Experimental Organic Chemistry

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