S.y. carboxylic acid

Dr. B. R. Thorat
Government of Maharashtra
Ismail Yusuf Arts, Science andCommerce College, Mumbai
Carboxylic acid
and
Salfonic acid

 Nomenclature
 Structure and physical properties
 Acidity of carboxylic acids
 Effects of substituents on acid strength of aliphatic and aromatic carboxylic acids.
 Preparation of carboxylic acids: Oxidation of alcohols and alkyl benzene
 Preparation of carboxylic acids: Carbonation of Grignard and hydrolysis of nitriles
Acidity
 Salt formation
 Decarboxylation
 Reduction of carboxylic acids with LiAlH4
 Reduction of carboxylic acids with diborane
 Hell-Volhard-Zelinsky reaction
 Conversion of carboxylic acid to acid chlorides, esters, amides and acid anhydrides and
their relative reactivity
 Mechanism of nucleophilic acyl substitution
 Acid-catalysed nucleophilic acyl substitution
 Interconversion of acid derivatives by nucleophilic acyl substitution
 Mechanism of Claisen condensation
 Dieckmann condensation
Content
Preparations
Reactions

Nomenclature
A carboxylic acid - Contains a carboxyl group, which is a carbonyl group (C=O) attached
to a hydroxyl group (—OH). The carboxyl group carbon is numbered as 1.
R
O
O H
carbonyl group
hydroxyl group
1
carboxylic acid
H3C
O
O H
1
acetic acid
Some naturally occurring carboxylic acid:
Glycolic acid
(Sugarcane, sugar beet)
O
O H
12
HO
Lactic acid
(milk)
O
O H
1
2
HO
3
Tartaric acid
(grapes)
O
O H
1
2
HO
3
O
OHO
H
4
Malic acid
(apples, grapes)
O
O H
1
2
HO
3
O
O
H
4
Citric acid
(citrus fruits, lemons, oranges, grapefruit)
O
O
H
O
O
H
OH
O
O
H
General Molecular formula
of Saturated aliphatic
monocarboxylic acids

Some important examples of carboxylic acid
H3C O
O
H
acetic acid
(in vinegar)
O
HO
(CH2)6COOH
(CH2)4CH3
HO
PGE1 (lower blood pressure)
OH
O
O
O CH3
aspirin
Some important Derivatives of Carboxylic Acid
R O
O
H
carboxylic
acid
R O
O
R1
Ester
R O
O
acid anhydride
R1
O
R Cl
O
acid chloride
R Br
O
acid bromide
R NH2
O
amides
R NHR1
O
R NR'2
O

Common Names
HCO2H formic acid L. formica ant, bees, etc
CH3CO2H acetic acid L. acetum vinegar
CH3CH2CO2H propionic acid G. “pro-first, pion - fat”
CH3CH2CH2CO2H butyric acid L. butyrum butter
CH3CH2CH2CH2CO2H valeric acid L. valerans
CH3(CH2)4CO2H caproic acid L. caper goat milk
CH3(CH2)6CO2H caprylic acid --
CH3(CH2)8CO2H capric acid --
CH3(CH2)10CO2H lauric acid oil of lauryl
CH3CH2CH2CHCOOH
Br
CH3CHCH2COOH
CH3
 bromovaleric acid
 -methylbutyric acid
isovaleric acid
C—C—C—C—C=O
used in common names
δ γ β α
5 4 3 2 1
Carboxylic acids containing six or fewer carbons are frequently called by their common names.
The position of a
substituent is designated
by a lowercase Greek
letter, and the carbonyl
carbon is not given a
designation.

Special names
COOH
COOH COOH COOH
CH3
CH3
CH3
benzoic acid
o-toluic acid m-toluic acid
p-toluic acid
COOH
OH
salicylic acid
COOH
COOH
phthalic acid

IUPAC Nomenclature
The IUPAC names of carboxylic acids -
 Find the longest carbon chain that contains the –COOH group.
 Number the longest chain. Carbon number 1 is the carboxyl carbon.
 Write the name of parent hydrocarbon and replace the -e in the hydrocarbon name
with -oic acid.
 Name and number other substituents.
 The ring is numbered to give the lowest possible numbers for any substituents.
 Aromatic acid names are derived from the parent compound, benzoic acid,
naphthaloic acid. The prefixes ortho, meta, and para may be used to show the position
of one other substituent.
H
O
O H
1
Methanoic acid (formic acid)
H3C
O
O H
1
Ethanoic acid (acetic acid)
H
H
H
1 H H3C
H
H
1 H
ethanemethane
O
O H
1
CH3
H3C
2
34
5
3-methylpentanoic acid

Cycloalkanes bonded to -COOH are named as cycloalkanecarboxylic acids.
Double bonds in the main chain are signaled by the ending -enoic acid, and their position is
designated by a numerical prefix. Double-bond stereochemistry is specified by using either
the cis–trans or the E–Z notation
OH
O
(Z)-9-octadecenoic acidacrylic acid
propenoic acid H
H3C(H2C)7 (CH2)7COOH
H
COOH
COOH
CH3 COOH
COOH
COOH
cyclohexane-
carboxylic acid trans-/ (1R,3R)-3-
methylcyclopentane-
carboxylic acid
benzene-1,2,4-tricarboxylic acid

OH
O
OH
O
H2N
OH
O
Cl
Cl
H H
OH
O
Cl
Br
OH
O
Br
Cl
Ph
H
H
OH
O
OH
O
Cl OH
O
ClOH
O
Cl
H
OH
O
Cl
H
benzoic acid
4-aminobenzoic acid
3,4-dichlorobenzoic acid
3-bromo-4-chlorobenzoic acid
5-bromo-2-chlorobenzoic acid cinnamic acid
2-chlorobutanoic acid
2-chloro-3-methylbutanoic acid
(S)-2-chloro-3-methylbutanoic acid
(R)-2-chloro-3-methylbutanoic acid
H O
O
H
methanoic acid
formic acid
H3C O
O
H
ethanoic acid
acetic acid
H3CH2C O
O
H
propanoic acid
propinoic acid
H3CH2CH2C O
O
H
butanoic acid
butyric acid
H3CH2CH2CH2C O
O
H
pentanoic acid
valeric acid
H3CH2CH2CH2CH2C O
O
H
hexanoic acid
caproic acid
C
H
O
O
H
propenoic acid
acrylic acid
H2C
COOH
benzenecarboxylic acid
benzoic acid
systematic name
common name

 For these compounds, both ends of a chain will end with a –COOH group. The parent
chain is the one that involves both –COOH groups.
 Compounds with two carboxyl groups are distinguished by the suffix -dioic acid or -
dicarboxylic acid as appropriate. The final –e in the base name of the alkane is
retained.
1,2-benzenedicarboxylic acid
propanedioic acid
COOH
COOH
HOOC COOH COOH
HOOC
phthalic acid
malonic acid succinic acid
butanedioic acid
Dicarboxylic acid

Salts of carboxylic acids
Writing the name of the cation followed by the name of the acid with the –ic acid ending
replaced by an –ate ending.
sodium ethanoate
sodium acetate
H3C O-
Na+
O
potassium propanoate
potassium propionate
H3CH2C O-
K+
O
sodium methanoate
sodium formate
H O-
Na+
O
potassium ethanoate
potassium acetate
H3C O-
K+
O
O-
Na+
O
sodium benzenecarboxylate
sodium benoate

