FOUNDATIONS OF ORGANIC CHEMISTRYUNITY AND DIVERSITY OF STRUCTURES, PATHWAYS, AND REACTIONS

David R. Dalton

A JOHN WILEY & SONS, INC., PUBLICATION

ffirs02.indd iiiffirs02.indd iii 4/11/2011 11:58:41 AM4/11/2011 11:58:41 AM

ffirs01.indd iiffirs01.indd ii 4/11/2011 11:58:41 AM4/11/2011 11:58:41 AM

FOUNDATIONS OF ORGANIC CHEMISTRY

ffirs01.indd iffirs01.indd i 4/11/2011 11:58:41 AM4/11/2011 11:58:41 AM

ffirs01.indd iiffirs01.indd ii 4/11/2011 11:58:41 AM4/11/2011 11:58:41 AM

FOUNDATIONS OF ORGANIC CHEMISTRYUNITY AND DIVERSITY OF STRUCTURES, PATHWAYS, AND REACTIONS

David R. Dalton

A JOHN WILEY & SONS, INC., PUBLICATION

ffirs02.indd iiiffirs02.indd iii 4/11/2011 11:58:41 AM4/11/2011 11:58:41 AM

Copyright © 2011 by John Wiley & Sons, Inc. All rights reserved

Published by John Wiley & Sons, Inc., Hoboken, New JerseyPublished simultaneously in Canada

No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, scanning, or otherwise, except as permitted under Section 107 or 108 of the 1976 United States Copyright Act, without either the prior written permission of the Publisher, or authorization through payment of the appropriate per-copy fee to the Copyright Clearance Center, Inc., 222 Rosewood Drive, Danvers, MA 01923, (978) 750-8400, fax (978) 750-4470, or on the web at www.copyright.com. Requests to the Publisher for permission should be addressed to the Permissions Department, John Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, (201) 748-6011, fax (201) 748-6008, or online at http://www.wiley.com/go/permissions.

Limit of Liability/Disclaimer of Warranty: While the publisher and author have used their best efforts in preparing this book, they make no representations or warranties with respect to the accuracy or completeness of the contents of this book and specifi cally disclaim any implied warranties of merchantability or fi tness for a particular purpose. No warranty may be created or extended by sales representatives or written sales materials. The advice and strategies contained herein may not be suitable for your situation. You should consult with a professional where appropriate. Neither the publisher nor author shall be liable for any loss of profi t or any other commercial damages, including but not limited to special, incidental, consequential, or other damages.

For general information on our other products and services or for technical support, please contact our Customer Care Department within the United States at (800) 762-2974, outside the United States at (317) 572-3993 or fax (317) 572-4002.

Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic formats. For more information about Wiley products, visit our web site at www.wiley.com.

Library of Congress Cataloging-in-Publication Data:

Dalton, David R. Foundations of organic chemistry : unity and diversity of structures, pathways, and reactions / by David R. Dalton. p. cm. ISBN 978-0-470-47908-7 (cloth) 1. Chemistry, Organic–Textbooks. I. Title. QD251.3.D35 2011 547–dc22 2010043290

Printed in Singpore

oBook ISBN: 978-1-118-00539-2ePDF ISBN: 978-1-118-00537-8ePub ISBN: 978-1-118-00538-5

10 9 8 7 6 5 4 3 2 1

ffirs03.indd ivffirs03.indd iv 4/11/2011 11:58:42 AM4/11/2011 11:58:42 AM

CONTENTS

PREFACE xviiACKNOWLEDGMENTS xix

PART I BACKGROUND 1

1. An Introduction to Structure and Bonding 5

A. The Sources of Carbon Compounds 5 I. How Do We Know a Material Is Pure? 6

B. More about Hydrocarbons 11 I. Combustion—Heats of Reaction 12

C. On the Nature of the Chemical Bond 17 I. Ionic and Nonpolar Covalent Bonds 17 II. Polar Covalent Bonds 22 III. Orbital Hybridization 26 IV. Allotropes of Carbon 39 V. Combination of Ionic and Covalent Bonding 40Notice to the Student 43Additional Problems 43Reference 45

2. An Introduction to Spectroscopy and Selected Spectroscopic Methods in Organic Chemistry 46

A. General Introduction 46B. X-ray Crystallography 49C. Photon Spectroscopy 50

I. General Introduction 50 II. UV and VIS Spectroscopy 52 III. IR Spectroscopy 55 IV. Raman Spectroscopy 60 V. Microwave Spectroscopy 60 VI. Magnetic Resonance Spectroscopy 61

a. NMR 61b. ESR 79

D. MS 80 I. Creation of Ions in the Mass Spectrometer:

The Ionization Chamber 81

v

ftoc.indd vftoc.indd v 4/11/2011 11:58:42 AM4/11/2011 11:58:42 AM

vi CONTENTS

II. The Separation of Ions by Mass: The Mass Analyzer 82 III. Detecting the Ions 83Additional Problems 83Reference 84

3. Structure: The Nomenclature of Hydrocarbons and the Shape of Things to Come 85

A. Introduction 85B. Nomenclature and Spectroscopy 86

I. Alkanes 86a. Acyclic Alkanes 86b. Cyclic Alkanes 93

II. Alkenes, Arenes, and Alkynes 97a. Alkenes 98b. Arenes 103c. Alkynes 108

C. Physical and Chemical Properties; Oxidation and Reduction of Hydrocarbons 111 I. The Concept of Homology 111 II. Oxidation and Reduction 113

a. Oxidation 113b. Reduction 116

Additional Problems 120References 123

4. An Introduction to Dynamics 124

A. Introduction 124B. Review of Some Energy Considerations 126C. The Barrier between Reactants and Products 128D. More about the Transition State 130E. Rotation about Sigma (σ) Bonds in Acyclic Alkanes, Alkenes,

