Types Of Solvents
1. Aprotic solvents
2. Protophilic solvents
3. Protogenic solvents
4. Amphiprotic solvents
Non Aqueous Titration Of Weak Acids
Non Aqueous Titration Of Weak Bases
3. Non-aqueous titrations
Titrations involving any non-aqueous solvent instead of water are known
as non-aqueous titrations.
Reasons for Non-aqueous titrations
The reactant is insoluble in water.
The reactant is reactive with water (i.e. undergoes chemical
decomposition in water)
The reactant is too weak acid or weak base (water due to its
amphiprotic nature will compete with the sample)
4. Non aqueous titration are those in which titration of weakly acidic or basic
substances are carried out using non aqueous solvents so as to get sharp end
Moisture and carbon dioxide should be avoided using non aqueous procedures
(Moisture should be held to less than 0.05%.)
Standardization &titration should be carried out as far as possible at the same
In non aqueous solvents the acidity decreases in the following order
5. Water should not be present even in minute amounts because
If we are doing titration of weak acid, water will act as strong acid
as compared to sample and donates protons to base. Thus there is
interference in reaction of weak acid with base.
If we are doing titration of weak base, water will act as strong base
as compared to sample and accepts protons from acid. Thus there
is interference in reaction of weak base with acid.
6. Types of Non-aqueous solvents
The solvents are divided into 4 groups
7. Protogenic solvents
These are acidic in nature and donate protons.
They have high dielectric constant and ionised because of their
strength and ability to donate protons.
They enhance basicity of weak bases.
Ex:- Sulphuric acid, Formic acid, Glacial Acetic acid, Propionoic
acid, Acetic anhydride etc.
Basic in character and enhance acidity of weak acids.
They accept protons from acids to form solvated proton
HB + Sol. ⇌ Solvated H+ + B-
Acid + Basic solvent ⇌ Solvated proton + Conjugate base of acid
Ex:-Acetone, ether, pyridine, liquid ammonia, DMF
8. Aprotic solvents (Inert solvents)
Aprotic solvents are neutral and chemically inert.
Have low dielectric constant, do not react with either acids or bases
and therefore do not favor ionization.
The picric acid gives a colorless solution in benzene or toluene which
becomes yellow on adding aniline shows that picric acid is not
dissociated in benzene or toluene solution.
This type of solvents neither accept nor donate protons
Ex:-Benzene, dioxan, chloroform, ethyl acetate, carbon tetra chloride.
9. Amphiprotic solvents
Have both protophillic and protogenic properties.
Can accept as well as donate protons.
Ex:-water, alcohols, acetic acid
CH3COOH ⇌ H+ + CH3COO-
Here the acetic acid is functioning as an acid.
If a very strong acid such as perchloric acid is dissolved in
acetic acid, the latter can function as a base and combine with
protons donated by the perchloric acid to form protonated acetic
acid., an onium ion”
HClO4 ⇌ H+ + ClO4
CH3COOH + H+ ⇌ CH3COOH2
+ (onium ion)
Since the CH3COOH2
+ ion readily donates its proton to a base, a
solution of perchloric acid in glacial acetic acid functions as a
strongly acidic solution.
10. When a weak base, such as pyridine is dissolved in acetic
acid, equivalent amount of acetate ions are produced which
have more tendency to accept protons.
Therefore, a solution of a weak base in acetic acid can be
titrated with perchloric acid in acetic acid to obtain a sharp
HClO4 + CH3COOH ⇌ CH3COOH2
+ + ClO4
C5H5N + CH3COOH ⇌ C5H5NH+ + CH3COO-
11. Selection of solvent
The solvent selected should be soluble to both the drug sample
It should be selected based on the nature of drug i.e. whether it
is weak acid or weak base. For example, if sample is weak
acid, then basic solvents like DMF, pyridine is used or vice-
The solvent selected should not react with the drug sample.
The solvent should be readily available, of low toxicity,
12. The most commonly employed non-aqueous solvents are
• Glacial Acetic acid (Glacial ethanoic acid): used for titration of
weak bases, Nitrogen containing compounds.
• Acetonitrile (generally used along with chloroform and acetic
acid): Used in titration of metal ethanoates with perchloric acid.
• Alchohols (Methanol/Ethanol/Butanol/Glycols): For soaps & salts
of organic acid
• Dioxane (Can be used as replacement of glacial acetic acid)
• DMF (Dimethyl Formamide): Used for titration of amides and
13. 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.
14. DETERMINATION OF END POINT
Potentiometric titration :
The end point is determined by using indictor electrode (glass
electrode) and reference electrode (saturated calomel electrode).
