24.

CARBOXYLIC ACID AND

DERIVATIVES

1. INTRODUCTION
Compounds containing the carboxyl group are distinctly O O
acidic and are called carboxylic acids. R C O C R Anhydride

R C  N Nitrile
O
R C OH
R C X Acyl halide
On simple O
They have general formula CnH2nO2 acidic / basic
hydrolysis R C NH2 Amide
Carboxylic acid derivatives are compounds with functional O
groups that can be converted to carboxylic acids by a R C O R’ Ester
simple acidic or basic hydrolysis. O
Flowchart 24.1: Derivatives of carboxylic acid

2. CLASSIFICATION OF CARBOXYLIC ACIDS

Dicarboxylic Aromatic
acids carboxylic acids
- Structure contain two R = Aromatic ring
COOH grps.

Classification
of
Carboxylic acids
R-COOH

Hydroxy acids Amino acids

- R will contain - R = Contains NH2 group
(-OH) groups

Unsaturated
carboxylic acid
- R will contain double/
Triple bond

Flowchart 24.2: Classification of carboxylic acid

2 4 . 2 | Carboxylic Acid and Derivatives

3. NOMENCLATURE OF CARBOXYLIC ACIDS

Name Alkane Alkanoic acid
The IUPAC system of nomenclature assigns a characteristic suffix to these
classes. The ending “e” is removed from the name of the parent chain and Given the  1 location
is replaced –”oic” acid.
Position in numbering.

  O

   OH

Adjacent to C
O

Table 24.1: IUPAC name of simple carboxylic acid

Formula Common Name Source IUPAC Name Melting Point Boiling Point

HCOOH Formic acid Ants (L. Formica) Methanoic acid 8.4 ºC 101 ºC

CH3COOH Acetic acid Vinegar (L. Acetum) Ethanoic acid 16.6 ºC 118 ºC

CH3CH2COOH Propionic acid Milk (Gk. Protus prion) Propanoic acid -20.8 ºC 141 ºC

CH3(CH2)2COOH Butyric acid Butter (L. Butyrum) Butanoic acid -5.5 ºC 164 ºC

CH3(CH2)3COOH Valeric acid Valerian root Pentanoic acid -34.5 ºC 186 ºC

CH3(CH2)4COOH Caproic acid Goats (L. Caper) Hexanoic acid -4.0 ºC 205 ºC

CH3(CH2)5COOH Enanthic acid Vines (Gk. Oenanthe) Heptanoic acid -7.5 ºC 223 ºC

CH3(CH2)6COOH Caprylic acid Goats (L. Caper) Octanoic acid 16.3 ºC 239 ºC

CH3(CH2)7COOH Pelargonic acid Pelargonium (an herb) Nonanoic acid 12.0 ºC 253 ºC

CH3(CH2)8COOH Capric acid Goats (L. Caper) Decanoic acid 31.0 ºC 219 ºC

Example:

O O

OH CH3CH2C
OH
Butanoic acid Propanoic acid
(Butyric Acid)
(Propionic Acid)

O O

ClCH2CH2C
OH
OH
3-Chloropropanoic acid
2-Methylpentanoic acid (-Chloropropionic acid)
(-Methylvaleric acid)
 Chem i str y | 24.3

Table 24.2: IUPAC naming of substituted carboxylic acid

(1) Naming carboxyl - Carboxyl group added to a ring. Example

groups attached to
- Suffix “ carboxylic acid” added to O
a ring
name of the cyclic compound
C
OH

Cyclopentanecarboxylic acid
O

C
OH

Br
Cis-2-Bromocyclohexanecarboxylic acid

(2) Naming - Carboxyl group attached to a cation O

carboxylates Acetate
Sodium
C
H3 C O Na
Cation “-ic acid”
Sodium ethanoate
replaced by
(Sodium Acetate)
“-ate” O

H3C C
CH2 O K

Potassium Propanoate
(Potassium propionate)

(3) Naming the acids i) Hydroxyl substituent –OH O

containing other
‘’ from hydroxyl is removed
functional groups OH
(-COOH = highest OH OH
priority )
2, 4- Dihydroxybutanoic acid

ii) Aldehyde / ketone substituent Name as “ OXO-”

O
O O
or
H OH

Aldehyde / Ketone O
2- Oxobutanoic acid

iii) Amino substituent – NH2 O

OH
NH2
2-Aminobutanoic acid
2 4 . 4 | Carboxylic Acid and Derivatives

iv) Alkene substituent O

OH
Butanoic acid
O
cis/trans or E/Z nomenclature for
the alkene needs to be included if OH
necessary. 3-Butenoic acid

Position
O

OH
Trans-3-pentenoic acid

OH

(E) -2-Methyl-2-butenoic
acid
(4) Di-carboxylic acids - Carboxyl groups occupy the ends of O O
the chain
OH
HO
Propanedioic acid

4.PHYSICAL PROPERTIES OF ACIDS AND ACID DERIVATIVES

(a) Physical appearance and odour
C1 – C3 = Liquid = Colourless & pungent smelling
C4 – C6 = Liquid (oily) = Colourless & unpleasant smell
C > C7 = waxy solids= Colourless
(b) Boiling oints: Refer the following Flow-chart for a better understanding.
(L.H.S.=Left Hand Side)
Reasons

Similar molecular weight Gives a stable hydrogen bonded

dimer
Alcohols O H O
O R C C R
O H O
R C OH
Aldehyde Possess a higher
b.p as compared
to L.H.S.
In alcohols, OH bond is less
Ketone
polar than OH of COOH due
to the presence of
C = O group.

