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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5986_Библиотеки_им_академика_М_И_Перельмана.pdf
87
Volumetric Analysis
Volume of silver nitrate taken 50 mL; y M
Since, M
1
V
1
M
2
V
2
where M
1
is the molarity of ammonium thiocyanate, M
2
is the molarity of silver
nitrate, V
1
is the amount of ammonium thiocyanate reacting with excess silver
nitrate, i.e. burette reading and V
2
is the amount of silver nitrate reacting with
ammonium thiocyanate
Therefore,
Amount of silver nitrate reacting with chlorbutol (a) 50 V
2
Since, 1 mL of y M AgNO
3
{ (0.06216 u y) g of chlorbutol
a mL of y M AgNO
3
{ (0.06216 u y u a) g of chlorbutol
Since,
10 mL of chlorbutol solution contains (0.06216 u y u a) g of chlorbutol
1 mL will contain [(0.06216 u y u a)/10] g of chlorbutol
100 mL will contain [(0.06216 u y u a u 100)/10] g of chlorbutol
So
g mL of Chlorbutol
Equivalent factor Burette reading
M
/
-
100
50
=
()
u
u
oolarity AgNO
3
100
10
()
u
Pharmaceutical use
It is used as an antimicrobial preservative.
Category: Pharmaceutical aid (antimicrobial preservative)
Result The given chlorbutol solution was found to contain _______
g/100 mL of chlorbutol.
2.4 Diazotization Titration
Diazotization is a reaction that converts an aromatic primary amine into
diazonium compound.
In this titration, amino group is connected to a phenyl ring and to a
diazonium salt. The nitrous acid formed after the reaction of sodium nitrite
and hydrochloric acid provides –NO
which replaces a hydrogen on the
NH
3
group to produce nitrosamine, i.e. NH
2
NO
group and water.
Tautomerization and loss of water lead to produce the N
2
group, i.e.
diazonium ion.
88
Practical Pharmaceutical Analytical Chemistry
In diazotization titrations or sodium nitrite titrations, the substance containing
primary aromatic amino group is converted into the respective diazonium
salt by treating with sodium nitrite at low temperature in the presence of
hydrochloric acid. In general, aromatic primary amino moiety (ArNH
2
), as
present in sulpha drugs and other pharmaceutical preparations (sodium and
calcium aminosalicylate, isocarboxazid, primaquine phosphate and dapsone)
react with sodium nitrite in an acidic medium to yield the diazonium salts as
expressed here.
ArNH NaNO HCl
A e Sodium nitrate
Hydrochloric acid
C
o
22
04
min
-
++
⎯→⎯⎯⎯⎯⎯
++
+
ArN Cl NaCl H O
Diazonium salt
Sodium chloride
Water
22
-
At the end point a drop of nitrous acid (formed from sodium nitrite in acid
medium) reacts with the starch-iodide paper and gives blue colour due to
liberation of iodine.
NaNO HCl NaCl
Sodium nitrate
Hydrochloric acid
Sodium chlor
2
+⎯→⎯⎯⎯
iide
Nitrous acid
Nitrous acid
Hydrogen iodide
HNO
HNO HI
+
+⎯→⎯⎯⎯
3
3
2IINOHO
I Starch paper Blue Colou
Iodine Water
Iodine
22
2
22+↑+
+⎯→⎯⎯⎯ rr
2.4.1 Factors Affecting Diazotization Titration
Two factors that affect the diazotization titration depending upon the properties
of the amines are analysed as:
1. Rate of reaction: Sodium nitrite added in the reaction needs time to
change into nitrous acid and enter into the reaction with amine. Amines
are classified as rapidly or slowly diazotisable depending upon the rate of
conversion into diazo compounds.
a. Rapidly diazotisable amino compounds which include compounds
containing sulpha group, nitro group or carbonyl group besides amino
group. Example: Sulphanilic acid, nitroaniline and anthranilic acid.
b. Slowly diazotisable amino compounds which include compounds
containing methyl group or hydroxyl group besides amino group or
which do not contain any substituent group other than amino group.
Example: Toluidine, amino phenol and aniline.
89
Volumetric Analysis
Remedy: The rate of diazotisation can be increased by
s Adding KBr.
s Sufficient time about 510 min should be given so that the last portion
of sodium nitrite could fully react with amine.
s By efficient stirring and slow addition of sodium nitrite.
2. Temperature: Diazo compounds are unstable and readily decomposed at
higher temperature. This can lead to side reactions and give wrong results.
To eliminate this, titrations are carried out at low temperature. The opti-
mum temperature of most amines is 1520qC where they are relatively
stable diazo compounds. Amines that form unstable diazo compounds are
titrated at temperature of 04qC.