Alkynes, and Alkyl-Substituted Arenes 133 I. Alkanes 133 II. Alkenes, Alkynes, and Arenes 137

F. Conformational Analysis of Medium-Ring Cyclic Alkanes 138G. The Conservation of Symmetry during Reactions 156H. The Measurement of Chirality 169

I. The Wave Nature of Light 169 II. Plane-Polarized Light and Handedness 172 III. Optical Rotatory Dispersion (ORD) and Circular

Dichroism (CD) 175Additional Problems 177

5. Classes of Organic Compounds—A Survey: An Introduction to Solvents and to Acids and Bases and to Computational Chemistry 180

ftoc.indd viftoc.indd vi 4/11/2011 11:58:42 AM4/11/2011 11:58:42 AM

CONTENTS vii

A. Introduction 180B. General Characteristics of Functional Group Placement 182C. The Functional Groups and Their Names 183

I. Hydrocarbons 183a. Alkanes 184b. Alkenes 184c. Alkynes 186d. Arenes 187

II. Alkyl and Aryl Halides 188 III. Alcohols and Phenols 194 IV. Ethers 200 V. Thiols, Thioethers, Disulfi des, and Their Oxides 204 VI. Amines, Hydrazines, and Other Nitrogenous Materials 207 VII. Phosphines, Phosphonium Salts, and Other Phosphorus

Derivatives 212 VIII. An Introduction to Organometallic Compounds 214 IX. Compounds Containing Unsaturated Functional Groups 217

a. Aldehydes 217b. Ketones 223c. Nitrogen, Sulfur, and Phosphorus Analogues of Aldehydes

and Ketones 227d. Carboxylic Acids 227e. Carboxylic Acid Derivatives 232

D. An Introduction to Solvents 254 I. Protic and Aprotic Solvents 255 II. Polar and Nonpolar Solvents 256 III. Polarizability 257 IV. Choosing a Solvent 257

a. Solvents for Spectroscopy 257b. Immiscible Liquids 259c. Organic Compounds that Dissolve in Water 259d. Phase Transfer Catalysts 261

E. Acids and Bases 261 I. Brønsted Acids and Bases 262 II. Lewis Acids and Bases 264 III. Hard and Soft Acids and Bases (HSABs) 270

F. Computational Methods 271 I. MM 272

a. Stretching Energy Contribution (Estretch) 272b. Bending Energy Contribution (Ebend) 272c. Stretch-Bend Energy Contribution (Estretch-bend) 272d. van der Waals Energy Contribution (Evan der Waals) 272e. Torsional Energy Contribution (Etorsional) 273f. Dipole Interaction Energy and Dipole Moment

Contribution (Edipole) 273Additional Problems 274

ftoc.indd viiftoc.indd vii 4/11/2011 11:58:42 AM4/11/2011 11:58:42 AM

viii CONTENTS

PART II MIDDLEGROUND 277

6. The Reactions of Hydrocarbons: Oxidation, Reduction, Substitution, Addition, Elimination, and Rearrangement 291

A. Introduction 291B. Alkanes 292

I. Oxidation 292 II. Reduction 295 III. Substitution 296 IV. Rearrangement 301

C. Alkenes 301 I. Oxidation 301 II. Reduction 312 III. Addition 316

a. Electrophilic Addition 317b. Nucleophilic Addition to Alkenes, Dienes, and Polyenes 351c. Radical Addition to Alkenes, Dienes, and Polyenes 354d. Intermolecular Cheletropic and Other Cycloaddition

Reactions 359 IV. Substitution 369 V. Rearrangement 371

D. Alkynes 382 I. Oxidation 382 II. Reduction 385 III. Addition 386

a. Electrophilic Addition 387b. Nucleophilic Addition to Alkynes and Conjugated

Enynes 394c. Radical Addition to Alkynes 398d. Intermolecular Cheletropic and Other Cycloaddition

Reactions 398E. Arenes and Aromaticity: Special Introduction 403

I. Oxidation 413a. Oxidation of the Aromatic Ring 413b. Oxidation of Alkyl Substituents on the Aromatic Ring 419

II. Reduction 420 III. Addition 422 IV. Substitution 424

a. Electrophilic Aromatic Substitution 425b. Nucleophilic Aromatic Substitution 447c. Free Radical Substitution 448

Additional Problems 450

7. The Reactions of Alkyl, Alkenyl, and Aryl Halides: Oxidation, Reduction, Substitution, Addition, Elimination, and Rearrangement 452

ftoc.indd viiiftoc.indd viii 4/11/2011 11:58:42 AM4/11/2011 11:58:42 AM

CONTENTS ix

A. Introduction 452B. Fluorocarbons 456

I. Freons and Halons 457 II. Polymers of Highly Fluorinated Monomers 459 III. Use of Fluorocarbons to Carry Oxygen 459

C. Oxidation 459D. Reduction of Alkyl, Alkenyl, and Aryl Halides 462

I. Dehalogenation and Reductions at Carbon 462a. Hydrogenolysis 463b. Substitution of Hydride for Halide 463c. Radical Replacement of Halogen by Hydrogen 464d. Reaction of Alkyl, Alkenyl, and Aryl Halides with Metals 466

