18
General, Organic, and
Biochemistry, 8e
Bettelheim, Brown
Campbell, & Farrell
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18-1
18 Chapter 18
Carboxylic Acids
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18-2
18 Carboxylic Acids
• In this chapter, we study carboxylic acids, a class
of organic compounds containing the carbonyl
group.
• The functional group of a carboxylic acid is a
carboxyl group, which can be represented in any
one of three ways.
O
C-OH
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COOH
CO2 H
18-3
18 Nomenclature
• IUPAC names
• For an acyclic carboxylic acid, take longest carbon
chain that contains the carboxyl group as the parent
alkane.
• Drop the final -e from the name of the parent alkane
and replace it by -oic acid.
• Number the chain beginning with the carbon of the
carboxyl group.
• Because the carboxyl carbon is understood to be
carbon 1, there is no need to give it a number.
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18-4
18 Nomenclature
• In these examples, the common name is given in
parentheses.
O
6
O
1
3
OH
Hexanoic acid
(Caproic acid)
1
OH
3-Methylbutanoic acid
(Isovaleric acid)
• An -OH substituent is indicated by the prefix hydroxy-;
an -NH2 substituent by the prefix amino-.
OH
5
O
1
OH
5-Hydroxyhexan oic acid
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H2 N
COOH
4-A min ob enzoic acid
18-5
18 Nomenclature
• To name a dicarboxylic acid, add the suffix -dioic acid
to the name of the parent alkane that contains both
carboxyl groups; thus, -ane becomes -anedioic acid.
• The numbers of the carboxyl carbons are not indicated
because they can be only at the ends of the chain.
O
HO
2
O
1
3
OH
HO
O
1
OH
O
Ethan edioic acid Prop aned ioic acid
(Malonic acid )
(Oxalic acid )
O
HO
4
O
5
1
OH
O
Butaned ioic acid
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(Succinic
acid)
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HO
O
O
1
OH
Pen tanedioic acid
(Glutaric acid)
HO
6
1
OH
O
Hexan edioic acid
(Ad ipic acid)
18-6
18
Structure
HCOOH
CH 3 COOH
CH 3 CH2 COOH
CH 3 (CH 2 ) 2 COOH
CH 3 (CH 2 ) 3 COOH
CH 3 (CH 2 ) 4 COOH
CH 3 (CH 2 ) 6 COOH
CH 3 (CH 2 ) 8 COOH
CH 3 (CH 2 ) 1 0 COOH
CH 3 (CH 2 ) 1 2 COOH
CH 3 (CH 2 ) 1 4 COOH
CH 3 (CH 2 ) 1 6 COOH
CH 3 (CH 2 ) 1 8 COOH
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IU PAC N ame
(acid)
methanoic
ethan oic
propanoic
bu tanoic
pen tanoic
hexan oic
octanoic
decanoic
dodecanoic
tetradecan oic
hexad ecanoic
octadecanoic
eicosan oic
Common
N ame
D erivation
formic
acetic
propionic
bu tyric
valeric
cap roic
cap rylic
cap ric
Latin : formica, ant
Latin : acet um, vinegar
Greek: propion, firs t fat
Latin : buty rum, b utter
Latin : valere, to be s trong
Latin : caper, goat
Latin : caper, goat
Latin : caper, goat
Latin : laurus , laurel
lauric
myristic Greek: my ris tikos, fragrant
palmitic Latin : palma, palm tree
stearic
Greek: st ear, solid fat
arachid ic Greek: arachis, p eanut
18-7
18 Nomenclature
• For common names, use, the Greek letters alpha (a),
beta (b), gamma (g), and so forth to locate substituents.
O
C-C-C-C-OH
g b a
4
3 2 1
O
O
H2 N
4
g
2
1
OH
OH
a
OH
4-A min ob utanoic acid
2-Hyd roxypropan oic acid
(g-A min obu tyric acid; GABA) (a-Hydroxyprop ion ic acid;
lactic acid)
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18-8
18 Physical Properties
• The carboxyl group contains three polar covalent
bonds; C=O, C-O, and O-H.
• The polarity of these bonds determines the major
physical properties of carboxylic acids.
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18-9
18 Physical Properties
• Carboxylic acids have significantly higher boiling
points than other types of organic compounds of
comparable molecular weight.
