Organic Chemistry,: Alcohols, Ethers, Epoxides
Organic Chemistry,: Alcohols, Ethers, Epoxides
Chapter 9
Alcohols, Ethers, Epoxides
Prepared by Rabi Ann Musah
State University of New York at Albany
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
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Alcohols, Ethers and Epoxides
Chapter 9 Topics:
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Alcohols, Ethers and Epoxides
Introduction: Structure and Bonding
• Compounds having a hydroxy group on a sp2
hybridized carbon (enols and phenols) undergo
different reactions than alcohols.
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Alcohols, Ethers and Epoxides
Introduction: Structure and Bonding
• Epoxides are ethers having the oxygen atom in a three-
membered ring. Epoxides are also called oxiranes or
alkene oxides.
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Alcohols, Ethers and Epoxides
Nomenclature of Alcohols:
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Alcohols, Ethers and Epoxides
Nomenclature of Alcohols:
• When an OH group is bonded to a ring, the ring is numbered
beginning with the OH group.
• Because the functional group is at C1, the 1 is usually omitted
from the name.
• The ring is then numbered in a clockwise or counterclockwise
fashion to give the next substituent the lowest number.
Figure 9.2 Examples: Naming cyclic alcohols
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Alcohols, Ethers and Epoxides
Nomenclature of Alcohols:
• Common names are often used for simple alcohols. To
assign a common name:
Name all the carbon atoms of the molecule as a single
alkyl group.
Add the word alcohol, separating the words with a
space.
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Alcohols, Ethers and Epoxides
Nomenclature of Alcohols:
• Compounds with two hydroxy groups are called diols
or glycols. Compounds with three hydroxy groups are
called triols and so forth.
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Alcohols, Ethers and Epoxides
Nomenclature of Ethers:
• Simple ethers are usually assigned common names.
To do so:
Name both alkyl groups bonded to the oxygen, arrange
these names alphabetically, and add the word ether.
For symmetrical ethers, name the alkyl group and add
the prefix “di-”.
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Alcohols, Ethers and Epoxides
Nomenclature of Ethers:
• More complex ethers are named using the IUPAC system. One
alkyl group is named as a hydrocarbon chain, and the other is
named as part of a substituent bonded to that chain:
Name the simpler alkyl group as an alkoxy substituent by
changing the –yl ending of the alkyl group to –oxy.
Name the remaining alkyl group as an alkane, with the
alkoxy group as a substituent bonded to this chain.
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Alcohols, Ethers and Epoxides
Nomenclature of Epoxides:
• Epoxides bonded to a chain of carbon atoms can also be
named as derivatives of oxirane, the simplest epoxide
having two carbons and one oxygen atom in a ring.
• The oxirane ring is numbered to put the O atom at
position one, and the first substituent at position two.
• No number is used for a substituent in a
monosubstituted oxirane.
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Alcohols, Ethers and Epoxides
Nomenclature of Epoxides:
• Epoxides are also named as alkene oxides, since they
are often prepared by adding an O atom to an alkene.
To name an epoxide in this way:
Mentally replace the epoxide oxygen with a double
bond.
Name the alkene.
Add the word oxide.
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Alcohols, Ethers and Epoxides
Physical Properties:
• Alcohols, ethers and epoxides exhibit dipole-dipole interactions
because they have a bent structure with two polar bonds.
• Alcohols are capable of intermolecular hydrogen bonding.
Thus, alcohols are more polar than ethers and epoxides.
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Alcohols, Ethers and Epoxides
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Alcohols, Ethers and Epoxides
Interesting Alcohols:
Figure 9.4 Some simple alcohols
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Alcohols, Ethers and Epoxides
Interesting Ethers:
• The ability of crown ethers to complex cations can be
exploited in nucleophilic substitution reactions, as shown
in Figure 9.5.
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Alcohols, Ethers and Epoxides
Preparation of Alcohols, Ethers, and Epoxides:
2o substrates
give mixed
mechanisms,
SN2 & E2. 21
Alcohols, Ethers and Epoxides
Preparation of Alcohols, Ethers, and Epoxides:
• An alkoxide salt is needed to make an ether.
• Alkoxides can be prepared from alcohols by a BrØnsted-
Lowry acid—base reaction. For example, sodium
ethoxide (NaOCH2CH3) is prepared by treating ethanol
with NaH.
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Alcohols, Ethers and Epoxides
Reactions of Alcohols:
• Recall that, unlike alkyl halides in which the halogen atom
serves as a good leaving group, the OH group in alcohols
is a very poor leaving group.
