Diazotization – Titrations
BY:RANJEET RANJAN
Diazotization Titration or Nitrite Titration:
Diazotization is used in the analysis of aromatic compounds containing an amino
group in the molecules. This analysis is based on the reaction between aromatic
primary amine (–NH2), HONO, in presence of excess mineral or inorganic acids.
NaNO2 is generally used in direct method of diazotization. It gives HNO2 in acidic
solution. Many aromatic primary amine with free –NH2 group can be analyzed
quantitatively by measuring the volume of NaNO2 solution required to convert
them into diazonium salts. The typical reaction of diazotization reaction in
presence of HCl is given as:
NaNO2 + HCl HONO + NaCl
ArNH2 + HONO + HCl ArN2Cl + 2H2O
When all the aromatic amine has reacted with NaNO2 then next portion (excess) of
NaNO2 added to the solution under test, converted to HONO that remain in the
solution and can be detected by the starch paper or paste as an external indicator.
This appearance of free HNO2 in solution indicates that diazotization reaction is
complete and equivalence point is attained.
Starch iodide paper or paste is the starch solution plus equal volume of 5% KI
solution in H2O. Starch iodide paste with reaction mixture is as follows-
KI + HCl HI+ KCl
2HI +2HONO I2 +2NO +2H2O
(excess)
I2 + Starch blue color (end point)
The liberated I2 reacts with starch to give blue colour. The diazotization proceeds
quantitatively only in presence of inorganic acid. It is important to check the
acidity at the end of the titration. If there is no excess of acid present, starch –
iodide paper will not detect excess HNO2 and so will not indicate the end point.
Condition for diazotization:
(1) Rate of titration
(2) Temperature of the solution
(1) Rate of titration: Different amino compound react 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 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 some times 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. In case of slowly
diazotisable compound sufficient time (5-10 min) should be given to the solution
under test. So, that last portion of nitrous acid could fully react with amine.
If the test for end point determination is carried out immediately after addition of
the sodium nitrite, the nitrous acid so formed has not yet entered into the reaction
with amine will be taken as excess nitrous acid, indicate the end point has reached.
By sufficient stirring and slow addition of NaNO2 and keeping in view the time
factor, a large excess of NaNO2 is not allowed to build up. It is also suggested that
the burette tip is placed below the surface of reaction mixture to prevent the loss of
HNO2.
(2) Temperature: The diazonium compounds so formed are instable and readily
decompose at elevated temperature. This can lead to side reaction and give wrong
result to eliminate this titration as carried out at low temperature (0-50 C), optimum
temperature for most amine is 10- 150 C, when they form relatively stable diazo
compounds.
End point determination: - is done by two methods.
a. Visual end point determination method
b. Electrometric end point determination method.
(a) Visual end point determination method:
Principle: - aromatic primary amine reacts with sodium nitrite in acid solution
(i.e, nitrous acid) to form diazonium salts.
C6H5NH2 + NaNO2 +HCl C6H5N2Cl +NaCl + 2H2O
Under controlled condition reaction is quantitative and can be used for the
determination of most substance containing a free primary amino group as in
sulphanilamide and other sulpha drugs. Observation of end point depends upon the
detection of small excess of nitrous acid, which is then present. This can be
demonstrated visually by using starch iodide paste as external indicator .
KI + HCl HI + KCl
2HI + 2HNO2 I2 +2NO + 2H2O
The liberated iodine (I2) reacts with starch to give blue colours.
Method: - weigh 2.5 gm of sample; transfer it into a 250 ml flask. Add 50 ml of
concentrated HCl and 5 gm of KBr, adjust the final volume to 250 ml. pipette out
50 ml of this solution into a conical flask cool the solution so that the temperature
is maintained between 10 to15 0C. Titrate the solution with N/10 NaNO2 and
shaking continuously until distinct blue color is produced on a small piece of
starch iodide paper. The reaction is slow initially but behaves normal as the
reaction proceeds.
(b) Electrometric End Point determination method:
Principle- End point may be detected electrometrically using a pair of bright
platinum electrodes immersed in the titration liquid. Electrode polarization occurs
in the titration liquid. Electrode polarization occurs when a small voltage (30-50
mµ) is applied across the electrodes and no
current flows through the sensitive galvanometer included in the circuit, during the course of
titration. Liberation of excess of nitrous acid at the end point depolarizes the electrode, current
flows and full deflection in galvanometer needle is observed. This is known as the
dead stop end point.
The electrode must be clean other wise the end point is sluggish cleaning can be
accomplished by immersing the electrodes in boiling nitric acid containing a little
ferric chloride for about 30 sec and then washing with water. The blank
determination is necessary, the difference between the two titrations represent the
volume of sodium nitrite solution equivalent to the aromatic amine.
Method : Weigh accurately the sample (about 0.5 gm) and transfer into a 250 ml
beaker and dissolve in the HCl 10 ml and water 75 ml. insert a pair of bright
platinum electrodes into the solution, connected through a sensitive
galvanometer and suitable potentiometer at a 2V battery in such a way as to
produce a potential drop between 30-50 mµ across the electrodes.
Titrate slowly with N/10 NaNO2 with continuous stirring until a permanent
deflection of the galvanometer is observed at the end point.
Application of diazotization titration: An important pharmaceutical
application of sodium nitrite titration is the analysis of sulphonamides by
diazotization of primary aromatic amino group usually present in this class of
drugs. Several sulphonamides require the formation of primary amine prior to
diazotization step.
Example – phthalylsulphathiazole and succinyl sulphathiazole are first
hydrolyzed to give primary aromatic amine and determined by NaNO 2 titration
method.
List of compounds assayed by sodium nitrite titration:
(1) Dapsone
(2) Benzocaine
(3) Procaine hydrochloride
(4) Calcium amino salicylate
(5) Sodium amino salicylate
(6) Sulphacetamide tablet
(7) Sulphadoxine
(8) All sulpha drugs
