Non Aqueous Acid

Non Aqueous Acid-Base Titration and
its importance in pharmaceutical Field
Prepared by
Asmaa Hosny Hassan

Group A1
Supervised by
Prof.Dr Hesham Salem
2016/2017
Quantitative Chemical Analysis
People are curious about the substances contained in material

with which they come in contact. Precious metals may make
them rich, medications may cure diseases and toxins and
1
poisons may make them ill or worse. Analytical chemistry is the
science which helps to satisfy such curiosity. Qualitative
Analysis tries to answer the question "What's in this stuff?" and
Quantitative Analysis tries to answer "How much?"
In 1894 the renowned chemist Wilhelm Ostwald summed up

the matter when he wrote
Non aqueous of acid base titration
Twenty-five years ago, Conant, Hall, and Werner showed that

many substances which exhibit little or no basic properties in
water behave as relatively strong bases in glacial acetic acid
and may be quantitatively determined in this solvent by
titration with a strong mineral acid ([1] ), [(2)] .2 Unfortunately,
the potentialities of this method and its distinct advantages, as
compared to many volumetric procedures carried out in
aqueous media, were not immediately realized. It is only within
the last two years that nonaqueous titrimetry has found a
considerable number of novel applications and become a
valuable analytical method of wide scope [(3)] , [(4)] . The
studies reported in this paper demonstrate that the
quantitative estimation of narcotic drugs and alkaloids of
widely different structures and degrees of basicity may also be
achieved by means of nonaqueous titration, using acetic acid as
solvent and perchloric acid as titrant.
2
All compounds except the halide acid salts were analysed by
dissolving about 0.5 milliequivalents in 80 ml. of glacial acetic
acid and titrating directly with 0.05 N perchloric acid to a blue-
green end point. A microburet calibrated to 0.01 ml. was used
for measuring the volume of acid consumed.
The halide acid salts were dissolved in 80 ml. of glacial acetic
acid, reacted with 5 ml. of 6 per cent mercuric acetate solution
and subsequently neutralized by means of perchloric acid as
indicated above. A magnetic stirrer was used to carry out the
determinations more conveniently.
Acetic acid is generally considered an amphiprotic solvent for it
can act as both a proton donor and acceptor. The dissociation
constant of its autoprotolysis which proceeds in accordance
with the equation:
2CH 3COOH === CH 3COOH 2+ + CH 3COO- was found by
Kolthoff to be equal to 2.5X10-13 at 25°C. (6).
When a base B is dissolved in acetic acid the ionization process:
B + CH 3COOH BH + + CH 3COO -
takes place to an appreciable extent and even with bases that
are considered weak in aqueous media the equilibrium of the
reaction lies far to the right. This "levelling effect" of the
solvent was first observed by Hall who showed by means of
electrochemical measurements that all bases stronger than
aniline, which is a very weak base in water (pK A=4.75), are of
3
considerable and almost equal strength in acetic acid
solution[(7)] , [(8)] . It is evident that in these reactions the
solvent displays strong protogenic or acidic properties.
Addition of perchloric acid to acetic acid is associated with the
formation of a solvated proton:
HClO 4 + CH 3COOH ==== CH 3COOH 2+ + ClO 4-
and under normal conditions this reaction tends to go to
completion [(6)] , [(9)] . Hence, in a perchloric acidacetic acid
mixture, acetic acid displays protophilic or basic properties. The
solvated ion generated is a powerful proton donor, i.e., an acid
of exceptional strength. It will readily neutralize any base that is
stronger than the solvent itself and the fundamental process
underlying nonaqueous titration of bases in glacial acetic acid
by means of perchloric acid may thus be visualized to proceed
in the following manner:
B + CH 3COOH === BH+ + CH 3COO-
CH 3COO- + CH 3COOH 2+ + ClO 4 - =
2 CH 3COOH + C10 4 -
Salts of organic bases - except sulfates and halides - are
neutralized in a similar fashion as may be shown for codeine
phosphate:
C 18H 21NO 3 H 3PO 4=== C 18H 21NO 3H+ + H 2PO 4-
H 2PO 4- + CH 3COOH 2 + = H 3PO 4 + CH 3COOH
4
Sulfates are titrated to bisulfates only because the in the
reaction
SO 4-- + H+ (acetic acid) HSO 4- the equilibrium lies far to the
right whereas in the succeeding reaction
HSO 4- + H+ (acetic acid) H 2SO 4 it lies far to the left. Bisulfates
therefore do not behave as bases in glacial acetic acid (10).
Halide ions are extremely weak bases and the reaction
X - + CH 3COOH 2 + === HX + CH 3COOH
does not go to completion, the strong mineral acid generated
during the titration causing the end point to occur long before
the equivalence point is reached.
Correct results can be obtained however by either boiling the
solution to volatilize the hydrogen halide formed and thereby
force the reaction to completion - a method analogous to the
titration of carbonates in aqueous solution - or by adding to the
system prior to titration a slight excess of mercuric acetate so
as to convert the anion to undissociated mercuric halide which
will not take part in the neutralization process [(l1)] , [(12)] .
The latter procedure is to be preferred because of the tendency
of many organic compounds to decompose on prolonged
boiling. The reaction appears to proceed in accordance with the
following scheme:
R 3N. HX + 1/2 Hg (CH 3COO) 2 =
R 3NH+ + CH 3COO- + ? HgX 2
5
CH 3COO + CH 3COOH 2 + = 2 CH 3COOH
Applications
Budeprion
Perchloric acid
Perchloric acid is a mineral acid with the formula HClO4.

