Titrimetric

Analysis
1
 Physical Properties Of
Analytes
conductivity, electrode
potential, light emission
absorption, mass to
Methods of charge ratio and
Analysis fluorescence, many
more…

Classical/old Instrumental/
modern/new
Quantitativ
Qualitative e
Spectroscopi Chromatogr Electro-
c Methods aphic
recogni analytical
zed by Methods
color, Titration/
boiling Gravimetr Methods
point, y volumetric
solubili
ty, taste

2
 Quantitative
Chemical analysis
Measure volume
Measure consumed by
mass of the Titrimetric/
Gravimetry analyte
analyte volumetric

Based on
Based
method
type of rxn
employed

Direct
Indirect
titration
titration
Complex One std
Acid –base Preciptation Redox Two std soln
ometric soln

Permanganimetric Dichromatometric Titration involving iodine

Iodometri
iodimetric
c
3
Principles of Volumetric Analysis
Titration
Titrant
Analyte
Indicator
Equivalence point vs. end point
Titration error
Blank titration
Standardization
Standard solution
Secondary standard solution

4
 Principles of Volumetric Analysis…
Analyte: the s/b being analysed.
Titrate/Titrand : the substance being titrated i.e. the
analyte
Titrant: a solution of reagent that reacts with the
analyte. Has accurately known concentration.

Titration: a process where a standard solution

(titrant) is being added in a drop wise manner to
analyte to gain (to reach) a certain point. It is a
quantitative analysis b/c volume is recorded and so it
is => Volumetric analysis 5
Titration could be direct or back titration
Each can be accompanied by blank titration
Direct Titration

One in which the analyte is directly treated with titrant, and

the volume of titrant required for complete reaction is
measured
Titrant is added to analyte until the end point is observed
Titrant (known) + Analyte (unknown) →
Product

Blank Titration

The titration is carried out without any sample being present

Allows the analyst to measure any changes that occur to the
6
 Back Titrations
A process in which excess amount of standard solution is
added to a sample, and the amount of standard unreacted
with the sample determined by titration with a second
standard solution

Two steps involved

1. A known excess of standard reagent is added to the analyte

Reagent 1(known) + Analyte (unknown) → Product + Excess 1

2. A second standard reagent is used to titrate the excess of the first

reagent Reagent 2 (known) + Excess 1 (unknown) → Product

Amount of standard solution reacted with the sample is the
difference between total standard added & standard not reacted
with sample 7
 Back titrations…

Back titration is used in the case of:

 Volatile substances

Some amount would be lost during titration

 Substances for which a quantitative reaction

proceeds rapidly only in presence of excess of the
reagent

 Insoluble substances
8
 Back titration with blank determinations

Used if the procedure involves heating & subsequent

cooling of the sample, some of the volumetric reagent
may be lost either by evaporation or mechanically due to
splashing or bubbling
Used if the volumetric solution is unstable or if it alters
in strength during the assay
e.g. it is necessary to perform blank determinations in
assays which involve heating a liquid containing excess
of standard alkali, cooling, & back titrating the excess
Heating & cooling an alkaline liquid results in an apparent
change in strength if certain indicators are used

9
 Back titration with blank…
 This may be due to interaction of the reagent with glass
or absorption of atmospheric CO2
 Amount of change will be dependent upon the conditions
used
 In effect, the alkali must be standardized under the
conditions to be used in the determination, i.e. blank
determination
 The blank determination must be identical to the test
determination in every way except, of course, that there
is no sample in the blank
 This means that heating times, dilutions, etc... must
all be duplicated exactly 10
TITRATION IN PRACTICE
1
Accurately add of specific
volume of sample solution to a
conical flask using a pipette

Known: volume of sample

Unknown: concentration of
analyte in sample
2
Slowly add standard
solution from a burette to
the sample solution

Known: concentration of
the titrant
3
Add until just enough titrant
is added to react with all the
analyte

