Non Aqueous titration: Definition, Principle and Application
- 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