II. Reductions at Halogen 473E. Nucleophilic Substitution 476

I. Nucleophiles and Nucleophilicity 480 II. SN1 481

a. The Kinetics 482b. Electronegativity Differences 485c. The Structure of the Alkyl Group 486d. The Role of the Solvent 487e. The Substrate Stereochemistry Attending the SN1 Reaction 488

III. SN2 492a. The Kinetics 495b. The Stereochemistry of the SN2 Reaction 498c. The Nature of the Leaving Group 500d. The Nature of the Nucleophile 501e. The Nature of the Solvent 502

IV. The SN2′ Reaction 502 V. Nucleophilic Aromatic Substitution 504

a. The Elimination-Addition Pathway (Benzyne) 504b. The Addition-Elimination Pathway (SNAr Substitution) 506

VI. Electrophilic Aromatic Substitution 506 VII. Substitution by Carbon 507 VIII. Photochemically Induced Substitution of Vinyl and

Aryl Halides 510F. Addition Reactions 512

I. Addition Reactions to Vinyl Halides 513G. Elimination Reactions of Alkyl and Alkenyl Halides 517

I. α-Elimination (1,1-Elimination) 519a. α-Elimination of HX (X = Cl, Br) from Alkyl

and Alkenyl Halides 519b. α-Elimination of X2 (X = Cl) from Alkyl Dihalides 521

II. β-Elimination (1,2-Elimination) 521a. β-Elimination of HX (X = F, Cl, Br, I) from Alkyl

and Alkenyl Halides 521

ftoc.indd ixftoc.indd ix 4/11/2011 11:58:43 AM4/11/2011 11:58:43 AM

x CONTENTS

b. 1,2- or α,β-Elimination of X2 (X = Cl, Br) from Alkyl and Alkenyl Dihalides 551

III. γ-Elimination (1,3-Elimination) and δ-Elimination (1,4-Elimination) 551a. γ-Elimination of HX (X = Cl, Br, I) from Alkyl

and Alkenyl Halides 551b. γ-Elimination of X2 (X = Cl, Br, I) from Alkyl Halides 553c. δ-Elimination of X2 (X = Cl, Br, I) from Alkenyl Halides 553

H. Rearrangement Reactions of Alkyl and Alkenyl Halides 553Additional Problems 560References 561

8. Part I. The Reactions of Alcohols, Enols, and Phenols: Oxidation, Reduction, Substitution, Addition, Elimination, and Rearrangement Part II. Ethers Part III. Selected Reactions of Alkyl and Aryl Thiols and Thioethers 562

Special Introduction to Chapter 8 562

Part I. Alcohols, Enols, and Phenols 566

A. Acidity and Basicity 566B. Oxidation of Alcohols, Enols, and Phenols 573

I. Introduction 573 II. Oxidation at the Hydroxyl-Bearing Carbon 574

a. Chemical Oxidation of Alcohols 574b. Biological Oxidation of Alcohols 594

III. Oxidation at Sites That Do Not Bear Hydroxyl 596a. Oxidation of Enols 596b. Oxidation of Phenols 600c. Oxidation at the Double Bond of Allylic Alcohols 604

C. Reduction of Alcohols, Enols, and Phenols 608 I. Reduction of Alcohols 608 II. Reduction of Enols and Phenols 613

D. Substitution Reactions of Alcohol, Enols, and Phenols 615 I. Introduction 615 II. Substitution Reactions of Alcohols, Enols, and Phenols

at Oxygen 617 III. Substitution Reactions of Alcohols at Carbon 618

a. Formation of Alkyl Halides 618b. Replacement of the Hydroxyl (–OH) Functional Group

by Other Substituents 623c. Replacement of the Hydroxyl (–OH) Functional Group

by Carbon: An Example from Nature 627 IV. Substitution Reactions of Enols and Phenols at Carbon 630

a. Substitution at the Carbon-Bearing Oxygen 630b. Electrophilic Aromatic Substitution of Phenols 632

ftoc.indd xftoc.indd x 4/11/2011 11:58:43 AM4/11/2011 11:58:43 AM

CONTENTS xi

E. Addition Reactions of Alcohols, Enols, and Phenols 642 I. Introduction 642 II. Addition of the Oxygen of Alcohols to Carbon

(with Loss of Hydrogen) 643F. Elimination Reactions of Alcohols, Enols, and Phenols 663

I. Introduction 663 II. Acid-Catalyzed Elimination of Water 665 III. Elimination from Derivatives of Alcohols 669

G. Rearrangement Reactions of Alcohols, Enols, and Phenols 678 I. Introduction 678

Part II. Ethers 690

A. Introduction 690B. The Reactions of Ethers 692

Part III. Thiols, Thioethers, and Some Products of Their Oxidation 708

Additional Problems 717References 718

9. Part I. The Reactions of Aldehydes and Ketones: Oxidation, Reduction, Addition, Substitution, and Rearrangement Part II. The Reactions of Carboxylic Acids and Their Derivatives: Oxidation, Reduction, Addition, Substitution, Elimination, and Rearrangement 719