Usually found as an aqueous solution, this colorless compound
is a stronger acid than sulfuric and nitric acid. It is a powerful
oxidizer when hot, but its aqueous solutions up to
approximately 70% by weight at room temperature are
generally safe, only showing strong acid features and no
oxidizing properties. Perchloric acid is useful for preparing
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perchlorate salts, especially ammonium perchlorate, an
important rocket fuel component. Perchloric acid is
dangerously corrosive and readily forms potentially explosive
mixtures.
Determination of Water Content in Perchloric acid Using Karl

Fischer Titration
Sample: Perchloric acid
Report No.: 406
Group(s): Inorganic Acids
Strong acids shift the pH of the KF reagent and must be

neutralized. This can be carried out directly in the titration cell
providing a sufficient amount of buffer is added, e.g.
HYDRANAL-Buffer Acid, imidazole or pyridine. Highly
concentrated acids, such as sulfuric or hydrochloric acids, may
undergo esterification. This leads to the formation of water
which also gets titrated. Therefore, it is necessary to neutralize
these substances in a methanol-free solvent prior to the
titration, e.g. in pyridine or in a solution of imidazole in dioxan.
In pure methanol perchloric acid cause an error on the
endpoint indication. This effect can be suppressed by using
HYDRANAL-CompoSolver E or by addition of HYDRANAL-Buffer
Acid.
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I. Coulometric Procedure (cell without diaphragm)
Procedure: The coulometric determination is less

recommended for this product. We favour a volumetric
determination.
II. Coulometric Procedure (cell with diaphragm)
Procedure: The coulometric determination is less

recommended for this product. We favour a volumetric
determination.
III. Volumetric Procedure (one-component reagents)
Titrating agent: HYDRANAL-Composite 5
Working medium: 30 ml HYDRANAL-CompoSolver E or (20 ml

HYDRANAL-Methanol dry or HYDRANAL-Methanol Rapid + 20
ml HYDRANAL-Buffer Acid)
Sample handling: The sample is added with a plastic syringe

without a needle. Weigh by difference.
Sample amount: 0.1 g
Procedure: The working medium is placed in the titration cell

and titrated to dryness with the titrant. Then the sample is
added and titrated in the same way to a stable end-point.
IV. Volumetric Procedure (two-component reagents)
8
Titrating agent: HYDRANAL-Titrant 5 or HYDRANAL-Titrant 5 E
Working medium: 30 ml HYDRANAL-Solvent or HYDRANAL-

Solvent E
Sample handling: The sample is added with a calibrated syringe

or with a plastic syringe. Weigh by difference.
Sample amount: 0.1 g
Procedure: The working medium is placed in the titration cell

and titrated to dryness with the titrant. Then the sample is
added and titrated in the same way to a stable end-point.
A direct determination of taurine in perchloric acid-

deproteinized biological samples.
A high-performance liquid chromatographic method was

developed to estimate the amount of taurine in tissue extracts
and body fluids. Shodex Ionpak C-811, an adsorption-
distribution type column, was chosen and combined with 3 mM
perchloric acid as the mobile phase. The eluted taurine was
derivatized with o-phthaladehyde-2-mercaptoethanol reagent
and measured at an absorbance of 350 nm instead of
fluorescent intensity. Using this method, it was possible to
isolate and estimate the amount of taurine from other
coexisting substances or structural analogs such as
hypotaurine, cysteamine, or cysteinesulfinic acid. For rapid
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routine assays of taurine in many biological samples, it is
advisable that the tissue extracts be pretreated with cation-
exchange resin to exclude other interfering substances
including O-phosphoserine. The linear relationship between the
concentration of taurine and absorbance achieved over the
concentration range 0.1-10.0 nmol and the recoveries obtained
were 98-101% by the internal standard method. The specificity,
reproducibility, and sensitivity of this method for taurine were
good enough to be used for biological applications. Examples of
the tissue levels of taurine in various organs of the rat, as
determined by this new method, are also presented.
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Non Aqueous Acid-Base Titration and

its importance in pharmaceutical Field

Asmaa Hosny Hassan

Prof.Dr Hesham Salem

People are curious about the substances contained in material

In 1894 the renowned chemist Wilhelm Ostwald summed up

Non aqueous of acid base titration

Twenty-five years ago, Conant, Hall, and Werner showed that

Perchloric acid is a mineral acid with the formula HClO4.

Determination of Water Content in Perchloric acid Using Karl

Sample: Perchloric acid

Report No.: 406

Group(s): Inorganic Acids

Strong acids shift the pH of the KF reagent and must be

Procedure: The coulometric determination is less

II. Coulometric Procedure (cell with diaphragm)

Procedure: The coulometric determination is less

III. Volumetric Procedure (one-component reagents)

Titrating agent: HYDRANAL-Composite 5

Working medium: 30 ml HYDRANAL-CompoSolver E or (20 ml

Sample handling: The sample is added with a plastic syringe

Sample amount: 0.1 g

Procedure: The working medium is placed in the titration cell

IV. Volumetric Procedure (two-component reagents)

Working medium: 30 ml HYDRANAL-Solvent or HYDRANAL-

Sample handling: The sample is added with a calibrated syringe

Sample amount: 0.1 g

Procedure: The working medium is placed in the titration cell

A direct determination of taurine in perchloric acid-

A high-performance liquid chromatographic method was

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