CARBOXYLIC ACIDS AND THEIR DERIVATIVES

Carboxylic acids and their derivatives are found extensively (widespread) in nature and are
among the most prevalent of synthetic materials. Many natural products are either carboxylic
acids or derived from them.

Carboxylic acids are often combined with other functional groups. Simple alkyl carboxylic
acids, composed of four to ten carbon atoms, are liquids or low melting solids having very
unpleasant odors.
The carboxyl functional group that characterizes the carboxylic acids is unusual in that it is
composed of two functional groups i.e. the carboxyl group is made up of a hydroxyl group
bonded to a carbonyl group. It is often written in condensed form as –CO2H or –COOH.

The change in chemical and physical properties resulting from the interaction of the hydroxyl
and carbonyl group are so profound that the combination is customarily treated as a distinct and
different functional group.

RELATED CARBONYL DERIVATIVES

Other functional group combinations with the carbonyl group can be prepared from carboxylic
acids, and are usually treated as related derivatives. Five common classes of these carboxylic
acid derivatives are listed in the following table. Although nitriles do not have a carbonyl group,
they are included here because the functional carbon atoms all have the same oxidation state. The
top row shows the general formula for each class, and the bottom row gives a specific example
of each. As in the case of amines, amides are classified as 1º, 2º or 3º, depending on the number
of alkyl groups bonded to the nitrogen.

1
NOMENCLATURE
As with aldehydes, the carboxyl group must be located at the end of a carbon chain. In the
IUPAC system of nomenclature the carboxyl carbon is designated #1, and other substituents are
located and named accordingly. The characteristic IUPAC suffix for a carboxyl group is "oic
acid", and care must be taken not to confuse this systematic nomenclature with the similar
common system.

IUPAC Names are obtained by dropping the final –e of the name alkane corresponding to the
longest chain in the acid and replaced by –oic acid. The carboxyl carbon is assigned number 1.

These two nomenclatures are illustrated as below

Egs
CH2CH3
‫׀‬
CH3-C- CH2-COOH
‫׀‬
Cl
3-chloro-3-methylpentanoic acid (IUPAC)
CH3

CO2H
m-toluic acid(COMMON NAME)
m-methylbenzoic acid(IUPAC)
CH3CH=CH-CH2-CH2-COOH
4-Hexenoic acid (IUPAC)

Substituted carboxylic acids are named either by the IUPAC system or by common names.
Some common names, the amino acid threonine for example, do not have any systematic origin
and must simply be memorized. In other cases, common names make use of the Greek letter
notation for carbon atoms near the carboxyl group. Some examples of both nomenclatures are
provided below.

2
Simple dicarboxylic acids having the general formula HO2C–(CH2) n–CO2H (where n = 0 to 5)
are known by the common names: Oxalic (n=0), Malonic (n=1), Succinic (n=2), Glutaric (n=3),
Adipic (n=4) and Pimelic (n=5) Acids. Common names, such as these can be troublesome to
remember, so mnemonic aids, which take the form of a catchy phrase, have been devised. For
this group of compounds one such phrase is: "Oh My Such Good Apple Pie".

Formula Common IUPAC

HOOC.COOH Oxalic acid Ethanedioic acid
HOOC.CH2 COOH Malonic acid Propanedioic acid
COOH
Phthalic acid
COOH

Carboxylic salts are named as –ates.

E.g.
CH3COO- Na+
Sodium ethanoate or sodium acetate

NB; the carboxyl group has the highest priority in functional group nomenclature.

3
The following are some examples of other naturally occurring carboxylic acids. The molecular
structures range from simple to complex and often incorporate a variety of other functional
groups, and many are chiral.

PHYSICAL PROPERTIES
Carboxylic acids are polar substances as they form strong hydrogen bonds with each other and
with water.
Carboxylic acids have exceptionally high boiling points, (bpts) due in large part to dimeric
associations involving two hydrogen bonds.