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Alcohols, Ethers and Epoxides
Reactions of Alcohols: Dehydration
• Dehydration, like dehydrohalogenation, is a elimination
reaction in which the elements of OH and H are removed
from the and carbon atoms respectively.
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Alcohols, Ethers and Epoxides
Reactions of Alcohols: Dehydration
• When an alcohol has two or three carbons, dehydration
is regioselective and follows the Zaitsev rule.
• The more substituted alkene is the major product when a
mixture of constitutional isomers is possible.
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Alcohols, Ethers and Epoxides
Reactions of Alcohols: Dehydration
• Secondary and 3° alcohols react by an E1 mechanism,
whereas 1° alcohols react by an E2 mechanism.
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Alcohols, Ethers and Epoxides
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Alcohols, Ethers and Epoxides
Reactions of Alcohols: Dehydration
• Since 1° carbocations are highly unstable, their dehydration
cannot occur by an E1 mechanism involving a carbocation
intermediate. Therefore, 1° alcohols undergo dehydration
following an E2 mechanism.
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Alcohols, Ethers and Epoxides
Reactions of Alcohols: Dehydration
• Although entropy favors product formation in
dehydration (i.e., one molecule of reactant forms two
molecules of product), enthalpy does not, since the
bonds broken in the reactant are stronger than the
and bonds formed in the products.
Figure 9.6 Dehydration of CH3CH2OH to CH2=CH2, an endothermic reaction.
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Alcohols, Ethers and Epoxides
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Alcohols, Ethers and Epoxides
Carbocation Rearrangements:
• Often, when carbocations are intermediates, a less stable
carbocation will be converted into a more stable carbocation
by a shift of a hydrogen or an alkyl group. This is called a
rearrangement.
• Because the migrating group in a 1,2-shift moves with two
bonding electrons, the carbon it leaves behind now has only
three bonds (six electrons), giving it a net positive (+) charge.
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Alcohols, Ethers and Epoxides
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Alcohols, Ethers and Epoxides
Carbocation Rearrangements:
• A 1,2-shift can convert a less stable carbocation into
a more stable carbocation.
• Rearrangements are not unique to dehydration
reactions. Rearrangements can occur whenever a
carbocation is formed as a reactive intermediate.
Consider the example below: 2° Carbocation A
rearranges to the more stable 3° carbocation by a 1,2-
hydride shift, whereas carbocation B does not rearrange
because it is already 3°.
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Alcohols, Ethers and Epoxides
Dehydration of Alcohols Using POCl3 and Pyridine:
• Some organic compounds decompose in the presence of
strong acid, so other methods have been developed to
convert alcohols to alkenes.
• A common method uses phosphorus oxychloride (POCl3)
and pyridine (an amine base) in place of H2SO4 or TsOH.
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Alcohols, Ethers and Epoxides
Conversion of Alcohols to Alkyl Halides with HX:
• Substitution reactions do not occur with alcohols unless
¯OH is converted into a good leaving group.
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Alcohols, Ethers and Epoxides
Conversion of Alcohols to Alkyl Halides with HX:
• More substituted alcohols usually react more rapidly with HX:
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Alcohols, Ethers and Epoxides
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Alcohols, Ethers and Epoxides
Conversion of Alcohols to Alkyl Halides with HX:
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Alcohols, Ethers and Epoxides
Conversion of Alcohols to Alkyl Halides with HX:
• The reactivity of hydrogen halides increases with increasing
acidity.
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Alcohols, Ethers and Epoxides
Conversion of Alcohols to Alkyl Halides with SOCl2
and PBr3:
• Primary and 2° alcohols can be converted to alkyl
halides using SOCl2 and PBr3.
• SOCl2 (thionyl chloride) converts alcohols into alkyl
chlorides.
• PBr3 (phosphorus tribromide) converts alcohols into
alkyl bromides.
• Both reagents convert ¯OH into a good leaving group
in situ (that is, directly in the reaction mixture) as well
as provide the nucleophile, either Cl¯ or Br¯, to
displace the leaving group.
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Alcohols, Ethers and Epoxides
Conversion of Alcohols to Alkyl Halides with SOCl2
and PBr3:
• When a 1° or 2° alcohol is treated with SOCl2 and
pyridine, an alkyl chloride is formed, with HCl and SO2
as byproducts.
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Alcohols, Ethers and Epoxides
Conversion of Alcohols to Alkyl Halides with SOCl2
and PBr3:
• Treatment of a 1o or 2o alcohol with PBr3 forms an alkyl
halide.
