PURIFICATION OF LABORATORY CHEMICALS Wilfred L. F.Armarego Christina U Un Chai COMMON PHYSICAL TECHNIQUES USED IN PURIFICATION 1 INTRODUCTION 1 THE QUESTION OF PURITY 1 SOURCES OF IMPURITIES 3 PRACTICES TO AVOID IMPURITIES 3 Cleaning practice 3 Silylation of glassware and plasticware .4 SAFETY PRECAUTIONS ASSOCIATED WITH THE PURIFICATION OF LABORATORY CHEMICALS 4 SOME HAZARDS OF CHEMICAL MANIPULATION IN PURIFICATION AND RECOVERY OF RESIDUES 5 Perchlorates and perchloric acid 5 Peroxides 5 Heavy -metal-containing explosives 5 Strong acids 6 Picric acid 6 Reactive halides and anhydrides 6 Salts and organic esters of some inorganic acids 6 Solvents 6 METHODS OF PURIFICATION OF REAGENTS AND SOLVENTS 7 SOLVENT EXTRACTION AND DISTRIBUTION 7 DISTILLATION 8 Techniques 8 Distillation of liquid mixtures 9 Types of distillation 10 The distilling flask 10 Types of columns and packings 10 Types of condensers 11 Vacuum distillation 11 Spinning-band distillation 12 Steam distillation 12 Azeotropic distillation 13 Kugelrohr distillation 13 Isopiestic or isothermal distillation 14 RECRYST ALLIS ATION 14 Techniques 14 Filtration 15 Solvents 15 Choice of solvents 15 Water 16 Petroleum ethers 16 Mixed solvents 16 Recrystallisation from the melt 17 Zone refining 17 CHROMATOGRAPHy 18 Vapour phase chromatography (GC or gas-liquid chromatography) 18 Liquid chromatography 18 Adsorption chromatography 19 Thin layer chromatography (TLC) 19 Paper chromatography 20 Column chromatography 20 Graded adsorbents and solvents 20 Preparation and standardisation of alumina 20 Preparation of other adsorbents 21 Silica 21 Diatomaceous earth 21 Charcoal 21 Cellulose 21 Supelco products 21 Flash Chromatography (FC and HPFC) 22 Paired- ion Chromatography (PIC) 22 Ion-exchange Chromatography 23 Ion-exchange Resins 23 Ion-exchange celluloses and sephadex 24 Sephadex 24 Sepharose 24 Cellex CM 25 Cellex D 25 Crystalline hydroxylapatite 25 Gel filtration 25 High performance liquid chromatography (HPLC) 25 Other types of liquid chromatography 26 Automated column chromatography 27 ELECTROPHORESIS 27 DRyING 27 Removal of solvents 27 Removal of water 27 Intensity and capacity of common desiccants 28 Suitability of individual desiccants 28 Molecular sieves 30 MISCELLANEOUS TECHNIQUES 31 Freeze-pump-thaw and purging 31 Vacuum lines, Schlenk and glovebox techniques 31 PROPERTIES USEFUL IN PURIFICATION 32 Ionisation constants - pK 32 pK and temperature 33 pK and solvent 33 Solubilities of gases in liquids 33 CHEMICAL AND BIOCHEMICAL SOURCES 34 TABLES 34 TABLE 1. FIGURE 1. TABLE 2A. TABLE 2B. TABLE 3. TABLE 4. TABLE 5. TABLE 6. TABLE 7. TABLE 8. TABLE 9. TABLE 10. TABLE 11. TABLE 12. TABLE 13. TABLE 14. SOME COMMON IMMISCIBLE OR SLIGHTLY MISCIBLE PAIRS OF SOLVENTS 34 NOMOGRAM 35 PREDICTED EFFECT OF PRESSURE ON BOILING POINT 36 PREDICTED EFFECT OF PRESSURE ON BOILING POINT 37 HEATING BATHS 38 WHA TMAN FILTER PAPERS 38 MICRO FILTERS 39 COMMON SOLVENTS USED IN RECRYSTALLISATION .40 PAIRS OF MISCIBLE SOLVENTS .40 MATERIALS FOR COOLING BATHS .41 LIQUIDS FOR STATIONARY PHASES IN GAS CHROMATOGRAPHy 42 METHODS OF VISUALISATION OF TLC SPOTS .42 GRADED ADSORBENTS AND SOLVENTS .43 REPRESENTATIVE ION-EXCHANGE RESINS .43 MODIFIED FIBROUS CELLULOSES FOR ION-EXCHANGE 43 BEAD FORM ION-EXCHANGE PACKAGINGS .44 LIQUIDS FOR DRYING PISTOLS .44 VAPOUR PRESSURES (mm Hg) OF SATURATED AQUEOUS SOLUTIONS IN EQUILIBRIUM WITH SOLID SALTS .45 DRYING AGENTS FOR CLASSES OF COMPOUNDS 46 STATIC DRYING FOR SELECTED LIQUIDS (25°C) 46 AQUEOUS BUFFERS 47 SOLUBILITY COEFFICIENTS OF AIR AT 1atm IN WATER .48 SOLUBILITY COEFFICIENTS OF O 2 AT 1atm IN WATER 48 