The Esters
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Fischer Esterification
R
C
O
+
O
H
OH
+
R
OH
R
C
+
O
R
O
H
H
This is not necessarily the best method of
preparing esters, but it does serve to illustrate
that esters are essentially the products of a
reaction between a carboxylic acid and an
alcohol.
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Lactones
Lactones are cyclic esters formed by the intramolecular
interaction of an alcohol functional group with a carboxylic
acid functional group:
R
O
R
CH2
CH
O
H
CH
C
CH2
OH
CH2
CH2
O
C
O
a lactone
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The Triacylglycerols
• A very important class of esters, from a
biological point of view, is in the
triacylglycerols -- the common simple fats.
• “Triacylglycerol” is a relatively modern
term; you may also hear of these substances
as “simple lipids” or as “triglycerides.”
• The triacylglycerols are esters of long-chain
carboxylic acids combined with glycerol.
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The Triacylglycerols
O
O
R
C
O
CH2 O
C
H
O
CH2 O
C
C
R
R
The nature of the R groups can vary.
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Glycerol
CH2 OH
CH
OH
CH2 OH
Since glycerol has three -OH groups, it can react with three
molecules of carboxylic acid to form a triester.
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The Fatty Acids
• The carboxylic acid components of
triacylglycerols are known as fatty acids.
• Fatty acids are simple, long-chain
carboxylic acids -- their name comes from
the simple fact that they occur in fats!
• Naturally-occurring fatty acids always have:
– an unbranched carbon chain
– an even number of carbon atoms
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The Fatty Acids
O
CH3 (CH2)10 C
O
OH
CH3 (CH2)12 C
Lauric acid
O
OH
CH3 (CH2)14 C
Myristic acid
Palmitic acid
O
CH3 (CH2)16 C
OH
O
OH
CH3 (CH2)7 CH
Stearic acid
CH (CH2)7
C
OH
Oleic acid
O
CH3 (CH2)7 CH
CH
CH2 CH
CH (CH2)7
C
OH
Linoleic acid
O
CH3 CH2 CH
CH
CH2
CH
CH
CH2 CH
CH (CH2)7
C
OH
Linolenic acid
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Saturated versus Unsaturated
Fatty Acids
• When the carbon chain (excluding the C=O bond)
contains single bonds only, the fatty acid is known
as a saturated fatty acid, and the triacylglycerol
thus becomes a saturated fat.
• When the carbon chain contains one or more C=C
double bonds, the fatty acid becomes an
unsaturated fatty acid, and the triacylglycerol thus
becomes an unsaturated fat.
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Unsaturated Fatty Acids
• Naturally-occurring unsaturated fatty acids
have the following characteristics:
– The first double bond appears at carbon #9
– If there are two or more double bonds, they are
separated by a -CH2- group -- the double bonds
are never conjugated.
– Double bonds always have the cis geometry.
The so-called trans fatty acids are not naturallyoccurring.
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Hydrogenation of Fats
O
CH2 O
CH
C
(CH2)7 CH
CH
R
H2
OCOR'
Pt
CH2 OCOR"
O
CH2 O
CH
C
H
H
(CH2)7 CH
CH
R
OCOR'
CH2 OCOR"
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Hydrogenation of Fats
• The hydrogenation of an unsaturated fat converts
it into a saturated fat.
• This is an important process in the food industry,
where unsaturated (liquid) fats are converted into
saturated (solid) fats.
• Often, in an effort to retain some of the nutritional
benefits of an unsaturated fat, food manufacturers
will only partially hydrogenate a liquid fat -- just
sufficiently for the material to turn semi-solid.
This would be a partially hydrogenated fat.
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OH
CH3 CH2
CH2 C
CH2 CH2
CH2 CH2
CH2 CH2
O
CH2 CH2
CH2 CH2
C
CH2 CH2
C
H
cis-Oleic Acid
H
H2
Platinum catalyst
surface
CH3 CH2
CH2 CH2
Isomerization of
Fatty Acids
CH2 CH2
CH2 CH2
C
H
H
C
CH2 CH2
CH2 CH2
trans-Oleic Acid
CH2 CH2
O
CH2 C
OH
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R
O
C
O
O
O
C
R
O
O
C
O
O
CH2
O
C
O
R
O
O
O
R
C
CH2
O
R
R
C
CH2
O
O
O
R
O
C
O
Olestra
(“Olean”)
C
R
CH3 CH2
R=
CH2 CH2
CH2
CH2
CH2 CH2
CH2
CH2 CH2
C
H
CH2
CH2
CH2
CH2
C
H
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Molecular Model of Triolein
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Molecular Model of Olestra
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Fischer Esterification
R
C
O
+
O
H
OH
+
R
OH
R
C
+
O
R
O
H
H
This is the most direct way of preparing esters.
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Fischer Esterification
•This is a reversible reaction; the equilibrium constant
is only slightly greater than unity (between 1 and 10).