The end point is signaled by

some physical change or
detected by an instrument

Note the volume of titrant

used

Known: volume of the titrant

Titration with an Indicator

14
Equivalence pt, end pt and indicators
Equivalence point
 Occur when the volume of titrant added to the analyte is the exact stoichiometric
amount that is needed to bring the rxn to completion.
- Ideal /theoretical result
- Determined from titration curve—inflection pt
- Mostly not determined practically because no association with physical change

Analyte Titrant (colorless) (colorless)

Oxalic acid (purple)
(colorless)

Equivalence point occurs when 2 moles of MnO4- is added to 5 moles of Oxalic acid

15
Equivalence pt, end pt and indicators…
End point
 What we actually measure
- Marked by a sudden change in the physical property of the solution
- Associated with physical change such as change in color, pH, voltage,
current, absorbance of light.

 Occurs from the addition of a slight excess of titrant

- Endpoint does not equal equivalence point

Analyte Titrant (colorless) (colorless)

Oxalic acid (purple)
(colorless)
After equivalence point occurs, excess MnO 4- turns solution purple  Endpoint
16
 Titrations
End point…
 Titration Error
- Difference between endpoint and equivalence
point
- Corrected by a blank titration
i. repeat procedure without analyte
ii. Determine amount of titrant needed to
observe change
iii. subtract blank volume from titration

Titration error ： Et ＝ Vedp － Veqp

Ved ： actual volume of reagent ； Veq ： is the theoretical
volume to reach the equivalence point.

17
Introduction

Methods used to detect end point

PH meter => for neutralization
Color change/indicator
Precipitate formation

Potentiometery
Conductance

Thermometric/T0
Light absorption/Spectroscopy

18
 Titration Curve

 Titration curve is a plot of changes of some selected

solution property during titration

 Property selected depends on the titration

 In the case of alkalimetric titration we look for the changes in
solution pH

 In the case of complexometric titration we will usually trace

changes in metal concentration (using its logarithm or minus
logarithm on the plot)

 During redox titrations we are interested in the redox potential

in the solution and so on

19
Titration Curve…
Most titration curves have the same shape - plateau in the
first part, sharp rise (or fall) near equivalence point
(inflection point of the curve), followed by the second flat
part
The most important part of the curve is the one where the
changes are the fastest - close to the inflection point
Thanks to the fact that changes occur so fast there, and are
so large, they are usually easily detectable

That in turn helps us detect titration end point

20
 Titration Curve…
Titration of 25.0 mL Titration curve of acetic acid
solution of 0.100 M HCl with titrated with sodium
0.100 M NaOH hydroxide

21
Introduction Standard Solution
Solution whose concentration is exactly known by the analyst.

Primary standard solution

Prepared by dissolving carefully weighed quantity of a primary
standard in a suitable solvent and diluting it to a known volume in a
volume flask.
Eg. KHP( KH phthalate) = 204g=1mol in 1L = 1M
But for NaOH we won’t get exact 1M because it is not primary
standard
Secondary Standard solution
-Is a tirtant whose concentration is determined from the
stoichiometry of its reaction with a primary standard; Eg. NaOH
22
 Primary Standards/requirements
1. High purity
2. Atmospheric stability

3. Absence of hydrate water so that the composition of the solid

does not change with variations in relative humidity
4. Readily availability at modest cost
5. React quantitatively with other substances

6. Large in molecular weight => decrease weighing error

7. Dissolves readily in a solvent of choice
Standardization
Titrations
 Required when a non-primary titrant is used
- Prepare titrant with approximately the desired conc.
- Use it to titrate a primary standard
- Determine the concentration of the titrant
Standardization
Titration
titrant unknown
titrant known concentration
concentration

analyte known
analyte unknown concentration
concentration

25
26
 Introduction...…

Advantage of Titrmatric analysis

 Cheep
 Easy to conduct
 High precision and accuracy
 Portable
Limitation
 Non selective
 Time consuming

 Require large sample and reagent

27
Introduction

Requirements for Titrimetric reaction

 Reaction must be simple, rapid and complete

 Single reaction must occur at a time/no side rxn.