A. Introduction 719

Part I. Aldehydes and Ketones 725

A. Oxidation of Aldehydes and Ketones 725B. Reduction of Aldehydes and Ketones 743

I. Introduction 743 II. Reduction of Aldehydes and Ketones to Hydrocarbons 744 III. Reduction of Aldehydes and Ketones to Alcohols 745

C. Addition to Aldehydes and Ketones 758 I. Introduction 758 II. Photochemical Reactions of Aldehydes and Ketones 762

a. Nonconjugated Carbonyl Compounds 762b. Conjugated Carbonyl Compounds 764

III. Thermal Electrocyclic and Related Reactions of Aldehydes and Ketones 769a. Nonconjugated Carbonyl Compounds 769b. Conjugated Carbonyl Compounds 770c. The Carbonyl “ene” Reaction 771

IV. Nucleophilic Addition Reactions Retaining the Carbonyl Oxygen 772a. General Comments 772

ftoc.indd xiftoc.indd xi 4/11/2011 11:58:43 AM4/11/2011 11:58:43 AM

xii CONTENTS

b. Addition of H–X 774c. Addition of Carbon Nucleophiles 775

V. Nucleophilic Addition Reactions with Loss of the Carbonyl Oxygen 800a. General Comments 800b. Formation of Acetals, Ketals, and Thioketals 800c. Reaction of Aldehydes and Ketones with

Nitrogen Nucleophiles 803d. Replacement of the Carbonyl Oxygen by Halogen

and Sulfur 813e. Replacement of the Oxygen of the Carbonyl by Carbon 816f. Addition to the Carbon Alpha (α) to the Carbonyl (C=O) 831

D. Substitution Reactions Producing Aldehydes and Ketones 841 I. Introduction 841 II. Reimer–Tiemann Synthesis 842 III. Gatterman–Koch (Friedel–Crafts) Formylation 844 IV. The Pauson–Khand Reaction 846

E. Rearrangement Reaction of Aldehydes and Ketones 847 I. Introduction 847 II. The Benzilic Acid Rearrangement 847 III. The Dienone–Phenol Rearrangement 847 IV. Anionic Rearrangements 849

Part II. Carboxylic Acids and Their Derivatives 852

A. General Introduction 852B. Oxidation 854C. Reduction 861D. Substitution: Addition and Elimination 870E. Additional Reactions and Rearrangements of Esters

and β-Dicarbonyl Compounds 926Additional Problems 936

10. Part I. The Reactions of Amines: Oxidation, Reduction, Addition, Substitution, and RearrangementPart II. Some Organophosphorus ChemistryPart III. Some Organosilicon Chemistry 937

Part I. The Reactions of Amines 937

A. Introduction 937B. Some Comments on the Preparation of Amines 945C. Oxidation of Amines 951

I. Oxygen and Peroxide Oxidations 951 II. Other Oxidizing Agents 959

a. General 959b. Oxidation by Halogen 960c. Oxidation with Nitrous Acid 963

ftoc.indd xiiftoc.indd xii 4/11/2011 11:58:43 AM4/11/2011 11:58:43 AM

CONTENTS xiii

D. Reduction of Amines 966E. Addition and Substitution Reactions of Amines 967

I. General Introduction 967F. Addition and Rearrangement Reactions of Amines 977

Part II. Some Organophosphorus Chemistry 995

Part III. Some Organosilicon Chemistry 1005

Additional Problems 1019References 1019

PART III FOREGROUND 1021

11. An Introduction to Carbohydrates, Acetogenins, and Steroids 1027

A. Introduction 1027B. The Calvin Cycle 1028C. Carbohydrates 1037

I. Biosynthesis 1037 II. Chemistry 1039 III. Oligosaccharides 1052 IV. Polysaccharides 1057

D. Acetogenins 1058 I. Acetyl-CoA (CH3COSCoA) 1058 II. Acetyl-CoA (CH3COSCoA) to Fatty Acids and Related

Compounds 1062 III. Isoprenoides: To Dimethylallyl Diphosphate and Beyond 1071

a. Dimethylallyl Diphosphate from Acetyl-CoA via Mevalonate 1071

b. Dimethylallyl Diphosphate from Pyruvate and Glyceraldehyde 1072

c. Terpenes 1076d. Loose Ends 1108

Additional Problems 1120References 1120

12. An Introduction to Amino Acids, Peptides and Proteins, Enzymes, Coenzymes, and Metabolic Processes 1121

A. Introduction 1121B. Amino Acids 1129

I. Biosynthesis 1129 II. Synthesis 1157

C. Peptides and Proteins—Introduction 1184 I. Amino Acids from Peptides 1185 II. Peptides from Amino Acids—In Vivo 1194 III. Peptides from Amino Acids—In Vitro 1206

ftoc.indd xiiiftoc.indd xiii 4/11/2011 11:58:43 AM4/11/2011 11:58:43 AM

xiv CONTENTS

D. The Coenzymes 1210 I. Pyridoxal Phosphate 1212 II. Lipoic Acid 1215 III. Thiamine Diphosphate 1217

a. 4-Amino-5-hydroxymethyl-2-methylpyrimidine 1218b. 4-Methyl-5-(2-Phosphonooxyethyl)thiazole 1219c. Thiamine Diphosphate 1220

IV. Biotin 1223 V. Adenosine 1227 VI. NAD+ 1232 VII. Coenzyme A (CoA-SH) 1236 VIII. FAD 1239 IX. SAM 1246 X. Tetrahydrofolate 1247Reference 1251

