AY 2016-2017
Alexander S. Basada
At the end of the lecture, the students should be able to:
1. Explain on the basic concepts involving reduction-oxidation
reactions
2. Explain the reasons for important steps in a number of assay
methods as indicated in the monograph
3. Utilize pharmaceutical analytical computations in assay involving
reduction-oxidation reaction
I. Review of Reduction-Oxidation Concepts
II. The Nernst Equation
III. Chemical Equivalents
IV. Fundamentals of Reduction-Oxidation Titrations
V. Reduction-Oxidation Methods
Review of Reduction-Oxidation Concepts
OA RA
Arrange the species in decreasing strength as oxidizing agents: H+,
Ag+, Cd2+, Zn2+
Ag+> H+ > Cd2+ > Zn2+
EAg /Ag - reading shows the potential of the
+
complete cell measured against SHE
Ecell Value Reaction
(+) Spontaneous
(-) Non spontaneous
↑ EO - ↑ reduction potential
↓ EO - ↑ oxidation potential
Will the reaction occur?
EO = 1.610 V
EO = -0.771 V
Yes. EO = 0.839 V (Spontaneous)
Determine the Eelectrode of the
following redox pairs:
a. Fe, Sn4+
b. I–, Fe3+
c. I2, Cl–
• Identify the reducing agent
and the oxidizing agent
Indicate the EO and determine which of the following species are the
OA’s and RA’s during a spontaneous reaction. Write the half reactions
and the complete, balanced net ionic equation. (See Appendix 5 of
Skoog et al. 2014).
1. Ce3+ + Cr2O72-
2. I2 + Fe
3. Zn2+ + Ag
4. NO3- + Cl-
5. H2O + Mg
6. C2O42- + MnO4- + H+
Describes the effect of the concentration on the electrode potentials
↑ ↑
[𝑹]
[𝑶]
How much 5% Sodium oxalate solution will react
completely with 20 mL of 0.1M Potassium
Permanganate?
Given the following reactions, compute for the gram-equivalent
weight:
1. Ce(SO4)2 + Na2C2O4
2. I2 + Na2S2O3 1. Half-reactions
3. FeSO4 + KMnO4
2. e- involved
4. NaNO2 + KMnO4
5. I2 + NaAsO2 3. Analyte and MW
6. KI + K2Cr2O7
Fundamentals of Reduction-Oxidation Titrations
I. Permanganometry
II. Cerimetry
III. Iodimetry
IV. Iodometry
V. Miscellaneous RedOx
Direct
Indirect
Residual (Back)
Self-indicating
Indicator dyes
Use of extracting solvents
Potentiometric
Permanganometry
0.1 N Potassium Permanganate VS and or 0.1 N Oxalic Acid VS
Titration medium is acidified with sulfuric acid
with oxalic acid: 70-80oC
Endpoint: appearance of the pink color
A very powerful oxidizing agent (E0 = +1.51 V)
Self-indicating titrant
Primary standard: Na2C2O4
Stable when proper precautions are observed in its preparation and
preservation
4 KMnO4 + 2 H2O 4 KOH + 4 MnO2 + 3 O2
autocatalytic
decomposition
Dissolve about 3.3 g of potassium permanganate in 1000 mL of water
in a flask, and boil the solution for about 15 minutes. Insert the stopper
in the flask, allow to stand for at least 2 days, and filter through a fine-
porosity, sintered-glass crucible. If necessary, the bottom of the
sintered-glass crucible may be lined with a pledget of glass wool.
MnO4− + 8H+ + 5 e− → Mn2+ + 4H2O
𝑓=5
Accurately weigh about 200 mg of sodium oxalate, previously dried at
1100 to constant weight, and dissolve it in 250 mL of water. Add 7 mL
of sulfuric acid, heat to about 700, and then slowly add the
permanganate solution from a buret, with constant stirring, until a pale
pink color, which persists for 15 seconds, is produced. The temperature
at the conclusion of the titration should be not less than 600.
MnO4− + 8H+ + 5 e− → Mn2+ + 4H2O x2
C2O42− → 2𝐶𝑂2 + 2 𝑒- x5
2 MnO4- + 16 H+ + 5 C2O42- → 2 Mn2+ + 8 H2O + 10 CO2
A B
What’s wrong in this set-up?
Dissolve 6.45 g of oxalic acid in sufficient water to make 1000 mL.
Standardize by titration against freshly standardized 0.1 N potassium
permanganate V.S. as directed under Potassium Permanganate, Tenth-
Normal (0.1 N).
