INDUSRTIAL
TITRATION OF
COMPOUNDS BY
NON AQUEOUS
TITRATION
PRESENTED TO: SIR ALI ABBAS
PRESENTED BY:GROUP C
Group C members
Storyset
Sana Javed Musarat Kareem Faria
Shehr Bano Umme Yarza Muqaddas Adia Masoora
Shafiq
Titration
Definition A programmed reaction meant to
determine the concentration of a
solution with a known composition.
Titration is defined as a
A solution called a titrant (one
common laboratory method
reactant) with a precisely known
of quantitative chemical
composition and concentration is
analysis that is used to
slowly added to the solution of
determine the unknown
unknown concentration (which
concentration of a known
becomes the other reactant).
reactant.
Non-aqueous titration refers to a
type of titration in which the
analyte substance is dissolved in
a solvent which does not contain
water(non- aqueous solvents.)
NON AQUEOUS TITRATION
Advantages Disadvantages
Organic acids and bases that are insoluble in water Temperature ,moisture, CO2 should be
are soluble in non-aqueous solvent. 1 1` control.
Organic acid, which is of comparable strength to
water, can be titrated easily in non-aqueous solvent 2 2 Solvents are expensive.
Volatile solvents can pollute
A non-aqueous solvent may help two or
more acids in mixture 3 3 environment
Enlargement of solubility range: Indicator must be prepare in
many substances that are not soluble 4 4 non aquous medium.
in water can be easily titrated in
water-free media (e.g. fats and oils)
Selection of solvent
Solubility of analyte Nature of the analyte Reactivity of the analyte
Classification of non Aqueous solvents
1. Aprotic Solvent
2. Protogenic Solvent
3. Protophillic Solvent
4. Amphiprotic Solvent
Aprotic Solvent
They have low dielectric
This solvent are
constant and do not react
chemically with either
inert. acid or base and therefore
do not favour ionization.
The most important examples
of aprotic solvent are
Neither acidic nor
basic (inert • Chloroform
solvent) • Benzene
• Dioxan
• Ethyl acetate
Protogenic Solvent
Protogenic solvent
are acidic in nature
and they can donate
Examples of Protogenic
the proton.
solvent are:
Glacial acetic acid
Used to dissolved formic acid
basic analyte. They propanoic acid
have high dielectric
constant and
ionised
Protophilic Solvent
Protophillic Used to dissolved
solvent are basic acidic analytes.
in nature.
Examples
1
Amines and ketone.
Possess a high
affinity for proton.
2 3 Pyridine,ethylenedi
amine, DMF
4
Amphiprotic Solvent
Amphiprotic solvent are those
solvent they work as a
both mean protogenic or
protophillic.
It means Amphiprotic solvent
are acidic and basic in
nature.
And they are accept the proton
and donate the
proton.
For examples
Alcohols and weak organic
acids
Major solvents used in non aqueous
titration
Acetonitrile
Glacial acetic acid Alcohols Dioxane DMF
(CH3CN)
Non-Aqueous Indicators
The ionized form and un-
ionized form or different
resonant form of indicators
generally apply equally for
nonaqueous titration, but the color change
at the end point vary
from titration to
titration, as they
depend on the nature
of the titrant.
Determination of End Point
Potentiometric titration Color change of the
indicator
1. Potentiometric Titration
Potentiometric method
for the detection of the
equivalence point
The end point is determined
by using indicator electrode
(glass electrode) and
reference electrode
(saturated calomel
electrode)
2. Indicator Method
Visual indicator are formed to the most
suitable for the detection of end point in
non-aqueous titration.
The important indicator used for
non-aqueous titration are follow:-
• Crystal violet
• Oracet Blue B Indicatort
• Quinaldine Red
• Thymol Blue
Crystal violet Quinaldine Red
It is considered as the most common It is employed as indicator in the
indicators in the titration of the bases. determination of the drug substance
It is used as 0.5% solution in glacial in dimethylformamide (DMF).
acetic acid, it gives violet color in basic It is used as 0.1% w/v solution in
medium and yellowish green in acidic ethanol.
medium.
The color change is from purple red
It is most widely use for the titration of to pale green
pyridine with prechloride acid.