• Their higher boiling points are a result of their polarity
and the fact that hydrogen bonding between two
carboxyl groups creates a dimer that behaves as a
higher-molecular-weight compound.
hydrogen bondin g
betw een tw o
molecules
H3 C
O
O
C
C
O
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+
H
H
+
CH 3
O
-
18-10
18 Physical Properties
• Carboxylic acids are more soluble in water than are
alcohols, ethers, aldehydes, and ketones of
comparable molecular weight.
Boilin g
Solubility
Molecular Poin t
Weigh t
(°C) (g/100 mL H 2O)
Structu re
N ame
CH3 COOH
CH3 CH2 CH2 OH
CH3 CH2 CHO
acetic acid
60.5
1-prop anol
prop anal
CH3 (CH2 ) 2 COOH butan oic acid
CH3 (CH2 ) 3 CH2 OH 1-pentan ol
pentan al
CH3 (CH2 ) 3 CHO
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60.1
58.1
118
97
48
infinite
infinite
16
88.1
88.1
86.1
163
137
103
infinite
2.3
slight
18-11
18 Fatty Acids
• Fatty acids; long chain carboxylic acids derived
•
•
•
•
from animal fats, vegetable oils, or phospholipids
of biological membranes.
More than 500 have been isolated from various
cells and tissues.
Most have between 12 and 20 carbons in an
unbranched chain.
In most unsaturated fatty acids, the cis isomer
predominates; trans isomers are rare.
Unsaturated fatty acids have lower melting points
than their saturated counterparts.
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18-12
18 Fatty Acids
• Table 18.3
Carbon Atoms:
Double Bonds *
Structure
Saturated Fatty Acids
12:0
CH3 ( CH2 ) 1 0 COOH
Common
Name
Melting Point
(°C)
lauric acid
44
14:0
CH3 ( CH2 ) 1 2 COOH
myristic acid
58
16:0
CH3 ( CH2 ) 1 4 COOH
palmitic acid
63
18:0
CH3 ( CH2 ) 1 6 COOH
stearic acid
70
20:0
CH3 ( CH2 ) 1 8 COOH
arachidic acid
77
Uns aturated Fatty Acids
16:1
CH3 ( CH2 ) 5 CH= CH( CH2 ) 7 COOH
palmitoleic acid
1
18:1
CH3 ( CH2 ) 7 CH= CH( CH2 ) 7 COOH
oleic acid
16
18:2
CH3 ( CH2 ) 4 ( CH= CHCH2 ) 2 ( CH 2 ) 6 COOH linoleic acid
18:3
CH3 CH2 ( CH= CHCH2 ) 3 ( CH 2 ) 6 COOH
20:4
CH3 ( CH2 ) 4 ( CH= CHCH2 ) 4 ( CH 2 ) 2 COOH arachidonic acid
linolenic acid
-5
-11
-49
* The first number is the number of carbons in the fatty acid; the s econd is the
number of carbon-carbon double bonds in its hydrocarbon chain.
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18-13
18 Fatty Acids
• Unsaturated fatty acids generally have lower
melting points than their saturated counterparts.
COOH Stearic acid (18:0)
(mp 70°C)
COOH Oleic acid (18;1)
(mp 16°C)
COOH Linoleic acid (18:2)
(mp-5°C)
COOH Linolenic acid (18:3)
(mp -11°C)
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18-14
18 Fatty Acids
• Saturated fatty acids are solids at room
temperature; the regular nature of their
hydrocarbon chains allows them to pack together
in such a way as to maximize interactions (by
London dispersion forces) between their chains.
COOH
COOH
COOH
COOH
COOH
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18-15
18 Fatty Acids
• In contrast, all unsaturated fatty acids are liquids
at room temperature because the cis double
bonds interrupt the regular packing of their
hydrocarbon chains.
COOH
COOH
COOH
COOH
COOH
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18-16
18 Soaps
• Natural soaps are sodium or potassium salts of
fatty acids.
• They are prepared from a blend of tallow and
palm oils (triglycerides).
• Triglycerides are triesters of glycerol.
• the solid fats are melted with steam and the water
insoluble triglyceride layer that forms on the top
is removed.
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18-17
18 Soaps
• Preparation of soaps begins by boiling the
triglycerides with NaOH. The reaction that takes
place is called saponification (Latin: saponem,
“soap”). Boiling with KOH gives a potassium
soap.