Acyl halides
By using the acid name and replacing “ic acid” with “yl chloride” (or “yl
bromide”). For acids ending with “carboxylic acid,” “carboxylic acid” is replaced
with “carbonyl chloride” (or “bromide”)
H3C Cl
O
ethanoyl chloride
acetyl chloride cyclopentanecarbonyl
chloride
Br
O
3-methylpentanoyl bromide
-methylvaleryl bromide
Cl
O

Acid anhydride
If the two carboxylic acid molecules forming the acid anhydride are the same, the
anhydride is a symmetrical anhydride.
Symmetrical anhydrides are named by using the acid name and replacing “acid” with
“anhydride.”
If the two carboxylic acid molecules are different, the anhydride is a mixed anhydride.
Mixed anhydrides are named by stating the names of both acids in alphabetical order,
followed by “anhydride.”
H3C O
O
ethanoic anhydride
acetic anhydride
symmetrical anhydride
CH3
O
H3C O
O
ethanoic methanoic anhydride
acetic formic anhydride
mixed anhydride
H
O

Ester
The name of the group (R’) attached to the carboxyl oxygen is stated first, followed by the
name of the acid, with “ic acid” replaced by “ate.”
ethyl ethanoate
ethyl acetate
R O
O
R'
carbonyl oxygen
alkoxy oxygen
H3C O
O
CH2CH3
H3C O
O
phenyl propanoate
phenyl propionate
methyl 3-bromobutanoate
methyl -bromobutyrate
ethyl cyclohexanecarboxylate
O
O
CH3
Br
O
O
CH3

Lactones
In systematic nomenclature, they are named as “2-oxacycloalkanones.”
Their common names are derived from the common name of the carboxylic acid, which
designates the length of the carbon chain, and a Greek letter to indicate the carbon to
which the carboxyl oxygen is attached. Thus, four-membered ring lactones are β-lactones
(the carboxyl oxygen is on the β-carbon), five-membered ring lactones are γ-lactones and
six-membered ring lactones are δ-lactones. The “ic acid” replaced with “lactone.”
2-oxacyclopentanone
-butyrolactone
O
O
O
O
O
O
O
O
CH2CH3 CH3
2-oxacyclohexanone
-valerolactone
3-ethyl-2-
oxacyclopentanone
-caprolactone
3-methyl-2-oxacyclohexanone
-valerolactone

Amide
Amides are named by using the acid name, replacing “oic acid” or “ic acid” with “amide.”
For acids ending with “carboxylic acid,” “ylic acid” is replaced with “amide.”
ethanamide
-chlorobutyramide
H3C NH2
O
NH2
O
NH2
O
NH2
O
Cl
4-chlorobutanamide
acetamide benzamide
(1R,2S)-2-
ethylcyclohexanecarboxamide
benzenecarboxamide
If a substituent is bonded to the nitrogen, the name of the substituent is stated first (if
there is more than one substituent bonded to the nitrogen, they are stated alphabetically),
followed by the name of the amide. The name of each substituent is preceded by a capital
N to indicate that the substituent is bonded to nitrogen.
N
OH
N
O
N
O
N-cyclohexylpropanamide N-ethyl-N-methylpentanamide N,N-diethylbutanamide

Lactams
They are named as “2-azacycloalkanones” in systematic nomenclature (“aza” is used to
designate the nitrogen atom). In their common names, the length of the carbon chain is
indicated by the common name of the carboxylic acid, and a Greek letter indicates the
carbon to which the nitrogen is attached. The “ic acid” replaced with “lactam.”
2-azacyclopentanone
-butyrolactam
NH
O
NH
O
2-azacyclohexanone
-valerolactam
2-azacyclobutanone
-propiolactam
N
H
O

Carboxylic acids with other functional groups
Carboxylic acids are given the highest nomenclature priority by the IUPAC system. This
means that the carboxyl group is given the lowest possible location number.
If molecules containing carboxylic acid and alcohol functional groups the OH is named as a
hydroxyl substituent.
If molecules containing a carboxylic acid and aldehydes and/or ketones functional groups
the carbonyl is named as a "Oxo" substituent.
If molecules containing a carboxylic acid an amine functional group the amine is named as
an "amino" substituent.
OH
OOH
3-hydroxypentanoic acid
OH
OOH
OH
2,3-dihydroxypentanoic acid
OH
O
O
H
4-oxobutanoic acid
OH
O
O
2-oxobutanoic acid
N OH
O
H
H
3-aminopropanoic acid
OH
O
NH2
2-aminobutanoic acid

Give the IUPAC names of following compounds
Write the structure of following compounds
1. Methyl salicylate 2. Succinic acdid
3. Phthalic acid 4. p-Toluic acid
5. Benzoic anhydride 6. Methyl salicylate
7. Propionamide 8. Malonic acid
9. 2-methyl butanoic acid
1. COOH Ph
COOH
2. HOOC COOH3.
4.
H
COOHHOOC
H
5.
COOH
Br
6.
COOH
CONH2 COOCH3 COCl
7. 8. 9.

Structure
H3C O
O
acetic acid
sp2
-hybridized
H
1190
1.36
1.21
The C=O is shorter
than the C-O
H3C O
O
sp2
-hybridized
33% s-character
H
1.36
The C-O single bond of a carboxylic acid is shorter than the C- O single bond of an alcohol.
In the alcohol, 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 carboxylic acid.
Partial double bond character due to resonance effect.
The carbonyl carbon in carboxylic
acids and derivatives is sp2
hybridized.
The three atoms attached to the
carbonyl carbon via sigma bond
and are in the same plane, and
their bond angles are each
approximately 120°.

Physical properties
At ordinary temperature, aliphatic carboxylic acids (upto nine carbon) are colorless liquids
at room temperature with unpleasant smell.
The higher acids are wax like solids and odorless due to their low volatility..
The melting points and boiling points of carboxylic acids are higher than those of
hydrocarbons and oxygen-containing organic compounds because of strong
intermolecular attractive forces.
b.p. at 1 atm pressure
O OH
OH
O
propionic acidbutan-2-olbutan-2-one2-methylbut-1-ene
310
C 800
C 990
C 1410
C
The carboxylic acid molecules are held together by strong H-bonding.
R
O
O
H R
O
O
H
the hydrogen bonded dimer
of a carboxylic acid

Simple aliphatic carboxylic acids, lower carboxylic acids having higher melting than higher
member because of increasing alkyl porting, decrease the strength of hydrogen bonding.
Melting point in K at 1 atm. pressure
H OH
O
H3C OH
O
H3CH2C OH
O
H3CH2CH2C OH
O
H3CH2CH2CH2C OH
O
pentanoic acidbutyric acidpropionic acidacetic acidformic acid
281 289.6 251 267
240

dipole-dipole
interactions
C N
N
O
H
H
N
O
H
H
N
O
H
H
N
O
H
H CN
intermolecular
H-bonding
dipole-dipole
interactions

 
Among the derivatives, amides have the highest boiling points, because they have strong
dipole–dipole interactions between the resonance structures of the molecules having
charge separation.
Amide > Carboxylic acid > Nitrile >> Ester ~ Acyl chloride ~ Aldehyde ~ Ketone
b.p. at 1 atm pressure
NH2
O
2130
C 970
C1410
C
OH
O
N
propionamide propionic acid propiononitrile

Solubility
Simple aliphatic carboxylic acids having upto four carbon atoms miscible in water due
intermolecular hydrogen bonding with water.
The solubility decreases with increasing number of carbon atoms.
Higher carboxylic acids are insoluble in water due to the increased hydrophobic
interaction of hydrocarbon part of acid with water.
Carboxylic acids are also soluble in less polar organic solvents like benzene, ether, alcohol,
chloroform etc.