Visual indicator are considered as most suitable for the
detection of end point in non-aqueous titration.
15. The important indicator used for non-aqueous titration are follows:-
Crystal violet (0.5% w/v solution in GAC)
It is considered as most common indicator in titration of 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 perchloric acid.
16. Thymol Blue (0.2% w/v solution in methanol)
The colour change is from yellow to blue.
Used as an indicator for the titration of substances acting as acids in
Quinaldine Red (0.1% w/v solution in ethanol)
It is also employed as indicator in determination of drug substance in
The colour change is from purple red to pale green.
17. Oracet Blue B Indicator (0.5%w/v solution in glacial acetic acid)
It gives blue color in basic medium while pink color in acidic medium.
Methyl Red Indicator (0.2%w/v solution in dioxane)
It changes yellow to red color
18. Titrants for Non-Aqueous Titration
Perchloric acid in acetic acid
Amines, amine salts, amino acids, salts of acids
Potassium Methoxide or Sodium Methoxide in Toluene-
19. Non Aqueous Titration of weak Bases
Generally 0.1-0.05N solution of perchloric acid in glacial
acetic acid or dioxane.
Preparation of titrant (0.1N HClO4)
Dissolve 8.5ml of 70-72% perchloric acid with stirring in a
mixture of 500 ml GAC and 25 ml acetic anhydride and then
make up the volume to IL with GAC.
Keep the solution for at least 24 hours and then check the
moisture content. It should be between 0.02-0.05% otherwise
it should be adjusted with acetic anhydride as acetic anhydride
will neutralize the trace amount of water present in titrant
which otherwise would interfere with end point
20. Standardization of prepared 0.1N solution
It is done by using potassium hydrogen phthalate as primary standard and end point is
determined either potentiometrically or by using 0.5% crystal violet in GAC as indicator
which will change the color from violet to turqoise (bluish green color at end point).
Accurately 0.7g of potassium hydrogen phthalate is dissolved in 50ml of glacial acetic
acid. To which few drops of crystal violet indicator is added and then the solution is
titrated with prepared perchloric acid solution.
Perform blank determination using only 50 ml glacial acetic acid with indicator and
without sample and observe the perchloric acid used for neutralization.
Subtract this amount from volume observed for perchloric acid with sample.
Each ml of 0.1N HClO4 acid is equivalent to 0.02042g of potassium hydrogen phthalate.
Normality of perchloric acid = Wt of potassium hydrogen phthalate taken/ Vol of
perchloric acid x 0.02042
Erlenmeyer flask with glass stopper is used as titration vessel.
(An Erlenmeyer flask, also known as a conical flask made up of
borosilicate glass, is a widely used type of laboratory
flask which features a flat bottom, a conical body, and a
cylindrical neck. It is named after the German chemist...
Burette with teflon stop cork is used for carrying out titration
Neutral solvents :
Ex: Alcohol, Chloroform, Benzene, Chlorobenzene
Ex:-Formic acid, glacial acetic acid, propionic acid
Ex:- Oracat blue B (0.5% w/v in GAC)
Crystal violet (0.5% w/v in GAC)
Methyl red, methyl orange (0.1% in anhydrous methanol)
(For potentiometric determination of end point)
Combination of saturated calomel (mercury electrode) and
glass indicator electrodes are used.
Aq. Saturated KCl solution in calomel electrode can be
replaced with saturated solution of KCl in GAC or
Examples of Titrations of Weak Bases
Titration of Ephedrine alkaloid in Glacial Acetic Acid by
acetous perchloric acid.
Titration of Ephedrine alkaloid in Dioxane by acetous
26. Non Aqueous titration of weak acids
Many weakly acidic substances (alcohol or aprotic solvent)
can be titrated in an appropiate non aqueous solvents with
a sharp end point .
Ex:- acidic halides, acids, amino acids, enols (barbiturates,
xanthines), phenols, pyroles, sulphonamides etc,.
1) Solvents used in the titration of weak acids:
2) Titrant used in the titration of weak acids:
Ex:-sodium methoxide, lithium methoxide,
potasium methoxide ,tetrabutyl ammonium hydroxide etc.
3) Indicators used in the titration of weak acids
Ex:-azo violet.thymol blue,thymolphthalein.,O-
27. Methoxides of alkali metals
Add 2g Na, 0.6g Li in mixture of 40ml ethanol + 50ml of
dry benzene in Erlenmeyer flask
Add small amount of methanol to produce color solution
Add benzene slowly to prepare cloudy solution.
Then again add methanol followed by benzene until 1L of
solution is prepared.
Standardize it using benzoic acid in DMF as primary
indicator and 0.5% thymol blue in anhydrous methanol