Chapter 8
Reactions of Alcohols, Ethers,
Epoxides, and Thiols
Many reactions in this chapter
are extensions from chapter 7.
Strongly Basic Leaving Groups
Cannot Be Displaced
alcohols
Acid Converts the Poor Leaving Group
into a Good Leaving Group
Alcohols have to be protonated or converted into good leaving groups
SN2 chemistry
alcohols
The Reactions of Secondary and Tertiary Alcohols
with Hydrogen Halides are SN1 Reactions
alcohols
The Reactions of Primary Alcohols
with Hydrogen Halides are SN2 Reactions
alcohols
Why is It Important to Be Able
to Convert Alcohols to Alkyl Halides?
All SN2 reactions
alcohols
Other Methods to Convert
Alcohols into Alkyl Halides
NEW REACTIONS!
phosphorus tribromide & thionyl chloride
You do not need to know the mechanism of these reactions
alcohols
Sulfonate Esters in SN2 reactions
alcohols
A Sulfonate Ester is a good leaving group
alcohols
Stereochemical Considerations
2 inversions
1 inversion
alcohols
Two SN2 Reactions or
One SN2 Reaction?
inversion
inversion
inversion
Stereochemistry is important here.
alcohols
Dehydration of an Alcohol
Dehydration of an alcohol either E1 or E2
depending on the substitution of the alcohol
alcohols
Dehydration is a Reversible Reaction
The difference between concentrated and dilute acids
alcohols
Dehydration of Secondary and Tertiary
Alcohols are E1 Reactions
alcohols
Dehydration (E1) is a Regioselective
Reaction
The major product is the more stable alkene.
alcohols
Dehydration of a Primary Alcohol
is an E2 Reaction
alcohols
Dehydration is Stereoselective
The major product is the stereoisomer with the
largest groups on opposite sides of the double bond.
alcohols
A better way to eliminate an alcohol
Non-acidic conditions
alcohols
Ethers are alkylated alcohols
ethers
Ethers react with hydrogen halides
ethers
Ethers Are Common Solvents
Because They React Only with Hydrogen Halides
Common solvents
ethers
Devise a mechanism that accounts for the
following reaction
THF is a common organic solvent that is stable under many reaction
conditions except those including HCl, HBr, and HI. Under these strongly
acidic conditions, THF undergoes the following reaction. Draw a mechanism
that accounts for the formation of product using the curved arrow notation to
show all bond making and bond breaking.
ethers
Devise a mechanism that accounts for the
following reaction
Under these strongly acidic conditions (1 equivalent of HI), What would
happen with 2 equivalents of HI?
What mechanism is shown above?
ethers
Tert-butyl ethers are often used to reversibly
protect the hydroxyl group
When isobutylene gas is reacted with a compound containing a hydroxyl
group in the presence of a non-aqueous acid, a tert-butyl ether may be
formed as shown below. Devise a mechanism that accounts for the formation
of this product.
ethers
Tert-butyl ethers are often used to reversibly
protect the hydroxyl group
Start by remembering electrophilic addition of the proton to the alkene to
give the tert-butyl cation. The cation is attacked by the hydroyl group to give
the ether.
ethers
Tert-butyl ethers are often used to reversibly
protect the hydroxyl group
This reaction is reversible depending on conditions.
H+
(TFA)
ethers
Recall synthesis of an epoxide
from a per-acid
Naming epoxides: add oxide to the end of the alkene name.
For example, cyclohexene is converted to cyclohexene oxide when
reacted with m-chloroperbenzoic acid (mCPBA) in dichloromethane.
epoxides
Synthesis of an Epoxide from a
halohydrin intramolecular SN2
chlorohydrin
epoxides
Epoxides can be easily ring opened with S N2
or SN1 type chemistry because of ring strain
When the epoxide isnt symmetric
epoxides
The Acid-Catalyzed Mechanism
SN1-like
epoxides
If the Epoxide is Not Symmetrical,
Which Carbon Does the Nucleophile Attack?
The nucleophile attacks the more substituted epoxide carbon.
epoxides
Under Acidic Conditions the Nucleophile Attacks
the More Substituted Ring Carbon
epoxides
Under Neutral or Basic Conditions the Nucleophile Attacks the Less
Substituted Carbon
SN2-like
epoxides
Using Epoxides in Synthesis
P.T.
P.T. = proton transfer
epoxides
Forming a trans-1,2-Diol
enantiomers
1,2-diols
Forming a cis-1,2-Diol
: :
: :
Sulfur containing compounds
Sulfur containing compounds
Nomenclature of Thiols
Sulfur containing compounds
Chemistry of thiols
Acid/base & SN2
Thiols have pKa values of about 10.
The conjugate base form (thiolates) are excellent nucleophiles and less
prone to elimination chemistry
Sulfur containing compounds
Chemistry of thiols
Redox
Sulfur containing compounds
Chemistry of sulfides
Redox
Sulfur containing compounds
Polar aprotic solvents
SN2
Sulfur containing compounds
Sulfonate esters are good leaving
groups
Sulfur containing compounds
Secondary Alcohols can be
oxidized to ketones
Redox chemistry
Primary alcohols can be oxidized
to acids and aldehydes
aldehyde
Redox chemistry
Tertiary Alcohols Cannot Be Oxidized
to a Carbonyl Compound
Redox chemistry