Cerimetry
0.1 N Ceric Sulfate VS
Self-indicating
Requires acidic medium
Useful in potentiometric titrations
Advantages over 0.1 N Potassium Permanganate VS
1. Potential can be varied by choice of acid
2. Stable even on boiling
3. May be standardized by sodium oxalate or arsenic trioxide
4. Cerous ion does not obscure endpoint
5. No intermediate formed in the reduction of Ce4+
6. Does not oxidize chloride ions
7. Can utilize a redox indicator
1 F HCl +1.28 V
1 F HNO3 +1.61 V
1 F H2SO4 +1.44 V
1 F HClO4 +1.71 V
8 F HClO4 +1.87 V
Hamilton and Simpson (1964). pg. 250
Indicator Solution E0, V Red Ox
Nitroferroin 1 M H2SO4 1.25 red pale blue
Ferroin 1 M H2SO4 1.06 red pale blue
Diphenylaminesulfonic diluted
0.84 colorless purple
acid acid
Diphenylamine 1 M H2SO4 0.76 colorless violet
Methylene blue 1 M acid 0.53 blue colorless
Indigo tetrasulfonate 1 M acid 0.36 colorless blue
Orthophenanthroline
Forms soluble ferrous complex salts
Most ideal, non-specific redox indicator
ferroin ferric orthophenanthroline complex
Diphenylamine
Insoluble in water (1 M sulfuric acid is used as the solvent)
N N N
H H H
diphenylamine diphenylbenzidine
N N
diphenylbenzidine violet
Transfer 59 g of ceric ammonium nitrate to a beaker, add 31 mL of
sulfuric acid, mix, and cautiously add water, in 20-mL portions until
solution is complete. Cover the beaker, allow to stand overnight. Filter
through a fine-porosity, sintered glass crucible, dilute to 1000 mL,
and mix. USP25/NF20
Ce(NO3)4· 2 NH4NO3 (primary standard)
Dissolve 33.22 g in water to make 1000 mL. USP35/NF30
Weigh accurately 200 mg of arsenic trioxide, previously dried at 1000C for
1 hour, and transfer to a 500-mL conical flask. Wash down the inner walls
of the flask with 25 mL of sodium hydroxide solution (2 in 25), swirl to
dissolve the sample and when the solution is complete, add 100 mL of
water, and mix. Add 10 mL of dilute sulfuric acid (1 in 3), then add 2 drops
each of orthophenanthroline TS and a 1 in 400 solution of osmium
tetroxide in 0.1 N sulfuric acid, and slowly titrate with the ceric sulfate
solution until the pink color is changed to a very pale blue. Each 4.946 mg
of arsenic trioxide is equivalent to 1 mL of 0.1 N ceric sulfate. USP25/NF20
As2O3 + 6 NaOH 2 Na3AsO3 + 3 H2O
2 Ce(SO4)2 + Na3AsO3 + H2O Ce2(SO4)3 + Na3AsO4 + H2SO4
Accurately weigh about 0.2 g of sodium oxalate, primary standard,
previously dried for 2 hours at 1050, and dissolve in 75 mL of water.
Add, with stirring, 2 mL of sulfuric acid that has previously been
mixed with 5 mL of water, mix well, add 10 mL of hydrochloric acid,
and heat to between 700 and 750. Titrate with 0.1 N ceric sulfate to a
permanent slight yellow color. Each 6.700 mg of sodium oxalate is
equivalent to 1 mL of 0.1 N ceric sulfate. USP30/NF25
Iodine Titrations
Iodimetry - direct processes in which a standard solution of iodine
(or sodium thiosulfate) is the titrating agent
Iodometry - indirect processes in which the sample is reduced with
excess potassium iodide, thereby liberating iodine
• A moderately strong oxidizing agent
• Reacts rapidly with strong reducing agents
• Uses starch TS to indicate endpoint
Dissolve about 10 g of iodine in a solution of 36 g of potassium iodide
in 100 mL of water, add 3 drops of hydrochloric acid, dilute with water
to 1000 mL. Standardize and preserve in amber-colored, glass
stoppered bottles. USP35/NF30.