Monocarboxylic acids have higher bpts than the corresponding alcohols of the same molecular
weight. The low molecular weight members show appreciable solubility in water and these
decreases as the carbon chain increases.
A unique hydrogen bonding arrangement between two carboxylic acid molecules leads to the
formation of dimmers in the solid and liquid states and even in the gas phase.
O H O
R C C R Dimers
O H O

O H O H
R C Solubility in water
O H O H
H

4
In general, dipolar attractive forces between molecules act to increase the boiling point of a given
compound, with hydrogen bonds being an extreme example. Hydrogen bonding is also a major
factor in the water solubility of covalent compounds.

The melting points and boiling points of carboxylic acids are generally higher than those
hydrocarbons and oxygen-containing organic compounds of comparable shape and size as stated
above

ACIDITY OF CARBOXYLIC ACIDS

Why should the presence of a carbonyl group adjacent to a hydroxyl group have such a
profound effect on the acidity of the hydroxyl proton?

Carboxylic acids are much stronger acids than water and alcohols. Electronegative substituent
near the carboxyl group act to increase the acidity.

Resonance and inductive effects also play major role in the acidity of carboxylic acids

E.g.
Cl Cl H H
↑ ↑ ‫׀‬ ‫׀‬
Cl←C-COOH > Cl←C-COOH > Cl←C-COOH > H ─C-OOH
↓ ‫׀‬ ‫׀‬ ‫׀‬
Cl H H H

pka 0.70 1.48 2.86 4.76

(→ Negative inductive effect)

Dicarboxylic acids and acidity

Common in Nature (metabolic cycles)
Electron-withdrawing effect of 2nd carboxyl group leads to enhanced acidity. But the effect
diminishes with distance
HOOCCOOH (oxalic acid) pKa 1.23; 4.19
HOOCCH2 COOH (malonic acid) pKa 2.83; 5.69
HOOC CH2 CH2COOH (succinic acid) pKa 4.16; 5.61

5
Carboxylic Acid Preparation Reactions
Oxidation of Primary Alcohols

Oxidation of Aldehydes

Oxidation of Substituted Aromatics

Hydrolysis of Acid derivatives and Nitriles

Oxidative Cleavage of Alkenes/Alkynes

Carboxylic Acids via Oxidation

(a) From Primary Alcohols

(b) From Aldehydes

(c) From Substituted Aromatics

(a)

(b)

(c)

6
 Carboxylic Acids via Hydrolysis
(a) From carboxylic acid derivatives

(b) From nitriles

Carboxylic Acids via Oxidative Cleavage of

Alkenes/Alkynes

7
Typical Carboxylic Acid Reactions
Conversion to carboxylate salts
Conversion to acid halides
Conversion to esters
Conversion to amides
Conversion to anhydrides
Reduction to alcohols
Decarboxylation

Carboxylates from Carboxylic Acids

(a) Reaction with active metals

(b) Reaction with strong base

(c) Reaction with weak base

8
 Acid Chlorides from Acids
(a) Reaction with Thionyl chloride

(b) Reaction with Phosphorus trichloride

(c) Reaction with Phosphorus pentachloride

(a)

(b)

(c)

Ester formation From Carboxylic Acids

(a) Via acid catalyzed reaction with ROH

(b) Methyl esters via diazomethane

(c) From Acid Chlorides

(d) From Acid Anhydrides

(a)

(b)

(c)

(d)

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 Amide formation
(a) Direct Conversion of RCOOH to Amides

(b) From Acid Chlorides

(c) From Acid Anhydrides

(d) From Esters

(d) From Esters

(a)

(b)

(c)

(d)

10
 Anhydride formation
(a) Via Dehydration of Carboxylic Acids

(b) Via Reaction of Acid Halides with RCOOH

(c) Via reaction of Acid Halides with Carboxylate Salts

(a)

(b)

(c)

