DIAZOTIZATION TITRATION
The process of forming diazonium compounds or salts is called diazotation,
diazoniation, or diazotization. Diazonium compounds or diazonium salts are a
group of organic compounds sharing a common functional group with the
characteristic structure of R-N2+X
where R can be any organic residue such alkyl or aryl and
X is an inorganic or organic anion such as a halogen.
Benzene diazonium
The reaction was discovered by Peter Griess in 1858, who subsequently
discovered several reactions of the new compound.
In general, diazonium salts are prepared by treatment of aromatic amines with
nitrous acid and additional acid. Usually, the nitrous acid is generated in situ (in
the same flask) from sodium nitrite and the excess mineral acid (usually aqueous
HCl, H2SO4, p-toluene sulfonic acid, or Tetrafluoroboric acid).
Diazonium salts have been developed as important intermediates in the organic
synthesis of dyes.
Diazotization titrations are carried out for the estimation of drugs containing
primary aromatic amino group. Several drugs contain either primary aromatic
amino group or they can be converted to have such groups by simple reaction like
hydrolysis or reduction.
Primary aromatic amine reacts with nitrous acid produced by the reaction of
sodium nitrite in acidic medium to form diazonium salt. The reaction is
quantitative under the controlled conditions of temp. (approx 150C) and the end
point can be detected when a small quantity of excess nitrous acid present at the
end point gives colour change with indicator or by electrometrically.
It uses the titrant- “Sodium Nitrite” hence method is Sodium Nitrite Titration /
Nitrite Titration.
CONDITION FOR DIAZOTIZATION RATE OF TITRATION
Different amino compound reacts with HONO at different rates.
NaNO2 added from the burette needs time to react with amino group
accumulating in the solution
Amines are classified as rapidly, slowly diazotisable depending on the rate of
conversion into azo compounds.
Slow diazotisable compounds include compounds that contain sulpha groups,
nitrous oxide group, or carboxylic group in aromatic ring or besides aromatic
ring
Example: isomeric nitro aniline, sulphanilic acid and anthranilic acid
Fast diazotisable compounds do not contain any substituent group other than
amino group but sometimes they may contain –CH3 or –OH group along with NH2
group.
Example: aniline, toluidine and aminophenol Adding KBr to the solution
can increase the rate of titration.
TEMPERATURE:
The diazonium compounds formed are unstable and readily decompose at
elevated temperature. This can lead to side reaction and give wrong result.
To eliminate this problem, this titration is carried out at low temperature (0-50C).
Optimum temperature for most amine is 10-150 C, when they form relatively
stable diazo compounds.
PRINCIPLE:
The first involved is addition of sodium nitrite to hydrochloric acid cause
formation of nitrous acid
NaNO2 + HCl --------------------→ HONO + NaCl
This nitrous acid diazotises the aromatic amino group
R−NH2 + NaNO2 + HCl --------------------→ R−N+ ≡ N−Cl− + NaCl
After the end point, excess nitrous acid formed is shown by instant formation of
blue colour with starch iodide paper.
KI + HCl --------------------→ HI+ KCl
NaNO2 + HCl --------------------→ HNO2 + NaCl
2HI +2HONO --------------------→ I2↑ +2NO +2H2O
Starch iodide paper is prepared by immersing a filter paper in starch mucilage
and potassium iodide solution.
The iodine formed reacts with starch mucilage to give the blue colour. I2 +
Starch blue color (end point).
The end point can also be determined by dead stop end point and potentiometric
technique.
It is important to check the acidity at the end of the titration. If there is no excess
of acid present in the solution, starch–iodide paper will not detect excess HNO2
and so will not indicate the end point.
TYPES OF DIAZOTISATION TITRATIONS
Direct Titrations: These are carried out by treating 1 mole of the drug with 3
moles of acid solution. Ice can be used to lower the temperature to about 0-5°c.
0.1M sodium nitrite is added in small amounts and titration is carried out. The end
point is determined by starch iodide paper techniques or by potentiometrically.
Reverse Method: In this method a solution of amine and sodium nitrite are
added into a solution of acid. This method is used when the diazonium salts are
insoluble.
Example: naphtylamine sulphonic acids form insoluble diaonium salts due to
formation of zwitter ions.
Special Method: Aminophenol are readily oxidized by nitrous acid to quinones.
For such substances, the titration is carried out in the presence of copper sulphate
which forms diazo-oxide. These diazo-oxides are more stable and undergo
coupling reaction.
APPLICATIONS:
This method is suitable for the assay of most of the pharmacopoeial
sulphonamides & its preparations as well as the drugs which contains primary
aromatic amines.
It is used in the assay of sulpha drugs like dapsone, sulphonamides,
sulphacetamide sodium, sulphadiazine, sulphamethazole, sulphadoxine,
sulphamethoxazole & sulphaphenazone etc.
It is also used in the assay of various drugs like benzocaine, procainamide,
procaine, suramin, sodium amino salicylate, primaquine sulphate etc.
