Title: Ethers, Epoxides, and Sulfides
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2013 Pearson Education, Inc. Chapter 14 1
Chapter 14
Lecture
Organic Chemistry ,
8th Edition
L. G. Wade, Jr.
Ethers, Epoxides, and
Thioethers
> 2013 Pearson Education, Inc.
Rizalia Klausmeyer
Baylor University
Waco, TX 2013 Pearson Education, Inc. Chapter 14 2
## Ethers
Formula is ROR where R and R are
alkyl or aryl groups.
Symmetrical or unsymmetrical
Dr.Suaad Audat 2013 Pearson Education, Inc. Chapter 14 3
## Structure and Polarity
Oxygen is sp 3 hybridized.
Bent molecular geometry.
Tetrahedral C OC angle is 110 .
Polar C O bonds.
Dr.Suaad Audat 2013 Pearson Education, Inc. Chapter 14 4
## Boiling Points
Similar to alkanes of comparable molecular weight.
Dr.Suaad Audat 2013 Pearson Education, Inc. Chapter 14 5
## Hydrogen Bond Acceptor
Ethers cannot hydrogen bond with other ether molecules,
so they have a lower boiling point than alcohols .
Ether molecules can hydrogen bond with water and alcohol
molecules or molecules containing N-H groups .
They are hydrogen bond acceptors .
Dr.Suaad Audat 2013 Pearson Education, Inc. Chapter 14 6
## Ethers as Solvents
Ethers are widely used as solvents because
they can dissolve nonpolar and polar
substances.
they are unreactive toward strong bases.
their relatively low boiling points simplify their
evaporation from the reaction products
> Dr.Suaad Audat 2013 Pearson Education, Inc. Chapter 14 7
## Solvation of Ions with Ether
An ionic substance such as lithium iodide is moderately
soluble in ethers because the small lithium cation is
strongly solvated by the ether s lone pairs of electrons.
Unlike alcohols, ether cannot serve as hydrogen bond
donors, so they do not solvate small anions well.
Dr.Suaad Audat 2013 Pearson Education, Inc. Chapter 14 8
## Ether Complexes
Grignard reagents : Complexation of
an ether with a Grignard reagent
stabilizes the reagent and helps keep it
in solution.
Electrophiles : The ether s nonbonding
electrons stabilize the borane (BH 3). O BHHH+ _BH 3 THF
Dr.Suaad Audat 2013 Pearson Education, Inc. Chapter 14 9
## Crown Ether Complexes
Crown ethers can complex metal cations in the center of the
ring.
The size of the ether ring will determine which cation it can
solvate better.
Complexation by crown ethers often allows polar inorganic
salts to dissolve in nonpolar organic solvents.
Dr.Suaad Audat 2013 Pearson Education, Inc. Chapter 14 10
## Common Names of Ethers
Name the two alkyl groups attached to the
oxygen and add the word ether .
Name the groups in alphabetical order .
Symmetrical : Use dialkyl or just alkyl .
diethyl ether or
ethyl ether t-butyl methyl ether
CH3CH2 O CH2CH3 CH3 O C
CH3
CH3
CH3
Dr.Suaad Audat 2013 Pearson Education, Inc. Chapter 14 11
## IUPAC Names: Alkoxy Alkanes
## Names
The more complex alkyl group is the alkane
name . The small group (with the oxygen)
becomes an alkoxy group .
2-Methoxy -2-methylpropane Methoxycyclohexane
CH3 O C
CH3
CH3
CH3
O CH3
Dr.Suaad Audat 2013 Pearson Education, Inc. Chapter 14 12
## Additional Problems
Dr.Suaad Audat 2013 Pearson Education, Inc. Chapter 14 13
## Williamson Ether Synthesis
This method involves an SN2 attack of the alkoxide on
an unhindered primary halide or tosylate .
