Non-Aqueous Titrations

Non-aqueous titration is the one under which the analyte compound is dissolved or suspended in a solvent that does not contain water molecules. Let’s look at the theory behind non-aqueous titrations theory. The involvement of water molecules in titration is one of the reasons why non-aqueous titrations are relevant. A water molecule retains both weak acid and weak basic characteristics. Water molecules interact with various bases and acids dissolved in them for proton donation and proton acceptance. The end-point of the titration is more challenging to estimate due to the solvent containing water molecules. As a result, a titration process that does not include the involvement of water molecules is necessary. Non-aqueous solvents are thus employed to analyse chemicals, and the process is known as non-aqueous titration. Titrations in non-aqueous solvents produce precise results with sharp end-points.

Generally, there are two significant requirements for non-aqueous titrations:

1. They make it much easier to titrate extremely weak bases and acids.
2. They behave as a solvent, helping the organic component to dissolve.

Solvent Selection Parameters in non-aqueous titration:

In a non-aqueous titration, the solvent selection is mainly based upon the following parameters: 

1. Solubility of the sample.
2. Nature of the material.
3. Sharp end-point.
4. High dielectric constant.
5. Ease of purification.

Solvents used in non-aqueous titration:

There are four types of solvents used in non-aqueous titration which does not contain water molecule:

1. Protic solvents.
2. Protogenic solvents.
3. Protophilic solvents.
4. Amphiprotic solvents.

Protic solvents: They are neutral in their chemical nature. Protic solvents do not interact with acids and bases as they are non-reactive. Protic solvents have a low dielectric constant. Ionisation of solutes does not occur in protic solvents. Protic solvents are mostly used to dilute reaction mixtures.

Examples: Benzene, toluene, etc.  

Protogenic solvents: The protons are produced by protogenic solvents. Protogenic solvents are acidic. These solvents are frequently more acidic than water. Protogenic solvents are mostly used to boost the basic strength of weak bases. They donate protons to weak bases, making them stronger. They have a levelling effect on weak bases due to their strong proton donating capacity.

Examples: Sulphuric acid, formic acid, etc. 

Protophilic solvents: Solvents with higher basicity than water are known as protophilic. These solvents have a strong attraction to positively charged protons. The synthesis of a conjugate base of the acid and a solvated proton occurs when protophilic solvents are present in an acidic solution. A protophilic solvent’s primary role is to increase the acidic strength of relatively weak acids. They make weak acids stronger by quickly absorbing protons. They have a levelling effect on weak acids due to their significant proton affinity.

Examples: Ketones, amines, etc.    

Amphiprotic solvents: Amphiprotic solvents combine the features of protophilic and protogenic fluids. Amphiprotic solvents are comparable to water molecules in that they can be both acidic and basic. Depending on the type of solute, they can readily receive or donate protons. They easily donate protons in the presence of a weak base, enhancing the basicity strength of the base employed. They quickly take protons in the presence of a mild acid, increasing the acidic power of the acid utilised.

Examples: Acetic acid, methanol, etc. 

Advantages & Disadvantages of Non-aqueous Titrations

Advantages:

1. Weak acids and bases can be determined more easily with non-aqueous titrations
2. It’s tough to titrate weak acids and bases in aqueous solutions
3. Volumetric analysis of insoluble organic acids in water is performed using non-aqueous titrations
4. A mixture of acids can also be tested using non-aqueous titrations
5. Non-aqueous titrations provide precise results with well-defined end-points
6. Titrations in non-aqueous media are easy to do
7. In pharmaceutical product testing, non-aqueous titrations are significant
8. Non-aqueous media titrations provide excellent selectivity
9. Tetracycline, antihistamines, codeine phosphate, and other drugs are tested using non-aqueous titrations

Disadvantages:

1. Non-aqueous solvents are less steady compared to the aqueous solvents
2. Temperature corrections are occasionally required in non-aqueous titrations.l
3. Calibration is necessary after every use

Detection of End-point with the help of indicators in the Non-aqueous titrations:

1. Crystal Violet: In a basic medium, it turns violet; in an acidic medium, it turns yellowish-green. It is commonly used for pyridine titration
2. Oracet Blue B: In a basic medium, it is blue, while in an acidic medium, it is pink
3. Other indicators include alpha naphtholbenzein and quinaldine red

Applications of Non-aqueous titrations:

1. To determine the assay’s purity
2. To determine the concentration of a specific analyte, non-aqueous titrations are used
3. To determine the hydrophobic drugs such as steroids, diuretics, etc
4. Adrenergic and antitubercular agents’ drug composition is determined using non-aqueous titrations

Conclusion

The involvement of water molecules in titration is one of the reasons why non-aqueous titrations are relevant. A water molecule retains both weak acid and weak basic characteristics. Water molecules interact with various bases and acids dissolved in them for proton donation and proton acceptance. The analyte chemical is dissolved in a solvent that does not include water in non-aqueous titration. Their types of solvents such as protogenic solvents, amphiprotic solvents, etc. Its application is critical in pharmacopoeial assays. Advantages like non-aqueous titration are accurate, and disadvantages like solvent are expensive.