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