EXPERIMENTS IN ORGANIC CHEMISTRY From Microscale to Macroseale

Jonathan S. Nimitz University of New Mexico

WM PRENTICE HALL, Englewood Cliffs, New Jersey 07632

PREFACE xiii

LABORATORY The First Steps 1 ESSENTIALS

Safety Practices in the Organic Laboratory 4 First Aid 7 Guidelines for Notebooks 8 Note on Calculating Theoretical Yields 10 Typical Organic Chemistry Desk Equipment 12 General Hints on Using Glassware and Equipment 12

SECTION 1 Recrystallization and Melting Points 22 Experiment 1.1: Recrystallization of Benzoic Acid from

Water 29 Experiment 1.2: Recrystallization of Naphthalene from Methanol

Using Decolorizing Charcoal 30 Experiment 1.3: Choosing a Recrystallization Solvent 31

SECTION 2 Distillation 34 Application: Fractional Distillation of Petroleum 40 Experiment 2.1: Fractional Distillation of an Acetone-Toluene

Mixture 42

SECTION 3 Acid-Base Extraction 45 Application: History, Cultivation, and Composition of Tea 53 Experiment 3.1: Separation of Benzoic Acid, m-Nitroaniline, and

Naphthalene 59 Experiment 3.2: Extraction of Caffeine from Tea Leaves 61

SECTION 4 Thin-Layer Chromatography 63 Application: Forensic Chemistry 65 Experiment 4.1: Determining Rf Values and Unknowns by

TLC 68

SECTION 5 Column Chromatography 72 Application: High-Performance Liquid Chromatography

(HPLC) 77 Experiment 5.1: Microscale Separation of Azobenzenes 79

Experiment 5.2: Isolation of Chlorophyll and ß-Carotene from Spinach by Gradient Elution 80

SECTION 6 Acid-Cataiyzed Dehydration of Alcohols 82 Experiment 6.1: Cyclohexene from Cyclohexanol 85 Experiment 6.2: Pentenes from 2-Pentanol 86

SECTION 7 Hydration of Alkenes and Alkynes 88 Experiment 7.1: Hydration of 2-Methyl-3-butyn-2-ol 93

SECTION 8 Stereochemistry: Adding Bromine to Alkenes 95 Experiment 8.1: Addition of Bromine to Cinnamic Acid 98

SECTION 9 Alkyne Formation from Vicinal Dihalides 102 Application: Alkynes and Birth Control 103 Experiment 9.1: Phenylpropynoic Acid by Double

Dehydrobromination of Cinnamic Acid Dibromide 104

Experiment 9.2: Microscale Preparation of Diphenylacetylene from Stilbene Dibromide 105

SECTION 10 SN2 Reactions 107 Experiment 10.1: Conversion of 1 -Butanol to 1 -Bromobutane

112 Experiment 10.2: Displacement of Bromide by lodide: Preparation

of 1-lodohexane by the Finkelstein Reaction 115

Experiment 10.3: Conversion of Isobutyl Alcohol to Isobutyl Bromide Using PBr3 116

Experiment 10.4: Conversion of 1-Pentanol to 1-lodopentane Using Phosphorus and lodine 116

Mechanisms Review: 117

SECTION 11 SN1 Reactions and Kinetics 120 Experiment 11.1: Conversion of f-Amyl Alcohol to f-Amyl Chloride

Using HCl 123 Experiment 11.2: Kinetic Study of the Hydrolysis of f-Butyl

Chloride 124

SECTION 12 Radical Halogenation and Gas Chromatography 126 Application: Gas Chromatography and Environmental

Protection 131 Experiment 12.1: Chlorination of 1-Chlorobutane 135 Experiment 12.2: Bromination of m-Toluic Acid Using NBS 137

Contents VÜ

SECTION 13 Infrared Spectroscopy Experiment 13.1: Unknown Determination by IR

Spectroscopy 147

SECTION 14 Structure Determination Practice (No experiment)

SECTION 15 Diels-Alder Reactions and Insecticides Experiment 15.1: Cycloaddition of Cyclopentadiene and Maleic

Anhydride 187

SECTION 16 Catalytic Hydrogenation Application: Catalytic Hydrogenation of Vegetable Oil 191 Experiment 16.1: Hydrogenation of C/'s-5-Norbornene-Eno'o-2,3-

Dicarboxylic Acid Using Pt/H2 194

SECTION 17 Isolation of Natural Flavors and Fragrances Application: Commercial Distiliation of Essential Oils 200 Application: Vanilla Flavor from Wood 204 Experiment 17.1: Steam Distiliation of Eugenol from Cloves 206 Experiment 17.2: Steam Distiliation of Orange Oil 207

