Microscale and miniscale organic chemistry laboratory experiments

Microscale
and Miniscale
Organic Chemistry
Laboratory Experiments
Second Edition

Allen M. Schoffstall
The University of Colorado
at Colorado Springs
and

Barbara A. Gaddis
The University of Colorado
at Colorado Springs
with

Melvin L. Druelinger
Colorado State University-Pueblo


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MICROSCALE AND MINISCALE ORGANIC CHEMISTRY LAB EXPERIMENTS
SECOND EDITION
Published by McGraw-Hill, a business unit of The McGraw-Hill Companies, Inc., 1221 Avenue of the Americas, New York,
NY 10020. Copyright © 2004, 2000 by The McGraw-Hill Companies, Inc. All rights reserved. No part of this publication
may be reproduced or distributed in any form or by any means, or stored in a database or retrieval system, without the prior
written consent of The McGraw-Hill Companies, Inc., including, but not limited to, in any network or other electronic storage or transmission, or broadcast for distance learning.
Some ancillaries, including electronic and print components, may not be available to customers outside the United States.
This book is printed on acid-free paper.
1 2 3 4 5 6 7 8 9 0 VNH/VNH 0 9 8 7 6 5 4 3

ISBN 0–07–242456–7
Publisher: Kent A. Peterson
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"Permission for the publication herein of Sadtler Standard Spectrar has been granted, and all rights are reserved, by BIORAD Laboratories, Sadtler Division."
"Permission for the publication of Aldrich/ACD Library of FT NMR Spectra has been granted and all rights are reserved by
Aldrich Chemical."
All experiments contained in this laboratory manual have been performed safely by students in college laboratories under the
supervision of the authors. However, unanticipated and potentially dangerous reactions are possible due to failure to follow
proper procedures, incorrect measurement of chemicals, inappropriate use of laboratory equipment, and other reasons. The
authors and the publisher hereby disclaim any liability for personal injury or property damage claimed to have resulted from
the use of this laboratory manual.
Library of Congress Cataloging-in-Publication Data
Schoffstall, Allen M.
Microscale and miniscale organic chemistry laboratory experiments / Allen M.
Schoffstall, Barbara A. Gaddis, Melvin L. Druelinger.—2nd ed.
p. cm.
Includes bibliographical references and index.

ISBN 0–07–242456–7 (acid-free paper)
1. Chemistry, Organic—Laboratory manuals. I. Gaddis, Barbara A. II. Druelinger,
Melvin L. III. Title.
QD261 .S34 2004
547.0078—dc21
www.mhhe.com

2003008663
CIP


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Dedication
To Carole, Larry, and Judy for their patience, help, and encouragement.
To organic students who develop a passion for doing and learning from organic laboratory experiments
and to the instructors who make laboratory learning meaningful.


