Williamson Ether Synthesis Reaction Mechanism

Summary

This video delves into the Williamson Ether Synthesis reaction, illustrating its two-step process involving deprotonation by a base and alkylation via an SN2 reaction. It uses examples like phenol and alcohols to demonstrate how ethers are formed and discusses the impact of using different bases and alkyl halides on the reaction's outcome.

Takeaways

• 🧪 The Williamson Ether Synthesis is a two-step reaction for producing ethers, involving deprotonation by a base followed by alkylation through an SN2 reaction.
• 🔬 Phenol reacts with sodium hydroxide to form a phenoxide ion, which then reacts with methyl bromide in an SN2 reaction to produce an ether.
• 🔄 The reaction mechanism involves the hydroxide acting as a base to remove a hydrogen atom, creating a nucleophilic alkoxide ion that can attack a primary alkyl halide.
• 📉 Alcohols with a lower pKa than phenol require stronger bases like sodium hydride for complete deprotonation, as hydroxide is not strong enough for alcohols with pKa around 16-18.
• 🌐 The reaction of 1-butanol with sodium hydride demonstrates the need for a stronger base and results in the formation of butylpropyl ether through an SN2 reaction.
• 📚 The naming convention for ethers involves listing the alkyl groups in alphabetical order, such as butyl and propyl in butylpropyl ether.
• 🔍 Predicting the major product in a Williamson Ether Synthesis involves identifying the alkyl group from the alcohol and the alkyl halide that will replace the hydrogen.
• ⚠️ Tert-butyl alcohol reacts with sodium metal to form a sodium alkoxide and hydrogen gas, which can lead to both SN2 and E2 reactions, but with a preference for E2 due to the bulky nature of the base.
• 🔬 The reaction of cyclopentanol with sodium amide and bromobutane can lead to both E2 and SN2 reactions, with E2 being the major product due to the strong base and secondary alkyl halide.
• 🔁 The presence of both an alkyl halide and an alcohol in a reaction can lead to side reactions such as SN2 attack by the hydride ion on the alkyl halide, forming an alcohol.
• 🔁 Intramolecular SN2 reactions can occur, leading to the formation of cyclic ethers when the alkoxide ion attacks a carbon with a bromine atom within the same molecule.

Q & A

What is the Williamson Ether Synthesis reaction?

The Williamson Ether Synthesis reaction is a two-step organic reaction that produces ethers. It involves deprotonation of an alcohol by a base to form an alkoxide ion, which then reacts with an alkyl halide via an SN2 reaction to form the ether.

Why is sodium hydroxide used in the first step of the Williamson Ether Synthesis with phenol?

Sodium hydroxide is used because it acts as a strong base that can remove the hydrogen from phenol, forming a phenoxide ion. This ion is a good nucleophile and can react with methyl bromide in an SN2 reaction to form an ether.

What is the role of the hydroxide ion in the reaction with phenol?

The hydroxide ion acts as a base and removes the hydrogen from phenol, resulting in the formation of a phenoxide ion. This ion has three lone pairs and a negative charge, making it a strong nucleophile that can attack the carbon in methyl bromide.

Why is a stronger base needed when reacting with 1-butanol compared to phenol?

A stronger base like sodium hydride is needed for 1-butanol because most alcohols have a lower pKa (around 16-18) compared to phenol (pKa of 10). Sodium hydroxide is not strong enough to completely deprotonate 1-butanol and drive the reaction to completion.

What is the significance of the pKa values in choosing the appropriate base for the Williamson Ether Synthesis?

The pKa values indicate the acidity of a substance. A lower pKa value means the substance is more acidic and requires a stronger base for deprotonation. In the Williamson Ether Synthesis, a stronger base is needed for alcohols with higher pKa values to ensure complete deprotonation.

What is the major product of the reaction between 1-butanol and propyl bromide in the Williamson Ether Synthesis?

The major product is butyl propyl ether, formed through the SN2 reaction between the alkoxide ion derived from 1-butanol and propyl bromide.

Why is sodium metal used instead of sodium hydroxide or sodium hydride in the reaction with tert-butyl alcohol?

Sodium metal is used because it is an alkaline metal and a reducing agent, which can react with the hydroxyl group in tert-butyl alcohol to form an alkoxide ion and hydrogen gas, without the need for a proton to be removed.

What is the difference between the SN2 and E2 reactions in the context of the Williamson Ether Synthesis?

The SN2 reaction involves a nucleophilic attack on the carbon with the leaving group, leading to the formation of an ether. The E2 reaction, on the other hand, involves the elimination of a leaving group and a hydrogen from adjacent carbons, forming an alkene. The choice of base and alkyl halide can influence which reaction predominates.

What is the major product when cyclopentanol is reacted with sodium amide and bromobutane?

The major product is an alkene formed through the E2 reaction, due to the strong base (sodium amide) reacting with a secondary alkyl halide (bromobutane). However, a minor amount of ether can also be formed through the SN2 reaction.

What can happen when an alkyl halide and an alcohol are reacted together in the presence of sodium hydride?

In addition to the desired ether formation through an SN2 reaction, a side reaction can occur where sodium hydride acts as a nucleophile to displace the bromine atom, forming an alcohol and sodium bromide. Additionally, intramolecular SN2 reactions can lead to the formation of cyclic ethers.