Chapter 14 – Ethers, Epoxides, and Sulfides
Many of these reactions are review from previous chapters (8, 10, 11), with only a few reactions being something you have not seen before.
Ethers are generally unreactive, commonly used as solvents for reactions, so there are very few reactions that occur with them. With epoxides,
keep in mind the stereochemistry and regiochemistry of the product! This is very important! I have underlined the reaction name for the
reactions you need to know, and bolded the reaction name that you need to know the mechanism for!
Synthesis of Ethers
Reaction
Williamson
ether
synthesis
(Ch 11)
Example (Mechanism)
An ether is formed by extracting a hydrogen is from an alcohol using a
base,(NaH is commonly used, NaOH can be used as well), forming an
alkoxide
The resulting alkoxide ion then reacts as a nucleophile, attacking an alkyl
halide, forming the ether.
Keep in mind pKa values! The base must be basic enough to extract the
hydrogen from the alcohol. The more acidic the alcohol, the faster the
reaction
Reactants, Reagent,
Products
Reactant- Alcohol
o
o
(can be either 1 , 2 ,
o
or 3 )
Reagent – A strong
+
base (Na ), and
then any
electrophile (alkyl
halide)
Product – alkoxide,
then an ether
Stereochemistry and
Regiochemistry
N/A
Important things to
note
- Know the entire
mechanism and
reagents used!
-Keep in mind pKa
values! A hydrogen
can’t be extracted
from a stronger acid!
-Will also compete
with E2 reactions!
Reaction by
oxymercur
ationdemurcatio
n Hg(OAc)2
(Ch 8)
-Hg(OAc)2 will split into Hg(OAc)
-Hg(OAc) will react with the alkene, to form a mercurinium ion, a three
membered ring with Hg. (Think of the bonds to Hg more of as partial
bonds)
-An alcohol will attack the mercurinium ion. The bond with the most
substituted carbon will break, with the ether forming on the most
substituted carbon, and the Hg(OAc) attached to the other carbon. The OH
and the Hg(OAc) will be on the opposite side of each other (Anti Addition)
NaBH4 will replace the Hg(OAc) with a hydrogen
The overall reaction is below. You don’t need to know the mechanism for
O.Chem 2 unlike O.Chem 1
Reactant – Alkene
Reagent – Hg(OAc)2,
an alcohol, than
NaBH4
Product – An ether
Stereochemistry- anti
addition – The
nucleophile (water or
alcohol) and the
hydrogen will add to
opposite sides of the
double bond
Regiochemistry –
Markovnikov addition
without
rearrangement. The
nucleophile will attack
the most substituted
carbon, and the partial
bond to the Hg(OAc)
bond will break.
However, a carbocation
on the alkane never
forms, so there is no
possibility for a
rearrangement.
-For O.Chem 2, don’t
need to know the
mechanism! You will
rarely get a question
regarding this reaction
-This forms
markovnikov’s
product. However,
because a carbocation
never really forms on
the alkane itself, no
rearrangement is
possible.
-Remember, the
nucleophile and
hydrogen add in an
anti-addition
(opposite
configurations)
Reactions with Ethers
Reaction
Example (Mechanism)
Alkyl
cleavage
with HI or
HBr
-An ether can react with an Acid halide, extracting the hydrogen, with the resulting
halide ion attacking the ether. Initially, 1 alkyl halide, and an alcohol is formed.
-The resulting alcohol is then reacted with another addition of HBr (similar to Ch 11
reaction), resulting in another alkyl halide.
-The overall reaction is shown below, with the total formation of 2 alkyl halides.
Note that it does not matter which alkyl halide is formed first, assuming both alkyl
halides are able to form.
Reactants, Reagent,
Products
Reactant- An ether
Reagent – HI or HBr (HCl
will give poor yields, but
could react as well). The
reactivity is
HI>HBr>>>HCl
Product – 2 products – (2
alkyl halides, with each
halide attached to each
substituent of the ether)
Note: during the
conversion of the alcohol
step, this cannot occur
with phenol group, only 1
alkyl halide will form,
phenol will remain an
alcohol
Important things to note
-Know the reaction and the
mechanism!
-2 alkyl halides are formed, if
possible
-Remember that phenol
can’t react any further!
-Know the reactivity of the
reaction as well! (The
reactivity is HI>HBr>>>HCl)
If an acid halide is reacting with an ether that is attached to a benzene ring, the alkyl
halide will form on the other substituent instead of the benzene ring. This will form
phenol and an alkyl halide. Phenol can’t react any further with an acid halide
because it can’t undergo an SN2 reaction, and will remain an alcohol.
Ether
autooxidation
An ether that is exposed to air will oxidize over time, forming peroxides. This
reaction is not important, but just interesting to note because they are explosive!
Reactant- An ether
Reagent – Air (O2) and a
lot of time (monthsyears)
Product – peroxides
-Not important at all, I doubt
you will be asked this
reaction
Synthesis of Epoxides
Reaction
Example (Mechanism)
Epoxidation
of alkenes
(Ch 8)
Remember from Chapter 8, an alkene can react with a peroxyacid
(Structure usually is –CO3H), forming an epoxide. This reacts in a syn
addition, with both sides of the epoxide forming in the same direction!
