T.W. Graham Solomons did his undergraduate work at The Citadel and received his doctorate in organic chemistry in 1959 from Duke University where he worked with C.K. Bradsher. Following this he was a Sloan Foundation Postdoctoral Fellow at the University of Rachester where he worked with V. Boekelheide. in 1960 he became a charter member of the faculty of the University of South Florida and became Professor of Chemistry in 1973. In 1992 he was made Professor Emeritus. His research interests have been in areas of heterocyclic chemistry and unusual aromatic compounds. He has published papers in the Journal of the American Chemical Society, the Journal of Organic Chemistry, and the Journal of Heterocyclic Chemistry. He has received several awards for distinguished teaching.

Craig B. Fryhle is Chair and Professor of Chemistry at Pacific Lutheran University. He earned his B.A. degree from Gettysburg College and Ph.D. from Brown University. His experiences at these institutions shaped his dedication to mentoring undergraduate students in chemistry and the liberal arts, which is a passion that burns strongly for him. His research interests have been in areas relating to the shikimic acid pathway, including molecular modeling and NMR spectrometry of substrates and analogues, as well as structure and reactivity studies of shikimate pathways enzymes using isotopic labeling and mass spectrometry.

 1 The Basics Bonding and Molecular Structure 1

1.1 Life and the Chemistry of Carbon Compounds—We Are Stardust 2

1.2 Atomic Structure 3

1.3 Chemical Bonds: The Octet Rule 5

1.4 How To Write Lewis Structures 7

1.5 Formal Charges and How To Calculate Them 12

1.6 Isomers: Different Compounds that Have the Same Molecular Formula 14

1.7 How To Write and Interpret Structural Formulas 15

1.8 Resonance Theory 22

1.9 Quantum Mechanics and Atomic Structure 27

1.10 Atomic Orbitals and Electron Configuration 28

1.11 Molecular Orbitals 30

1.12 The Structure of Methane and Ethane: sp³ Hybridization 32

1.13 The Structure of Ethene (Ethylene): sp² Hybridization 36

1.14 The Structure of Ethyne (Acetylene): sp Hybridization 40

1.15 A Summary of Important Concepts that Come from Quantum Mechanics 43

1.16 How To Predict Molecular Geometry: The Valence Shell Electron Pair Repulsion Model 44

1.17 Applications of Basic Principles 47

[ Why do these topics matter? ] 48

2 Families of Carbon Compounds Functional Groups, Intermolecular Forces, and Infrared (IR) Spectroscopy 55

2.1 Hydrocarbons: Representative Alkanes, Alkenes, Alkynes, and Aromatic Compounds 56

2.2 Polar Covalent Bonds 59

2.3 Polar and Nonpolar Molecules 61

2.4 Functional Groups 64

2.5 Alkyl Halides or Haloalkanes 65

2.6 Alcohols and Phenols 67

2.7 Ethers 69

2.8 Amines 70

2.9 Aldehydes and Ketones 71

2.10 Carboxylic Acids, Esters, and Amides 73

2.11 Nitriles 75

2.12 Summary of Important Families of Organic Compounds 76

2.13 Physical Properties and Molecular Structure 77

2.14 Summary of Attractive Electric Forces 85

2.15 Infrared Spectroscopy: An Instrumental Method for Detecting Functional Groups 86

2.16 Interpreting IR Spectra 90

2.17 Applications of Basic Principles 97

[ Why do these topics matter? ] 97

3 Acids and Bases An Introduction to Organic Reactions and Their Mechanisms 104

3.1 Acid–Base Reactions 105

3.2 How To Use Curved Arrows in Illustrating Reactions 107

3.3 Lewis Acids and Bases 109

3.4 Heterolysis of Bonds to Carbon: Carbocations and Carbanions 111