138

150

179

189

196

SECTION 18 Electrophilic Aromatic Substitution 208

SECTION 19

SECTION 20

Experiment 18.1 Experiment 18.2 Experiment 18.3

Experiment 18.4:

Nitration of Methyl Benzoate 214 Dinitration of Benzoic Acid 215 Microscale Bromination of Resorcylic Acid 216 Microscale Friedel-Crafts Alkylation of p-Dimethoxybenzene 216

Oxidation of a Side Chain on an Aromatic Ring Experiment 19.1: Oxidation of o-Chlorotoluene to o-Chlorobenzoic

Acid Using KMn04 221 Oxidation of p-Nitrotoluene to p-Nitrobenzoic Acid Using Na2Cr207/H2S04 222 Oxidation of 2-Methylpyridine to 2-Pyridinecarboxylic Acid Using KMn04 223

219

Experiment 19.2:

Experiment 19.3:

Ether Synthesis

Experiment 20.1:

Experiment 20.2:

Experiment 20.3:

224 Williamson Synthesis of Ethyl Phenyl Ether Using Phase-Transfer Catalysis 228 Williamson Synthesis of p-Ethoxynitrobenzene 230 Conversion of Acetaminophen into Phenacetin 230

Experiment 20.4: Microscale Preparation of Trityl Ethyl Ether 231

SECTION 21 Epoxidation of Afkenes Application: Epoxy Glue 234 Experiment 21.1: Preparation of Stilbene Oxide Using

MCPBA 236

233

SECTION 22 Carbenes Experiment 22.1:

Experiment 22.2:

237 Addition of Dichlorocarbene to Cyclohexene 242 Microscale Addition of Dibromocarbene to 1,1-Diphenylethylene 244

SECTION 23 Carbocation Rearrangements 246 Experiment 23.1 Experiment 23.2 Experiment 23.3

The Pinacol Rearrangement 251 Rearrangement of Benzopinacol 252 Three-Step Synthesis of Camphor from Camphene 252

SECTION 24 Hydride Reductions Experiment 24.1: Reduction of Cyclohexanone to Cyclohexanol

Using NaBH4 260 Reduction of Vanillin Using NaBH4 261 Stereochemistry of the Reduction of 4-f-Butylcyclohexanone 262

255

Experiment 24.2: Experiment 24.3:

SECTION 25 Oxidation of Alcohols and Aldehydes Experiment 25.1: Jones Oxidation of 2-Methylcyclohexanol 266 Experiment 25.2: Oxidation of Furfural to Furoic Acid Using

K2Cr207/H2S04 267 Experiment 25.3: Oxidation of Heptanal to Heptanoic Acid Using

KMn04 268

263

SECTION 26 Reactions of Aldehydes and Ketones with Amines Experiment 26.1: Microscale Synthesis of Benzophenone

Oxime 273

270

SECTION 27 The Beckmann Rearrangement Experiment 27.1: Microscale Conversion of Cyclohexanone Oxime

to Caprolactam 276

274

Contents IX

SECTION 28 Malonic and Acetoacetic Ester Synthesis 277 Experiment 28.1: Malonic Ester Synthesis of Cyclobutanecarboxylic

Acid 281 Experiment 28.2: Acetoacetic Ester Synthesis of

2-Heptanone 284

SECTION 29 Alkylation and Acylation of Carbonyl Compounds 286 Experiment 29.1: Acylation of Cyclohexanone Using the Morpholine

Enamine 289

SECTION 30 The Wittig Reaction 291 Experiment 30.1: Wittig Synthesis of Trans-Stilbene 293

SECTION 31 Reactions and Spectroscopy of Aldehydes and Ketones 295 Experiment 31.1: Identification of an Unknown Aldehyde or

Ketone 301

SECTION 32 Qualitative Organic Analysis 311 Experiment 32.1: Identification of an Unknown Organic

Compound 317

SECTION 33 Grignard Reactions and MultiStep Syntheses 330 Experiment 33.1: Synthesis of Triphenylmethanol by Reaction of

Methyl Benzoate and Phenylmagnesium Bromide 335

SECTION 34 Organolithium Compounds 340 Experiment 34.1: Synthesis of Fluorene-9-Carboxylic Acid 342

SECTION 35 Hydrolysis of Nitriles to Carboxylic Acids 344 Experiment 35.1: Hydrolysis of Benzonitrile to Benzoic Acid 346

SECTION 36 Base-Catalyzed Hydrolysis of Esters: Soap Making 347 Experiment 36.1: Soap from Shortening 350

