Chapter 20: Carboxylic

Acids and Nitriles

羧酸 與氰化物

Based on McMurry’s Organic Chemistry, 9th edition

 The Importance of Carboxylic Acids (RCO2H)
 Starting materials for acyl derivatives (esters, amides, and
acid chlorides)
 Abundant in nature from oxidation of aldehydes and alcohols
in metabolism
 Acetic acid, CH CO H, - vinegar
3 2

 Butanoic acid, CH3CH2CH2CO2H (rancid butter)

 Long-chain aliphatic acids from the breakdown of fats

2
 Why this Chapter?
 Carboxylic acids present in many industrial
processes and most biological processes
 They are the starting materials from which
other acyl derivatives are made
 An understanding of their properties and
reactions is fundamental to understanding
organic chemistry

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20.1 Naming Carboxylic Acids and Nitriles

 Carboxylic Acids, RCO2H

 derived from open-chain alkanes, replace the

terminal -e of the alkane name with -oic acid

 The carboxyl carbon atom is C1

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 Alternative Names
 Compounds with CO2H bonded to a ring are named using
the suffix -carboxylic acid
 The CO2H carbon is not itself numbered in this system
 Use common names for formic acid (HCOOH) and acetic
acid (CH3COOH)
 As a substituent, the CO2H group is called a carboxyl group

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 O

R C
 Naming Nitriles
 Nitriles, RC≡N 氰化物
 Compounds containing the –C≡N functional group
 Simple open chain nitriles are named by adding
nitrile as a suffix to the alkane name
 Nitrile carbon numbered C1
 Also named as derivatives of carboxylic acids
 Replacing the -ic acid or -oic acid ending with –onitrile
 Replacing the –carboxylic acid ending with -carbonitrile

IUPAC

Common names
20.2 Structure and Properties of Carboxylic Acids
 Carboxyl carbon sp2 hybridized
 carboxylic acid groups are planar with C–C=O and O=C–O
bond angles of approximately 120°
 Carboxylic acids form hydrogen bonds, existing as cyclic
dimers held together by two hydrogen bonds
 causes much higher boiling points than the corresponding
alcohols

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Structure and Properties of Carboxylic Acids

 Higher boiling points than similar alcohols, due to

dimer formation.

Acetic acid, b.p. 118C

兩分子羧酸間經由兩個氫鍵結合在一起，形成雙分子化合物。
 Dissociation of Carboxylic Acids
 Carboxylic acids are proton donors toward weak and
strong bases,

Produces metal carboxylate salts, RCO2 +M
 Carboxylic acids with more than six carbons are only
slightly soluble in water,
 But their conjugate base salts are water-soluble

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 Naming Carboxylic Acid Salts
 Name the cation.
 Then name the anion by replacing the
-ic acid with -ate.

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 Acidity Constant and pKa
 Carboxylic acids transfer a proton to water to give
H3O+ and carboxylate anions, RCO2
 The acidity constant, Ka,, is about 10-4 ~10-5 for a
typical carboxylic acid (pKa 4~ 5)
 Gives the extent of acidity dissociation

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 Acidity of Carboxylic Acids
For most Carboxylic Acids Ka is about 10-4 to 10-5
 Acidity of Caboxylic Acid
 Carboxylic acids are more acidic than alcohols and
phenols

 Carboxylic acid dissociate to give carboxylate ion

 Carboxylic ion is a stabilized resonance hybrid of two
equivalent structures
 Resonance Effects on Acidity
•
An alkoxide ion has its charge localized on one oxygen
atom and is less stable,
• A carboxylate ion has the charge spread equally over

both oxygens and is therefore more stable.

Formate Ion Structure: Resonance Stabilization

•Structure of the formate ion. Each C-O bond has a bond

order of 3/2 from one  bond and half a  bond, 127 pm in
length.
•The negative charge is dispersed equally over both oxygen.
Each oxygen atom bears half of the negative charge.
 20.3 Biological Acids and the Henderson-
Hasselbalch Equation
 Henderson-Hasselbalch equation: Calculates the
% of dissociated [A-] and undissociated [HA] forms
when pKa of given acid and the pH of the medium
are known
[H3O+ ][A - ] + [A -
]
pKa = -log = -log[H 3O ] - log
[HA] [HA]
[A - ]
= pH - log
[HA]
 Rearranging

-
[A ]
pH = pK a + log Henderson-Hasselbalch equation
[HA]
 20.4 Substituent Effects on Acidity
Inductive Effects on Acidity
 Electro-withdrawing substituents promote formation of the carboxylate ion
 Fluoroacetic, chloroacetic, bromoacetic, and iodoacetic acids are stronger acids than acetic acid
 electro-withdrawing substituents increase the acid strength
 Inductive effects operate through σ bonds and are dependent on distance
 Substituent moves farther from the carboxyl causing the effect of halogen substitution to decrease

• Inductive effec 誘導效應 : 拉電子基使酸性增加，給電子基使酸性降低

• 誘導效應隨著距離的增長對羧酸的影響減弱
The more stable the conjugate base,
the stronger its acid
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Substituent Effects on Acidity of p-Substituted
Benzoic Acids

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 Aromatic Substituent Effects
 An electron-withdrawing group (-NO2) increases acidity by
stabilizing the carboxylate anion, and an electron-donating
(activating) group (OCH3) decreases acidity by destabilizing
the carboxylate anion

• By finding the acidity of the corresponding benzoic acid, we

can be predicted the reactivity of reaction.
Hammett equation
quantitative
relationships
between structure
and activity.
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 Synthesis of Carboxylic Acids
O
R–OH or New
10 alcohol R H