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Brief Contents
Preface xxi

Introduction 1
Chapter One

Techniques in the Organic Chemistry Laboratory 9

Chapter Two

Spectroscopic Methods and Molecular
Modeling 109

Chapter Three

Chapter Four

Alcohols and Alkyl Halides

Chapter Five

Synthesis of Alkenes

Chapter Six
Chapter Seven
Chapter Eight

Chapter Nine
Chapter Ten

221

229

Alkene Addition Reactions

237

Stereochemistry 255

Introduction to Nucleophilic Substitution
Reactions 261
Dienes and Conjugation

271

Qualitative Organic Analysis I

281

Chapter Eleven

Reactions of Aromatic Side Chains

Chapter Twelve

Electrophilic Aromatic Substitution 298

Chapter Thirteen

Combined Spectroscopy and Advanced
Spectroscopy 323

Chapter Fourteen

Organometallics 351

Chapter Fifteen
Chapter Sixteen
Chapter Seventeen

Chapter Eighteen

iv

Applications Using Laboratory Resources and
Techniques 183

Alcohols and Diols

364

Ethers 376
Aldehydes and Ketones

385

Enols, Enolates, and Enones

404

290


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Brief Contents

Chapter Nineteen
Chapter Twenty

Carboxylic Acids

419

Carboxylic Acid Esters

430

Chapter Twenty-One

Dicarbonyl Compounds 441

Chapter Twenty-Two

Amines

Chapter Twenty-Three

450

Aryl Halides

475

Chapter Twenty-Four

Phenols

Chapter Twenty-Five

Carbohydrates 489

Chapter Twenty-Six
Chapter Twenty-Seven
Chapter Twenty-Eight
Chapter Twenty-Nine

Lipids

480

507

Amino Acids and Derivatives

518

Qualitative Organic Analysis II
Projects

529

578

Appendix A

Tables of Derivatives for Qualitative Organic
Analysis 627

Appendix B

Laboratory Skills and Calculations

Appendix C

Designing a Flow Scheme

Appendix D

Material Safety Data Sheet 639

Appendix E

Tables of Common Organic Solvents and Inorganic
Solutions 643
Index 645

632

637

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Contents
Preface xxi

Introduction 1
1

Important Features of the Organic Lab

1

Goals for the Organic Laboratory

2

Working in the Laboratory

Laboratory Safety

3

Material Safety Data Sheet (MSDS) 5

6

Your Laboratory Notebook

Laboratory Reports

6

How to Be a Successful Organic Laboratory Student 7

Chapter One
Technique A

Techniques in the Organic Chemistry Laboratory 9
9

Glassware and Equipment: Heating and Cooling

Microscale Glassware and Related Equipment 9

Miniscale Glassware 11

13

Additional Glassware and Equipment

13

How to Clean Glassware

How to Heat and Cool Glass Reaction Vessels 14
Technique B

17

Weighing and Measuring

17

How to Weigh Solids and Liquids

Introduction to Measuring Volumes of Liquids

17

How to Use a Calibrated Glass Pipet 18

How to Use an Automatic Delivery Pipet

19

How to Use a Syringe 19
Exercise B.1: Determining Density of an Aqueous Solution

Exercise B.2: Determining Density of an Organic Liquid

Exercise B.3: Calibrating a Pasteur Pipet

Technique C

Melting Points

20
21

21

22

Mixed Melting Behavior

23

Melting Behavior of Solids

23

24

Calibration of the Thermometer

Apparatus for Measuring Melting Points

How to Determine a Melting Point

24

24

Exercise C.1: Calibration of a Thermometer

26

Exercise C.2: Melting Point of an Unknown Solid

Exercise C.3: Mixed Melting Point

26

27

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Contents
Technique D

Boiling Points

28

28

Intermolecular Attractions

How to Do a Microscale Boiling Point
Determination 29

29

How to Do a Miniscale Boiling Point Determination

Exercise D.1: Determining the Micro Boiling Point of an
Unknown Liquid 30
Exercise D.2: Determining the Boiling Point of an Unknown
Liquid 30

Technique E

Index of Refraction

32

How to Use the Abbe Refractometer 33
Exercise E.1: Measuring the Refractive Index of an Unknown

Liquid
Technique F

33

34

Recrystallization, Filtration, and Sublimation

Solvents for Recrystallization

35

Choosing a Solvent 38

Choosing a Solvent Pair 38

39

How to Do a Microscale Recrystallization

How to Do a Miniscale Recrystallization 41

42

Important Tips Concerning Recrystallization

Introduction to Filtration

43

How to Use a Microscale Filter Pipet 44

How to Do a Miniscale Suction Filtration

44

How to Do a Miniscale Gravity Filtration

44

Important Tips Concerning Filtration

Introduction to Sublimation

45

45

Exercise F.1: Recrystallizing an Impure Solid (microscale)

48
48
Exercise F.3: Recrystallizing an Impure Solid with Hot Gravity
Filtration 49
Exercise F.4: Purifying an Unknown Solid by Solvent-Pair
Recrystallization 50
Exercise F.5: Sublimation of Caffeine 50
Exercise F.6: Sublimation of Caffeine 51

Exercise F.2: Recrystallizing an Impure Solid (miniscale)

Technique G

Distillation and Reflux

52

Microscale Apparatus for Simple Distillation and
Assembly 56

How to Do a Simple Microscale Distillation

56

Important Tips Concerning Microscale Distillation 58

Miniscale Apparatus for Simple Distillation 59

How to Do a Simple Miniscale Distillation 59

Important Tips Concerning Miniscale Distillation

Introduction to Reflux

61

How to Do a Microscale Reaction with Reflux

61

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Contents

62

How to Do a Miniscale Reaction with Reflux

Important Tips on Reflux

62

Evaporation of Solvents

62

Exercise G.1: Distilling a Mixture of Cyclohexane and Toluene

(microscale)

63

Exercise G.2: Distilling a Mixture of Cyclohexane and

Toluene (miniscale)
Technique H

64

Fractional Distillation and Steam Distillation 65

How to Do a Miniscale Fractional Distillation

67

Practical Tips about Miniscale Fractional Distillation

Introduction to Steam Distillation

68

69

Exercise H.1: Miniscale Fractional Distillation of a Mixture

of Cyclohexane and Toluene

70

Exercise H.2: Microscale Fractional Distillation

of Cyclohexane and Toluene

70

Exercise H.3: Steam Distillation of Lemon Grass Oil

(miniscale)
Technique I

71

Extraction and Drying 72

How to Do a Microscale Extraction

74

How to Do a Miniscale Extraction 76

Important Tips Concerning Extraction 76

Drying and Drying Agents

78

How to Do Microscale Drying

How to Do Miniscale Drying

78

79

Important Tips Concerning Drying Agents

79

Exercise I.1: Determining the Distribution Coefficient

of Caffeine (microscale)

80

Exercise I.2: Determining the Distribution Coefficient

of Caffeine (miniscale)

80

Exercise I.3: Using Distribution Coefficients to Identify

Technique J

an Unknown Solid (microscale)

81

Gas-Liquid Chromatography

83

Gas-Liquid Chromatography Basics

Quantitative Analysis

83

87

How to Use the Gas Chromatograph 89
Exercise J.1: Determining Relative Detector Response Factors

in GC

89

Exercise J.2: Determining Mass Percent of a Mixture

Using GC

90

Exercise J.3: Determining Mass Percent of a Mixture

of Alcohols 90
Technique K

Thin-Layer, Column, and High-Performance Liquid
Chromatography 92

Introduction to Thin-Layer Chromatography (TLC)

Introduction to Column Chromatography

How to Do a Miniscale Gravity Column
Chromatography 98

97

92

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Contents

How to Do Microscale Column Chromatography

99

Introduction to High-Performance Liquid
Chromatography (HPLC) 99
Exercise K.1: Analysis of Analgesic Tablets by TLC

101

Exercise K.2: Separating Ferrocene and Acetylferrocene Using

Column Chromatography (microscale) 101
Exercise K.3: Separating Ferrocene and Acetylferrocene Using
Column Chromatography (miniscale) 102
Exercise K.4: HPLC Analysis of Benzaldehyde and Benzyl
Alcohol 102
Technique L

Polarimetry 103

Optical Purity and Enantiomeric Excess 104

How to Measure Optical Rotation

106

Exercise L.1: Determining the Optical Purity of an Unknown
Liquid 107
Exercise L.2: Determining the Melting Points of Enantiomers
and Racemates 107

Chapter Two
Technique M

Spectroscopic Methods and Molecular Modeling 109
Infrared Spectroscopy

110

General Approach to Solving an IR Spectrum 116

Recording an IR Spectrum 116

How to Prepare a Sample for IR Analysis 118

Important Tips Concerning IR 120
Exercise M.1: Recording the IR Spectrum of an Organic