 Easy to express reaction in chemical equation
 Suitable standard solution
 Detectable end point

28
 Introduction…
Sources of errors in titrimetric analysis
 Loss of sample in weighing and transfer
 Contamination
 In proper mixing
 Impurities in primary standards (99.999%)
 Errors in weighing and reading of buretts
o Reading on burette should be done by seeing the lower
minscus
o And weighing with high significant digits
 Use of wrong indicators
 Personal errors

29
Introduction…

Units for expressing concentration

Percentage (%)
% (V/V) ml of solute per 100ml of solution.
%(W/V) g of solute per 100ml of solution.
%(W/W) g of solute per 100 g
PPM and PPB (part per million and part per billion)
For impurities specially metal impurities
PPM g of solute per 106 g of solution
PPB g of solutes per 109 g of solution

30
 Introduction…

Molarity (M)
No of moles of solute per volume on litter
M = No of moles/ Volume (l)

aA + tT  pP

Where:

n (A)= m/mwt and n (T) = M.V(l)

31
Introduction

A 40mg powder NaOH was added to a flask. Then a

distlled water was added to the flask up to 250 ml
mark. Calculate the molarity of the solution
Mwt NaOH = 40 gm

Molarity = No of moles / Volume (l)

= (given mass / molecular mass) / Volume (l)
= (0.04/40) / 0.25
= 0.004 M

32
 Introduction

A powder weighing 1.825gm was dissolved in half litter

distilled water and the morality was founded to be 0.1M
by strong acid base titration. What is the compound?

Given Given mass = 1.825 gm

Volume = 0.5 L
Molarity = 0.1 M

0.1 = (1.825 / X) / 0.5

X = 36.5

The compound X is HCL

33
Introduction

Normality (N)
no of equivalent of solute per litter.

N = no of equivalent (no.Eqwt) / V (l)

= no of mili equivalent / V (ml)

No of equivalent = given mass (m)/equivalent weight (Eqwt)

equivalent weight = Mwt/n, n— no. reaction unit

N= (no.Eqwt)/V(l)= (m/Eqwt)/V(l)= (m/ (Mwt/n))/V(l)

N= (n*m/Mwt)/V(l)= n*(m/Mwt)/V(l)= n* (mol/V(l))=n*M

34
 Introduction…

n=?
Neutralization no of H+ involved in the reaction

Redox reaction no of e- transfered in reaction, PPt and

complexometric rxn
Mostly normality is used for Neutralization

Dependent on the reaction

no. of equivalent A = no. of equivalent T

35
 Calculations in Titrimetry
Standard solution preparation
1. If 0.400grams of KHP (MW=204.23 g/mol) is titrated with approximately 0.100M NaOH,
what is the approximate volume (mL) of NaOH required to reach the endpoint? (the rxn
b/n them is 1:1. Reaction: NaOH + HOOC-C6H4-COOK NaOOC-C6H4-COOK + H2O

 Give; KHP= 0.4g, 204.23 g/mol, NaOH=0.1M, Required,

volume of NaOH
 mole of KHP=0.4g/204.23g/mole=1.96mmole
 mmole of KHP = mmole of NaOH…1.96mmole of NaOH.
MNaOH….mmole/volume
Volume of NaOH……………19.6ml
2. A beaker containing 0.400 g KHP (204.22g/mol) was titrated with NaOH solution. The pale pink
end point was reached after 19.24 mL of NaOH solution was dispensed. What is the molarity (in
mol/L) of the NaOH solution?(1:1)

 From question one millimole of NaOH’….1.96mmole,,,,,, so molarity of

NaOH….millimole/volume
36
 Molarity=1.96/19.24……………0.1M
 Calculations in titrimetry…
Back titration
1.435 g sample of dry CaCO3 and CaCl2 mixture was dissolved in 25.00 mL of
0.9892 M HCl solution. What was CaCl2 percentage in original sample, if 21.48
mL of 0.09312 M NaOH was used to titrate excess HCl(1:2)?

Moles of excess HCL-Moles of CaCO3 react with HCl = Moles of excess unreacted HCl

25ml*0.9892M-X = 21.48ml*0.0931M HCl

 Moles of CaCO3=22.73mmole.