Flowchart 24.3: Comparison of B.p of carboxylic acid with other carbonyl compound
 Chem i str y | 24.5

(c) Melting Points:

(i) Carboxylic acid with more than 8 carbon atom and a double bond have low melting point due to the
inability to form a stable lattice.
Low m.p.
High m.p.
COOH
CH3 COOH
H 3C

Lie on
Lie on opposite side same side

(ii) Structures with even number of C atoms have a higher melting point as compared to structures having
odd number of C-atoms.
(iii) The high M.Pof primary and secondary amides is due to the strong hydrogen bonding and the presence
of electron-withdrawing and electron-donating group.

e - withdrawing
:

O:
C R/H
:

R N
e - donating
R/H

H-bo
O ndin
g
C 
H O
R N
C  H
H R N
H

(d) Solubility:
(i) Lower carboxylic acid ( C1 – C2 ) are - miscible with water acids
(ii) Instead of dimerization, they form H-bonds with water.
(iii) As the length of chain increases, the solubility decreases.
(iv) The derivatives like acid chlorides and anhydrides react with solvents like H2O & alcohol.

5. METHODS OF PREPARATION OF CARBOXYLIC ACIDS

General reaction of preparation of carboxylic acid

O
RMgX + C=O dry ether
+ R CH2 COOH
H3O
(CO2)
H+ or OH-
Grignard reagent
hydrolysis
carboxylation
R C  N+2H2O
Acid / Alkaline
hydrolysis of
nitriles
2 4 . 6 | Carboxylic Acid and Derivatives

(a) Synthesis of carboxylic acids by the carboxylation of Grignard reagents

:
:O O
- +

:
:
R MgX + C=O C =O

Dry ether

O MgX
R C =O : :

H3 O
OH X
R C= O + Mg
:

:
Carboxylic OH
acid

-RMgX acts as a nucleophile

Example:
1. Mg / diethyl ether
CH C HCH CH → CH C HCH CH
3| 2 3 2. CO 3| 2 3
2
Cl CO H
3. H O+ 2
3
2-Chlorobutane 2-Methylbutanoic acid (78 - 88%)

1.Mg/diethylether
2. CO2
CH3 3. H3O+ CH3
Br CO2H
9-Bromo-10-methylphenanthrene 10-Methylphenanthrene-8-carboxylic acid

(i) CO2
CH3 CH MgBr CH3 CH COOH
(ii) H2O/H+
CH3 CH3
Isobutyric acid (2-methyl propanoic acid)

(b) Synthesis of Carboxylic acids by the hydrolysis of nitriles Mechanism:

Hydrolysis of cyanides (Acid catalysed):
O
Heat
RCN +2H2O + H +
R C OH + NH+4
Nitrile Water Carboxylic Ammonium
acid ion

Mechanism:
(a) Formation of Amide
 
R-CN H
:

R-C=N-H
: :

O
H H
:

R-C=N-H
O
:

H  H
tautomerisation
R C NH2
O
:
 Chem i str y | 24.7

(b) Formation of Acid

H H  H
:
:O:

:
R C NH2 O
H
 OH

:
R C NH2
:

:
OH

: :
:OH
H+ transfer 
R C NH3
:
OH

: :
:O

R C + NH4
OH

Example:
O
H2O
CH2Cl NaCN H2SO4
CH2CN CH2COH
DMSO heat

Benzyl chloride Benzyl cyanide (92%) Phenylacetic acid (77%)

PLANCESS CONCEPTS

•• Alkyl cyanides needed for the purpose can easily be prepared from the corresponding alkyl halides
with alcoholic KCN or NaCN.
R – Cl + KCN → R – C ≡ N + KCl
•• This reaction is used to ascend the series having one carbon atom more than the corresponding alkyl
halides which are prepared from alcohol on treating with phosphorus halide.
ROH + PX5 → R – X + POX3 + HX
•• This hydrolysis of alkyl cyanide provides a useful method to get carboxylic acid having one carbon
atom more than the original alkyl halide and alcohols.

By Oxidation of alkyl benzenes – aromatic acids are produced.

