This document discusses non-aqueous titration, including the types of solvents used, titration of weak bases with perchloric acid, preparation of 0.1N perchloric acid solution, standardization, advantages and disadvantages, precautions, and applications. Non-aqueous titration allows for the titration of organic acids and bases that are insoluble in water by using solvents like acetic acid. Perchloric acid is used as the titrant for weak bases, forming onium ions that more readily donate protons. Proper solvent selection and indicators allow selective titration of acid or base functional groups.

1. NON-AQUEOUS TITRATION
**PRESENTED BY**
SRIDEBESH GHORUI
B.PHARM
GURU NANAK INSTITUTE OF PHARMACEUTICAL SCIENCE AND TECHNOLOGY

2. CONTENTS
1) INTRODUCTION OF NON-AQUEOUS TITRATION
2) TYPES OF SOLVENTS IN NON AQUEOUS TITRATION
3) NON-AQUEOUS TITRATION OF WEAK BASES WITH
PERCHLORIC ACID
4) PREPARATION OF 0.1(N) PERCHLORIC ACID
5) STANDARDISATION OF 0.1(N) PERCHLORIC ACID
6) ADVANTAGES & DISADVANTAGES
7) PRECAUTIONS & APPLICATIONS
8) CONCLUSION
9) REFERENCE
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3. INTRODUCTION OF NON-AQUEOUS TITRATION
› Non-aqueous titrations are those in which the titration of
weakly basic or acidic substances are carried out using non-
aqueous solvent so as to get sharp end point.
› The most commonly used procedure is the titration of organic
base
› Water behaves as both a weak acid and weak base; thus in
aqueous environment, it can compete effectively with very
weak acids and bases with regard to proton donation and
acceptance.
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4. TYPES OF SOLVENTS IN NON AQUEOUS TITRATION
› Solvents are classified according to their properties as follows:
› Aprotic Solvents: are neutral, chemically inert substances
examples- Chloroform, benzene.
› Protogenic Solvents: are acidic substances examples-sulphuric
acid, hydrochloric acid, nitric acid.
› Protophilic Solvents: are basic in character examples-Sodium
hydroxide
› Amphiprotic Solvents: have both Protophilic and Protogenic
properties examples- acetic acid, alcohol.
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5. NON-AQUEOUS TITRATION OF WEAK BASES WITH
PERCHLORIC ACID
When a strong acid (Perchloric acid) is added to acetic acid,
formation of onium ions takes place, which has more tendency to
donate protons.
HClO4 [H]+ + ClO4-
CH3COOH + [H]+ CH3COOH2+
(ONIUM ION)
When weak bases like pyridine are dissolved in acetic acid then
amount of acetate ions are produced which has more tendency to
accept protons.
C5H5N+ CH3COOH C5H5NH+ + CH3COO-
(ACETATE ION)
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6. PREPARATION OF 0.1(N) PERCHLORIC ACID
› Materials required: 8.5ml of perchloric acid(70-72%); 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 of 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:
› H2O+(CH3CO)2O 2CH3COOH
Water+ Acetic anhydride Acetic acid
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7. STANDARDISATION OF 0.1(N) PERCHLORIC ACID
› Weigh accurately about 0.5g of potassium hydrogen phthalate
in a 100ml conical flask.
› Add 25ml of glacial acetic acid into the conical flask. The salt is
warmed to dissolve.
› When the salt get dissolved completely. Cool and titrate with
0.1(N) perchloric acid solution using 2 drops of 5% w/v crystal
violet indicator.
› The colour changes from blue to blue green.
› 0.020414 gm of potassium hydrogen phthalate = 1ml of 0.1N
HClO4
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8. ADVANTAGES & DISADVANTAGES
› ADVANTAGES:
 Organic acids and bases
which are insoluble in
water, are soluble in non-
aqueous solvent.
 Non- aqueous titrations
are simple and accurate.
 By the proper choice of
solvents and indicator, the
biological ingredients of
substance whether acids
or bases can be selectively
titrated.
› DISADVANTAGES:
 Solvents are expensive.
 For some solvents the
evaporation rate of the solvent
is rapid ,so the concentration of
standards may be difficult to
maintain.
 Indicator must be prepared in
non-aqueous medium.
 Temperature, moisture, carbon
dioxide should be controlled
because non-aqueous solvents
have high thermal coefficient.
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9. PRECAUTIONS & APPLICATIONS
› Precautions:
› Have to store in sodium free
glass.
› Have to protect it from
atmospheric carbon dioxide.
› Perchloric acid is not only a
powerful oxidising agent but
also a strong acid. Hence it
must be handled carefully.
› In Non- aqueous titrations
water should be avoid through
the hole titration process.
› Applications:
› Non-aqueous titration have
been used to quantify the
mixtures of primary,
secondary and tertiary
amines.
› It is used for the titration of
halogen acid salts of weak
bases.
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10. CONCLUSION
› This method is use to assay the following drug.
Weak organic base- Metronidazole
Halogen acid salt of base- Chlorpromazine HCl
› With proper precautions, this method of analysis can give
accurate assay of the drugs.
› Proper environment and safety is needed.
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11. REFERENCES
A.H. BECKETT AND J.B. STENLAKE “PRACTICAL
PHARMACEUTICAL CHEMISTRY” , ‘VOLUME I’ 4TH EDITION ,
2005, CHAPTER 6, PAGE NO.-165-175
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12. ***Thank you***
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