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