CH3 COOH CH2CH3

KMnO4/OH- KMnO4/OH-
+ +
(ii) H /H2O (ii) H /H2O

Toluene Benzoic acid Ethylbenzene

E.g
K2Cr2O7
CH3 CH2 + 6[O] HOOC COOH + 2H2O
H2SO4

p-Xylene Terephthalic acid

Vaibhav Krishnan (JEE 2009, AIR 22)

2 4 . 8 | Carboxylic Acid and Derivatives

6. CHEMICAL REACTIONS

6.1. Acidic Strength


Acidity of carboxylic acids : R C O H

: :
: :
R C O: + H
O O

Exists as

2 Equivalent cannonical strs.

O O
R C R C
O O

O
R C
O
Resonance Hybrid

Table 24.3: Comparative acidity of Carboxylic acid with electron withdrawing group vs Carboxylic acid with electron donating
group

R= Electron withdrawing Group R= Electron Donating Group

⇒ Shows -I effect ⇒ Shows +I effect

⇒ Stabilises anion & increases acidic nature ⇒ Destabilizes anion & decrease acidic nature

⇒ Example ⇒ Example

O O
R C R C
O O

Tips and Tricks

Acidity of acids is compared by comparing stability of conjugate base
 Chem i str y | 24.9

6.2 Reactions Involving Removal of Proton From–OH Group

Removal of proton
from -OH Grp.
* Blue litmus turns red

R-COOH

R’MgX
Na2CO3/ ether
NaHCO3
NaOH
Na R’- H + RCOO MgX
RCOO Na + H2O (with Grignard reagent)
+ CO2
Brisk effervescence

RCOO Na + H2O
(with alkalis)
RCOONa + H2
(with metals)

Flowchart 24.4: n Reaction involving displacement of H from -OH group.

Important Point:
A stronger acid displaces a weaker acid from the salt of the weaker acid.
Example: CH3COOH (Strongeracid) + CH3ONa → CH3COONa + CH3 − OH
culsalenacid

Example: CH3COOH (Stronger acid) + NaHCO3 → CH3COONa + H2CO3 (Weaker acid) → H2O +CO2↑ (lab. test of
carboxylic acid)

6.3 Reactions Involving Replacement of –OH Group

Replacement
of
-OH Group
R C OH
P2O5 PCl5
O
R C O C R R C Cl
O O NH3 R’OH; O
Anhydride
R C NH2 R C OR’
O O
Amide Fischer
Esterification

Flowchart 24.5: Reaction Involving removal of OH group.

O O
:

G
R C OH R C G + OH

Strong base so not a basicity must be less

good leaving group than basicity of G‒
2 4 . 1 0 | Carboxylic Acid and Derivatives

(a) Formation of acid chlorides

O
PCl5
R C Cl + POCl3 + HCl
Pyridine
O
R-COOH PCl3
R C Cl + H3PO3
Pyridine
O
SOCl2 R C Cl + SO2 + HCl

O O
Example:
reflux
C + SOCl2 C + SO2 + HCl
OH OH
Benzoic acid Benzoyl chloride

Example: COOH COCl

heat
+ PCl5
O2N NO2 O2N NO2 + POCl3 + HCl

3, 5-Dinitrobenzoic 3, 5-Dinitrobenzoyl
acid chloride

(b) Fisher Esterification: Carboxylic acid react with alcohol to form esters through a condensation reaction
known as esterification.

General Reaction:
O O
H
R C OH + R’ OH R C OR’ + H2O

Specific Examples:

O O
H
CH3 C OH+CH3CH2 OH CH3 C OC2H5+H2O
O O
H
C6H5 C OH+CH3 OH C6H5 C OCH3 +H2O

Mechanism : (Acid catalysed esterification)

(i) A reactive electrophile is generated by addition of a proton or a Lewis acid.
(ii) A tetrahedral intermediate containing two equivalent hydroxyl groups is obtained by the nucleophilic
attack of the alcohol .
(iii) Elimination of these hydroxyl groups after a proton shift (tautomerism) occurs leading to the formation
of water and the ester.
 Chem i str y | 24.11

:O: 
:O H


:
R C OH +H O H R C OH
H

:
:O H
R’ OH
R C OH
O Proton

:
R’  H Transfer


:
H O H

:
R C O H
:O R’

:
: :
R C O H
:O R’
:


:
:
+
R C O: + H O H (H3O )
OR’ H

The forward reactions give acid catalysed esterification of an acid while the reverse account for the acid catalysed
hydrolysis of an ester
Acid catalysed ester hydrolysis.
O O

H3 O
R C OR’ + H2O R C OH + R’ OH

For esterification of an acid we can use an excess of the alcohol and removal of water to prevent the reverse
reaction, Hydrolysis of an ester uses a large excess of water and refluxing the ester with dilute aqueous HCl or dilute
aqueous H2SO4 occurs.

(c) Formation of amides:

O O O
  150-200C
R C OH + NH3 R C ONH4 R C NH2 + H2O

In fact, amides cannot be prepared from carboxylic acids and amines unless the ammonium salt is heated
strongly to dehydrate it. This is not usually a good method of preparing amides.

(d) Formation of acid anhydride:

O
O RC
P2O5
2R C OH O+ H2O
RC
O

6.4 Decarboxylation Reactions

DECARBOXYLATION
REACTIONS
O
R C OH
Soda-lime
O H Ele H2 O Kolbe’s
decarboxylation
Na aO ctr electrolysis
oly
Na2CO3+ R- H C sis R R +CO2+H2
2 4 . 1 2 | Carboxylic Acid and Derivatives

(a) Soda-lime decarboxylation:

General reaction:
O
NaOH + CaO
R C OH R H + CO2
Mechanism
NaOH 
R C OH R C ONa
-H2O
O O
OH
CaO 
R C ONa

O


R Na + NaHCO3
Carbanion
RH + Na2CO3
Alkane

(i) The stability of carbanion intermediate decides the rate of reaction .

