Williamson Ether Synthesis Practice Problems

Provide the mechanism for the reaction below:

Identify the ether for which Williamson ether synthesis fails.

For the synthesis of the following ether, 

what is the best pair of alkoxide ion and alkyl halide to use?

Identify the set of alkyl halide and nucleophile that could be used as starting materials in the synthesis of the given ether.

(i) Illustrate how ethanol and cyclopentanol can be used to synthesize cyclopentyl ethyl ether via tosylation and subsequent Williamson ether synthesis.
(ii) Cyclopentyl ethyl ether can't be synthesized via bimolecular dehydration of the two alcohols. Explain why.

In the proposed synthesis of ethyl isopropyl ether shown below, first, ethanol is reacted with an acid to protonate the hydroxy group, and then sodium isopropoxide is added to displace water. What is wrong with the synthesis?

Synthesize 2-methoxypropane using (1) alkoxymercuration-demercuration and (2) Williamson ether synthesis.

Phenols have an acidic proton that can be deprotonated easily using sodium hydroxide or potassium hydroxide to give phenoxide anions. These ions can be used in the Williamson ether synthesis. Show how the following compound can be synthesized using 2-methylphenol, dimethyl sulfate, and other necessary reagents.

2-ethoxybutane can be made by either reacting butan-2-ol with sodium metal and then ethyl iodide, or by reacting butan-2-ol with tosyl chloride and pyridine and then with sodium ethoxide. When pure (S)-butan-2-ol of specific rotation −13.9º is subjected to the first procedure, 2-ethoxybutane with a specific rotation of −14.3º is obtained as the product. Propose a detailed mechanism, and predict the rotation of 2-ethoxybutane obtained using the second procedure.

Propose a Williamson ether synthesis of the following compound using 3,3-dimethylcyclohexanol and ethanol as your starting materials.

Identify the product of the reaction shown below:

Modify the reaction shown below to produce the ether instead of the alcohol.

(i) Why does the reaction of the alkoxide with the secondary haloalkane below not form the ether? 

(ii) However, the structurally similar thioether can be created by an analogous reaction. Explain.

Which condition stereoselectively adds the indicated ether function group to the given compound?

Predict the structure of the compound formed when the dihydroxybenzene reacts with one equivalent of alkyl halide and base.

Identify the product of the reaction involving phenoxides shown below:

Will the given reaction undergo Williamson ether synthesis? What is its product?

Suggest an alcohol and alkene pair to produce the given ether.

Determine the phenoxide and alkyl halide that produces the aryl alkyl ether shown below.

Determine whether the product formed is via the Williamson ether synthesis or not.

Two different Williamson ether syntheses can be used to form the compound below. Draw these syntheses.

Draw the haloalkane and alkoxide that were used in a Williamson ether synthesis to give the product below. Provide a brief explanation as to why it is the only possible combination.

Predict the product of the following reaction.

Crown ethers are used to increase the rate of S_N2 reactions. Choose the reactants that could potentially synthesize 18-Crown-6.

Determine the phenoxide and the alkyl halide needed to produce the given molecule.

Determine the reagents needed for each step of the given multistep reaction and determine the objective of steps (i) and (v).

Give the two alkoxide and haloalkane pairs that produce the ether below.

Provide a reaction scheme in which 1-((3,3-dimethylbutan-2-yl)oxy)-3,3-dimethylbutane is synthesized using 3,3-dimethylbutan-2-ol as the only carbon source.

Give the product of the reaction sequence below.

What are the best ways (alkoxide ion and alkyl halide pairs) to synthesize the following ethers?

A chemist was surprised when he did not synthesize the ether, 1-ethoxy-1-methylcyclopentane, when he used 1-bromo-1-methylcyclopentane and ethoxide ion. Determine the major product of his synthesis. What starting materials should have been used instead to produce that ether via Williamson ether synthesis?

For this given product, provide its synthesis via Williamson ether synthesis using an intramolecular reaction.

Show how the following compound can be synthesized utilizing an intramolecular reaction.

