1. NON AQUEOUS
TITRATION
PRESENTED BY- MANISHA
M.SC 1ST SEMESTER
PHAMACEUTICAL CHEMISTRY

2. TITRATION
INDICATOR
TYPES OF
TITRATION
PRIMARY &
SECONDARY
STANDARD
STANDARD
-IZATION
SOLVENT
i.e. water
or organic
sol.
TITRANT &
TITRAND

3. INTRODUCTON
• Most of titrations are performed in the aqueous media,means water is used as a solvent.
• There may be difficulty if reactant is
• insoluble in water
• Reactant is reactive with water or
• The analyte is either too weak acid or base
• Last reason creates more difficulty due to amphoteric nature of water.
Suppose if analyte is weak acid (HA) in comparison to water and it is titrated with standard
base (B). Both analyte and water will compete each other to give up its proton to the
standard base.Hence ,weak acid are not titrable in aqueous media.

4. Amphoteric nature of water means it react as acids as
well as base.
• The simple solution to this problem is to replace water as solvent.
• Hence,this type of titration are designated as “Non aqueous titration”.
• For example:
1-In case of weak acid-we will take a non acidic solvent.
2-In case of weak base we wil take a non basic solvent.
(TO BLOCK THE COMPETITION)

5. Non aqueous titrations have the following advantage
Organic acids and bases that are insoluble in water are soluble in non aqueous solvent.
A non aqueous solvent may help two or more acids in mixture.the individual acid can give
a separate end point in different solvent.
Enlargement of solubility range many substance that are not soluble in water can be easily
titrated in water free media.
Enlargement of application range,weak bases and acids can be easily titrated.
Non aqueous solvents are useful for the titration of weak acids and weak bases that can
not be titrated in water.
Non aqueous titration are simple and accurate.

6. Disadvantage
Temperature,moisture and
CO2 should be control.
Solvents are expensive.
Volatile solvent can pollute
environment.
Indicator must be prepare
in non aqueous medium.

7. Basic concept regarding
acid and base
• There are three well known theories that
may be used to explain neutralization
reactions in any solvent system.
Arrhenius concept:acid is a substance that
dissociates in water to give hydrogen ion and
base is a substance that dissociates in water
to give hydroxide ion.NOT APPLICABLE IN NON
AQUEOUS
Lewis theory:According to this theory,a base is
an electron donor and a acid is an electron
acceptor.

8. Bronsted theory
• According to this theory an acid is a
substance having tendency to lose
a proton and a base is substance
having the tendency to accept a
proton.every acid on dissociation
gives the proton and conjugate
base and similarly base accept the
proton and gives the conjugate
acid.

9. Acids and
bases
• An acid can only exhibit its properties in presence
of a base and base can only function in the
presence of acid.
• The relative strength of an acid and base are
measured by their tendency to give up or take
proton respectively.
• The strength of acid and base depends on solvent
in which they are dissolved.

10. Levelling
effect:
• The strength of acids can not be compared if
they are dissolved in basic solvent.it means
their acidic strength are levelled.this is called
levelling effect.
It means,the strength of an acid depend not
only on its own inherent property but also on
the ability of the solvent(in which it is
dissolved)to take up the proton.e.g.Acetic acid
behaves as strong acid in ammonia
solution.Also the basicity of the weak base can
be enhanced in the presence of acidic solvent.

11. Selection of solvent
1-solubility of analyte
2-nature of the analyte
3-reactivity of the analyte

12. Classification of non aqueous solvents
They are following types:
1-Aprotic solvent
2-Protogenic solvent
3-Protophilic solvent
4-Amphiprotic solvent

13. Aprotic solvent
Aprotic solvent are most imp. Solvent in this
titration.
• The solvent are chemically inert.
• Neither acidic nor basic(inert solvent)
• They have low dielectric constant and do not react either
acid or base and therefore do not favour ionization.
• The most imp. Examples of aprotic solvents are
• Chloroform
• Benzene
• Dioxan
• Ethyl acetate