O
O CH2 OCR
saponific ation
+ 3 N aOH
RCOCH
O
CH2 OCR
A triglyceride
( a triester of glycerol)
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CH2 OH
CHOH
+
O
+
3 RCO N a
CH2 OH
1,2,3-Propanetriol Sodium soaps
(Glycerol; glycerin)
18-18
18 Soaps
• In water, soap molecules spontaneously cluster
into micelles, a spherical arrangement of
molecules such that their hydrophobic parts are
shielded from the aqueous environment, and their
hydrophilic parts are in contact with the aqueous
environment.
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18-19
18 Soaps
• When soap is mixed with dirt (grease, oil, and fat
stains), soap micelles “dissolve” these nonpolar,
water-insoluble molecules.
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18-20
18 Soaps
• Natural soaps form water-insoluble salts in hard
water.
• Hard water contains Ca(II), Mg(II) and Fe(III) ions.
2+
2 CH3 ( CH2 ) 1 4 COO Na + + Ca
A sodium s oap
(soluble in water as micelles)
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-
[ CH3 ( CH2 ) 1 4 COO ] 2 Ca
Calcium s alt of a fatty acid
(insoluble in water)
2+
+
2 Na
18-21
+
18 Detergents
• The problem of formation of precipitates in hard
water was overcome by using a molecule
containing a - SO3- group ( sulfonic acid group) in
the place of a -CO2- group.
• Calcium, magnesium and iron salts of sulfonic acids,
RSO3H, are more soluble in water than salts of fatty
acids.
• Following is the preparation of the synthetic detergent,
SDS, a linear alkylbenzene sulfonate (LAS), an anionic
detergent.
CH 3 ( CH 2 ) 1 0 CH 2
Dodecylbenzene
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1 . H 2 SO 4
+
SO 3 N a
CH 3 ( CH 2 ) 1 0 CH 2
2 . Na OH
Sodium 4-dodecylbenzenes ulfonate
(SDS)
(an anionic detergent)
18-22
18 Detergents
• Among the most common additives to detergents
are foam stabilizers, bleaches, and optical
brighteners.
O
CH3 ( CH2 ) 1 0 CNH CH 2 CH2 OH
N -(2-Hydroxyethyl)dodecanamide
(a foam s tabilizer)
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O= B- O-O - N a + • 4 H2 O
Sodium perborate tetrahydrate
(a bleach)
18-23
18 Acidity of RCOOH
• Carboxylic acids are weak acids:
• Values of Ka for most unsubstituted aliphatic and
aromatic carboxylic acids fall within the range 10-4 to
10-5 (pKa 4.0 - 5.0).
O
O
+
CH3 COH + H2 O
CH3 CO + H3 O
Ka =
[CH3 COO-][ H3 O+ ]
[ CH3 COOH]
= 1.74 x 10-5
pK a = 4.76
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18-24
18 Acidity of RCOOH
• Substituents of high electronegativity, especially -OH,
-Cl, and -NH3+, near the carboxyl group increase the
acidity of carboxylic acids.
• Both dichloroacetic acid and trichloroacetic acid are
stronger acids than H3PO4 (pKa 2.1).
Formula: CH3 COOH
N ame:
pK a:
Acetic
acid
4.76
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ClCH2 COOH
Cl2 CHCOOH
Cl3 CCOOH
Chloroacetic D ichloroacetic Trich loroacetic
acid
acid
acid
2.86
1.48
0.70
In creasing acid strength
18-25
18 Acidity of RCOOH
• When a carboxylic acid is dissolved in aqueous
solution, the form of the carboxylic acid present
depends on the pH of the solution in which it is
dissolved.
O
R- C-OH
OH-
+
H
predominant
species when
the pH of the
solution is 2.0
or less
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O
O
R- C-OH + R- C-O -
present in equal
concentrations when
the pH of the
solution is equal to
the pK a of the acid
OHH+
O
R- C-O -
predominant
species when the
pH of the
solution is 7.0 or
greater
18-26
18 Reaction With Bases
• All carboxylic acids, whether soluble or insoluble
in water, react with NaOH, KOH, and other strong
bases to form water-soluble salts.
