Loudon 01-Table of Contents

OrganlcChemlstry

FrFTH EDrrloN r

Marc LoudonPurdue University

ROBERTS AND COMPANY PUBLISHERSGreenwood Village, Colorado

1

PrefaceReviewers and ConsultantsAbout the Author

CHEMIGAT BONDING AND CHEMIGAT STRUGTURE

Contents

xxxlxxxvixxxix

1

1.1

1.2

1.3

1.4

1.5

1.6

1.7

1.8

lntroductionA. What Is Organic Chemistry?B. Emergence of Organic ChemistryC. Why Study Organic Chemistry?

Classical Theories of Chemical BondingA. Electrons in AtomsB. The Ionic BondC. The Covalent BondD. The Polar Covalent Bond

Structures of Covalent GompoundsA. Methods for Determining Molecular GeometryB. Prediction of Molecular Geometry

Resonance StructuresWave Nature of the Electron

Electronic structure of the Hydrogen AtomA. Orbitals, Quantum Numbers, and EnergyB. Spatial Characteristics of OrbitalsC. Summary: Atomic Orbitals of Hydrogen

Electronic Structures of More Complex Atoms

Another took at the Covalent Bond: Molecular OrbitalsA. Molecular Orbital TheoryB. Molecular Orbital Theory and the Lewis Structure of H,

Hybrid OrbitalsA. Bonding in MethaneB. Bonding in Ammonia

11

1

2

33359

1313I4

20

22

23232528

29

323236

373740

vii

1.9

viii coNrENrs

2

Key ldeas in Chapter 1

Additional Problems

ALKANES

4243

46

2.1 Hydrocarbons

2.2 Unbranched Alkanes

2.3 conformations of AlkanesA. Conformation of EthaneB. Conformations of Butane

2.4 Gonstitutional lsomers and NomenclatureA. IsomersB. Organic NomenclatureC. Substitutive Nomenclature of AlkanesD. Highly Condensed StructuresE. Classification of Carbon Substitution

2.5 Cycloalkanes and skeletal structures2.6 Physical Properties of Alkanes

A. Boiling PointsB. Melting PointsC. Other Physical Properties

2.7 Gombustion2.8 occurrence and use of Alkanes

2.9 Functional Groups, Gompound Classes, and the "R" NotationA. Functional Groups and Compound ClassesB. "R" Notation

Key ldeas in Chapter 2Additional Problems

ACIDS AND BASES. THE CURVED.ARROW NOTATION

46

48

505053

575758596466

67

70707374

76

78

3

818182

8383

87

3.1 Lewis Acid-Base Association ReactionsA. Electron-Deficient CompoundsB. Reactions of Electron-Deficient Compounds with Lewis BasesC. The Curved-Arrow Notation for Lewis Acid-Base Association and

Dissociation Reactions

878788

89

4

3.2 Electron-pair oisplacement ReactionsA. Donation of Electrons to Atoms That Are Not Electron-DeficientB. The Curved-Arrow Notation for Electron-Pair Displacement Reactions

3.3 Review of the Curued-Arrow NotationA. Use of the Curved-Arrow Notation to Represent ReactionsB. Use of the Curved-Arrow Notation to Derive Resonance Structures

3.4 Bronsted-Lowry Acids and BasesA. Definition of Brgnsted Acids and BasesB. Nucleophiles, Electrophiles, and Leaving GroupsC. Strengths of Brpnsted AcidsD. Strengths of Brgnsted BasesE. Equilibria in Acid-Base Reactions

3.5 Free Energy and Chemical Equilibrium3.6 Relationship of Structure to Acidity

A. The Element EffectB. The Charge EffectC. The Polar Effect


INTRODUGTION TO AIKENES.STRUCTURE AND REACTIVITY

CONTENTS iX

909091

949494

959698

101103104

106

108108110lll

116117

122

4"1 Structure and Bonding in RfkenesA. Carbon Hybridization in AlkenesB. The n- (Pi) BondC. Double-Bond Stereoisomers

4.2 Nomenclature of AlkenesA. IUPAC Substitutive NomenclatureB. Nomenclature of Double-Bond Stereoisomers: The E,Z Svstem

4.3 Unsaturation Humber4.4 Phy$ical Propefties of Alkenes4.5 Relative $tabilities of Allcene lsomers

A. Heats of FormationB. Relative Stabilities of Alkene Isomers

4.5 Additisn Reactions of Alkenes4"7 Addition of Hydrcgen Halides to nlilrenas

A. Regioselectivity of Hydrogen Halide AdditionB. Carbocation Intermediates in Hydrogen Halide Addition

122r23r25128

131131t34

139

140

141I4Ir44

147

147148r49

CONTENTS

4.8

4.9

C. Structure and Stability of CarbocationsD. Carbocation Rearrangement in Hydrogen Halide Addition

Reaction RatesA. The Transition StateB. The Energy BarrierC. Multistep Reactions and the Rate-Limiting StepD. Hammond's Postulate

catalysisA. Catalytic Hydrogenation of AlkenesB. Hydration of AlkenesC. Enzyme Catalysis


