Carboxylic Acids and the Acidity of the O–H Bond

228 Pages·2012·7.97 MB·English

19
Carboxylic Acids and the Acidity
of the O–H Bond
19.1 Structure and bonding
19.2 Nomenclature
19.3 Physical properties
19.4 Spectroscopic properties
19.5 Interesting carboxylic
acids
19.6 Aspirin, arachidonic acid,
and prostaglandins
19.7 Preparation of carboxylic
acids
19.8 Reactions of carboxylic
acids—General features
19.9 Carboxylic acids—Strong
organic Brønsted–Lowry
acids
19.10 Inductive effects in
aliphatic carboxylic acids
19.11 Substituted benzoic acids
19.12 Extraction
19.13 Sulfonic acids
19.14 Amino acids
Hexanoic acid is a low molecular weight carboxylic acid with the foul odor associated with dirty
socks and locker rooms. Its common name, caproic acid, is derived from the Latin word caper,
meaning “goat.” The fl eshy coat of ginkgo seeds contains hexanoic acid, giving the seeds an
unpleasant and even repulsive odor. It is likely that this foul odor served as an attractant for
seed dispersal at some time during the 280 million years that Ginkgo biloba has existed on
earth. Since only female ginkgo trees produce seeds, male trees, which are propagated by cut-
tings and grafts, are generally planted by landscapers in the United States. In Chapter 19 we
learn about the properties of hexanoic acid and other carboxylic acids.
688
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19.1 Structure and Bonding 689
Chapter 19 serves as a transition between the preceding discussion of resonance and
aromaticity, and the subsequent treatment of carbonyl chemistry. We pause to study the chemis-
try of the OH group by examining carboxylic acids (RCOOH), and to a lesser extent, phenols
(PhOH) and alcohols (ROH).
In Chapter 19 we concentrate on the acidity of carboxylic acids, and revisit some of the fac-
tors that determine acidity, a topic fi rst discussed in Chapter 2. Then, in Chapters 20 and 22 we
will learn other reactions of carboxylic acids that occur at the carbonyl group.
19.1 Structure and Bonding
Carboxylic acids are organic compounds containing a carboxy group (COOH). Although
the structure of a carboxylic acid is often abbreviated as RCOOH or RCO H, keep in mind that
2
the central carbon atom of the functional group is doubly bonded to one oxygen atom and singly
bonded to another.
O O
The word carboxy (for a COOH
C C
group) is derived from carbonyl R OH OH
(C––O) + hydroxy (OH).
carboxylic acid carboxy group
The carbon atom of a carboxy group is surrounded by three groups, making it sp2 hybridized
and trigonal planar, with bond angles of approximately 120°. The C––O of a carboxylic acid is
shorter than its C–O.
sp2 hybridized O 121 pm The C O is shorter
136 pm than the C O.
C H =
CH O
3
acetic acid 119°
The C–O single bond of a carboxylic acid is shorter than the C–O single bond of an alcohol.
This can be explained by looking at the hybridization of the respective carbon atoms. In the alco-
hol, the carbon is sp3 hybridized, whereas in the carboxylic acid the carbon is sp2 hybridized. As
a result, the higher percent s-character in the sp2 hybrid orbital shortens the C–O bond in the car-
boxylic acid.
143 pm
O 136 pm
C H O
CH O CH H
3 3
sp2 hybridized sp3 hybridized
33% s-character 25% s-character
higher percent s-character lower percent s-character
shorter bond longer bond
Because oxygen is more electronegative than either carbon or hydrogen, the C–O and O–H
bonds are polar. The electrostatic potential plot of acetic acid in Figure 19.1 shows that the car-
bon and hydrogen atoms are electron poor and the oxygen atoms are electron rich.
Figure 19.1
δ(cid:150)
Electrostatic potential plot of
acetic acid (CH COOH) O δ+
3
C H = δ+
CH O
3 δ(cid:150)
acetic acid
Acetic acid contains two electron-rich oxygen atoms (in red). Its carbonyl carbon and hydroxy
hydrogen are both electron defi cient.
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690 Chapter 19 Carboxylic Acids and the Acidity of the O–H Bond
19.2 Nomenclature
Both IUPAC and common names are used for carboxylic acids.
19.2A IUPAC System
In IUPAC nomenclature, carboxylic acids are identifi ed by a suffi x added to the parent name of
the longest chain, and two different endings are used depending on whether the carboxy group is
bonded to a chain or ring.