Liquid

122

Exercise M.2: Recording the IR Spectrum of an Organic

Solid

122

Exercise M.3: Spectroscopic Identification of Unknowns

Technique N

122

Nuclear Magnetic Resonance Spectroscopy 125

Chemical Shifts in 1H NMR Spectroscopy 127

Equivalence of Protons in 1H NMR Spectroscopy 129

Integration in 1H NMR Spectroscopy 130

Splitting (coupling) in 1H NMR Spectroscopy 131

Coupling Constants

134

Protons in a Chiral Environment 135

Diastereotopic Protons in Alkenes 136

Protons on Heteroatoms

137

1

Solvents for H NMR Spectroscopy 139

How to Prepare a Sample for 60–90 MHz CW 1H NMR
Spectroscopy 140

How to Prepare a Sample for FT NMR 140

Structural Identification from the NMR Spectrum

140

13

Introduction to C NMR Spectroscopy 143

Solvents for 13C NMR Spectroscopy 146

How to Prepare a Sample for 13C NMR Spectroscopy 146


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Contents

General Approach to Determining an Unknown
Structure 146
Exercise N.1: Recording a 1H NMR Spectrum

148
Exercise N.2: Recording a C NMR Spectrum 148
Exercise N.3: 1H NMR Spectral Problems 148
Exercise N.4: 13C NMR Spectral Problems 150
Exercise N.5: Spectral Identification Using 1H
and 13C NMR 151
13

Technique O

Ultraviolet and Visible Spectroscopy

154

Uses of UV-Visible Spectroscopy 156

How to Operate a Spectronic 20 158

How to Operate a UV-Visible Spectrometer 159
Technique P

Mass Spectrometry 160

Principles of Mass Spectrometry 160

Fragmentation Patterns

163

Molecular Ion Peak 166

Isotopes

167

167

Gas Chromatography/Mass Spectrometry (GC/MS)

Strategy for Solving Structural Problems Using MS, IR,
and NMR 168

Mass Spectrometric Analysis Guidelines 168
Exercise P.1: Solving Problems in Mass Spectrometry

Technique Q

Molecular Modeling

172

173

Organic Molecular Models

174

Drawing Organic Molecules Using Computer
Software 174

Molecular Modeling Using Computer Software 174

Molecular Mechanics

175

Quantum Mechanics

178

Exercises

180

Exercise Q.1: Conformational Analysis of Butane and Other

Molecules 180
Exercise Q.2: Conformational Analysis of Propane 180
Exercise Q.3: Conformational Analysis of 2-Methylbutane 181
Exercise Q.4: Identifying Reactive Sites 181
Exercise Q.5: Heats of Formation and Dipole Moments 181
Exercise Q.6: LUMO Energies of Alkenes 181
Exercise Q.7: Conformational Analysis of 3-Fluoropropene 182

Chapter Three
Experiment 3.1

Applications Using Laboratory Resources and
Techniques 183
Scavenger Hunt: Introduction to Chemical Data Reference
Books and Calculations

184

Part A: Scavenger Hunt in the Chemical Reference Books

Part B: Scavenger Hunt and Stoichiometric Calculations

187
188

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Contents

Experiment 3.2

Identification of Organic Liquids by Physical
Properties 189

General Directions 190
Part A: Boiling Point Determination

190
190

Part B: Refractive Index Determination

Experiment 3.3

Relationships Between Structure and Physical
Properties 192
Part A: Determination of the Effect of Structure on Boiling
Point 194
Part B: Determination of the Effect of Structure on Refractive
Index 194
Part C: Determination of the Effect of Structure on Melting

Point 194

Experiment 3.4

Properties of Solvents and Recrystallization of Organic
Solids 197
Part A: Selecting an Appropriate Solvent

198
Part B: Microscale Recrystallization of an Organic Solid
Experiment 3.5

199

Separations Based upon Acidity and Basicity 200
Part A: Determination of Solubilities

202

Part B: Microscale Separation of Naphthalene, Benzoic Acid,

and Ethyl 4-Aminobenzoate 203
Part C: Miniscale Separation of Benzoic Acid and Ethyl
4-Aminobenzoate 204
Experiment 3.6

Isolation of a Natural Product 205
Part A: Miniscale Extraction of Caffeine from Tea Leaves

207

Part B: Miniscale Extraction of Caffeine from Instant

Coffee 208
Part C: Miniscale Isolation of Caffeine from NoDoz 209
Part D: Miniscale Isolation of Cholesterol from Simulated
Gallstones 209
Experiment 3.7

Solvent and Polarity Effects in Thin-layer
Chromatography (TLC) 210
Part A: Determining the Effect of Polarity on Elution

212

Part B: Separation and Identification of Components of a Mixture

of trans-Stilbene, 9-Fluorenone, and Benzoic Acid 214
Experiment 3.8

Purification and Analysis of a Liquid Mixture: Simple
and Fractional Distillation

216

Part A: Microscale Distillation

217
Part B: Microscale Fractional Distillation
218

Part C: Miniscale Distillation 218
Part D: Miniscale Fractional Distillation 219

Chapter Four

Alcohols and Alkyl Halides

221

Experiment 4.1

Synthesis of an Alkyl Halide from an Alcohol 221

Experiment 4.2

Selectivity of Free Radical Chlorination
of 2,3-Dimethylbutane 224


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Contents

Chapter Five
Experiment 5.1

Synthesis of Alkenes

229

Alkenes Via Acid-catalyzed Dehydration

of Alcohols 229
Part A: Microscale Synthesis of Alkenes Via Acid-catalyzed

Dehydration of 3-Methyl-3-pentanol

231

Part B: Miniscale Synthesis of Alkenes Via Acid-catalyzed

Dehydration of 3,3-Dimethyl-2-butanol 231
Part C: Microscale Synthesis of Alkenes Via Acid-catalyzed
Dehydration of an Unknown Alcohol 232
Experiment 5.2