The alkoxide is commonly made by adding Na, K, or
NaH to the alcohol
Dr.Suaad Audat
SN2 2013 Pearson Education, Inc. Chapter 14 14
Examples of the Williamson
Synthesis
Dr.Suaad Audat 2013 Pearson Education, Inc. Chapter 14 15
## Phenyl Ethers
Phenoxide ions are easily produced by using
sodium hydroxide because the Phenols are more
acidic than aliphatic alcohols .
Phenyl halides or tosylates cannot be used in the
Williamson ether synthesis .
A phenol can be used as the alkoxide fragment only
not halide fragment . Dr.Suaad Audat 2013 Pearson Education, Inc. Chapter 14 16
(a) Why is the following reaction a poor method for the synthesis of t-butyl propyl ether?
(b) What would be the major product from this reaction?
(c) Propose a better synthesis of t-butyl propyl ether.
(a) The desired S N2 reaction cannot occur on the tertiary alkyl halide .
## Solved Problem 1
Solution
Dr.Suaad Audat
(b) The alkoxide ion is a strong base as well as a nucleophile, and elimination
prevails 2013 Pearson Education, Inc. Chapter 14 17
(c) A better synthesis would use the less hindered alkyl group as the S N2 substrate
and the alkoxide of the more hindered alkyl group.
## Solved Problem 1 (Continued)
Solution (Continued)
Dr.Suaad Audat 2013 Pearson Education, Inc. Chapter 14 18
# HINT
To convert two alcohols to an ether, convert
the more hindered alcohol to its alkoxide.
Convert the less hindered alcohol to its
tosylate (or an alkyl halide). Make sure the
tosylate (or halide) is a
good S N2 substrate.
Dr.Suaad Audat 2013 Pearson Education, Inc. Chapter 14 19
## Additional Problems
Dr.Suaad Audat 2013 Pearson Education, Inc. Chapter 14 20
## Alkoxymercuration
## Demercuration Reaction
Use mercuric acetate with an alcohol .
Alkoxymercuration adds the OR group of the alcohol to
the more substituted carbon atom of the C=C double
bond Dr.Suaad Audat 2013 Pearson Education, Inc. Chapter 14 21
## Cleavage of Ethers by HBr and
## HI
Ethers are unreactive, which makes them ideal solvents
for a lot of different reactions .
They can be cleaved by heating with concentrated HBr
and HI .
Reactivity : HI > HBr
A protonated ether can undergo substitution with an
alcohol serving as a neutral leaving group by either SN1 or
SN2 mechanisms depend on the nature of alkyl groups
attached to the oxygen .
Dr.Suaad Audat 2013 Pearson Education, Inc. Chapter 14 22
## Mechanism of Ether Cleavage
Step 1: Protonation of the oxygen .
Step 2: The halide will attack the carbon and
displace the alcohol via SN2 mechanism if alkyl
groups R and/or R are primary or secondary, but
if R or R is tertiary cleavage occur via SN1
mechanism
Dr.Suaad Audat 2013 Pearson Education, Inc. Chapter 14 23
## Mechanism of Ether Cleavage
Step 3: The alcohol reacts further with the acid to
produce another mole of alkyl halide.
This does not occur with aromatic alcohols
(phenols).
Dr.Suaad Audat 2013 Pearson Education, Inc. Chapter 14 24
## Ether cleavage: an S N2 reaction:
Dr.Suaad Audat 2013 Pearson Education, Inc. Chapter 14 25
## Ether cleavage: an S N1 reaction:
Dr.Suaad Audat 2013 Pearson Education, Inc. Chapter 14 26
## Phenyl Ether Cleavage
Phenol cannot react further to become a halide
because an SN2 reaction cannot occur on an
sp 2 carbon .
Dr.Suaad Audat 2013 Pearson Education, Inc. Chapter 14 27
## Autoxidation of Ethers
In the presence of atmospheric oxygen, ethers slowly oxidize
to hydroperoxides and dialkyl peroxides.
Both are highly explosive.
Precautions:
Do not distill to dryness.
Store in full bottles with tight caps.