151r54

157158160r62r64

166168r69172

172174

1785 ADDITION REACTIONS OF ALKENES

5.1

5.2

5.3

5.4

5.5

5.6

An Overuiew of Electrophilic Addition Reactions

Reactions of Alkenes with HalogensA. Addition of Chlorine and BromineB. Halohydrins

writing organic Reactions

Gonverion of Alkenes into AlcoholsA. Oxymercuration-Reduction of AlkenesB. Hydroboration-Oxidation of AlkenesC. Comparison of Methods for the Synthesis of Alcohols from Alkenes

Ozonolysis of Alkenes

Free-Radical Addition of Hydrogen Bromide to RlkenesA. The Peroxide EffectB. Free Radicals and the "Fishhook" NotationC. Free-Radical Chain ReactionsD. Explanation of the Peroxide EffectE. Bond Dissociation Energies

5.7 Polymeni: Free-Radical Polymerization of Alkenes

5.8 Alkenes in the Ghemical lndustry


178

181181183

186

187r87190194

196

20020020r202207zrl

214

216

219220

6 PRINCIPLES OF STEREOCHEMISTRY

CONTENTS xl

226

7

6.1 Enantiomelri, Chirality, and SymmetryA. Enantiomers and ChiralityB. Asymmetric Carbon and StereocentersC. Chirality and Symmetry

6.2 Nomenclature of Enantiomers: The R,S System

6.3 Physical Properties of Enantiomers: Optical ActivityA. Polarized LightB. Optical ActivityC. Optical Activities of Enantiomers

6.4 Racemates

5.5 Stereochemical Correlation

6.6 Diastereomers

6.7 Meso Compounds

6.8 Enantiomeric Resolution

6.9 Ghiral Molecules without Asymmetric Atoms

6.10 Conformational StereoisomersA. Stereoisomers Interconvefied by Internal RotationsB. Asymmetric Nitrogen: Amine Inversion

6,17 Drawing Structures That ContainThree-Dimensional lnformation

6.12 The Postulation of Tetrahedral Carbon


cYcHc coMPouNDs.STEREOCHEMISTRY OF REACTIONS

226226229229

231

234235235238

239

241

242

246

249

251

253253255

257

2s9

263253

268

7.1 Relative Stabilities of the Monocyclic Alkanes7.2 Conformations of Gyclohexane

A. The Chair ConformationB. Interconversion of Chair ConformationsC. Boat and Twist-Boat Conformations

268

269269273274

xtl CONTENTS

7.3

7.4

7,5

7.6

7.7

7.8

7.9

INTRODUCTION TO ATKYL HAIIDES, ALCOHOLS,ETHERS, THIOLS, AND SUTFIDES

Monosubstituted Gyclohexalres. Gonformational Rnalysis

Disu bstituted GyclohexanesA. Cis-Trans Isomerism in Disubstituted CyclohexanesB. Conformational AnalysisC. Use of Planar Structures for Cyclic CompoundsD. Stereochemical Consequences of the Chair Interconversion

Gyclopentar€, Gyclobutane, and GyclopropaneA. CyclopentaneB. Cyclobutane and Cyclopropane

Bicyclic and Polycyclic GompoundsA. Classification and NomenclatureB. Cis and Trans Ring FusionC. Trans-Cycloalkenes and Bredt's RuleD. Steroids

Relative Reactivities of StereoisomersA. Relative Reactivities of EnantiomersB. Relative Reactivities of Diastereomers

Reactions That Form StereoisomersA. Reactions of Achiral Compounds That Give Enantiomeric ProductsB. Reactions That Give Diastereomeric Products

Stereochemistry of Ghemical ReactionsA. Stereochemistry of Addition ReactionsB. Stereochemistry of Substitution ReactionsC. Stereochemistry of Bromine AdditionD. Stereochemistry of Hydroboration-OxidationE. Stereochemistry of Other Addition Reactions


277

281281283284285

288288289

290290292294296

298298300

301301304

30530s306308312313

314316

323I8.1 Nomenclature

A. Nomenclature of Alkyl HalidesB. Nomenclature of Alcohols and ThiolsC. Nomenclature of Ethers and Sulfides

8.2 Structures

8.3 Effect of Molecular Polarity andHydrogen Bonding on Physical PropertiesA. Boiling Points of Ethers and Alkyl Halides

324324326330

332

333333

CONTENTS XI II

9

B. Boiling Points of AlcoholsC. Hydrogen Bonding

8,4 Solvents in Organic ChemistryA. Classification of SolventsB. Solubility

8,5 Application$ of Solubility and Solvation principle$A. Cell Membranes and Drug SolubilityB. Cation-Binding Molecules

8,6 Acidity of Alcohols and ThiolsA. Formation of Alkoxides and MercaptidesB. Polar Effects on Alcohol AcidityC. Role of the Solvent in Alcohol Acidity

8.7 Bssicity of Alcohols and Ethers

8.8 Grignard and Organolithium ReagentsA. Formation of Grignard and Organolithium ReagentsB. Protonolysis of Grignard and Organolithium Reagents

8.9 Industrial Prepsration and Use ofAlkyl Halides, Alcohols, and EthersA. Free-Radical Halogenation of AlkanesB. Uses of Halogen-Containing CompoundsC. Production and Use of Alcohols and EthersD. Safety Hazards of Ethers