13. An Introduction to Alkaloids and Some Other Heterocyclic Compounds 1252

A. Introduction 1252B. Tropane Alkaloids 1254

I. Chemistry of Hyoscyamine 1254 II. Chemistry of Nicotine 1262 III. Biosynthesis of Hyoscyamine and Nicotine 1267

a. The Common Feature 1267b. The Biosynthesis of Nicotine 1269c. The Biosynthesis of Hyoscyamine 1271d. The Biosynthesis of Tropic Acid 1272

C. Morphine (and Codeine and Thebaine) 1275 I. Chemistry of Morphine (and Codeine and Thebaine) 1275 II. The Biosynthesis of Morphine (and Codeine and Thebaine) 1290 III. The Synthesis of Morphine 1296

D. Vinblastine 1301 I. Chemistry of Vinblastine 1301 II. Biosynthesis of Vinblastine 1311

E. Caffeine 1315 I. Some History and the Synthesis of Caffeine 1315 II. Biosynthesis of Caffeine 1318

14. Part I. On the Genetic Code: Unity and Diversity Part II. The Tetrapyrrolic Cofactors: Unity and Diversity 1322

Part I. On the Genetic Code: Unity and Diversity 1322

A. Introduction (the Genetic Code) 1322B. Part A 1323

I. The Bases of DNA and RNA 1323

ftoc.indd xivftoc.indd xiv 4/11/2011 11:58:43 AM4/11/2011 11:58:43 AM

CONTENTS xv

a. Adenine (A) 1324b. Guanine (G) 1324c. Uracil (U) and Thymine (T) 1326d. Cytosine (C) 1329

II. Deoxynucleotides 1331 III. The Role of Phosphate 1336

C. Part B 1340 I. The Sequencing of DNA 1340 II. Chemical Synthesis of DNA 1340 III. Modifi cation to DNA 1345

Part II. The Tetrapyrrolic Cofactors: Unity and Diversity 1347

A. The Tetrapyrrolic Cofactors 1347 I. Introduction 1347 II. Some Early Chemistry 1349 III. Current Biosynthetic Understanding 1354

EPILOGUE 1365

APPENDIX I THE SCHRÖDINGER EQUATION 1366

APPENDIX II THE LITERATURE 1371

INDEX 1373

ftoc.indd xvftoc.indd xv 4/11/2011 11:58:43 AM4/11/2011 11:58:43 AM

ftoc.indd xviftoc.indd xvi 4/11/2011 11:58:43 AM4/11/2011 11:58:43 AM

PREFACE

Welcome! The study of organic chemistry can be fi lled with either the joy of discov-ery of one of the great ongoing intellectual efforts of human beings or the sad drudgery afforded a task seen only as a barrier to “ getting on. ” If you consider it the latter, you will lose the richness of what is offered and will have cheated yourself of a major inheritance.

The organizational tree of organic chemistry, built up over generations, has many branches. Some branches are rich with fruit that should be savored at length; others, fragrant with blossom, invite shorter pause. Still other limbs may be mostly dead-wood, on which some new growth is seen, or may be new sprouts from the main trunk ready for a growth spurt. To appreciate this vibrant life takes time; plan now on budgeting enough.

You will probably fi nd that you are expected to master suffi cient material from lecture and text to be able to make predictions and to justify observations. Although it is true that you must discover for yourself (if you do not already know) what you must do to learn, the time - tested methods of reading, rereading, doing more prob-lems than assigned, and, when you have thought it through and still cannot quite understand, asking your instructor will work here too. However, I hope you are not intimidated by hard work!

D avid R. D alton Philadelphia, Pennsylvania March 2011

xvii

fpref.indd xviifpref.indd xvii 4/11/2011 11:58:42 AM4/11/2011 11:58:42 AM

fpref.indd xviiifpref.indd xviii 4/11/2011 11:58:42 AM4/11/2011 11:58:42 AM

ACKNOWLEDGMENTS

It is clear that I cannot suffi ciently acknowledge the contributions of my family, friends, and colleagues as well as all of the men and women from whom I have learned. However, there are some who, more than others, directly contributed to this volume.

The men and women with whom I worked at Clemson University and, in particu-lar, John Huffman, Karl Dieter, and Melanie Cooper deserve an early mention as their perception of teaching played a signifi cant role. Subsequently, colleagues and students at Temple University struggled with various portions of the manuscript over many revisions and years and the fortitude of Linda Mascavage (Arcadia University), Serge Jasmin (Temple University), Phil Sonnet (USDA, retired), Charlie DeBrosse (Temple University) and Harry Gottlieb (Temple University) in particu-lar, was beyond what any reasonable person could expect.

The staff at John Wiley were left to cope with my efforts and that anything rea-sonable has come out clearly is the responsibility of Jonathan Rose, Lauren Hilger, Amanda Amunullah, Lisa Morano Van Horn and their colleague Stephanie Sakson.

Everything that you don ’ t like and the blunders and errors are mine alone!

