Transcript Classical Methods - Villanova University

Classical and Thermal Methods
Lecture Date: March 26th, 2008
Classical and Thermal Methods

Karl Fischer (moisture determination)
– Representative of a wide variety of high-performance, modern
analytical titration methods
– The only titration discussed in detail during this class

Thermal Methods
– Thermogravimetry (TG)
– Differential thermal analysis (DTA)
– Differential scanning calorimetry (DSC)

Reading:
– KF:
 Skoog et al. pgs 707-708
– Thermal methods:
 Skoog et al. Chapter 31
 Cazes et al. Chapter 15
Karl Fischer Titration (KFT)


Karl Fischer titration is a widely used analytical technique
for quantitative analysis of total water content in a material
Applications
– Food, pharma, consumer products
– Anywhere where water can affect
stability or properties

Karl Fischer (German chemist)
developed a specific reaction for
selectively and specifically
determining water at low levels.
– reaction uses a non-aqueous
system containing excess of sulfur
dioxide, with a primary alcohol as
the solvent and a base as the
buffering agent
For more information about KFT, see US Pharmacopeia 921
A modern KF titrator

Karl Fischer Reaction and Reagents
Reaction:
ester
CH3OH + SO2+ RN
[RNH]+SO3CH3- + H2O + I2 + 2RN

[RNH]+SO3CH3-
[RNH]+SO4CH3 + 2[RNH]+I-
Reagents:
0.2 M I2, 0.6M SO2, 2.0 M pyridine in methanol/ethanol
Pyridine Free (e.g. imidazole)


Endpoint detection: bipotentiometric detection of by a
dedicated pair of Pt electrodes
Detector sees a constant current during the titration, sudden
drop when endpoint is reached (I- disappears, and only I2 is
around when the reaction finishes)
Volumetric Karl Fischer Titration

Volumetric KFT (recommended for larger samples > 50
mg)
– One component
 Titrating agent: one-component reagent (I2, SO2,
base)
 Analyte of known mass added
– Two component (reagents are separated)
 Titrating agent (I2 and methanol)
 Solvent containing all other reagents used as
working medium in titration cell
Columetric of Karl Fischer Titration


Coulometric KFT (recommended for smaller samples < 50
mg)
– Iodine is generated electrochemically via dedicated Pt
electrodes
Q = 1 C = 1A x 1s where 1 mg H2O = 10.72 C
Two methods:
– Conventional (Fritted cell): frit separates the anode
from the cathode
– Fritless Cell: innovative cell design (through a
combination of factors but not a frit), impossible for
Iodine to reach cathode and get reduced
Common Problems with Karl Fischer Titrations

Titration solvents: stoichiometry of the KF reaction must be
complete and rapid
 solvents must dissolve samples or water may remain trapped
 solvents must not cause interferences

pH
– Optimum pH is 4-7
– Below pH 3, KF reaction proceeds slowly
– Above pH 8, non-stoichiometric side reactions are significant

Other errors:
– Atmospheric moisture is generally the largest cause of error in
routine analysis

When operated properly, KFT can yield reproducible water
titration values with 2-5% w/w precision
– E.g. sodium tartrate hydrate (15.66% water theory) usually yields
KFT values in the 15.0-16.4% w/w range
Common Problems with Karl Fischer Titrations

Aldehydes and Ketones
– Form acetals and ketals respectively with normal
methanol-containing reagents
– Water formed in this reaction will then be titrated to give
erroneously high water results
– With aldehydes a second side reaction can take place,
consuming water, which can lead to sample water
content being underestimated
– Replacing methanol with another solvent can solve the
difficulties (commercial reagents are widely available)
Oven Karl Fischer


Some substances only release their water at high
temperatures or undergo side reactions
– The moisture in these substances can be driven off in
an oven at 100°C to 300°C.
– The moisture is then transferred to the titration cell
using an inert gas
Uses:
– Insoluble materials (plastics, inorganics)
– Compounds that are oxidized by iodine
 Results in anomalously high iodine consumption
leading to an erroneously high water contents
 Includes: bicarbonates, carbonates, hydroxides,
peroxides, thiosulphates, sulphates, nitrites, metal
oxides, boric acid, and iron (III) salts.
Thermal Analysis


Thermal analysis: determining a specific physical
property of a substance as a function of temperature
In modern practice:

– The physical property and temperature are measured
and recorded simultaneously
– The temperature is controlled in a pre-defined manner
Classification:
– Methods which measure absolute properties (e.g.
mass, as in TGA)
– Methods which measure the difference in some
property between the sample and a reference (e.g.
DTA)
– Methods which measure the rate at which a property is
changing
Thermal Gravimetric Analysis (TGA)


