Pharmaceutical Analytical Chemistry 3 Lecture Notes PDF

Academic Year: 2024/2025 Pharmaceutical Analytical Chemistry 3 (PA203) Lecture No. (3) Applications of Redox Titrations By...

Academic Year: 2024/2025 Pharmaceutical Analytical Chemistry 3 (PA203) Lecture No. (3) Applications of Redox Titrations By Dr: Ahmed Mogahed Haredy Pharmaceutical Analytical Chemistry Department 28 October 2024 www.merit.edu.eg 1  Academic Year: 2024/2025 Lecture’s Aim 1. Understanding Redox Reactions: Explain the principles of oxidation- reduction (redox) reactions, including oxidation states and electron transfer concepts. 2. Titration Techniques: Introduce the different types of redox titrations and discuss how they are performed. 3. Quantitative Analysis: Demonstrate how redox titrations can be used for quantitative analysis to determine the concentration of oxidizing or reducing agents in a solution. 28 October 2024 www.merit.edu.eg 2  Academic Year: 2024/2025 Lecture’s Competencies 1. Knowledge of Redox Principles: Understand the concepts of oxidation and reduction. Identify oxidizing and reducing agents in reactions. 2. Data Analysis and Interpretation: Analyze titration data, including the ability to construct and interpret titration curves. Calculate concentrations and equivalents based on titration results. 3. Application of Theoretical Concepts: Apply stoichiometric principles to solve problems related to redox reactions. Relate redox titration results to real-world scenarios in various fields, such as chemistry, environmental science, and medicine. 4. Critical Thinking and Problem Solving: Evaluate experimental designs and troubleshoot issues encountered during titrations. Assess the reliability and limitations of redox titration methods. 28 October 2024 www.merit.edu.eg 3  Academic Year: 2024/2025 Lecture’s Contents 1. Free elements I. Reducing free elements (Metallic iron) II. Oxidizing free elements (Free halogens) 2. Determination of peroxides: a. H2O2 b. ZnO2 c. Higher oxides of heavy metals. 3. Determination of oxides 4. Determination of cations A. Determination of Iron: 1. Ferrous 2. Ferric 3. Substances that reduce Fe+3 to Fe+2 4. Substances that oxidize Fe+2 to Fe+3 5. Determination of ferrocyanide and ferricyanide B. Determination of HgCl2 C. Determination of cations that form insoluble oxalates. 28 October 2024 www.merit.edu.eg 4  Academic Year: 2024/2025 Lecture’s Contents 5. Determination of Anions A. Determination of soluble oxalates B. Determination of sulphide, sulphite, thiosulphate, sulphate & persulphates. C. Determination of halides, chlorate and hypochlorite. 6. Determination of moisture content (Karl-Fischer reagent) 7. Determination of organic pharmaceutical compounds 8. Analysis of mixtures. 28 October 2024 www.merit.edu.eg 5  Academic Year: 2024/2025 Standard Oxidation Potential (Eo) 28 October 2024 www.merit.edu.eg 6 6  Academic Year: 2024/2025 1. Free elements 1. Metallic iron (Fe) It can be determined by dissolving it in a ferric chloride solution. The produced ferrous chloride is titrated with standard permanganate in the presence of Zimmermann reagent. Fe + 2FeCl3 3FeCl2 Iron oxides do not interfere. ≠ St. KMnO4 (self indicator) in the presence of Zimmermann reagent 28 October 2024 www.merit.edu.eg 7  Academic Year: 2024/2025 1. Free elements 2. Free halogens Iodine can be determined by