkylation is a fundamental reaction in organic chemistry used to introduce alkyl groups into an aromatic ring. In this type of reaction, benzene reacts with an alkyl halide in the presence of a strong Lewis acid, often aluminum chloride (AlCl₃). This catalyst helps in generating a more reactive electrophile from the alkyl halide. The process works because the Lewis acid coordinates to the halogen, making the carbon more positively charged and, therefore, more susceptible to the attack by the electron-rich benzene ring.

Here’s how it works:

• A Lewis acid, like AlCl₃, facilitates the cleavage of the carbon-halogen bond in the alkyl halide.
• This generates a carbocation or an equivalent reactive species.
• The aromatic ring, such as benzene, donates electron density to this electrophile, forming a new carbon-carbon bond.

For the preparation of benzyl chloride from benzene, chloromethyl methyl ether acts as the source of the alkyl group. This step is crucial because it primes benzene for subsequent reactions, attaching the functional group necessary for forming benzyl phenyl ether. Despite its usefulness, be cautious with Friedel-Crafts reactions as they may also lead to polyalkylation or rearrangements of the carbocation.

Williamson Ether Synthesis

Williamson Ether Synthesis is a reliable method to form ethers from alkoxides and alkyl halides via nucleophilic substitution. In this reaction, an alcohol is first converted into its sodium alkoxide using a strong base like sodium hydroxide. This deprotonation step enhances the nucleophilicity of the oxygen, making it ready to attack an alkyl halide.

Here’s the core process:

• The alcohol (phenol in this case) is treated with NaOH to form sodium phenoxide.
• The phenoxide ion acts as a strong nucleophile due to its negative charge.
• This ion attacks the positively charged carbon atom in benzyl chloride, leading to the formation of benzyl phenyl ether.

This mechanism works best with primary alkyl halides to avoid unwanted side reactions. The Williamson Ether Synthesis is particularly valued for its efficiency and straightforward approach to creating diverse ether linkages. Remember that for the best results, it's important to ensure that both the alkoxide and the alkyl halide are clean and moisture-free, as water can deactivate the nucleophile.

Nucleophilic Substitution

Nucleophilic Substitution is a key reaction mechanism that involves the replacement of a leaving group in a molecule by a nucleophile. This is a broad class of reactions that take two main forms: S_N1 and S_N2.

Let’s break down these pathways:

• S_N2: This is a bimolecular reaction where the nucleophile simultaneously attacks the substrate as the leaving group leaves. It is a one-step process and often occurs with primary substrates, like in Williamson Ether Synthesis.
• S_N1: This involves a two-step process where the leaving group departs first, forming a carbocation, which is then attacked by the nucleophile. It's more common with tertiary substrates.

In the context of synthesizing benzyl phenyl ether, the reaction between sodium phenoxide and benzyl chloride is an S_N2 type, where sodium phenoxide directly displaces the chloride in a concerted mechanism. It's crucial because it efficiently forms the desired ether bond with minimal byproducts. Nucleophilic substitution reactions are versatile and widely applied in organic synthesis to create a diverse range of products.