Solubility – Some examples of carboxylic acids

Acidity of carboxylic acids
Carboxylic acids are the most acidic class of hydrocarbons containing C,H, and O. The pKa
value of the acid-base pair in the equilibrium reaction was used to explain the strength of
acid.
H3C O
O
H
acetic acid
(strong acid)
pKa = 4.8
+ NaOH H3C O-
Na+
O
+ H2O
pKa = 15.7
weaker acid(base)
O
O
H
benzoic acid
(strong acid)
pKa = 4.2
+ NaHCO3 O-
Na+
O
+ H2CO3
pKa = 6.4
weaker acid(base)
Lesser the value of pKa < 1 value, stronger the acid;
moderately strong acids pKa value ranges from 1 to 5;
for weak acids pKa values are from 5 to 15;
for extremely weak acids pKa > 15.
H3C O
O
H
acetic acid
pKa = 4.8 pKa = 10
OH
phenol
H3C O
H
ethanol
pKa = 16

Carboxylic acids are weaker than mineral acids but stronger than alcohols and phenols.
Structure Ka pKa
HCl 107 -7
0.23 0.64
3.3 x 10-2 1.48
1.4 x 10-3 2.85
1.77 x 10-4 3.75
6.46 x 10-5 4.19
5.6 x 10-5 4.25
1.76 x 10-5 4.75
10-16 16
ionization of ethanol:
H3C
H2
C
O
H
ethanol
H3C
H2
C
O
+ H+
H3C
C
O
H
H3C
C
O
+ H+
O O
acetic acid
ionization of acetic acid:
Ionization energy = 91 kJ/mol Ionization energy = 27 kJ/mol

Effects of substituent's on acid strength of
aliphatic and aromatic carboxylic acids
 Inductive effect of substituent
 Resonance effect of substituent

H3C O-
O
acetate ion
O-
positively polarized
carbon attracts electrons
from negatively charged
oxygen of acetate ion ethoxide ion


CH2 group has negligible + ve
charge so, less stabilize
electrons density at negatively
charged oxygen of ethoxide ion
R O-
O
carboxylate ion
the electrons are delocalized
over system
R O
O-
R O
O
1/2
1/2
OR
R O
O
the negative charge over the oxygen of
carboxylate ion is equally spread over
the both oxygen atom carboxylate ion
i.e. both C-O bonds are equivalent
The carbonyl group of acetate ion is electron-withdrawing, and by attracting electrons away
from the negatively charged oxygen, acetate anion is stabilized.
Electron delocalization, expressed by resonance between the following Lewis structures,
causes the negative charge in acetate to be shared equally by both oxygens.

Effects of substituent's on acid strength of aliphatic and aromatic carboxylic acids
The electron donating groups such as alkyl group has slightly decreases the acidic
character of carboxylic acid.
H3C O
O
H
acetic acid
pKa = 4.8
H O
O
H
formic acid
pKa = 3.7
An electronegative substituent, particularly if it is attached to the -carbon, increases the
acidity of a carboxylic acid. All the monohaloacetic acids are about 100 times more acidic
than acetic acid.
H3C O
O
H
acetic acid
pKa = 4.8 pKa = 1.7 pKa = 1.8
C
H2
O
O
H
C
H2
O
O
H
C
H2
O
O
H
C
H2
O
O
HO2N Me3+N NC
O
pKa = 2.4 pKa = 3.6
Effect of electron withdrawing group on pKa value of acid:
C
H2
O-
O
Cl
pKa = 2.81
chloroacetate anion is stabilized
by electron withdrawing effect of
chlorine

 The  electrons in the carbon–chlorine
bond of chloroacetate ion are drawn
toward chlorine, leaving the -carbon
atom with a slight positive charge.

H3C O
O
H
acetic acid
pKa = 4.8 pKa = 3.15 pKa = 2.86
C
H2
O
O
H
C
H2
O
O
H
C
H2
O
O
H
C
H2
O
O
HI Br Cl F
pKa = 2.81 pKa = 2.66
Effect of halogen on pKa value of acid:
Effect of the halogen on the strength of acetic acid is shown below. Fluoroacetic acid is
more acidic than iodoacetic acid.
Inductive effects fall off rapidly as the number of  bonds between the carboxyl group and
the substituent increases.
pKa = 4.8
O
O
H
pKa = 2.8
O
O
H
pKa = 4.1
O
O
H
pKa = 4.5
O
O
H
Cl
Cl
Cl
Structure Ka pKa
0.23 0.64
3.3 x 10-2 1.48
1.4 x 10-3 2.85
1.76 x 10-5 4.75

Effects of substituent's on acid strength of aliphatic and aromatic carboxylic acids
Substituents on a benzene ring either donate or withdraw electron density, depending on
the balance of their inductive and resonance effects.
An electron-donor group (+R/+I; +R is more
dominant than –I) destabilizes a conjugate
base by donating electron density onto a
negatively charged carboxylate anion. group D destabilized
the carboxylate anions
O
O
H
pKa > 4.2
D
O-
O
D
It is less acidic
than benzoic acid
+ H+
Effect of electron donor group on acidity of benzoic acid

An electron-withdrawing group (-R/-I;
-R is more dominant than +I)
stabilizes a conjugate base by
removing electron density from the
negatively charged carboxylate anion. group W stabilized the
carboxylate anion
O
O
H
pKa < 4.2
W
O-
O
W
It is more acidic
than benzoic acid
+ H+
Effect of electron withdrawing group on acidity of benzoic acid

Match each of the following pKa values (3.2, 4.9, and 0.2) to the appropriate carboxylic
acid: (a) CH3CH2COOH; (b) CF3COOH; (c) ICH2COOH.
Explain why HCOOH (formic acid) has a lower pKa than acetic acid (3.8 versus 4.8).
Which would be you expect to be the strongest acid – benzoic acid or p-nitrobenzoic acid.
Rank the compounds in each group in order of increasing acidity.
a. CH3COOH, HSCH2COOH, HOCH2COOH b. ICH2COOH, I2CHCOOH, ICH2CH2COOH.

•Rank the compounds in each group in order of increasing acidity and explain.
O
OH
O
OH
O
OH
H Cl H3C
O
OH
H3C
O
OH
C
O
OH
H3CO
H3C
O
a.
b.
O
OH
O
OH
O
OH
H F3C H3Ca.
b.
OH
O
OH
O
Cl
OH
O
Br

Preparation of carboxylic acids
Oxidation of Alkyl benzenes
alkyl group at benzylic position (activated by benzene) is oidized to –COOH by using
oxidizing agent such as chromic acid (H+, Na2Cr2O7), HNO3, alkaline or aqueous KMnO4,
heating in air in presence of catalyst such as V2O5.
OH
O
CH3
toluene benzoic acid
1. KMnO4,
2. H+
OH
OH2
CCH
HO
O
Na2Cr2O7, H+
1-butyl-3-isopropylbenzene isophthalic acid
Regardless of the length of the alkyl substituent, it will be oxidized to a COOH group,
provided that hydrogen is bonded to the benzylic carbon i.e. CH or CH2 or CH3 group attach
to aromatic ring .
tert-benzylic carbon is not susceptible to the oxidation under these conditions.
C
H3C
H3C
Na2Cr2O7, H+
No reaction
CH3
1-tert-butylbenzene
does not have a benzylic hydrogen