3.5 The Strength of Brønsted–Lowry Acids and Bases: K^a and pK^a 113

3.6 How To Predict the Outcome of Acid–Base Reactions 118

3.7 Relationships between Structure and Acidity 120

3.8 Energy Changes 123

3.9 The Relationship between the Equilibrium Constant and the Standard Free-Energy Change, ΔG ° 125

3.10 Acidity: Carboxylic Acids versus Alcohols 126

3.11 The Effect of the Solvent on Acidity 132

3.12 Organic Compounds as Bases 132

3.13 A Mechanism for an Organic Reaction 134

3.14 Acids and Bases in Nonaqueous Solutions 135

3.15 Acid–Base Reactions and the Synthesis of Deuterium- and Tritium-Labeled Compounds 136

3.16 Applications of Basic Principles 137

[ Why do these topics matter? ] 138

4 Nomenclature and Conformations of Alkanes and Cycloalkanes

4.1 Introduction to Alkanes and Cycloalkanes 145

4.2 Shapes of Alkanes 146

4.3 How To Name Alkanes, Alkyl Halides, and Alcohols: The IUPAC System 148

4.4 How to Name Cycloalkanes 155

4.5 How To Name Alkenes and Cycloalkenes 158

4.6 How To Name Alkynes 160

4.7 Physical Properties of Alkanes and Cycloalkanes 161

4.8 Sigma Bonds and Bond Rotation 164

4.9 Conformational Analysis of Butane 166

4.10 The Relative Stabilities of Cycloalkanes: Ring Strain 168

4.11 Conformations of Cyclohexane: The Chair and the Boat 170

4.12 Substituted Cyclohexanes: Axial and Equatorial Hydrogen Groups 173

4.13 Disubstituted Cycloalkanes: Cis–Trans Isomerism 177

4.14 Bicyclic and Polycyclic Alkanes 181

4.15 Chemical Reactions of Alkanes 182

4.16 Synthesis of Alkanes and Cycloalkanes 182

4.17 How To Gain Structural Information from Molecular Formulas and the Index of Hydrogen Deficiency 184

4.18 Applications of Basic Principles 186

[ Why do these topics matter? ] 187

5 Stereochemistry Chiral Molecules 193

5.1 Chirality and Stereochemistry 194

5.2 Isomerism: Constitutional Isomers and Stereoisomers 195

5.3 Enantiomers and Chiral Molecules 197

5.4 Molecules Having One Chirality Center are Chiral 198

5.5 More about the Biological Importance of Chirality 201

5.6 How To Test for Chirality: Planes of Symmetry 203

5.7 Naming Enantiomers: The R,S-System 204

5.8 Properties of Enantiomers: Optical Activity 208

5.9 Racemic Forms 213

5.10 The Synthesis of Chiral Molecules 214

5.11 Chiral Drugs 216

5.12 Molecules with More than One Chirality Center 218

5.13 Fischer Projection Formulas 224

5.14 Stereoisomerism of Cyclic Compounds 226

5.15 Relating Configurations through Reactions in Which No Bonds to the Chirality Center Are Broken 228

5.16 Separation of Enantiomers: Resolution 232

5.17 Compounds with Chirality Centers Other than Carbon 233

5.18 Chiral Molecules that Do Not Possess a Chirality Center 233

[ Why do these topics matter? ] 234

6 Nucleophilic Reactions Properties and Substitution Reactions of Alkyl Halides 240

6.1 Alkyl Halides 241

6.2 Nucleophilic Substitution Reactions 242

6.3 Nucleophiles 244

6.4 Leaving Groups 246

6.5 Kinetics of a Nucleophilic Substitution Reaction: An S^N2 Reaction 246

6.6 A Mechanism for the S^N2 Reaction 247

6.7 Transition State Theory: Free-Energy Diagrams 249

6.8 The Stereochemistry of S^N2 Reactions 252

6.9 The Reaction of tert-Butyl Chloride with Water: An S^N1 Reaction 254

6.10 A Mechanism for the S^N1 Reaction 255

6.11 Carbocations 257

6.12 The Stereochemistry of S^N1 Reactions 259

6.13 Factors Affecting the Rates of S^N1 and S^N2 Reactions 262

6.14 Organic Synthesis: Functional Group Transformations Using S^N2 Reactions 272