Formation of Cyclic anhydrides

11
Reduction of Carboxylic Acids
Lithium Aluminum Hydride reduction

Diborane reduction

Decarboxylation of RCOOH
Thermolysis of beta-diacids

Thermolysis of beta-keto acids

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 CARBOXYLIC ACID DERIVATIVES

O
R C O R ESTERS

O O
R C O C R ACID ANHYDRIDE

O
R C Cl ACYL OR ACID CHLORIDE

R-C≡N NITRILE

O O O
R C NH2 , R C NHR' , R C NR'R'' AMIDE

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 ESTERS
Formed when carboxylic acids react with alcohols through a condensation reaction –
Esterification. The reaction is acid catalysed.

H+

RCOOH + RI OH RCOORI + H2O

(strong acid)

Nomenclature: Esters derive their names from the name of the alcohol (-yl) and the acid (ate or
oate).

H+

CH3COOH + CH3CH2OH CH3COOCH2CH3 + H2O

Ethanoic acid Ethanol Ethylethanoate

The reverse rxn, which is acid- catalyzed hydrolysis of an ester is also possible.

H3O+

RCOORI + H2O RCOOH + RI OH

Dil. Aq. acid

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 Mechanism for Esterification

+
O H O
+ H O H
C +H C + CH3 O H
C6 H5 C6H5 C O+ CH3
O CH3 - H+ C6 H5 O H - CH3 O H
O H

O
- H+ H O+ - H2 O
C +
H O:
C6 H5 O CH3 + H C + H2 O
C 6H 5 C 6H 5 C O CH3
O CH3
+O H
H

Esters can also be prepared from acyl chlorides and acid anhydrides with alcohols

From acyl chlorides

RCOCl + RI OH ───────→ RCOORI + HCl

From acid anhydrides

O
R C
O + R'O H RCOO R' + RCOOH
R C
O

Transesterification
This is a method of preparing one ester from another. It is catalyzed by an acid.
H+, heat

RCOORI + RII OH ───────→ RCOORII + RI OH

15
Eg

H+

CH3CH2COOCH3 + CH3CH2CH2OH─→ CH3CH2COOCH2CH2CH3 + CH3OH

SAPONIFICATION - Base-Promoted Hydrolysis of Esters

Refluxing an ester with aq. NaOH gives the Na salt of the acid and alcohol (soap making). The
triglycerides (oil) are used for soap making

RCOORI + NaOH ─────→ RCOO- Na+ + RI OH

ACYL CHLORIDES
These are the most reactive of the acid derivatives. They are prepared by reactions between the
acid chlorides of inorganic acids (PCl3, PCl5, SOCl2) and carboxylic acids.

Nomenclature: Change the “-ic acid” of the carboxylic acid to “yl halide”.

E.g. CH3COCl is ethanoyl chloride

O
RCOOH + SOCl2 ─────→ R C Cl + SO2 + HCl

O
3RCOOH + PCl3 ─────→ 3 R C Cl + H3PO3

O
RCOOH + PCl5 ─────→ R C Cl + POCl3 + HCl

REACTIONS

O
1. R C Cl + RI OH ─────→ RCOORI + HCl

NaOH Ester

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 O
2. R C Cl + RI COO- Na+ ─────→ R(CO)2O -RI + NaCl

Acid anhydride

O
3. R C Cl + 2NH3 ─────→ RCONH2 + NH4Cl

Amide

O
4. R C Cl + 2RI NH2 ─────→ RCONHRI + RINH3+ Cl-

1o amine N- substituted amide

O
5. R C Cl + 2RI RIINH ─────→ RCONRI RII + RIRIINH2+ Cl-

2o amine N,N- disubstituted amide

Hydrolysis

O
6. R C Cl + H2O ─────→ RCOOH

O
7. R C Cl + OH - ─────→ RCOO- + Cl-

H2O

CARBOXYLIC ACID ANHYDRIDES

Nomenclature: Change the “acid” of the carboxylic acid to “anhydride”.

