CH 14 Klein Ethers, Epoxides, Sulfides

14.
1 Introduction to Ethers
An ether group includes an oxygen atom that
is bonded to TWO R groups:
R groups can be alkyl, aryl, or vinyl groups.

Would the compound below be considered an
ether?
Copyright 2012 John Wiley &

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Klein, Organic Chemistry 1e
14.1 Introduction to Ethers

Compounds containing ether groups are
quite common.

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14.2 Naming Ethers

Common names are used frequently:
1. Name each R group.
2. Arrange them alphabetically.
3. End with the word ether.

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14.2 Naming Ethers

IUPAC systematic names are often used as
well:
1. Make the larger of the R groups the parent
chain.
2. Name the smaller of the R groups as an alkoxy
substituent.

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14.2 Naming Ethers

Name the following molecule.
Draw the structure for (R)-1methoxycyclohexen-3-ol.

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14.3 Structure and Properties

of Ethers
The bond angle in ethers is very similar to
that found in water and in alcohols.
Is the oxygen atom in an ether sp3, sp2, or sp

hybridized?
How do the R groups affect the bond angle?
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of Ethers
In Chapter 13, we learned that due to
hydrogen-bonding (H-bonding), alcohols
have relatively high boiling points.
What is the maximum number of H-bonds an

alcohol can have?
Draw an H-bond between an ether and an
alcohol.
What is the maximum
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number Klein,
of H-bonds
an
Organic Chemistry
1e
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of Ethers
In Chapter 13, we learned that due to
hydrogen-bonding (H-bonding), alcohols
have relatively high boiling points.
Would you expect the boiling point of an

ether to be elevated similar to alcohols?
WHY or WHY not?
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of Ethers
Explain the boiling point trends below using
all relevant intermolecular attractions.
Trend 1:
Trend 2:

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of Ethers
Ethers are often used by organic chemists as
solvents:
Relatively low boiling points allow them to be
evaporated after the reaction is complete.
Their dipole moment allows them to stabilize
charged or partially charged transition states.
HOW?
. They are NOT protic. WHY is that an advantage
for a solvent in many reactions?

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14.4 Crown Ethers

Metal atoms with a full or partial positive
charge can be stabilized by ether solvents.
Ethers are generally used as the solvent in
Grignard reactions.
Give another reason why an ether makes a

good solvent in this reaction.
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14.4 Crown Ethers

Crown ethers have been shown to form
especially strong attractions to metal atoms.
WHY?
Note how many carbon atoms separate the

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oxygen.
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14.4 Crown Ethers

The size of the metal must match the size of
the crown to form a strong attraction.
18-crown-6 fits a K+ ion just right.

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14.4 Crown Ethers

Normally metal ions are not soluble in low
polarity solvents. WHY?
The crown ethermetal complex should
dissolve nicely in low polarity solvents. WHY?
Imagine how a crown ether could be used to
aid
reactions
between ions
(especially anions) and low
polarity organic
substrates.

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14.4 Crown Ethers

The F ion below is ready to react because
the K+ ion is sequestered by the crown ether.
Without the crown ether, the solubility of KF

in benzene is miniscule.
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14.4 Crown Ethers

Generally, the F ion is not used as a
nucleophile because it is strongly solvated by
polar solvents.
Such solvation greatly reduces its
nucleophilic strength.
In the presence of the crown ether and in a
nonpolar solvent, the F ion is soluble enough
that it can readily attack an electrophile.

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14.4 Crown Ethers

Smaller crown ethers bind smaller cations.
Practice with CONCEPTUAL CHECKPOINT

14.4.
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14.5 Preparation of Ethers

Diethyl ether is prepared industrially by the
acid-catalyzed dehydration of ethanol.
How is it a dehydration?
Can this method be used to make
asymmetrical ethers?

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The Williamson ether synthesis is a viable
approach for many asymmetrical ethers.
What happens to the halide?

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The Williamson ether synthesis is a viable
approach for many asymmetrical ethers.
The alkoxide that forms in step 1 is also a

strong base.
Are elimination products likely for methyl,
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Organic Chemistry 1e
primary, secondary,
or tertiaryKlein,
alkyl
halides?
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Use the Williamson ether approach to
prepare MTBE.
Consider a retrosynthetic disconnect on the

t-butyl side.
It is better to make your retrosynthetic
-21 methyl side.Klein,
Organic Chemistry 1e
disconnect on 14the
WHY?
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Use the Williamson ether approach to
synthesize the following molecule.

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Recall from Section 9.5 that oxymercurationdemercuration can be used to synthesize
alcohols.
Is the addition Markovnikov or antiMarkovnikov?

Is the addition syn or anti?
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Similarly, alkoxymercuration-demercuration
can be used to synthesize ethers.
Is the addition Markovnikov or antiMarkovnikov?

Is the addition syn or anti?
Practice CONCEPTUAL CHECKPOINTs 14.814 -24
14.10.
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14.6 Reactions of Ethers

As we mentioned earlier because they are
aprotic, ethers are generally unreactive.
However, ethers can react under the right
conditions.
Consider the ether below.
Where are the most reactive sites?