direct titration with sodium thiosulphate solution. Bromine or chlorine displaces iodine from potassium iodide. I2 + 2Na2S2O3 → 2NaI + Na2S4O6 (sod. tetrathionate) Br2 + 2KI → I2 + 2KBr Cl2 + 2KI → I2 + 2KCl ≠ Stand. Na2S2O3 (Using starch as indicator) 28 October 2024 www.merit.edu.eg 8  Academic Year: 2024/2025 2. Determination of peroxides 1. Hydrogen peroxide A. as reducing agent By direct titration  Ce+4 (using ferroin indicator) 2Ce+4 + H2O2 → 2Ce+3 + O2 + 2H+ B. as an oxidizing agent By direct titration  KMnO4. (self indicator) 2MnO4− + 5H2O2 + 6H+ → 2Mn+2 + 5O2 + 3H2O (iodometrically) H2O2 + 2H+ + 2I− → I2 + 2H2O ≠ Stand. Na2S2O3 2. Zinc peroxide (Using starch as an indicator) ZnO2 + 2H+ → Zn+2 + H2O2  Ce+4, KMnO4 or + KI → I2  S2O3-2. 28 October 2024 www.merit.edu.eg 9  Academic Year: 2024/2025 2. Determination of peroxides Organic peroxides 1. Carbamide peroxide ✓ Topical antiseptic and disinfectant solution H2N-CO-NH2..H2O2 → H2N-CO-NH2 + H2O2 ✓ is assayed for H2O2 content iodometrically 2. Hydrous benzoyl peroxide ✓ Keratolytic and keratogenic agents for acne. ✓ It can be determined iodometrically. (C6H5COO)2 + 2I− + 2H+ → 2C6H5COOH + I2 28 October 2024 www.merit.edu.eg 10  Academic Year: 2024/2025 3. Determination of oxides 1. Higher oxides of manganese and heavy metals as MnO2, PbO2, Pb3O4 a. Iodometrically MnO2 + 4HCl → MnCl2 + Cl2 + 2H2O Cl2 + 2KI → I2  S2O3−2 b. Indirect titration with reducing agents MnO2 + 2Fe 2+ + 4H+ → Mn2+ + 2Fe 3+ + 2H2O MnO2 + C2O42- + 4H+ → Mn2+ + 2CO2 + 2H2O 2MnO2 + 2AsO33- + 4H+ → 2Mn2+ + 2AsO43- + 2H2O Known excess ≠ Stand. KMnO4 standard (self indicator) 28 October 2024 www.merit.edu.eg 11  Academic Year: 2024/2025 3. Determination of oxides PbO can be determined by dissolving the sample in glacial acetic acid → lead acetate and precipitating it as lead oxalate PbO + CH3COOH → Pb (CH3COO)2 + 2H+ Pb (CH3COO)2 + H2C2O4 → Pb C2O4  + 2 CH3COOH Known excess Filter and wash the ppt standard ≠ Stand. KMnO4 (self indicator) 28 October 2024 www.merit.edu.eg 12  Academic Year: 2024/2025 4. Determination of Cations A. Iron I. Ferrous salts: ferrous sulphate (FeSO4), ferrous ammonium sulphate ((NH₄)₂Fe(SO₄)₂)(Mohr’s salt), ferrous carbonate (FeCO3), ferrous sulphide (FeS), 1. Fe+2  KMnO4 after addition of Zimmermann’s reagent, self indicator. 2. Fe+2  K2Cr2O7 after adding H3PO4 and internal redox (diphenylamine) or external indicator. 3. Fe+2  Ce+4, irreversible methyl red indicator. 4. Fe+2  I2 in presence of F− or PO4−3 using starch. 28 October 2024 www.merit.edu.eg 13  Academic Year: 2024/2025 4. Determination of Cations A. Iron II. Ferric salts: by three methods ✓Ferric (Fe3+) reduced to (Fe2+) by pre-reductants 1- SnCl2 + Fe+3 → SnCl4 + Fe+2  KMnO4 after the addition of Zimmermann’s reagent, the self-indicator 2- Zn and H2SO4: 2Fe+3 + Znº + H+ → Zn+2 + 2Fe+2  KMnO4 H2SO4 accelerates the reduction by Znº, and the unreacted Znº is removed by filtration. 3- Amalgamated Znº (Znº + HgCl2). Excellent reducing agent (Jones reductor). 