Nonaqueous Titration

Nonaqueous titration
From Wikipedia, the free encyclopedia

Nonaqueous titration is the titration of substances dissolved in solvents other than

water. It is the most common titrimetric procedure used in pharmacopoeial assays and
serves a double purpose: it is suitable for the titration of very weak acids and very
weak bases, and it provides a solvent in which organic compounds are soluble.

The most commonly used procedure is the titration of organic bases with perchloric
acid in anhydrous acetic acid. These assays sometimes take some perfecting in terms
of being able to judge the endpoint precisely.

For obvious reasons Karl Fischer titration for water content is nonaqueous, usually
done in methanol or sometimes in ethanol.

 1 Theory
o 1.1 Acid-base reactions
o 1.2 Organic solvents
 2 Nonaqueous solvents used
 3 Titration of halogen acid salts of bases
 4 Visual indicators
 5 Potentiometric titration

Theory
Acid-base reactions

The theory is that 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, as shown below:

H2O + H+ ⇌ H3O+
Competes with RNH2 + H+ ⇌ RNH3+

or

H2O + B ⇌ OH− + BH+

Competes with ROH + B ⇌ RO− + BH+

The effect of this is that the inflection in the titration curves for very weak acids and
very weak bases is small, because they approach the pH limits in water of 14 or 0
respectively, thus making endpoint detection relatively more difficult.

A general rule is that bases with pKa < 7 or acids with pKa > 7 cannot be determined
accurately in aqueous solution.

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Nonaqueous Titration

Substances which are either too weakly basic or too weakly acidic to give sharp
endpoints in aqueous solution can often be titrated in nonaqueous solvents. The
reactions which occur during many nonaqueous titrations can be explained by means
of the concepts of the Brønsted-Lowry theory. According to this theory an acid is a
proton donor, i.e. a substance which tends to dissociate to yield a proton, and a base is
proton acceptor, i.e. a substance which tends to combine with a proton. When an acid
HB dissociates it yields a proton together with the conjugate base B of the acid:

HB H+ B−
⇌ +
acid proton base

Alternatively, the base B will combine with a proton to yield the conjugate acid HB of
the base B, for every base has its conjugate acid and, every acid has its conjugate
base.

It follows from these definitions that an acid may be either:

 an electrically neutral molecule, e.g. HCl, or

 a positively charged cation, e.g. C6H5NH3+, or
 a negatively charged anion, e.g. HSO4−.

A base may be either:

 an electrically neutral molecule, e.g. C6H5NH2, or

 an anion, e.g. Cl−.

Substances which are potentially acidic can function as acids only in the presence of a
base to which they can donate a proton. Conversely basic properties do not become
apparent unless an acid also is present.

Organic solvents

Various organic solvents may be used to replace water since they compete less
effectively with the analyte for proton donation or acceptance.

Nonaqueous solvents used

Aprotic solvents are neutral, chemically inert substances such as benzene and
chloroform. They have a low dielectric constant, do not react with either acids or
bases and therefore do not favor ionization. The fact that picric acid gives a colorless
solution in benzene which becomes yellow on adding aniline shows that picric acid is
not dissociated in benzene solution and also that in the presence of the base aniline it
functions as an acid, the development of yellow color being due to formation of the
picrate ion.

Since dissociation is not an essential preliminary to neutralization, aprotic solvents are

often added to 'ionizing' solvents to depress solvolysis (which is comparable to
hydrolysis) of the neutralization product and so sharpen the endpoint.

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Nonaqueous Titration

Protophilic solvents are basic in character and react with acids to form solvated
protons.

HB + Sol. ⇌ Sol.H+ + B−
Acid + Basic solvent ⇌ Solvated proton + Conjugate base of acid

A weakly basic solvent has less tendency than a strongly basic one to accept a proton.
Similarly a weak acid has less tendency to donate protons than a strong acid. As a
result, a strong acid such as perchloric acid exhibits more strongly acidic properties
than a weak acid such as acetic acid when dissolved in a weakly basic solvent. On the
other hand, all acids tend to become indistinguishable in strength when dissolved in
strongly basic solvents owing to the greater affinity of strong bases for protons. This
is called the leveling effect. Strong bases are leveling solvents for acids, weak bases
are differentiating solvents for acids.