Experiment 1 To prepare and standardize 0.1 M sodium nitrite.
Primary standard Sulphanilic acid
Indicator: Starchiodide paper
Method
x Preparation: Weigh accurately 68.99X g of sodium nitrite and dissolve it in
water. Finally adjust the volume to 1 L to give XM or XN solution.
x Standardization: Dissolve 0.3 g of sulphanilic acid in 50 mL of 2 M
hydrochloric acid, add 3 g of potassium bromide, cool in ice and titrate it
with the sodium nitrite solution until gives blue colour with starch-iodide
paper.
End point: Appearance of blue colour.
Reaction involved
NaNO
2
2HCl
Sodium nitrite Hydrochloric
acid
Sodium chloride
0-5°C
+++
NaCl
+
H
2
O
Water
Sulfanilic acid
SO
3
H
NH
2
Diazonium salt
SO
3
H
N
Cl
-
+
-
Calculation
N
W
EV
=
×
×
1000
where N is the normality of given sodium nitrite, W is the weight of primary
standard, E is the equivalent weight of primary standard and V is the volume of
sodium nitrite consumed, i.e. burette reading
Result The prepared sodium nitrite solution was found to be
90
Practical Pharmaceutical Analytical Chemistry
Experiment 2 To find out g/100 mL of dapsone in the given sample.
IP followed: 1996
Principle: Diazotization titration
Molecular formula: C
12
H
12
N
2
O
2
S
H
2
N
SO
2
NH
2
Molecular weight: 248
Indicator: Galvanometer (for electrometrically titration)
IP limit: It contains not less than 99.0% and not more than 101.0% of dapsone,
calculated with reference to the dried substance.
Procedure
Weigh accurately 0.3 g of dapsone and dissolve it in a mixture of 20 mL of
distilled water and 20 mL of hydrochloric acid. Cool the solution to about
15qC and slowly titrate with previously standardized sodium nitrite solution
with continuous stirring until a permanent deflection of galvanometer needle is
observed at the end point.
or
Pipette out 10 mL of dapsone solution and to this add mixture of 20 mL
of distilled water and 20 mL of hydrochloric acid. Cool the solution to about
15qC and slowly titrate with previously standardized sodium nitrite solution
with continuous stirring until a permanent deflection of galvanometer needle is
observed at the end point.
Reactions involved
2NaNO
2
4HCl
2NaCl
Sodium nitrite Hydrochloric acid
Sodium chloride
15°C
4H
2
O
Water
Dapsone
H
2
N
SO
2
NH
2
Diazonium salt
Cl
N
2
SO
2
N
2
Cl
91
Volumetric Analysis
THEORY Dapsone is a white or creamy white crystalline powder, very slightly
soluble in water, soluble in dilute mineral acids. In this method, sodium nitrite
reacts with dapsone in nitrous acid form to give diazonium salts. At the end
point excess of nitrous acid depolarizes the electrode which causes the flow
of current in the galvanometer and the permanent deflection of galvanometer
needle is observed.
Equivalent factor
2NaNO
2
{ 1 C
12
H
12
N
2
O
2
S
2000 mL of 1 M NaNO
2
{ {(12 u 12) (1 u 12) (2 u 14) (2 u 16) (1 u
32)} g of C
12
H
12
N
2
O
2
S
2000 mL of 1 M NaNO
2
{ (144 12 28 32 32) g of C
12
H
12
N
2
O
2
S
2000 mL of 1 M NaNO
2
{ 248 g of C
12
H
12
N
2
O
2
S
1 mL of 1 M NaNO
2
{ (248/2000) g of C
12
H
12
N
2
O
2
S 0.124 g of
C
12
H
12
N
2
O
2
S
Calculation
1 mL of 1 M NaNO
2
0.124 g of C
12
H
12
N
2
O
2
S
a mL of 1 M NaNO
2
{ (0.124 u a) g of C
12
H
12
N
2
O
2
S
a mL of y M NaNO
2
{ (0.124 u a u y) g of C
12
H
12
N
2
O
2
S
Since 10 mL of dapsone solution contains (0.124 u a u y) g of C
12
H
12
N
2
O
2
S
1 mL will contain (0.124 u a u y)/10) g of C
12
H
12
N
2
O
2
S
100 mL will contain (0.124 u a u y u 100)/(10) g of C
12
H
12
N
2
O
2
S
So
g mL of Dapsone
Equivalent factor Burette reading
Molarity N
/100 =
u
u
aaNO
2
100
10
()
u
Category: Antileprotic
Result The given dapsone solution was found to contain g/100 mL
of dapsone.