To name a carboxylic acid using the IUPAC system:
[1] If the COOH is bonded to a chain of carbons, fi nd the longest chain containing the COOH
group, and change the -e ending of the parent alkane to the suffi x -oic acid. If the COOH
group is bonded to a ring, name the ring and add the words carboxylic acid.
[2] Number the carbon chain or ring to put the COOH group at C1, but omit this number from
the name. Apply all of the other usual rules of nomenclature.
Sample Problem 19.1 Give the IUPAC name of each compound.
CH
3 CH
a. CH3 CH CH CH2CH2COOH b. CH3 CH3
3
CH
3
COOH
Solution
a. [1] Find and name the longest chain [2] Number and name the substituents:
containing COOH:
C4
CH3 O CH3 O
CH CH CH CH CH C CH CH CH CH CH C
3 2 2 3 2 2
CH OH CH OH
3 3
C5 C1
hexane hexanoic acid
two methyl substituents on C4 and C5
(6 C’s)
The COOH contributes Answer: 4,5-dimethylhexanoic acid
one C to the longest chain.
b. [1] Find and name the ring bonded to [2] Number and name the substituents:
COOH.
C5
C2
CH CH
3 3
CH CH
CH 3 CH 3
3 3
COOH COOH
C1
Number to put COOH at C1 and give the second
cyclohexane + carboxylic acid
substituent (CH ) the lower number (C2).
(6 C’s) 3
Answer: 2,5,5-trimethylcyclohexanecarboxylic acid
Problem 19.1 Give the IUPAC name for each compound. O
a. CH CH CH C(CH ) CH COOH d.
3 2 2 32 2
OH
b. CH CH(Cl)CH CH COOH
3 2 2
c. (CH CH ) CHCH CH(CH CH )COOH
3 22 2 2 3
Problem 19.2 Give the structure corresponding to each IUPAC name.
a. 2-bromobutanoic acid d. 2-sec-butyl-4,4-diethylnonanoic acid
b. 2,3-dimethylpentanoic acid e. 3,4-diethylcyclohexanecarboxylic acid
c. 3,3,4-trimethylheptanoic acid f. 1-isopropylcyclobutanecarboxylic acid
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19.2 Nomenclature 691
19.2B Common Names
Most simple carboxylic acids have common names that are more widely used than their IUPAC
names.
• A common name is formed by using a common parent name followed by the suffi x -ic acid.
Table 19.1 lists common parent names for some simple carboxylic acids. These parent names are
used in the nomenclature of many other compounds with carbonyl groups (Chapters 21 and 22).
Greek letters are used to designate the location of substituents in common names.
• The carbon adjacent to the COOH is called the ` carbon.
• The carbon bonded to the ` carbon is the a carbon, followed by the f (gamma) carbon,
the c (delta) carbon, and so forth down the chain. The last carbon in the chain is
sometimes called the W (omega) carbon.
The ` carbon in the common system is numbered C2 in the IUPAC system.
IUPAC system: Start numbering here.
C1C2C3C4C5
HOOC C C C C
α β γ δ
Common system: Start lettering here.
Table 19.1 Common Names for Some Simple Carboxylic Acids
Number of C atoms Structure Parent name Common name
O
1 C form- formic acid
H OH
O
2 acet- acetic acid
C
CH OH
3
O
3 C propion- propionic acid
CH CH OH
3 2
O
4 C butyr- butyric acid
CH CH CH OH
3 2 2
O
5 valer- valeric acid
C
CH CH CH CH OH
3 2 2 2
O
6 capro- caproic acid
C
CH CH CH CH CH OH
3 2 2 2 2
O
benzo- benzoic acid
C
OH
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692 Chapter 19 Carboxylic Acids and the Acidity of the O–H Bond
Problem 19.3 Draw the structure corresponding to each common name:
a. α-methoxyvaleric acid c. α,β-dimethylcaproic acid
b. β-phenylpropionic acid d. α-chloro-β-methylbutyric acid
Problem 19.4 Give an IUPAC and common name for each of the following naturally occurring carboxylic acids:
(a) CH CH(OH)CO H (lactic acid); (b) HOCH CH C(OH)(CH )CH CO H (mevalonic acid).
3 2 2 2 3 2 2
19.2C Other Nomenclature Facts
Many compounds containing two carboxy groups are also known. In the IUPAC system, diacids
are named by adding the suffi x -dioic acid to the name of the parent alkane. The three simplest
diacids are most often identifi ed by their common names, as shown.