Oxidation of Alkyl benzenes
COOHCH3 O2
air oxidation, heat,
Co-naphthalene
+ H2O
benzoic acidtoluene
1.
H2
C
CH3
C
CH3
COOH
benzoic acid
2.
O
KMnO4
alkaline
KMnO4
alkaline
1-ethylbenzene acetophenone
3.
CH3
COOH
K2Cr2O7, H2SO4, heat
2-naphthoic acid2-methylnaphthalene
4.
CH3
CH3
1. Alk. KMnO4
2. H+
o-xylene
COOH
CH3
1. Alk. KMnO4
2. H+
COOH
COOH
2-methylbenzoic acid phthalic acid

Oxidation of alcohols
1. Alk. KMnO4
2. H+
C
H
H3C
Na2Cr2O7, H+
OH
1-phenylethanol
OH
O
benzoic acid
1.
2.
C
H
H3C
OH
1-phenylethanol
3.
C
H
H
OH
phenylmethanol
benzyl alcohol
MnO2 CH3
O
MnO2 H
O
acetophenone
benzaldehyde
C
H
H3C
OH
Strong oxidizing agents - Chromic acid, CrO3 or Na2Cr2O7, HNO3, alkaline or aqueous
KMnO4, etc oxidizes alcohol to acid.
Mild oxidizing agents such as MnO2 oxidize alcohol to aldehyde or ketone.
Carbonyl compound formed is an aldehyde, a ketone, or a carboxylic acid depends on the
alcohol and on the oxidizing agent.
aldehyde carboxylic acid
R OH
primary alcohol
R OH
O
R H
O
oxidize oxidize

Oxidation of Alkyl benzenes - V2O5 catalyst
Preparation of phthalic acid
CH3
CH3
o-xylene
COONa
COONa
Salt
O2, V2O5, heat
-3H2O
C
C
O
O
O
NaOH
H2O
COOH
COOH
phthalic acid
H+
phthalic anhydride
Oxidation by using KMnO4
alkyl benzene
R
H
R
OH
O
KMnO4
benzoic acid
similarly all aromatic
hydrocarbon undergoes
oxidation reaction
alkyl benzene contain atleast one
benzylic C-H bond
H
H
H
H
H
R
R
H
R
or or
OH
O
KMnO4
benzoic acid

Oxidation of alcohols
Chromic acid (H2CrO4) oxidation – primary and secondary alcohol
aldehyde carboxylic acid
OH
primary alcohol
OH
O
H
O
butan-1-ol butyraldehyde butyric acid
H2CrO4 further
oxidation
sodium dichromate in presence
of sulfuric acid (chromic acid)
R
OHH
H
HO Cr OH
O
O
H+
HO Cr OH2
O
O
HO Cr O
O
O
H
R
H H
HO Cr O
O
O R
H H
R H
O
+ H2CrO3
+ H+
+ H2O
aldehyde
primary alcohol
an E2 reaction
chromic acid
The carbon bearing the OH group in a tertiary alcohol is not bonded to hydrogen, so the OH
group cannot be oxidized to a carbonyl group
chromate ester

Acidic or basic aqueous potassium permanganate - Oxidation
H2O
R H
O
aldehyde
R H
OH
OH
Mn
O
-
O
O
O
R H
O
OH
Mn
O
O
O
R OH
O
+ Mn
O
HO
O
carboxylic acid
Mn(V)
Mn(VII)
oxidation by using Mn(VII) of aldehyde
Aldehyde is oxidized to carboxylic acid with Tollens reagent (AgNO3 in NH4OH).
CrO3
H3CH2CH2CH2C OH
O
pentanoic acid
H3CH2CH2CH2C
H2
C OH
pentan-1-ol
H2SO4, H2O
AgNO3
H3CH2CH2CH2C OH
O
pentanoic acid
H3CH2CH2CH2C
C
H
O
pentanal
NH4OH

Hydrolysis of nitriles or cyanides
Nitriles are slowly hydrolysis than amides. It slowly hydrolyzed to carboxylic acids when
heated with water and an acid.
C
N
OH
O
+ H2O
HCl
+ NH4
+
propiononitrile
propionic acid
mechanism for acid catalyzed hydrolysis of nitrile
C
N
OH
O
+ H2O
+ NH4
+
propiononitrile
propionic acid
H+
C
N
H
C
N
H
O
H
H C
N
H
O
H
H+
C
N
H
O
H
H
C
N
H
O
H
H
H2O
protonated amide
Protonation make the carbon of the
cyano group more electrophilic

Hydrolysis of nitriles or cyanides
The nitrile is important intermediate to convert alkyl halide into carboxylic acid which has
one more carbon than the alkyl halide.
Synthesis of propanoic acid from ethyl bromide
C
N
OH
O
+ NH4
+
propiononitrile
propionic acid
Br CN-
DMF
bromoethane
OH
NH
H2O
HCl
O
NH2
H2O
HCl,
propionamide
Synthesis of benzoic acid from chlorobenzene
C
N
OH
O
+ NH4
+
Cl
CN-
DMSO
OH
NH
H2O
HCl O
NH2
H2O
HCl,
1-chlorobenzene
benzonitrile
benzamide benzoic acid

Carbonation of Grignard
Grignard reagents treated with carbon dioxide; addition reaction takes place to yield
magnesium salts of carboxylic acids which on acidification converts these magnesium
salts to the desired carboxylic acids.
R OH
O
carboxylic acid
R O-
BrMg+
O
carboxylate salt
H+
R MgBr
1. CO2, Et2O
2. H3O+
grignard reagent
C OO
R
BrMg


 
grignard reagent acts
as a nucleophile
towards carbon dioxide

Reactions of carboxylic acids
The polar C-O and O-H bonds, nonbonded electron pairs on oxygen, and the π
bond give a carboxylic acid many reactive sites.
Carboxylic acids are strong organic acids so that they are showing acid–base reactions,
any nucleophile that is also a strong base will react with a carboxylic acid by removing a
proton first, before any nucleophilic substitution reaction can take place.
R O
O
carboxylic acid
H + Nu-
R O-
O
+ Nu-H
This reaction is faster with
many nucleophiles in absebce
of catalyst
Acid - base type reaction:
R OH
O
carboxylic acid
+ Nu-
R
HO
OH
Nu
tetrahedral intermediate
acidic condition
addition or substitution reaction with nucleophile:
R
-
O
O-
Nu
tetrahedral intermediate
alkaline condition

Carboxylic acids can be converted to a variety of other acyl derivatives using special
reagents, with acid catalysis, or sometimes, by using rather forcing reaction conditions.
These nucleophilic substitution reactions take place in two steps - formation of a
tetrahedral intermediate and collapse of the tetrahedral intermediate.
The weaker the base attached to the acyl group, the easier it is for both steps of the
reaction to take place i.e. higher the rate of reaction.
increases
relative basicities of the leaving groups
Cl-
< RCOO-
< RO-
< HO-
< H2N- Strongest baseWeakest base
R OH
O
carboxylic acid
relative reactivities of the carboxylic acid derivatives
most
reactive R Cl
O
R O
O
R1
O
R OR1
O
R NH2
O
amideesteracid anhydrideacid chloride
> > > > least
reactive
Reactions of carboxylic acids

Salt formation
Reaction of polar O– H bond carboxylic acid
stronger acid
R OH
O
carboxylic acid
+ HO-
hydroxide ion
k = 1011
stronger base weaker acid
R O-
O
carboxylate ion
+ H2O
water
weaker base
Neutralization of carboxylic acids
O
O
H
benzoic acid
(strong acid)
pKa = 4.2
+ NaHCO3 O-
Na+
O
+ H2CO3
pKa = 6.4
weaker acid(base)
H3C O
O
H
acetic acid
(strong acid)
pKa = 4.8
+ NaOH H3C O-
Na+
O
+ H2O
pKa = 15.7
weaker acid(base)
1.
2.