Is it most likely to react as an acid, base,
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nucleophile, electrophile,
etc.? Klein, Organic Chemistry 1e
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Ethers can undergo acid-promoted cleavage.

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Draw a complete mechanism and predict the
products for the following acid-promoted
cleavage.

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To promote cleavage, HI and HBr are
generally effective.
HCl is less effective, and HF does not cause
significant cleavage.
Explain the trend above considering the
relative strength of the halide nucleophiles.
Why is the cleavage considered acidpromoted rather than acid-catalyzed?
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14.11.
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Predict products for the reaction below, and
draw a complete mechanism.

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Recall from Section 11.9 that ethers can
undergo autooxidation.
Hydroperoxides can be explosive, so

laboratory samples of ether must be
frequently tested for the presence of
hydroperoxides before they are used.
The autooxidation occurs through a free
radical mechanism.
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Recall that the net reaction is the sum of the

propagation steps:

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14.7 Naming Epoxides

For cyclic ethers, the size of the ring
determines the parent name of the molecule.
Oxiranes are also known as epoxides.

Which cyclic ether system do you think is
most reactive? WHY?
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An epoxide can have up to 4 R groups.
Although they are unstable, epoxides are

found commonly in nature.

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There are two methods for naming epoxides:

1. The oxygen is treated as a side group, and two
numbers are given as its locants.
2. Oxirane is used as the parent name.

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Name the molecules below by both methods
if possible.
Practice CONCEPTUAL CHECKPOINTs 14.12

14 -36
and 14.13.
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14.8 Preparation of Epoxides

Recall from Section 9.9 that epoxides can be
formed when an alkene is treated with a
peroxy acid.
MCPBA and peroxyacetic acid are most

commonly used.

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Recall that the process is stereospecific.

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Epoxides can also be formed from
halohydrins.
What is a halohydrin?
How are halohydrins formed from alkenes?
When a halohydrin is treated with NaOH, a
ring-closing reaction can occur.

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Assess the overall stereochemistry of the
epoxidation that occurs through the
halohydrin intermediate.
Practice with SKILLBUILDER 14.3.

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14.9 Enantioselective
Epoxidation
The epoxidation methods we have discussed
so far are NOT enantioselective.
Draw the products.

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Epoxidation
The epoxidation forms a racemic mixture
because the flat alkene can react on either
face.

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Epoxidation
To be enantioselective at least one of the
reagents (or the catalyst) in a reaction must
be chiral.
The Sharpless catalyst forms such a chiral
complex with an allylic alcohol.

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Epoxidation
The desired epoxide can be formed if the
right catalyst is chosen. Note the position of
the OH group.
How does the catalyst

favor just
one
epoxide
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Klein,
Organic
Chemistry 1e
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14.10 Ring-opening of
Epoxides
Because of their significant ring strain,
epoxides have great synthetic utility as
intermediates.
Propose some reagents that might react with
an epoxide to provide a specific functional
group.
Propose some reagents that might react with
an epoxide to alter the carbon skeleton.
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Epoxides
Strong nucleophiles react readily with
epoxides.
Predict whether each step is product- or

reactant- favored, and explain WHY.
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Epoxides
In general, alkoxides are not good leaving
groups.
The ring strain associated with the epoxide

increases its potential energy making it more
reactive.
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Epoxides
The epoxide reaction is both more kinetically
and more thermodynamically favored. WHY?

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Epoxides
Epoxides can be opened by many other
strong nucleophiles as well.
Both regioselectivity and stereoselectivity

must be considered.
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Epoxides
Given that the epoxide ring-opening is SN2,
predict the outcome of the following
reactions.
Pay attention to regio- and stereoselectivity.
Explain WHY.
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Practice with SKILLBUILDER
14.4.
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Epoxides
Acidic conditions can also be used to open
epoxides.

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Epoxides
Water or an alcohol can also be used as the
nucleophile under acidic conditions.
Predict the products and draw a complete
mechanism.

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Epoxides
Propose an explanation for the following
regiochemical observations.
Consider both steric and electronic effects
(induction).

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Epoxides
If the nucleophile preferentially attacks the
tertiary carbon under acidic conditions, is the
mechanism likely SN1 or SN2?
Considering the observations below, is the
mechanism likely SN1 or SN2?

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Epoxides
When the nucleophile attacks a tertiary
center of the epoxide, the intermediate it
attacks takes on some carbocation character
(SN1), but not completely.
Give reaction conditions for the following
reaction.

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14.11 Thiols and Sulfides

Sulfur appears just under oxygen on the
periodic table.
Sulfur appears in THIOLS as an SH group
analogous to the OH group in alcohols.
The name of a compound with an SH group
ends in thiol rather than ol.
Note that the e

14 -57 of butane is not
dropped
Klein, Organic
Chemistryin
1e
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Thiols are also known as mercaptans.
The SH group can also be named as part of
a side group rather than as part of the parent
chain.
The mercaptan name comes from their

ability to complex mercury.
2,3-dimercapto-1-propanol
is used
to treat
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Klein, Organic
Chemistry 1e
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Thiols are known for their unpleasant odor.
Skunks use thiols as a defense mechanism.
Methanethiol is added to natural gas
(methane) so that gas leaks can be detected.
Your nose is a very sensitive instrument.
The hydrosulfide ion (HS) is a strong
nucleophile and a weak base.
HS promotes SN2 rather than E2.
Look At Picture, NOT ON BOOK
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Predict the outcome of the following
reactions, and draw a complete mechanism.

