Ether Synthesis and Reactions

Question 1

Williamson Ether Synthesis: Reactants

Answer 1

ROH reacts with:

1. Na⁺H^-, THF
   ——————————->
2. 1°RX

Question 2

Williamson Ether Synthesis: Process

Answer 2

1) NaH deprotonates ROH to produce an alkoxide ion (RO-) and release H₂ gas

2) The alkoxide ion reacts with 1°RX

==> SN2 mechanism = Alkoxide attacks halogen carbon causing the halogen knock off

–> Produces an ether and NaX

Question 3

What is the limitation of Williamson ether synthesis?

Answer 3

Can only form an ether from reaction with a 1°RX

Question 4

Alkoxymercuration: Reactants

Answer 4

Alkene reacts with:

1. Hg(OAc)₂, ROH
   ——————————>
2. NaBH₄, NaOH

Question 5

Alkoxymercuration: Process

Answer 5

1) Alkene attacks Hg to form the mercurinium ion

2) ROH attacks MOST SUB side of the mercurinium ion
==> Backside attack = stereochem inversion

3) NaBH₄, NaOH swaps Hg out for H

4) OAc^- deprotonates the added ROH⁺

–> An ether forms!

Question 6

Acid-Cat Alcohol Dehydration: Reactants

Answer 6

2 eq. 1°ROH + H₂SO₄
———————————————>

Question 7

Acid-Cat Alcohol Dehydration: Process

Answer 7

1) One of the 1°ROH deprotonates H₂SO₄ to create an H₂O LG

2) H₂O LG spontaneously leaves forming carbocation (rearrangement if needed)

3) SECOND 1°ROH attacks the carbocation

4) HSO₄^- deprotonates the ROHR to produce an ether and reform the acid catalyst!

Question 8

What is the issue with acid catalyzed alcohol dehydration?

Answer 8

If you use a mix of alcohols in the reaction, you will get a mixture of products and the resultants will not be predictable

–> This form of ether synthesis really only works when using 2 eq. of the SAME alcohol to produce a symmetrical ether (because this way the product is predictable!)

Question 9

What is the reaction ethers undergo?

Why are there two variants of this reaction?

Answer 9

Ethers undergo ACIDIC CLEAVAGE

–> Depending on the degree of the R groups on the ether, the reaction will undergo a different mechanism!!

ONLY 1°/2° R grps. present = SN2 mechanism

A 3°R grp. present = SN1 mechanism! (carbocation forms)

Question 10

Ether (1°/2° R grps.) Acidic Cleavage: Reactants and process

Answer 10

1°/2° Ether + HX
————————–>

1) Ether oxygen deprotonates HX to form ROH⁺R

2) X^- attacks the LEAST SUB R grp in a backside attack (SN2) mechanism

==> Alkyl halide (inverted stereo if applicable) + alcohol forms

Question 11

Ether (3° R grp. present) Acidic Cleavage: Reactants and process

Answer 11

3° containing Ether + HX
———————————–>

1) Ether oxygen deprotonates HX to form ROH⁺R

2) ROH spontaneously dissociates! (Takes “with it” the R group that would not form the better carbocation)
==> ROH + carbocation-R

3) Carbocation rearrangement occurs if needed

4) X^- attacks the carbocation to form an alkyl halide

==> Overall: forms alykyl halide + alcohol