Decarboxylation
Carboylic acid or Carboxylate ions or carboxylate salt do not undergoes decarboxylation
(loss of CO2) on heating, because of least stabilization of intermediate carbanion or
shifting of H from O to C.
not possible because of
carbanion is less stable
H3CH2C O-
O
propionate ion
H3CH2C H
ethane
If, the –COO- or –COOH group is bonded to a carbon that is adjacent to a carbonyl carbon,
CN, C=N, NO2, etc the CO2 group can be removed because the electrons left behind on
carbon (carbanion) can be delocalized onto the carbonyl oxygen forming enolate ion or
enol like intermediates. The loss of carbon dioxide is called decarboxylation.
Carboylic acid or Carboxylate ions or carboxylate heated with soda lime goes
decarboxylation at higher temperature.
H3CH2C OH
O
propionate ion
H3CH2C H
ethane
+ NaOH
CaO
+ CO2
decarboxylation of acetoacetate ion
R C
H2
O
O-
O
3-oxocarboxylate ion
ketoacetate ion
R CH2
O
+ CO2
R CH2
O

Decarboxylation
HO C
H2
O
O
O
malonic acid
HO CH2
OH
+ CO2
HO CH3
O
H
acetic acid
1350
CExamples:
C
H2
O
O
O
+ CO2CH3
O
H
3-oxohexanoic acid
pentan-2-one
1. HO CH
O
O
O
+ CO2HO CH2
O
H
CH3CH3
2-methylmalonic acid propionic acid
2.
R C
H2
O
O-
O
3-oxocarboxylate ion
ketoacetate ion
R CH2
O
+ CO2
R CH2
O
Under acidic conditions:
H3C C
H2
O
O
O
3-oxobutanoic acid
acetoacetic acid
H3C CH2
OH
+ CO2
H3C CH3
O
 - keto acid
H
propan-2-one

Reduction of carboxylic acids with LiAlH4
Sodium borohydride (NaBH4) is not a sufficiently strong hydride donor to react with the
less reactive (compared with aldehydes and ketones) esters, carboxylic acids, and amides,
so esters, carboxylic acids, and amides must be reduced with lithium aluminum hydride
(LiAlH4) a more reactive hydride donor.
H3C OH
O
acetic acid
OH
O
benzoic acid
1. LiAlH4
2. H3O+
1. LiAlH4
2. H3O+
H3C OH
OH
H H
H H
ethanol
phenylmethanol
1.
2.
primary alcohol
The chemoselectivity of these two most commonly used reducing agents is listed -
R H
O
aldehyde
R OH
O
carboxylic acid
R OR1
O
R NR'2
O
amideester
> > >>
R R1
O
ketone
reduced by LiAlH4
reduced by NaBH4 not reduced by NaBH4

hydride ion removes
an acidic proton
primary alcohol
R OH
O
carboxylic acid
LiAlH4
R O-
O
-H2
AlH3
R O
O
Al H
H
H
R O
O
Al
H
H
H
R H
O
aldehyde
AlH3
R O
H
Al
H
H
H
R OH
O
R
O
H
Al
O
O
H H
H
R
H
H
R
H
H
O
H
H
RH3O+
R OH
H H
new hydride
donor
second addition
of hydride ion
Mechanism for the reaction of a carboxylic acid with hydride ion
electrophile

Reduction of carboxylic acids with Borane
The best reducing reagent for reduction of carboxylic acid to alcohol is borane, BH3. Solvents
used are - ether (Et2O), THF, or dimethyl sulfide (DMS, Me2S).
R OH
O
carboxylic acid primary alcohol
R OH
H H
BH3, THF
Esters are usually less electrophilic because of conjugation between the carbonyl group and
the lone pair of the sp3 hybridized oxygen atom - but, in triacylborates, the oxygen next to
the boron has to share its lone pair between the carbonyl group and the boron’s empty p
orbital, so they are considerably more reactive than normal esters, or the lithium
carboxylates formed from carboxylic acids and LiAlH4.
unreactive
R OH
O
carboxylic acid
primary alcohol
R OH
H H
BH3, THFLiAlH4
R O-
Li+
O
R O
O
B
O
RO
O
O
R
reactive
BH3, THFfast
triacylborate
oxygen donates lone pair of electrons
into boron's empty p-orbital
R O
O
B
OR
OR

Borane is a highly chemoselective reagent for the reduction of carboxylic acids in the
presence of other reducible functional groups such as esters, and even ketones.
HOOC COOCH3 HOH2C COOCH3
1.
O
COOH
O
CH2OH2.
BH3
BH3
borane’s reactivity (Lewis acid) is dominated by its
desire to accept an electron pair into its empty p
orbital. In the context of carbonyl group
reductions, this means that it reduces electron-
rich carbonyl groups fastest - acyl chlorides and
reduces esters only slowly, but it will reduce
amides.
R NMe2
O
amide
BH3, THF
R NMe2
amine
H H
R N
O
amide
R NMe2
amine
H H
Me
Me
H B
H
H
R N
O
Me
Me
B
H
HH
R
N
O
Me
Me
B H
H
H
R
N
Me
Me
H
H B
H
H
R
N
Me
Me
B H
H
H
H
H2O
empty p-orbital tetrahedral intermediate collapses
to give an iminium ion

Hell-Volhard-Zelinsky reaction (C-bromination)
A carboxylic acid is treated with PBr3 and Br2 then the -carbon can be brominated. (Red
phosphorus can be used in place of PBr3, since P and excess Br2 react to form PBr3). This
halogenation reaction is called the Hell–Volhard–Zelinski reaction or, more simply, the HVZ
reaction.
OH
O
carboxylic acid
R 1. PBr3 (or P), Br2
2. H2O
OH
O
bromo
carboxylic acid
R
Br
mechanism for the Hell-Volhard-Zelinski reaction
OH
O
carboxylic acid
R
bromo
carboxylic acid
H H or P/Br2
PBr3 Br
O
R
H H
Br
OH
R
H
enol
Br2
Br
O
R
H
Br
H
+ Br
Br
O
R
H
Br
+ HBr
H2O
OH
O
R
H
Br
bromo
acid bromide
OH
O
carboxylic acid
R
bromo
carboxylic acid
H H or P/Br2
PBr3 OH
O
R
H
Br
excess NH3
O
O
RH
H3N + NH4Br
amino acid
example

Formation of carbonyl compounds (by using calcium carboxylate)
When carboxylic acids are heated with MnO, carbonyl compounds are formed
MnO
ketone
R OH
O
+ H2O + CO22 R R
O
carboxylic acid
573 K
When calcium salt of fatty acids are dry distilled, carbonyl compounds are formed
2 (RCOO)2Ca
ketone
dry distillation
R R
O
+ 2 CaCO3

Hunsdiecker reaction
When silver salt of carboxylic acids are treated with halogen such as bromine in suitable
solvent forming alkyl halide (alkyl bromide) with loss of one carbon as carbon dioxide
R O
O
Ag
+ Br2
CCl4
R Br + AgBr + CO2
1. How will you prepared –
a. Butanoic acid by oxidation of alcohol.
b. Benzoic acid from aromatic alcohol.
c. p-tuloic acid by using Grignard reagent.
d. Phenyl acetic acid by hydrolysis of suitable nitrile.

