Classical and Thermal Methods docx

4/30/2012 1 Lecture Date: March 26 th , 2008 Classical and Thermal Methods 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 4/30/2012 2 Karl Fischer Titration (KFT)  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 A modern KF titrator  Karl Fischer titration is a widely used analytical technique for quantitative analysis of total water content in a material For more information about KFT, see US Pharmacopeia 921 Karl Fischer Reaction and Reagents CH 3 OH + SO 2 + RN [RNH] + SO 3 CH 3 - [RNH] + SO 3 CH 3 - + H 2 O + I 2 + 2RN [RNH] + SO 4 CH 3 + 2[RNH] + I - 0.2 M I 2 , 0.6M SO 2 , 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 I 2 is around when the reaction finishes)  Reaction:  Reagents: ester 4/30/2012 3 Volumetric Karl Fischer Titration  Volumetric KFT (recommended for larger samples > 50 mg) – One component  Titrating agent: one-component reagent (I 2 , SO 2 , base)  Analyte of known mass added – Two component (reagents are separated)  Titrating agent (I 2 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 H 2 O = 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 4/30/2012 4 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  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) Common Problems with Karl Fischer Titrations 4/30/2012 5 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 4/30/2012 6 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 4/30/2012 7 Applications of TGA H 2 0 Ca(C00) 2 CO CaC0 3 CO 2 Ca0 200 400 600 800 1000 Sample Temperature (°C) Sample Weight Decomposition of calcium oxalate  Composition  Moisture Content  Solvent Content  Additives  Polymer Content  Filler Content  Dehydration  Decarboxylation  Oxidation  Decomposition Typical TGA of a Pharmaceutical 1.080% (0.06419mg) 9.615% (0.5717mg) 18.90% (1.124mg) 0.0 0.2 0.4 0.6 0.8 1.0 1.2 Deriv. Weight (%/°C) 20 40 60 80 100 Weight (%) 0 50 100 150 200 250 300 350 Temperature (°C) Sample: SB332235 Size: 5.9460 mg Method: Standard Method Comment: CL42969-112A1 TGA File: Y: \TGA\SB332235\CL42969-112A1.001 Operator: J Brum Run Date: 18-Feb-05 14:45 Instrument: TGA Q500 V6.3 Build 189 Universal V3.8B TA Instruments Blue line shows derivative Green line shows mass changes 4/30/2012 8 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 4/30/2012 9 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 Glass transitions Crystallization Melting Oxidation Decomposition T = T s - T r Endothermic Rxns: fusion, vaporization, sublimation, ab/desorption dehydration, reduction, decomposition Exothermic Rxns: Adsorption, Crystallization oxidation, polymerization and catalytic reactions 4/30/2012 10 Applications of DTA Jacobson (1969) - studied effects of stearic acid and sodium oxacillin monohydrate  simple inorganic species  Phase transitions  determine melting, boiling, decomposition  polymorphism 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 [...]... 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 12 4/30/2012 Applications of DSC  DSC...4/30/2012 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... 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 . 2008 Classical and Thermal Methods Classical and Thermal Methods  Karl Fischer (moisture determination) – Representative of a wide variety of high-performance, modern analytical titration methods. class  Thermal Methods – Thermogravimetry (TG) – Differential thermal analysis (DTA) – Differential scanning calorimetry (DSC)  Reading: – KF:  Skoog et al. pgs 707-708 – Thermal methods: . 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 4/30/2012 6 Thermal