O O O
O O
HO
HO OH OH
HO OH
O
oxalic acid malonic acid succinic acid
(ethanedioic acid) (propanedioic acid) (butanedioic acid)
Metal salts of carboxylate anions are formed from carboxylic acids in many reactions in Chapter
19. To name the metal salt of a carboxylate anion, change the -ic acid ending of the carboxylic
acid to the suffi x -ate and put three parts together:
name of the metal cation + parent + suffix
common
or -ate
IUPAC
Two examples are shown in Figure 19.2.
Problem 19.5 Give the IUPAC name for each metal salt of a carboxylate anion: (a) C H CO – Li+; (b) HCO – Na+;
6 5 2 2
(c) (CH ) CHCO – K+; (d) (CH CH ) CHCH CH(Br)CH CH CO – Na+.
32 2 3 22 2 2 2 2
Problem 19.6 Depakote, a drug used to treat seizures and bipolar disorder, consists of a mixture of valproic acid
[(CH CH CH ) CHCO H] and its sodium salt. Give IUPAC names for each of these compounds.
3 2 22 2
19.3 Physical Properties
Carboxylic acids exhibit dipole–dipole interactions because they have polar C–O and O–H
bonds. They also exhibit intermolecular hydrogen bonding because they possess a hydrogen
atom bonded to an electronegative oxygen atom. Carboxylic acids often exist as dimers, held
together by two intermolecular hydrogen bonds between the carbonyl oxygen atom of one mole-
cule and the OH hydrogen atom of another molecule (Figure 19.3). Carboxylic acids are the
most polar organic compounds we have studied so far.
How these intermolecular forces affect the physical properties of carboxylic acids is summarized
in Table 19.2.
Figure 19.2 sodium cation potassium cation
O O
Naming the metal salts of
C C
carboxylate anions CH3 O(cid:150) Na+ CH3CH2 O(cid:150) K+
parent + suffix parent + suffix
acet- -ate propano- -ate
sodium acetate potassium propanoate
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19.4 Spectroscopic Properties 693
Figure 19.3
hydrogen bond
Two molecules of acetic acid
(CH COOH) held together by
3 two hydrogen bonds H O H O H
H
C C = = C C
H
H O H O H
hydrogen bond
Table 19.2 Physical Properties of Carboxylic Acids
Property Observation
Boiling point and • Carboxylic acids have higher boiling points and melting points than other compounds of
melting point comparable molecular weight.
CH CH CH CH CH CH CHO CH CH CH OH CH COOH
3 2 2 3 3 2 3 2 2 3
VDW VDW, DD VDW, DD, HB VDW, DD, two HB
MW = 58 MW = 58 MW = 60 MW = 60
bp 0 °C bp 48 °C bp 97 °C bp 118 °C
Increasing strength of intermolecular forces
Increasing boiling point

Solubility • Carboxylic acids are soluble in organic solvents regardless of size.
• Carboxylic acids having ≤ 5 C’s are water soluble because they can hydrogen bond with H O
2
(Section 3.4C).
• Carboxylic acids having > 5 C’s are water insoluble because the nonpolar alkyl portion is too
large to dissolve in the polar H O solvent. These “fatty” acids dissolve in a nonpolar fat-like
2
environment but do not dissolve in water.
Key: VDW = van der Waals, DD = dipole–dipole, HB = hydrogen bonding, MW = molecular weight
Problem 19.7 Rank the following compounds in order of increasing boiling point. Which compound is the most
water soluble? Which compound is the least water soluble?
CH COOH COOCH CH CH CH OH
2 3 2 2 2
19.4 Spectroscopic Properties
Carboxylic acids have very characteristic IR and NMR absorptions. In the IR, carboxylic acids
show two strong absorptions.
• The C––O group absorbs at about 1710 cm–1, in the usual region for a carbonyl.
• The O–H absorption occurs from 2500–3500 cm–1. This very broad absorption some-
times obscures the C–H peak at 3000 cm–1.
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694 Chapter 19 Carboxylic Acids and the Acidity of the O–H Bond
Figure 19.4 100
O
The IR spectrum of butanoic
C
acid, CH CH CH COOH
3 2 2 CH CH CH OH
3 2 2
e
c C O
n
a
mitt 50
s
n O H
a
Tr
% C H
0
4000 3500 3000 2500 2000 1500 1000 500
Wavenumber (cm(cid:150)1)
• A strong C––O absorption occurs at 1712 cm–1.