Dr.Suaad Audat 2013 Pearson Education, Inc. Chapter 14 28
## Alcohol -Protecting Groups
If the molecule has more than one functional
group, sometimes their reactivity can interfere
with the desired reaction .
Dr.Suaad Audat 2013 Pearson Education, Inc. Chapter 14 29
## Silyl Ethers as Protecting Groups
## for alcohol
Resistant to some acids, bases, and oxidizing
agents.
More easily formed and more easily hydrolyzed.
These properties used as protecting groups for
alcohols.
Dr.Suaad Audat 2013 Pearson Education, Inc. Chapter 14 30
## Silyl Ethers as Protecting Groups
Protecting the alcohol as a silyl ether will ensure
the Grignard will react with the carbonyl .
The silyl ether group can be removed in aqueous
or organic solvents .
Dr.Suaad Audat 2013 Pearson Education, Inc. Chapter 14 31
## Silyl Ethers as Protecting Groups
Dr.Suaad Audat 2013 Pearson Education, Inc. Chapter 14 32
## Cyclic Ethers (Heterocycles)
Heterocyclic: Oxygen is part of the ring.
Epoxides (oxiranes) H2C CH 2
O
Oxetanes O
Furans (Oxolanes THF )OO
Pyrans (Oxanes THP )OO
Dioxanes OO
Dr.Suaad Audat 2013 Pearson Education, Inc. Chapter 14 33
## Epoxide Nomenclature
Name the starting alkene and add oxide.
The oxygen can be treated as a substituent (epoxy) on the
compound. Use numbers to specify position.
Dr.Suaad Audat 2013 Pearson Education, Inc. Chapter 14 34
## Epoxide Nomenclature
## (Continued)
The three -membered oxirane ring is the parent
(oxygen is 1, the carbons are 2 and 3).
Substituents are named in alphabetical order.
Dr.Suaad Audat 2013 Pearson Education, Inc. Chapter 14 35
## Synthesis of Epoxides
Peroxyacids (peracids ) are used to convert alkenes to epoxides .
Most commonly used peroxyacid is meta -chloroperoxybenzoic
acid (MCPBA) .
The reaction is carried out in an aprotic solvent to prevent the
opening of the epoxide .
Dr.Suaad Audat
1. Peroxyacid Epoxidation 2013 Pearson Education, Inc. Chapter 14 36
## Selectivity of Epoxidation
The most electron -rich double bond reacts faster, making selective
epoxidation possible .
The epoxidation takes place in a one -step, stereospecific reaction that
maintains the stereochemistry of any substituents on the double bond .(cis
or trans substituents remain the same .
When forming epoxide that is chiral, always racemic mixture will be
formed because the epoxide can b formed on either face of the alkene with
equal likehood . Dr.Suaad Audat
## Synthesis of Epoxides 2013 Pearson Education, Inc. Chapter 14 37
2. Halohydrin Cyclization
If an alkoxide and a halogen are located in the
same molecule, the alkoxide may displace a halide
ion and form a ring .
Treatment of a halohydrin with a base leads to an
epoxide through this internal SN2 attack .
Dr.Suaad Audat
## Synthesis of Epoxides 2013 Pearson Education, Inc. Chapter 14 38
## Epoxides via Halohydrins
Dr.Suaad Audat 2013 Pearson Education, Inc. Chapter 14 39
Acid -Catalyzed Opening of Epoxides in
Water
Step 1: Protonation of the oxygen to form a strong electrophile .
Step 2: Water attacks the protonated epoxide and open the ring (S N2)
attack. Anti stereochemistry results from the back -side attack
Step 3: Deprotonation of the trans -1,2 -diol
Dr.Suaad Audat 2013 Pearson Education, Inc. Chapter 14 40
Acid -Catalyzed Opening of
Epoxides in Alcohol Solution
A molecule of alcohol acts as the nucleophile and
attacks and opens the epoxide .
This reaction produces an alkoxy alcohol with anti
stereochemistry .