Experiment 3 To find out g/100 mL of sulphacetamide sodium in the given
sample.
IP followed: 1996
92
Practical Pharmaceutical Analytical Chemistry
Principle:
Diazotization titration
Molecular formula: C
8
H
9
N
2
NaO
3
S, H
2
O
SO
2
NH
2
, H
2
O
H
3
COCN
Na
Molecular weight: 254 (with water); 236 (anhydrous)
Indicator: Galvanometer (for electrometrically titration)
IP limit: It contains not less than 99.0% and not more than 101.0% of
sulphacetamide sodium, calculated with reference to the anhydrous substance.
Procedure
Weigh accurately 0.25 g of sulphacetamide sodium and dissolve it in a mixture of
50 mL of distilled water and 20 mL of 2 M hydrochloric acid. To this solution add
3 g of potassium iodide. Cool the solution to about 15qC and slowly titrate with
previously standardized sodium nitrite solution with continuous stirring until a
permanent deflection of galvanometer needle is observed at the end point.
or
Pipette out 10 mL of sulphacetamide sodium solution and to this add mixture
of 50 mL of distilled water and 20 mL of 2 M hydrochloric acid. To this solution
add 3 g of potassium iodide. Cool the solution to about 15qC and slowly titrate
with previously standardized sodium nitrite solution with continuous stirring
until a permanent deflection of galvanometer needle is observed at the end point.
Reaction involved
NaNO
2
2HCl
NaCl
Sodium nitrite Hydrochloric
acid
Sodium chloride
15°C
H
2
O
Water
Sulphacetamide sodium
SO
2
NH
2
H
3
COCN
Na
Diazonium salt
SO
2
N
2
Cl
H
3
COCN
Na
THEORY Sulphacetamide sodium is a white or yellowish white crystalline
powder, very freely soluble in water. In this method sodium nitrite reacts with
93
Volumetric Analysis
sulphacetamide sodium in nitrous acid form to give diazonium salts. At the end
point excess of nitrous acid depolarizes the electrode which causes the flow
of current in the galvanometer and the permanent deflection of galvanometer
needle is observed.
Equivalent factor
1 NaNO
2
{ 1 C
8
H
9
N
2
NaO
3
S
1000 mL of 1 M NaNO
2
{ {(8 u 12) (9 u 1) (2 u 14) (1 u 23) (3 u 16)
(1 u 32)} g of C
8
H
9
N
2
NaO
3
S
1000 mL of 1 M NaNO
2
{ (96 9 28 23 48 32) g of C
8
H
9
N
2
NaO
3
S
1000 mL of 1 M NaNO
2
{ 236 g of C
8
H
9
N
2
NaO
3
S
1 mL of 1 M NaNO
2
{ (236/1000) g of C
12
H
12
N
2
O
2
S 0.236 of
C
8
H
9
N
2
NaO
3
S
Calculation
1 mL of 1 M NaNO
2
0.236 g of C
8
H
9
N
2
NaO
3
S
a mL of 1 M NaNO
2
{ (0.236 u a) g of C
8
H
9
N
2
NaO
3
S
a mL of y M NaNO
2
{ (0.236 u a u y) g of C
8
H
9
N
2
NaO
3
S
Since 10 mL of C
8
H
9
N
2
NaO
3
S solution contains (0.236 u a u y) g of
sulphacetamide sodium
1 mL will contain (0.236 u a u y)/10) g of C
8
H
9
N
2
NaO
3
S
100 mL will contain (0.236 u a u y u 100)/(10) g of C
8
H
9
N
2
NaO
3
S
So
g mL of Sulphacetamide sodium
Equivalent factor Burette read
/100 =
u
iing
Molarity NaNOuu
2
100
10
()
Category: Antibacterial
Result The given sulphacetamide sodium solution was found to contain
_______ g/100 mL of sulphacetamide sodium.
Experiment 4 To find out g/100 mL of sulphadiazine in the given sample.
IP followed: 1996
Principle: Diazotization titration
94
Practical Pharmaceutical Analytical Chemistry
Molecular formula:
C
10
H
10
N
4
O
2
S
N
N
SO
2
NH
2
NH
Molecular weight: 250
Indicator: Galvanometer (for electrometrically titration)
IP limit: It contains not less than 99.0% and not more than 101.0% of sul-
phadiazine, calculated with reference to the dried substance.
