Based on McMurry’s Organic Chemistry, 7th edition

Dr M. Mehrdad University of Guilan, Department of

Chemistry, Rasht, Iran

m-mehrdad@guilan.ac.ir

2شیمی آلی

Chapter 20: Carboxylic Acids and Nitriles

The Importance of Carboxylic Acids

(RCO2H)

Abundant in nature from oxidation of aldehydes

and alcohols in metabolism

◦ Acetic acid, CH3CO2H, - vinegar

◦ Butanoic acid, CH3CH2CH2CO2H (rancid butter)

◦ Long-chain aliphatic acids from the breakdown of fats

Carboxylic acids present in many industrial

processes and most biological processes

An understanding of their properties and reactions

is fundamental to understanding organic chemistry

2

The Importance of Carboxylic Acids

(RCO2H)

They are the starting materials from which

other acyl derivatives are made

3

The Importance of Carboxylic Acids

(RCO2H)

They are the starting materials from which

other acyl derivatives are made

4

20.1

Naming Carboxylic Acids & Nitriles

Carboxylic Acids, RCO2H

If derived from open-chain alkanes, replace the terminal -e of the alkane name with -oic acid

The carboxyl carbon atom is C #1

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20.1

Naming Carboxylic Acids & Nitriles

Carboxylic Acids, RCO2H

If derived from open-chain alkanes, replace the terminal -e of the alkane name with -oic acid

The carboxyl carbon atom is C #1

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Propanoic acid 4-Methylpentanoic acid 3-Ethyl-6-methyloctanedioic acid

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

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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

8

trans-4-Hydroxycyclohexanecarboxylic acid 1-cyclopentenecarboxylic acid

Common Names: Carboxylic acids some of the 1st compound

studied so some of their common names are still used. Especially for those with biological interest.

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Names

accepted

by IUPAC

Common Names:

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Nitriles, RCN

Closely related to carboxylic acids named by adding -nitrile

as a suffix to the alkane name, with the

nitrile carbon numbered C #1

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4-Methylpentanenitrile

Nitriles, RCN

Complex nitriles are named as derivatives of carboxylic

acids.

◦ Replace -ic acid or -oic acid ending with –onitrile

◦ or by replacing the –carboxylic acid ending with -carbonitrile

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Nitriles, RCN

Complex nitriles are named as derivatives of carboxylic

acids.

◦ Replace -ic acid or -oic acid ending with –onitrile

◦ or by replacing the –carboxylic acid ending with -carbonitrile

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2,2-Dimethylcyclohexanecarbonitrile

(From 2,2-dimethylcyclohexanecarboxylic acid)

Acetonitrile

(From acetic acid) Benzonitrile

(From benzoic acid)

20.2 Structure & Properties

Carboxyl carbon sp2 hybridized:

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planar with bond angles of approximately 120°

20.2 Structure & Properties:

15

Carboxylic acids form hydrogen bonds,

exist as cyclic dimers held together by 2 hydrogen bonds

Strong hydrogen bonding causes much higher boiling points

than the corresponding alcohols

1-Propanal

(MW = 58)

1-Propanol

(MW = 60)

Ethanoic Acid (Acetic acid)

MW = 60

CH3CH2CH2-OH

Boiling

Point 49oC 97oC 118oC

Dissociation of Carboxylic Acids

Carboxylic acids are proton donors toward weak and strong

bases, producing metal carboxylate salts, RCO2 +M

16

Carboxylic acids with more than six carbons are only

slightly soluble in water, but their conjugate base salts are

water-soluble

Acidity Constant and pKa

Carboxylic acids transfer a proton to water to give H3O+

and carboxylate anions, RCO2, but H3O

+ is a much

stronger acid

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The acidity constant, Ka,, is about 10-5 for a typical

carboxylic acid (pKa ~ 5)

pKa = -1.7Lower pKa means stronger acid so

equilibrium favors starting materials

pKa = ~5pKa = 15.7

(acts as a base here)

Substituent Effects on AcidityElectron withdrawing (electronegative) substituents (like F, Cl, Br, I) promote

formation of the carboxylate ion so raise the Ka (lower the pKa)

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The acidity constant, Ka,, is about 10-5 for atypical carboxylic acid (pKa ~ 5)

Ka,, ~10-15 to -16 for alcohols and water (pKa~ 15 to 16)

CH3OH 15.5

H2O 15.7

Resonance Effects on Acidity

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Alcohols

Phenols

Carboxylic acid

Inorganic acids

Resonance Effects on Acidity

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Alcohols weaker acids since O- not stabilized by resonance

Carboxylic acids more acidic since O- stabilized by resonance

Negative charge spread over O-C-O

C-O Bond

lengths same

(127 pm)

C=O Bond length

(120 pm)

C-O Bond length

(134 pm)

20.3 Biological Acids and the

Henderson-Hasselbalch Equation

If pKa of given acid and the pH of the medium are known, %

of dissociated and undissociated forms can be calculated

using the Henderson-Hasselbalch eqn

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هاسل بالخ-اسید های بیولوژیکی و معادله هندرسون

20.4 Substituent Effects on Acidity

Electron withdrawing (electronegative) substituents (like F, Cl, Br, I)

promote formation of the carboxylate ion so raise the Ka (lower the

pKa)