[ Why do these topics matter? ] 275

7 Alkenes and Alkynes I Properties and Synthesis. Elimination Reactions of Alkyl Halides 282

7.1 Introduction 283

7.2 The (E )–(Z ) System for Designating Alkene Diastereomers 283

7.3 Relative Stabilities of Alkenes 284

7.4 Cycloalkenes 287

7.5 Synthesis of Alkenes: Elimination Reactions 287

7.6 Dehydrohalogenation 288

7.7 The E2 Reaction 289

7.8 The E1 Reaction 297

7.9 Elimination and Substitution Reactions Compete With Each Other 299

7.10 Elimination of Alcohols: Acid-Catalyzed Dehydration 303

7.11 Carbocation Stability and the Occurrence of Molecular Rearrangements 308

7.12 The Acidity of Terminal Alkynes 312

7.13 Synthesis of Alkynes by Elimination Reactions 313

7.14 Terminal Alkynes Can Be Converted to Nucleophiles for Carbon–Carbon Bond Formation 315

7.15 Hydrogenation of Alkenes 317

7.16 Hydrogenation: The Function of the Catalyst 319

7.17 Hydrogenation of Alkynes 320

7.18 An Introduction to Organic Synthesis 322

[ Why do these topics matter? ] 326

8 Alkenes and Alkynes II Addition Reactions 337

8.1 Addition Reactions of Alkenes 338

8.2 Electrophilic Addition of Hydrogen Halides to Alkenes: Mechanism and Markovnikov’s Rule 340

8.3 Stereochemistry of the Ionic Addition to an Alkene 345

8.4 Addition of Water to Alkenes: Acid-Catalyzed Hydration 346

8.5 Alcohols from Alkenes through Oxymercuration–Demercuration: Markovnikov Addition 349

8.6 Alcohols from Alkenes through Hydroboration–Oxidation: Anti-Markovnikov Syn Hydration 352

8.7 Hydroboration: Synthesis of Alkylboranes 353

8.8 Oxidation and Hydrolysis of Alkylboranes 355

8.9 Summary of Alkene Hydration Methods 358

8.10 Protonolysis of Alkylboranes 359

8.11 Electrophilic Addition of Bromine and Chlorine to Alkenes 359

8.12 Stereospecific Reactions 363

8.13 Halohydrin Formation 364

8.14 Divalent Carbon Compounds: Carbenes 366

8.15 Oxidation of Alkenes: Syn 1,2-Dihydroxylation 368

8.16 Oxidative Cleavage of Alkenes 371

8.17 Electrophilic Addition of Bromine and Chlorine to Alkynes 374

8.18 Addition of Hydrogen Halides to Alkynes 374

8.19 Oxidative Cleavage of Alkynes 375

8.20 How to Plan a Synthesis: Some Approaches and Examples 376

[ Why do these topics matter? ] 381

9 Nuclear Magnetic Resonance and Mass Spectrometry Tools for Structure Determination 391

9.1 Introduction 392

9.2 Nuclear Magnetic Resonance (NMR) Spectroscopy 392

9.3 How To Interpret Proton NMR Spectra 398

9.4 Shielding and Deshielding of Protons: More about Chemical Shift 401

9.5 Chemical Shift Equivalent and Nonequivalent Protons 403

9.6 Spin–Spin Coupling: More about Signal Splitting and Nonequivalent or Equivalent Protons 407

9.7 Proton NMR Spectra and Rate Processes 412

9.8 Carbon-13 NMR Spectroscopy 414

9.9 Two-Dimensional (2D) NMR Techniques 420

9.10 An Introduction to Mass Spectrometry 423

9.11 Formation of Ions: Electron Impact Ionization 424

9.12 Depicting the Molecular Ion 424

9.13 Fragmentation 425

9.14 Isotopes in Mass Spectra 432

9.15 GC/MS Analysis 435

9.16 Mass Spectrometry of Biomolecules 436

[ Why do these topics matter? ] 436

10 Radical Reactions

10.1 Introduction: How Radicals Form and How They React 449

10.2 Homolytic Bond Dissociation Energies (DH °) 451

10.3 Reactions of Alkanes with Halogens 454

10.4 Chlorination of Methane: Mechanism of Reaction 456

10.5 Halogenation of Higher Alkanes 459

10.6 The Geometry of Alkyl Radicals 462

10.7 Reactions that Generate Tetrahedral Chirality Centers 462

