Experimental Organic Chemistry

Experimental Organic Chemistry, is designed for a two semester, sophomore level organic lab course and can be used as a primary text or a valuable reference tool for students. Rather than emphasizing microscale or macroscale, this lab manual focuses on the actual experiments and the learning process by using a multiscale approach. Palleros has great depth and a wide variety of experiments targeting chemistry, pre-med, biochemistry, and molecular biology students.

Section 1 The Basics 1 Unit 1 Laboratory Safety 3 1.1 General Safety Guidelines 3 1.2 Chemical Toxicity 6 1.3 Dealing with Chemicals and Waste Disposal 7 1.4 Online Safety Resources 15 Unit 2 Basic Concepts 19 2.1 Polarity and H-Bonds 19 2.2 Physical Data 23 2.3 Solvents 24 2.4 Balancing Chemical Equations 26 2.5 Concentration Units 28 2.6 Moles and Millimoles 29 2.7 Mineral Acids 31 2.8 Calculation of Yields 32 2.9 Scaling Up, Scaling Down 34 2.10 Keeping Lab Books and Writing Lab Reports 34 2.11 Chemical Literature 35 Unit 3 Basic Operations 45 3.1 Handling Liquids 45 3.2 Heating 46 3.3 Filtration 47 3.4 Refluxing 51 3.5 Evaporation 53 3.6 Centrifugation 55 3.7 Caring for Glassware 55 3.8 Measuring Pressure 57 Section 2 The Experiments 59 Unit 4 Recrystallization and Melting Point 61 4.1 Overview 61 4.2 Recrystallization 62 4.3 Decolorizing Charcoal 69 4.4 Recrystallization from Mixed Solvents 70 4.5 Microscale Recrystallization 70 4.6 Melting Point 71 4.7 Sublimation 75 Experiment 4 Recrystallization of Acetanilide and Urea 79 E4.1 Recrystallization of Acetanilide 80 E4.2 Microscale Recrystallization of Urea 82 E4.3 Determination of Melting Points 82 Unit 5 Extraction 86 5.1 Introduction 86 5.2 Solvent-Solvent Partitioning 86 5.3 Macroscale Liquid-Liquid Extraction 92 5.4 Microscale Liquid-Liquid Extraction 93 5.5 Drying the Organic Layer 94 5.6 Solid-Liquid Extraction 95 5.7 Countercurrent Distribution 97 Experiment 5 Isolation of Caffeine from Tea 103 E5.1 Tea, Coffee, and Caffeine 103 E5.2 Caffeine from Tea: Overview of the Experiment 105 E5.3 Isolation of Caffeine 109 E5.4 Purification of Caffeine by Sublimation 110 E5.5 Purification of Caffeine by Recrystallization (Alternative Procedure) 111 Unit 6 Distillation — Separation and Purification of Organic Liquids 113 6.1 Boiling Point 113 6.2 Boiling Point and Molecular Structure 114 6.3 Simple Distillation 115 6.4 Fractional Distillation 120 6.5 Ideal and Nonideal Solutions 123 6.6 Azeotropic Mixtures 124 6.7 Fractionating Columns 125 6.8 Microscale Distillation 126 6.9 Boiling Point Determination 128 6.10 Vacuum Distillation 129 6.11 Steam Distillation 130 Experiment 6A Distillation of Alcohols 136 E6A.1 Distillation of Methanol from a Mixture with Ferric Chloride 136 E6A.2 Separation of Methanol-Water by Simple Distillation 137 E6A.3 Separation of Methanol-Water by Fractional Distillation 138 E6A.4 Analysis of the Distillation Fractions by Density 139 Experiment 6B Isolation of Anise Oil 142 E6B.1 Overview 142 E6B.2 Isolation of Anise Oil 142 Unit 7 Gas Chromatography 144 7.1 Introduction 144 7.2 The Chromatographic Methods 144 7.3 Partition Chromatography 146 7.4 Gas Chromatography 149 7.5 The Gas Chromatograph 151 7.6 Measuring the Retention Time 155 7.7 Integration 156 7.8 