Diazotization Titrations - Pharmaceutical Analysis 1 B. Pharma 1st semester

Diazotization Titrations

Contents

• Diazotization titration

• Principle involved

• Preparation & Standardization of Sodium nitrite solution

• Types of diazotization titrations

• Applications

Objectives

By the end of this lecture, students will be able to:

• Explain the principle involved in Diazotisation titrations

• Outline the method of preparation and standardization of sodium nitrite standard solution

• Brief the applications of diazotization titrations

Diazotization Titrations

• Carried out for the estimation of drugs containing primary aromatic amino group

• Several drugs contain primary amino group or

• Can be converted to have such groups by simple reactions

• Like hydrolysis, reduction, etc

• Resulting amino group is diazotized by reaction with sodium nitrite solution in cold acid solution

• Nitrous acid formed diazotizes the compound

• End point can be determined by using external indicator method using starch iodide paper

• Alternatively, potentiometric method or dead stop end point technique can be used

Principle

• General reaction of diazotization,

• Addition of sodium nitrite to hydrochloric acid causes formation of nitrous acid

• Nitrous acid formed diazotizes the aromatic amino group

• After end point, excess nitrous formed is shown by instant formation of blue color with starch iodide paper

• Starch iodide paper is prepared by immersing a filter paper in starch mucilage and potassium iodide solution

• Color change of indicator paper is because of the reaction

• KI + HCl àKCl + HI

• 2HI + 2HNO2 àI2 + 2NO + 2H2O

• Iodine formed reacts with starch mucilage to give the blue color

• End point can also be determined by dead stop end point technique

• Here a potential of 30-50 mV is applied across two platinum electrodes

• Automatic pipette is used for the delivery of nitrite solution

• At the end point delivery of nitrite solution stops automatically

Preparation & Standardization

Preparation of 0.1M sodium nitrite solution

• 7.5 g of sodium nitrite is dissolved in sufficient water to produce 1000 ml

Standardization of 0.1M sodium nitrite solution

• About 0.5 g of sulphanilamide (previously dried at 105 0C for three hours) is transferred to a suitable beaker

• 50 ml of water and 20 ml of HCl is added, stirred until it dissolves

• Cooled to 15 ⁰C

• Contents of beaker are titrated against 0.1M sodium nitrite solution

• Each ml of 0.1M sodium nitrite solution = 0.01722 g of sulphanilamide

Diazotisation Titration

• Specified amount of drug is dissolved in about 50 ml of water and 20 ml of HCl

• Solution is stirred and cooled to about 15 0C

• Mixture is titrated against 0.1M sodium nitrite solution

• End point is determined by

• Using external indicator- starch iodide paper

• Electrometric technique by using platinum electrodes

Types of Diazotization Titrations

Direct titrations

• Here, direct titration of amine in acid against sodium nitrite solution

Reverse method

• Here, solution of amine and sodium nitrite are run into a solution of acid

• Method is used when diazonium salts are insoluble

• For example, naphthylamine sulphonic acids

Special method

• Aminophenols are readily oxidized by nitrous acid to quinones

• For such substances, titration is carried out in the presence of copper sulfate

• It forms diazo oxide

• Diazo oxides are more stable and undergo diazo coupling reaction

Applications of diazotization titrations

1. Direct titration with sodium nitrite solution

• Benzocaine

• Dapsone

• Primaquine phosphate

• Procaine

• All sulpha drugs containing free aromatic amino group like sulfacetamide, sulfadiazine, sulfamethoxazole, etc

2. Conversion of amino group by chemical reactions

A. By reduction

• Metronidazole

• Secnidazole

• Chloramphenicol

• These drugs contain nitro group

• Can be reduced by using any reducing agent to get primary amino group

• Primary aromatic amino group can be diazotized by sodium nitrite

B. Hydrolysis

• Paracetamol (acetyl derivative)

• Phthalyl sulphathiazole (phthalyl derivative)

• Succinyl sulphathiazole (succinyl derivative)

• These drugs are derivatives of amino groups

• Like acetyl or phthalyl or succinyl derivative

• After hydrolysis to free amino group can be titrated with sodium nitrite

• Isocarboxazid- acid solution of the drug liberates benzylhydrazine which can be diazotized to give benzylazide

 

 

SUMMARY

• Carried out for the estimation of drugs containing primary aromatic amino group

• Resulting amino group is diazotized by reaction with sodium nitrite solution in cold acid solution

• End point can be determined by using external indicator method using starch iodide paper

• Addition of sodium nitrite to hydrochloric acid causes formation of nitrous acid

• Nitrous acid formed diazotizes the aromatic amino group

• Starch iodide paper is prepared by immersing a filter paper in starch mucilage and potassium iodide solution