 As calcium carbonate reacts with hydrochloric acid 1:2 (2 moles of acid per

1 mole of carbonate), original sample contained 22.73/2=11.37 mmole of

CaCO3, or 1.137 g (assuming molar mass of CaCO3 is 100.0 g).

 So original sample contained 1.137/1.435×100%=79.27% CaCO3 and 100.0-
72.27%=20.73% CaCl2.
37
Types Of Volumetric Titration

 The type of reaction provides us with a simple way to

discuss titrimetry under the following four categories:
Acid-base titrations
Depends on neutralization reactions

Complexometric titrations
Depends on complex formation

Preciptimetric titrations
Depends on precipitation reactions

Reduction-oxidation titrations
Depends on redox reactions

38
ACID BASE TITRATION
Of two type:
In Aqueous Medium
In Non-aqueous Medium

39
 Acid Base titration in aqueous medium

Defn: An acid base titration is a technique in which a solution

containing an acid (or base) is added drop wise to a
solution containing a base (or acid)

Acidic drugs: include aspirin, penicillin, sulfonamides, and

barbiturates
Basic drugs: include Alkaloids, atropine, codeine, and
epinephrine
Amphotoric drugs include amino acids, peptides

40
Aqueous cont…
 pH calculation
pH = -log [H+]
Importance of pH adjustment in pharmaceuticals
1. Formulation of aqueous and partially aqueous solution
a. Insure solubility
e.g. Procaine penicillin increases solubility by pH
b. Insures Stability
Riboflavin stable in acidic media
c. Insure compatibility (biological or dosage form)
2. Absorption, distribution and excretion of drugs
3. Pharmaceutical analysis
a. Ensures reaction
b. Separation
e.g., Alkaloid separation
41
Aqueous cont…

Buffer

Is a solution that resists change in pH when small amount

of acid or base is added
Buffer capacity
Amount of strong acid required to change the pH of 1L
buffer by 1 unit
Phosphate buffer is the most widely used buffer in
pharmaceuticals

42
 TITRATION CURVES
K
(A) + (R) (P)
analyte titrant product

Important points and regions:

2 points: before titration (at 0%) I. [A]
at the end point (at 100 %) III. [A] = [R]
2 regions: before the end point (0.00..1 – 99.99…%) II. [A] + [P]
after the end point (100.00..1 – ∞) IV. [P] + [R]

Titration curves:
1. Strong acid with strong base, Strong base with strong acid
2. Weak acid with strong base, Weak base with strong acid
3. Polyprotic acid with strong base
43
 TITRATION CURVES
1. Strong base with Strong acid with strong base
strong acid

e.g.
HCl + NaOH Cl– + Na+(H2O)
acid1 + base2 base1 + acid2
I. At the start: (very weak)
[H+] = [H3O+]=[HCl]0 [OH–] = [NaOH]0
pH = – log [HCl]0 pOH = – log [NaOH]0 pH = 14 – pOH
II. Before the end point:
[H+] = [H3O+]=[HCl]unreacted [OH–] = [NaOH]unreacted
pH = – log [HCl]unreacted pOH = – log [NaOH]unreacted
III. At the end point: [H+]≡ [OH–]
KW = 10–14 pH ≡ 7
IV. After the end point:
[OH–] = [NaOH]excess [H+] = [H3O+]=[HCl]excess
pOH = – log [NaOH]excess pH = – log [HCl]excess44
Aqueous cont…

Direct titration in neutralization reaction

1. Direct titration of strong acids with strong bases
Analyte = strong acid
Titrant = Strong Base e.g., NaOH, KOH, Ba(OH)2
Equivalence point is about PH 7
pH change at equivalence point is very sharp which means color
change will be immediate
E.g. HCl titrated with NaOH
Also for aldehydes and ketones in essential oils,
but first the compounds must first be treated with NH2OH.HCl
(Hydroxyl amine hydrochloride) and there will be production of HCl
which will be titrated.
RCHO + NH2OH.HCl R-CH=N-OH + HCl +H2O
45
Aqueous cont…