Procedure
Weigh accurately 0.2 g of sulphadiazine and dissolve it in a mixture of 50 mL
of distilled water and 20 mL of 2 M hydrochloric acid. To this solution add
3 g of potassium bromide. Cool the solution to about 15qC and slowly titrate
with previously standardized sodium nitrite solution with continuous stirring
until a permanent deflection of galvanometer needle is observed at the end
point.
or
Pipette out 10 mL of sulphadiazine solution and to this add mixture of
50 mL of distilled water and 20 mL of 2 M hydrochloric acid. To this solution
add 3 g of potassium bromide. Cool the solution to about 15qC and slowly
titrate with previously standardized sodium nitrite solution with continuous
stirring until a permanent deflection of galvanometer needle is observed at the
end point.
Reaction involved
NaNO
2
2HCl
NaCl
Sodium nitrite Hydrochloric acid
Sodium chloride
15°C
H
2
O
Water
Sulphadiazine
SO
2
NH
2
HN
N
N
Diazonium salt
SO
2
NCl
HN
N
N
95
Volumetric Analysis
THEORY Sulphadiazine is a white, yellowish white or pinkish white crystals or
crystalline powder, practically insoluble in water. It dissolves in solutions of alkali
hydroxides and in dilute mineral acids. In this method sodium nitrite reacts with
sulphadiazine in nitrous acid form to give diazonium salts. At the end point excess
of nitrous acid depolarizes the electrode which causes the flow of current in the
galvanometer and the permanent deflection of galvanometer needle is observed.
Equivalent factor
1 N aNO
2
{ 1 C
10
H
10
N
4
O
2
S
1000 mL of 1 M NaNO
2
{ {(10 u 12) (10 u 1) (4 u 14) (2 u 16) (1 u
32)} g of C
10
H
10
N
4
O
2
S
1000 mL of 1 M NaNO
2
{ (120 10 56 32 32) g of C
10
H
10
N
4
O
2
S
1000 mL of 1 M NaNO
2
{ 250 g of C
10
H
10
N
4
O
2
S
1 mL of 1 M NaNO
2
{ (250/1000) g of C
12
H
12
N
2
O
2
S 0.250 of
C
10
H
10
N
4
O
2
S
Calculation
1 mL of 1 M NaNO
2
0.250 g of C
10
H
10
N
4
O
2
S
a mL of 1 M NaNO
2
{ (0.250 u a) g of C
10
H
10
N
4
O
2
S
a mL of y M NaNO
2
{ (0.250 u a u y) g of C
10
H
10
N
4
O
2
S
Since 10 mL of C
10
H
10
N
4
O
2
S solution contains (0.250 u a u y) g of
sulphadiazine
1 mL will contain (0.250 u a u y)/(10) g of C
10
H
10
N
4
O
2
S
100 mL will contain (0.250 u a u y u 100)/(10) g of C
10
H
10
N
4
O
2
S
So
g mL of Sulphadiazine
Equivalent factor Burette reading
Mol
/100 =
u
u
aarity NaNO
2
100
10
()
u
Category: Antibacterial
Result The given sulphadiazine solution was found to contain _______
g/100 mL of sulphadiazine.
Experiment 5 To find out g/100 mL of sulphadimidine in the given sample.
IP followed: 1996
Principle: Diazotization titration
96
Practical Pharmaceutical Analytical Chemistry
Molecular formula:
C
12
H
14
N
4
O
2
S
N
N
SO
2
NH
2
HN
CH
3
H
3
C
Molecular weight: 278
Indicator: Galvanometer (for electrometrically titration)
IP limit: It contains not less than 99.0% and not more than 101.0% of sul-
phadimidine, calculated with reference to the dried substance.
Procedure Weigh accurately 0.25 g of sulphadimidine and dissolve it in a
mixture of 50 mL of distilled water and 20 mL of 2 M hydrochloric acid. To this
solution add 3 g of potassium bromide. Cool the solution to about 15qC and
slowly titrate with previously standardized sodium nitrite solution with continu-
ous stirring until a permanent deflection of galvanometer needle is observed at
the end point.
or
Pipette out 10 mL of sulphadimidine solution and to this add mixture of 50 mL
of distilled water and 20 mL of 2 M hydrochloric acid. To this solution add 3 g
of potassium bromide. Cool the solution to about 15qC and slowly titrate with
previously standardized sodium nitrite solution with continuous stirring until a
permanent deflection of galvanometer needle is observed at the end point.
Reaction involved
NaNO
2
2HCl
NaCl
Sodium nitrite Hydrochloric acid
Sodium chloride
15°C
H
2
O
Water
Sulphadiazine
SO
2
NH
2
HN
N
N
CH
3
H
3
C
Diazonium salt
SO
2
NCl
HN
N
N
CH
3
H
3
C