28 October 2024 www.merit.edu.eg 14  Academic Year: 2024/2025 4. Determination of Cations A. Iron ✓ Iodometrically: Fe+3/Fe+2 system E°= 0.77 I2/2I− system E°= 0.54 You must  difference between the two systems either by  I− conc. by addition of XSS I− or  I2 conc. by extraction with immiscible solvent as CHCl3 or CCl4. Fe+3 + I− → Fe+2 + I2  S2O3-2 using starch ✓ Direct titration with titanous chloride using methylene blue (irreversible) or thiocyanate as indicators (the endpoint is colorless due to the disappearance of either the blue color of MB or the red color of Fe(SCN)3, which is formed at the beginning) FeCl3 ≠ TiCl3 → FeCl2 + TiCl4 28 October 2024 www.merit.edu.eg 15  Academic Year: 2024/2025 4. Determination of Cations A. Iron III. Reductants that reduce Fe+3 → Fe+2 : 1- SnCl2 + Fe3+ → SnCl4 + Fe2+  KMnO4 2- Znº + 2Fe3+ → Zn+2 + 2Fe2+  KMnO4 3- Feº + 2Fe3+ → 3Fe2+  KMnO4 IV. Oxidants that oxidize Fe+2 → Fe+3 : 1- K2S2O8 + 2Fe2+ + 2H+ → 2Fe3+ + 2KHSO4 2- KClO3 + 6Fe2+ + 6H+ → 6Fe3+ + KCl + 3H2O 3- MnO2 + 2Fe2+ + 4H+ → 2Fe3+ + Mn2+ + 2H2O Known excess standard ≠ Stand. KMnO4 or K2Cr2O7 (self indicator) (Ferroin ind.) 28 October 2024 www.merit.edu.eg 16  Academic Year: 2024/2025 4. Determination of Cations A. Iron V. Ferrocyanide By direct titration  KMnO4 or  Ce4+ 1- 5[Fe(CN)6]4-  MnO4- +8H+→ 5[Fe(CN)6]3- + Mn2++3H2O (self indicator) 2- [Fe(CN)6]4-  Ce4+ → [Fe(CN)6]3- + Ce3+ (ferroin indicator) Ferricyanide 1- By iodometrical titration 2[Fe(CN)6]3- + 2I- → 2[Fe(CN)6]4- + I2  S2O3-2 (starch) we add H2SO4 and ZnSO4 (to precipitate Zn2[Fe(CN)6]) to ↑↑ the E° of [ferri]/[ferro] to oxidize iodide to iodine. 2- [Fe(CN)6]3- + pre-reductants → [Fe(CN)6]4-  MnO4- Remove xss e.g., Sulphite or sulphide, or sod. peroxide 28 October 2024 www.merit.edu.eg 17  Academic Year: 2024/2025 4. Determination of Cations B. Determination of HgCl2 HgCl2 is reduced firstly to Hg° by HCHO in Ca(OH)2 medium. Hg2+ + HCHO + 3OH- → Hg° + HCOO- + H2O Hg° + I2 → HgI2  + 2I- → [HgI4]2- known red ppt colorless Excess stand complex ≠ Stand. Na2S2O3 (starch as an indicator) 28 October 2024 www.merit.edu.eg 18  Academic Year: 2024/2025 4. Determination of Cations C. Cations form insoluble oxalates. (Ca2+, Ba2+ Sr2+, Mg2+, Cd2+, Bi3+, Zn2+, Ni2+, Co2+ & Pb2+) Ca2+ + H2C2O4 → Ca C2O4  + xss. H2C2O4 known Filter and then follow one of the Excess stand wash the ppt 2 ways (i) The washed precipitate is dissolved in dil. H2SO4 and ≠ KMnO4 at 60°C. or (ii) The excess oxalic acid in the filtrate and washing is back titrated with standard KMnO4 at 60°C. Oxidizing substances such as K2S2O8, KClO3, NO3-, and MnO2 can be determined by treating them with a known excess of oxalic acid. The residual oxalic acid is then back-titrated with standard KMnO4. 28 October 2024 www.merit.edu.eg 19  Academic Year: 2024/2025 5. Determination of Anions A. Soluble oxalates. Soluble oxalates  KMnO4 or Ce+4 in the presence of sulphuric acid and heating to 60°C. The slow reaction at the start becomes rapid after forming the reduction product (Mn+2 or Ce+3). 28 October 2024 www.merit.edu.eg 20  Academic Year: 2024/2025 5. Determination of Direct titration Anions 1. Sulphide S−2 ≠ I2 → 2I− + Sº  b. S2-, SO32-, S2O32- & Use dilute soln. to decrease the inclusion of I2 by Sº SO42- 2. Thiosulphate 2S2O3−2 ≠ I2 → S4O6−2 + 2I− Back titration. 