10.8 Allylic Substitution and Allylic Radicals 466

10.9 Benzylic Substitution and Benzylic Radicals 469

10.10 Radical Addition to Alkenes: The Anti-Markovnikov Addition of Hydrogen Bromide 472

10.11 Radical Polymerization of Alkenes: Chain-Growth Polymers 474

10.12 Other Important Radical Reactions 478

 [ Why do these topics matter? ] 482

11 Alcohols and Ethers Synthesis and Reactions 489

11.1 Structure and Nomenclature 490

11.2 Physical Properties of Alcohols and Ethers 492

11.3 Important Alcohols and Ethers 494

11.4 Synthesis of Alcohols from Alkenes 496

11.5 Reactions of Alcohols 498

11.6 Alcohols as Acids 500

11.7 Conversion of Alcohols into Alkyl Halides 501

11.8 Alkyl Halides from the Reaction of Alcohols with Hydrogen Halides 501

11.9 Alkyl Halides from the Reaction of Alcohols with PBr3 or SOCl2 504

11.10 Tosylates, Mesylates, and Triflates: Leaving Group Derivatives of Alcohols 505

11.11 Synthesis of Ethers 507

11.12 Reactions of Ethers 513

11.13 Epoxides 514

11.14 Reactions of Epoxides 516

11.15 Anti 1,2-Dihydroxylation of Alkenes via Epoxides 519

11.16 Crown Ethers 522

11.17 Summary of Reactions of Alkenes, Alcohols, and Ethers 523

[ Why do these topics matter? ] 525

12 Alcohols from Carbonyl Compounds Oxidation –Reduction and Organometallic Compounds 534

12.1 Structure of the Carbonyl Group 535

12.2 Oxidation–Reduction Reactions in Organic Chemistry 536

12.3 Alcohols by Reduction of Carbonyl Compounds 537

12.4 Oxidation of Alcohols 542

12.5 Organometallic Compounds 547

12.6 Preparation of Organolithium and Organomagnesium Compounds 548

12.7 Reactions of Organolithium and Organomagnesium Compounds 549

12.8 Alcohols from Grignard Reagents 552

12.9 Protecting Groups 561

[ Why do these topics matter? ] 562

13 Conjugated Unsaturated Systems

13.1 Introduction 573

13.2 The Stability of the Allyl Radical 573

13.3 The Allyl Cation 577

13.4 Resonance Theory Revisited 578

13.5 Alkadienes and Polyunsaturated Hydrocarbons 582

13.6 1,3-Butadiene: Electron Delocalization 583

13.7 The Stability of Conjugated Dienes 586

13.8 U ltraviolet–Visible Spectroscopy 587

13.9 Electrophilic Attack on Conjugated Dienes: 1,4-Addition 595

13.10 The Diels–Alder Reaction: A 1,4-Cycloaddition Reaction of Dienes 599

[ Why do these topics matter? ] 608

14 Aromatic Compounds

14.1 The Discovery of Benzene 618

14.2 Nomenclature of Benzene Derivatives 619

14.3 Reactions of Benzene 621

14.4 The Kekulé Structure for Benzene 622

14.5 The Thermodynamic Stability of Benzene 623

14.6 Modern Theories of the Structure of Benzene 625

14.7 Hückel’s Rule: The 4n + 2π Electron Rule 628

14.8 Other Aromatic Compounds 636

14.9 Heterocyclic Aromatic Compounds 639

14.10 Aromatic Compounds in Biochemistry 641

14.11 Spectroscopy of Aromatic Compounds 644

[ Why do these topics matter? ] 649

15 Reactions of Aromatic Compounds

15.1 Electrophilic Aromatic Substitution Reactions 661

15.2 A General Mechanism for Electrophilic Aromatic Substitution 662

15.3 Halogenation of Benzene 664

15.4 Nitration of Benzene 665

15.5 Sulfonation of Benzene 666

15.6 Friedel–Crafts Reactions 668

15.7 Synthetic Applications of Friedel–Crafts Acylations: The Clemmensen and Wolff–Kishner Reductions 673

15.8 Existing Substituents Direct the Position of Electrophilic Aromatic Substitution 677

15.9 Activating and Deactivating Effects: How Electron-Donating and Electron-Withdrawing Groups Affect the Rate of an EAS Reaction 684