D. R. D.

xix

flast.indd xixflast.indd xix 4/11/2011 11:58:42 AM4/11/2011 11:58:42 AM

flast.indd xxflast.indd xx 4/11/2011 11:58:42 AM4/11/2011 11:58:42 AM

PART I

BACKGROUND

Nullius addictus iurare in verba magistri … (I am not bound to swear allegiance to the word of any master … )

— Horrace, Epistulae

INTRODUCTION TO PART I

As is generally true for established subjects, it is diffi cult to know exactly where to begin learning. If a linear historical route is taken, the advantages gained by subse-quent organizational insights are lost. For example, the use of ethyl alcohol ( ethanol , CH 3 CH 2 OH, 1 ) ( Alcohols , Chapter 8 ) as an intoxicant from fermentation of sucrose containing plants ( Carbohydrates , Chapter 11 ) is buried in antiquity, preceding the written record, and the substance we call morphine ( 2 , below) ( Alkaloids , Chapter 13 ) has a recorded history of at least 4000 years. Indeed, the use of the former is attributed to the gods themselves! The latter (albeit in crude form) was apparently obtained from the unripe seed pods (as is done today) of what may have been the opium poppy ( Papaver somniferum L.) by the Sumerians, the early inhabitants of part of what was later called Babylonia and is currently called Iraq. These materials are still being actively studied, and a representation for each of them is shown below. However, to begin to study a well - organized subject with two such diverse materials whose major link appears to be some interesting physiological activity would deny the benefi ts of that organization.

NCH3

OHO

CH3CH2OH

HO

21

H

Thus, we will take, as is usually done, a mixed approach — selectively using history to suit our needs.

Foundations of Organic Chemistry: Unity and Diversity of Structures, Pathways, and Reactions, First Edition. David R. Dalton.© 2011 John Wiley & Sons, Inc. Published 2011 by John Wiley & Sons, Inc.

1

p01.indd 1p01.indd 1 4/11/2011 11:58:43 AM4/11/2011 11:58:43 AM

2 BACKGROUND

Only about 2500 years ago, a Greek school led by Demokritos of Abdera (468 – 370 BCE) laid down ideas we interpret as similar to those of the atomic theory, reformulated in the fi rst decade of the nineteenth century by the English school-teacher and meteorologist John Dalton. *

The years between Demokritos and Dalton had seen advances in the arts of metallurgy, distillation (heating to cause vaporization followed by condensation of the vapors), wine making, and so on, which gradually advanced with the passing generations. In retrospect, the frustration of that slow pace and the absence of tools with which to accelerate it, to satisfy both curiosity and greed, clearly accompanied mankind ’ s plunge into the Dark Ages. That sad period saw the rise of magic and superstition, which still enslave some today, and the mad search for al - kimiya , the Philosopher ’ s Stone. While the alchemist practitioners did slowly advance the tools and techniques of manipulation of materials, that advance was sometimes justifi ed as a search for the “ true names ” of things, so their transformations could be properly affected.

The progress that might have been anticipated following Dalton was not immedi-ately forthcoming. As we shall see, being able to say how many atoms of any given element are present in a molecule is related to the structure of that molecule as the number of bricks in a pile is related to a building, which might be built with them. Thus, some 30 years after Dalton, we fi nd the “ father ” of modern dye chemistry, W. H. Perkin, † apparently assuming (at age 18) that twice the number of atoms in p - N - allyltoluidine (C 10 H 13 N) ( 3 , Chapter 10 ) plus oxygen (3/2 O 2 ) should be equivalent to quinine (C 20 H 24 N 2 O 2 ) ( 4 , Alkaloids, Chapters 12 and 13 ) plus water (H 2 O). When he did the experiment, he treated the p - N - allyltoluidine (C 10 H 13 N), 3 , with the known oxidizing agent potassium dichromate (K 2 Cr 2 O 7 ), a dark brown material was obtained, which, although subsequently leading Perkin to dyestuffs (Chapter 10 ) for wool and cotton, was not the well - defi ned construction quinine (C 20 H 24 N 2 O 2 ) ( 4 ).

N

NH

CH3O

HOH

CH3

N

3 4

H

These retrospective glimpses clearly require our carrying to them our current ideas and tools. Indeed, it can be argued that the development of tools, which con-fi rmed some ideas and not others, has led to our present understandings. However, the tools of organic chemistry are the same as those used elsewhere, and so it is frequently suggested that the study of organic chemistry might begin with those things that distinguish it from other disciplines.

† William Henry Perkin, FRS (1838 – 1907), found, among other colors, “ mauveine ” (today sometimes called simply “ mauve ” ) while working with aniline ( vide infra , Chapter 10 ) and other aromatic amines.

* John Dalton (1766 – 1844) was a teacher of “ natural philosophy ” in Manchester, England, where he studied chemistry and physics. He is known for his research into color blindness (called Daltonism) and atomic theory.

p01.indd 2p01.indd 2 4/11/2011 11:58:43 AM4/11/2011 11:58:43 AM

INTRODUCTION TO PART I 3

In that vein, historically, the subject of organic chemistry was divided from other branches of chemistry fi rst by the idea that organic compounds were exclusive to living systems and that, somehow, such materials possessed special characteristics. Second, having disabused ourselves of that idea, the subject was considered as the domain, for the most part, of compounds of carbon and their interrelationships. Third, and most recently, organic chemistry has evolved into what it is that individu-als who practice the art choose to call what they do. Nonetheless, it is still generally true that the distinguishing characteristic of the study of organic chemistry is the central role played by compounds containing carbon.

So it is, today, very important that you realize, fi rst, that the enormous, yet incom-plete, structure you face, which shares both praise and blame for our current way of life, did not leap into being full grown. The process was slow.

