Carboxylic acids and their derivatives react through nucleophilic acyl substitution reactions. Esters can undergo hydrolysis reactions with water to form carboxylic acids and alcohols. Amines can also perform nucleophilic acyl substitutions on esters to form amides. The reactivity of these compounds depends on the strength of the leaving group, with acyl chlorides being the most reactive due to having the weakest leaving group. Carboxylic acids are strong acids due to resonance stabilization of the carboxylate ion over the carboxylic acid.

1. Carboxylic Acid
Prepared by – Debadatta Mahapatra (MSc Chemistry)

3. Esters, acyl chlorides, and amides are called carboxylic acid derivatives, because
they differ from a carboxylic acid only in the nature of the group or atom that has
replaced the OH group of the carboxylic acid.
The second class of carbonyl compounds are those in which the acyl group is attached
to a group that cannot be replaced by another group. Aldehydes and ketones belong to
this class.
The H bonded to the acyl group of an aldehyde and the R group bonded to the
acyl group of a ketone cannot be replaced by a nucleophile.

6.  The acyl groups of carboxylic acids and carboxylic acid derivatives are attached
to weaker bases than are the acyl groups of aldehydes and ketones. ( Remember that the
lower the pK, the stronger the acid and the weaker its conjugate base.)
 The hydrogen of an aldehyde and the alkyl group of a ketone are too basic to be replaced by
another group.

7. In systematic (IUPAC) nomenclature, a carboxylic acid is named by
replacing the terminal “e” of the alkane name with “oic acid.” For
example, the one-carbon alkane is methane, so the one-carbon carboxylic
acid is methanoic acid.

8. Formic acid is found in ants, bees, and other stinging insects;
its name comes from formica, which is Latin for “ant.”
Acetic acid—contained in vinegar—got its name
from acetum, the Latin word for “vinegar.”
 Propionic acid is the smallest acid that shows some of the
characteristics of the larger fatty acids its name comes from the
Greek word's pro (“the first”) and pion (“fat”).

9.  Butyric acid is found in rancid butter; the Latin word
for “butter” is butyrum
 Valeric acid got its name from valerian, an herb that has
been used as a sedative since Greco-Roman times.
 Caproic acid is found in goat’s milk. If you have ever
smelled a goat, then you know what caproic acid smells
like. Caper is the Latin word for “goat.”

10. Difference between systematic (IUPAC) and common nomenclature:

13. Did you know !!

14. Bonding in a carbonyl group. The
pi bond is formed by the side-to-side
overlap of a p orbital of carbon with a
p orbital of oxygen.

21. Physical Properties of Carboxylic Acids
(a) Physical state: The first three aliphatic acids are colorless liquids with pungent smell.
The next six are oily liquids with an odor of rancid butter while the higher members are
colorless, odorless, waxy solids.
 Benzoic acid is a crystalline solid.
(b) Solubility: Carboxylic acid molecules are polar, like alcohols, and can form
intermolecular hydrogen bonds.
 The first four acids are miscible with water, the is partly soluble and the
higher acids are insoluble.
 It is because of the increase in the magnitude of non-polar part in the molecule.
 Benzoic acid is practically insoluble in water.
Carboxylic acids are soluble in less polar solvents like ether, benzene, alcohol, etc.

22.  Boiling points: Because of their ability to form intermolecular hydrogen bonding,
carboxylic acids have high boiling points.
The hydrogen bonds formed by the carboxylic acids are stronger than those in alcohols
because O—H bond in COOH is strongly polarized due to the presence of electron
withdrawing carbonyl group in adjacent position than the O—H bond of alcohols.
Therefore, the boiling points of carboxylic acids particularly lower members are higher
than alcohols of comparable

23. The reactivity of carbonyl compounds is due to the polarity of the carbonyl
group, which results from oxygen being more electronegative than carbon.
The carbonyl carbon is, therefore, electron deficient (it is an electrophile),
so it reacts with nucleophiles.

25. In this case, no new product is
formed. The nucleophile adds
to the carbonyl carbon, but the
tetrahedral intermediate
eliminates the nucleophile and
re-forms the reactants.

26. A carboxylic acid derivative will undergo a nucleophilic acyl
substitution reaction, provided that the newly added group in the
tetrahedral intermediate is a stronger base than the group attached
to the acyl group in the reactant.