Complete the following reactions –
1. Acetic acid + Ca(OH)2
2. Butanoic acid + Br2 (in red P)
3. Benzoic acid + BH3
4. Butyl bromide + Mg followed by carbonylation
How benzoic acid prepared by using –
1. Aromatic alcohol
2. A nitrile
3. Grignard Reagent
4. Alkyl benzene

Conversion of carboxylic acid to their derivatives
Synthesis of Acid halides
A carboxylic acid can be converted into an acyl chloride by heating it either with SOCl2,
PCl3, PBr3, POCl3, PCl5, COCl2, C2O2Cl2, etc in presence of base such as Et3N,
pyridine, etc.
H3C OH
O
+ SOCl2
H3C Cl
O
+ SO2 + HCl
acetic acid acetyl chloride
sulfuryl
dichloride
1.
H3CH2CH2C OH
O
+ PCl33 H3CH2CH2C Cl
O
+3 H3PO3
butyric acid butyryl chloridetrichloro
phosphine
2.
O
OH + PBr33
O
Br +3 H3
PO
3
benzoic acid benzoyl bromide
tribromo
phosphine
3.
All these reagents convert the OH group of a carboxylic acid into a better leaving group
than the halide ion.
R O
O
S
Cl
O
R O
O
P
Cl
Cl
R O
O
P
Br
Br
good leaving groups
R O
O
S
Cl
O
Cl
R
O
O
S
Cl
O
Cl
R Cl
O
acid chloride
+ SO2 + Cl-

Synthesis of anhydride
Dicarboxylic acids readily lose water when heated or by treating dehydrating agent such
as P2O5 form a cyclic anhydride with a five- or a six-membered ring.
H2O1.
O
HO
O
HO
O
O
O
+
or P2O5
glutaric acid
dihydro-3H-pyran-2,6-dione
glutaric anhydride
Anhydride was synthesized by treating acid with dehydrating agent or acid chloride with
carboxylic acid or its salt.
R O
O
R
O
R OH
O
carboxylic acid
anhydride
+
R OH
O
P2O5
R ONa
O
+
R Cl
O
sodium
carboxylate acid chlodie
Cyclic anhydrides are more easily prepared if the dicarboxylic acid or ester is heated in the
presence of acetyl chloride or acetic anhydride.
3.
O
HO
O
OH
+
O
O O
O
O
O
+
OH
O
succinic acid
acetic anhydride
succinic anhydride
O
RO
O
Cl

Synthesis of ester
Carboxylic acids have approximately the same reactivity as esters because the HO- of a
carboxylic acid and RO- as leaving group of an ester has approximately same basicity.
H2OR OH
O
carboxylic acid
+ R1OH
H+
R OR1
O
ester
+
excess
alcohol
R O
O
R
O
anhydride
R ONa
O
+
sodium
carboxylate
Not formed
Cl-
R Cl
O
Carboxylic acids react reversibly with alcohols to form esters therefore reaction should be
catalyzed. Ester could be prepared by treating a carboxylic acid with excess alcohol in the
presence of an acid catalyst, so the reaction is called a Fischer esterification.
H2OR OH
O
carboxylic acid
+ R1OH
H+
R OR1
O
ester
+
excess
alcohol

Synthesis of Amide
Carboxylic acids do not undergo nucleophilic acyl substitution reactions with amines.
Because a carboxylic acid has a lower pKa than a protonated amine, the carboxylic acid
immediately donates a proton to the amine when the two compounds are mixed forming
salt.
H3C OH
O
+ CH3CH2NH2
H3CH2C OH
O
+ NH3
H3C O CH3CH2NH3
O
H3CH2C O NH4
O
1.
2.
acetic acid
ethanamine
propionic acid
ammonium
carboxylate salt
But at higher temperature, ammonium salts undergoes dehydration forming amide.
1. NH3OH
O
benzoic acid
2.
NH2
O
benzamide

Synthesis of phthalimide from phthalic acid
strong heat
-2H2O
OH
O
O
OH
phthalic acid
+ 2 NH3
ONH4
O
O
ONH4
NH2
O
O
NH2
NH
O
O
isoindoline-1,3-
dione
phthalamide
A carboxylic acid and an amine readily react to form an amide in the presence of an
dehydrating agent such as, dicyclohexylcarbodiimide (DCC).
amine
+R OH
O
carboxylic acid
R NHR'
O
amide
+ R'NH2
N C N
dicyclohexylcarbodiimide
(DCC)-dehydrating agent
+
N
H
C
N
H
O
dicyclohexylurea

Cl
O
O
O O
ONa
O
O
O
OH
O
OH
O
O
OH
Cl
O
OH
O
O
O
Cl
O
+
ONa
O
ONH4
O
OH
O
OH
O
P2O5
NH2
O
NaOH
1.
2.
3.
4.
a.
b.
c.
d.
Exercise

Mechanism of nucleophilic acyl substitution
Attack of the nucleophile takes place on carbonyl carbon atom forming tetrahedral
intermediate. The carboxylic acid their derivatives bearing group (OH, OR, Cl, OCOR, NR2)
which acts as leaving group therefore the intermediate further undergoes elimination
reaction forming substitution product.
+R Y
O
Y - is leaving group
Nu or
NuH R Nu
O
Y or H-Y
nucleophile
Step I: Nucleophile attacks the carbonyl carbon of a carboxylic acid derivative forming
intermediate is called a tetrahedral intermediate because the trigonal sp2-carbon in the
reactant has become a tetrahedral sp3-carbon in the intermediate – Addition reaction.
+R Y
O
R Y
O
nucleophile
Z
Zcarbonyl
compound
k1
k-1
k2
k-2
+R Z
O
carbonyl
compound
Y
leaving
group
tetrahedral
intermediate
sp2
carbon sp3
carbon sp2
carbon
Step II: The tetrahedral intermediate is unstable because Y and Z are both electronegative
atoms. A lone pair on the oxygen reforms the π-bond, and either Y-(k2) or Z-(k-1) is expelled
with its bonding electrons – elimination reaction.

A carboxylic acid derivative will undergo a nucleophilic acyl substitution reaction – if newly
added nucleophile should stronger base than the group depart.
R OH
O
carboxylic acid
R NH2
O
amide
R OR1
O
ester
R O
O
R1
O
acid anhydride
R Cl
O
acid chloride
SOCl2
or
PCl5
or
(COCl)2
R1OH
R1OH
NH3
NH3
H2O
strong acid or base
R1OH, H+
H2O, acid or base
H2O
slow at 200
C
H2O
fast at 200
C
R1CO2
-
relative basicities of the leaving groups
Cl-
< RCOO-
< RO-
< HO-
< H2N- Strongest baseWeakest base

Acid-catalysed nucleophilic acyl substitution
The nonbonded electron pairs on oxygen create electron-rich sites that can be protonated by
strong acids (H – A).
+
R OH
O
carboxylic acid
H A
R OH
O
H
R OH
O
H
R O
O
H
H + A
Protonation of C=O (preferred pathway)
three resonance structures for the conjugate acid
Protonation of -OH (non-preferred pathway)
+
R OH
O
carboxylic acid
H A R O
O
H
H
+ A
not resonance stabilized
H3O+
-H2O
R OH
O
carboxylic acid
R OH
O
H
R1OH
R
OH
O
H
O
R1
H
R
OH
OH
OR1
tetrahedral
intermediate
R
HO
O
H
O R1
H
+
R OR1
O
H
R OR1
O
+H+
ester
-H+
Example