Second, it is continuing to grow. Indeed, the present increasing rate of accretion of information, in part due to a confl uence of trends that include, most apparently, a major refi nement of our tools as they are interfaced with microprocessors, an ever - increasing population of active workers, and rapid communication of results upon which new building can occur, is leading to a better understanding of our world and our place in it. Nonetheless, much of the early work remains important as it serves as the foundation of our present edifi ce, and it will serve as a starting place for us.

p01.indd 3p01.indd 3 4/11/2011 11:58:44 AM4/11/2011 11:58:44 AM

p01.indd 4p01.indd 4 4/11/2011 11:58:44 AM4/11/2011 11:58:44 AM

CHAPTER 1

An Introduction to Structure and Bonding

To every thing there is a season, and a time to every purpose under the sun. — Ecclesiastes 3

A. THE SOURCES OF CARBON COMPOUNDS

An ever - increasing amount of carbon dioxide (CO 2 ) is found in the atmosphere and the oceans, apparently as a result of continuing combustion of fossil fuels and normal life processes. Additionally, much of the biosphere contains carbon locked in plants (as carbohydrates [Chapter 11 ] and related materials about which you will learn). However, most of the compounds of carbon in use today in our technology are obtained either directly from coal or from petroleum — thought by many to have arisen by application of heat and pressure to the decaying products of earlier bio-sphere inhabitants or by laboratory modifi cation of those materials.

Petroleum and coal consist mainly of compounds that contain only carbon and hydrogen. These materials are called hydrocarbons . While the reason for the name should appear clear, it is hoped you might ask how it is known that only hydrogen and carbon are present.

The complete combustion of a hydrocarbon in an oxygen atmosphere generates carbon dioxide (CO 2 ) and water (H 2 O). If all of the carbon is converted to CO 2 and all of the hydrogen to H 2 O, and if there are no other elements besides carbon and hydrogen present in the hydrocarbon, then, as matter is conserved, the amount of carbon in the CO 2 plus the amount of hydrogen in the water must equal the amount of carbon and hydrogen, respectively, in the hydrocarbon combusted.

5

Foundations of Organic Chemistry: Unity and Diversity of Structures, Pathways, and Reactions, First Edition. David R. Dalton.© 2011 John Wiley & Sons, Inc. Published 2011 by John Wiley & Sons, Inc.

Problem 1.1. A pure material is isolated from petroleum and 5.8 mg of the material is burned in a stream of oxygen to yield 17.6 mg of carbon dioxide (CO 2 and 9.0 mg of water (H 2 O). (a) Show how you know the material isolated from petroleum contains only carbon

and hydrogen. (b) Suggest an empirical formula for the material.

c01.indd 5c01.indd 5 4/11/2011 11:52:55 AM4/11/2011 11:52:55 AM

6 AN INTRODUCTION TO STRUCTURE AND BONDING

There is a signifi cant amount of technology required to carry out the determina-tion of the carbon dioxide and water produced in the process Problem 1.1 exempli-fi es. You will note that the material on which the combustion is being carried out is specifi ed as “ pure. ” Second, a weight is given (5.8 mg). Third, a stream of oxygen (O 2 ) is needed. Fourth, the carbon dioxide (CO 2 ) must be weighed, as must the water (H 2 O). Finally, having solved the problem, it should be clear to you that atomic weights for the elements involved were needed.

We will not deal here with the establishment of atomic weights, save to indicate that current usage assigns the atomic weight of 12 C as 12 (exactly) and, for the cal-culations, it is suffi cient to allow 1 H to be 1.00 and 16 O to be 16.00. Figure 1.1 is a pictorial representation of combustion analysis equipment.

You will note, as shown in Figure 1.1 , that there are two removable sections (at the right - hand side of the combustion train). The fi rst contains magnesium perchlo-rate [Mg(ClO 4 ) 2 ] and the second soda lime (a mixture of sodium hydroxide [NaOH] and calcium oxide [CaO]). Magnesium perchlorate [Mg(ClO 4 ) 2 ] readily absorbs water (H 2 O), while soda lime (NaOH + CaO) absorbs carbon dioxide (CO 2 ). Thus, weighing the removable tubes before and after combustion will provide the weights of water (H 2 O) and carbon dioxide (CO 2 ), respectively. Purifi ed, dry oxygen (O 2 ) is currently obtained by distillation from liquefi ed air (another technology we will not discuss here). However, it should be clear to you that the development of the ana-lytical balance, allowing accurate weights to be taken, is critical to the operation of the system. Finally, there is the problem of the analysis being carried out on pure material.

I. How Do We Know a Material Is Pure?

Classically, pure organic compounds were defi ned as those that had the correct elemental composition (within a few tenths of 1% of that calculated) and had sharp melting points (mp) or constant boiling points (bp). * However, your exposure to

Figure 1.1. A schematic representation of a combustion train for the determination of carbon and hydrogen in combustible substances.

Sample in

boat Copper(II) oxide

Excess oxygen

outletOxygen gas

inlet

FurnaceMagnesium perchlorate

Soda lime

NaOH + CaO

* While these values are called “ points, ” you should keep in mind that they are really “ temperatures, ” and usually, for pure materials, the temperature range over which melting (or boiling) occurs is very small.

c01.indd 6c01.indd 6 4/11/2011 11:52:55 AM4/11/2011 11:52:55 AM

THE SOURCES OF CARBON COMPOUNDS 7

general principles of chemistry should be suffi cient for you to recognize that, by today ’ s standards, these criteria may be insuffi cient. Nonetheless, signifi cant basic principles were enunciated with work done on less - than - pure materials (errors often cancel, and frequently, within the limits of the errors, differences could not be detected).

