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

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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 à
KCl + HI

• 2HI + 2HNO2 à
I2 + 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