A Comprehensive Note from Pharm-Analysis

1. NON AQUEOUS
TITRATION

2. • L1F16PHMD0097 Muhammad Awais
• L1F16PHMD0102 Fiza Areeb
• L1F16PHMD0121 Wajdan Rasheed
• L1F16PHMD0126 Ahmad Hasan Faizi
• L1F16PHMD0129 Noor Fatima
PRESENTATION BY
GROUP 8, SECTION-B

3. Non aqueous titration is the titration
in which titration of “weak acidic or
weak basic substance” is carried out
using “non- aqueous substance” to
get end point.
INTRODUCTION

5. WEAK ACID
A weak acid is an acid that is ‘partially
dissociated’ into its ions in an aqueous
solution or water. In contrast, a strong acid
fully dissociates into its ions in water, e.g.
Hydrofluoric acid(HF)
WEAK BASE
A weak base is a base that is ‘partially
dissociated’ in an aqueous solution, e.g.
NH4OH.

6. Many substances like therapeutic agents are mostly, not
only poorly soluble, but also weakly reactive in water.
This disadvantage is overcome by Non aqueous
solvents.
Non-aqueous titration is a titration of substance which
doesn’t dissolve in an aqueous solvent and a ‘Non-
aqueous solvent’ is required for it.

7. Water behaves as both a weak acid and a
weak base; thus, in an aqueous environment,
it can compete effectively with very weak
acids and bases with regard to proton
donation and acceptance.
PRINCIPLE

8. The effect is that, the change in the titration curves for
very weak acids and very weak bases is small, because
they approach the pH limits in water of 14 and 0
respectively, thus making end-point detection more
difficult.
A general rule is that bases with pKa < 7 or acids with
pKa > 7 cannot be determined accurately in aqueous
solution.
Various organic solvents may be used to replace water
since they compete less effectively with the analyte for
proton donation or acceptance.
PRINCIPLE (CONT’D)

9. Substances which are either too weakly basic or
too weakly acidic to give sharp endpoints in
aqueous solution can often be titrated in non-
aqueous solvents.
The reactions which occur during many non-
aqueous titrations can be explained by means of
the concepts of the “Bronsted-Lowry Theory”.
According to this theory,
“An acid is a proton donor and a base
is proton acceptor.”

10. For example, Acetic acid in water is weakly
acidic where as acetic acid in ammonia is
strongly acidic, thus the acidic or basic
characters of a compound depend on the
uses of appropriate solvent.
PRINCIPLE (CONT’D):

11. NON-AQUEOUS SOLVENTS
Solvent which are used in non aqueous
titration are called non aqueous solvent.
They are following types:-
i. Aprotic Solvent
ii. Protogenic Solvent
iii. Protophillic Solvent
iv. Amphiprotic Solvent
THEORY

12. • Aprotic solvents are most important
solvent in this titration. These
solvents are chemically inert and
they work as a catalyst. These
solvents increase the rate of speed
in reaction and also decrease the
rate of speed in reaction during the
chemical process or reaction (it
depends on condition).
• The most important examples of
aprotic solvent are; Chloroform,
Benzene, Carbon tetra Chloride,
Dioxan, Ethyl acetate &Toluene
APROTIC
SOLVENTS
(INERT /
NEUTRAL)

13. • Protogenic solvents are
acidic in nature and they can
donate the proton, and
enhance the strength of
weak bases.
• Examples of Protogenic
solvents are; HCL, H2SO4.
PROTOGENIC
SOLVENTS

14. • Protophillic solvents are
basic in nature, which
possess a high affinity for
proton.
• Example are; Liquid
ammonia, aminesand
ketone.
PROTOPHILLIC
SOLVENTS

15. • Amphiprotic solvents are those
solvents, which work as a both
mean Protogenic or Protophillic.
• It means Amphiprotic solvents are
acidic and basic in nature. And
they accept the proton and
donate the proton.
• For example; Alcohols and weak
organic acids.
AMPHIPROTIC
SOLVENTS:

16. SOLVENT SELECTION
In non-aqueous titration, the solvent
selection is mainly based upon the following
parameters:
• Solubility of the sample
• Nature of the sample
• Should produce sharp end point
• Should have the high dielectric
constant
• Should be of low toxicity
• Should be easily purified
• Should be in expensive

17. The procedure is same as general titration
techniques (e.g. Acid-Base Titration,Redox Titration,
etc.)
SOLVENTS FOR NAT
- Acetic acid is used for titration of weak bases
and Nitrogen containing compounds.
- Acetonitrile/with AcOH: Metal
Ethanoates.
- Alcohols: Soaps and salts of organic acids.
- Dimethylformamide: Benzoic acidand
Amides.
PROCEDURE

18. TITRANTS FOR NAT
- Perchloric acid in acetic acid (for Amines,
Amine salts, Aminoacid, salts of acids).
- Potassium methoxide in toluene-
methanol.
- Quaternary Ammonium Hydroxide in
Acetonitrile-Pyridine (for Acids, enols,
imides &sulfonamides).

