Table Of ContentLIST OF OTHER TITLES IN THIS SERIES:
VOL. 1. The Determination of Epoxide Groups by
B. DOBINSON. W. HOFMANN AND B. P. STARK
VOL. 2. Periodate Oxidation of Diol and Other Functional Groups by
G. DRYHURST
THE DETERMINATION
OF CARBOXYLIC
FUNCTIONAL GROUPS
by
R. D. TIWARI, M.Sc, D.Phil.
Professor of Chemistry, University of Allahabad, India
and
J. P. SHARMA, M.Sc, D.Phil., D.Sc.
Department of Chemistry, University of Allahabad, India
PERGAMON PRESS
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Copyright © 1970 R. D. Tiwari and J. P. Sharma
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First edition 1970
Library of Congress Catalog Card No. 73-104121
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08 015516 2
PREFACE
THE subject-matter presented in this book deals with the quantitative
determination of carboxylic acids, anhydrides, acid chlorides, esters,
lactones, and amides. The separation of chemically similar components
of mixtures by chromatographic and allied techniques has also been
described. The final chapter deals with the quantitative estimation of
the components of binary and ternary mixtures. An account of the
strength of carboxylic acids in aqueous and non-aqueous solvents,
included at the beginning of the second chapter, may be helpful when
selecting the optimum conditions for the titrimetric determination of
carboxylic acids.
It has been our aim to include those methods which may be applicable
to almost all types of compounds containing the carboxyl group and
its derivatives mentioned above. Although a short account of the prin-
ciples of the techniques described is presented wherever appropriate to
give readers, especially beginners, the basis of the methods, compre-
hensive theoretical details have been omitted, since they are, in our
opinion, beyond the scope of this Monograph. Likewise, no attempt has
been made to record a complete bibliography of the subject; the em-
phasis has been placed on the key methods useful in general analytical
work. If some useful methods for particular purposes have been omitted,
it has not been our intention to underrate their possible importance.
We thank the General Editors and the Publishers for their help and
co-operation in the production of this Monograph. It will be a pleasure
for us to receive any criticisms and suggestions from readers.
Department of Chemistry, R. D. TIWARI
University of Allahabad, J. P. SHARMA
India
vii
CHAPTER 1
INTRODUCTION
IT IS needless to emphasize the importance of the analytical aspects of
organic chemistry, which is expanding at an ever-increasing pace. A
new substance, whether prepared in the laboratory or isolated from
natural sources, requires qualitative and quantitative evaluation. The
study of fundamental problems such as the mechanism of organic
reactions, whether occurring in the test-tube or in nature, frequently
demands that the intermediate products or species be identified and the
extent of their formation ascertained, if a complete understanding of
the process is to be attained. The need for methods which facilitate
these objectives is evident.
In this book we are concerned primarily with the quantitative aspect
of organic analysis. Analyses of organic compounds via the reactions
of their functional groups are more fundamental than elemental
analysis, because their characteristic properties arise from the functional
group (or groups) present. Functional group analysis is important to
research workers because it gives information which may provide a
tentative structure for an unknown compound. For example, the simple
determination of the neutralization equivalent of an unknown carboxy-
lic acid can provide an important clue to its structure.
This Monograph deals with the functional group analysis of the
carboxyl group and its anhydride, acid chloride, ester, lactone, and
amide derivatives. Since workers in the field of natural products and
biosynthesis are frequently confronted with the problem of separating
chemically similar components from a mixture, the possible application
of the various separation techniques such as paper, adsorption, partition,
column, thin-layer, and gas chromatographies, counter-current distri-
bution, electrophoresis, and fractional distillation have been described
at appropriate places in the text. Some other chemical methods for the
1
2 CARBOXYLIC FUNCTIONAL GROUPS
resolution of binary mixtures (and occasionally of ternary mixtures) are
discussed in the final chapter.
No attempt has been made to keep chemical and physical methods
separate; the essential physical methods such as ultraviolet, visible, and
infrared spectrophotometry, polarography, etc., have been discussed
and their applications to qualitative and quantitative analyses of car-
boxylic acids and their derivatives have been described. In fact, the
physical methods, particularly the spectroscopic methods, provide
information so readily about an unknown substance that they have
become indispensible.
The methods used in functional group analysis have been classified
on the basis of the amount of sample used. At least 2 m-equiv. is
required for macro methods; in terms of weight this may approximate
to 0-5 g. Semimicro methods employ about 1 m-equiv. (50-200mg) of
sample. Micro-scale determinations use a sample size of 0-1 m-equiv.
(5-20 mg) and the material is weighed on a micro balance with an
accuracy of at least 0· 005 mg. Methods which employ still smaller
samples are termed submicro methods, the weight of substance analysed
ranging from 0 03 to 0-05 mg (30-50/xg). These submicro methods
find important applications in bio- and physiological chemistry. In the
following chapters methods using each of these four scales of working
are described. It must be mentioned that almost all the macro methods
may be modified to the semimicro or micro scales with suitable changes
in the conditions of the experiment and the size of apparatus used.
