Question

Which of the following ethers cannot be synthesized by directly williamson's ether synthesis?

Short answer

Ethers from tertiary alkyl halides cannot be synthesized by Williamson's method.

Step-by-step solution

Understanding Williamson's Ether Synthesis

Williamson's ether synthesis involves the formation of an ether from an alcohol and an alkyl halide, where the alcohol is converted into its corresponding alkoxide ion by treatment with a strong base, usually sodium or potassium. The alkoxide then reacts with the alkyl halide to form an ether through an S_N2 mechanism.

Determine Conditions Ideal for the Synthesis

In the S_N2 mechanism, the alkyl halide should ideally be either a primary or sometimes secondary halide to prevent steric hindrance and competition from elimination reactions such as E2, which are more common with tertiary alkyl halides.

Analyze Options

Evaluate each ether option given in the exercise. Identify the alkyl halide portion of each ether and determine if it is a primary, secondary, or tertiary structure.

Identify Problematic Ether

If an ether results from a reaction of a tertiary alkyl halide, it cannot be synthesized directly by Williamson's ether synthesis as it will favor elimination over substitution.

Key concepts

SN2 mechanism

The SN2 mechanism is a cornerstone of Williamson's ether synthesis. It is a one-step process where a nucleophile attacks the electrophile and the leaving group exits simultaneously. In this reaction, it's crucial to have a strong nucleophile and a suitable leaving group. The SN2 reaction takes place with an inversion of configuration, also known as a backside attack. This means the nucleophile must approach the atom from the opposite side of the leaving group. Key features of the SN2 mechanism include:

• Concerted mechanism: There is only one transition state as the nucleophile approaches the electrophile.
• Rate dependence: The reaction rate is determined by both the concentration of the nucleophile and the alkyl halide.
• Sterics: The reaction is sensitive to steric hindrance; less bulky groups allow the nucleophile easier access.

Because of these properties, SN2 reactions are more effective with primary and secondary substrates, whereas tertiary substrates are typically unsuitable due to steric hindrance.

Alkyl halide

An alkyl halide is an organic compound containing a halogen atom bonded to an alkyl group. Alkyl halides are crucial in Williamson's ether synthesis as they act as the electrophile that the nucleophile attacks. They are classified based on the substituents around the carbon attached to the halogen:

• Primary alkyl halides: The carbon attached to the halogen is bonded to only one other carbon. These are preferred in Williamson's synthesis because they minimize steric hindrance.
• Secondary alkyl halides: The carbon attached to the halogen is bonded to two other carbons. They can participate in SN2 reactions but are less favorable than primary halides.
• Tertiary alkyl halides: The carbon is bonded to three other carbons. Tertiary structures are generally avoided due to steric hindrance, making elimination reactions more likely.

Understanding the type of alkyl halide is essential for predicting the reaction outcome in Williamson's ether synthesis.

Steric hindrance

Steric hindrance is a crucial factor in determining the feasibility of reactions involving bulky molecules. In the context of the SN2 mechanism, steric hindrance refers to the interference experienced by the nucleophile when trying to approach the electrophilic center. For Williamson's ether synthesis to succeed, the alkyl halide should have minimal steric hindrance, which is why primary and sometimes secondary alkyl halides are recommended. Tertiary alkyl halides pose a significant challenge because bulkiness around the reaction site makes nucleophilic attack difficult. The presence of large substituents near the reaction center can lead to slower reaction rates or may altogether prevent the reaction from occurring. This is why understanding the sterics of a molecule is vital in anticipating the reaction pathway it will follow.

Elimination reactions

Elimination reactions are processes where elements of a molecule are removed, resulting in the formation of a double bond. In the context of Williamson's ether synthesis, they are often competing reactions that can interfere. When working with alkyl halides, especially tertiary ones, the likelihood of an E2 elimination reaction increases, especially under strong basic conditions. Key characteristics of elimination reactions include:

• Reaction pathway: Often, elimination occurs alongside substitution reactions, especially with steric hindrance.
• The Zaitsev rule: This rule predicts that elimination reactions lead to the most substituted alkene as the major product.
• Conditions favoring elimination: Strong bases, high temperatures, and tertiary substrates encourage elimination over substitution.

In Williamson's ether synthesis, careful choice of reaction conditions and substrates helps prioritize the desired substitution over elimination.

Alkoxide ion

The alkoxide ion plays a pivotal role in Williamson's ether synthesis as the nucleophile. It is formed when an alcohol reacts with a strong base, typically sodium or potassium hydroxide, to remove a proton from the alcohol, resulting in the alkoxide ion. This ion is a strong nucleophile, which means it has a high affinity for attacking electron-deficient centers like those found in alkyl halides. Important characteristics:

• Strong nucleophile: Alkoxide ions are powerful in driving the SN2 mechanism towards ether formation.
• Preparation: Achieved by deprotonating an alcohol with a strong base.
• Reactivity: Directly related to the alcohol from which it is derived and influences its capability in nucleophilic substitution.

The reactivity and stability of the alkoxide ion determine its success in the ether-forming reaction and are essential for a successful Williamson's ether synthesis.