Dr.Suaad Audat 2013 Pearson Education, Inc. Chapter 14 41
## Ring Opening with Hydrohalic
## Acids
After protonation the halide ion attacks the
protonated epoxide.
The halohydrin initially formed reacts further
with HX to give a 1,2 -dihalide.
> Dr.Suaad Audat 2013 Pearson Education, Inc. Chapter 14 42
Base -Catalyzed Opening of
Epoxides
The hydroxide ion attacks and opens the ring in an
SN2 process .
The diol is obtained after protonation of the
alkoxide with water . Dr.Suaad Audat 2013 Pearson Education, Inc. Chapter 14 43
## Ring Opening in Base
An epoxide is higher in energy than an acyclic ether by
about 25 kcal/ mol ring strain .
Release of the ring strain makes the opening of an epoxide
thermodynamically favored .
Dr.Suaad Audat 2013 Pearson Education, Inc. Chapter 14 44
## Regioselectivity of Epoxidation
Dr.Suaad Audat
Under basic conditions, the
alkoxide ion simply attacks the
less hindered carbon atom in an
SN2 displacement.
Acid -catalyzed : The nucleophile
(solvent ) adds to the more substituted
carbon, which bears more + charge 2013 Pearson Education, Inc. Chapter 14 45
## Regioselectivity of Epoxidation
Dr.Suaad Audat
Acid -catalyzed : The nucleophile
(solvent ) adds to the more substituted
carbon, which bears more + charge 2013 Pearson Education, Inc. Chapter 14 46
Predict the major products for the reaction of 1-methyl -1,2 -epoxycyclopentane with
(a) sodium ethoxide in ethanol
(b) H 2SO 4 in ethanol
(a) Sodium ethoxide attacks the less hindered secondary carbon to give ( E)-2-ethoxy 1
methylcyclopentanol .
(b) Under acidic conditions, the alcohol attacks the more electrophilic tertiary carbon atom
of the protonated epoxide. The product is ( E)-2-ethoxy -2-methylcyclopentanol.
## Solved Problem 2
Solution
Dr.Suaad Audat 2013 Pearson Education, Inc. Chapter 14 47
## Reaction of Epoxides with
## Grignard and Organolithiums
Strong bases, such as Grignards and organolithiums ,
open the epoxide ring by attacking the less hindered
carbon.
Dr.Suaad Audat 2013 Pearson Education, Inc. Chapter 14 48
## Additional Problems
Dr.Suaad Audat 2013 Pearson Education, Inc. Chapter 14 49
## Biosynthesis of Steroids
Role of squalene in the biosynthesis of steroids . The biosynthesis of steroids starts with
epoxidation of squalene to squalene -2,3-epoxide . The opening of this epoxide promotes
cyclization of the carbon skeleton under the control of an enzyme . The cyclized intermediate
is converted to lanosterol, then to other steroids . 2013 Pearson Education, Inc. Chapter 14 50
Thioethers
RSR, analog of ether
Name sulfides like ethers, replacing sulfide for ether in the
common name, or alkylthio for alkoxy in the IUPAC system.
Thiols and Thiolates
Thioethers are easily synthesized by the Williamson
ether synthesis using a thiolate ion as the
nucleophile.
> Dr.Suaad Audat 2013 Pearson Education, Inc. Chapter 14 51
Sulfides are easily oxidized to sulfoxides and sulfones .
Sulfides react with unhindered alkyl halides to give sulfonium salts.
CH3 S CH3
H2O2
CH3COOH CH3 S CH3
O
CH3COOH
H2O2 CH3 S CH3
O
O
+C H 3 S C H 3 C H 3 I C H 3 S C H 3
C H 3
+
I
_
Sulfide Reactions
Thioethers as Reducing Agents
Because sulfides are easily oxidized, they are often used as mild reducing agents.
Dr.Suaad Audat 2013 Pearson Education, Inc. Chapter 14 52
Dr.Suaad Audat 2013 Pearson Education, Inc. Chapter 14 53
MECHANISM?????
Dr.Suaad Audat