Formation
of epoxide
from a
halohydrin
(Ch 8, and
Ch 11)
-Remember from Ch 8, a halohydrin can form from an addition of a
halogen and water to an alkene. This adds in an anti-addition,
markovnikov addition, with the water and halogen attaching on opposite
sides, and the water attack the most substituted carbon
A base can come and extract a hydrogen from the alcohol, forming an
alkoxide. The alkoxide will then attack the halide carbon in a
intramolecular Williamson ether synthesis reaction, forming an epoxide
Reactants, Reagent,
Products
Reactant – Alkene
Reagent – Any
peracid (Acid with a
-CO3H structure) A
common one you
could see is
peroxyacetic acid,
or MCPBA (mchloroperoxybenzoi
c acid)
Product – An
epoxide
Stereochemistry and
Regiochemistry
Stereochemistry – Syn
addition. The bonds
attached to the
oxygen are on the
same stereochemistry
(both wedge, or both
dash)
Regiochemistry – no
specific
regiochemistry
ReactantHalohydrin (formed
by halogen + H2O
and alkene)
Reagent – Any base
Product – Epoxide
Stereochemistry – Syn
addition. The
halohydrin that is
originally formed is
initially in antistereochemistry.
However, after
reacting with a base,
the bonds of the
epoxide that is
formed is in syn
addition
Regiochemistry- No
specific Regiochemistry
since an epoxide is nonregiospecific
Important things to note
Don’t need to know the
mechanism but know the
reaction!. They like to ask
about epoxides
-Usually a dead giveaway
is the extra oxygen (–
CO3H), or MCPBA.
-Remember, it is a syn
addition (any
substituents already
attached will be the
opposite
stereochemistry)
Know the mechanism of
this reaction! (Don’t need
to know the mechanism
of the halohydrin
formation)
-Same stereochemistry
to the previous epoxide
reaction!
Reactions with Epoxides
Reaction
Example (Mechanism)
Acidcatalyzed
opening
of
epoxides
(Ch 8)
-In the acid catalyzed reaction of an epoxide, an epoxide is initially protonated
to activate the epoxide, making it a better electrophile
-Any weak nucleophile (water, alcohol, etc…) will react in a back-side attack on
the most substituted carbon. Note the stereochemistry and regiochemistry of
the reaction! The nucleophile will attack the MOST substituted carbon, with the
alcohol forming on the opposite side. The nucleophile and the alcohol form in
on opposite sides, in an anti-addition
-Another example is shown below. Be very careful with epoxide
stereochemistry! You will get an epoxide with a complex stereochemistry such as
the one listed below!
Reactants, Reagent,
Products
Reactant – An
epoxide
Reagent – H+ and
any weak
nucleophile
Product – Depends
on the nucleophile.
An alcohol will
always form on the
least substituted
side
Stereochemistry
and Regiochemistry
Stereochemistry –
Anti addition. The
nucleophile and the
alcohol are in
opposite
configurations
Regiochemistry –
Most substituted
carbon! Nucleophile
will react on the
most substituted
carbon. If water is
used, doesn’t
matter, but if an
alcohol is used, it
will attach on the
most substituted
carbon
Important things to
note
- Know this reaction
and the entire
mechanism! This
reaction is very
important!
-This mechanism only
occurs in an acidic
media! The acidic
media is used to make
the epoxide a better
electrophile so a weak
nucleophile can attack
it.
Basecatalyzed
ring
opening
of
epoxides
(Ch 10)
-In a basic catalyzed reaction, a strong and/or basic nucleophile, (NH3, grignard’s
reagent, OCH3, etc…), will react in a SN2 mechanism and attack the LEAST
substituted carbon due to less sterics involved, with the nucleophile and
alcohol forming again on opposite sides in an anti addition. The main difference
between a base catalyzed reaction and the acid catalyzed reaction is the
Regiochemistry! Acid catalyzed reacts on the MOST substituted carbon, base
catalyzed reacts on the LEAST substituted carbon. Both, however, react in an
anti-addition, with the alcohol and the nucleophile on opposite sides
-Here’s an example of an epoxide reacting with grignards with stereochemistry of
the substitutent present. The grignard reagent and the alcohol form on opposite
sides!
Reactant- Epoxide
Reagent – A strong
nucleophile! (usually
basic, but not always,
such as grignards)
Product –An alcohol
formed on the more
substituted carbon,
and a substituent on
the less substituted
carbon
Stereochemistry-Anti-Addition: The
nucleophile will
attack and bond on
the opposite side of
the epoxide, with the
OH placed opposite
the nucleophile
RegiochemistryLEAST substituted
carbon! The
nucleophile will
attack the LEAST
substituted carbon
due to sterics.
- Know this reaction
and the entire
mechanism! This
reaction is very
important
-Know the
stereochemistry and
the Regiochemistry!
-Only occurs with
strong and/or basic
nucleophiles!