BUNSEN COEFFICIENTS (~) OF GASES AT 1atm IN ORGANIC SOLVENTS AT 20°C 48 OSTWALD COEFFICIENTS (l)/L OF O 2 AT 1atm IN AQUEOUS SOLUTIONS AT 25°C .49 SOLUBILITIES OF HCI AND NH 3 AT 760mm (g/lOOg OF SOLUTION) 50 BOILING POINTS OF SOME USEFUL GASES AT 760 mm 50 PREFIXES FOR QUANTITIES 50 BIBLIOGRAPHy 51 TABLE 15. TABLE 16. TABLE 17. TABLE 18. TABLE 19. TABLE 20. TABLE 21. TABLE 22. TABLE 23. TABLE 24. TABLE 25. TABLE 26. CHEMICAL METHODS USED IN PURIFICATION 61 GENERAL REMARKS 61 REMOVAL OF TRACES OF METALS FROM REAGENTS 61 METAL IMPURITIES 61 DISTILLATION 61 SCAVENGER RESINS AND OTHER SUPPORTS 62 USE OF ION EXCHANGE RESINS 62 PRECIPITATION 62 Removal of lead contaminants 62 Removal of iron contaminants 62 Removal of other metal contaminants 63 EXTRACTION 63 COMPLEXATION 63 USE OF METAL HYDRIDES 63 LITHIUM ALUMINIUM HYDRIDE 63 CALCIUM HyDRIDE 63 SODIUM BOROHYDRIDE 63 POTASSIUM BOROHYDRIDE 64 PURIFICATION via DERIV ATIVES 64 ALCOHOLS 64 ALDEHYDES 65 AMINES 65 Picrates 65 Salts 65 Double salts 66 N- Acetyl derivatives 66 N- Tosy I derivatives 66 AROMATIC HyDROCARBONS 66 Adducts 66 Sulfonation 66 CARBOXYLIC ACIDS 66 4-Bromophenacy I esters 66 Alkyl esters 66 Salts 67 HYDRO PEROXIDES 67 KETONES 67 Bisulfite adduct 67 Semicarbazones 67 PHENOLS 67 Benzoates 67 Acetates 68 PHOSPHATE AND PHOSPHONATE ESTERS 68 MISCELLANEOUS 68 GENERAL METHODS FOR THE PURIFICATION OF CLASSES OF COMPOUNDS 68 PROCEDURES 68 CRITERIA OF PURITY 69 GENERAL PROCEDURES FOR THE PURIFICATION OF SOME CLASSES OF ORGANIC COMPOUNDS 69 ACETALS 70 ACIDS 70 Carboxylic acids 70 Sulfonic acids 70 Sulfinic acids 70 ACID CHLORIDES 71 ALCOHOLS 71 Monohydric alcohols , 71 Polyhydric alcohols 71 ALDEHYDES 71 AMIDES 71 AMINES 72 AMINO ACIDS 72 ANHYDRIDES 72 CAROTENOIDS 72 ESTERS 73 ETHERS 73 HALIDES 74 HyDROCARBONS 74 IMIDES 75 IMINO COMPOUNDS 75 KETONES 75 MACROMOLECULES 75 NITRILES 75 NITRO COMPOUNDS 76 NUCLEIC ACIDS 76 PHENOLS 76 POLYPEPTIDES AND PROTEINS 76 QUINONES 76 SALTS 76 With metal ions 76 With organic cations 77 With sodium alkane sulfonates 77 SULFUR COMPOUNDS 77 Disulfides 77 Sulfones 77 Sulfoxides 77 Thioethers (sulfides) 77 Thiols 77 Thiolsulfonates (disulfoxides) 77 THE FUTURE OF PURIFICATION 80 INTRODUCTION 80 ORGANOCATAL YSIS 80 MICROWAVE TECHNOLOGIES 81 SOLID PHASE SyNTHESIS 81 SOLID PHASE PEPTIDE SYNTHESIS (SPPS) 82 SOLID PHASE DEOXYRIBONUCLEOTIDE SYNTHESIS 82 POLYMER SUPPORTED REACTANTS 82 SCAVENGER RESINS 82 COMBINATORIAL CHEMISTRy 83 ALTERNATIVE SOLVENTS 83 SUPERCRITICAL FLUIDS 83 IONIC LIQUIDS 84 FLUOROUS CHEMISTRY 84 BIBLIOGRAPHy 85 PURIFICATION OF ORGANIC CHEMICALS INTRODUCTION 88 ALIPHATIC COMPOUNDS 89 ALICYCLIC COMPOUNDS 194 AROMATIC COMPOUNDS 223 HETEROCYCLIC COMPOUNDS 353 PURIFICATION OF INORGANIC AND METAL· ORGANIC CHEMICALS (Including Organic compounds of B, Bi, P, Se, Si, and ammonium and metal salts of organic acids) INTRODUCTION 445 INORGANIC COMPOUNDS 446 METAL-ORGANIC COMPOUNDS 505 PURIFICATION OF BIOCHEMICALS AND RELATED PRODUCTS INTRODUCTION 577 AMINO ACIDS and PEPTIDES 583 PROTEINS, ENZYMES, DNA and RNA 607 CAROTENOIDS 625 CARBOHyDRATES 631 STEROIDS 650 MISCELLANEOUS COMPOUNDS (including biologically useful reagents, Low-molecular-weight bioactive substances, antibiotics, coenzymes, vitamins, lipids, phospholipids, nucleosides, nucleotides and polynucleotides) 662 . PRECAUTIONS ASSOCIATED WITH THE PURIFICATION OF LABORATORY CHEMICALS 4 SOME HAZARDS OF CHEMICAL MANIPULATION IN PURIFICATION AND RECOVERY OF RESIDUES 5 Perchlorates. METHODS FOR THE PURIFICATION OF CLASSES OF COMPOUNDS 68 PROCEDURES 68 CRITERIA OF PURITY 69 GENERAL PROCEDURES FOR THE PURIFICATION OF SOME CLASSES OF ORGANIC