Alkenes Via Base-Induced Elimination of Alkyl
Halides 234

Chapter Six

Alkene Addition Reactions 237

Experiment 6.1

Catalytic Hydrogenation of Alkenes

237

Part A: Microscale Hydrogenation of 1-Decene

239

240
Part C: Microscale Partial Hydrogenation of Olive Oil 241
Part B: Microscale Hydrogenation of Allylbenzene

Experiment 6.2

Hydration of Alkenes 242
Part A: Microscale Hydration of 2-Ethyl-1-butene

Part B: Microscale Hydration of Norbornene

Part C: Miniscale Hydration of Norbornene

Experiment 6.3

244

245
245

Preparation of Alcohols from Alkenes
by Hydroboration-oxidation 246
Part A: Microscale Hydroboration-oxidation

of 3,3-Dimethyl-1-butene 249
Part B: Miniscale Hydroboration-oxidation
of 3,3-Dimethyl-1-butene 249
Experiment 6.4

Addition Polymers: Preparation of Polystyrene and Polymethyl

Methacrylate

251

Part A: Miniscale Polymerization of Styrene (Bulk Method)

253

Part B: Microscale Polymerization of Styrene (Solution

Method) 253
Part C: Miniscale Polymerization of Methyl Methacrylate (Bulk
Method) 253

Chapter Seven
Experiment 7.1

Stereochemistry 255
Stereochemistry of Alkenes and Derivatives 255
Part A: Microscale Cis-Trans Isomerization of an Alkene

Part B: Microscale Addition of Bromine to Fumaric Acid

258
258

Part C: Determining the Mechanism of the Isomerization
of Dimethyl Maleate to Dimethyl Fumarate (Miniscale) 259

Chapter Eight

Introduction to Nucleophilic Substitution
Reactions 261

Experiment 8.1

Relative Rates of Nucleophilic Substitution
Reactions 261
Part A: Determination of Factors Affecting the Relative Rates

of SN2 Reactions 263
Part B: Determination of Factors Affecting the Relative Rates

of SN1 Reactions 264

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Contents
Experiment 8.2

Nucleophilic Aliphatic Substitution: Synthesis
of 1-Bromobutane

267

Part A: Microscale Synthesis of 1-Bromobutane

Part B: Miniscale Synthesis of 1-Bromobutane

Chapter Nine
Experiment 9.1

Dienes and Conjugation

268
269

271

Dienes and the Diels-Alder Reaction 271
Part A: Microscale Reaction of 1,3-Butadiene

with Maleic Anhydride 276
Part B: Miniscale Reaction of 2,3-Dimethyl-1,3-butadiene
with Maleic Anhydride 277
Part C: Microscale Reaction of Cyclopentadiene with Maleic
Anhydride 277
Part D: Miniscale Reaction of Cyclopentadiene with Maleic
Anhydride 277
Part E: Miniscale Reaction of Anthracene with Maleic
Anhydride 278

Chapter Ten

Qualitative Organic Analysis I

Experiment 10.1

Qualitative Analysis of Alkyl Halides, Alkenes, Dienes,
and Alkynes 281

Chapter Eleven
Experiment 11.1

281

Reactions of Aromatic Side Chains

290

Benzylic Oxidation: Benzoic Acid from Toluene; A Phthalic Acid
from an Unknown Xylene

290

Part A: Microscale Oxidation of Toluene to Benzoic Acid

Part B: Microscale Oxidation of a Xylene to a Phthalic Acid

Chapter Twelve

292
293

Electrophilic Aromatic Substitution 298

Experiment 12.1

Activating and Deactivating Effects of Aromatic
Substituents: Relative Rates of Bromination 299

Experiment 12.2

Nitration of Methyl Benzoate or an Unknown

304

Part A: Microscale Nitration of Methyl Benzoate

306
306
Part C: Miniscale Nitration of an Unknown Aromatic
Compound 307
Part B: Miniscale Nitration of Methyl Benzoate

Experiment 12.3

Friedel-Crafts Acylation Reactions

310

Part A: Microscale Procedure for Acetylation of Biphenyl

312

Part B: Microscale Procedure for Acetylation of Phenanthrene

with TLC Analysis 313
Part C: Microscale Benzoylation of Ferrocene with Column
Chromatography 314
Experiment 12.4

Aromatic Bromination

316

Part A: Microscale Bromination of Acetanilide

317

Part B: Microscale Bromination of p-Methylacetanilide with

TLC and Column Chromatography or HPLC Analysis 319
Part C: Experimental Design of a Procedure for Bromination
of an Acetanilide Derivative 320


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Contents

Chapter Thirteen
Experiment 13.1

Combined Spectroscopy and Advanced
Spectroscopy 323
Infrared and Nuclear Magnetic Resonance

Spectroscopy of Alcohols, Ethers, and Phenols

323

Part A: Experimental Procedure for Infrared Spectroscopy

326

Part B: Experimental Procedure for IR and NMR
Spectroscopy 326
Part C: Exercises for IR and NMR Spectroscopy 327

Experiment 13.2

Combined Spectral Analysis: Infrared, Ultraviolet, and Nuclear

332

Magnetic Resonance Spectroscopy and Mass Spectrometry

Solved Examples of the Use of Combined
Spectroscopy 333
Part A: Purification of the Unknown

341
Part B: Preparation of the Sample and Spectroscopic
Analysis 341
Part C: Spectroscopic Exercises 342

Chapter Fourteen

Experiment 14.1

Organometallics 351
Grignard Synthesis: Preparation of Triphenylmethanol and
3-Methyl-2-phenyl- 2-butanol

351

Part A: Microscale Synthesis of Triphenylmethanol

from Benzophenone

354

Part B: Miniscale Synthesis of Triphenylmethanol from Ethyl

Benzoate 355
Part C: Microscale Synthesis of
3-Methyl-2-phenyl-2-butanol 358
Experiment 14.2

Using Indium Intermediates: Reaction of Allyl Bromide
with an Aldehyde

Chapter Fifteen
Experiment 15.1

360

Alcohols and Diols

364

Stereoselective Reduction of Ketones with Sodium
Borohydride 364
Part A: Microscale Reduction of Benzil