(ii) Rate of decarboxylation increases with the presence of electron withdrawing group at R-COOH.

Example: CH3
HCOOH CH3 COOH CH3 CH COOH CH3 C COOH
CH3 CH3

(iii) Presence of some functional groups on aliphatic acids enable the decarboxylation.

: :

O
:
: :

R C O O :O :
-CO2
:

CH2 C R C R C
:

: O: CH2 CH2
:

Resonance
stabilized anion
Aliphatic acids that do undergo successful decarboxylation have certain functional groups or double or triple
bonds in the α or β positions.

Table 24.4: Decarboxylation product of substituted carboxylic acid

Acid type Decarboxylation product

(1) Malonic | |
HOOC − C− COOH HOOC − C− H
| |

(2) α-Cyano | |
NC − C− COOH NC − C− H
| |

(3) α-Nitro | |
O2N − C− COOH O2N − C− H
| |

(4) α-Aryl | |
Ar − C− COOH Ar − C− H
| |
 Chem i str y | 24.13

Acid type Decarboxylation product

(5) β-Keto | |
− C − C− COOH − C − C− H
|| | || |
O O

(6) α, α, α-Trihalo X3C–COOH X3C–H

(7) β, γ-Unsaturated | |
− C = C− C− COOH − C = C− C− H
| | | | | |

(b) Kolbe’s electrolysis

Electrolysis
2RCOOK + 2HOH  → R – R + 2CO2 + H2 + 2KOH

ANODE CATHODE

R C O: -e R C O:
: :

K +e K+H2O
O O RCOOK RCOO + K
R + CO2
+2e- 
2H2O 2OH + 2H

R
R -R H2

RCOOK + H2O

Electrolysis
Example: 2CH3 – COOK + 2H2O 
→ CH3CH3 +2CO2 + H2 + 2KOH

6.5 HVZ Reaction (Halogenation of Aliphatic Acids and Substituted Acids)

Converts a carboxylic acid possessing an α-hydrogen to an α-halocarboxylic acid when treated with phosphorus
and halogen. It is called as Hell-Volhard-Zelinsky reaction where regioselectivity allows alpha-halogenation only.
Cl ,P
2 → ClCH COOH 
2 → Cl CHCOOH Cl ,P
2 → Cl CCOOH Cl ,P
CH3COOH  2 2 3

Mechanism
(a) Carbonyl oxygen reacts with phosphorus trihalide to form a P-O bond giving the release of a halide anion.
(b) Attack of halide forms an intermediate to release a rearranged acyl halide, an acid and a phosphine oxide.
(c) Enol tautomer of acyl halide attacks the halogen molecule to form α-halo acyl halide.
(d) On hydrolysis, α-halocarboxylic acid is formed.

RCHCOOH + large excess of NH3 RCHCOOH

Br NH2
An -halogenated acid An -amino acid
+
H
RCHCOOH + NaOH RCHCOONa RCHCOOH

Br OH OH
An -hydroxy acid
+
H
RCH2CHCOOH + KOH (alc) RCH =CHCOO- RCH=CHCOOH
An , -unsaturated
Br acid
2 4 . 1 4 | Carboxylic Acid and Derivatives

7. CARBOXYLIC ACID DERIVATIVES

Functional derivatives of carboxylic acids
-Acid chlorides
-Anhydrides
-Amides
-Esters
The above are compounds in which the replacement of –OH of a carboxyl group is done by –Cl,–COOR , –NH2,or
–OR.

Characteristic reaction of acid derivatives (Nucleophilic acyl substitution):

Nucleophilic acyl substitution

-An addition - elimination mechanism

Nu
R R
Nu
:

: :
C O: C O:
L L
Tetrahedral
carbon - SP3
- L, the substituent is
protonated, to serve
as a better leaving
group. Nu
R
: :

- L = Leaving Group O:
- Nu = Nucleophile L

- Weaker the base, better

will be the leaving group.
R
C=O +:L
Nu
- The Nu should be a
stronger base.
O
L = -X - O- C - R - OR - OH - NH2
[Order of Reactivity]

Examples:

(a) O O O O O
R C Cl + CH3 C O R C Cl R C O C CH3 + Cl
Stronger base
O C CH3
(pka of CH3COOH is 5)
weaker base
O
(pka of HCl = -7)
(b) O O

R C OH + NH2 R C NH2 +OH

Stonger base weaker base
(pka of NH2 is 35) (pka of HOH is 15)
 Chem i str y | 24.15

(c) O O O

CH3 C O C CH3 + ROH CH3 C OR + CH3COO

pka = 16 pka = 5
(d) O O

C6H5 C OCH3 + NH3 C6H5 C NH2 + CH3O

pka = 35 pka = 16
(e) O O
C6H5 C NH2 + CH3OH C6H5 C OCH3 + NH2
pka = 16 pka = 35

PLANCESS CONCEPTS

Condition for nucleophilic substitution reaction:

O O

R C L + Nu R C Nu + L

• L must be better leaving group than Nu⊖, i.e., basicity of Nu should be more than that of L.
• Must be a strong enough nucleophile to attack RCOL.
• Carbonyl carbon must be enough electrophilic to react with
Nikhil Khandelwal (JEE 2009, AIR 94)

7.1 Acid Halides

(a) Methods of preparation Acyl halides

By-Products
PCl5 By-Products
PCl5 POCl3+HCl
SOCl2 POCl3+HCl
R - COOH R - COCl SO2 + HCl
SOCl2
Pyridine
R - COOH R - COCl SO
H 2 + HCl
Pyridine 3PO3
PCl3 H PO
O PCl3 O 3 3
CH3 O C OH + SOCl2 CH3 OC Cl + SO2 + HCl
CH3 C acid
E.g Ethanoic OH + SOCl2 CH3 C chloride
Ethanoyl Cl + SO2 + HCl
E.g Ethanoic acid Ethanoyl chloride

O O
C OH + SOCl2 C Cl + SO2 +HCl
Benzoic acid Benzoyl chloride
2 4 . 1 6 | Carboxylic Acid and Derivatives

(b) Chemical Reactions O

O O
R’ C OH
R C O C R’+ HCl
Py Anhydride
O
R’ OH
R C O R’+ HCl
Py Ester
O
R C Cl NH3/R’NH2 O
R C NH2 + H2O + Cl
Base Amide (Substituted)
H2O O
R C OH + HCl
Acid
Flowchart 24.5: General reactions of Acid halides

(i) Reaction with carboxylic acids

Carboxylic acids with acyl chlorides yield acid anhydrides with the help of a weak organic base, pyridine.
Pyridine acts both as a catalyst and a base, which neutralizes the formed hydrogen chloride.
O O O O
Pyridine
CH3(CH2)5CCl + CH3(CH2)5COH CH3(CH2)5COC(CH2)5CH3
Heptanoyl Heptanoic Heptanoic anhydride
chloride acid (78 - 83%)

(ii) Reaction with alcohols

O O
Pyridine
C6H5CCl + (CH3)3COH C6H5COC(CH3)3

Benzoyl tert-Butyl tert-Butyl

chloride alcohol benzoate (80%)

(iii) Reaction with ammonia and amines

O O
NaOH
C6H5CCl + HN C6H5C-N
H2O

Benzoyl Piperidine N-Benzoylpiperidine

chloride (87-91%)

(iv) Hydrolysis
O O

C6H5CH2CCl + H2O C6H5CH2COH + HCl

Phenylacetyl Water Phenylacetic Hydrogen

chloride acid chloride

(v) Reaction of acid halide with organometallic

• With Grignard reagent
• Reaction with Gilmann reagent
(Grignard’s Reagent)
R’MgX O R’MgX
OMgX
O
R C R’ R C R’
R C Cl
R’ CuLi R’
(Gilmann’sReagent) H2O
O OH
R C R’ R C R’
Ketone
R’
 Chem i str y | 24.17

(vi) Reduction of acid halides

• By LiAlH4
• By H2/Pd/BaSO4 (Rosenmund reduction)
O O
H2 LiAlH4
R C H R C Cl R CH2 OH
Pd/BaSO4
Rosenmund
reduction

7.2 Acid Amides

Methods of preparation of acid amide

(a) With ammonia
CH2 CH2
C C
O OH HO O
Succinic acid
O
R C O R’ - R’OH
Ester O
R C NH2
- NH4Cl NH3 Amide
O
R C Cl
Acid chloride
H4
OON 
- RC
O
R C
O O O
R C NH
Succinimide
O (82 - 83%)
Anhydride

Flowchart 24.6: Preparation of amides from acid derivative

(b) With (i) Cyanide (ii) Ammonia salt of acid

General reaction:

H2O2 O

R_ C  N NaOH
R C NH2 R C O NH4
Or
+ HCl O
H2O Ammonia
salt of acid

(i) From ammonia salts of carboxylic acid

∆
CH3COONH4  → CH3CONH2

(ii) From cyanides

dil.H SO
2 4 → CH – CONH
CH3C ≡ N + H2O  3 2
2 4 . 1 8 | Carboxylic Acid and Derivatives

Example: O O

_
_

_
_
_ NH3 _
H C=C CNH
H C=C COCH
2 3 + 2 2 + CH3OH

_
_
CH3 Ammonia CH3 Methyl
Methyl-2-methylpropenoate 2-Methylpropenamide alcohol
(75%)

Amines, which are substituted derivatives of ammonia, react similarly

Example: O O
heat
FCH2COCH2CH3 + NH2 FCH2CNH + CH3CH2OH

Ethyl fluoroacetate Cyclohexylamine N-Cyclohexyl- Ethyl

fluroacetamide (61%) alcohol

Important Chemical Reactions

General reaction:

