Synthesis of Ethers

There are several methods for the synthesis of ethers starting from alcohols:
 
 

Acid catalyzed condensation of Alcohols
Williamson Ether synthesis (Ch16)
Alkoxymercuration-demercuration (review)
Ring opening of Epoxides

Synthesis of Ethers via Acid-catalyzed Condensation of Alcohols

Summary

• Reagents typically H₂SO₄ and heat.
• In general, typically limited to symmetrical ethers of primary alcohols.
• The method is not suitable for unsymmetrical ethers.
• The substitution involves the O nucleophile of one alcohol attacking the electrophilic C in the other displacing a water molecule.

Questions:
Why can this reaction be termed a condensation reaction ? 
Why is the reaction unsuitable for unsymmetrical ether synthesis ? 

Related reactions

• Williamson ether synthesis

MECHANISM FOR ALCOHOL CONDENSATION TO GIVE AN ETHER
Step 1: An acid/base reaction. Protonation of the alcoholic oxygen to make a better leaving group. This step is very fast and reversible.  The lone pairs on the oxygen make it a Lewis base.
Step 2: The O of the second alcohol molecule functions as the nucleophile and attacks to displace the good leaving group, a neutral water molecule, by cleaving the C-O bond. This creates an oxonium ion intermediate.
Step 3: Another acid / base reaction. The proton is removed by a suitable base (here a water molecule, ROH is another alternative) to give the ether product.

Williamson Ether Synthesis

Summary

• Reagents : typically use Na metal as the base to generate the alkoxide then add the alkyl halide.
• Since the reaction is S_N2, the halide should be methyl or primary.
• Alkoxide character (primary, secondary or tertiary) is less important.
• This reaction is suitable for either symmetrical or unsymmetrical ethers.
• The method could also be used for cyclic ethers.

Questions:
What reaction is likely to interfere if the halide is tertiary ?
Can you write a balanced equation for the reaction of sodium metal with the alcohol ? 
What is the oxidation state and charge of the sodium metal ? 
What makes the methyl and primary halides most suitable ? 

Related Reactions

• Ether synthesis via Alcohol condensation
• Substitution Reactions of Alkyl Halides

MECHANISM OF THE WILLIAMSON ETHER SYNTHESIS
The alkoxide functions as the nucleophile and attacks the electrophilic C of the alkyl halide displacing the bromide and creating the new C-O bond.

Alkoxymercuration-Demercuration of Alkenes
(review of Chapter 14)

Summary

• Overall transformation C=C to H-C-C-OR
• Typical reagents are mercury acetate, Hg(OAc)₂ in ROH / THF
• Unfortunately, mercury compounds are generally quite toxic
• Regioselectivity predicted by Markovnikov's rule
• The reaction is not stereoselective
• Reaction proceeds via the formation of a cyclic mercurinium ion

• The mercurinium ion is opened by the attack of alcohol to complete the alkoxymercuration.
• When the alcohol attacks, it does so at the more highly substituted carbon.
• Demercuration is effected by a reduction using sodium borohydride, NaBH₄

• Are rearrangements a problem with this process ? 
• Why does the alcohol attack the more highly substituted carbon ? 

• Oxymercuration-demercuration of alkenes (Ch 14)