The equilibrium is pushed towards the ester side by using an excess of alcohol or
carboxylic acid (usually the reactions are done in a solution of the alcohol or the carboxylic
acid).
H3O+
R OH
O
carboxylic acid R OH
O
H
R1OH
R
OH
O
H
O
R1
H
R
OH
OH
OR1
tetrahedral
intermediate
R
HO
O
H
O R1
H
+
R OR1
O
H
R OR1
O
+ H+
ester
-H+
H2O
excess water forcess
reaction forward
excess ester or removal of water
forcess reaction backward
acid-catalysed acid-catalysed
ester hydrolysis ester formation

Inter-conversion of acid derivatives by nucleophilic acyl substitution
R O
O
R1
O
acid anhydride
H2O or base
R Z
O
carbonyl
compound
R1OH
R1CO2
-
NH3
or RNH2
or R2NH
R OH
O
carboxylic acid
R OR1
O
ester
R NH2
O
10
, 20
, or 30
amides
R NHR
O
R NR2
O
Examples of
nucleophilic
acy substitution
Acid chlorides
H3CH2C Cl
O
propionyl chloride
+ + HClH3CH2C O
O
OH
phenyl propionate
example

Acid anhydrides
No reaction
H3C O
O
CH3
O
+ Cl
acetic anhydride
1.
2. H3C O
O
CH3
O
acetic anhydride
+ CH3CH2OH
H3C O
O
+
H3C OH
O
ethyl acetate acetic acid
3. O
O O
+ H2O
benzoic anhydride
OH
O
2
benzoic acid
4.
H3CH2C O
O
CH2CH3
O
propionic anhydride
+ 2 CH3NH2 H3CH2C NHCH3
O
CH2CH3
O
OCH3NH3
+
N-methylpropionamide

Esters
1.
H3C O
O
CH3 +
H3C OH
O
methyl acetate acetic acid
H2O + CH3OH
HCl
2.
O
O
CH3 + CH3CH2OH HCl O
O
CH2CH3 + CH3OH
methyl benzoate ethyl benzoate
transesterification
reaction
Both hydrolysis and alcoholysis of an ester can be catalyzed by acids or base (HO- or RO-).
is more reactive than H3C O
O
CH3
methyl acetate
H3C O
O
phenyl acetate
A reaction with an amine that converts one compound into two compounds is called
aminolysis.
H3CH2C O
O
CH2CH3 + CH3NH2
H3CH2C NHCH3
O
+ CH3CH2OH
ethyl propionate N-methylpropionamide

Amides
No reaction
H2O
+
H3C NHCH2CH2CH3
O
Cl +
NH-CH3
O
CH3OH
+
H3CH2C N(CH3)2
O
H3C O
O
+
H3CH2C NHCH2CH3
O
N-propylacetamide
N-methylbenzamide
N,N-dimethylpropionamide
N-ethylpropionamide
Amides do, however,
react with water and
alcohols if the reaction
mixture is heated in the
presence of an acid.
H2O1. +
H3C NHCH2CH3
O
N-propylacetamide
HCl
H3C OH
O
+ CH3CH2NH3
acetic acid
2. NH-CH3
O
CH3CH2OH
N-methylbenzamide
+
HCl
OCH2CH3
O
+
ethyl benzoate
CH3NH3
Amide with an NH2 group can
be dehydrated to a nitrile.
3.
H3CH2C NH2
O
propionamide
P2O5
800
C
H3CH2C C N

Which of the following reactions will not give the carbonyl product shown?
a. b.
OH
O
O
O
+
O
O O
Cl
O
O
O
+
O
O O
c. d.
NHCH3
O
O
O
+
O
O O
Cl
O
NH2
O
+ Cl
e. f.
OH
O
+ CH3NH2
NHCH3
O
OCH3
O
+
Cl
O
Cl
g. h. + H2O
OCH3
O
+ CH3NH2
NHCH3
O
Cl
O
OH
O

Mechanism of Claisen condensation
When two molecules of an ester in presence of base undergo a condensation reaction
forming β-keto ester, the reaction is called a Claisen condensation.
O
O
H3C
H
2
O
H3C
O
H CH3
O
+ CH3CH2OH1. CH3CH2O
2. HCl
ethyl 2-methyl-3-oxopentanoate
-keto ester
ethyl propionate
Mechanism
Enolate ionstrong base
Removing a proton from keto ester prevents the reverse reaction from occurring, because the
negatively charged alkoxide ion will not react with the negatively charged β-keto ester anion.
-keto ester anion
O
H3C
O
CH3
O
CH3CH2OH
O
O
H3C
H
+
CH3CH2OH
ethyl 2-methyl-3-oxopentanoate
-keto ester
ethyl propionate
CH3CH2O
O
O
H3C
O
O
H3C
+
O
O
H3C
O
CH3
O
CH3
O
O
O
H3C
O
CH3
O
+CH3CH2O
HCl
+
prevents the
reverse reaction

In the Claisen condensation, the negatively charged oxygen reforms the carbon–oxygen π-
bond while in Aldol addition, the negatively charged oxygen obtains a proton from the
solvent.
Claisen condensation: formation of a bond byexpulsion of RO-
O
O
H3C
H
ethyl 2-methyl-3-
oxopentanoate
-keto ester
ethyl propionate
CH3CH2O
O
CH3
O
CH3
O
O
O
H3C
O
CH3
O
2
CH3CH2O+
H
O
H3C
H
aldol
HO
O
CH3
H
CH3
O
H
OH
H3C
H
CH3
O
2
+
H2O
propionaldehyde
3-hydroxy-2-methylpentanal
HO
Aldol addition/condensation: protonation of O-

A mixed Claisen condensation is a condensation reaction between two different esters.
One ester does not have -hydrogen otherwise it gives mixture of products – two self
condensed and two cross condensed.
-keto ester
O
H3C
O
CH3
O
O
O
H3C
H
CH3CH2O
+ H+O
O
Ph
H
-keto ester
O
Ph
O
Ph
O
CH3CH2O
H+
CH3CH2O
H+
CH3CH2O
H+
-keto ester
O
H3C
O
Ph
O
-keto ester
O
Ph
O
CH3
O
2. HCl
O
O
H
1. CH3CH2O
add slowly
CH3CH2OH+ +H3C
ethyl butyrate
OCH2CH3
O O
O
O
ethyl benzoate ethyl 2-benzoylbutanoate
excess
Example:

Dieckmann condensation
Diester molecule undergoes intramolecular condensation reaction in presence of base
forming five- or six-membered ring cycloketone containing ester group at C2-position. An
intramolecular Claisen condensation is called a Dieckmann condensation.
2. HCl
O
O
O O
1. CH3OO
O
O
O
dimethyl adipate
O
O
O
methyl 2-oxocyclopentane
carboxylate
-keto ester
1,6-diester
+ CH3OH
A six-membered ring β-keto ester is formed from a Dieckmann condensation of a 1,7-
diester.
O
O
O
O
O
O
O
O
dimethyl heptanedioate
1,7-diester
2. HCl
1. CH3O
O
O
O
+ CH3OH
methyl 2-oxocyclohexane
carboxylate
-keto ester
O
O
O
O
dimethyl adipate
O
O
O
methyl 2-oxocyclopentane
carboxylate
-keto ester1,6-diester
+
- CH3OH
CH3O
O
O
O
O
O
O
O
OCH3
CH3O