46
Aqueous cont…

2. Direct titration of strong base with strong acid

• Equivalence point PH is 7.
• pH change at the equivalence point is sharp

• Usually indicators with transition interval between

4 and 10 are used

E.g. Sodium carbonate, Sodium bicarbonate,

Thiopenton injection, methohexitone injection,
thiamine

47
Aqueous cont…

48
 TITRATION CURVES
II. Weak acid with strong base Weak base with strong acid
e.g. Titration of CH3COOH with NaOH , Titration of NH4OH with HCl:
I. At the start:
Weak acid Weak base
pH 
H  

K a C acid H  

K a CH 3 COOH OH   K b C base OH  

K b NH 4 OH

II. Before the end point:

Buffer (acid / salt) Buffer (base / salt)
H   K C

H   K CH COOH
acid
pH OH   K C
 a 3
OH   K NH OH  base  b 4
a
C salt CH COO 
3
 b
C salt NH 
4


III. At the end point:

Hydrolysing salt (Brönsted acid)
Hydrolysing salt (Brönsted base) pH Kw
OH    Kw
C salt H  


Kb
C salt
Ka

OH  

K b C salt OH  


K b CH 3 COO   H  

K a C salt H  


K a NH 4



IV. After the end point:

Excess of strong base Excess of strong acid
pH
[OH–] = [NaOH]excess [H+] = [HClexcess
49
[OH–] = Cexcess base [H+] = Cexcess acid
Aqueous cont…

1. Direct titration of week acids with strong bases

pH of the solution at the equivalence point is above pH 7

Week acid ions act as strong base.

CH3COOH CH3COONa CH3COO- + Na+

E.g. Benzoic acid, Salicylic acid, acetic acid,

chlorambucil, Busulfan.
N.B. Acid value of fixed oil which is number of mg of KOH
consumed by 1 g of fixed oil where increase in value is
increase in rancidity

50
Aqueous cont…

51
Aqueous cont…

CH3SO2(CH2)4OSO2CH3 + 2H2O

HO(CH2)4OH + 2CH3SO2OH

Buslfan methane sulfonic acid

nbusulfan = nmethane sulfonic acid = nNaOH
2 2
nbusulfan = nNaOH
2

52
Aqueous cont…

2. Direct titration of week bases with strong acids

Equivalence point pH is <7

pH at equivalence point is not sharp

E.g. Determination of aminophylline

53
Aqueous cont…

54
 TITRATION CURVES
III. Polyprotic acid with strong base
e.g. Titration of H3PO4 with NaOH
H3PO4 + OH– H2PO4– + H2O Ka1 = 7x10–3
H2PO4– + OH– HPO42– + H2OKa2 = 6x10–8
HPO42– + OH– PO43– + H2O Ka3 = 10–12

55
 TITRATION CURVES
EFFECTS ON THE TITRATION CURVE:
1. Effect of the temperature:
25°C [H+]·[OH–] = Kw = 10–14 Neutr. point: pH = 7
100°C [H+]·[OH–] = Kw = 10–12 Neutr. point: pH = 6

56
 EFFECTS ON THE TITRATION CURVE
2. Dependence on the initial concentrations (e.g. [HCl]):

[HCl]0 0% 50% 90% 99% 99.9% 100% 100.1% 101% 110%

↓
1N 0 0,3 1 2 3 7 11 12 13
0.1 N 1 1,3 2 3 4 7 10 11 12
0.01 N 2 2,3 3 4 5 7 9 10 11
0.001 N 3 3,3 4 5 6 7 8 9 10

pH change around the end point

ΔpH
3 – 11
4 – 10
5– 9
6– 8 57
0 100
 EFFECTS ON THE TITRATION CURVE
3. Dependence on the acid strength (dissociation constants):