14. PROTOGENIC SOLVENT
Prorotogenic
solvent are acidic in
nature and they can
donate the proton.
Used to dissolved
basic analyte.
They have high
dielectric constant
and ionsed.
Examples of
protogenic solvent
are:
Glacial acetic acid Formic acid Propanoic acid

15. Protophilic
solvent
Protophilic solvent are basic in nature.
Which possess a high affinity for proton.
Used to dissolved acidic analytes.
Example:amines and ketones
• Pyridine
• Ethylenediamine
• DMF

16. Amphiprotic
solvent
• Amphiprotic solvent are those solvent they
work as a both mean protogenic or
protophilic .
• It means amphiprotic solvent are acidic
and basic in nature.
• And they are accept the proton and
donate the proton.
• For examples:
• Alcohols
• Weak organic acids

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

18. Non aqueous
indicators
• The ionized form and unionized form or
different resonant form of indicators
generally apply equally for non-aqueous
titration,but the color 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 color
change of the indicator.

19. Determining End
Point
• Potentiometric titration
• Indicator method
POTENTIOMETRIC METHOD
Potentiometric method for detection of
the equivalence point
The end point is determined by using
indicator electrode(glass electrode) and
reference electrode(saturated calomel
electrode)

20. Indicator method
Visual indicator are formed to the
most suitable for the detection of
end point in non aqueous titration.
• The imp. Indicator used in non aqueous
titration are follow:
1—crystal violet:
• It is considered as most common indicator
in titration of the bases.
• It is used as 0.5%solution in glacial acetic
acid,it gives violet colour in basic medium
and yellowish green in acidic medium.
• It is most widely use for the titration of
pyridine with perchloride acid.

21. 2—oracet blue B
indicator:
it is prepapred 0.5% glacial acetic acid.it gives
blue color in basic medium while pink color in
acidic medium.
3—quinaldine red: it is employed as indicator
in the determination of drug substance in
dimethylformamide(DMF).it is used as
0.1%w/v solution in ethanol.the color change
is from purple red to pale green.
4—Thymol blue: it is used as 0.2% w/v
solution in methanol.the color change is from
yellow to blue as an indicator for the titration
of substance acting as acids in DMF.

22. Selection of solvent
for NAT
ACETIC ACID: used for the titration
of weak bases,nitrogen containing
compounds.
Acetonitrile /with ACOH:metal
ethanoates
Alcohols(IPA,nBA):soaps and salts of
organic acids
DMF:benzoic acid,amides etc.

23. Titrant for NAT
Perchloric acid in acetic
acid
Potasium methoxide in
toluene –methanol
Quan ammonium
hydroxide in
acetonitrilepyridine

24. Assay by non
aqueous titration
• Acidimetry in non aqueous titration:
It can be further divided into two
types,namely;
1-titration of primary secondary and tertiary
amines.
2-titration of halogen acid salts of bases.
• Alkalimetry in non aqueous titration:
Titiration of acidic substances

25. Non aqueous
titration of weak
bases
• Solvent used in the titration of weak bases:
1-neutral solvents:
ex:alcohol,chloroform,benzene,chlorobenzen
e
2-acidic solvents:
Ex:formic acid,glacial acetic acid,propionic
acids
• Titrant used in the titration of weak bases:
Ex:perchloric acid
• Indicators used in the titration of weak
bases
Ex:oracet blue,crystal violet,1-naptholbenzein

26. Non aqueous
titration of weak
acids
1) Solvents used in the titration of weak
acids:
Ex:ethylenediamine,n-butylamine,morpholine
2)Titrant used in the titration of weak acids:
Ex:sod.methoxide,lithium methoxide,pot.
Methoxide,tetrabutyl ammonium hydroxide
etc.

27. REFERANCES
• Anees A Siddique,Seemi Siddique (2014) , pharmaceutical analysis ,
vol.1 , 3rd ed. , page no. (44-54) , CBS Publishers and distributors
PVT. LTD. New Delhi
• P. C. Kamboj(2012) , pharmaceutical analysis , vol.1st , 2nd ed. , page
no.(308-321) , Vallabh Publications
ONLINE RESOURCES
• www.Wikipedia.com
• www.researchgate.net