Puan Rozaini Abdullah
School of Bioprocess Engineering
Carboxylic Acid
Carboxylic acids (RCO2H) are a common and important functional group
(e.g. amino acids, fatty acids etc.) and provide the point of access to the
carboxylic acids derivatives (acyl chlorides, acid anhydrides, esters,
amides etc.).
Carboxylic acids are the most acidic of the common organic functional
groups.
Structure: The CO2H unit is planar and consistent with sp2 hydridization and a
resonance interaction of the lone pairs of the hydroxyl oxygen with the p system of
the carbonyl.
Example of Carboxylic Acid:
Physical Properties:
The polar nature of both the O-H and C=O bonds (due to the electonegativity
difference of the atoms) results in the formation of strong hydrogen bonds
with other carboxylic acid molecules or other H-bonding systems (e.g. water).
The implications are:
higher melting and boiling points compared to analogous alcohols
high solubility in aqueous media
hydrogen bonded dimers in gas phase and dimers or aggregates in
pure liquid
Reaction of Carboxylic Acid:
Conversion carboxylic acid to :
1. Ester
2. Acyl halide
3. Acid Anhydrides
4. Amides.
 Reduction to alcohol
 Hell-Volhard-Zelinsky reaction
 Decarboxylation reaction

Relative reactivity of carboxylic
acid:
The image shows the electrostatic potential for
acetic acid (ethanoic acid).
The more red an area is, the higher the electron
density and the more blue an area is, the lower
the electron density. There is low electron density
(blue) on H atom of the -CO2H group alcohol, i.e.
H+ character.
The H atom of the RCO2H is acidic (pKa ~ 5).
The most important reactions of carboxylic acids
converts them into carboxylic acid derivatives
such as acyl halides, esters and amides via
nucleophilic acyl substitution reactions.
Relative reactivity of carboxylic
acid:
The image shows the electrostatic
potential for the acetate ion
(ethanoate
ion)
The more red an area is, the higher
the electron density and the more
blue an area is, the lower the
electron density.
There is high
electron density (red) on both O
atoms of the -CO2- group alcohol,
i.e. resonance and basic or
nucleophilic behavior
Relative reactivity of carboxylic
acid derivatives:
Carboxylic acid derivatives react tend to react via
Nucleophilic Acyl substitution where the group on the acyl
unit, R-C=O undergoes substitution:
The observed reactivity order is shown below:
It is useful to view the carboxylic acid derivatives as an acyl group, RC=O, with a different substituent attached.
The important features of the carboxylic acid derivatives that influence their
reactivity are governed by this substituent in the following ways:
the effect the substituent has on the electrophilicity of the carbonyl C?
if the substituent is electron donating, then the electrophilicity is reduced, \
less reactive
if the substituent is electron withdrawing, the electrophilicity is increased, \
more reactive
the ability of the substituent to function as a leaving group.
Derivative
Substituent
Electronic effect
Leaving Group
Availbility
Relative
Reactivity
Acyl chloride
-Cl
withdrawing group
(inductive)
very good
1 (most)
Anhydride
-OC=OR
donating
good
2
Ester
-OR
strongly donating
poor
=3
Acid
-OH
strongly donating
poor
=3
Amide
-NH2
very strongly
donating
very poor
4
Carboxylate
-O-
very, very strongly
donating
appalling !
5 (least)
Preparation of Acyl Chlorides
Reaction type:
Nucleophilic Acyl
Substiution
•Acyl chlorides are prepared by treating the carboxylic acid
with thionyl chloride, SOCl2, in the presence of a base.
•Acyl chlorides are by far the most commonly encountered of
the acyl halides.
Esterification Reaction:
Reaction type:
Nucleophilic Acyl
Substitution
This reaction is also known as the Fischer esterification.
Esters are obtained by refluxing the parent carboxylic acid with the
appropriate alcohol with an acid catalyst.
The equilibrium can be driven to completion by using an excess of either
the alcohol or the carboxylic acid, or by removing the water as it forms.
Alcohol reactivity order : CH3OH > 1o > 2o > 3o (steric effects)
If a compound contains both hydroxy- and carboxylic acid groups, then
cyclic esters or lactones can form via an intramolecular reaction. Reactions
that form 5- or 6-membered rings are particularly favorable.
Step 1:
An acid/base reaction. Protonation of the carbonyl makes it more
electrophilic.
Step 2:
The alcohol O functions as the nucleophile attacking the electrophilic C
in the C=O, with the electrons moving towards the oxonium ion,
creating the tetrahedral intermediate.
Step 3:
An acid/base reaction. Deprotonate the alcoholic oxygen.
Step 4:
An acid/base reaction. Need to make an -OH leave, it doesn't matter
which one, so convert it into a good leaving group by protonation.
Step 5:
Use the electrons of an adjacent oxygen to help "push out" the leaving
group, a neutral water molecule.
Step 6:
An acid/base reaction. Deprotonation of the oxonium ion reveals the
carbonyl in the ester product.
Hell-Volhard-Zelinsky Reaction
Reaction type:
Substitution
Reagents most commonly : Br2 and either PCl3, PBr3 or red
phosphorous in catalytic amounts.
Carboxylic acids can be halogenated at the C adjacent to the carboxyl
group.
This reaction depends on the enol type character of carbonyl
compounds.
The product of the reaction, an a-bromocarboxylic acid can be
converted via substitution reaction to a-hydroxy- or a-amino carboxylic
acids.
Synthesis of Paracetamol &
Aspirin:
Acetic Anhydride
Salicylic acid
Acetyl salicylic
acid, aspirin
Acetic Acid
Synthesis of Paracetamol &
Aspirin:
Para-nitrophenol
Orto-nitrophenol
4-aminophenol
Paracetamol
N-(4-hydroxyphenyl)ethanamide