I2 + I- I3-
I2 + 2 OH- IO- + H2O
3 IO- IO3- + 2 I-
4 I- + O2 + 4 H+ 2 I2 + 2 H2O
I2 + H2O + hv HI + HIO
Weigh accurately about 150 mg of arsenic trioxide, and dissolve in 20 mL of
1 N sodium hydroxide by warming if necessary. Dilute with 40 mL of water,
add 2 drops of methyl orange TS, and follow with diluted hydrochloric acid
until yellow color is changed to pink. Then, add 2 g of sodium bicarbonate,
dilute with 50 mL of water, add 3 mL of starch TS. Slowly add the iodine
solution from a buret until a permanent blue color is produced. Each 4.946
mg of arsenic trioxide is equivalent to 1 mL of 0.1 N iodine. (USP XIX/NF
XIV)
As2O3 + 6 NaOH 2 Na3AsO3 + 3 H2O
2 NaOH + I2 NaIO + NaI + H2O
H3AsO3 + H2O + I2 H3AsO4 + 2 HI
Na3AsO3 + I2 + 2 NaHCO3 Na3AsO4 + 2 NaI + 2 CO2 + H2O
Transfer 25.0 mL of the iodine solution to a 250-mL flask, dilute with
water to 100 mL, add 1 mL of 1 N hydrochloric acid, swirl gently to mix,
and titrate with 0.1 N sodium thiosulfate VS until the solution has a
pale yellow color. Add 2 mL of starch TS and continue titrating until the
solution is colorless. (USP 35/NF30)
I2 + 2 Na2S2O3 2 NaI + Na2S4O6
S2O32- + 2 H+ H2SO3 + S
Dissolve about 26 g of sodium thiosulfate and 200 mg of sodium
carbonate in 1000 mL of recently boiled and cooled water. (USP
35/NF30)
Na2S2O3 + 2 H2CO3 2 NaHCO3 + H2S2O3
H2S2O3 H2SO3 + S
CO32- + H2O HCO3- + OH-
S2O32- + 4 O2 + 2 OH- 2 SO42- + 5 H2O
• Potassium bromate (KBrO3)
• Potassium iodate (KIO3)
• Potassium biiodate [KH(IO3)2]
• Potassium dichromate (K2Cr2O7)
• Metallic copper
Accurately weigh about 210 mg of primary standard potassium dichromate,
previously pulverized and dried at 120 for 4 hours, and dissolve in 100 mL of
water in a glass-stoppered, 500-mL flask. Swirl to dissolve the solid, remove the
stopper, and quickly add 3 g of potassium iodide, 2 g of sodium bicarbonate,
and 5 mL hydrochloric acid. Insert the stopper gently in the flask, swirl to mix,
and allow to stand in the dark for exactly 10 minutes. Rinse the stopper and
the inner walls of the flask with, and titrate the liberated iodine with the sodium
thiosulfate solution until the solution is yellowish green in color. Add 3 mL of
starch TS, and continue the titration until the blue color is discharged. Perform a
blank determination. (USP 35/NF30)
Cr2O72- + 14 H+ + 6 e- Cr3+ + 7 H2O
6 I - 3 I 2 + 6 e-
K2Cr2O7 + 6 KI + 14 HCl 3 I2 + 2 CrCl3 + 8 KCl + 7 H2O
4 I- + O2 + 4 H+ 2 I2 + 2 H2O
Accurately measure about 25 mL of the solution into a 500-mL iodine
flask, and dilute with 120 mL of water. Add 5 mL of hydrochloric acid,
insert the stopper in the flask, and shake it gently. Then add 5 mL of
potassium iodide TS, again insert the stopper, shake the mixture, allow
it to stand for 5 minutes, and titrate the liberated iodine with 0.1 N
sodium thiosulfate VS, adding 3 mL of starch TS as the endpoint is
approached. (USP 35/NF30)
Assignment: Reasons for Important Steps
Arrowroot starch
Potato starch
Soluble starch
Mix 1 g of soluble starch with 10 mg of red mercuric iodide and
sufficient cold water to make a thin paste. Add 200 mL of boiling water,
and boil for 1 minute with continuous stirring. Cool, and use only the
clear solution. (USP 35/NF30)
• Amylose (~ 20–30% by weight) and amylopectin (~70 – 80% by
weight)
OH OH
H2C H2C
H O H H O H
H H
OH H OH H
O O O
H OH H OH
alpha-1,4-glucosidic bond
amylose (β-amylose)
amylopectin (α-amylose)
OH OH
H2C H2C
H O H H O H
H H
OH H OH H
O O O
H OH H OH alpha-1,6-glucosidic bond
OH
CH2 H2C
H O H H O H
H H
OH H OH H
O O O
H OH H OH
alpha-1,4-glucosidic bond
• Sensitive when the concentration of the iodine I2 is as low as 2 x
10-5 M at 20 °C
• The sensitivity of the indicator is greater in slightly acidic media and
is markedly decreased by temperatures above 250C, strong solutions
of electrolytes, alcohols, and other organic solvents
• Hydrolyze slowly in the presence of acid
• The reversibility of color formation is decreased when the I2
concentration is high
Remember
1. Starch may be added at the start of titration if the endpoint is
towards the appearance of blue color.
2. When iodine is present in excess, starch is added when the solution
is straw-colored.
Miscellaneous Reactions
• Dichromate Assays
• Nitrite Titrations
• Iodate Titrations