E.g. CH3CO.O.COCH3 is acetic anhydride or ethanoic anhydride

C6H5CO.O.COC6H5 is benzoic anhydride

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 1. Reaction of carboxylic acids and acyl chlorides in the presence of pyridine give acid
anhydrides.

O O N+ Cl-
N R C O C R' + H
RCOOH + RI COCl + ─────→

O O

2. RCOO- Na+ + RI COCl ─────→ R C O C R' + NaCl

3. Heating appropriate dicarboxylic acids sometimes yield cyclic anhydrides

O O
C OH C
230 oC
O + H2O
C OH C
O
O
Phthalic acid Phthalic anhydride

(Approx. 100% yield)

REACTIONS

O O

1. R C O C R' + RI OH ─────→ RCOORI + R’COOH

Ester

O O

2. R C O C R' + 2NH3 ─────→ RCONH2 + R’COO- NH4+

Amide

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 O O

3. R C O C R' + 2RI NH2 ─────→ RCONHRI + R’COO- RINH3+

1o amine N- substituted amide

O O

4. R C O C R' + 2RI RIINH ──→ RCONRI RII + R’COO- RIRIINH2+

2o amine N,N- disubstituted amide

Hydrolysis

O O

5. R C O C R' + H2O ────→ 2 RCOOH

O O
R C O C R' + OH - ─────→ 2RCOO-

H2O

AMIDES

They can be synthesized from RCOCl, (RCO)2O, RCOOR, RCOOH and RCOO- (carboxylic
salts). There is nucleophilic substitution reaction by ammonia or an amine at the acyl carbon.
(These have all been discussed already).

Nomenclature: change -ic or -oic acid of the carboxylic acid to –amide.

E.g. CH3CONH2 is ethanamide or acetamide

C6H5CONH2 is benzamide

RCONH2 Unsubstituted

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RCONHRI Monosubstituted

RCONRIRII Disubstituted

Amides from Esters

0-50C

ClCH2 COOCH2CH3 + NH3 ────→ ClCH2 CO NH2 + C2H5 OH

Ethylchloroacetate Chloroacetamide

Hydrolysis
Acid hydrolysis yields a RCOOH while base hydrolysis yields a salt of carboxylic acid.

H2O

RCONH2 + H3O+ ────→ RCOOH + NH4+

heat

H2O

RCONH2 + NaOH ────→ RCOO- Na+ + NH3

Heat

NITRILES
They are prepared by dehydration of amides. Two pathways are possible.

P2O5

1. RCONH2 ────→ R-C≡N + H3PO3 + H2O

heat

(CH3CO)2O

2. RCONH2 ────→ R-C≡N + CH3COOH + H2O

heat

20
Nitriles undergo hydrolysis (acid or base) to yield products similar to that of amides

H3O+, H2O

R-C≡N ───────→ RCOOH

heat

OH-, H2O

R-C≡N ───────→ RCOO-

Heat

LACTAMS
These are cyclic amides and the size of the ring determines the type and name of the lactam

O
O
O C C
CH2 C CH2 N H CH2 N H
R CH N H CH2 CH R CH R
CH2
CH2

β-lactam γ-lactam δ-lactam

Example of a group of drugs that contains a lactam ring is the penicilins.

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 LACTONES
These are cyclic esters formed by the intramolecular esterification of carboxylic acids whose
molecules have a hydroxyl group on the γ and δ- carbon. They are therefore called γ and δ-
lactones.

H O
O+
R CH CH2 CH 2 CH 2 C OH O
+
+ H 3O
O:
R
H

δ – Lactone

 - Lactone

Example of a lactone is vit C (γ-lactone)

OH
HO
O
H O
HO C H
CH2OH
Vitamin C

Relative reactivity of acyl compounds

RCOCl > (RCO)2 O > RCOOR > RCONH2

Acyl chloride Acid anhydride Esters Amides

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