Non-aqueous titration is a method used to determine the concentration of substances in solvents that do not contain water, allowing for the titration of weak acids and bases without interference from water's acid-base properties. Various types of non-aqueous solvents, including aprotic and protogenic solvents, are utilized, and specific indicators are employed to signal the endpoint of titrations. The document provides detailed procedures for preparing and standardizing non-aqueous titrants such as perchloric acid and methoxide, along with assay methods for compounds like sodium benzoate and ephedrine hydrochloride.

1. NON AQUEOUS TITRATION
By Dr. Neetu Soni, SHUATS,
PRAYAGRAJ, UP

2. 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.

3. The procedure of non aqueous titration is very useful
because:
 It satisfies two different requirements, namely – suitable
titration of very weak acids or bases
 It 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.

4. An example of a reaction in which water is not a suitable solvent
is the reaction given by:
R-NH2 + H+ ⇌ R-NH3
+
which is competed with in an aqueous solvent by the reaction
given by:
H2O + H+ ⇌ H3O+
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.

5. Types of Non Aqueous
Solvents
Aprotic Solvents – these solvents are neutral in charge and are
chemically inert. They also generally have a low dielectric constant.
Examples of these types of solvents include chloroform and benzene.
Protophilic Solvents – these solvents have a basic character and tend to
react with the acids they come in contact with, leading to the formation of
solvated protons. Examples of protophilic solvents are ammonia and
pyridine.
Protogenic Solvents – these solvents have a more acidic character and
tend to have a levelling effect on the bases they come in contact with.
Examples of protogenic solvents used in non-aqueous titration are sulphuric
acid and acetic acid.
Amphiprotic Solvents – these solvents have properties which are
protophilic as well as protogenic. Examples of these types of solvents are

6. Major solvents used in non aqueous titration
(1) Glacial acetic acid
(2) Acetonitrile (CH3CN)
(3) Alcohols
(4) Dioxane
(5) DMF

7. Levelling Effect:
The acidity of the weak acids can be enhanced using basic
solvents because the basic solvent has higher affinity to take
up protons from acid. So, acetic acid behaves as a strong
acid in ammonia solution. Also the basicity of the weak bases
can be enhanced in the presence of acidic solvent. This is
called the levelling effect of the solvent.

8. NON AQUEOUS INDICATORS
The ionised form and unionised form or different resonant
form of indicators generally apply equally for nonaqueous
titration, but the colour change at the end point vary from
titration to titration, as they depend on the nature of the
titrant.
The end point may be determined either by potentiometric
titration or by colour change of the indicator.

9. 1. Crystal voilet:- • It is considered as the most common
indicators in the titration of the bases.
• It is used as 0.5% solution in glacial acetic acid, it gives
voilet colour in basic medium and yellowish green in acidic
medium.
• It is most widely use for the titration of pyridine with
prechloride acid.
2. Oracet Blue B Indicator:- It is prepared o.5% glacial acetic
acid. It gives blue colour in basic medium while pink colour
in acidic medium.

10. 3. Quinaldine Red: it is employed as indicator in the
determination of the drug substance in
dimethylformamide (DMF). It is used as 0.1% w/v
solution in ethanol. The colour change is from purple
red to pale green.
4. Thymol Blue: it is used as 0.2% w/v solution in methanol.
The colour change is from yellow to blue.

12. PREPARATION OF 0.1 N PERCHLORIC ACID
Materials Required : 8.5 ml of perchloric acid (70.0 to 72.0%) ; 1 Litre of
glacial acetic acid ; 30 ml of acetic anhydride.
Procedure : Gradually mix 8.5 ml of perchloric acid to 900 ml of glacial
acetic acid with vigorous and continuous stirring. Now add 30 ml acetic
anhydride and make up the volume to 1 litre with glacial acetic acid and allow
to stand for 24 hours before use.
The acetic anhydride reacts with the water (approx. 30%) in perchloric acid
and some traces in glacial acetic acid thereby making the resulting mixture
practically anhydrous. Thus, we have :
Titration of weak base by non aqueous titration

13. Precautions : The following precautions must be observed :
(a) Perchloric acid is usually available as a 70 to 72% mixture with water (sp. gr. 1.6). It usually undergoes a
spontaneous explosive decomposition and, therefore, it is available always in the form of a solution.
(b) Conversion of acetic anhydride to acetic acid requires 40-45 minutes for its completion. It being an exothermic
reaction, the solution must be allowed to cool to room temperature before adding glacial acetic acid to volume,
(c) Avoid adding an excess of acetic anhydride especially when primary and secondary amines are to be assayed,
because these may be converted rapidly to their corresponding acetylated non-basic products :
(d) Perchloric acid is not only a powerful oxidising agent but also a strong acid. Hence, it must be handled very
carefully.
Perchloric acid has a molecular weight of 100.46 and 1 L of 0.1 N solution shall contain 1 /10th the equivalent weight or
10.046 g. To prepare 1 L of standard perchloric acid solution, it requires 8.5 ml (sp. gr. 1.6) volume and a purity of 72%
which will calculate out as 9.792 g of HClO4.