Key ldeas in Chapter Il\dditional Problems

THE CHEMISTRY OF ALKYL HALIDES

335336

339339340

346346351

3S5356358358

359

361361362

3643643653683tl

372373

377

9.1 An Overview of ruucleophilic Substitutionand p-Elimination ReactionsA. Nucleophilic Substitution ReactionsB. B-Elimination ReactionsC. Competition between Nucleophilic Substitution and B-Elimination Reactions

9.2 Equilibria in tUucleophilic Substitution Reactaons

9.3 Reaction RatesA. Definition of Reaction RateB. The Rate LawC. Relationship of the Rate Constant to the Standard Free Energy of Activation

9.4 The S*2 ReactionA. Rate Law and Mechanism of the S*2 Reaction

377377378380

381

382382383384

385386

XIV CONTENTS

B. Comparison of the Rates of S*2 Reactions and Bronsted Acid-Base ReactionsC. Stereochemistry of the S*2 ReactionD. Effect of Alkyl Halide Structure on the S0.2 ReactionE. Nucleophilicity in the S*2 ReactionF. Leaving-Group Effects in the S*2 ReactionG. Summary of the S*2 Reaction

9.5 The E2 ReactionA. Rate Law and Mechanism of theE2 ReactionB. Why theE2 Reaction Is ConcertedC. Leaving-Group Effects on the E2 ReactionD. Deuterium Isotope Effects in the E2 ReactionE. Stereochemistry of the E2 ReactionF. Regioselectivity of the E2 ReactionG. Competition between theE2 and S,o2 Reactions: A Closer LookH. Summary of the E2 Reaction

9.5 The S*1 and El ReactionsA. Rate Law and Mechanism of S*1 and El ReactionsB. Rate-Limiting and Product-Determining StepsC. Reactivity and Product Distributions in S*1-E1 ReactionsD. Stereochemistry of the S"l ReactionE. Summary of the S*l and El Reactions

9.7 Summary of Substitution and EliminationReactions of Alkyl Halides

9.8 Carbenes and CarbenoidsA. a-Elimination ReactionsB. The Simmons-Smith Reaction


10 THE CHEMISTRY OF AICOHOIS AND THIOTS

388388390392398399

4004004004024024044064074tl

4124124t44t6418420

429

424424426

428429

436

10.1 Dehydration of Alcohols

1O.2 Reactions of Alcohols with Hydrogen Halides

10.3 Sulfonate and Inorganic Ester Derivatives of AlcoholsA. Sulfonate Ester Derivatives of AlcoholsB. Alkylating AgentsC. Ester Derivatives of Strong Inorganic AcidsD. Reactions of Alcohols with Thionyl Chloride and Phosphorus Tribromide

1O.4 Conversion of Alcohols intoAlkyl Halides: Summary

435

440

443443447448449

450

11

10.5 Oxidation and Reduction in Organic GhemistryA. Half-Reactions and Oxidation NumbersB. Oxidizing and Reducing Agents

10.6 Oxidation of AlcoholsA. Oxidation to Aldehydes and KetonesB. Oxidation to Carboxylic Acids

1O"7 Biological Oxidation of Ethanol

10.8 Chemlcal and Stereochemical Grcup RelationshipsA. Chemical Equivalence and NonequivalenceB. Stereochemistry of the Alcohol Dehydrogenase Reaction

10.9 Oxidation of Thiols

1O.1O $ynthesis of Alcohols

10.11 Desigil of Organic Synthesis


THE CHEMISTRY OF ETHERS, EPOXIDES,GLYGOLS, AND SULFIDES

CONTENTS XV

452452156

45945946r

462

465465469

471

474

474

476477

482

11.'l Synthesis of Ethers and SulfidesA. Williamson Ether SynthesisB. Alkoxymercuration-Reduction of AlkenesC. Ethers from Alcohol Dehydration and Alkene Addition

11,2 Synthesis of EpoxidesA. Oxidation of Alkenes with Peroxycarboxylic AcidsB. Cyclization of Halohydrins

11.3 Gleavage of Ethers

11.4 Nucleophilic Substitutioil Reactisns of EpoxidesA. Ring-Opening Reactions under Basic ConditionsB. Ring-Opening Reactions under Acidic ConditionsC. Reaction of Epoxides with Organometallic Reagents

11.5 Preparation and Oxldative Cleavage of GlycolsA. Preparation of GlycolsB. Oxidative Cleavage of Glycols

11.5 oxonium and sulfonium saltsA. Reactions of Oxonium and Sulfonium SaltsB. S-Adenosylmethionine: Nature's Methylating Agent

482482484485

48848849r

492

495495497500

503503s06

508508509

xvl CONTENTS

11.7 tntramolecular Reactlons and the Proximity EffectA. Neighboring-Group ParticipationB. The Proximity Effect and Effective MolarityC. Stereochemical Consequences of Neighboring-Group Participation