A. Weak acid with strong bases ,

e.g. 10–1 N CH3COOH is titrated with NaOH (Ka = 2x10–5)
% 0 50 90 99 99.9 100 100.1 101 110

pH 2.9 4.7 5.7 6.7 7.7 8.9 10 11 12

B. Weak base with strong acid ΔpH pKInd ≈ 9 → PHENOLPHTALEIN

e.g. 10–1 N NH4OH is titrated with HCl (Kb = 2x10–5)
% 0 50 90 99 99.9 100 100.1 101 110

pH 11.1 9.3 8.3 7.3 6.3 5.1 4 3 2

ΔpH pKInd ≈ 5 → METHYL

58 RED
Aqueous cont…
Indicators used to detect end point in neutralization
reaction is governed by:
Ostwald’s theory
Because of ionization.
E.g. Phenolphthalein is color less in ionized state at
acidic media and get colored when it gets none
ionized or dissociated in basic media.
Chromophoric theory
Because of the change in double bond.
This theory says indicators should contain double
bond.
E.g azo-compouds

59
 ACID / BASE INDICATORS
1. PHTHALEIN-derivatives
General structure: INDICATOR R R1 R2 R3 pH
∆ Acidic
color
Basic
color
PHTALEINS COOH basic colorless colored
PHENOLPHTHALEIN COOH H H H 8.2 – colorless red
10.0
THYMOLPHTHALEIN COOH CH(CH3)2 H CH3 8.3 – colorless blue
10.5

SULFON- SO3H basic / colored colored

PHTHALEINS acidic
PHENOL RED SO3H H H H 6.4 – yellow red
8.0
THYMOL BLUE SO3H CH(CH3)2 H CH3 a)1.2 – red yellow
2.8 yellow blue
b)8.0 –
9.6

Mechanism: Thymol blue

Colorless Colorless Purple

(acidic) (intermediate) (basic) 60
 ACID / BASE INDICATORS
2. Azo-compounds
Genearal structure:
INDICATOR R1 R2 R3 pH
∆ Acidic Basic
color color
METHYL- -N(CH3)2 H SO3Na 3.1 – 4.4 red orange
ORANGE
METHYL -N(CH3)2 COOH H 4.4 – 6.2 red yellow
-RED
p-ETHOXY- -OC2H5 NH2 NH2 3.5 – 5.5 red yellow
CHRISOIDINE
TROPAEOLIN -SO3Na OH OH 11.1 – yellow orange
0 12.7!

Mechanism:

Yellow Yellow Red

(basic) (intermediate) (acidic)
(aromatic ) (protonated) (quinoid) 61
Acid-Base Titrations
2.) Choosing an Indicator
Transition Interval

- PH interval where the indicator shows

color change
-Eg. neutral red (6.8-8.0)

The difference between the end point

(point of detected color change) and the
true equivalence point is the indicator
error

Amount of indicator added should be

negligible

Indicators cover a range of pHs

Titrations
Back Titration
 Add excess of one standard reagent (known concentration)
- Mainly used: slow and incomplete rxn, undetectable end point, volatile analyte.
Completely react all the analyte
- Add enough MnO4- so all oxalic acid is converted to product

Analyte Titrant (colorless) (colorless)

Oxalic acid (purple)
(colorless)

 Titrate excess standard reagent to determine how much is left

- Add Fe2+ to determine the amount of MnO4- that did not react with oxalic acid

- Differences is related to amount of analyte

- Useful if better/easier to detect endpoint 63

Back Titration

Is advantageous if
End point of the reverse titration is easier to
identify than the end point of the normal titration

If the titration (reaction) between the analyte and

titrant is slow

Volatile analyte

Insoluble substances requiring excess volumetric

solution to affect solubility and reaction
64
Back Titration

Exercise
A 0.5130g sample of aspirin prepared by a standard
required 27.98 ml of 0.100M NaOH for neutralization.
42.78ml of 0.100M NaOH was added and the sample was
heated to hydrolyze the acetyl salicylic acid. After the
reaction mix cooled, the excess base was back titrated with
14.96ml of 0.1056M HCl.
a) how many grams of acetyl salicylic acid are in the sample
b) What is the percentage purity of the sample