Concept: Sample is loaded onto an accurate balance
and it is heated at a controlled rate, while its mass is
monitored and recorded. The results show the
temperatures at which the mass of the sample changes.
Selected applications:
– determining the presence and quantity of hydrated
water
– determining oxygen content
– studying decomposition
TG Instrumentation

Components:
– Sensitive analytical
balance
– Furnace
– Purge gas system
– Computer
Applications of TGA
Decomposition of calcium oxalate
Sample Weight
 Composition
 Moisture Content
 Solvent Content
 Additives
 Polymer Content
 Filler Content
 Dehydration
 Decarboxylation
 Oxidation
 Decomposition
H20
Ca(C00)2
CO
CaC03
CO2
Ca0
200
400
600
800
1000
Sample Temperature (°C)
Typical TGA of a Pharmaceutical
Sample: SB332235
Size: 5.9460 mg
Method: Standard Method
Comment: CL42969-112A1
File: Y:...\TGA\SB332235\CL42969-112A1.001
Operator: J Brum
Run Date: 18-Feb-05 14:45
Instrument: TGA Q500 V6.3 Build 189
TGA
100
1.2
1.080%
(0.06419mg)
9.615%
(0.5717mg)
18.90%
(1.124mg)
1.0
80
Weight (%)
60
0.6
Blue line shows derivative
Deriv. Weight (%/°C)
0.8
Green line shows mass changes
0.4
40
0.2
20
0
50
100
150
200
Temperature (°C)
250
300
0.0
350
Universal V3.8B TA Instruments
Differential Thermal Analysis (DTA)


Concept: sample and a reference material are heated at
a constant rate while their temperatures are carefully
monitored. Whenever the sample undergoes a phase
transition (including decomposition) the temperature of
the sample and reference material will differ.
– At a phase transition, a material absorbs heat without
its temperature changing
Useful for determining the presence and temperatures at
which phase transitions occur, and whether or not a
phase transition is exothermic or endothermic.
DTA Instrumentation
General Principles of DTA
H (+) endothermic reaction - temp of sample lags behind temp of
reference
H (-) exothermic reaction - temp of sample exceeds that of
reference
General Principles of DTA
T = Ts - Tr
Glass transitions
Crystallization
Melting
Oxidation
Decomposition
Endothermic Rxns:
fusion, vaporization, sublimation, ab/desorption
dehydration, reduction, decomposition
Exothermic Rxns:
Adsorption, Crystallization
oxidation, polymerization and catalytic reactions
Applications of DTA



simple inorganic
species
Phase transitions
determine melting,
boiling,
decomposition
 polymorphism
Jacobson (1969) - studied effects of stearic acid and sodium
oxacillin monohydrate
Differential Scanning Calorimetry (DSC)


Analogous to DTA, but the heat input to sample and
reference is varied in order to maintain both at a constant
temperature.
Key distinction:
– In DSC, differences in energy are measured
– In DTA, differences in temperature are measured

DSC is far easier to use routinely on a quantitative basis,
and has become the most widely used method for thermal
analysis
DSC Instrumentation

There are two common DSC methods
– Power compensated DSC: temperature of sample and
reference are kept equal while both temperatures are
increased linearly
– Heat flux DSC: the difference in heat flow into the
sample/reference is measured while the sample
temperature is changed at a constant rate
Heat Flow in DSC
DSC Step by Step
Glass transition
Recrystallization
Melting
Applications of DSC


DSC is usually carried
out in linear increasingtemperature scan mode
(but can do isothermal
experiments)
– In linear scan mode,
DSC provides
melting point data for
crystalline organic
compounds and Tg
for polymers
DSC trace of polyethyleneterphthalate (PET)
Easily used for detection of bound crystalline water
molecules or solvents, and measures the enthalpy of
phase changes and decomposition
Applications of DSC


DSC is useful in studies
o polymorphism in
organic molecular
crystalline compounds
(e.g. pharmaceuticals,
explosives, food
products)
Example data from two
“enantiotropic”
polymorphs
DSC of a Pharmaceutical Hydrate
Sample: SB332235
Size: 3.0160 mg
Method: STANDARD DSC METHOD
Comment: CL42969-112A1
DSC
File: Y:...\DSC\SB332235\CL42969-112A1.002
Operator: J Brum
Run Date: 24-Feb-05 09:53
Instrument: DSC Q1000 V9.0 Build 275
0.5
0.0
Heat Flow (W/g)
56.35°C
34.97J/g
134.06°C
116.0J/g
-0.5
84.39°C
-1.0
Loss of water
153.30°C
Melt
Decomposition
-1.5
0
Exo Up
50
100
150
Temperature (°C)
200
250
300
Universal V3.8B TA Instruments
Optional Homework
Questions: 31-1, 31-3, 31-4, 31-6, 31-9, 31-10