• The broad O–H absorption (2500–3500 cm–1) nearly obscures the C–H peak at ~3000 cm–1.
The IR spectrum of butanoic acid in Figure 19.4 illustrates these characteristic peaks.
Carboxylic acids have two noteworthy 1H NMR absorptions and one noteworthy 13C NMR
absorption.
• The highly deshielded OH proton absorbs in the 1H NMR spectrum somewhere
between 10 and 12 ppm, farther downfi eld than all other absorptions of common organic
compounds. Like the OH signal of an alcohol, the exact location depends on the degree of
hydrogen bonding and the concentration of the sample.
• The protons on the α carbon to the carboxy group are somewhat deshielded, absorbing at
2–2.5 ppm.
• In the 13C NMR spectrum, the carbonyl absorption is highly deshielded, appearing at
170–210 ppm.
Figure 19.5 illustrates the 1H and 13C NMR spectra of propanoic acid.
Problem 19.8 Explain how you could use IR spectroscopy to distinguish among the following three compounds.
OH
O O
C C O
CH CH CH CH OH CH CH CH CH OCH
3 2 2 2 3 2 2 2 3
Problem 19.9 Identify the structure of a compound of molecular formula C H O that gives the following 1H NMR
4 8 2
data: 0.95 (triplet, 3 H), 1.65 (multiplet, 2 H), 2.30 (triplet, 2 H), and 11.8 (singlet, 1 H) ppm.
Problem 19.10 How could 1H NMR spectroscopy be used to distinguish between formic acid (HCO H) and malonic
2
acid [CH (CO H) ]?
2 2 2
19.5 Interesting Carboxylic Acids
Several simple carboxylic acids have characteristic odors and fl avors.
HCOOH
• Formic acid, a carboxylic acid with an acrid odor and a biting
taste, is responsible for the sting of some types of ants. The
name is derived from the Latin word formica, meaning “ant.”
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19.5 Interesting Carboxylic Acids 695
Figure 19.5
The 1H and 13C NMR spectra 1H NMR spectrum Ha
of propanoic acid
CH CH COOH
3 2
H H H
a b c
H
b
Sometimes the OH absorption
of a carboxylic acid is very
broad, so that it is almost
buried in the baseline of the
1H NMR spectrum, making it
diffi cult to see.
H
c
12 10 8 6 4 2 0
ppm
The OH proton is highly deshielded.
C
13C NMR spectrum b
C
a
CH CH COOH
3 2
C C C
a b c
C
c
200 180 160 140 120 100 80 60 40 20 0
ppm
The carbon of the C O is highly deshielded.
• 1H NMR spectrum: There are three signals due to three different kinds of H atoms. The H and H
a b
signals are split into a triplet and quartet, respectively, but the H signal is a singlet.
c
• 13C NMR spectrum: There are three signals due to three different kinds of carbon atoms.
CH COOH
Pure acetic acid is often called 3
gl acial acetic acid, because • Acetic acid is the sour-tasting component of vinegar. The
it freezes just below room name comes from the Latin acetum, meaning “vinegar.” The
temperature (mp = 17 °C), air oxidation of ethanol to acetic acid is the process that
forming white crystals makes “bad” wine taste sour. Acetic acid is an industrial
reminiscent of the ice in starting material for polymers used in paints and adhesives.
a glacier.
CH CH CH COOH
3 2 2
• Butanoic acid is an oxidation product that contributes to the
disagreeable smell of body odor. Its common name, butyric
acid, is derived from the Latin word butyrum, meaning
“butter,” because butyric acid gives rancid butter its peculiar
odor and taste.
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696 Chapter 19 Carboxylic Acids and the Acidity of the O–H Bond
Oxalic acid and lactic acid are simple carboxylic acids quite prevalent in nature. Oxalic acid
occurs naturally in spinach and rhubarb. Lactic acid gives sour milk its distinctive taste.
O H OH
C OH C OH
HO C = CH C =
3
O O
oxalic acid lactic acid
Although oxalic acid is toxic, 4-Hydroxybutanoic acid, known by its common name γ-hydroxybutyric acid (GHB), is an illegal
you would have to eat about recreational drug that depresses the central nervous system and results in intoxication. GHB is
nine pounds of spinach at one highly addictive and widely abused, and because its taste can be easily masked in an alcoholic
time to ingest a fatal dose. beverage, it has been used as a “date rape” drug.
