1. Part II Non-Aqueous Titration
Non-aqueous titration refers to a type of titration in which the analyte substance is dissolved in
a solvent which does not contain water. The need for non-aqueous titration arises because water
can behave as a weak base and a weak acid as well, and can hence compete in proton acceptance
or proton donation with other weak acids and bases dissolved in it. This type of competition
provided by water towards weak bases or weak acids makes it difficult to detect the end point
of the titration. Therefore, these substances which have very sharp end points when titrated in
aqueous solutions due to their weakly basic or weakly acidic nature generally need to be titrated
in non-aqueous solvents. The procedure of non-aqueous titration is very useful because it
satisfies two different requirements, namely – suitable titration of very weak acids or bases
along with providing a solvent with an ability to dissolve organic compounds.
Many reactions which occur in non-aqueous titration procedures can be explained via the
Bronsted-Lowry theory and its definition of acids and bases. Basically, acids can be thought of
as proton donors, whereas bases can be thought of as proton acceptors.
Reasons for titration in non-aqueous solvent
There are three common reasons why in non-aqueous titration non-aqueous solvent is used,
they are-
1. The reactants or product may be insoluble in water.
2. The reactants or product might react with water.
3. The analyte is too week acid or base to be titrate in water.
Non-aqueous solvents used are
Aprotic solvents are neutral, chemically inert substances such as benzene, carbon tetrachloride
and chloroform. These are Solvents which neither donate nor accept protons. They have a low
dielectric constant, do not react with either acids or bases and therefore do not favor ionization.
The fact that picric acid gives a colorless solution in benzene which becomes yellow on adding
aniline shows that picric acid is not dissociated in benzene solution and also that in the presence
of the base aniline it functions as an acid, the development of yellow color being due to
formation of the picrate ion.
Since dissociation is not an essential preliminary to neutralization, aprotic solvents are often
added to ionizing solvents to depress solvolysis (which is comparable to hydrolysis) of the
neutralization product and so sharpen the endpoint.
Protophilic solvents have greater tendency to accept protons, i.e., water, alcohol, liquid
ammonia, etc. They are basic in character.
NH3 + H+
NH4
+
A weakly basic solvent has less tendency than a strongly basic one to accept a proton. Similarly,
a weak acid has less tendency to donate protons than a strong acid. As a result a strong acid
such as perchloric acid exhibits more strongly acidic properties than a weak acid such as acetic
acid when dissolved in a weakly basic solvent. On the other hand, all acids tend to become
indistinguishable in strength when dissolved in strongly basic solvents owing to the greater
affinity of strong bases for protons. This is called the leveling effect. Strong bases are leveling
solvents for acids; weak bases are differentiating solvents for acids.
Protogenic solvents have the tendency to produce protons, i.e., water, liquid hydrogen
chloride, glacial acetic acid, etc. They are acidic substances. Protogenic solvents are those that
generate protons (Hydrogen ions). These solvents are typically more acidic than water. The
2. primary function of protogenic solvents is to increase the basic strength of weak bases. They
make weak bases stronger by donating protons. Because of their high proton donating capacity,
they have a levelling effect on weak bases.
H2O H+
+ OH-
Amphiprotic solvents have both protophilic and protogenic properties. Examples are water,
acetic acid and the alcohols. They are dissociated to a slight extent. The dissociation of acetic
acid, which is frequently used as a solvent for titration of basic substances, is shown in the
equation below:
CH3COOH ⇌ H+
+ CH3COO-
Here the acetic acid is functioning as an acid. If a very strong acid such as perchloric acid is
dissolved in acetic acid, the latter can function as a base and combine with protons donated by
the perchloric acid to form protonated acetic acid, an onium ion.
HClO4⇌ H+
+ ClO4
-
CH3COOH + H+
⇌ CH3COOH2
+
(onium ion)
Since the CH3COOH2
+
ion readily donates its proton to a base, a solution of perchloric acid in
glacial acetic acid functions as a strongly acidic solution.
When a weak base, such as pyridine, is dissolved in acetic acid, the acetic acid exerts its
levelling effect and enhances the basic properties of the pyridine. It is possible, therefore, to
titrate a solution of a weak base in acetic acid with perchloric acid in acetic acid, and obtain a
sharp endpoint when attempts to carry out the titration in aqueous solution are unsuccessful.
HClO4 + CH3COOH ⇌ CH3COOH2
+
+ ClO4
-
C5H5N + CH3COOH ⇌ C5H5NH+
+ CH3COO-
CH3COOH2
+
+ CH3COO-
⇌ 2CH3COOH
Adding HClO4 + C5H5N ⇌ C5H5NH+
+ ClO4
-
Advantages of non-aqueous solvent over aqueous solvent
1. The substances, which are either to weakly acidic or too weakly basics to give sharp end
point in aqueous solutions, can easily be titrated with accuracy in non-aqueous solvent.
2. Organic acids and bases that are insoluble in water are soluble in non-aqueous solvent.
3. Organic acid, which is of comparable strength to water, cannot be titrated easily non-aqueous
solvent. Bases also follow the same rules.
4. A non-aqueous solvent may help two are more acids in mixture. The individual acid can give
separate end point in different solvent.
5. By the proper choice of the solvents or indicator, the biological ingredients of a substance
whether acidic or basic can be selectively titrated.
6. Non aqueous titrations are simple and accurate, examples of non-aqueous titration are-
Ephedrine preparations, codeine phosphate in APC, tetracycline, teramycin, Anti- histamines
and various piperazine preparations.
Disadvantages of non-aqueous titrations
1. Solvents are comparatively expensive and less stable than ones used in aqueous titrations
2. Indicators have to be prepared in a non-aqueous medium
3. Solvents require calibrations after each use
4. Volatile solvents can pollute the environment
5. This titration is non-specific; hence there are chances that impurities may interfere
3. Detection of end point
In non-aqueous titrations there are two methods are used to determine the endpoint,
potentiometric method and the indicator method in which the end point is detected by the color
change.
Sr. No. Indicator Colour change
1 Crystal violet Violet yellowish green
2 A-naptholbenzein Blue dark green
3 Oracet blue Blue pink
4 Olinadine red Magneto colourless
References
1. Rao DG. Text Book of Pharmaceutical Analysis. Vol- I. New Delhi: Birla Publication; P.
76.
2. Chaluvaraju KC, Zaranappa. Textbook of Pharmaceutical Analysis. First Edition, New
Delhi: Paging Publishers; 2018. P. 64- 68.