Protogenic solvents are acidic substances, e.g. sulfuric acid. They exert a leveling
effect on bases.

Amphiprotic solvents have both protophilic and protogenic properties. Examples are
acetic acid and the alcohols. They are dissociated to a slight extent. The dissociation
of acetic acid, which is frequently used as a solvent for titration of basic substances, is
shown in the equation below:

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.

When a weak base, such as pyridine, is dissolved in acetic acid, the acetic acid exerts
its levelling effect and enhances the basic properties of the pyridine. It is possible,
therefore, to titrate a solution of a weak base in acetic acid with perchloric acid in
acetic acid, and obtain a sharp endpoint when attempts to carry out the titration in
aqueous solution are unsuccessful.

HClO4 + CH3COOH ⇌ CH3COOH2+ + ClO4−

C5H5N + CH3COOH ⇌ C5H5NH+ + CH3COO−
CH3COOH2+ + CH3COO− ⇌ 2CH3COOH
Adding HClO4 + C5H5N ⇌ C5H5NH+ + ClO4−

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Nonaqueous Titration

Titration of halogen acid salts of bases

The halide ions - chloride, bromide and iodide - are too weakly basic to react
quantitatively with acetous perchloric acid. Addition of mercuric acetate (which is
undissociated in acetic acid solution) to a halide salt replaces the halide ion by an
equivalent quantity of acetate ion, which is a strong base in acetic acid.

2R.NH2.HCl ⇌ 2RNH3+ + 2Cl−

(CH3COO)2Hg(undissociated) + 2Cl− → HgCl2 (undissociated) + 2CH3COO−
2CH3COOH2+ + 2CH3COO− ⇌ 4CH3COOH

Visual indicators
The following indicators are in common use:

Color
Indicator Color change Color change
change
basic neutral acidic
Crystal violet (0.5 per cent in glacial yellowish-
violet blue-green
acetic acid) green
α-Naphtholbenzein (0.2 per cent in blue or blue-
orange dark-green
glacial acetic acid) green
Oracet Blue B (0.5 per cent in glacial
blue purple pink
acetic acid)
Quinaldine Red (0.1 per cent in almost
magenta
methanol) colorless

Potentiometric titration
The end point of most titrations is detected by the use of visual indicator but the
method can be inaccurate in very dilute or colored solutions. However under the same
conditions, a potentiometric method for the detection of the equivalence point can
yield accurate results without difficulty. The electrical apparatus required consists of a
potentiometer or pH meter with a suitable indicator and reference electrode. The other
apparatus consists of a burette, beaker and stirrer.

The actual potential of the reference electrode need not be known accurately for most
purposes and usually any electrode may be used provided its potential remains
constant throughout the titration. The indicator electrode must be suitable for the
particular type of titration (i.e. a glass electrode for acid-base reactions and a platinum
electrode for redox titrations), and should reach equilibrium rapidly.

The electrodes are immersed in the solution to be titrated and the potential difference
between the electrodes is measured. Measured volumes of titrant are added, with
thorough (magnetic) stirring, and the corresponding values of emf (electromotive
force) or pH recorded. Small increments in volume should be added near the
equivalence point which is found graphically by noting the burette reading

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Nonaqueous Titration

corresponding to the maximum change of emf or pH per unit change of volume.

When the slope of the curve is more gradual it is not always easy to locate the
equivalent point by this method. However, if small increments (0.1 cm³ or less) of
titrant are added near the end point of the titration and a curve of change of emf or pH
per unit volume against volume of titrant is plotted, a differential curve is obtained in
which the equivalence point is indicated by a peak.