Quantitative Analysis 157 7.9 Quantitative Analysis: A Closer Look (Advanced Level) 158 7.10 Qualitative Analysis 161 7.11 Running GC: Step by Step 162 7.12 Gas Chromatography Do’s and Don’ts 163 Experiment 7A Gas Chromatography of Alcohols 167 E7A.1 Analysis of Alcohols 167 E7A.2 Separation of Methanol and Water 168 Experiment 7B Analysis of Anise Oil 170 E7B Analysis of Anise Oil 170 Unit 8 Thin-Layer Chromatography 172 8.1 Overview 172 8.2 The Adsorption Process 173 8.3 Selection of TLC Conditions 175 8.4 Running TLC Plates 178 8.5 Adsorption Isotherms (Advanced Level) 182 8.6 Applications of TLC 184 8.7 Other Stationary Phases 186 8.8 TLC Do’s and Don’ts 186 Experiment 8 TLC Analysis of Vegetable Extracts 190 E8.1 Plant Pigments 190 E8.2 Isolation and Analysis of Plant Pigments 192 Unit 9 Column Chromatography 197 9.1 Overview 197 9.2 Practical Aspects 197 9.3 Applications 202 9.4 Column Chromatography Do’s and Don’ts 203 Experiment 9 Isolation of C60 from Fullerene Soot 206 E9.1 Fullerenes 206 E9.2 Isolation of Fullerenes 207 E9.3 A Chemical Test for Fullerenes 208 E9.4 Overview of the Experiment 209 E9.5 Isolation of C60 from Fullerene Soot 209 Unit 10 High-Performance Liquid Chromatography 214 10.1 Overview 214 10.2 HPLC Systems 214 10.3 HPLC Versus GC 215 10.4 Solvents 216 10.5 Pumps 217 10.6 Injection Port 217 10.7 Columns 218 10.8 Detectors 219 10.9 Why is HPLC High Performance? 220 10.10 Reversed-Phase Chromatography 221 10.11 Other Chemically Bonded Stationary Phases 222 10.12 Size-Exclusion Chromatography 223 10.13 Quantitative Determinations: Standard Curve Method 224 10.14 HPLC Do’s and Don’ts 224 Experiment 10 Vitamin Analysis—A Quantitative Study 227 E10.1 Water-Soluble and Fat-Soluble Vitamins 227 E10.2 Vitamin Stability 229 E10.3 International Units 230 E10.4 Characterization of Vitamin A 230 E10.5 Overview of the Experiment 231 Unit 11 Refractometry and Polarimetry 238 11.1 Refractive Index 238 11.2 The Refractometer 239 11.3 Measuring the Refractive Index 240 11.4 Polarimetry 242 11.5 The Polarimeter 245 11.6 Measuring the Optical Rotation 246 11.7 Optical Rotation of Mixtures 247 Experiment 11A Analysis of Essential Oils 250 E11A.1 Terpenoids 250 E11A.2 Essential Oils 252 E11A.3 Specific Rotation 253 E11A.4 Refractive Index 253 E11A.5 Composition of Essential Oils 253 Experiment 11B Separation of Carvone and Limonene 255 E11B.1 Carvone and Limonene 255 E11B.2 Analysis of the Crude Oils 256 E11B.3 Separation of Carvone and Limonene 257 Unit 12 Alcohols and Alkenes 261 12.1 Alkenes from Alcohols 261 12.2 Dehydration Mechanisms 262 12.3 Characterization of Alkenes 264 Experiment 12 The Dehydration of Methylcyclohexanols 268 E12.1 Overview 268 E12.2 Dehydration of Methylcyclohexanols 269 E12.3 Analysis of the Product Mixture 270 Unit 13 Alkyl Halides 273 13.1 Preparation 273 13.2 Reactions 274 13.3 Alkyl Halides from Alcohols 274 13.4 Characterization Tests 276 Experiment 13 Synthesis of n-ButyI Bromide and 2-ChIoro-2-MethyIbutane 280 E13.1 Synthesis of n-Buty1 Bromide 280 E13.2 Synthesis of 2-Ch1oro-2-Methy1butane 284 E13.3 Characterizahon Tests 285 Unit 14 Acid-Base Extraction 292 14.1 Introduction 292 14.2 Acids and Bases 292 14.3 Structural Effects on Acid-Base Properties 294 14.4 Acid-Base Extraction 