COOH COONa
O
O C CH3 OH

+ 2NaOH CH3COONa +

65
Back Titration

First we will identify the excess NaOH

nNaOH = nHCl
0.1M * VNaOH = 14.96ml * 0.1056M
VNaOH excess = 15.8ml

Then we will identify the amount NaOH consumed

VNaOH consumed = VNaOH added --- VNaOH excess
VNaOH consumed = 42.78ml --- 15.8ml
VNaOH consumed = 26.98ml

66
Back Titration

Then we will identify the amount of ACA reacted with

NaOH
nACA = nNaOH / 2
X / 180.2 g = (26.98ml * 0.1M) ∕ 2
X = 243.0 mg = 0.2430g

Therefore 0.243g grams of acetyl salicylic acid are

in the sample

67
Back Titration

b) % purity
(Calculated / theoretical) * 100%
(0.243 / 0.513) * 100%
47.39%

Therefore the percentage purity of the sample is

47.39%.

68
Application

Estimation of esters by back titration

Excess of sodium hydroxide is added to the ester.

The following reaction occurs:

RCOOR’ + XSNaOH RCOONa + R’OH

The XSNaOH is back titrated with HCI using an

indicator.
69
Application cont…

Saponification value

The saponification value for a fixed oil is the number of

mg of KOH equivalent to 1 g of oil.

A high value means rancidity, a low value possible

adulteration with mineral oil.

Almost all edible oils have a saponifIcation value

between 188 and 196.

70
Application cont…

Calculation example
The following data were obtained for a sample of cod
liver oil:
Weight of oil taken for analysis 2.398 g
Ethanolic KOH (MW 56.1)
Amount of ethanolic KOH used for hydrolysis and in blank titration
25 ml
Amount of 0.470 M HCI required to neutralize excess KOH is
35.2 ml
Amount of 0.470 M HCI required in the titration of blank = 52.3 ml
71
Application cont…

First we will identify the concentration of KOH from

the blank.
nHCl = nKOH
0.470M * 52.3 ml = X * 25ml
X = 0.98

Then we will determine the volume excess of KOH

nHCl = nKOH
0.470M * 35.2ml = 0.98M * VKOH excess
VKOH excess = 16.88 ml

72
Application cont…

After that we will determine the amount of KOH

consumed by the codliver oil
VKOH consumed = VKOH added --- VKOH excess
VKOH consumed = 25ml --- 16.88ml
VKOH consumed = 8.12ml

Then we will determine the mg of KOH present in

8.12ml.
0.00812L * 56.1 g *0.98M = 0.44642g = 446.42mg

73
Application cont…

Note that 446.42mg of KOH was consumed by 2.398

g of cod liver oil.
So if 446.42mg by 2.398 g oil
Then X mg by 1g oil.

X = 186.2mg

74
Neutralization titration in non-aqueous medium

H2O is mostly commonly used solvent because

Easily available

Non toxic
Inexpensive
There are some circumstances where water can’t be used

If reactants are insoluble in H2O

Reactant and/or product may reacts with water

If analyte are too weakly basic and too weakly acidic

75
non-aqueous cont…

Types of Solvents
Aprotic solvent

o Neutral and chemically inert

o E.g. Tolune, benzene, CCl4 , Chloroform
(CHCl3)

Protrophilic solvent
o Are basic
o E.g. Pyridine, ethylene diamine
76
non-aqueous cont…

Protogenic solvent
o Are acidic
o E.g. Sulphuric acid
Amphiprotic solvents
o Having both protophilic and protogenic behavior
o E.g. Water, alcohol, weak acids
CH COOH + NaOH
3 CH3COONa + H2O

CH COOH + HClO
3 4 CH COOH2+ + ClO4-
3

77
non-aqueous cont…

Non-aqueous titration of basic drugs

Solvent
Non basic solvents: aprotic or acidic (protogenic)
E.g. Glacial acetic acid, formic acid, chloroform

Titrants
If we use sulfuric or hydrochloric acid, the acidity will be
reduced in the presence of acetic acid. So very strong
acids are needed.
E.g. Perchloric acid, para toluene sulphonic acid, floro
sulfonic acid

78
non-aqueous cont…

Preparation of 0.1 M HClO4

Slowly add 8.5 ml 72% HClO4 to about 900ml
glacial acetic acid with continuous mixing.
Similarly add about 30ml acetic anhydride, adjust
the volume to one litter with glacial acetic acid and
allow the solution to stand for 24hrs before use.