11.8 Oxidation of Ethers and Sulfides

11.9 The Three Fundamental Operations of Organic Synthesis11.10 Synthesis of Enantiomerically pure Compounds:

Asymmetric Epoxidation

Key ldeas in chapter 11Additional Problems

ITUTRODUCTION TO SPECTROSCOPY. INFRAREDSPECTROSCOPY AND MASS SPECTROMETRY12

5r05r05135r6

518

520

5e2

5?7s?8

s36

12,1 Introduction to SpectroscopyA. Electromagnetic RadiationB. Absorption Spectroscopy

12.2 lnfrared SpectroscopyA. The Inf-rared SpectrumB. Physical Basis of IR Spectroscopy

12.3 lnfrared Absorption and Chemical StructureA. Factors That Determine IR Absorption PositionB. Factors That Determine IR Absorption Intensity

12.4 Functional-Group Infrared AbsorptionsA. IR Spectra of AlkanesB. IR Spectra of Alkyl HalidesC. IR Spectra of AlkenesD. IR Spectra of Alcohols and Ethers

12.5 Obtaining an Infrared Spectrum12.6 lntroduction to Mass Spectrometry

A. Electron-Impact Mass SpectraB. Isotopic PeaksC. FragmentationD. The Molecular Ion. Chemical-Ionization Mass SpectraE. The Mass Spectrometer


536536538

54054054?

544545548

5525s2552553556

557

558558560563566569

571571

CONTENTS XVI I

13 NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY 578

13.1 An Overview of Proton NMR Spectroscopy

13.2 physlcal Basls of NMR spectroscopy

13.3 The NMR Spectrum: Ghemlcal Shift and htegralA. Chemical ShiftB. Chemical Shift ScalesC. Relationship of Chemical Shift to StructureD. The Number of Absorptions in an NMR SpectrumE. Counting Protons with the IntegralF. Using the Chemical Shift and Integral to Determine Unknown Structures

13.4 The NMR Spectrum: spin-spln spllttingA. The n * 1 Splitting RuleB. Why Splitting OccursC. Solving Unknown Structures with NMR Spectra Involving Splitting

13.5 Complex NMR SpecffaA. Multiplicative SplittingB. Breakdown of the n * I Rule

13.6 Use of Deuterlum in Proton NMR

13.7 Characterlstic Functlonal-Group NMR AbsorptionsA. NMR SPectra of AlkenesB. NMR Spectra of Alkanes and CycloalkanesC. NMR Spectra of Alkyl Halides and EthersD. NMR SPectra of Alcohols

13.8 NMR Spectroscopy of Dynamic Systems

13.9 Carbon NMR

13.10 Solving Structure Problems with Spectroscopy

13.11 The NMR Spectrometer

13.12 Other Uses of NMR

Key ldeas in ChaPter 13Additional Problems

14 THE CHEMISTRV OF ATKYNES

578

581

s83583585586589592593

59S596599601

603603607

611

6',12

612614616616

619

629

6e9

639

634

63563S

644

14.1 Nomenclature of AlkYnes

t{.e $tructure and Bonding in Alltynes

644

646

XViii CONTENTS

14.3

14.4

14.5

14.6

14.7

14.9

14.9

14.10

Physical Properties of RlkynesA. Boiling Points and SolubilitiesB. IR Spectroscopy of AlkynesC. NMR Spectroscopy of Alkynes

Introduction to Addition Reactions of the Triple Bond

Conversion of Alkynes into Aldehydes and KetonesA. Hydration of AlkynesB. Hydroboration-Oxidation of Alkynes

Reduction of AlkynesA. Catalytic Hydrogenation of AlkynesB. Reduction of Alkynes with Sodium in Liquid Ammonia

Acidity of l-AlkynesA. Acetylenic AnionsB. Acetylenic Anions as Nucleophiles

Organic Synthesis Using AlkynesPheromones

Occurrence and Use of Alkynes


6496496496s0

5s2

654654657

659659660

662662665

666

668

574

57 1

671

67615 DIENES, RESONANCE, AND AROMATICITY

15.1 Structure and Stability of DienesA. Stability of Conjugated Dienes. Molecular OrbitalsB. Structure of Conjugated DienesC. Structure and Stability of Cumulared Dienes

15.2 Ultraviolet-Visible SpectroscopyA. The UV-Vis SpectrumB. Physical Basis of UV-Vis SpectroscopyC. UV-Vis Spectroscopy of Conjugated Alkenes

15.3 The Diels-Alder ReactionA. Reaction of conjugated Dienes with AlkenesB. Effect of Diene Conformation on the Diels-Alder ReactionC. Stereochemistry of the Diels-Alder Reaction

15.4 Addition of Hydrogen Halides to conjugated DienesA. 1,2- and 1,4-AdditionsB. Allylic Carbocations. The Connection between Resonance and StabilitvC. Kinetic and Thermodynamic Control

677677680682

684684686687

690690694696

700700702705

CONTENTS XIX

15,5 Diene Polymers

15.6 ResonanceA. Drawing Resonance StructuresB. Relative Importance of Resonance StructuresC. Use of Resonance Structures

15.7 Introduction to Aromatic Compound$A. Benzene, aPuzzling 'Alkene"B. Structure of BenzeneC. Stability of BenzeneD. Aromaticity and the Hiickel an | 2 RuleE. Antiaromatic Compounds


