Non-Aqueous Acid-Base
Titration
Non-aqueous acid-base titration is the titrimetric method
in which the neutralization reaction between acid and
base is conducted in purely non-aqueous medium.
Reasons for performing non-aqueous
acid-base titration
Non-aqueous titration was introduced to eliminate 3 basic problems related
to aqueous acid-base titration.
1.
Interaction of water with the titrant: Water behaves as both weak
acid and weak base. If the drug is very weakly acidic (weaker acid than
water) or very weakly basic (weaker base than water), then water will
compete with the drug for the titrant.
H 2O + B
OH-
+
BH+
H2O + H+
competes with
competes with
ROH + B
acid
RO- + BH+
H3O+
RNH2 + H+
RNH3+
Base
Hence, the end-point may not be detected (the inflection in the
titration curve is small) or may give wrong result.
Reasons for performing non-aqueous
acid-base titration
2.
Poor solubility of the drug in water: Most of the weak acids and weak
bases are non-polar and organic. Thus they tend to be less soluble or
insoluble in water. So aqueous titration becomes impossible.
3.
Water sensitivity: There are many drugs which are sensitive to water
and therefore should be assayed via non-aqueous titration (e.g.
)
Acidity and basicity
An acid can only donate its proton in presence of a base. So an acid can
show its acidity only in the presence of a base and vice versa.
Now when a weak base is added to water then, only a fraction of the
base accepts proton. This is because the base has weak proton accepting
capacity and water has weak donating capacity. So, the base shows weak
basicity in water. Now, suppose the base is dissolved in acetic acid (a weak
acid). The solvent has greater tendency to donate proton than water. So the
base can more easily accept proton. Thus the basicity of the base is higher
in acetic acid.
Acidity and basicity
Thus a sharper end point can be achieved when acetic acid is used as
solvent rather than water.
Generally, bases with pKa<7 and acids with pKa>7 can’t be accurately
titrated in aqueous media and non-aqueous titration becomes necessary.
Solvents used in non-aqueous titration
According to the acid-base character, non-aqueous solvents are categorized
into four groups –
Protophillic solvents:
1.
They are basic in nature – possess high affinity for protons.
2.
When weak acid is added to a strongly protophillic solvent, the weak
acid act as a strong acid. Thus they are used for titration of weak acids so
that they would act as strong acids.
e.g. ethers (and dioxane), ketones (e.g. acetone), amines (including liquid
ammonia), pyridine, acetic anhydride etc.
Solvents used in non-aqueous titration
Protogenic solvents:
1.
They are acidic in nature
2.
Donate protons.
3.
When a weak base is added to a strongly protogenic solvent, the weak
base act as strong base. Thus they are utilized for the titration of weak
bases.
All acids can act as protogenic solvent. e.g. sulfuric acid, hydrochloric acid.
Solvents used in non-aqueous titration
Amphiprotic solvents:
1.
They can donate or accept proton.
2.
They are both acidic and basic in nature.
3.
They are all capable of slight dissociation.
4.
They can produce levelling effect (enhance acidity or basicity) on both
weak acids and weak bases.
e.g. acetic acid, alcohols and water itself.
Solvents used in non-aqueous titration
Aprotic solvents:
1.
They neither donate nor accept proton.
2.
They are neutral, chemically inert substances.
3.
They have low dielectric constant.
4.
They do not participate in the neutralization reaction, rather act as
carriers. Thus they are useful to study reactions free from solvent effects.
5.
They are non-dissociating.
e.g. benzene, chloroform, hydrocarbons.
Acidimetry
Acidimetry is the determination of acidic substance by titrating with a
standard base solution (this definition was taken from Pharmaceutical
chemistry – Leslie G. Chatten vol. 1 and also sources from internet, other
books define acidimetry as the determination of basic substances with a
standard acid solution).
Exemplary, determination of aspirin with sodium hydroxide,
determination of phenytoin with sodium methoxide etc.
Principle of Acidimetry
Solvents: Commonly used solvents are –
1.
Strong protophillic (basic) solvents: e.g. Ethylenediamine, n-butylamine
etc. These are suitable for very weak acids.
2.
Weak protophillic (basic) solvents: e.g. Dimethylformamide (DMF),
pyridine etc. These are suitable for medium strength acidic substance.
3.
Relatively neutral solvents: Suitable for strongly acidic compounds.
Examples – acetone, acetonitrile, ,methylethyl ketone.
All solvents commonly used are non-acidic. Basic solvents e.g. n-butylamine
can be used for enhancing the acidic character. But since those solvents exert a
leveling effect on acids, these solvents are not suitable for titration of mixtures.
Principle of Acidimetry
Titrants:
Methoxides of alkali metals e.g. Na-methoxide, Li-methoxide, K-methoxide etc.
are most widely used as titrants in non-aqueous acidimetry. Among them Na-
oMe is probably most used. Potassium methoxide is not used anymore due to
the formation of gelatinous reaction product (sodium methoxide can also form
gels).
Other than that, terbutyl ammonium hydroxide, KOH in methanol etc. are
also used.
Apparatus:
Three-necked flask. This flask contains an inlet and a outlet for nitrogen
atmosphere and on opening for the burette tip.