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DrX Whiz Niraj
Diazotisation Titration: Principle & Methods
Master the analytical estimation of primary aromatic amines (Sulpha drugs). Complete notes on basic principles, methods, and applications.
Diazotisation Titration (also known as Sodium Nitrite Titration) is a quantitative analytical method used specifically for the estimation of compounds containing a Primary Aromatic Amino Group (-NH₂).
Basic Principle:
When a primary aromatic amine is treated with Nitrous Acid (HNO₂) in a cold, strongly acidic medium, it yields a diazonium salt.
Since Nitrous acid is highly unstable, it is prepared in situ (during the reaction) by reacting standard Sodium Nitrite (NaNO₂) with Hydrochloric Acid (HCl).
Ar-NH₂ + HNO₂ + HCl (at 0-5°C) → Ar-N₂⁺Cl⁻ (Diazonium Salt) + 2H₂O
Practical Alert: Why maintain 0-5°C?
Diazonium salts formed during the reaction are highly unstable. If the temperature exceeds 5°C, the diazonium salt decomposes rapidly by reacting with water to form a Phenol and liberates Nitrogen gas. This will completely ruin the titration and give false endpoints. Hence, an ice bath is strictly mandatory.
Because the reaction mixture is often colored or turbid, detecting the exact endpoint is crucial. Two main methods are used:
1. Visual Method (External Indicator)
Starch-Iodide Paper is used as an external indicator. During titration, a drop of the reaction mixture is taken out using a glass rod and touched to the starch-iodide paper.
- Before endpoint: No color change.
- At endpoint: A faint Blue-Black spot appears instantly. This indicates that all amine is consumed and there is a slight excess of Nitrous acid (HNO₂) in the flask.
2. Electrometric Method
Also known as the Potentiometric or Dead Stop End Point method. This is the most accurate method.
- Two identical platinum electrodes are immersed in the solution with a small voltage (50 mV) applied.
- At endpoint: The sudden presence of excess HNO₂ depolarizes the electrodes, causing a sharp, permanent deflection in the galvanometer.
Diazotisation titration is widely applied in the pharmaceutical industry for the assay of drugs containing a free primary aromatic amine group. If the amine group is substituted (like in Phthalylsulfathiazole), the drug is first hydrolyzed to free the -NH₂ group before titration.
| Category | Examples of Drugs Assayed |
|---|---|
| Sulphonamides (Sulpha Drugs) | Sulfadiazine, Sulfamethoxazole, Sulfacetamide. |
| Local Anaesthetics | Procaine Hydrochloride, Benzocaine. |
| Antileprotic Drugs | Dapsone. |
| Anti-tubercular Drugs | PAS (Para-aminosalicylic acid). |