COOH + NaOH
H2 O
Ben zoic acid
(slightly soluble in w ater)
+
COO Na + H2 O
Sodiu m b enzoate
(60 g/100 mL w ater)
• They also form water-soluble salts with ammonia and
amines.
COOH + NH3
Benzoic acid
(s ligh tly solub le in w ater)
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H2 O
-
COO NH4
+
Ammoniu m b enzoate
(20 g/100 mL water)
18-27
18 Reaction With Bases
• Like inorganic acids, carboxylic acids react with
sodium bicarbonate and sodium carbonate to form
water-soluble sodium salts and carbonic acid.
• Carbonic acid then decomposes to give water and
carbon dioxide, which evolves as a gas.
CH3 COOH + NaHCO3
A cetic acid
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H2 O
-
+ +
CO2 + H2 O
CH3 COO Na
Sodium acetate
18-28
18 Fischer Esterification
• Fischer esterification is one of the most
commonly used preparations of esters.
• In Fischer esterification, a carboxylic acid is reacted
with an alcohol in the presence of an acid catalyst,
most commonly concentrated sulfuric acid.
O
H2 SO4
CH3 C-OH + H-OCH2 CH3
Eth anoic acid
Ethanol
(Acetic acid) (Ethyl alcohol)
O
CH3 COCH2 CH3 + H2 O
Ethyl ethanoate
(Ethyl acetate)
• Fischer esterification is reversible.
• It is possible to drive it in either direction by the choice
of experimental conditions (Le Chatelier’s principle).
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18-29
18 Fischer Esterification
• In Fischer esterification, the alcohol adds to the
carbonyl group of the carboxylic acid to form a
tetrahedral carbonyl addition intermediate.
• The intermediate then loses H2O to give an ester.
H
O
CH3 C + OCH2 CH3
OH
H2 SO4
O-H
CH3 C OCH 2 CH 3
OH
A tetrahed ral carbonyl
add ition in termediate
H2 SO4
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O
CH3 COCH2 CH3 + H2 O
18-30
18 Phosphoric Esters
• Phosphoric acid forms mono-, di-, and triphosphoric
esters.
• In more complex phosphoric esters, it is common to
name the organic molecule and then indicate the
presence of the phosphoric ester by either the word
"phosphate" or the prefix phospho-.
• Dihydroxyacetone phosphate and pyridoxal phosphate
are shown as they are ionized at pH 7.4, the pH of
blood plasma.
O
CH3 O-P-OH
OCH3
D imethyl ph os phate
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CH2 OH
CO O
CH2 -O-P-O
O
D ih yd roxyacetone
p hosphate
O
CHO
HO
CH 2 O-P-O
O
H3 C N
Pyridoxal ph os phate
18-31
18 Decarboxylation
• Decarboxylation: the loss of CO2 from a carboxyl
group.
O
RCOH
decarboxylation
RH +
CO 2
• Almost all carboxylic acids, when heated to a
very high temperature, will undergo thermal
decarboxylation.
• Most carboxylic acids, however, are resistant to
moderate heat and melt and even boil without
undergoing decarboxylation.
• An exception is any carboxylic acid that has a
carbonyl group on the carbon b to the COOH
group.
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18-32
18 Decarboxylation
• Decarboxylation of a b-ketoacid.
O
O
O
b a
OH
3-Oxobutanoic acid
(Acetoacetic acid)
warm
+
CO 2
Acetone
• The mechanism of thermal decarboxylation
involves (1) redistribution of electrons in a cyclic
transition state, (2) followed by keto-enol
enol of
tautomerism.
a ketone
O
H
O
(1)
O
(A cyclic six-membered
transition state)
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O
H
O
C
(2)
O
+
CO 2
O
18-33
18 Decarboxylation
• An important example of decarboxylation of a b-
ketoacid in biochemistry occurs during the
oxidation of foodstuffs in the tricarboxylic acid
(TCA) cycle. Oxalosuccinic acid, one of the
intermediates in this cycle, has a carbonyl group
(in this case a ketone) b to one of its three
carboxyl groups.
only this carboxyl
has a C=O beta to it .
H OOC
O
a b
COOH
COOH
Oxalosuccinic acid
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O
H OOC
COOH + CO 2
a-Ketoglutaric acid
18-34
18 Chapter 18
End
Chapter 18
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18-35