Williamson Ether Synthesis

Summary

In this video, Professor Dave explains the Williamson ether synthesis, a straightforward method for creating ethers. The process begins with deprotonating an alcohol using sodium hydride, forming an alkoxide. The alkoxide then attacks an alkyl halide via an SN2 mechanism, resulting in an ether. The reaction works best with unhindered alkyl halides and alkoxides. The video also covers examples of the synthesis, including intramolecular cyclization leading to cyclic ethers. The explanation emphasizes both the forward and reverse aspects of the reaction, helping viewers understand how to identify and predict products and substrates.

Takeaways

• 😀 Ethers are functional groups with an oxygen atom bound to two alkyl groups.
• 😀 Williamson ether synthesis is a common and straightforward method for synthesizing ethers.
• 😀 The reaction begins with the deprotonation of an alcohol using a strong base like sodium hydride (NaH).
• 😀 Sodium hydride is commonly used because it efficiently deprotonates alcohols without interfering with other reactions.
• 😀 After deprotonation, the resulting alkoxide ion undergoes an SN2 reaction with an alkyl halide to form an ether.
• 😀 A primary alkyl halide is ideal for the reaction as it allows for an unhindered SN2 substitution.
• 😀 Increased steric hindrance in either the alkoxide or the alkyl halide reduces the reaction's efficiency.
• 😀 In examples, identifying the substrate and product helps to deduce the starting reagents for the reaction.
• 😀 When going backwards in the reaction, the alkyl halide and the alkoxide can be identified in the product to deduce the starting materials.
• 😀 In some cases, a molecule can undergo intramolecular Williamson ether synthesis, forming a cyclic ether if the alkoxide and alkyl halide are part of the same molecule.

Q & A

What is the basic definition of an ether?

An ether is a functional group that consists of an oxygen atom bonded to two alkyl groups.

What is the main concept behind the Williamson ether synthesis?

The Williamson ether synthesis involves deprotonating an alcohol to form an alkoxide, which then performs an SN2 reaction on an alkyl halide to form an ether.

Why is sodium hydride often used in the Williamson ether synthesis?

Sodium hydride is commonly used because it effectively deprotonates alcohols to form alkoxides without causing competing reactions, ensuring the synthesis proceeds smoothly.

What happens when sodium hydride deprotonates an alcohol?

When sodium hydride deprotonates an alcohol, it removes a proton from the hydroxyl group, producing an alkoxide ion and hydrogen gas, which bubbles out of the solution.

What kind of reaction does the alkoxide ion undergo in the Williamson ether synthesis?

The alkoxide ion undergoes an SN2 reaction with an alkyl halide, leading to the formation of a new carbon-oxygen bond and the creation of an ether.

What factors affect the yield of the Williamson ether synthesis?

The yield is affected by the steric hindrance of both the alkoxide and the alkyl halide. The reaction works best with relatively unhindered reagents, such as primary alkyl halides.

What would be an ideal candidate for the Williamson ether synthesis reaction?

An ideal candidate would be a primary alkyl halide because it undergoes the SN2 mechanism more readily due to lower steric hindrance.

How do you deduce the starting materials in a Williamson ether synthesis when given the product?

To deduce the starting materials, you can analyze the structure of the ether product and work backwards to identify the alkyl halide and alcohol used in the reaction.

What happens when you perform a Williamson ether synthesis with an intramolecular reaction?

In an intramolecular reaction, the alkoxide attacks an alkyl halide on the same molecule, leading to the formation of a cyclic ether.

How does the reaction mechanism change when using aqueous base instead of sodium hydride?

Using aqueous base like hydroxide can also deprotonate the alcohol to form an alkoxide, but this can lead to additional reactions, including intramolecular reactions, resulting in the formation of cyclic ethers.