15.10 Directing Effects in Disubstituted Benzenes 685

15.11 Reactions of Benzene Ring Carbon Side Chains 686

15.12 Synthetic Strategies 689

15.13 The S^NAr Mechanism: Nucleophilic Aromatic Substitution by Addition-Elimination 691

15.14 Benzyne: Nucleophilic Aromatic Substitution by Elimination– Addition 694

15.15 Reduction of Aromatic Compounds 697

[ Why do these topics matter? ] 699

16 Aldehydes and Ketones Nucleophilic Addition to the Carbonyl Group 711

16.1 Introduction 712

16.2 Nomenclature of Aldehydes and Ketones 712

16.3 Physical Properties 714

16.4 Synthesis of Aldehydes 715

16.5 Synthesis of Ketones 720

16.6 Nucleophilic Addition to the Carbon–Oxygen Double Bond: Mechanistic Themes 723

16.7 The Addition of Alcohols: Hemiacetals and Acetals 726

16.8 The Addition of Primary and Secondary Amines 731

16.9 The Addition of Hydrogen Cyanide: Cyanohydrins 736

16.10 The Addition of Ylides: The Wittig Reaction 737

16.11 Oxidation of Aldehydes 741

16.12 The Baeyer–Villiger Oxidation 741

16.13 Chemical Analyses for Aldehydes and Ketones 743

16.14 Spectroscopic Properties of Aldehydes and Ketones 743

16.15 Summary of Aldehyde and Ketone Addition Reactions 746

[ Why do these topics matter? ] 747

17 Carboxylic Acids and Their Derivatives Nucleophilic Addition – Elimination at the Acyl Carbon 761

17.1 Introduction 762

17.2 Nomenclature and Physical Properties 762

17.3 Preparation of Carboxylic Acids 770

17.4 Acyl Substitution: Nucleophilic Addition–Elimination at the Acyl Carbon 773

17.5 Acyl Chlorides 775

17.6 Carboxylic Acid Anhydrides 777

17.7 Esters 778

17.8 Amides 784

17.9 Derivatives of Carbonic Acid 792

17.10 Decarboxylation of Carboxylic Acids 795

17.11 Polyesters and Polyamides: Step-Growth Polymers 797

17.12 Summary of the Reactions of Carboxylic Acids and Their Derivatives 798

[ Why do these topics matter? ] 802

18 Reactions at the α Carbon of Carbonyl Compounds Enols and Enolates 811

18.1 The Acidity of the α Hydrogens of Carbonyl Compounds: Enolate Anions 812

18.2 Keto and Enol Tautomers 813

18.3 Reactions via Enols and Enolates 815

18.4 Lithium Enolates 821

18.5 Enolates of β-Dicarbonyl Compounds 824

18.6 Synthesis of Methyl Ketones: The Acetoacetic Ester Synthesis 825

18.7 Synthesis of Substituted Acetic Acids: The Malonic Ester Synthesis 830

18.8 Further Reactions of Active Hydrogen Compounds 833

18.9 Synthesis of Enamines: Stork Enamine Reactions 834

18.10 Summary of Enolate Chemistry 837

[ Why do these topics matter? ] 838

19 Condensation and Conjugate Addition Reactions of Carbonyl Compounds More Chemistry of Enolates 849

19.1 Introduction 850

19.2 The Claisen Condensation: A Synthesis of β-Keto Esters 850

19.3 β-Dicarbonyl Compounds by Acylation of Ketone Enolates 855

19.4 Aldol Reactions: Addition of Enolates and Enols to Aldehydes and Ketones 856

19.5 Crossed Aldol Condensations 861

19.6 Cyclizations via Aldol Condensations 867

19.7 Additions to α,β-Unsaturated Aldehydes and Ketones 869

19.8 The Mannich Reaction 874

19.9 Summary of Important Reactions 876

[ Why do these topics matter? ] 877

20 Amines

20.1 Nomenclature 891

20.2 Physical Properties and Structure of Amines 892

20.3 Basicity of Amines: Amine Salts 894

20.4 Preparation of Amines 901

20.5 Reactions of Amines 909

