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Deokate U. A.
Copyright © by U. A. Deokate, all
rights reserved.
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Points to be covered
• Types of solvents,
• End point detection,
• Application in assay of Sodium acetate,
• Sodium benzoate,
• Norfloxacin tablet
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Introduction
• 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.
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Protogenic solvents
• Protogenic solvents are acidic substances, e.g.
sulfuric acid. They exert a leveling effect on bases.
• Anhydrous acids such as hydrogen fluoride and
sulphuric acid fall in this category, because of their
strength and ability to donate protons, they enhance
the strength of weak bases.
• Ex:- sulphuric acid , formic acid, propanoic acid
,acetic anhydride etc.
• They have high dielectric constant and ionised
because of their strength and ability to donate
protons.
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Protophilic Solvents :
Deokate U.A. 11/1/2018
Amphiprotic solvents
Deokate U.A. 11/1/2018
Other solvent
• Formic acid: is only used for the titratin of
weakest base eg caffeine or urea
• Trifluoroacetic acid: suitable as solvent for
weakest base where acetic anhydride cannot be
used because of acetylation. But it is expensive
solvent.
• Amphipotic basic solvent: eg Ethylendiamine,
Butylamine, Benzylamine
• Aprotic basic solvent: Pyridine,
Dimethylformamide, Dimethylsulphoxide,
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• Acidic titrants:
▫ Perchloric acid
▫ p- Toluenesulfonic acid,
▫ 2,4-Dinitrobenzenesulfonic acid
• Basic titrants
▫ Tetrabutylammonium hydroxide
▫ Sodium acetate
▫ Potassium methoxide
▫ Sodium aminoethoxide
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Precautions
• Perchloric acid is usually available as a 70 to 72% mixture with
water .It usually undergoes a spontaneous explosive
decomposition and, therefore, it is available always in the form
of a solution.
• Conversion of acetic anhydride to acetic acid requires 40-45
minutes for its completion.
• It being an exothermic reaction, the solution must be allowed
to cool to room temperature before adding glacial acetic acid
to volume,
• Avoid adding an excess of acetic anhydride especially when
primary and secondary amines are to be assayed, because
these may be converted rapidly to their corresponding
acetylated non-basic products :
• R—NH2 + (CH3CO)2O → R.NH.(CH3CO) + CH3COOH
Primary amine Acetylated product
• Perchloric acid is not only a powerful oxidising agent but also a
strong acid. Hence, it must be handled very carefully.
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Acidimetry
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Alkali Metry
• Many weakly acidic pharmaceutical substances may
be titrated effectively by making use of a suitable
non-aqueous solvent with a sharp end-point.
• 0.1 N Potassium Methoxide in Toluene-Methanol
• 0.1 N Sodium Methoxide or 0.1 N Lithium
Methoxide
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