Propose a method to achieve the transformation shown below. This may involve multiple steps.

6-bromohex-1-ene → 2-methyloxane

Each —OH group of the following compound has a different acidity. What products are formed when the compound is treated with various amounts of NaH and then treated with a methylating agent? Explain.

(i) reaction using 1 eq. of NaH followed by 1 eq of CH₃I with heat

(ii) reaction using 2 eq. of NaH followed by 2 eq of CH₃I with heat

(iii) reaction using 3 eq. of NaH followed by 3 eq of CH₃I with heat

Provide a reaction scheme for the syntheses of the following ethers using Williamson ether synthesis. (Note: Use alcohols or phenols as the starting materials.)

(i) (ii)

Suggest how the following transformations can be achieved.

2-bromo-4-methylpentan-1-ol → 1,2-epoxy-4-methylpentane

Will the following transformation occur by producing a tosylate and then displacing it with an alkoxide? If so, show the reaction sequence. If not, explain why not and give an alternative reaction sequence that would work.

A student wanted to synthesize (S)-2-methoxypentane from (R)-pentan-2-ol using the Williamson ether synthesis.

Remembering that the Williamson ether synthesis involves S_N2 and works best with primary halides and tosylates, the student prepared methyl tosylate and sodium (R)-pent-2-oxide substrates and warmed them together. The reaction produced a high yield of 2-methoxypentane.

(i) What enantiomer of 2-methoxypentane was obtained? Rationalize how this particular enantiomer formed from the reaction performed.

(ii) What would have been the best synthetic scheme for producing (S)-2-methoxypentane?

(iii) Suggest a scheme involving tosylate formation and the Williamson ether synthesis that could be used to convert (R)-pentan-2-ol to (S)-2-methoxypentane.

Show how you would synthesize the following compound using the following two-step process:

(1) Use Grignard reagent to react with a carbonyl compound to give an alkoxide ion intermediate.

(2) Use this alkoxide to react with 1° or methyl alkyl halides to form the given ether products.

As starting materials, you may use any reactants containing 7 carbons or fewer.

Provide the steps required to produce 1-methyl-3-propoxycyclopentane from 3-methylcyclopentanol and propan-1-ol in good yield. You may use additional reagents if needed.

Propose the plausible synthesis of 1-ethoxy-1-methylcyclohexane through (i) alkoxymercuration-reduction and (ii) Williamson ether synthesis. If one method cannot be used to synthesize the desired product, explain why.

Show the plausible synthesis of 1-isopropoxy-1-methylcyclohexane through (i) alkoxymercuration-reduction and (ii) Williamson ether synthesis. If one method cannot be used to synthesize the desired product, explain why.

Propose the plausible synthesis of ((3-ethylpentan-3-yl)oxy)benzene through the following reactions:

(i) alkoxymercuration-reduction

(ii) Williamson ether synthesis.

If one method cannot be used to synthesize the desired product, explain why.

Show how you would synthesize (tert-butoxymethyl)benzene from phenylmethanol and 2-methylpropan-2-ol in good yield. You may use additional reagents if needed.

Provide synthetic steps to produce the following compound using the following two-step process:

(1) Use Grignard reagent to react with a carbonyl compound to give an alkoxide ion intermediate.

(2) Use this alkoxide to react with 1° or methyl alkyl halide to form the given ether products.

As starting materials, you may use any reactants containing 7 carbons or fewer.

Show the synthetic steps needed to produce the following compound using the following two-step process:

(1) Use Grignard reagent to react with a carbonyl compound to give an alkoxide ion intermediate

(2) Use this alkoxide to react with 1° or methyl alkyl halide to form the given ether products

As starting materials, you may use any reactants containing 7 carbons or fewer.

2,4-D is a compound found in Agent Purple. The deprotonation of 2,4-dichlorophenol with sodium hydroxide, followed by the reaction with 2-chloroacetic acid, yields this compound. Provide the equations for these reactions using bond-line structures.

For the given product, devise a synthesis using an intramolecular reaction.

Write the product formed in the reaction given below