19. DETECTION OF END POINT
1. VISUAL INDICATORS are formed to the
most suitable for the detection of end point in
NAT. The important indicators used for NAT are
as follow;
i. CRYSTAL VOILET: It is used as 0.5 % solution
in glacial acetic acid. It gives violet color in
basicmedium and yellowish green in acidic
medium. It is most widely used for the
titration of pyridine with perchloric acid.
ii. QUINALDINE RED INDICATOR: It is used 0.1
% solution in methanol/ethanol. Methanol is
more stable, it gives yellow color in basic
medium and colorless in acidic medium.

20. SOME IMPORTANT
INDICATORS

21. ASSAY BY NON-AQUEOUS
TITRATION
- Acidimetry in nonaq. Titration
- Alkalimetry in non aq.Titration
ACIDMETRY IN NON-AQ. TITRATIONS:
“The term Acidimetry refers to that part of volumetric
analysis whereby an acid solution at known
concentration, along with a specific indicator, is used
to titrate a base solution and thus work out its
concentration”
is further divided into two types:
i. Titration of primary, secondary or tertiary
amines.
ii. Titration of halogen acid salts of bases.

22. ALKALIMETRY IN NON AQ. TITRATIONS
“The term Alkalimetry refers to that part of
volumetric analysis whereby a base solution at
known concentration, along with a specific
indicator, is used to titrate an acidic solution and
thus work out its concentration”
• Many weakly acidic substances may be titrated
effectively by making use of suitable non-
aqueous solvent with a sharp end point i.e.,
o 0.1N Potassium Methoxide in Toluene
Methanol
o 0.1N Sodium Methoxide or 0.1 N Lithium
Methoxide

23. FACTORS AFFECTING THE
NON-AQUEOUS TITRATIONS
• Acid-base characteristics of the non-aqueous
solvents affect the end-point in the non-aqueous
titration.
• In the titration of weak base or acids, the addition
of highly acidic or basic solvents increases the
acidity or basicity and that increases the
consumption of the titrant.
• Protolysis of the substance leads to the increase in
the end point.
• The low dielectric constant solvents are commonly
employed in the non-aqueous titrations which
produce the accurate end points.

24. PRECAUTIONS FOR THE NON-
AQUEOUS TITRATIONS
• Moisture must be avoided for non-aqueous
titrations.
• Carbon dioxide must be avoided for non-
aqueous procedures.

25. ADVANTAGES
• Organic acids and bases that are insoluble in
water are soluble in non- aqueous solvent.
• A non-aqueous solvent may help two are
more acids in mixture. The individual acid
can give separate end point in different
solvent.
• Enlargement of solubility range: Many
substances that are not soluble in water can
be easily titrated in water-free media (e.g.
fats and oils).
• Enlargement of application range:weak
bases and acids can be easily titrated.

26. • Substance compositions that cannot be
separately determined in aqueous media
can often be titrated in non-aqueous
media.
• Non-aqueous solvents are useful for the
titration of very weak acids or bases that
cannot be titrated in water.
• Non aqueous titrations are simple and
accurate.

27. • Solvents are expensive.
• Volatile solvents can polluteenvironment.
• Indicator must be prepared innon-aqueous
medium.
• Temperature corrections are necessary for
the non-aqueous solvents.
• Non-aqueous solvents are not stable
compared to aqueous solvents.
DISADVANTAGES

28. APPLICATIONS
• Percentage of purity is determined by the assays i.e.,
Sulphonylamides.
• Used in the determination of hydrophobic compounds like
Amantadine HCL Barbiturates alkaloids.
• Used in the determination of diuretics.
• Used to quantify mixtures of primary , secondary & tertiary
amines.
• For many other organic amino compounds and salts of
organic acids.
• Used in the Analysis of Certain Pharmaceutical Preparations
Like steroids, anti-tubercular drugs, adrenergic drugs etc.

29. THANK
YOU