20.6 Reactions of Amines with Nitrous Acid 911

20.7 Replacement Reactions of Arenediazonium Salts 913

20.8 Coupling Reactions of Arenediazonium Salts 917

20.9 Reactions of Amines with Sulfonyl Chlorides 919

20.10 Synthesis of Sulfa Drugs 921

20.11 Analysis of Amines 921

20.13 Summary of Preparations and Reactions of Amines 924

[ Why do these topics matter? ] 927

21 Transition Metal Complexes Promoters of Key Bond –Forming Reactions 938

21.1 Organometallic Compounds in Previous Chapters 939

21.2 Transition Metal Elements and Complexes 939

21.3 How to Count Electrons in a Metal Complex 940

21.4 Mechanistic Steps in the Reactions of Some Transition Metal Complexes 942

21.5 Homogeneous Hydrogenation: Wilkinson’s Catalyst 944

21.6 Cross-Coupling Reactions 947

21.7 Olefin Metathesis 955

21.8 Transition Metals in Nature: Vitamin B12 and Vanadium Haloperoxidases 958

[ Why do these topics matter? ] 959

22 Carbohydrates

22.1 Introduction 966

22.2 Monosaccharides 968

22.3 Mutarotation 973

22.4 Glycoside Formation 974

22.5 Other Reactions of Monosaccharides 976

22.6 Oxidation Reactions of Monosaccharides 979

22.7 Reduction of Monosaccharides: Alditols 984

22.8 Reactions of Monosaccharides with Phenylhydrazine: Osazones 984

22.9 Synthesis and Degradation of Monosaccharides 986

22.10 The d Family of Aldoses 988

22.11 Fischer’s Proof of the Configuration of D-(+)-Glucose 988

22.12 Disaccharides 990

22.13 Polysaccharides 994

22.14 Other Biologically Important Sugars 998

22.15 Sugars that Contain Nitrogen 999

22.16 Glycolipids and Glycoproteins of the Cell Surface: Cell Recognition and the Immune System 1001

22.17 Carbohydrate Antibiotics 1003

22.18 Summary of Reactions of Carbohydrates 1004

[ Why do these topics matter? ] 1004

23 Lipids

23.1 Introduction 1012

23.2 Fatty Acids and Triacylglycerols 1012

23.3 Terpenes and Terpenoids 1021

23.4 Steroids 1026

23.5 Prostaglandins 1035

23.6 Phospholipids and Cell Membranes 1036

23.7 Waxes 1040

[ Why do these topics matter? ] 1040

24 Amino Acids and Proteins

24.1 Introduction 1046

24.2 Amino Acids 1047

24.3 Synthesis of α-Amino Acids 1053

24.4 Polypeptides and Proteins 1055

24.5 Primary Structure of Polypeptides and Proteins 1058

24.6 Examples of Polypeptide and Protein Primary Structure 1062

24.7 Polypeptide and Protein Synthesis 1065

24.8 Secondary, Tertiary, and Quaternary Structures of Proteins 1071

24.9 Introduction to Enzymes 1075

24.10 Lysozyme: Mode of Action of an Enzyme 1077

24.11 Serine Proteases 1079

24.12 Hemoglobin: A Conjugated Protein 1081

24.13 Purification and Analysis of Polypeptides and Proteins 1083

24.14 Proteomics 1085

[ Why do these topics matter? ] 1087

25 Nucleic Acids and Protein Synthesis

25.1 Introduction 1091

25.2 Nucleotides and Nucleosides 1092

25.3 Laboratory Synthesis of Nucleosides and Nucleotides 1095

25.4 Deoxyribonucleic Acid: DNA 1098

25.5 RNA and Protein Synthesis 1105

25.6 Determining the Base Sequence of DNA: The Chain-Terminating (Dideoxynucleotide) Method 1113

25.7 Laboratory Synthesis of Oligonucleotides 1116

25.8 Polymerase Chain Reaction 1118

25.9 Sequencing of the Human Genome: An Instruction Book for the Molecules of Life 1120

[ Why do these topics matter? ] 1121

Glossary GL-1

Index I-1

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