366
Part B: Microscale Reduction of (1R)-(+)-Camphor 366

369

Experiment 15.2

Experimental Design for an Alcohol Oxidation

Experiment 15.3

Photochemical Oxidation of Benzyl Alcohol 373

Chapter Sixteen
Experiment 16.1

Ethers 376
Ether Synthesis by SN2 Displacement 376
Part A: Microscale Preparation of an Alkyl Halophenyl

Ether 378
Part B: Miniscale Preparation of Benzyl tert-Butyl Ether 379
Experiment 16.2

Nucleophilic Aliphatic Substitution Puzzle: Substitution
Versus Elimination

Chapter Seventeen
Experiment 17.1

380

Aldehydes and Ketones

385

Stereoselective Synthesis of Alkenes 386
Part A: Microscale Wittig Synthesis of

trans-9-(2-phenylethenyl)anthracene 388

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Contents
Part B: Miniscale Wittig Synthesis of
trans-9-(2-phenylethenyl)anthracene 389
Part C: Microscale Horner-Emmons Reaction of Diethylbenzyl
Phosphonate and Benzaldehyde 390

Experiment 17.2

393

Conversion of Cyclohexanone to Caprolactam
Part A: Microscale Conversion of Cyclohexanone

to Caprolactam

395

Part B: Miniscale Conversion of Cyclohexanone

to Caprolactam
Experiment 17.3

395

Pinacol Rearrangement and Photochemical Synthesis
of Benzopinacol 399
Part A: Microscale Synthesis of Pinacolone

400

Part B: Miniscale Photoreduction of Benzophenone

401
402

Part C: Miniscale Synthesis of Benzopinacolone

Chapter Eighteen
Experiment 18.1

Enols, Enolates, and Enones

404

Preparation of `,a-Unsaturated Ketones Via Mixed Aldol
Condensation 404
Part A: Miniscale Synthesis of 1,9-Diphenyl-1,3,6,8-

nonatetraen-5-one (Dicinnamalacetone) 407
Part B: Microscale Synthesis of Dibenzalacetone
(1,5-Diphenyl-1,4-pentadien-3-one) 408
Part C: Identification of a Mixed Aldol Product from the
Miniscale Condensation of an Unknown Aromatic Aldehyde
with a Ketone 410
Experiment 18.2

Reduction of Conjugated Ketones with Sodium
Borohydride 411
Part A: Microscale Reduction of 2-Cyclohexenone

412

Part B: Microscale Reduction of

trans-4-Phenyl-3-buten-2-one 413
Experiment 18.3

Identification of Products of Catalytic Transfer
414
Hydrogenation of an Enone
Part A: Microscale Reaction of 2-Cyclohexenone

Part B: Miniscale Reaction of 2-Cyclohexenone

Chapter Nineteen

Carboxylic Acids

416
416

419

Experiment 19.1

Synthesis and Identificatoin of an Unknown Carboxylic
Acid 419

Experiment 19.2

Synthesis of trans-Cinnamic Acid Via the Haloform
Reaction 425

Chapter Twenty
Experiment 20.1

Carboxylic Acid Esters

430

Combinatorial Chemistry and the Synthesis of Fruity
Esters 430
Part A: Combinatorial Selection

432
Part B: Microscale Synthesis of an Ester
Experiment 20.2

433

Synthesis of Esters by Baeyer-Villiger Oxidation

436

Part A: Microscale Oxidation of an Unknown Cyclic Ketone

Part B: Miniscale Oxidation of Cyclohexanone

438

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Contents

Chapter Twenty-One
Experiment 21.1

Dicarbonyl Compounds 441
Base-Catalyzed Condensations of Dicarbonyl
Compounds 441
Part A: Microscale Preparation of Coumarin or a Coumarin

Derivative 444
Part B: Miniscale Preparation of Coumarin or a Coumarin

Derivative 444
Experiment 21.2

Reactions of Diketones: Synthesis of 2,5-Dimethyl1-phenylpyrrole and Preparation of an Unknown Pyrrole

445

Part A: Microscale Synthesis of

2,5-Dimethyl-1-phenylpyrrole 447
Part B: Microscale Preparation of an Unknown Pyrrole

Chapter Twenty-Two
Experiment 22.1

Amines

448

450

Relating Color to Structure: Synthesis of Azo Dyes

450

Part A: Miniscale Diazotization of an Aromatic Amine

454
455
Part B.2: Miniscale Coupling with an Amine 455
Part C: Direct Dyeing with an Azo Dye 455
Part D: Recording the UV-Visible Spectrum of the Prepared
Dyes 455
Part E: Determining the pH Indicator Range of the Prepared
Dyes 455
Part F: Determining Antibacterial Properties of the Dye 456
Part B.1: Miniscale Coupling with a Phenol

Experiment 22.2

Synthesis of Pyrazole and Pyrimidine Derivatives 457
Part A: Microscale Synthesis of a Five-Member Ring

Heterocycle from Hydrazine and an Unknown Diketone

461

Part B: Miniscale Synthesis of a Five-Member Ring

Heterocycle from Hydrazine and an Unknown Diketone 461
Part C: Microscale Synthesis of a Substituted Pyrimidine 462
Part D: Miniscale Synthesis of a Substituted Pyrimidine 462
Experiment 22.3

Synthesis of Heterocyclic Compounds

464

Part A: Miniscale Reaction of Benzaldehyde and Pyrrole

Part B: Microscale Reaction of o-Phenylenediamine and

Formic Acid 467
Experiment 22.4

Synthesis of Heterocycles and Kinetics
by Spectroscopic Analysis 469
Part A: Miniscale Preparation of Lophines

(2-Aryl-4,5-diphenylimidazoles) 471
Part B: Miniscale Synthesis of Substituted Lophinyl