14.22.
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Thiols have a pKa of about 10.5.

More acidic because of size of the molecule, electrons on
the outer shell are not held as tightly, so it is more acidic
than water
Recall that water has a pKa of 15.7.
Predict whether the equilibrium below will favor products or
reactants and draw the mechanism.
Thiolates are excellent nucleophiles.
thiolate ion

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Once a thiolate forms, it can attack Br2 to
produce a disulfide. If left out, thiols can get
oxidized by O2
How does the oxidation number change?

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Disulfides can be reduced by the reverse
reaction.
The interconversion between thiol and

disulfide can also occur directly via a free
radical mechanism. Propose a mechanism.
The bond dissociation energy of a SS bond
is only about 53 kcal/mol. WHY is that
significant?
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Sulfur analogs of ethers are called SULFIDES
or THIOETHERS.
Sulfides can also be named as a side group.

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Sulfides are generally prepared by
nucleophilic attack of a thiolate on an alkyl
halide.
How are thiolates generally prepared?

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Sulfides undergo a number of reactions:
1. Attack on an alkyl halide:
. The process produces a strong alkylating reagent

that can add an alkyl group to a variety of
nucleophiles.

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2. Sulfides can also be oxidized.
. Sodium meta-periodate can be used to form the

sulfoxide.

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2. Sulfides can also be oxidized.
. Hydrogen peroxide can be used to give the

sulfone.

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Sulfoxides and sulfones have very little

double bond character.
Which resonance contributor for each is the
major contributor, and WHY?

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Because sulfides are readily oxidized, they

make good reducing agents.
Recall the ozonolysis reaction from Section
9.11.

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14.23.

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Predict any products or necessary reagents

in the reaction sequence below.
Verify the formal charge on the sulfur in the

final product above.
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14.12 Synthetic Strategies

Involving Epoxides
Epoxides can be used to install functional

groups on adjacent carbons.
Give necessary reagents for the reaction

below.

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Involving Epoxides
By reacting an epoxide with a Grignard

reagent, the carbon skeleton can be
modified.
You may think of an alkyl halide as the

starting material.
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Involving Epoxides
Recall that a carbonyl can be

used to install a one carbon
chain between an R group and
an OH group.
An epoxide can be used to install a two
carbon chain between an R group and an
OH group.

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Involving Epoxides
Give necessary reagents for the reaction

below.
Practice with SKILLBUILDER 14.7.

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CH 14 Klein Ethers, Epoxides, Sulfides

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14.

R groups can be alkyl, aryl, or vinyl groups.

Copyright 2012 John Wiley &

Klein, Organic Chemistry 1e

14.1 Introduction to Ethers

Copyright 2012 John Wiley &

Klein, Organic Chemistry 1e

14.2 Naming Ethers

Copyright 2012 John Wiley &

Klein, Organic Chemistry 1e

14.2 Naming Ethers

Copyright 2012 John Wiley &

Klein, Organic Chemistry 1e

14.2 Naming Ethers

Draw the structure for (R)-1methoxycyclohexen-3-ol.

Copyright 2012 John Wiley &

Klein, Organic Chemistry 1e

14.3 Structure and Properties

Is the oxygen atom in an ether sp3, sp2, or sp

Klein, Organic Chemistry 1e

14.3 Structure and Properties

What is the maximum number of H-bonds an

14.3 Structure and Properties

Would you expect the boiling point of an

Klein, Organic Chemistry 1e

14.3 Structure and Properties

Copyright 2012 John Wiley &

Klein, Organic Chemistry 1e

14.3 Structure and Properties

Copyright 2012 John Wiley &

Klein, Organic Chemistry 1e

14.4 Crown Ethers

Give another reason why an ether makes a

Klein, Organic Chemistry 1e

14.4 Crown Ethers

Note how many carbon atoms separate the

14.4 Crown Ethers

Copyright 2012 John Wiley &

Klein, Organic Chemistry 1e

14.4 Crown Ethers

Copyright 2012 John Wiley &

Klein, Organic Chemistry 1e

14.4 Crown Ethers

Without the crown ether, the solubility of KF

Klein, Organic Chemistry 1e

14.4 Crown Ethers

Copyright 2012 John Wiley &

Klein, Organic Chemistry 1e

14.4 Crown Ethers

Practice with CONCEPTUAL CHECKPOINT

Klein, Organic Chemistry 1e

14.5 Preparation of Ethers

Copyright 2012 John Wiley &

Klein, Organic Chemistry 1e

14.5 Preparation of Ethers

What happens to the halide?

Copyright 2012 John Wiley &

Klein, Organic Chemistry 1e

14.5 Preparation of Ethers

The alkoxide that forms in step 1 is also a

14.5 Preparation of Ethers

Consider a retrosynthetic disconnect on the

14.5 Preparation of Ethers