H2CrO4
R –MgX + CO2

Hot, concd. O
KMnO4

R OH
New
KMnO4
heat H+, H2O

R –C N 
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 20.5 Preparation of Carboxylic Acids
From alkylbenzenes
 Oxidation of a substituted alkylbenzene with KMnO4 or
Na2Cr2O7 gives a substituted benzoic acid
(Section 16.9)
 1° and 2° alkyl groups can be oxidized, but 3° groups are not

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 From Alkenes

 Oxidative cleavage of an alkene with KMnO4

gives a carboxylic acid if the alkene has at
least one vinylic hydrogen (Section 7.9)

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 From Alcohols
 Oxidation of a primary alcohol or an aldehyde with
CrO3 in aqueous acid yields a carboxylic acid (Section
17.7)

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 Hydrolysis of Nitriles
 Hydrolysis of nitriles
 Nitriles on heating with acid or base yields carboxylic acids
 Conversion of an alkyl halide to a nitrile (with cyanide ion) followed
by hydrolysis produces a carboxylic acid with one more carbon (RBr
 RCN  RCO2H)

Best with 1° halides because elimination reactions occur with 2° or 3°
alkyl halides

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 Carboxylation of Grignard Reagents
 Carboxylation of Grignard Reagents
 Grignard reagents react with dry CO2 to yield a
metal carboxylate
 The organomagnesium halide adds to C=O of
carbon dioxide
 Protonation by addition of aqueous HCl in a
separate step gives the free carboxylic acid
 Carboxylation in Biosystem
Fatty-acid biosynthesis
20.6 Reactions of Carboxylic Acids: An Overview
 Carboxylic acids transfer a proton to a base to give anions,
which are good nucleophiles in SN2 reactions
 Like ketones, carboxylic acids undergo addition of
nucleophiles to the carbonyl group
 In addition, carboxylic acids undergo other reactions
characteristic of neither alcohols nor ketones
10 alcohol

(CH 17.4)
General reactions
of carboxylic acids LiAlH4

(CH 22) (CH 21)

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 20.7 Chemistry of Nitriles 氰化物

 The functional group of a nitrile is a cyano group, -CN

 -CN can be hydrolyzed to carboxylic acid, so nitriles
are acid derivatives.
 Nitrogen is sp hybridized, lone pair tightly held, so not
very basic. (pKb about 24).
 Chemistry of Nitriles
 Nitriles and carboxylic acids both have a carbon atom with
three bonds to an electronegative atom, and contain a  bond
 Both both are electrophiles and undergo nucleophilic addition
reactions

electrophile

–

+
+ –

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 Preparation of Nitriles
 Preparation of Nitriles
 SN2 reaction of CN– with 1°or 2° alkyl halide
CN- + R-X  RCN

 Also prepared by dehydration of 1° amides RCONH2

with dehydrating agents SOCl2 亞硫醯氯 or POCl3 三氯氧化
磷
 Mechanism of Dehydration of Amides
 Nucleophilic amide oxygen atom attacks SOCl2
followed by deprotonation and elimination

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 Reactions of Nitriles
 RCN is strongly polarized and with an
electrophilic carbon atom
 Attacked by nucleophiles to yield sp2-hybridized
imine anions

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Reactions of Nitriles : An Overview
Hydrolysis: Conversion of Nitriles into
Carboxylic Acids
 Hydrolysis - Conversion of nitriles into carboxylic acids
 Nitriles are hydrolyzed in with acid or base catalysis to a
carboxylic acid and ammonia

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Mechanism of Hydrolysis of Nitriles

 Nucleophilic addition of hydroxide to CN bond

 Protonation gives a hydroxy imine, which
tautomerizes to an amide
 A second hydroxide adds to the amide carbonyl
group and loss of a proton gives a dianion
 Expulsion of NH2 gives the carboxylate

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酮 - 烯醇互變異構

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Base-Catalyzed Hydrolysis of a Nitrile
 Reduction: Conversion of Nitriles into Amines
 Reduction of a nitrile with LiAlH4 gives a 1° amine
 Nucleophilic addition of hydride ion to the polar CN bond, yieldis an imine anion
 The C=N bond undergoes a second nucleophilic addition of hydride to give a dianion, which is protonated by
water

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Reaction of Nitriles with Organometallic Reagents

 Grignard reagents add to give an intermediate imine anion

that is hydrolyzed by addition of water to yield a ketone

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20.8 Spectroscopy of Carboxylic Acids and Nitriles

Infrared Spectroscopy
 O–H bond of the carboxyl group gives a very broad

absorption 2500 to 3300 cm1

 C=O bond absorbs sharply between 1710 and 1760

cm1
 Free carboxyl groups absorb at 1760 cm1

 Commonly encountered dimeric carboxyl groups

absorb in a broad band centered around 1710

cm1

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IR spectrum of Carboxylic Acids

Butanoic acid, CH3CH2CH2CO2H

 IR of Nitriles

 Nitriles show an intense CN bond absorption near

2250 cm1 for saturated compounds and 2230 cm1
for aromatic and conjugated molecules
 This is highly diagnostic for nitriles

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Nuclear Magnetic Resonance Spectroscopy
 Carboxyl 13COOH signals are at 165 to 185
 Aromatic and ,-unsaturated acids are near 165
and saturated aliphatic acids are near 185
 13C  N signal 115 to 130

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 Proton NMR

 The acidic CO2H proton is a singlet near  12

 When D2O is added to the sample the CO2H proton
is replaced by D causing the absorption to disappear
from the NMR spectrum

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 Summary
 Carboxylic acids are among the most useful
building blocks for synthesizing other molecules
 Nitriles are compounds containing the –C≡N
functional group
 Extent of dissociation of a carboxylic acid in a
buffered solution of a given pH can be calculated
with the Henderson–Hasselbalch equation
 Carboxylation is the reaction of Grignard
reagents with CO2