They stabilize the carboxylate anion by induction

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Aromatic Substituent Effects

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electron-withdrawing

( deactivating) groups (like -NO2)

increase acidity by

stabilizing the carboxylate

anion

electron-donating (activating) group (like OCH3)

decreases acidity by

destabilizing the

carboxylate anion

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Aromatic Substituent Effects

20.5 Preparation of Carboxylic Acids:

From Oxidation of Benzylic Carbons

Oxidation of a substituted alkylbenzene with KMnO4 or Na2Cr2O7 gives a substituted benzoic acid

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1° and 2° alkyl groups can be oxidized, but 3° are not

CH2CH3

C

H3C

H3CCH3

CH CH3

CH3

C

C

H3C

H3CCH3

C

O

OH

O

OH

KMnO4

1o

2o

3o3o

From Oxidative Cleavage of Alkenes

Oxidative cleavage of an alkene with KMnO4 gives a

carboxylic acid if the alkene has at least one vinylic hydrogen

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KMnO4C C

H

CH3

CH3CH2

CH3H3O+

C

CH3CH2

CH3

O C

OH

CH3

O+

KMnO4C C

H

H

CH3CH2

H H3O+ C

CH3CH2

HO

O C

OH

OH

O+

CO2

From Oxidation of 1o Alcohols &

Aldehydes Oxidation of a 1o alcohols or aldehydes with CrO3 in

aqueous acid

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Hydrolysis of Nitriles

Hot acid or base yields carboxylic acids

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CH3 CH2 CH2 C NH3O+

CH3 CH2 CH2 C

O

OHor

1) NaOH

2) H3O+

Halides Nitriles Carboxylic Acids Conversion of an alkyl halide to a nitrile (by an SN2 with

cyanide ion) followed by hydrolysis produces a carboxylic

acid with one more carbon (RBr RCN RCO2H)

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Best with 1o halides

because competing

elimination reactions

occur with 2o or 3o

alkyl halides

Carboxylation of Grignard Reagents

Grignard reagents react with dry CO2 to yield a metal carboxylate◦ Limited to alkyl halides that can form Grignard reagents

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Protonation by

addition of aqueous

HCl in a separate

step gives the free

carboxylic acid

The organomagnesium

halide adds to C=O of

carbon dioxide

Halides Nitriles Carboxylic Acids

Halides Grignard Carboxylic Acids

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20.6 Reactions of Carboxylic Acids:

An Overview

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Carboxylic acid 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

Carboxylic acids undergo substitutions reactions characteristic of

neither alcohols nor ketones

1) LiAlH4

2) H3O+

NaOH

20.7 Chemistry of Nitriles

Nitriles and carboxylic acids both have a carbon atom

with three bonds to an electronegative atom, and contain

a bond

C’s of nitriles and carboxylic acids are electrophilic

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d+ d+d-

d-

d-

d+

Preparation of Nitriles:

Dehydration of Amides

Reaction of primary amides RCONH2 with SOCl2 or

POCl3 (or other dehydrating agents)

Not limited by steric hindrance or side reactions (as is the

reaction of alkyl halides with NaCN)

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Mechanism: Dehydration of Amides

Nucleophilic amide oxygen atom attacks SOCl2 followed by deprotonation and elimination

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Nucleophilic amide

oxygen atom

attacks SOCl2

Deprotonation of

acidic H on N

Elimination of the SO2

and Cl leaving groups

Reactions of Nitriles

RCN is strongly polarized and with an electrophilic carbon

Attacked by nucleophiles to yield sp2-hybridized imine anions

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Hydrolysis: Nitriles Carboxylic Acids

Hydrolyzed in with acid or base catalysis to a carboxylic

acid and ammonia or an amine

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Mechanism:

Hydrolysis of

Nitriles

Nucleophilic addition of

hydroxide to CN 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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Mechanism:

Step 4: Hydrolysis of Amides

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Reduction: Nitriles 1o Amines

◦Reduction of a nitrile with LiAlH4 gives a primary amine

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Nucleophilic addition

of hydride ion (H-) to

the polar CN bond,

yields an imine anion

The C=N bond undergoes a second

nucleophilic addition of hydride (H-) to give

a dianion, which is protonated by water

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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Reactions of Nitriles: Overview

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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 cm1

C=O bond absorbs sharply between 1710 and 1760 cm1

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Commonly encountered dimeric carboxyl groups absorb in a broad band centered around 1710 cm1

Free carboxyl groups absorb at 1760 cm1

Infrared Spectroscopy

O–H bond of the carboxyl group gives

a very broad absorption 2500 to

3300 cm1

Commonly encountered dimeric carboxyl groups absorb in a broad band centered around 1710 cm1

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IR of Nitriles Nitriles show an intense CN bond absorption near 2250

cm1 for saturated compounds and 2230 cm1 for

aromatic and conjugated molecules

This is highly diagnostic for nitriles

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C-13 NMR Carboxyl 13COOH signals are at d165 to d185

Aromatic and ,b-unsaturated acids are near d165 and

saturated aliphatic acids are near d185

13C N signal d115 to d130

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Proton NMR The acidic CO2H proton is a singlet near d 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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