3. Sulphite SO3−2 + I2 + H2O → SO4−2 + 2I− + 2H+ Known xss. St. S2O3−2 ≠ (starch indicator) standard 4. Sulphate SO4−2 + BaCrO4 → BaSO4 + CrO4−2 (filtrate) 2CrO4−2 (filtrate) + 2H+ → Cr2O7−2 + H2O Iodometrically +2KI → I2  S2O3−2 (starch) 28 October 2024 www.merit.edu.eg 21  Academic Year: 2024/2025 5. Determination of Anions C. Determination of halides, ClO3− and ClO− Chlorates (ClO3−) & Hypochlorites (ClO−) Iodometrically - - + - ClO3 + 6I + 6H Cl + 3I2 + 3H2O Chlorate ClO- + 2I- + 2H+ Cl- + I2 + H2O Hypochlorite ≠ Stand. Na2S2O3 (starch as an indicator) 28 October 2024 www.merit.edu.eg 22  Academic Year: 2024/2025 5. Determination of Anions C. Determination of halides, ClO3− and ClO− ✓e.g.,1: Chlorine in bleaching powder (calcium hypochlorite + basic chloride). Ca(OCl)2 CaCl2.Ca(OH)2.H2O + 4H+ → Cl2 + Ca2+ + 2H2O Acetic acid is used for acidification, e.g., 2,N-chlororganic compounds are used as water disinfectants; these in water release hypochlorous acid (HOCl), which is the active germicidal species. ClO− + 2I− + 2H+ → Cl− + I2 + H2O (iodometrically) 28 October 2024 www.merit.edu.eg 23  Academic Year: 2024/2025 5. Determination of Anions C. Determination of halides, ClO3− and ClO− (Chiniofon) 28 October 2024 www.merit.edu.eg 24  Academic Year: 2024/2025 Oxygen flask combustion method 1. The compound (e.g.,Chiniofon) is wrapped in filter paper attached to pt. wire and sealed in the stopper of a special oxygen-filled flask containing dilute Na2S2O5 (sodium metabisulphite) solution. 2. Combustion is complete within 30 sec at 1200°C. 3. The resulting iodine is absorbed (reduced) by Na2S2O5 forming iodide 28 October 2024 www.merit.edu.eg 25  Academic Year: 2024/2025 6. Determination of moisture content (Karl-Fischer reagent) Reagent: I2 + SO2 + anhyd. CH3OH and anhyd. pyridine. Sample containing moisture + reagent until the yellow color of the xss iodine appears. SO2 + I2 + H2O → SO3 + 2HI 3 N + SO3 + 2HI 2 N-HI + N-SO3 + CH3OH SO4CH3 N H 28 October 2024 www.merit.edu.eg 26  Academic Year: 2024/2025 7. Determination of organic pharmaceutical compounds Vitamin C (ascorbic acid) Iodimetrically HO OH O O + H + I2 + 2HI O O CH CH2 O O CH CH2 OH OH OH OH Polyhydroxy Alcohols Glycerol can be determined iodometrically: 3C3H8O3 + 7K2Cr2O7 + 28H2SO4 → 9CO2 + 40H2O + 7Cr2(SO4) + 7K2SO4 Known excess standard + 2KI → I2 ≠ Standard Na2S2O3 (chloroform) 28 October 2024 www.merit.edu.eg 27  Academic Year: 2024/2025 7. Determination Mercaptans (Thiol) compounds of organic Generally 2RSH ≠ I2 → RS-SR + 2HI e.g., Dimercaprol, Thioglycollic acid, D-penicillamine; can be determined pharmaceutical iodimetrically. compounds CH2 SH CH2 S S CH2 2 CH SH ≠+ 2I CH S S CH + 4HI 2 CH2 OH CH2 OH CH2OH Dimercaprol CH2 SH NaHCO3 CH2 S S CH2 2 ≠+ I2 + 2HI COOH COOH COOH Thioglycollic acid disulphide 28 October 2024 www.merit.edu.eg 28  Academic Year: 2024/2025 8. Analysis of Mixtures 1. Acetic & formic acids (Total ≠ OH ─ [ph.ph.] & formic ≠ MnO4─) 2. Oxalic acid & sulphuric acid (Total ≠ OH ─ [ph.ph.] & oxalic ≠ MnO4─) 3. Phenol & salicylic acid (Total ≠ bromometrically & salicylic acid ≠ OH ─ [ph.ph.]) 4. I2 & KI (Total I2/I− by Andrew's & I2 ≠ S2O3 2─ ) 5. Ferrous oxalate & oxalic acid (protoxalate) (Total ≠ MnO4 ─ & the produced Fe3+ pass through red. ≠ MnO4 ─ or iodometrically) 28 October 2024 www.merit.edu.eg 29  Academic Year: 2024/2025 Lecture’s References "Analytical Chemistry" by Gary D. Christian "Quantitative Chemical Analysis" by Daniel C. Harris "Chemistry: A Molecular Approach" by Nivaldo J. Tro "Principles of Instrumental Analysis" by Douglas A. Skoog, F. James Holler, and Timothy A. Nieman "Analytical Chemistry: A Modern Approach to Analytical Science" by David Harvey 28 October 2024 www.merit.edu.eg 30