Thymol Blue
Oracet Blue B Indicator
It is used as 0.2% w/v solution in
It is prepared o.5% glacial acetic acid. methanol.
It gives blue color in basic medium The color change is from yellow to blue.
while pink color in acidic medium. Used as an indicator for the titration of
substances acting as acids in DMF
Selection of solvent
Acetic acid: used for titration of weak
1 bases, Nitrogen containing compounds
Acetonitrile / with ACOH: Metal
2 ethanoates
Alcohols (IPA, nBA) : Soaps and salts of
3 organic acids.
DMF(dimethylformamide): Benzoic
4 acid, amides etc
Titrant for NAT
Perchloric acid in acetic acid
1.
o Amines, amine salts, amino
acids, salts of acids
Potassium Methoxide in
2.
Toluene-Methanol
Quan ammonium hydroxide in
Acetonitrilepyridine
3.
o Acids, enols, imides &
sulphonamides
Estimation of Ephedrine HCl
During non-aqueous titration of
Ephedrine HCl the chloride ion 1.
behaves as a weak proton acceptor.
In this titration, it is replaced as
acetate ion by adding Mercuric
2.
Acetate in Glacial acetic acid. A
titration is performed against
perchloric acid using crystal violet
as an indicator.
Procedure
Weigh accurately about 0.5 g, dissolve in 25 ml glacial
acetic acid and 10 ml of mercuric acetate solution.
This solution is shaken well.
Titrate against 0.1 N perchloric acid using crystal violet as
indicator.
Color change
Violet-Blue to emerald green (at end point)
A blank titration is performed and this volume
is subtracted from the volume of perchloric acid
needed by the sample.
Each ml of 0.1 N perchloric acid = 0.02017 gm
of ephedrine hydrochloride.
Estimation of Sodium Benzoate
Sodium benzoate is estimated by non-
aqueous titration where it is dissolved
in anhydrous glacial acetic acid which
enhances the strength of weak base
sodium benzoate. This solution is
titrated with 0.1 M Perchloric acid
using 1-naptholbenzein as an indicator.
Procedure
Weigh accurately 0.25 g sodium benzoate.
Dissolve in 20 ml of glacial acetic acid
Warm it to if necessary
Cool
Titrate with 0.1 M perchloric acid using 0.05 ml
of 1-naptholbenzein solution as an indicator.
Carry out blank titration.
Methlyldopa
1.
Materials Required :
Methyldopa 0.2 g ; anhydrous formic acid
: 15 ml ; glacial acetic acid : 30 ml ;
dioxane : 30 ml ; 0.1 N perchloric acid
and crystal violet solution.
Procedure
Weigh accurately about 0.2 g and dissolve in
15 ml of anhydrous formic acid, 30 ml of
glacial acetic acid and 30 ml of dioxane.
Add 0.1 ml of crystal violet solution and
titrate with 0.1 N perchloric acid.
Perform a blank determination and make any
necessary correction.
Each ml of 0.1 N perchloric acid is
equivalent to 0.02112 g of C10H13NO4.
Methacholine Chloride
Materials Required :
Methacholine chloride : 0.4 g ; Procedure :
glacial acetic acid : 50 ml ; mercuric Weigh accurately about 0.4 g,
acetate solution : 10 ml ; 0.1 N previously dried and stored in a
perchloric acid and crystal violet vacuum desiccator, and dissolve in
solution. 50 ml of glacial acetic acid, add 10
ml of mercuric acetate solution, one
drop of crystal violet solution and
titrate with 0.1 N perchloric acid to
a blue-green end point. Perform a
blank determination and make any
necessary correction. Each ml of 0.1
N perchloric acid is equivalent to
0.01957 g of C8Hl8ClNO2.
Mercuric acetate : It is essentially added to prevent the interference of the hydrochloric
acid dis-placed through the formation of the relatively un-ionized HgCl2, thereby making
a predominant shift in the equilibrium so that the titrimetric reaction is quantitative.
Blank Titration : It is usually carried out to account for the possible reaction of
atmospheric moisture with the titrant perchloric acid and also to check the titrant being
employed to bring about the blue-green end-point.
Calculations : The percentage of methacholine chloride in the sample may be calculated
by the following expression