Salfonic Acids
Ar S
O
O
OH Ar- Aromatic Ring
Aromatic Sulfonic Acid
Nomenclature: Name of hydrocarbon followed by sulfonic acid
SO3H
benzene
sulfonic acid
H3C S
O
O
OHR S OH
O
O
sulfonic acid
General structure Examples
TsOH
SO3H
benzene
sulfonic acid
H3C S OH
O
O
methansulfonic acid
SO3H
2-ethyl-1-methyl-
butansulfonic acid
SO3H
2-ethyl-1,2-dimethyl-
butansulfonic acid
SO3H
2-cyclobutyl-1-methyl-
ethansulfonic acid
Acidity of arene sulfonic acid
A sulfonic acid is a strong acid (pKa ~ -1) because its conjugate base is particularly stable
due to delocalization of its negative charge over three oxygen atoms.
"composite"
resonance structure
R S O-
O
O
R S O
O
O-
R S O
O-
O
H+
+
R S O
O
O

Acidity
R S OH
O
O
sulfonic acid
+ :B R S O-
O
O
R S O
O
O-
R S O
O-
O
+ H B+
pKa = -7 Three resonance structres -
all have a negative charge on oxygen
Explain - Sulfonic acids are more acidic than carboxylic acids.
- Resonance stabilization
- Solvation of conjugated base.
Carboxylate ion
4 - hydrogen bonds
R
C
O
O-
O
H
H
O
H
H
O H
H
O
H
H
R S
O
O
O-
O
H HOH
H
O
H
H
O HH
O
HH
O
HH
Sulfonate ion
6-hydrogen bonds

S
O
O
OH
Conc. H2
SO4
/
Fuming H2SO4/Oleum H2S2O7
SO3/Catalyst
Sulfonation reaction: Reagents:
Mechanism
H2SO4 SO3 H3
O HSO4
Step I: Generation of Electrophile
2 + -
+ +
S
O
O O
H
S
O
O
O
H
S
O
O
O
Step II: Attack of electrophile
+
+
-
+
- etc
H2
SO4HSO4
H
S
O
O
O
S
O
O
O
Step III: Aromatisation
-
++
+
-
-
H3
O
S
O
O
O SO3
H
OH2
Step IV: Protonation
+ ++
-

An advantage of the sulfonation reaction is its reversibility. Simply heating benzenesulfonic
acid with an aqueous acid removes the sulfonic acid group.
SO3H
benzene
sulfonic acid
H3O+
/1000
C
H
+ SO3

Sulfonation of toluene
Direct sulfonation of toluene with concentrated sulfuric acid gives a mixture of ortho and
para sulfonic acids from which about 40% of toluene para sulfonic acid can be isolated as
the sodium salt.
H2SO4
CH3
SO
O
ONa
CH3
SO
O
OH
++
CH3 CH3
SO3H
NaCl
40% para isomer
isolated as sodium
salt
toluene
SO3 as the also used as electrophile and draw the intermediate with the charge at the
ipso carbon to show the stabilization from the methyl group.
CH3
S
OO
O
CH3
H S
O O
O-
CH3
SO
O
O-
H+
CH3
SO
O
OH

Sulfonation of naphthalene
Sulfonation of naphthalene does not always lead to substitution at the 1-position; may
occur at 2-position. If the reaction is carried out under conditions which cause it to be
irreversible (800C), substitution occurs at the 1-position (90% yield; kinetically control).
SO3H
800
C
naphthalene naphthalene-1-
sulfonic acid
H2SO4
H
+ + H2O
the reaction is carried out under conditions which cause it to be readily reversible (1600C),
substitution occurs predominantly at the 2-position (90% yield, thermodynamically
control).
SO3H
SO3H
naphthalene
1600
C
naphthalene-1-
sulfonic acid
naphthalene-2-
sulfonic acid
H2SO4
H
++ H2O
(kinetic product) (thermodynamic product)

Sulfonation of naphthalene
The 1-substituted product is easier to form because the carbocation leading to its formation
is more stable. The 2-substituted product is more stable because there is more room for the
bulky sulfonic acid group at the 2-position.
H SO3H H
SO3H
H
21
H SO3H H SO3H
800
C
conc. H2SO4
H
H
-H+ kinetic control
1600
C
conc. H2SO4
thermodynamic
control
naphthalene
SO3H
H
-H+
1600
C
stable intermediates
less stable
intermediates
naphthalene-1-
sulfonic acid
naphthalene-2-
sulfonic acid
A sulfonic acid group on C1 comes within the van der Waals radius of the hydrogen at C8.
H SO3H
H
SO3H
H
an unfavorable
steric interaction
1 2
38 1

Orientation of monosubstituted benzene
Ortho/Para-Directing Groups
Meta-Directing Groups
Groups shows electron donating effect as +I and
+R effect. +R effect is strong than +I.
Groups shows electron withdrawing effect as -I and -R effect.
SO3
X
SO3
H
X X
SO3
H
+ +
(Ortho/2-)
(Para/4-)
Salfonation
Desalfonation
SO3
X
SO3H
X
+
Salfonation
Desalfonation
(Meta/3-)

Acidity of Arene Sulfonic acids
SO3
H SO3
OH2
H3O
+ +
-
+
Sulfonic acid Sulfonate
SO3H SO3
OH2NaOH
Na
+ +
- +
Sulfonic acid Sodium Sulfonate
(Base)
S
O
O O
S
O
O O S
O
O O S
O
O O
-
- -
-
Benzoate ion (Stabilisation of negative charge by resonance)
O O
O O
O
O- - -
Carboxylate ion (Stabilisation of negative charge by resonance)
Sulfonic acid donates proton in
its aqueous solution.
The acidic proton of the sulfonic
acid reacts with base forming salt
and water
The negative charged sulfonate
stabilized by three resonance
structures (three oxygen atoms)
The negative charged carboxylate
stabilized by two resonance
structures (two oxygen atoms)

Sulfonic Acids
Reagents:
NaOH,
NaHCO3
SO3Na
SO3
H
Heat to 100-175 C
Desulfonation
Heat/Water
PCl5/PCl3/POCl3
SOCl2
NH3
ROH
SO2
Cl
Sulfonyl chloride
SO2
OR
Sulfonate ester
SO2NR2
Sulfonamide
-SO3H is solubilising Agent
The sulfonic acid group is more polar than
any other group. It increases the solubility
of drugs, dyes, detergent in water.
-SO3H is blockinig Agent
-It is easily added by sulfonation and removed by
desulfonation on heating. It is very useful to block the
reacting position. E.g. Chlorination of toluene
OH
N
N SO3H
Orange II (Dye)
CH3
SO2NCl Na
+
_
(Chloramine T)
(Drug)
CH3
H2SO4
CH3
SO3H
Cl2
Fe
CH3
SO3H
Cl
CH3
Cl
dil HCl
Blocking
desulfonation
Toluene

IPSO substitution
In addition to o-, m- and p-attack on substituted benzene C6H5X, the electrophilic
substitution at the carbon atom bearing substituent X is occurred. The C6H5X undergoes
electrophilic substitution reactions with electrophile E+ forming an intermediate reversible
as shown below which would undergoes the displacement of X+. Such overall reaction is
called as ipso substitution
X
IPSO-substitution
X
E
E
-X+E+
Ipso-substitution usually occurs with reversible electrophilic substitution reaction such as
sulfonation.
OH OH
SO3H
HO3S
H2SO4 H3O+
O
SO3H
HO3S
H
H
IPSO substitution
OH
H
HO3S
+
S
O O
O
H
H2OSO O
HO
H
OH
H2SO4 + H+
2-naphthol

S.y. carboxylic acid

S.y. carboxylic acid

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