CHAPTER NINE: ALCOHOLS, ETHERS AND EPOXIDES
1. Structure/ Properties 9.4
a. Relative Boiling points: hydrogen bonding
b. Nomenclature
c. Acid/Base behavior (review)
i. pKa of MeOH ≈ 16
ii. Acidity trends with branching near C-OH: branching hinders anion
solvation
iii. Basicity of neutral alcohol (pKb(A-) = 14.0 - pKa(HA))
iv. Basicity of alkoxide ion
2. Preparation of Alcohols, ethers and epoxides 9.6
a. From Alkyl Halides with weakly basic nucleophiles (watch for
rearrangement, E2)
b. The Williamson Ether synthesis
o Alkoxide + 1° RX
o Epoxides from intramolecular Williamson 9.7
3. Reactivity of Alcohols
a. Formation of Alkoxide ion review
i. With Bronsted base (NaOH, NaH)
ii. With alkali metals (Na, Li)
b. Formation of alkenes 9.8
i. with non-nucleophilic acids (H2SO4, H3PO4)
o Via E1 for 2° and 3° alcohols
o Carbocation rearrangement
o Concerted loss of LG and rearrangement for 1° alcohols :
Question 9.82
o Via E2 for 1° alcohols in absence of rearrangement
ii. With POCl3 to form alkenes 9.10
o E2 mechanism/No rearrangement
c. Formation of alkyl halides
i. With HX
o Mechanism: hydronium as leaving group
o Carbocation Rearrangement
ii. With Thionyl chloride SOCl2 to form alkyl chlorides
o Mechanism/ no rearrangement/ inversion of configuration
iii. With phosphorus tribromide PBr3 to form alkyl bromides
o Mechanism/ no rearrangement/ inversion of configuration
d. Formation of Alkyl tosylates by reaction with sulfonyl chlorides
o Mechanism/ retention of configuration
o Subsequent reaction of alkyl tosylates with nucleophiles/bases:
9.12C: Can’t use acid and any nucleophile!
e. Formation of ketones or aldehydes: Chapter 12 Section 12.12
i. Oxidation of 2° alcohols to ketones with chromic acid
ii. Oxidation of 1° alcohols to carboxylic acids with chromic acid
iii. Oxidation of 1° alcohols to aldehydes with Pyridinium
Chlorochromate (PCC)
4. Reactivity of Ethers
a. Inert under Basic Conditions
b. Cleavage under highly Acidic conditions ( SN1 for 2° and 3°)
o Mechanism: alkylonium ion as leaving group
o Rearrangement
ii. With HX :9.14
iii. With H2SO4, H2O
Note: Book omits hydrolysis of ether with hydronium ion generated by
sulfuric acid in water- you must know this reaction!
c. Autooxidation to form explosive hydroperoxides
5. Epoxides
a. Synthesis from halohydrins in base: internal SN2 review
b. Reactivity: 9.15
i. Cleavage in Acid: “SN1 like”: Nucleophile to more substituted carbon
with inversion (examples: HBr, H3O+, CH3OH2+)
ii. Cleavage in Base: “SN2 like” Nucleophile to less crowded carbon with
inversion (examples: CH3NH2, CH3O–, HO–, SH–, CN–)
iii. Reduction to alcohols with hydride reducing agent LiAlH4 :Chapter
12, Section 12.6
LEARNING OUTCOMES:
 Use knowledge about nucleophilic substitution reactions to predict products of
reaction with ethers and their mechanism of formation.
 Predict the stereochemistry and optical activity of a product from an understanding of
its mechanism of formation.
 Propose a reaction or sequence of reactions to produce a target ether, alcohol or
epoxide in high yield.
 Predict the products of reactions involving alcohols, ethers and epoxides with
common reagents.
 Predict the likelihood of carbon skeleton rearrangement under a given set of
conditions.
 Predict the relative acidity of alcohols within a functional group class and compared
to other functional groups.
 Predict the relative boiling points of alcohols within a functional group class and
compared to other functional groups.
 Use curved-arrow formalism to depict the step-wise mechanism of reactions
involving alcohols whenever they are well understood.
 Predict the stereochemistry and optical activity of a product from an understanding of
its mechanism of formation.
 Recognize structural features of a molecule that are key to its stability and reactivity.
 Propose a reaction or sequence of reactions to produce a target alcohol in high yeild.
SAMPLE EXAM PROBLEMS:
1. Propose a reaction/ sequence of reactions to effect the following stereoselective
reaction in high yield:
(S)
(S)
OH
Br
2. Consider the reaction below and tell why it DOES NOT provide high yields of the
products shown. Draw alternative products, if any are formed.
OCH3
OH
CH3OH
H2SO4
3. Give the step-wise mechanism of the following chemical transformation using curved
arrow formalism. Show every step in sequence, including proton transfers and draw
all non-bonded electrons and formal charges.
O
OH
H2O
H2SO4
OH
4. Give the major organic product of the following reaction and include all
stereoisomers formed:
1. LiAlD4
O
(R)
2. H3O+
5. Give the step-wise mechanism of the following chemical transformation using curved
arrow formalism. Show every step in sequence, including proton transfers and draw
all non-bonded electrons and formal charges.
O
H2O
OH
H2SO4
OH
6. Consider the reaction below and answer the following:
A. Why doesn’t it provide high yields of the product shown?
B. Propose an alternative synthesis of the product (i.e How might the product be
synthesized in high yield via a different reaction).
Br
ONa
+
O