•To be successful, this reaction requires that one be
able to shift the equilibrium to the right
•This is accomplished by:
•removing water by azeotropic distillation
•using an excess of whichever reagent is
inexpensive.
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Fischer Esterification
CH3 O
CH3 O
CH3 C
C
CH3 C
OH
C
O
CH2 CH3
H2SO4
CH3
CH3
+
+
CH3 CH2 OH
O
H
H
84% yield
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Preparation of Esters
(Best Method)
O
R
C
O
Cl
+
R
OH
R
C
+
O
H
R
Cl
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Also Good:
O
R
C
O
O
O
C
R
+
R
OH
R
C
O
R
O
+
R
C
O
H
You would use this alternative when the acid anhydride
is cheaper than the corresponding acid chloride. There
are relatively few commercially-available acid
anhydrides, however.
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Methyl Ester Formation
• Carboxylic acids can be converted to
methyl esters by the action of
diazomethane.
CH2N2
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Methyl Ester Formation
O
R
C
O
O
H
R
C
+
+
CH2N2
N2
O
CH2 H
Notice that the CH2 of diazomethane appears to
insert itself between the O and the H of the O-H
bond!
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Diazomethane
• Diazomethane is a highly toxic and
dangerously explosive gas.
• In spite of its hazardous nature, it can be
handled relatively safely in dilute ether
solutions (and in small quantities)
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Diazomethane
(continued)
• In dilute solution it is a very useful reagent
for the preparation of methyl esters,
particularly in cases where only small
quantities of carboxylic acid are available.
• This reaction proceeds in nearly quantitative
(100%) yields!
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Structure of Diazomethane
CH2 N
N
CH2 N
N
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Reactivity of Diazomethane
• The high reactivity of diazomethane arises from
the fact that it possesses an exceedingly reactive
leaving group, the nitrogen molecule (which is
exceptionally stable).
• As the following mechanism shows, a
nucleophilic substitution reaction on the
protonated diazomethane molecule transfers a
methyl group to the oxygen atom of the carboxylic
acid, while liberating nitrogen gas (a very stable
product).
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Mechanism of Methyl Ester
Formation
1)
O
R
2)
C
O
OH
+
CH 2N2
R
C
O
O
R
C
+
H
CH 2 N
N
O
O
+
CH 3 N
N
slow
R
+
C
O
N
N
CH 3
This process is very favorable energetically, owing to the
great stability of N2.
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Reactions of Esters
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By far the most important reaction of
the esters is hydrolysis.
Hydrolysis can take place in either
acidic or basic solution.
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Hydrolysis of Esters
O
O
_
R
C
O
R + OH
O
R
C
R
H
O
R + H O
2
C
O
+
R
O
H
OH
+
R
O
H
O
+
R
C
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Example
O
H+
CH2
CH3
CH2
CH2
C
CH2
CH2
O
H 2O
+
CH3
Ethyl hexanoate
(Ethyl caproate)
"essence of
cognac"
O
CH2
CH3
CH2
CH2
C
CH2
H
O
+
CH3 CH2 OH
Hexanoic acid
(Caproic acid)
Can anyone suggest why an ester might not make a suitable
perfume?
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Another Example
O
O
CH3 CH2 C
+ OH
O
CH2 CH3
H 2O
CH3 CH2 C
+
O
CH3 CH2 OH
Notice that, in a basic medium, the product of the
hydrolysis is a carboxylate ion. The basic hydrolysis
of an ester is often known as a saponification.
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Hydrolysis of an Ester in Base
: O:
R
H
C
..
O
..
.. _
: O:
R'
slow
.. _
O
.. :
.. _
: O:
R
C
H
:
O
..
.. _
: O:
R
C
..
:O
..
O
..
R'
R
R
C
H
:
O
..
H
..
O
..
C
..
O
..
R'
.. _
:O:
R
R'
:O :_
..
+..
O
:O: H
.. _
C
+..
O
R'
:O: H
.. _
: O:
R'
R
C
:O:
.. _
+
....
:O
R'
H
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Hydrolysis of an Ester in Acid
+
O:
H
R
H
..
O
..
C
..
O
..
H
R'
slow
H
H
R
C
+
H O
..
H
+ ..
H O
..
O:
..
O:
..
O
..
R'
H
+..
O
R
C
H
:
O
.. H
R
C
H
:
O
..
..
O:
R
C
..
O
..
H
+
O
..
H
H
..
O
..
R'
R'
H
..
O:
R
C
H
:
O
.. H
+
H
+..
O
R'
: O:
R'
R
C
H
:
O
..
+
....
:O
R'
+
H
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Saponification – The World’s SecondOldest Known Organic Reaction
• Recall that the triacylglycerols (simple
lipids or fats) are esters.