708

7497t07Ir714

716l1771872172r728

730731

16 THE CHEMISTRY OF BENZENE AND ITS DERIVATIVES 74O

16.1 Nomenclature of Benzene Derivatives

16.2 Physical troperties of Benzene Derivatives

16.3 Spectroscopy of Benzene DerivativesA. IR SPectroscoPyB. NMR Spectroscopyc. r3C NMR spectroscopyD. UV Spectroscopy

16.4 Electrophilic Aromatic Substitution Reactions of BenzeneA. Halogenation of BenzeneB. Electrophilic Aromatic SubstitutionC. Nitration of BenzeneD. Sulfonation of BenzeneE. Friedel-Crafts Alkylation of BenzeneF. Friedel-Crafts Acylation of Benzene

16.5 Electrophilicaromatic Substitution Reactionsof Substituted BenzenesA. Directing Effects of SubstituentsB. Activating and Deactivating Effects of SubstituentsC. Use of Electrophilic Aromatic Substitution in Organic Synthesis

16.6 Hydrogenation of Benzene Derivatives

15.7 source and lndustrial Use of Aromatic ttydrocarbons

rey ldeas in ChaPter t6Additional Problems

744

743

743143744748748

75075r753754755756759

762762768772

776

777

780780

XX CO NTE NTS

17 ALTYLIG AND BENZYLIG REAGTIVITY 788

17.1 Reactions tnvolvlng Allylic and Benzyllc Carbocations17.2 Reactions lnvolvlng Allyllc and Benzylic Radicals17.3 Reactions tnvolvlng Allylic and Benzyllc Anions

A. Allylic Grignard ReagentsB. E2 Eliminations Involving Allylic or Benzylic Hydrogens

17.4 Allyllc and Benzylic Sn2 Reactions

17.s Allyllc and Benzylic OxidationA. Oxidation of Allylic and Benzylic AlcoholsB. Benzylic Oxidation of Alkylbenzenes

17.6 TerpenesA. The Isoprene RuleB. Biosynthesis of Terpenes

Key ldeas in chapter 17Additional Problems

789

793

798799801

802

803803805

807807810

813814

18 THE CHEM|STRY OF ARYL HAL|DES, VtNyLtc HALIDES,AND PHENOLS. TRANSITION.METAL CATALYSIS 822

18.1 Lack of Reactivity of vinylic and Aryl Halidesunder SNz Gonditlons

18.2 Elimination Reactions of vinylic Halides

18.3 Lack of Reactivlty of Vinylic andAryl Halldes under SNI Gonditions

18.4 NucleophilicAromatic substitutionReactions of Aryl Halides

18,5 Introduction to Transition-Metal Catalyzed ReactionsA. Transition Metals and Their ComplexesB. Oxidation StateC. The d'NotationD. Electron Counting: The 16- and lS-Electron RulesE. Fundamental Reactions of Transition-Metal Complexes

18-6 Examples ofTransition-Metal-Catalyzed ReactionsA. The Heck ReactionB. The Suzuki Coupling

8?3

825

826

828

831832835836836839

845845848

19

C. Alkene MetathesisD. Other Examples of Transition-Metal-Catalyzed Reactions

18.7 Acidity of PhenolsA. Resonance and Polar Effects on the Acidity of PhenolsB. Formation and Use of Phenoxides

18.8 Oxidation of Phenols to Quinones

18.9 Electrophillc eromatic Substitution Reactions of Phenols

18.10 Reactivity of the Aryl-oxygen BondA. Lack of Reactivity of the Aryl-Oxygen Bond in S*l and S*2 ReactionsB. Substitution at the Aryl-Oxygen Bond: The Stille Reaction

18.11 hdustrial Preparation and Use of Phenol


THE GHEMISTRY OF ALDEHYDES AND KETONES.CARBONYT.ADDITION REACTIONS

CONTENTS XXi

852857

858858861

862

867

870870872

874

875876

888

19.1 Nomenclature of Aldehydes and KetonesA. Common NomenclatureB. Substitutive Nomenclature

19.2 Physical Properties of Aldehydes and Ketones

19.3 Spectroscopy of Aldehydes and KetonesA. IR SpectroscopyB. Proton NMR SpectroscopyC. Carbon NMR SpectroscopyD. UV SpectroscopyE. Mass Spectrometry

19.4 Synthesis of Aldehydes and Ketones

19.5 htroduction to Aldehyde and Ketone Reactions

19.6 Basicity of Aldehydes and Ketones

19.7 Reversible Rddition Reactions of Aldehydes and KetonesA. Mechanisms of Carbonyl-Addition ReactionsB. Equilibria in Carbonyl-Addition ReactionsC. Rates of Carbonyl-Addition Reactions

19.8 Reduction of Aldehydes and Ketones to Alcohols

890890892

894

895895897898899901

903

903

904

997907910913

914

xxii coNrENrs

1g.g

19.10

19.11

19,12

19.13

19,14

19.15

Reactions of Aldehydes and Ketones withGrignard and Related Reagents

Acetals and Their Use as Protecting GroupsA. Preparation and Hydrolysis of AcetalsB. Protecting Groups

Reactions of Aldehydes and Ketones with AminesA. Reaction with Primary Amines and Other Monosubstituted