O
HO =
OH
4-hydroxybutanoic acid
GHB
Salts of carboxylic acids are commonly used as preservatives. Sodium benzoate, a fungal
growth inhibitor, is a preservative used in soft drinks, and potassium sorbate is an additive that
prolongs the shelf-life of baked goods and other foods.
O O
Soaps, the sodium salts of
C
fatty acids, were discussed in O(cid:150) Na+ O(cid:150) K+
Section 3.6.
sodium benzoate potassium sorbate
19.6 Aspirin, Arachidonic Acid, and Prostaglandins
Recall from Chapter 2 that aspirin (acetylsalicylic acid) is a synthetic carboxylic acid, similar
in structure to salicin, a naturally occurring compound isolated from willow bark, and salicylic
acid, found in meadowsweet.
O O O
C C C
OH OH OH O(cid:150) Na+
O O OH OH
C HO
O CH3 O
salicylic acid sodium salicylate
OH
aspirin HO (isolated from (sweet carboxylate salt)
(acetylsalicylic acid) meadowsweet)
OH
salicin
(isolated from
The word aspirin is derived willow bark)
from the prefi x a- for acetyl +
spir from the Latin name spirea Both salicylic acid and sodium salicylate (its sodium salt) were widely used analgesics in the
for the meadowsweet plant. nineteenth century, but both had undesirable side effects. Salicylic acid irritated the mucous
membranes of the mouth and stomach, and sodium salicylate was too sweet for most patients.
Aspirin, a synthetic compound, was fi rst sold in 1899 after Felix Hoffman, a German chemist
at Bayer Company, developed a feasible commercial synthesis. Hoffman’s work was motivated
by personal reasons; his father suffered from rheumatoid arthritis and was unable to tolerate the
sweet taste of sodium salicylate.
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19.7 Preparation of Carboxylic Acids 697
How does aspirin relieve pain and reduce infl ammation? Aspirin blocks the synthesis of prosta-
Aspirin is the most widely
glandins, 20-carbon fatty acids with a fi ve-membered ring that are responsible for pain, infl am-
used pain reliever and anti-
mation, and a wide variety of other biological functions. PGF contains the typical carbon
infl ammatory agent in the 2`
skeleton of a prostaglandin.
world, yet its mechanism of
action remained unknown HO
until the 1970s. John Vane,
Bengt Samuelsson, and Sune COOH
Bergstrom shared the 1982
Nobel Prize in Physiology or
HO
Medicine for unraveling the OH
details of its mechanism.
PGF2α
a prostaglandin
Prostaglandins are not stored in cells. Rather they are synthesized from arachidonic acid, a poly-
unsaturated fatty acid having four cis double bonds. Unlike hormones, which are transported
in the bloodstream to their sites of action, prostaglandins act where they are synthesized. Aspi-
rin acts by blocking the synthesis of prostaglandins from arachidonic acid. Aspirin inactivates
cyclooxygenase, an enzyme that converts arachidonic acid to PGG , an unstable precursor of
2
PGF and other prostaglandins. Aspirin lessens pain and decreases infl ammation because
2α
it prevents the synthesis of prostaglandins, the compounds responsible for both of these
physiological responses.
Aspirin acts here.
HO
COOH O COOH COOH
C5H11 cyclo- O
oxygenase
OOH HO OH
arachidonic acid
PGG2 PGF2α
unstable intermediate and other prostaglandins
Although prostaglandins have a wide range of biological activity, their inherent instability often
limits their usefulness as drugs. Consequently, more stable analogues with useful medicinal
properties have been synthesized. For example, latanoprost (trade name Xalatan) and bimato-
prost (trade name Lumigan) are prostaglandin analogues used to reduce eye pressure in individu-
als with glaucoma.
HO HO
CO CH(CH ) CONHCH CH
2 32 2 3
HO HO
OH OH
latanoprost bimatoprost
Problem 19.11 How many tetrahedral stereogenic centers does PGF2α contain? Draw its enantiomer. How many
of its double bonds can exhibit cis-trans isomerism? Considering both its double bonds and its
tetrahedral stereogenic centers, how many stereoisomers are possible for PGF2α?
19.7 Preparation of Carboxylic Acids
Our discussion of the reactions involving carboxylic acids begins with a brief list of reactions
that synthesize them. This list serves as a reminder of where you have seen this functional group
before. In these reactions, the carboxy group is formed in the product, and many different func-
tional groups serve as starting materials. Reactions that produce a particular functional group are
called preparations.
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