298 14.5 Overview 303 Experiment 14A Isolation of Eugenol from Cloves 307 E14A.1 Ancient Medicine 307 E14A.2 Eugenol from Cloves: Overview of the Experiment 307 E14A.3 Isolation of Eugenol 308 E14A.4 GC and IR Analyses 310 Experiment 14B Isolation of the Active Ingredients in an Analgesic Tablet 315 E14B.1 Overview 315 E14B.2 Separation of the Active Ingredients in Excedrin 317 E14B.3 Analysis 317 Unit 15 Phenols and Ethers 323 15.1 Phenols and Ethers 323 15.2 Williamson Ether Synthesis 323 15.3 Characterization of Phenols: Ferric Chloride Test 324 15.4 IR and NMR of Phenols and Ethers 325 Experiment 15 Medicinal Chemistry: From Tylenol to a Banned Chemical 327 E15.1 Analgesics 327 E15.2 The Experiment: Overview 329 E15.3 Conversion of Acetaminophen into Phenacetin 330 E15.4 Ferric Chloride Test 332 E15.5 Analysis of Analgesics by TLC 332 Unit 16 Electrophilic Aromatic Substitution 336 16.1 Mechanism of Electrophilic Aromatic Substitution 336 16.2 Nitration and Halogenation 337 16.3 Effects of Substituents 338 Experiment 16A lodinatian of Tyrosine 342 E16A.1 Synthesis of 3,5-Diiodotyrosine 342 Experiment 16B Two Substitution Puzzles 350 E16B.1 Overview 350 E16B.2 NMR Analysis 351 E16B.3 Nitration of Phenacetin 352 E16B.4 Bromination of Phenacetin 353 Unit 17 Nucleophilic Aromatic Substitution 355 17.1 Nucleophilic Aromatic Substitution 355 17.2 Dinitroanilines 356 Experiment 17 Dinitrocompounds—Herbicides 360 E17.1 Synthesis of Trifluralin 360 E17.2 Synthesis of N -(n-Buty1) -2,4-Dinitroani1ine 361 E17.3 Herbicide Effects of Trifluralin and N -(n-Butyl) -2,4-Dinitroaniline 362 Unit 18 Chemical Kinetics 368 18.1 Mechanistic Studies 368 18.2 Chemical Kinetics 368 18.3 Experimental Aspects 370 18.4 Integrated Rate Equations 370 18.5 Reaction Half-Life 372 18.6 Transition States 372 18.7 Dependence of the Rate Constant with Temperature: Arrhenius Equation 375 18.8 Following the Kinetics 375 18.9 Best Fit 377 Experiment 18 Nucleophilic Aromatic Substitution Kinetics 381 E18.1 The Problem 381 E18.2 To Follow the Kinetics 383 E18.3 Overview of the Experiment 383 E18.4 Synthesis of 2,4-Dinitroanisole 384 E18.5 Visible Spectrum of N-(n-Butyl) -2,4-Dinitroaniline 384 E18.6 Beer’s Law of N-(n-Butyl) -2,4-Dinitroaniline 385 E18.7 Kinetics of the Reaction of 2,4-Dinitroanisole with n-Butylamine in Methanol 385 Unit 19 Diels-Alder Reaction 391 19.1 Diels—Alder Reaction 391 19.2 Endo versus Exo 392 19.3 Solvent Effects 393 19.4 Experimental Considerations: Following the Reaction 395 Experiment 19A Diels—Alder Reactions in Toluene 398 E19A.1 Reaction of 9-Anthraldehyde with Maleic Anhydride 398 E19A.2 Reaction of Phencyclone with Norbornadiene 400 Experiment 19B Diels—Alder Reaction in Water 408 E19B.1 Reaction of 9-Anthracenemethanol with N-Ethylmaleimide 408 E19B.2 Kinetics of the Reaction of 9-Anthracenemethanol with NEM 409 Unit 20 Aldehydes and Ketones 415 20.1 Introduction 415 20.2 Preparation 416 20.3 Reactions of Aldehydes and Ketones 416 20.4 IR and NMR of Aldehydes and Ketones 423 Experiment 20A Identification of Aldehydes and Ketones 427 E20A.1 Characterization Tests 428 E20A.2 Preparation of Derivatives 430 E20A.3 The Unknown 430 Experiment 20B Synthesis of trans-Cinnamic Acid 433 E20B Synthesis of trans-Cinnamic Acid: Perkin