Derivatives of AmmoniaB. Reaction with Secondary Amines

Reduction of carbonyl Groups to Methylene Groups

The Wittig Alkene SynthesisOxidation of Aldehydes to Carboxylic AcidsManufacture and use of Aldehydes and Ketones


918

921921925

926

926929

931

933

936

938

93e940

94820 THE CHEMISTRY OF CARBOXYLIC ACIDS

20.1

20.2

20.3

2A,4

20.5

20,6

20.7

20.9

Nomenclature of Carboxylic RcidsA. Common NomenclatureB. Substitutive Nomenclature

Structure and Physical Properties of Carboxylic Rcids

Spectroscopy of Carboxylic RcidsA. IR SpectroscopyB. NMR Spectroscopy

Acid-Base Properties of Garboxylic RcidsA. Acidity of Carboxylic and Sulfonic AcidsB. Basicity of Carboxylic Acids

Fatty Acids, Soaps, and DetergentsSynthesis of Carboxylic Rcids

lntroduction to carboxylic Rcid Reactions

Gonversion of carboxylic Rcids into EstersA. Acid-Cataly zed Esterifi cationB. Esterification by Alkylation

948948951

953

955955955

957957960

960

963

964

965965968

20.9 Gonversion of Carboxylic Acids into AcidChlorides and AnhydridesA. Synthesis of Acid ChloridesB. Synthesis of Anhydrides

20.10 Reduction of Garboxylic Acids to Primary Alcohols

2O.11 Decarboxylation of Garboxylic Acids


CONTENTS XXI I I

9IO970972

974

976

978979

21 THE CHEMISTRY OF GARBOXYTIC AGID DERIVATIVES 986

21.1 Nomenclature and Glassificationof Carboxylic Acid DerivativesA. Esters and LactonesB. Acid HalidesC. AnhydridesD. NitrilesE. Amides, Lactams, and ImidesF. Nomenclature of Substituent GroupsG. Carbonic Acid Derivatives

21.2 Structures of Carboxylic Acid Derivatives

21.3 Physical Propefties of Carboxylic Acid DerivativesA. EstersB. Anhvdrides and Acid ChloridesC. NitrilesD. Amides

21.4 Spectroscopy of Carboxylic Rcid DerivativesA. IR SpectroscopyB. NMR Spectroscopy

21.5 Basicity of Garboxylic Acid Derivatives

21.6 Introduction to the Reactions of carboxylic Acid

21,7 llydrolysis of Carboxylic Acid Derivatives

Derivatives 1003

98698698898898998999r99r

992

99499499499599s

996996997

1000

10041004I 008r 0091011101 1

A. Hydrolysis of EstersB. Hydrolysis of AmidesC. Hydrolysis of NitrilesD. Hydrolysis of Acid Chlorides and AnhydridesE. Mechanisms and Reactivity in Nucleophilic Acyl Substitution Reactions

XX|V CoNTENTS

22

21.8 Reactions of Carboxylic ncidDerivatives with NucleophilesA. Reactions of Acid Chlorides with NucleophilesB. Reactions of Anhydrides with NucleophilesC. Reactions of Esters with Nucleophiles

21.9 Reduction of Garboxylic Acid DerivativesA. Reduction of Esters to Primary AlcoholsB. Reduction of Amides to Amines

s ftt*:ti:t :i xt#nffiT?:*il'ffT*'/

E. Relative Reactivities of Carbonyl Compounds

21 10 ffifiit?ll ""ff:[3fr]['il:#?$,3"'iva*vesA. Reaction of Esters with Grignard ReagentsB. Reaction of Acid Chlorides with Lithium Dialkylcuprates

21.11 Synthesis of Carboxylic Acid Derivatives21 12

Hi':11 lfilll'ffi "'**iTlox'r i c

A. Nylon and PolyestersB. Waxes, Fats, and Phospholipids

ffi1,iff::,.;':[il;T"

THE CHEMISTRY OF ENOTATE IONS, ENOLS,AND a,B-UNSATURATED CARBONYL GOMPOUNDS

101610161019I 020

1022t0221 023I 025t02l1 028

'1o29r029103 l

1032

10341 031l 036

1 0371 038

1047

22.1 Acidity of Garbonyl CompoundsA. Formation of Enolate AnionsB. Introduction to Reactions of Enolate Ions

22.2 Enolization of Carbonyl Compounds

22.3 orHalogenation of Carbonyl CompoundsA. Acid-Catalyzed a-HalogenationB. Halogenation of Aldehydes and Ketones in Base: The Haloform ReactionC. a-Bromination of Carboxylic AcidsD. Reactions of a-Halo Carbonyl Compounds

22.4 Aldol Addition and Aldol GondensationA. Base-Catalyzed Aldol ReactionsB. Acid-Catalyzed Aldol CondensationC. Special Types of Aldol ReactionsD. Synthesis with the Aldol Condensation

1048r 048105 1

1053

1057l 0571 0591060r062

1063I 0631066r067I 070

CONTENTS XXV

23

22.5 Gondensation Reactions |nvolving Ester Enolate lonsA. Claisen CondensationB. Dieckmann CondensationC. Crossed Claisen CondensationD. Synthesis with the Claisen Condensation

