Question

How would you prepare the following ethers using a Williamson synthesis? (a) Methyl propyl ether (b) Anisole (methyl phenyl ether) (c) Benzyl isopropyl ether (d) Ethyl 2,2-dimethylpropyl ether

Short answer

React the appropriate alkoxide ions with alkyl halides for each ether target.

Step-by-step solution

Understanding the Williamson Ether Synthesis

The Williamson ether synthesis involves reacting an alkoxide ion with a primary alkyl halide or tosylate to form an ether. The alkoxide is typically generated by deprotonating an alcohol with a strong base.

Methyl Propyl Ether Preparation

To prepare methyl propyl ether using Williamson synthesis, identify the alcohols involved: methanol (CH3OH) and 1-bromopropane (or another propyl halide). Convert methanol to its alkoxide form, sodium methoxide (CH3O^- Na^+), using sodium metal or a strong base like sodium hydride. React this with 1-bromopropane (CH3CH2CH2Br).

Anisole Preparation

For anisole (methyl phenyl ether), start with phenol (C6H5OH) and methyl iodide (or another methyl halide). Convert phenol to sodium phenoxide (C6H5O^- Na^+) using sodium hydroxide or another strong base. This phenoxide then reacts with methyl iodide (CH3I) to form anisole.

Benzyl Isopropyl Ether Preparation

For benzyl isopropyl ether, begin with benzyl alcohol (C6H5CH2OH) and isopropyl bromide (or another isopropyl halide). Make the alkoxide from benzyl alcohol, forming sodium benzylate (C6H5CH2O^- Na^+) with a strong base. This benzylate reacts with isopropyl bromide (CH(CH3)2Br) to yield benzyl isopropyl ether.

Ethyl 2,2-Dimethylpropyl Ether Preparation

For ethyl 2,2-dimethylpropyl ether, use ethanol (C2H5OH) and 2,2-dimethylpropyl bromide (or analogous halide). Convert ethanol into sodium ethoxide (C2H5O^- Na^+) with a strong base and react this with 2,2-dimethylpropyl bromide ((CH3)3CCH2Br) to obtain the desired ether.

Key concepts

Alkoxide Ion

In the world of chemistry, the alkoxide ion plays a crucial role in the Williamson Ether Synthesis. This ion is created through the process of alcohol deprotonation. When an alcohol reacts with a strong base, it loses a hydrogen ion (H^+) and forms an alkoxide ion.

Common bases used for this process include sodium metal or sodium hydride. These strong bases effectively strip the proton (H) from the hydroxyl group (OH) of the alcohol.

• This process transforms alcohol (R-OH) into an alkoxide ion (R-O^-).
• The alkoxide ion is an anion, meaning it carries a negative charge.
• Alkoxide ions are key players in nucleophilic substitution reactions.

The negative charge on the oxygen allows it to react with electrophiles, such as primary alkyl halides, to form ethers.

Primary Alkyl Halide

Primary alkyl halides are important in the formation of ethers via the Williamson Ether Synthesis. An alkyl halide contains a halogen (like bromine or iodine) bound to an alkyl group, and a primary alkyl halide has the halogen attached to a carbon that is connected to only one other carbon.

These halides are good electrophiles, which means they readily react with nucleophiles, like the alkoxide ion.

• They facilitate the transfer of the alkyl group from the halide to the alkoxide.
• The reaction occurs through an S_N2 mechanism, where the alkoxide ion attacks from the opposite side of the halogen.
• This leads to the displacement of the halogen and formation of the ether.

Primary alkyl halides are especially suitable for this reaction because they are more reactive in S_N2 reactions compared to secondary or tertiary halides.

Ether Formation

Ether formation in Williamson synthesis is the main goal when combining an alkoxide ion with a primary alkyl halide. This process is an elegant way to create ethers due to its straightforward execution and efficacy.

During the reaction, the nucleophilic alkoxide ion attacks the electrophilic carbon of the alkyl halide, leading to the formation of an ether linkage.

• The process replaces the halogen on the alkyl halide with the alkoxide ion.
• An S_N2 mechanism ensures the reaction generally proceeds without complication, if the conditions are correct.
• Ether, which has the general formula R-O-R', is the product of successful synthesis.

This method is widely used in organic chemistry to create a diverse range of ether compounds efficiently.

Alcohol Deprotonation

Alcohol deprotonation is the first step in preparing an alkoxide ion for use in the Williamson Ether Synthesis. By using a strong base, an alcohol can be deprotonated, meaning it loses a hydrogen ion and forms an alkoxide ion.

This step is vital as it activates the alcohol, transforming it from a relatively inert molecule into a reactive nucleophile.

• Strong bases such as sodium or potassium hydroxide are typically employed.
• Alcohol deprotonation results in the formation of a water molecule alongside the alkoxide ion.
• This transformation makes the oxygen highly nucleophilic and ready to form ethers.

Understanding and mastering this step is crucial for those aiming to successfully perform the Williamson Ether Synthesis.