Non-volatile solids and liquids should preferably be weighed in a
small pyrex glass vial and introduced directly into the reaction vessel.
Volatile samples should be weighed in sealed capillaries and the capillary
should be crushed in the reaction vessel after the reagent has been added.
The crushing rod should be rinsed with the solvent.
Organic analysis differs from inorganic analysis in the sense that, in
the majority of cases, organic reactions are slow and require a specific
time for completion. The possibility of side-reactions occurs in many
cases. Even members of the same homologous series may differ in speed
of reaction towards a reagent. For these reasons, the choice of a method
and its reaction conditions (especially time and temperature) should be
made with caution.
It cannot be claimed that the methods described in this book will give
INTRODUCTION 3
successful analyses of all possible carboxylic acids and their derivatives.
There may arise problems with individual compounds, and under cer-
tain conditions the methods may fail ; it is then for the chemist concerned
to determine which modifications to a particular method are necessary
to make it successful under the specific circumstances.
CHAPTER 2
THE DETERMINATION
OF CARBOXYLIC ACIDS
1. GENERAL
Arrhenius' definition of acids (and bases) was limited in scope.
Subsequently, Brönsted and Lowry (1) defined acids more generally as
those substances which act as proton donors. Eventually, the Lewis (2)
definition of acids covered the complete range of electron-deficient
molecules (electrophilic substances), enunciating that "all substances
which act as electron acceptors from electron-rich molecules (electron
donors, or bases) are acids". The Brönsted-Lowry acids (H-acids)
form a sub-class of Lewis acids, and we restrict this discussion to such
substances.
A wide variety of organic substances show acidic character. The
carboxylic acids are the most important of these; they contain the
carboxyl functional group
/°
— C — OH.
These acids are much weaker than mineral acids; they are not com-
pletely ionized in aqueous solution. In solution, the undissociated
form remains in equilibrium with the dissociated form as represented
in eqn. (1).
R-C — OH ^± R — C — Ο- + H+ (1)
4
DETERMINATION OF CARBOXYLIC ACIDS 5
The stability of the anion
L R - c - o J,
once formed, as compared with the undissociated acid
RC — OH,
is a very important factor governing the acidity of carboxylic acids. As
a result of the strong electronegative character of oxygen, relative to
carbon, the oxygen atom of the carbonyl group tends to attract π-elec-
trons. Consequently, to compensate the loss, the carbon atom tends
to draw electrons from the hydroxyl oxygen. The effect is transmitted
further to the hydroxyl group, weakening the hydrogen-oxygen bond
and facilitating the release of the proton (eqn. 2).
R—c—0-—H R—C + H"1 (2)
V
Once the carboxylate anion has formed it becomes resonance-stabilized
(eqn. 3) and its energy content is lowered, further favouring the dissocia-
tion of the molecule to donate the proton.
o'
/
R C
2. ACID-BASE EQUILIBRIUM IN WATER
(a) STRENGTH OF ACIDS IN WATER (p£« VALUES)
An estimate of the strength of an acid HA in water may be made by
considering the equilibrium shown in eqn. (4):
HA + H 0 H 0+ + A- (4)
2 3
6 CARBOXYLIC FUNCTIONAL GROUPS
By applying the law of mass action,
_ [A-] [H Q j
3
' [HA] [H 0]
2
where the quantities [A-], etc., represent the activities of the species.
However, since the [H 0] in eqn. (5) remains almost constant, a new
2
constant, K., may be defined by eqn. (6).
[A-] [H3O+]
* = — H AT ) (6
K is more commonly called the acidity constant or the dissociation
a
constant of the acid. Since the values of K run in negative powers
a
of ten, it is more convenient to convert K into pK, where pK =
a a a
— logioATa. It is apparent from the above relationships that the larger
the value of K„ (or the smaller the value of pK ) the greater will the
a
dissociation of the acid be and the stronger its acidic character.
The pK value of an unknown acid may be measured by some suitable
a
technique such as potentiometry, conductimetry, or spectrophotometry
by use of eqn. (7) :
[HA]
pK = pH + log — (7)
a
The value of pK may be calculated by determining the relative activi-
a
ties in a solution of known pH. Molar concentrations, instead of
activities, may be used if the solutions employed are sufficiently dilute.
(b) FACTORS AFFECTING THE pK VALUES
a
The structure of the group attached to the carbonyl carbon has a
marked effect on the strength of acids. Formic acid is the strongest
(pK = 3-77) of the simple saturated aliphatic carboxylic acids. Any
a
factor which increases the availability of electrons on the oxygen atoms
of the carboxylate ion destabilizes the ion, and encourages recombina-
tion of the proton with the anion. Consequently, the replacement of
the hydrogen atom attached to the carbonyl carbon by a methyl group