Within the last few decades, powerful tools for purifi cation of materials by sepa-ration have been developed. Distillation and crystallization are two with which you might already be familiar. A third is chromatography (from the Greek chroma , meaning color , and graph , meaning draw or record ). The latter, as you might gather from its name, was originally developed as a tool to separate the colored compo-nents of a mixture by differences in the way they became distributed between a solid stationary adsorbing phase and a liquid mobile phase in which they were soluble.

Today, the original concept has been expanded to include materials without absorption in the visible region of the spectrum (color) and any two different phases, for example, gas – liquid and gas – solid, two immiscible liquids, etc.

As an example, consider the case of two gases, ammonia (NH 3 ) and nitrogen (N 2 ). Ammonia (NH 3 ) is soluble in water (H 2 O) (at room temperature and 1 atm pres-sure) to the extent of about 90 g NH 3 per 100 g H 2 O. Nitrogen (N 2 ), under the same conditions, is soluble to the extent of about 4 g N 2 per 100 g H 2 O. If we have a mixture of N 2 and NH 3 gases in contact with water, ammonia will distribute (or partition ) itself mostly into the aqueous phase, whereas nitrogen, being relatively insoluble, will remain in the gas phase. If we now replace the aqueous solution with fresh water, a second partitioning will occur, and repetition of this process again and again will lead to relatively pure nitrogen (perhaps contaminated with water vapor) and an aqueous solution of ammonia. This tedious procedure can be replaced so that the process can be carried out with greater simplicity, automatically, and nearly continuously by utilizing chromatographic columns that, as originally developed, permit a moving phase containing the materials to be separated to pass over and through particles of a stationary phase that selectively absorbs (or, if only on the surface, adsorbs ) one or more of the materials in the moving phase. Thus, in the example given, if the gaseous mixture were to pass over and through a bed of glass beads, packed in a column and coated with water (H 2 O), then, as the mixture of gases moved through the column, it would continuously encounter fresh water (H 2 O). At each encounter, ammonia (NH 3 ) would be selectively absorbed into the water (H 2 O) as a function of the amount of water (H 2 O) and the various vapor pressures of the gases and water. The gases nitrogen (N 2 ) and ammonia (NH 3 ) could be pushed (continuously be adsorbed and desorbed as the vapor mixture changed) over this bed of beads by a carrier gas , which is relatively less soluble in water than either of them (e.g., helium [He], which has about half the solubility of nitrogen [N 2 ] in water). At a suitable detector (which might, e.g., measure changes in the thermal conductivity of the effl uent gases), the pure helium (the carrier ) would, as it left the column (or eluted ), fi rst fi nd itself contaminated with nitrogen (N 2 ) since it is less soluble in water (H 2 O) than ammonia (NH 3 ) and then with ammonia (NH 3 ), which was delayed by its greater absorption .

Such a process, in which material is partitioned between the gas and the liquid phases, is called gas – liquid partition chromatography (GLPC or, sometimes, GLC or GC). A schematic representation of such equipment is shown in Figure 1.2 , and,

c01.indd 7c01.indd 7 4/11/2011 11:52:55 AM4/11/2011 11:52:55 AM

8 AN INTRODUCTION TO STRUCTURE AND BONDING

commonly, organic compounds can be readily separated from each other, eluted in pure form and analyzed by combustion. For materials that do not lend themselves to this technique because they are too high boiling or because appropriate solid/liquid phases cannot be found, other methods (which include column chromatogra-phy and high - pressure liquid chromatography ) based on the same principle can be applied.

However, such techniques aside, large quantities of purifi ed volatile materials were obtained, historically, by distillation through long columns packed with glass beads or other materials (to increase the surface area on which equilibrium between liquid and vapor could occur). Even today, such distillation columns are part of petroleum refi ning and most mixtures of fuels are prepared by remixing purifi ed materials to obtain appropriate blends.

The technique of fractional distillation is a practical application of Raoult ’ s law . * Consider an ideal solution containing two volatile components, x (bp 80 ° C) and

y (bp 110 ° C), both at 1 atm. The total vapor pressure above a solution of the two materials ( P t ) is equal to the sum of the partial vapor pressures of all components (Equation 1.1 ):

P P P P N P Nt x y x y= + = ° + °x y , (1.1)

where P x , P y = the partial vapor pressure of x and y components, respectively, in the solution at the given temperature; P x ° , P y ° = the vapor pressure of pure x and pure y , respectively, at that temperature; and N x , N y = the mole fraction of x and y , respec-tively, in the solution .

The composition of the vapor mixture in terms of the mole fraction in the vapor state is given by Equation 1.2 for the mole fraction of x ( N ′ x ):

N P P P N P N P N′x x t x x y= = ° ° + °/ /( )x x y . (1.2)

Figure 1.2. A schematic representation of a gas chromatograph.

Heater

Injector

port

Gas regulator

Carrier gas inlet

Thermostated and heated

oven

Thermostated and heated

detector chamber

Vent

Recorder

Detector

* Fran ç ois - Marie Raoult (1830 – 1901), French chemist who long held the chair of chemistry at Grenoble.

c01.indd 8c01.indd 8 4/11/2011 11:52:55 AM4/11/2011 11:52:55 AM