(2-Aryl-4,5-diphenylimidazole) Dimers 471
Part C: Kinetics of the Recombination Reaction

Chapter Twenty-Three
Experiment 23.1

Aryl Halides

475

Nucleophilic Aromatic Substitution

475

Part A: Microscale Reaction of Sodium Ethoxide

with 1-Bromo-2,4-dinitrobenzene

477

Part B: Microscale Reaction of Sodium Ethoxide

with p-Fluoronitrobenzene

477

472

466

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Contents

Chapter Twenty-Four
Experiment 24.1

Phenols

480

Exploring Structure-function Relationships of Phenols:
Synthesis of Salicylic Acid, Aspirin, and Vanillin Derivatives

480

Part A: Miniscale Reactions of Vanillin

483
PartB: Miniscale Hydrolysis of Methyl Salicylate 485
Part C: Miniscale Synthesis of Acetylsalicylic Acid 486

Chapter Twenty-Five
Experiment 25.1

Carbohydrates 489
Classification of Sugars and Identification of an
Unknown Sugar 490

General Instructions for the Microscale Identification
of an Unknown Sugar 495
Part A: Osazone Formation

Part B: Chemical Tests

Experiment 25.2

496

496

Esterification of Sugars: Preparation of Sucrose Octaacetate
and `- and a-D-Glucopyranose Pentaacetate

498

Part A: Miniscale Preparation of D-Sucrose Octaacetate

500

Part B: Microscale Preparation of β-D-Glucopyranose

Pentaacetate 501
Part C: Microscale Conversion of β-D-Glucopyranose
Pentaacetate to the a-Anomer 502
Part D: Miniscale Preparation of α-D-Glucose Pentaacetate
and Measurement of Optical Rotation 503

Chapter Twenty-Six
Experiment 26.1

Lipids

507

Soap from a Spice: Isolation, Identification, and Hydrolysis
of a Triglyceride

507

Part A: Miniscale Isolation of a Triglyceride from Nutmeg

Part B: Microscale Hydrolysis of a Triglyceride

509

510

Part C: Determination of Properties of the Soap
from Nutmeg 511

Experiment 26.2

Chapter Twenty-Seven
Experiment 27.1

Preparation of Esters of Cholesterol and Determination
of Liquid Crystal Behavior 512

Amino Acids and Derivatives 518
Conversion of an Amino Acid to a Sunscreen: Multistep
Preparation of Benzocaine or a Benzocaine Analog

518

Part A: Miniscale Synthesis of p-Methylacetanilide

521

Part B: Miniscale Synthesis of p-Acetamidobenzoic Acid

522
523
Part D: Microscale Esterification of p-Aminobenzoic Acid 525
Part E: Determining the Effectiveness of the p-Aminobenzoic
Acid Ester as a Sunscreen 526
Part C: Miniscale Synthesis of p-Aminobenzoic Acid

Chapter Twenty-Eight
Experiment 28.1

Qualitative Organic Analysis II

529

Designing a Classification Scheme for Characterizing
an Organic Compound 529
Part A: Microscale Solubility Tests

Part B: Microscale Chemical Tests

530
531

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Contents
Part C: Microscale Classification of an Unknown
Compound 536

Experiment 28.2

Experimental Methods of Qualitative Organic
Analysis 537

Introduction to Qualitative Organic Analysis

537

538

Overall Approach to Identifying the Unknown

Step 1: Purify

538

Step 2: Determine the Physical Properties 538

Step 3: Examine the Physical State 538

Step 4: Perform Solubility Tests

538

540

Step 5: Identify the Functional Groups Present

Step 6: Select an Appropriate Derivative 551

Step 7: Prepare and Purify the Derivative 552

Step 8: Identify the Unknown

557

Experimental Procedure 557
Part A: Purification of the Unknown

559
559
Part C: Chemical Tests (Arranged Alphabetically)
Part D: Derivatives 566
Part B: Solubility Tests

Part E

560

Qualitative Organic Analysis of Unknowns 574
Part E.1: Qualitative Analysis of Aldehydes and Ketones

Part E.2: Qualitative Analysis of Alcohols and Phenols

574
575

Part E.3: Qualitative Analysis of Amines and Carboxylic

Acids 575
Part E.4: Qualitative Analysis of a General Unknown

575
Part E.5: Qualitative Analysis and Spectroscopic Analysis
of a General Unknown 575

Chapter Twenty-Nine
Experiment 29.1

Projects

578

Multistep Synthesis of 1-Bromo-3-chloro-5-iodobenzene
from Aniline 579
Part A: Synthesis of Acetanilide from Aniline

583

Part B: Miniscale Synthesis of 4-Bromoacetanilide

from Acetanilide 585

Part C: Synthesis of 4-Bromo-2-chloroacetanilide
from 4-Bromoacetanilide 586
Part D: Synthesis of 4-Bromo-2-chloroaniline from 4-Bromo2-chloroacetanilide 587
Part E: Miniscale Synthesis of 4-Bromo-2-chloro-6-iodoaniline
from 4-Bromo-2-chloroaniline 589
Part F: Synthesis of 1-Bromo-3-chloro-5-iodobenzene
from 4-Bromo-2-chloro-6-iodoaniline 590
Experiment 29.2

Multistep Synthesis of Sulfanilamide Derivatives as
Growth Inhibitors 592
Part A: Preparation of Acetanilide

594

Part B: Preparation of p-Acetamidobenzenesulfonyl

Chloride 595

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Part C: Reaction of p-Acetamidobenzenesulfonyl Chloride
with an Amine 595
Part D: Hydrolysis of the Acetamido Group 596
Part E: Bacterial Testing of Antibiotic Susceptibility 596

Part A: Miniscale Synthesis of Acetanilide

597

Part B: Miniscale Synthesis of p-Acetamidobenzenesulfonyl

Chloride 597
Part C: Miniscale Synthesis of Sulfonamides 598
Part D: Miniscale Synthesis of Sulfanilamides 599
Part E: Bacterial Testing of Antiobiotic Susceptibility
Experiment 29.3

