Non-aqueous titration is a volumetric analysis performed in solvents without water, allowing for accurate determination of endpoints due to the absence of water interference. It is particularly useful for titrating very weak acids and bases and employs various types of solvents including aprotic, protophilic, protogenic, and amphiprotic. The method has advantages like producing precise results and being applicable in pharmaceutical assays, though it also has drawbacks such as lower solvent stability compared to aqueous options.

1. Non Aqueous Titration
Mrs.Poonam Sunil Aher (M.Pharm, PhD)
Assistant Professor
Sanjivani College of Pharmaceutical Education and Research
(Autonomous),
Kopargaon, Ahmednagar-423603 (M.S.), INDIA
Mobile: +91-9689942854

2. • Non-aqueous titration is a volumetric analysis performed solely in
solvents with no water molecules.
• Titrations against acids or bases are performed in a non-aqueous
solvent with dissolved analytes or samples. The method used in active
pharmaceutical assays.
• The non-interference of water molecules in titration is what makes
non-aqueous titrations significant.
• Water is both a weak acid and a weak base. Water molecules compete
for proton donation with other bases and accept protons from other
acids dissolved in them. This makes it difficult to determine the
endpoint in titration. As a result, avoiding the interference of water
molecules in the titration procedure is critical. Due to the absence of
water molecules in non-aqueous titrations, it gives sharp endpoints and
accurate results.

3. • Non-aqueous titration is a highly helpful process because it satisfies
two requirements:
• 1. It is appropriate for titrating very weak acids or bases
• 2. It provides a solvent that may dissolve organic molecules.

4. Types of solvent in Non aqueous titration
• Types of Non-Aqueous Solvents
• There are four types of solvents that are commonly used in the non-aqueous
titration of a given analyte. They are as follows:
• 1. Aprotic Solvents: Aprotic solvents are chemically inert. These solvents
are non-reactive and do not react with acids or bases. They have a low
dielectric constant and do not cause solute ionisation. Aprotic solvents'
primary function is to dilute the reaction mixture.
• Examples: Toluene, acetonitrile, tetrachloride, benzene, chlorinated
hydrocarbons, etc.
• 2. Protophilic Solvents: Protophilic solvents are those that have higher
basicity than water. These solvents have a strong attraction to positively
charged protons. In the presence of an acidic solution, protophilic solvents
form a conjugate base of the acid and a solvated proton. A protophilic
solvent's primary function is to increase the acidic strength of very weak
acids. They increase the strength of weak acids by readily accepting
protons. Because of their high affinity for protons, they have a levelling
effect on weak acids.
• Examples: Liquid ammonia, ethers, amines and ketones.

5. • 3. Protogenic Solvents:
• Protogenic solvents are those that generate protons (Hydrogen ions). They
are acidic in nature. These solvents are typically more acidic than water. The
primary function of protogenic solvents is to increase the basic strength of
weak bases. They make weak bases stronger by donating protons. Because
of their high proton donating capacity, they have a levelling effect on weak
bases.
• Examples: Sulphuric acid, anhydrous hydrogen fluoride, formic acid, etc.
• 4. Amphiprotic Solvents: Amphiprotic solvents are those that have both
protophilic and protogenic properties. Amphiprotic solvents are chemically
similar to water molecules in that they have both acidic and basic
properties. Depending on the type of solute used, they can readily accept or
donate protons. They easily donate protons in the presence of a weak base,
increasing the basicity strength of the base used. They readily accept
protons in the presence of a weak acid, increasing the acidic strength of the
acid used.
• Examples: Weak organic acid such as acetic acid, and alcohols, such as
ethanol and methanol.
• Potentiometric titration procedures can also be used to precisely measure
the endpoints of these titrations.

6. Indicators
• Various visual indicators have been found to be the most suitable for the detection
of the endpoint in non-aqueous titration. These indicator changes the color or
undergoes precipitation at the endpoint. Some indicators have been used and
discussed below:
• 1.Crystal violet
• It is a triarylmethane dye. It is prepared in 0.5% w/v solution in glacial acetic acid.
Color changes from violet(basic) to light green (acidic). i.e. It gives a violet color
in the basic medium and a light green color in the acidic medium.
• 2.Methyl Red
• It is prepared in 0.2% solution in dioxane. The color change from yellow(basic) to
red(acidic).
• 3.Naptholbenzein
• It is prepared in 0.2% solution in glacial acetic acid. The color changes from
yellow(basic) to green(acidic).
• 4. Thymol Blue:
• 0.2 % w/v solution in methanol. The color changes from yellow to blue at the end
point

8. • Advantages of Non-Aqueous Titrations
• Non-aqueous titrations have the following advantages.
• 1. Non-aqueous titrations make it easier to titrate weak acids and bases.
Weak acids and bases are difficult to titrate with aqueous solvents.
• 2. Non-aqueous titrations are used to perform volumetric analysis on
organic acids that are insoluble in water.
• 3. Non-aqueous titrations are also used to analyse an acid mixture.
• 4. Non-aqueous titrations produce precise results with sharp endpoints.
• 5. Non-aqueous titrations are simple and straightforward.
• 6. Non-aqueous titrations are extremely important in pharmaceutical
product assays.
• 7. Non-aqueous titrations have a high degree of selectivity.
• 8. Non-aqueous titrations include the analysis of drugs such as tetracycline,
antihistamines, codeine phosphate, and many others.

9. • Disadvantages of Non-Aqueous Titrations
• The following are the drawbacks of non-aqueous titrations.
• 1. When compared to aqueous solvents, non-aqueous solvents are less
stable.
• 2. Temperature corrections are required from time to time in non-
aqueous titrations.
• 3. Calibration is required after each and every use.

10. • Applications of Non-Aqueous Titrations
• Non-aqueous titrations have the following applications
• 1. The purity of assays are determined by non-aqueous titrations.
• 2. To ascertain the concentration of the specified analyte, non-aqueous
titrations are employed.
• 3. Hydrophobic medications including phenobarbitone, steroids,
diuretics, tetracyclines, etc, are identified via non-aqueous titrations.
• 4. Adrenergic and anti-tubercular medications' drug compositions are
evaluated using non-aqueous titrations.

11. Types of Non Aqueous Titration
• Two Types
• 1. Acidimetry Non aqueous Titration:
• It involves quantitative determination of weak base by non aqueous
titration
• 2. Alkalimetry Non aqueous Titration:
• It involves quantitative determination of weak acid by non aqueous
titration

12. Difference between Acidimetry and Alkalimetry
Titration

15. Preparation of 0.1 M Perchloric acid in
dioxane
• Mix 8.5 ml perchloric acid in 1000 ml dioxane
• Standardisation procedure is same as previous explained manner.

16. Preparation and standardisation of 0.1 M
lithium methoxide