27. • In contrast, the weakest bond in a nucleophilic acyl
substitution reaction is the pi bond, so this bond breaks
first and the leaving group is eliminated in a subsequent
step.

29. Relative reactivity: acyl chloride >
ester ~ carboxylic acid > amide  Weak bases cause the carbonyl carbon to be more
electrophilic and, therefore, more reactive toward
nucleophiles.
 A weak base attached to the acyl group also makes the second step of the nucleophilic
acyl substitution reaction easier, because weak bases are easier to eliminate
when the tetrahedral intermediate collapses.

30. A carboxylic acid derivative can be converted into a less reactive carboxylic
acid derivative in a nucleophilic acyl substitution reaction, but not into one
that is more reactive.
For example, an acyl chloride can be converted into an ester, because an
alkoxide ion is a stronger base than a chloride ion.
An ester, however, cannot be converted into an acyl chloride because a chloride
ion is a weaker base than an alkoxide ion.

31. Carboxylic acids behave as strong acids:
 Carboxylic acids as well as carboxylate ion both are
stabilized by resonance.
 carboxylate ion is more stabilized by resonance than
carboxylic acid, therefore, equilibrium lies very much
in forward direction

34. Chemical Reactions

38. Ring substitution reaction: Aromatic carboxylic acids undergo electrophilic
substitution reactions in which —COOH group acts as a deactivating and meta-directing
group. They however do not undergo Friedel–Crafts reaction because the carboxyl group is
deactivating and the catalyst AlCl3 (Lewis acid) gets bonded to the carboxyl group.

41. An ester reacts with water to form a carboxylic acid and an alcohol. This is an example
of a hydrolysis reaction. A hydrolysis reaction is a reaction with water that converts one
compound into two compounds (lysis is Greek for “breaking down”).
An ester reacts with an alcohol to form a new ester and a new alcohol. This is an
example of an alcoholysis reaction—a reaction with an alcohol that converts one
compound into two compounds. This alcoholysis reaction is also called a
transesterification reaction because one ester is converted to another ester

42. Esters react with amines to form amides. A reaction with an amine that converts one
compound into two compounds is called aminolysis. The aminolysis of an
ester requires only one equivalent of amine, unlike the aminolysis of an acyl halide
 This is because the leaving group of an ester is more basic than the amine,

43. Amides are very unreactive compounds. They do not react with
halide ions, alcohols, or water because, in each case, the
incoming nucleophile is a weaker base than the leaving group of
the amide
However, that amides do react with water and alcohols if an acid is present
to catalyze the reaction

44. Amides react with water to form carboxylic acids and with alcohols
to form esters, if the reaction mixture is heated in the presence of an
acid.

45. Esters hydrolyze slowly because water is a poor nucleophile
and esters have relatively basic leaving groups. The rate of
hydrolysis can be increased by either acid or hydroxide ion
 All organic intermediates and products in acidic solutions are positively charged or
neutral; negatively charged organic intermediates and products are not formed in
acidic solutions.
 All organic intermediates and products in basic solutions are negatively charged or
neutral; positively charged organic intermediates and products are not formed in
basic solutions.
 when an acid is added to an ester, the acid protonates
the carbonyl oxygen.

46.  The resonance contributors of the ester show why the carbonyl
oxygen is the atom with the greatest electron density.
 An acid catalyst increases the
reactivity of a carbonyl group.

47. The rate of hydrolysis of an ester can be increased by hydroxide ion.
 Hydroxide ion adds to the carbonyl carbon of the ester.

48. Transesterification
Transesterification—the reaction of an ester with an alcohol—is also catalyzed
by acid.
As in ester hydrolysis, the leaving groups in the tetrahedral intermediate have
approximately the same basicity.
 Consequently, an excess of the reactant alcohol must be used to produce a
good yield of the desired product.

49. Prostaglandins have several different physiological functions One is to stimulate
inflammation and another to induce fever The enzyme prostaglandin synthase catalyzes
the conversion of arachidonic acid, a naturally occurring carboxylic acid into
PGH2, the precursor of all prostaglandins and the related thromboxanes.
It was found that the anti-inflammatory and fever-
reducing activity of aspirin was due to a
transesterification reaction that blocks the synthesis of
prostaglandins.
Friedrich Bayer