HOFMANN AMIDE
REARRANGEMENT HYDROLYSIS
General Reaction General Reaction
O H/R’ O
R _ N=C=O
:

NaOH + R C N + H2O R C OH
Isocyanate + H/R’ Acid
Amide
+ H/R’
Hydrolysis Br2
H N :
:

R-NH2 H/R’
Amine Amine

(a) Hoffmann rearrangement: In the Hofmann rearrangement an unsubstituted amide is treated with sodium
hydroxide and bromine to give a primary amine that has one carbon fewer than starting amide

General reaction:
O
Hydrolysis
R_C_ NH2 +NaOH + Br2 R_N C=O R NH2
isocyanate
Mechanism:
The mechanism is divided into 3 parts:-
(i) Formation of Isocyanate intermediate
(ii) Formation of carbamic acid
(iii) Decarboxylation to give Amine
 Chem i str y | 24.19

(i) Formation of Isocyanate intermediate

:
:O:

:
O:

: :
H :OH
R N:

:
R N
H H

:
:O

:
R N:
H

Br - Br

:
:O
Br

:
:
R N :O
Br

: :
:OH

: :
H R N

:
:O:
-Br

:
R N

:
Migration of O:
-R to Nitrogen

:
N- R
Isocyanate
(ii) Formation of carbamic acid

:

:O :
:

O:
: :

:O - H
C
C
:

N- R
:

N- R HO
Isocyanate
:

HO - H O:
C
HO NH - R
Carbamic acid

(iii) Decarboxylation to give Amine

:

O:
:

O:
C
:
:

H O NH R C + R NH2
Amine
:

:O
(CO2)
2 4 . 2 0 | Carboxylic Acid and Derivatives

(b) Hydrolysis of amides

Example: O O
H2O/H2SO4 +
CH3CH2CHCNH2 CH3CH2CHCOH + NH4HSO4


Ammonium hydrogen
sulfate
2-Phenylbutanamide 2-Phenylbutanoic
acid (88-90%)

Example: O O
KOH
CH3CNH Br ethanol
CH3CO-K + + H2N Br
water, heat
Potassium
N-(4-Bromophenyl) acetamide acetate p-Bromoaniline (95%)
(p-bromoacetanilide)

7.3 Esters

(a) Methods of Preparation

ESTERS
O
H+
=

R-C-O-R’
R C OH PREPARATION R C OH
=
=

O O
+ +
R’-OH R’-OH

Examples
Examples:
H +
(i) CH3COOH + C2H5OH → CH3COOC2H5 + H2O
Acetic acid

H +
C6H5COOH + CH3OH → C6H5COOCH3 + H2O

Pyridine
(ii) CH3COCl + C2H5OH  → CH3COOC2H5 + HCl

Alcohols react with acyl chlorides by nucleophilic acyl substitution to yield esters. These reactions are typically
performed in the presence of a weak base such as pyridine.
 Chem i str y | 24.21

Here conc. H2SO4 is used in the obove reactions which acts as a catalyst & a dehydeating agent.
O O
=

=
RCCl + R’OH + RCOR’ + Cl-
+ +
Acyl Alcohol N N
Ester
chloride H H
Pyridine Pyridinium
chloride

Example: O2N O2N

O O
Pyridine
CCl + (CH3)2CHCH2OH COCH2CH(CH3)2

Isobutyl
O2N alcohol O2N

3, 5-Dinitrobenzoyl Isobutyl
chloride 3, 5-dinitrobenzoate(85%)

NaOH
Example: C6H5COCl + CH3CH2OH   → C6H5COOCH2CH3 + HCl

(b) Chemical Reactions: The acid and base catalysed ester hydrolysis involves the acyl cleavage of the ester
group.
Acy cleavagel
O
R-C- O-R’

AAc2 is Acid catalysed ester hydrolysis by acyl cleavage through bimolecular mechanism.
BAc2 is Base catalysed ester hydrolysis by acyl cleavage through bimolecular mechanism.

Table 24.5: Mechanism of Acid catalysed and Base catalysed ester hydrolysis

Acid Catalysis Acyl Cleavage AAc2  

+H  slow 
:
: :

: :

R C O R’ R C O R’ R C O R’ R C
-R’OH
:O :OH :O H :O
:
:

:
slow 
R C OH2
H2 O
:

:O
:

-H 
R C OH
:

:OH
:

-H R C OH
:O
:

Base Catalysis Acyl Cleavage BAc2

:

:OH
: :

:OH
: :

: :

R C OR’ R C OR’ R C OH R C O
slow
: :

O: :O: :OR’ :O :O
:
:

+R’OH
2 4 . 2 2 | Carboxylic Acid and Derivatives

(i) Acid catalysed hydrolysis of ester (AAc2):

O
H
CH3 C O R + H2O CH3COOH + ROH

The yield of products would be raised by adding excess of water.