Condensation, 433 Unit 21 Oxidation-Reduction 438 21.1 Overview 438 21.2 Selectivity 439 21.3 Oxidations 440 21.4 Phase Transfer Catalysis 444 21.5 Reductions 445 Experiment 21 Oxidation-Reduction 451 E21.1 Reduction of Benzophenone 451 E21.2 Oxidation of Benzhydrol 452 E21.3 Reduction of trans-Cinnamaldehyde 453 E21.4 Oxidation of trans-Cinnamyl Alcohol 454 E21.5 Reduction of Camphor 455 E21.6 Oxidation of Isoborneol 456 E21.7 Synthesis of Terephthalic Acid 456 E21.8 Monoreduction of m-Dinitrobenzene 458 Unit 22 Esters 473 22.1 Esters in Nature and Society 473 22.2 Preparation of Esters 474 22.3 Acetylation 476 22.4 Ester Hydrolysis 476 22.5 Characterization of Esters 477 22.6 IR and NMR of Esters and Carboxylic Acids 477 Experiment 22A Preparation of Fruity Fragrances 480 E22A.1 Preparation of Methyl trans-Cirinamate: A Component of Strawberry Aroma 480 E22A.2 Preparation of n-Propy1 Acetate and Isoamyl Acetate 482 E22A.3 Hydroxamic Acid Test 484 Experiment 22B Transforming Bengay into Aspirin 491 E22B.1 Overview 491 E22B.2 Separation of Methyl Salicylate, 493 E22B.3 Hydrolysis of Methyl Salicylate, 493 E22B.4 Synthesis of Aspirin 494 E22B.5 Analysis 494 Unit 23 Multistep Synthesis 499 23.1 Overview 499 23.2 Multistep Synthesis 500 23.3 Retrosynthetic Analysis 502 23.4 Planning a Multistep Synthesis 507 23.5 Linear versus Convergent Synthesis 508 Experiment 23A Synthesis of an Ant Alarm Pheromone: 2-Methyl-4-Heptanone 511 E23A.1 Overview 511 E23A.2 Synthetic Route 511 E23A.3 Grignard Reactions 512 E23A.4 Oxidation of Secondary Alcohols 514 E23A.5 Synthesis of 2-Methyl-4-Heptanol 514 E23A.6 Synthesis of 2-Methyl-4-Heptanone 516 E23A.7 Vacuum Distillation 516 Experiment 23B Synthesis of Ionones: An Open-Ended Experiment 520 E23B.1 lonones 520 E23B.2 Synthetic Pathway 520 E23B.3 Characterization of lonones 522 E23B.4 Preparation of Pseudoionones 523 E23B.5 Cyclization with Sulfuric Acid-Acetic Acid 524 E23B.6 Cyclization with Phosphoric Acid 525 Unit 24 Molecules of Life 532 24.1 Proteins 532 24.2 Carbohydrates 539 Experiment 24 Chemistry of Milk 546 E24.1 Composition of Milk 546 E24.2 Isolation and Characterization of Casein 549 E24.3 Isolation and Characterization of Lactose 552 Unit 25 Lipids 556 25.1 Fats and Oils 556 25.2 Characterization of Oils 558 25.3 Uncommon Fatty Acids and Related Compounds 559 25.4 Saponification 560 25.5 Steroids 560 25.6 Bile Acids 562 25.7 Inclusion Compounds 562 Experiment 25 Lipids 566 E25.1 Analysis of Oils 566 E25.2 Trimyristin From Nutmeg 567 E25.3 Preparation of Azelaic Acid from Castor Oil 569 E25.4 Urea Complexes of Fatty Acids 570 E25.5 Solubility of Cholesterol 570 E25.6 Bile Acids 571 Unit 26 Polymers 577 26.1 Introduction 577 26.2 Chain-Reaction Polymerization 579 26.3 Step-Reaction Polymerization 581 26.4 Polymer Structure 583 26.5 Some Typical Polymers 584 26.6 Plasticizers 588 26.7 Applications and Recycling 589 26.8 Identification of Plastics 590 Experiment 26 Synthesis and Analysis of Polymers 595 E26.1 Overview 595 E26.2 Emulsion Polymerization of Styrene with Persulfate 596 E26.3 Emulsion Polymerization of Methyl Methacrylate 597 E26.4 Bulk Copolymerization of Styrene and Divinylbenzene: Effect of a Plasticizer 598 E26.5 Bulk Polymerization of Methyl Methacrylate 599 E26.6 Cellulose