600

Structural Determination of Isomers Using Decoupling
and Special NMR Techniques 602
Part A: Homonuclear Decoupling of a Known Alkene

and Determination of Coupling Constants 612
Part B: Characterization of an Unknown Compound Using
Homonuclear Decoupling in 1H NMR 612
Part C: Characterization of an Unknown Compound Using
1
H NMR, 13C NMR, 1H-1H (COSY) and HETCOR
(1H-13C COSY) 613
Experiment 29.4

The Library-Laboratory Connection

614

Part A: Chemical Abstracts (CA) and Beilstein

Part B: Searching Science Library Databases

Part C: Searching on the Web

Experiment 29.5

614
619

620

Stereochemistry, Molecular Modeling, and
Conformational Analysis 621
Part A: Molecular Models Using a Model Kit

624
625
Part C: Conformational Analysis of Rotational Isomers 625
Part D: Using Molecular Modeling to Analyze Rotational
Conformations of Stereoisomers 625
Part B: Computer Modeling

Appendix A

Tables of Derivatives for Qualitative Organic
Analysis 627

Appendix B

Laboratory Skills and Calculations

Appendix C

Designing a Flow Scheme

Appendix D

Material Safety Data Sheet 639

Appendix E

Tables of Common Organic Solvents and Inorganic
Solutions 643
Index 645

632

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Preface to Second Edition
This book is a comprehensive introductory treatment of the organic chemistry laboratory. The student will be guided in doing numerous exercises to learn basic laboratory
techniques. The student will then use many proven traditional experiments normally
performed in the two-semester organic laboratory course.

Several trends in organic laboratory education have emerged since publication of
the first edition. These trends are recognition of the pedagogical value of discovery
experiments, the increased emphasis on molecular modeling and computer simulations,
and the development of green experiments. All of these trends are incorporated into this
book along with the use of traditional experiments.

DISCOVERY EXPERIMENTS
Discovery experiments are given a special label in the Table of Contents and in each
chapter where they appear. Discovery experiments incorporate the pedagogical advantages of inductive inquiry experiments with the ease of design found in expository
experiments. Discovery experiments (or guided inquiry experiments) have a specific
procedure designed to give a predetermined but unspecified result. Students use a
deductive thought process to arrive at a desired conclusion. Students are “guided” by
inferring a general scientific principle. Discovery experiments have been employed
successfully in large laboratory sections, as well as in small classroom environments.
Student interest is increased during discovery experiments because the result of the
experiment is unknown to the student. The desired goal of discovery experiments is
increased student learning. Discovery experiments can also provide the opportunity
for individual reflection and class discussion and may involve students in developing
and interpreting laboratory procedures. These features and advantages of discovery
experiments have caused your text authors to emphasize discovery experiments in this
edition of the text.

MOLECULAR MODELING
Molecular modeling by computer saw a revolution in the late 1990s with the advent of
affordable, sufficiently fast personal computers with adequate memory. Computer modeling enhances the benefits of assembling molecular models using model kits. Use of
these kits is still encouraged. However, gone are the days where students had to depend
only on molecular model kits to represent molecules in three dimensions. While these
models still have their uses, computer modeling programs now provide exciting visualization of molecules and calculation of physical properties and thermodynamic parameters. Where possible, it is desirable to incorporate computer modeling into organic
laboratory programs. The exercises in this book can be done using relatively inexpensive commercial software from one or more providers.

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Preface

COMPUTER SIMULATION OF EXPERIMENTS
Another use of computers is for simulation of laboratory procedures and experiments.
Demonstrations of laboratory techniques are available as clips on the CD accompanying this text. Simulations of experiments are useful as prelab exercises to familiarize
students with the experiment and to enhance learning in the laboratory. Simulations are
also useful as illustrations of experiments that are difficult to carry out in the undergraduate laboratory environment. Experiments that require special equipment, inert gaseous
environments, or especially noxious and toxic reagents can be experienced by students
through virtual experiments on the computer. Examples of such experiments are available on the CD accompanying this text.

GREEN CHEMISTRY
Academic and industrial organic chemists have led an initiative to replace the use of
organic solvents with aqueous solvents. They have encouraged the recycling of chemicals in order to reduce production requirements of chemicals. They have encouraged
use of environmentally benign reagents in place of hazardous and toxic reagents where
possible. In this text, there have been efforts to reduce quantities of toxic reagents and
solvents wherever possible and to develop “green” experiments. For example, new
Experiment 14.2 is on the use of indium reagents in aqueous solvents to accomplish
coupling reactions similar to Grignard reactions. Another objective of green chemistry
is to prevent waste. In this book, microscale and miniscale experiments are used in
order to help minimize waste.

MICROSCALE AND MINISCALE TECHNIQUES
Microscale and miniscale organic techniques were first introduced two decades ago.
However, changing over to new, smaller glassware and equipment has been slow in

some laboratories for a number of reasons. One reason is the initial cost, but most institutions benefit by reduced costs of chemicals and hazardous waste disposal. The decision
of whether to use a microscale procedure or a miniscale procedure often depends on the
methods of characterization chosen by the instructor. This governs how much product is
required for analysis. If a distillation is desired, a miniscale procedure is often chosen
because of difficulties associated with distilling very small quantities of liquid. If an
analysis of liquid products is to be done only by gas chromatographic analysis, a
microscale procedure will cut down on costs of waste disposal.