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Alcohols, Ethers and Epoxides
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Alcohols, Ethers and Epoxides
Tosylate: A Good Leaving Group
• Alcohols can be converted into alkyl tosylates.
• An alkyl tosylate is composed of two parts: the alkyl group
R, derived from an alcohol; and the tosylate (short for
p-toluenesulfonate), which is a good leaving group.
• A tosyl group, CH3C6H4SO2¯, is abbreviated Ts, so an alkyl
tosylate becomes ROTs.
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Alcohols, Ethers and Epoxides
Tosylate: A Good Leaving Group
• Alcohols are converted to tosylates by treatment with
p-toluenesulfonyl chloride (TsCl) in the presence of
pyridine.
• This process converts a poor leaving group (¯OH) into
a good one (¯OTs).
• Tosylate is a good leaving group because its conjugate
acid, p-toluenesulfonic acid (CH3C6H4SO3H, TsOH) is a
strong acid (pKa = -7).
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Alcohols, Ethers and Epoxides
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Alcohols, Ethers and Epoxides
Tosylate: A Good Leaving Group
• Because alkyl tosylates have good leaving groups, they
undergo both nucleophilic substitution and elimination,
exactly as alkyl halides do.
• Generally, alkyl tosylates are treated with strong
nucleophiles and bases, so the mechanism of substitution
is SN2, and the mechanism of elimination is E2.
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Alcohols, Ethers and Epoxides
Tosylate: A Good Leaving Group
• Because substitution occurs via an SN2 mechanism,
inversion of configuration results when the leaving group
is bonded to a stereogenic center.
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Alcohols, Ethers and Epoxides
Tosylate: A Good Leaving Group
• Step 1, formation of the tosylate, proceeds with retention
of configuration at a stereogenic center.
• Step 2 is an SN2 reaction, so it proceeds with inversion of
configuration because the nucleophile attacks from the
backside.
• Overall there is a net inversion of configuration at a
stereogenic center.
Example:
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Alcohols, Ethers and Epoxides
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Alcohols, Ethers and Epoxides
Cleavage of Ethers with Strong Acid (HBr and HI):
• In order for ethers to undergo substitution or elimination
reactions, their poor leaving group must first be converted into
a good leaving group by reaction with strong acids such as
HBr and HI. HBr and HI are strong acids that are also sources
of good nucleophiles (Br¯ and I¯ respectively).
• When ethers react with HBr or HI, both C—O bonds are cleaved
and two alkyl halides are formed as products.
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Alcohols, Ethers and Epoxides
Cleavage of Ethers with Strong Acid:
• The mechanism of ether cleavage is SN1 or SN2, depending on
the identity of R.
• When 2° or 3° alkyl groups are bonded to the ether oxygen,
the C—O bond is cleaved by an SN1 mechanism involving a
carbocation. With methyl or 1° R groups, the C—O bond is
cleaved by an SN2 mechanism.
Example: In the reaction of (CH3)3COCH3 with HI, the 3° alkyl
group undergoes nucleophilic substitution by an SN1
mechanism, resulting in the cleavage of one C—O bond. The
methyl group undergoes nucleophilic substitution by an SN2
mechanism, resulting in the cleavage of the second C—O
bond.
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Alcohols, Ethers and Epoxides
Reaction of Ethers with Strong Acid:
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Alcohols, Ethers and Epoxides
Reactions of Epoxides:
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Alcohols, Ethers and Epoxides
Reactions of Epoxides:
• The reaction occurs readily with strong nucleophiles
and with acids like HZ, where Z is a nucleophilic atom.
• Unsymmetrical epoxides will open differently in acid
solution vs neutral or basic solution.
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Alcohols, Ethers and Epoxides
Reactions of Epoxides (neutral or basic media):
• Virtually all strong nucleophiles open an epoxide ring by a two-
step reaction sequence:
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Alcohols, Ethers and Epoxides
Reactions of Epoxides (neutral or basic media):
Let’s now consider the stereochemical consequences
of the reaction of 1,2-epoxycyclohexane with ¯OCH3.
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Alcohols, Ethers and Epoxides
Reactions of Epoxides (acid media):
Figure 9.9 Opening of an unsymmetrical epoxide ring with HCI
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Alcohols, Ethers and Epoxides
Reactions of Epoxides (base vs acid):
• Ring opening of an epoxide with either a strong nucleophile
or an acid HZ is regioselective because one constitutional
isomer is the major or exclusive product.
• Note that the site selectivity of these two reactions is exactly
opposite.
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Organic Chemistry, Second Edition
End Chapter 9
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
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