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

Use an alkoxide ion from the alcohol with a strong nucleophile to react with a primary alkyl halide.

Step-by-step solution

Understanding Williamson Ether Synthesis

The Williamson synthesis involves an S\( _N2 \) reaction between an alkoxide ion and a primary alkyl halide. This means we need to identify which part of the ether will be converted to the alkoxide ion and which will be the alkyl halide.

Methyl Propyl Ether Preparation

For methyl propyl ether, choose propoxide ion (from propanol) as the alkoxide ion and methyl iodide as the alkyl halide. The reaction will proceed as follows: \( ext{C}_3 ext{H}_7 ext{O}^- + ext{CH}_3 ext{I} ightarrow ext{C}_3 ext{H}_7 ext{OCH}_3 + ext{I}^- \)

Anisole Preparation

For anisole, select phenoxide ion (from phenol) as the alkoxide ion and methyl iodide as the alkyl halide. The reaction is: \( ext{C}_6 ext{H}_5 ext{O}^- + ext{CH}_3 ext{I} ightarrow ext{C}_6 ext{H}_5 ext{OCH}_3 + ext{I}^- \)

Benzyl Isopropyl Ether Preparation

For benzyl isopropyl ether, the best choice is isopropoxide ion (from isopropanol) as the alkoxide and benzyl chloride as the alkyl halide. The reaction will be: \( ext{(CH}_3 ext{)}_2 ext{CHO}^- + ext{C}_6 ext{H}_5 ext{CH}_2 ext{Cl} ightarrow ext{(CH}_3 ext{)}_2 ext{CHOCH}_2 ext{C}_6 ext{H}_5 + ext{Cl}^- \)

Ethyl 2,2-dimethylpropyl Ether Preparation

For ethyl 2,2-dimethylpropyl ether, use ethoxide ion (from ethanol) as the alkoxide ion and 2,2-dimethylpropyl bromide as the alkyl halide. The reaction is: \( ext{C}_2 ext{H}_5 ext{O}^- + ext{C}_5 ext{H}_{11} ext{Br} ightarrow ext{C}_2 ext{H}_5 ext{OC}_5 ext{H}_{11} + ext{Br}^- \)

Key concepts

S\( _N2 \) Reaction

In chemistry, one often encounters concepts that are staples in the toolbox for synthesis. The \( S_N2 \) reaction is one such important mechanism. The abbreviation \( S_N2 \) stands for bimolecular nucleophilic substitution, a type of chemical reaction that is characterized by a simultaneous process where a nucleophile attacks a substrate and the leaving group departs. Both processes happen in one concerted step.
The \( S_N2 \) reaction is known for its simplicity and effectiveness, especially in the formation of ethers through Williamson ether synthesis. Here, the nucleophile often takes the form of an alkoxide ion, which attacks a primary alkyl halide. This nucleophilic attack leads to the formation of a new carbon-oxygen bond while displacing the halide ion.
This type of reaction is preferred for primary alkyl halides due to minimal steric hindrance, which facilitates smoother and faster reaction rates. If the organic substrate is too bulky, the \( S_N2 \) reaction tends not to proceed effectively, which is why selecting appropriate substrates is crucial.

Alkoxide Ion

The alkoxide ion plays a central role in the Williamson ether synthesis. In its essence, an alkoxide is the conjugate base of an alcohol and is formed when an alcohol loses a proton from its hydroxyl group. This transformation typically occurs by treating an alcohol with a strong base, often sodium or potassium metal, or through direct deprotonation with a base like sodium hydride.
Example:
- Methanol \( \text{CH}_3\text{OH} \) losing a proton becomes methoxide ion \( \text{CH}_3\text{O}^- \).
Alkoxide ions are strong nucleophiles, and their high reactivity makes them perfect candidates for attacking electrophiles like alkyl halides in \( S_N2 \) reactions. The charged oxygen atom in the alkoxide ion donates a pair of electrons to form a new covalent bond with a carbon atom in an alkyl halide, leading to the formation of an ether and a leaving group. It is this powerful nucleophilic ability that allows the alkoxide ion to succeed in the clean conversion of alcohol derivatives into ethers.

Primary Alkyl Halide

Primary alkyl halides are crucial participants in \( S_N2 \) reactions because they offer less steric hindrance, increasing the likelihood and rate of successful nucleophilic attack. In these molecules, the carbon atom attached to the halogen is bonded to only one other alkyl group, minimizing the crowding around the reaction site.
This characteristic makes them ideal for \( S_N2 \) style transformations, such as the Williamson ether synthesis, where it's essential for the nucleophile (like an alkoxide ion) to access the reactive carbon center without much interference from neighboring groups.
By choosing primary alkyl halides:
- The reaction pathway is often more straightforward, avoiding side reactions.
- They facilitate faster and cleaner reactions, ensuring desired product formation with high yields.
In the Williamson synthesis, the use of primary alkyl halides thus plays a critical role in the efficient synthesis of ethers without complications from unwanted side reactions.