NEW FEATURES IN THE SECOND EDITION
Accompanying a new section on molecular modeling, significant additions to this edition include expanded coverage of Diels-Alder chemistry, inclusion of enone chemistry
with a chapter on enols, a new chapter on dicarbonyl compounds, and expanded coverage of heterocycles in the chapter on amines. New experiments and new options within
experiments are included in many chapters. Many are discovery experiments. Among
these are
Experiment 3.3, Relationships Between Structure and Physical Properties;
Experiment 3.8, Purification and Analysis of a Liquid Mixture;
Experiment 5.1B, Miniscale Synthesis of Alkenes Via Acid-catalyzed Dehydration
of 3,3-Dimethyl-2-butanol;


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Preface

Experiment 9.1C, Microscale Reaction of Cyclopentadiene with Maleic Anhydride;
Experiment 9.1E, Reaction of Anthracene with Maleic Anhydride;
Experiment 14.2, Using Indium Intermediates: Reaction of Allyl Bromide with an
Aldehyde;
Experiment 15.3, Photochemical Oxidation of Benzyl Alcohol;
Experiment 16.2, Nucleophilic Aliphatic Substitution Puzzle: Substitution Versus
Elimination;
Experiment 17.1C, Microscale Horner-Emmons Reaction of Diethylbenzyl

Phosphonate and Benzaldehyde;
Experiment 18.2A, Microscale Reduction of 2-Cyclohexenone;
Experiment 18.2B, Microscale Reduction of trans-4-Phenyl-3-buten-2-one;
Experiment 18.3, Catalytic Transfer Hydrogenation Miniscale Reaction
of Cyclohexenone;
Experiment 21.1, Base-Catalyzed Condensations of Dicarbonyl Compounds;
Experiment 22.2, Synthesis of Pyrazole and Pyrimidine Derivatives;
Experiment 24.1, Exploring Structure-function Relationships of Phenols;
Experiment 26.1, Soap from a Spice: Isolation, Identification and Hydrolysis
of a Triglyceride;
Experiment 26.2, Preparation of Esters of Cholesterol and Determination of Liquid
Crystal Behavior;
Experiment 29.2, Multistep Synthesis of Sulfanilamide Derivatives as Growth
Inhibitors;
Experiment 29.3, Structural Determination of Isomers Using Decoupling and
Special NMR Techniques.

INSTRUCTOR’S MANUAL
An instructor’s manual is available on the website accompanying this text. This manual
includes directions for laboratory preparators, instructor’s notes for each experiment,
solutions to problems, and prelab and postlab assignments. Test questions about many
experiments are available on the web CT.

COURSE WEBSITE
The website offers supportive backup for the organic
laboratory course. It presents updated helpful hints for lab preparators and instructors,
typical schedules, sample electronic report forms, sample quiz and exam questions,
examples of lab lecture or material for self-paced prelab student preparation, and relevant links to other websites. Some additional experiments are available on the website.

ACKNOWLEDGMENTS

We wish to acknowledge several individuals who have contributed to the second edition.
Connie Pitman, laboratory technician at the University of Colorado Springs, has made
numerous valuable comments about the experiments. She has also coauthored the
Instructor’s Manual and Solutions Guide. Shirley Oberbroeckling has served as the
Developmental editor and Joyce Watters as the Project Manager for this edition of the
text. The following faculty and students have contributed to the second edition by testing
experiments and suggesting improvements:
Robert A. Banaszak, Anna J. Espe, Sam T. Seal, Shannon J. Coleman, Shannon R.
Gilkes, Molly M. Simbric, Daniela Dumitru, Patricia D. Gromko, Amy M. Scott,

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Preface

Tomasz Dziedzic, Paul J. Lunghofer, Rafael A. Vega, Justin A. Russok, Darush Fathi,
and Michael Slogic.
We are grateful to the following individuals who served as reviewers for this edition. They are:
Monica Ali, Oxford College
Steven W. Anderson, University of Wisconsin - Whitewater
Satinder Bains, Arkansas State University - Beebe
David Baker, Delta College
John Barbaro, University of Alabama - Birmingham
George Bennett, Milikin University
Cliff Berkman, San Francisco State University
Lea Blau, Stern College for Women
Lynn M. Bradley, The College of New Jersey

Bruce S. Burnham, Rider College
Patrick E. Canary, West Virginia Northern Community College
G. Lynn Carlson, University of Wisconsin - Kenosha
Jeff Charonnat, California State University - Northridge
Wheeler Conover, Southeast Community College
Wayne Counts, Georgia Southwestern State University
Tammy A. Davidson, East Tennessee State University
David Forbes, University of South Alabama - Mobile
Eric Fossum, Wright State University - Dayton
Nell Freeman, St. Johns River Community College
Edwin Geels, Dordt College
Jack Goldsmith, University of South Carolina - Aiken
Ernest E. Grisdale, Lord Fairfax Community College
Tracy Halmi, Pennsylvania State Behrend - Erie
C. E. Heltzel, Transylvania University
Gary D. Holmes, Butler County Community College
Harvey Hopps, Amarillo College
William C. Hoyt, St. Joseph’s College
Chui Kwong Hwang, Evergreen Valley College
George F. Jackson, University of Tampa
Tony Kiessling, Wilkes University
Maria Kuhn, Madonna University
Andrew Langrehr, Jefferson College
Elizabeth M. Larson, Grand Canyon University
John Lowbridge, Madisonville Community College
William L. Mancini, Paradise Valley Community College
John Masnovi, Cleveland State University
Anthony Masulaitis, New Jersey City University
Ray Miller, York College
Tracy Moore, Louisiana State University - Eunice

Michael D. Mosher, University of Nebraska - Kearney
Michael J. Panigot, Arkansas State University
Neil H. Potter, Susquehanna University
Walda J. Powell, Meredith College
John C. Powers, Pace University
Steve P. Samuel, SUNY - Old Westbury
Greg Spyridis, Seattle University


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Preface

Paris Svoronos, Queensboro Community College
Eric L. Trump, Emporia State University
Patibha Varma Nelson, St. Xavier University
Chad Wallace, Asbury College
David Wiendenfeld, University of North Texas
Linfeng Xie, University of Wisconsin - Oshkosh
We hope you find your laboratory experience profitable and stimulating.

xxv