SECTION 37 Ester Synthesis 352 Application: The Painful History of Analgesics, Antipyretics, and

Anti-Inflammatory Agents 358 Experiment 37.1: Synthesis of Banana Fragrance (Isoamyl

Acetate) 360 Experiment 37.2: Ethyl Acetate from Ethanol and Acetic

Acid 361

X Contents

Experiment 37.3:

Experiment 37.4: Experiment 37.5:

Experiment 37.6:

Synthesis of Aspirin by Acetylation of Salicylic Acid 362 Acetylation of Furfuryl Alcohol 363 Microscale Acetylation of Benzoin with Acetic Anhydride 363 Preparation of f-Butyl Acetate from f-Butyl Alcohol and Acetyl Chloride 364

SECTION 38 Amide Synthesis Application: Mosquito Repellents 368 Experiment 38.1: Acetanilide from Aniline and Acetic

365

Experiment 38.2:

Experiment 38.3:

Experiment 38.4:

Anhydride 370 Acetylation of Glycine with Acetic Anhydride 371 Synthesis of the Insect Repellent N,N-Diethyl-m-Toluamide 371 Microscale Sulfonamide Formation by Reaction of p-Toluenesulfonyl Chloride and Methylamine 373

SECTION 39 Aldol Condensations Experiment 39.1: Microscale Aldol Condensation of Acetone and

Benzaldehyde 382 Condensation of Benzaldehyde and Nitromethane to form Nitrostyrene 383 Microscale Condensation of a Nitrile and an Aromatic Aldehyde: Preparation of a-(4-Nitrophenyl) Cinnamonitrile 384 Claisen Condensation of Ethyl Acetate and Benzaldehyde 384

374

Experiment 39.2:

Experiment 39.3:

Experiment 39.4:

SECTION 40 Amine Synthesis

Experiment 40.1:

Experiment 40.2:

Experiment 40.3:

386 Preparation of N-Ethyl-m-Toluidine from m-Toluidine and Ethyl Bromide 388 Microscale Gabriel Synthesis of Phthalimidoacetophenone 389 Synthesis of Acetanilide from Nitrobenzene 390

SECTION 41 Diazonium Reactions 391 Application: Natural and Synthetic Dyes 394 Experiment 41.1: Synthesis of Methyl Orange: Diazonium Coupling

Contents XJ

Experiment 41.2:

Reaction of Sulfanilic Acid and N,N-Dimethylaniline 396 p-lodophenol from p-Aminophenol Using a Diazonium Salt 397

SECTION 42 Isocyanate Formation and Reactions Application: Uses of Polyurethanes 403 Experiment 42.1: Formation of Undecyl Isocyanate by Curtius

Rearrangement and Its Reaction with Methanol 404

399

SECTION 43 Heterocycles Experiment 43.1:

Experiment 43.2 Experiment 43.3 Experiment 43.4 Experiment 43.5 Experiment 43.6

406 Preparation of 2,5-Dimethyl-1-Phenylpyrrole 412 Preparation of 4-Methyl-2-Quinolinone 413 Preparation of Benzimidazole 413 Preparation of Benzofurazan-1 -Oxide 414 Preparation of Barbituric Acid 415 Preparation of 3-Carbethoxycoumarin 415

SECTION 44 Carbohydrates Experiment 44.1: Structure Determination of a

Carbohydrate 420

417

SECTION 45 Polymers Application: Plastics 425 Experiment 45.1 Experiment 45.2 Experiment 45.3

Polymerization of Styrene 427 Formation of Nylon 6,10 428 Preparation of Cellulose Triacetate

422

428

SECTION 46 Enzymes in Organic Synthesis Application: Wine Making 435 Experiment 46.1: Reduction of Vanillin by Yeast

430

436

SECTION 47 Bio- and Chemiluminescence Experiment 47.1: Synthesis and Chemiluminescence of

Luminol 444

438

SECTION 48 Porphyrins Experiment 48.1: Synthesis and Metallation of a Porphyrin 448

445

SECTION 49 Chiral Resolution Experiment 49.1: Resolution of Methylbenzylamine 453

450

SECTION 50 Computers in Chemistry 454 Experiment 50.1: Online Chemical Information Retrieval 455 Experiment 50.2: Use of Educational Software 456

SECTION 51 Choose Your Own Experiment 458

APPENDIX A Names of Common Inorganic Ions 461

APPENDIX B Common Organic Functional Groups 462

APPENDIX C How to Use the Chemical Literature 464

Review of Important Terms in Organic Chemistry 469