22.6 Biosynthesis of Fatty Acids

22,7 Alkylation of Ester Enolate lonsA. Malonic Ester SynthesisB. Direct Alkylation of Enolate Ions Derived from MonoestersC. Acetoacetic Ester Synthesis

22.8 Conjugate-Addition ReactionsA. Conjugate Addition to a,B-Unsaturated Carbonyl CompoundsB. Conjugate Addition Reactions versus Carbonyl-Group ReactionsC. Conjugate Addition of Enolate Ions

22.9 Reduction of n,F-Unsaturated Carbonyl Gompounds

22.10 Reactions of c,F-Unsaturated GarbonylCompounds with Organometallic ReagentsA. Addition of Organolithium Reagents to the Carbonyl GroupB. Conjugate Addition of Lithium Dialkylcuprate Reagents

22.11 Organic Synthesis with Conjugate-Addition Reactions


THE CHEMISTRY OF AMINES

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1081

1084I 0841 086I 089

1492r092I 095t091

1 100

1 1011101I 102

1 103

1 1051146

1116

23.1 Nomenclature of AminesA. Common NomenclatureB. Substitutive Nomenclature

23.2 Structure of Amines

23.3 Physical Properties of Amines

23.4 Spectroscopy of AminesA. IR SpectroscopyB. NMR Spectroscopy

23.5 Basicity and Acidity of AminesA. Basicity of AminesB. Substituent Effects on Amine BasicityC. Separations Using Amine BasicityD. Acidity of AminesE. Summary of Aciditv and Basicity

1117IttTtln

1119

1124

1127ttzlttzl

1122tt22tt231 t271 128rr29

XXVI CoNTENTS

24

23.6 Quaternary Ammonium and Phosphonium Salts

23.7 Alltylation and Acylation Reactions of RminesA. Direct Alkvlation of AminesB. Reductive AminationC. Acylation of Amines

23.8 Hofmann Elimination of Quaternary Ammonium Hydroxides 1136

23.9 Aromatic Substitution Reactions of Aniline Derivatives23.10 Diazotization; Reactions of Diazonium lons

A. Formation and Substitution Reactions of Diazonium SaltsB. Aromatic Substitution with Diazonium IonsC. Reactions of Secondary and Tertiary Amines with Nitrous Acid

23.11 Synthesis of AminesA. Gabriel Synthesis of Primary AminesB. Reduction of Nitro CompoundsC. Amination of Aryl Halides and Aryl TriflatesD. Curtius and Hofmann RearrangementsE. Synthesis of Amines: Summary

23.12 Use and Occurrence of AminesA. Industrial Use of Amines and AmmoniaB. Naturally Occurring Amines


CARBOHYDRATES

1 138

11391 139Ir42II44

1145tr45t146tr47I 150lt54

11551 155I 155

11571158

1156

1129

113111311 1331 135

24,1 Glassification and Properties of Carbohydrates24.2 FischerProiections24.3 Structures of the Monosaccharides

A. Stereochemistry and Confi gurationB. Cyclic Structures of the Monosaccharides

24.4 Mutarotation of Garbohydrates

24.5 Base-Catalyzed lsomerization of Aldoses and Ketoses

24.6 Glycosides

24.7 Ether and Ester Derivatives of Garbohydrates24.8 Oxidation and Reduction Reactions of Carbohydrates

A. Oxidation to Aldonic Acids

1167

1168

1173tt731178

1183

1186

1188

1191

1193tt94

B. Oxidation to Aldaric AcidsC. Periodate OxidationD. Reduction to Alditols

24.9 Kiliani-Fischer Synthesis

24.10 Proof of Glucose StereochemistryA. Which Diastereomer? The Fischer ProofB. Which Enantiomer? The Absolute Configuration of n-(+)-Glucose

24.11 Disaccharides and Polysaf,charidesA. DisaccharidesB. Polysaccharides


CONTENTS XXVI I

1 1951 196rr97

r 198

11991199r203

12051205r209

12121213

25 THE CHEMISTRY OF THE AROMATIC HETEROGYCTES 1220

25.1 Nomenclature and Structure of the Aromatic HeterocyclesA. NomenclatureB. Structure and Aromaticity

25.2 Sasicity and Acidity of the Nitrogen HeterocyclesA. Basicity of the Nitrogen HeterocyclesB. Acidity of Pyrrole and Indole

25.3 The Chemistry of Furan, Pyrrolq and ThiopheneA. Electrophilic Aromatic SubstitutionB. Addition Reactions of FuranC. Side-Chain Reactions

25.4 The chemistry of eyridineA. Electrophilic Aromatic SubstitutionB. Nucleophilic Aromatic SubstitutionC. N-Alkylpyridinium Salts and Their ReactionsD. Side-Chain Reactions of Pyridine DerivativesE. Pyridinium Ions in Biology: Pyridoxal Phosphate

25.5 tuucleosides, Nucleotides, and Nucleic AcidsA. Nucleosides and NucleotidesB. The Structures of DNA and RNAC. DNA Modification and Chemical Carcinogenesis