O
H
CH3 C OR + H2O (excess) CH3COOH + ROH

(ii) Base-Promoted Hydrolysis of Esters : Saponification (BAc2):

The base catalysed hydrolysis is also known as Saponification.
O O
H2 O
RC OR’ + NaOH RC O-Na+ + R’OH
Ester Sodium Alcohol
carboxylate

The unreactive negatively charged carboxylate ion does not undergo nucleophilic substitution. The
irreversible nature of this reaction,i.e., the base-promoted hydrolysis of an ester is seen over here. The
mechanism for this reaction also involves a nucleophilic addition-elimination at the acyl carbon.

Mechanism:
H3C-CH2 H3C-CH2
H2 O 18
C=O+NaOH C=O+H3C-CH2-O -H
Ethanol containing
O Na
18
H3C-H2C-O18 labelled O

The mechanism is studied with the help of isotopically labelled esters. Ethyl propionate consisting of
labelled 18O in the ether-type oxygen of the ester undergoes hydrolysis with aqueous NaOH wherein the
18
O is observed to be contained in the produced ethanol only.
The result would have been different if it was an alkyl cleavage instead of the acyl one. But attack at the
alkyl is not possible.
Such kind of attack of the nucleophile at the alkyl carbon occurs rarely in the case of carboxylic acid
esters, but such attacks are preferred in case of esters of sulfonic acids (e.g. tosylates and mesylates)

H3C-CH2 H3C-CH2
H2 O
C=O+OH C=O+H3C-CH2-OH

H3C-H2C-O18 O18

O-
18
H3C-CH2-C=O
Cannot be formed
O CH3 O H3 C
H3C S O C H3 C S O + C OH
O H
CH2CH3 O H3CH2C
H
Inversion of
configuration

Alkyl attack is seen in cases of alkyl sulfonates.

 Chem i str y | 24.23

7.4 Acid anhydrides

O O
R C O C R’
Anhydride

PREPARATION
CHEMICAL
REACTIONS

From With aromatic

carboxylic compound
acids
With alcohols

From With NH3 & RNH2

acid &
acid halide Hydrolysis

Flowchart 24.6: Preparation and reactions of anhydride

(a) Method of Preparation

(i) From carboxylic acids

O O
R C R C
OH  O
+
P2O5 R C
OH
R C O
O ANHYDRIDE

Example:
O
C
(i) CH2 COOH  CH2
O
CH2 COOH P2O5 CH2
C
O
Succinic
anhydride

O
CH2 COOH O
(ii) CH2

P2O5
CH2 COOH O

(ii) From acid and acid halide

O O
R C R C
OH Pyridine O
+
R’ C
Cl
R’ C O
O
2 4 . 2 4 | Carboxylic Acid and Derivatives

O
O
Example: CH3 C
CH3 C  OH
O +
H3 C C Cl
CH3 C
O
O
 Pyridine
O O
CH3 C C CH3
Cl+NaO

(b) Chemical Reaction

Friedel-Crafts
O O Acylation O O
H2 O ArH
R’ C OH +R C OH dry ether R C Ar + R’ C OH
Acid Ketone
- Acid anhydrides give
two carboxylic acids REACTIONS
- Cyclic anhydrides O
yield dicarboxylic
acids R C
O
R C
O

O 2NH3 O O
or R”OH
R C NHR” R C O R” + R’ C OH
2R”NH2
Amide Ester

Flowchart 24.7: Important reaction of anhydride

(i) Reaction with aromatic compounds (Friedel-Crafts acylation)

F F
Example: O O O
Dry, AlCl3
CH2COCCH3 + OCH3 CH3C OCH3 + CH3COOH
Acid Acetic
anhydride o-Fluoroanisole 3-Fluro-4-methoxyacetophenone acid
(70-80%)
(ii) Reaction with alcohols: Esters are formed when acid anhydrides react with alcohols in presence of
pyridine or a catalytic acid.
The below given example shows the incorporation of only one acyl group in the ester while the other
forms an acetic acid molecule.

Example: O O O
H2SO4
CH3COCCH3 + HOCHCH2CH3 CH3COCHCH2CH3 + CH3COOH
Acid Acetic
CH3 CH3 acid
anhydride
sec-Butyl sec-Butyl
alcohol acetate (60%)
 Chem i str y | 24.25

(iii) Reaction with ammonia and amines: Amides are formed when acid anhydride reacts with 2 molar
equivalents of ammonia or amines.
The below given example shows the incorporation of only one acyl group into the amide and the other
forms the amine salt of acetic acid.

O O O
CH3COCCH3 + H2N CH(CH3)2 CH3CNH CH(CH3)2

Acetic p-Isopropylaniline p-Isopropylacetanilide (98%)

anhydride

(iv) Hydrolysis: Carboxylic acids are formed when acid anhydrides react with water. Cyclic anhydrides
hydrolyse to dicarboxylic acids.
O
O
COH
O + H2O
Water COH
O
O
Phthalic anhydride
Phthalic acid

8. HEATING EFFECTS

O
O
R C OH
+ R C
- H2O
R C OH O Anhydride
R C
O
Monocarboxylic acid O

COOH - CO2
CH2 CH3 COOH Acetic acid
COOH
Dicarboxylic acid

Table 24.8: Heating effects on hydroxy acids & ester

(1) a - Hydroxy acid O O O

OH HO  O
or O
O H HO - H2O O O
O O
O
(2) b - Hydroxy acid  O O
 
C H2 CH2 C OH CH2 = CH C OH
-H2O
OH Unstability of 4/8 - membered rings lead to
the formation of a,b - unsaturated acids

(3) g - Hydroxy acid O O



C H2 CH2 CH2 C OH O
-H2O
OH
2 4 . 2 6 | Carboxylic Acid and Derivatives

(4) d - Hydroxy acid O

  O
  
C H2 CH2 CH2 CH2 C OH O
-H2O
OH
(5) Ester 
R C OH
R C O CH2CH2R
O O
+
R C O CH2 CH R R CH = CH2
O H
Intermediate step.