14. STANDARDIZATION OF 0.1 N
PERCHLORIC ACID
Alkaline earth (e.g., Mg, Ca, Ba), and alkali (e.g., Na, K, Rb), salts of organic acids
behave as bases in acetic acid solution :
In usual practice, potassium hydrogen phthalate (or potassium biphthalate, KHC8H4O4) is
employed as a standardizing agent for acetous perchloric acid. The reaction may be
expressed as follows :

15. Procedure : Weigh accurately about 0.5 g of potassium hydrogen phthalate in a 100
ml conical flask. Add 25 ml of glacial acetic acid and attach a reflux condenser fitted
with a silica-gel drying tube. Warm until the salt gets dissolved completely. Cool and
titrate with 0.1 N perchloric acid by making use of either of the
following two indicators :
(a) acetous crystal violet-2 drops, end point Blue to Blue-Green (0.5% w/v)
(a) acetous oracet blue B-2 drops, end point Blue to Pink.

17. Titration of weak Acids by non aqueous titration
Preparation of 0.1 N Potassium Methoxide in Toluene-Methanol
Materials Required: Absolute methanol : 40 ml ; dry toluene : 50 ml ;
potassium metal : 4 g. Procedure:
Add into a dry flask, a mixture of methanol (40 ml) and dry toluene (50
ml) and cover it loosely. Carefully add freshly cut pieces of potassium
metal to the above mixture gradually with constant shaking. After
complete dissolution of potassium metal, add enough absolute
methanol to yield a clear solution. Toluene 50 ml is added with constant
shaking until the mixture turns hazy in appearance. The process is
repeated by the alternate addition of methanol and benzene until 1 litre
of solution is obtained, taking care to add a minimum volume of
methanol to give a visible clear solution.

18. Preparation of 0.1 N Sodiun Methoxide
It is prepared exactly in a similar manner as for 0.1 N
Potassium Methoxide, using 2.3 g of freshly-cut sodium in
place of potassium.

19. Standardization of 0.1 N Methoxide Solution
Materials Required: Dimethylformamide (DMF) : 80 ml ;
Thymol blue (0.3% in MeOH) ; benzoic acid : 0.4 g.
Procedure : Transfer 80 ml of DMF in a conical flask and
add to it 3 to 4 drops of thymolpthalein Quickly introduce
0.4 g of benzoic acid and titrate immediately with
Methoxide in toluene methanol.

20. Estimation of Sodium Benzoate
Sodium Benzoate : Formula : C7H5NaO2 Mol. Wt. 144.1 Sodium
Benzoate contains not less than 99.0 per cent and not more than
100.5 per cent of C7H5NaO2, calculated on the dried basis.
Description : A white, crystalline or granular powder or flakes;
odourless or with a faint odour; hygroscopic.
For the Estimation of Sodium Benzoate :
Assay Procedure : Weigh accurately about 0.25 g of Sodium
Benzoate, dissolve in 20 ml of anhydrous glacial acetic acid, warming
to 50º if necessary, cool. Titrate with 0.1 M perchloric acid, using 0.05
ml of 1-naphtholbenzein solution as indicator. Carry out a blank
titration. Equivalent or I.P factor : 1 ml of 0.1 M perchloric acid is
equivalent to 0.01441 g of C7H5NaO2.
.

21. Estimation of Ephedrine Hydrochloride :-
Ephedrine Hydrochloride : Formula : C10H15NO,HCl Mol. Wt. 201.7
Ephedrine Hydrochloride contains not less than 99.0 per cent and not more
than 101.0 per cent of C10H15NO,HCl calculated on the dried basis.
Description : Colourless crystals or a white, crystalline powder; odourless.
It is affected by light. For the Estimation of Ephedrine Hydrochloride :
Assay Procedure : Weigh accurately about 0.17 g of Ephedrine
Hydrochloride, dissolve in 10 ml of mercuric acetate solution, warming
gently, add 50 ml of acetone and mix. Titrate with 0.1 M perchloric acid,
using 1 ml of a saturated solution of methyl orange in acetone as indicator,
until a red colour is obtained. Carry out a blank titration. Equivalent or I.P
factor : 1 ml of 0.1 M perchloric acid is equivalent to 0.02017 g of