25.6 Other Biologically lmportant Heterocyclic Compounds

Key ldeas in Chapter 25Additional Problem$

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12241224r226

1226t226r229r230

1231I23Tt2341238r239r240

1245t245t248t253

r 255

1?571 258

xxviii coNrENrs

26 AMINO ACIDS, PEPTIDES, AND PROTEINS 1255

26.1 Nomenclature of Amino Acids and PeptidesA. Nomenclature of Amino AcidsB. Nomenclature of Peptides

26.2 Stereochemistry of the rAffiiro Acids

26.3 Acid-Base Properties of Amino Acids and PeptidesA. Zwitterionic Structures of Amino Acids and PeptidesB. Isoelectric Points of Amino Acids and PeptidesC. Separations of Amino Acids and Peptides Using Acid-Base Properties

26.4 Synthesis and Enantiomeric Resolution of a-Ami]ro AcidsA. Alkylation of AmmoniaB. Alkylation of Aminomalonate DerivativesC. Strecker SynthesisD. Enantiomeric Resolution of a-Amino Acids

26.5 Acylation and Esterification Reactions of Amino Acids

26.6 Solid-PhasePeptideSynthesis26.7 Hydrolysis of Peptides

A. Complete Hydrolysis and Amino Acid AnalysisB. Enzyme-C ataly zed Peptide Hydrolysis

26.8 Primary Structure of Peptides and ProteinsA. Peptide Sequencing by Mass SpectrometryB. Peptide Sequencing by the Edman DegradationC. Protein SequencingD. Posttranslational Modification of Proteins

26.9 Higher-Order Structures of ProteinsA. Secondary StructureB. Tertiary and Quaternary Structure

26.10 Enzymes: Biological CatalystsA. The Catalytic Action of EnzymesB. Enzymes as Drug Targets: Enzyme Inhibition


PERICYCLIC REACTIONS

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1270

1271r27 |t273r271

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1282

r 283

129?^r2921295

1296r299I 303I 3051 305

1 308I 3081310

131 513151318

1 3231324

133327

27.1 Molecular Orbitals of Gonjugated rrElectron SystemsA. Molecular Orbitals of Conjugated Alkenes

1 336I 336

B. Molecular Orbitals of Conjugated Ions and RadicalsC. Excited States

27.2 Electrocyclic ReactionsA. Ground-State (Thermal) Electrocyclic ReactionsB. Excited-State (Photochemical) Electrocyclic ReactionsC. Selection Rules and Microscopic Reversibility

27.3 Cycloaddition Reactions

27.4 Thermal Sigmatropic Reaction$A. Classiflcation and StereochemistryB. Thermal [3,3] Sigmatropic ReactionsC. Summary: Selection Rules for Thermal Sigmatropic Reactions

27.5 Fluxional Molecules

27.6 Biological Pericyclic Reactions:The Formation of Vitamin D

Key ldeas in Chapter 27Additional Prohlems

coNrENrs xxix

I 3401343

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1349

1 3S31353I 360t362

1364

1365

13671 368

A-1APPENDIGES

Appendix l.Appendix ll.

Appendix lll.

APPENDIX IV.

ITPPENDIX V.

Substitutive Nomenclature of Organic Gompounds

lnfrared Absorptions of Organic Compounds

Proton NMR Chemical Shifts in Organic CompoundsA. Protons within Functional GroupsB. Protons Adjacent to Functional Groups

t3C NMR Chemical Shifts in Organic GompoundsA. Chemical Shifts of Carbons within Functional GroupsB. Chemical Shifts of Carbons Adjacent to Functional Groups

Summary of Synthetic Method$A. Synthesis of Alkanes and Aromatic HydrocarbonsB. Synthesis of AlkenesC. Synthesis of AlkynesD. Synthesis of Alkyl, Aryl, and Vinylic HalidesE. Synthesis of Grignard Reagents and Related Organometallic CompoundsF. Synthesis of Alcohols and PhenolsG. Synthesis of GlycolsH. Synthesis of Ethers, Acetals, and SulfidesI. Synthesis of EpoxidesJ. Synthesis of Disulfides

A-1

A-2

A'5A-5A-5

A-7A-lA-1

A-gA-8A-9A-9A-9A-9

A-10A-10A- 10A-10A-10

xxx loNrENrs

K. Synthesis of AldehydesL. Synthesis of KetonesM. Synthesis of Sulfoxides and SulfonesN. Synthesis of Carboxylic and Sulfonic AcidsO. Synthesis of EstersP. Synthesis of AnhydridesQ. Synthesis of Acid ChloridesR. Synthesis of AmidesS. Synthesis of NitrilesT. Synthesis of AminesU. Synthesis of Nimo Compounds

Reactions Used to Form Garbon-Carbon Bonds

A. Acidities of Groups That Ionize to Give Anionic Conjugate BasesB. Basicities of Groups That Protonate to Give Cationic Conjugate Acids

CreditsIndex

A-11A-11A-11A-11A-T2A-T2A-t2A-12A-t2A.T2A-13

A-13APPENDIXVI.

APPENDIXVII. Typlcal Aclditles and Baslcltles of OGanlc Functlonal Groups A-14A-14A-15

c-1l-1

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