POINTS TO REMEMBER

(a) Summary of Reactions of Carboxylic Acids

Na Metal R-CH2-COONa + 1/2H2
NaOH R-CH2COONa + H2O
Na. metal
based reaction NaHCO3
R-CH2-COONa+CO2 + H2O
NaOH(CaO)
R-CH2-Na2CO3

Grignard CH3MgBr
R-CH2-COOMgBr+ CH4
Reaction

SOCl2
RCH2COCl + SO2
PCl3
R-CH2COCl
Halogenation
Reaction (i)P+X2 (ii)H2O
R-CH-COOH
O
AgOH;Br2 X
R-CH2-C R-CH2-Br + CO2
OH
NH3,
R-CH2C-NH2
Multiple O
P2O5,
Functional R-CH2C-O-C-CH2-R
group O O
R’OH/H2SO4
R-CH2C-OR’
O
(i)SOCl2(ii)CH3N2
R-CH2-CH2-COOH
(iii)Ag2O (iv) H2O
Chain
Lengthening Ca(OH)2 O
Reaction Dry distillation R-CH2-C-CH2-COOH

NaOH,electrolysis
R-CH2-CH2-R
 Chem i str y | 24.27

(b) Summary of Reactions of Acid Halides

Reaction of Acid Chloride

H2O
RCOOH + HCl (Hydrolysis)
R’OH RCOOR’ + HCl (Alcoholysis)
2NH3
RCONH2 + NH4Cl (Ammonolysis)
Multiple
R’NH2
Functional RCONHR’ + R’NH+Cl-
3

group C6H5/Anhyd,AlCl3
C6H5COR+HCl(Friedal -Craft reaction)
R2’Cd/Ether
2RCOR’ + CdCl2
LiAlH4/Ether
RCH2OH

RCOOH/Pyridine
(ROC)2O + HCl
O Anhydride
R-C-Cl Formation
RCOONa
(ROC)2O + NaCl

H2/Pd-BaSO4
RCHO + HCl
+S or quinoline
Reduction
Reaction
LiAlH4/Ether
RCH2OH
2 4 . 2 8 | Carboxylic Acid and Derivatives

(c) Summary of Reactions of Amides

Reaction of amide

+
H /H2O
RCOOH + NH4
Acid Forming
Reaction
SOCl2
RC  N + SO2 + HCl

NaOH
RCOONa + NH3
Na-metal
Based Reaction
2Na
RCONHNa + 1/2H2

O Hydrochloride
Conc. HCl
R-C- NH2 Formation RCONH2HCl
Reaction

P2O5
3RC  N + 2N3PO4
Cyanide
Forming
reaction SOCl2
RC  N + SO2 + Hcl

Hoffmann Br2 + 4KOH

Bromamide RNH2 + KCO2 + 2KBr + H2O
reaction

Reduction LiAlH4/dry ether RCH2NH2

reaction 1 Amie
 Chem i str y | 24.29

(d) Summary of Reactions of Esters

Reaction of Esters
+
H /H2O
RCOOH + R’OH (Hydrolysis)
Multiple
NaOH/H2O
Functional RCOONa + R’OH (Saponification)
group
+
R”OH/H
RCOR” + R’OH (Trans-esterification)
R”ONa

NH3
RCONH2” + R’OH (Ammonolysis)
Amide
Formation
R’NH2
RCOHNR” + R’OH
O
R-C-OR
H2/Copper chromite
RCH2OH + R’OH
Alcohol or LiAlH4

Forming
Reaction Na/alcohol
RCH2OH + R’OH (Bouveault-Blanc reduction)

R”

Grignard (i) 2R’MgX R-C-OH (In case of esters of formic acid,

Reaction
+
(ii) H /H2O 2 alcohols are combined)
R”
3”Alcohol

Solved Examples

JEE Main/Boards (A) (I) decarboxylates faster than (II) on heating.

(B) Only *CO2 is eliminated on heating of compound(I).
Example 1: Select the correct statement about the
(C) Compound (I) eliminates a mixture of CO2 and *CO2
following compounds I, II, II.
on heating.
COONa COONa (D) The rate of decarboxylation of (II) is faster than (III).
CH2 CH2
*
COOH
*
COONa Sol 1: (A) Nature of functional group also has an
(I) (II) influence on rate of decarboxylation. Presence of
Electron Withdrawing Group-Increases its rate of
CH3 C CH2 COONa decarboxylation.
O
(III)