O
O
R
C
O
CH2 O
C
H
O
CH2 O
C
C
R
R
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If we hydrolyze a fat in aqueous base:
O
O
R
C
O
_
CH2 O
C
H
O
CH2 O
C
C
O
R
R
C
O
+
O
+
R
R
+ 3 OH
C
+
CH2 OH
O
CH OH
CH2 OH
O
R
C
O
The products are three equivalents of carboxylate ion.
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If our starting fat were something like tristearin, which
would be representative of an animal fat:
O
CH2
CH2 O
C
O
CH2
CH2
CH2
CH2
CH2
CH O
C
O
CH2
CH2
C
CH2
CH2
CH2
CH2
CH2
CH3
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2 O
CH2
CH2
CH2
CH2
CH2
CH3
CH2
CH2
CH3
Tristearin
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Then basic hydrolysis would give us three equivalents
of the corresponding sodium carboxylate.
O
CH2
Na
Na
O
C
O
CH2
CH2
CH2
C
O
CH2
CH2
O
C
CH2
CH2
CH2
CH2
CH2
CH3
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
Na
CH2
CH2
O
CH2
CH2
CH2
CH2
CH2
CH3
CH2
CH2
CH3
Sodium stearate
This is the structural formula for ordinary soap!
(“Grandma’s lye soap”)
“Saponification” (from Latin: sapo = soap).
Saponification is a soap-making reaction.
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Transesterification
• Sometimes, it is more convenient to convert
the alkyl group of an ester to another alkyl
group.
• This process is known as
transesterification.
• Transesterification can take place under
either acidic or basic conditions, although
most commonly it is done under acidic
conditions.
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Transesterification
O
R
C
H
O
R
+
R
OH
O
+
R
C
+
O
R
O
H
R
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Transesterification (in base)
O
R
C
O
_
..
O
R
+
R
O:
..
R
C
O
_ ..
O
+ :..
R
R
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Example
O
CH2
CH3
O
C
CH2
CH3
CH2
O
H
+
+
CH3
C
CH2
CH2
O
+
CH2 OH
CH3 OH
Thus, we’ve converted a methyl ester to a benzyl ester.
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A Problem:
Suppose we have a sample of a fat.
O
R1
C
O
O
CH2
R2
C
O
O
CH
R3
C
O
CH2
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• What are R1, R2, and R3?
• With what frequency do they appear in a
sample of the fat?
• What is their relative distribution in the
sample?
• We can’t analyze the fat sample directly,
because it isn’t very soluble and it isn’t
volatile.
• We need to convert it from a glycerol ester
to some more convenient form of ester.
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Transesterification
O
O
R1
C
O
O
R1
CH2
R3
C
O
O
C
O
CH3
O
CH3
O
CH3
O
CH
CH3OH
O
+
-
CH3O
R2
C
R2
C
+
CH2
O
R3
C
+ glycerol
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• The methyl esters are much more volatile.
• The transesterified fat sample can now be
analyzed by gas chromatography.
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Reaction of Esters with
Organometallic Reagents
O
R
C
1) ether
O
R
+
2 R
MgBr
2) H2O, acid
OH
R
C
R
+
MgBr(OR)
+
MgBr(OH)
R
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We can outline (crudely) the mechanism as follows:
O
R
C
O
R
R
O
Metal
C
O
R
R
R
Metal
O
R
C
R
+
O
R
Metal
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BUT: The ketone can also react with the organometallic
reagent! So, addition of organometallic reagent happens a
second time.
O
Metal
O
R
C
R
R
R
C
R
R
Metal
H2O
H+
OH
So, the product is a tertiary
alcohol.
R
C
R
R
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Example
O
C
CH3
O
ether
+
H2O
H+
2
MgBr
OH
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Reduction of Esters
O
C
4
R
R
O
4 R
+
+ 2 LiAlH4
CH2 OH
2 LiOH +
+
4 R
OH
2 Al(OH)3
Lithium aluminum hydride (LiAlH4) reduces esters
through two 2-electron reduction steps, all the way to
the primary alcohol.
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Crude Outline of the Mechanism
O
Al
R
C
O
R
O
R
Al
C
H
O
R
H
O
BUT: The aldehyde can also be
reduced by LiAlH4!
R
C
H
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And so….
O
Al
R
C
H
O
R
Al
H
C
H
H
H+
H2O
OH
Sodium borohydride (NaBH4) will
not attack esters.
R
C
H
H
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Example
CH3 O
CH3 C
C
O
CH2 CH3
LiAlH4
H2O
ether
H+
CH3
CH3
CH3 C
CH2 OH
CH3
2,2-Dimethyl-1-propanol
(Neopentyl alcohol)
101%
yield
99
% yield
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Reduction of Esters to Aldehydes
O
R
DIBALH
C
O
R'
toluene
-78°C
H2O
O
R
HCl
C
H
+
R'
OH
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Example
O
O
DIBALH
CH3 CH
CH3
C
O
CH2 CH3
toluene
-78°C
CH3 CH
C
H
CH3
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