CH3COOH + HClO4 CH3COOH2+ + ClO4-

Onium ion

Acetic anhydride is important to remove water

from the system. 24Hrs
CH3COOCOCH3 + H2O --------> 2CH3COOH

79
non-aqueous cont…

To standardize, KHP is used.

Example of drugs(WB)
Levodopa Triametrene
Ethambutol HCL Diazepam
Adrenaline Chloradiazepoxide
Quinidine Mebendazole
Mentronidazole etc

80
non-aqueous cont…

OH L-dopa

OH CH2 CH COOH + CH3COOH2+

NH2

OH

OH CH2 CH COOH + CH3COOH

NH3+

81
non-aqueous cont…

Titration of halogen salts of bases

E.g. Amitriptyline HCl has very low basicity even

when titrated with non aqueous.
Hg acetate will remove HCL and form acetate ion
which is basic and can be titrated by onium ion.

The chloride or bromide salts of bases are too weakly

basic to react quantitatively with acetous perchloric
acid. Addition of mercuric acetate to a halide salt
replaces the halide ion by equivalent quantity of
acetate ion,
82
non-aqueous cont…

Be se
ba
c a Hi
us gh
Determination of amitripyline HCl

e ly
co ba
nj sic
ug
at
2C20H23N.HCl -------------- 2C20H23NH+ + 2Cl-

e
of
we
ek
(CH3COO)2Hg + 2Cl- -------- HgCl2 + 2CH3COO-
 
2CH3COO- + 2CH3COOH2+ -------------- 4CH3COOH

nAmp/2 = nCl-/2 = nonium /2 = nHClO4/2

nAmp = nHClO4

83
non-aqueous cont…

Non-aqueous titration of acidic drugs

Solvents: Non acidic, sometimes basic, Aprotic

Example: Ethylene diamine

n-butyl amine
Pyridine
DMF (N.N-dimethyl formamide)
Methanol
Ethanol, acetone, etc

84
non-aqueous cont…

Titrant:
Strong base
Methoxides of Li, Na, and K

Hydroxides such as NaOH can’t be used because

water will be formed and unlike basic, it is not
possible to remove it.

Tetra alkyl ammonium oxides

E.g. Tetra butyl ammonium hydroxide

85
non-aqueous cont…

Methoxides:
Metal + CH3OH ----------> Methoxides

we can’t use hydroxide of Na and K because they

will produce jelly products.
So hydroxide of Li or tetrabutyl ammonium
hydroxide is used.

86
non-aqueous cont…

1) 0.1560g pure benzoic acid was titrated to the metyl

blue end point in DMF solution with sodium methoxide
solution, 8.53ml being required. Calculate the molarity
of titrant.
COOH COONa

+ NaOCH3 + H20

Mwt benzoic = 122.12 g/mol

87
nbezoic = nMethox
0.1560g/122.12g/mol = M * (8.53/1000)l
M = 0.15 molar

88
 2) sample of Diphenhydramine HCl weighing 0.6120g was dissolved
by a glacial acetic acid. 15ml of 3.2% Hg(CH3COO)2 solution was added
and the mix was titrated to p-napholbenzein end point with 17.12 ml of
0.1145M HClO4. Calculate the % purity of the sample
Mwt DPH = 291.82 g/mol
CH3
CH3 +
N
HCl + 2Cl-
N O CH3
2 O CH3
2 H

2Cl- + Hg(CH3COO)2 --------> HgCl2 + 2CH3COO-

2CH3COO- + 2HClO4 --------> 2CH3COOH + ClO4- 89

nDp = nCl- = naceta = nHClO4

MassDph = MHClO4 * VHClO4

Mwt Dph

m = 0.1145M * 17.12 ml * 291.82g/mol

1000
= 0.572037

% = 0.572037 * 1000 = 93.47%

0.6120
90
THANK
YOU

91