Triacetate 599 E26.7 Phenolic Resins 601 E26.8 Preparation of Nylon 6.6: The Nylon Rope Trick 601 E26.9 Analysis of Polymers 602 Unit 27 Dyes and Pigments 27.1 Dyes, Pigments, and Colors 611 27.2 Azo Dyes 612 27.3 Synthesis of Azo Dyes 613 27.4 Cationic Dyes 615 27.5 Anthraquinone Dyes 616 27.6 Indigo Dyes 617 27.7 Other Dyes 618 27.8 Mode of Application 619 27.9 Dyeing 620 Experiment 27 Colored Chemistry 626 E27.1 Direct Dyes 627 E27.2 Mordant Dyeing 630 E27.3 Ingrain Dyes 630 E27.4 Vat Dyes 632 E27.5 Dye Fastness 633 Unit 28 Bioorganic Chemistry 635 28.1 Enzymes: Biological Catalysts 635 28.2 How Enzymes Work 635 28.3 Using Enzymes 637 28.4 Prochiral Molecules 639 28.5 Reduction of Ketones 640 28.6 Enantiomeric Excess 642 Experiment 28 Asymmetric Synthesis with Baker’s Yeast: An Open-Ended Experiment 645 E28.1 Overview 645 E28.2 Investigating the Course of the Reaction 646 E28.3 Conformational Analysis: Determining Whether the Diol is Threo or Erythro (Advanced Level) 647 E28.4 Reduction of 1-Pheny1-1,2-Propanedione with Baker’s Yeast 649 E28.5 Analysis 650 Unit 29 Molecules of Heredity 653 29.1 Nucleosides and Nucleotides 653 29.2 Base Pairing 656 29.3 Purine and Pyrimidine Bases 657 29.4 Chemical Transformations 658 Experiment 29 Analysis of Nucleosides 662 E29.1 Overview of the Experiment 662 E29.2 Analysis of an RNA Digest 662 E29.3 Deamination of Cytidine to Uridine 664 Section 3 Spectroscopy 667 Unit 30 Absorption Spectroscopy 669 30.1 The Nature of Light 669 30.2 Interaction between Electromagnetic Radiation and Matter 670 30.3 Absorption Spectroscopy 672 Unit 31 Infrared Spectroscopy 675 31.1 Molecular Vibrations 675 31.2 Stretching and Bending Vibrations 677 31.3 IR and Dipole Moment 679 31.4 Regions of the IR Spectrum 680 31.5 Experimental Aspects 681 31.6 Interpreting IR Spectra 685 31.7 Case Studies 693 31.8 Concentration and Solvent Effects on IR 695 31.9 Instrumentation 697 Unit 32 Ultraviolet-Visible Spectroscopy 707 32.1 Electronic Transitions 707 32.2 Chromophores and Auxochromes 709 32.3 Structural Effects on UV-Visible Spectra: Woodward—Fieser Rules 710 32.4 Applications of UV-Visible Spectroscopy 711 32.5 Spectrophotometers 714 Unit 33 Nuclear Magnetic Resonance 719 33.1 Nuclear Spin 719 33.2 The Resonance Phenomenon: A Closer Look 721 33.3 Obtaining the NMR Spectrum 724 33.4 1H-NMR 726 33.5 Electronic Shielding 727 33.6 The Chemical Shift 729 33.7 Effect of Pi Electrons 730 33.8 Hydrogen Equivalence: A Closer Look 732 33.9 Integrals 732 33.10 Spin-Spin Splitting 734 33.11 Typical Coupling Patterns 739 33.12 The Coupling Constant 739 33.13 Coupling: A Closer Look 742 33.14 Chemical Shift Correlations 750 33.15 Coupling of Hydrogens Attached to Heteroatoms 756 33.16 13C-NMR 758 33.17 13C-NMR Chemical Shifts 760 33.18 Aromatic Systems 765 33.19 Effect of Chirality on the NMR 768 33.20 Running the Spectrum 771 33.21 Two-Dimensional NMR 772 33.22 Interpreting 1H-NMR Spectra 774 Unit 34 Mass Spectrometry 783 34.1 Overview 783 34.2 Instrumentation 784 34.3 The Molecular Ion 785 34.4 Charge Localization 789 34.5 Fragmentations 790 34.6 MS Case Studies 796 34.7 Interpreting Mass Spectra 798 34.8 High-Resolution Mass Spectra 800 Answers to Odd-Numbered Exercises 803 Credits 821 Index 823 Index of Spectra 834