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Organic Chemistry

17.6 Reactions of Alcohols

Organic Chemistry17.6 Reactions of Alcohols

Table of contents
  1. Dedication and Preface
  2. 1 Structure and Bonding
    1. Why This Chapter?
    2. 1.1 Atomic Structure: The Nucleus
    3. 1.2 Atomic Structure: Orbitals
    4. 1.3 Atomic Structure: Electron Configurations
    5. 1.4 Development of Chemical Bonding Theory
    6. 1.5 Describing Chemical Bonds: Valence Bond Theory
    7. 1.6 sp3 Hybrid Orbitals and the Structure of Methane
    8. 1.7 sp3 Hybrid Orbitals and the Structure of Ethane
    9. 1.8 sp2 Hybrid Orbitals and the Structure of Ethylene
    10. 1.9 sp Hybrid Orbitals and the Structure of Acetylene
    11. 1.10 Hybridization of Nitrogen, Oxygen, Phosphorus, and Sulfur
    12. 1.11 Describing Chemical Bonds: Molecular Orbital Theory
    13. 1.12 Drawing Chemical Structures
    14. Chemistry Matters—Organic Foods: Risk versus Benefit
    15. Key Terms
    16. Summary
    17. Additional Problems
  3. 2 Polar Covalent Bonds; Acids and Bases
    1. Why This Chapter?
    2. 2.1 Polar Covalent Bonds and Electronegativity
    3. 2.2 Polar Covalent Bonds and Dipole Moments
    4. 2.3 Formal Charges
    5. 2.4 Resonance
    6. 2.5 Rules for Resonance Forms
    7. 2.6 Drawing Resonance Forms
    8. 2.7 Acids and Bases: The Brønsted–Lowry Definition
    9. 2.8 Acid and Base Strength
    10. 2.9 Predicting Acid–Base Reactions from pKa Values
    11. 2.10 Organic Acids and Organic Bases
    12. 2.11 Acids and Bases: The Lewis Definition
    13. 2.12 Noncovalent Interactions between Molecules
    14. Chemistry Matters—Alkaloids: From Cocaine to Dental Anesthetics
    15. Key Terms
    16. Summary
    17. Additional Problems
  4. 3 Organic Compounds: Alkanes and Their Stereochemistry
    1. Why This Chapter?
    2. 3.1 Functional Groups
    3. 3.2 Alkanes and Alkane Isomers
    4. 3.3 Alkyl Groups
    5. 3.4 Naming Alkanes
    6. 3.5 Properties of Alkanes
    7. 3.6 Conformations of Ethane
    8. 3.7 Conformations of Other Alkanes
    9. Chemistry Matters—Gasoline
    10. Key Terms
    11. Summary
    12. Additional Problems
  5. 4 Organic Compounds: Cycloalkanes and Their Stereochemistry
    1. Why This Chapter?
    2. 4.1 Naming Cycloalkanes
    3. 4.2 Cis–Trans Isomerism in Cycloalkanes
    4. 4.3 Stability of Cycloalkanes: Ring Strain
    5. 4.4 Conformations of Cycloalkanes
    6. 4.5 Conformations of Cyclohexane
    7. 4.6 Axial and Equatorial Bonds in Cyclohexane
    8. 4.7 Conformations of Monosubstituted Cyclohexanes
    9. 4.8 Conformations of Disubstituted Cyclohexanes
    10. 4.9 Conformations of Polycyclic Molecules
    11. Chemistry Matters—Molecular Mechanics
    12. Key Terms
    13. Summary
    14. Additional Problems
  6. 5 Stereochemistry at Tetrahedral Centers
    1. Why This Chapter?
    2. 5.1 Enantiomers and the Tetrahedral Carbon
    3. 5.2 The Reason for Handedness in Molecules: Chirality
    4. 5.3 Optical Activity
    5. 5.4 Pasteur’s Discovery of Enantiomers
    6. 5.5 Sequence Rules for Specifying Configuration
    7. 5.6 Diastereomers
    8. 5.7 Meso Compounds
    9. 5.8 Racemic Mixtures and the Resolution of Enantiomers
    10. 5.9 A Review of Isomerism
    11. 5.10 Chirality at Nitrogen, Phosphorus, and Sulfur
    12. 5.11 Prochirality
    13. 5.12 Chirality in Nature and Chiral Environments
    14. Chemistry Matters—Chiral Drugs
    15. Key Terms
    16. Summary
    17. Additional Problems
  7. 6 An Overview of Organic Reactions
    1. Why This Chapter?
    2. 6.1 Kinds of Organic Reactions
    3. 6.2 How Organic Reactions Occur: Mechanisms
    4. 6.3 Polar Reactions
    5. 6.4 An Example of a Polar Reaction: Addition of HBr to Ethylene
    6. 6.5 Using Curved Arrows in Polar Reaction Mechanisms
    7. 6.6 Radical Reactions
    8. 6.7 Describing a Reaction: Equilibria, Rates, and Energy Changes
    9. 6.8 Describing a Reaction: Bond Dissociation Energies
    10. 6.9 Describing a Reaction: Energy Diagrams and Transition States
    11. 6.10 Describing a Reaction: Intermediates
    12. 6.11 A Comparison Between Biological Reactions and Laboratory Reactions
    13. Chemistry Matters—Where Do Drugs Come From?
    14. Key Terms
    15. Summary
    16. Additional Problems
  8. 7 Alkenes: Structure and Reactivity
    1. Why This Chapter?
    2. 7.1 Industrial Preparation and Use of Alkenes
    3. 7.2 Calculating the Degree of Unsaturation
    4. 7.3 Naming Alkenes
    5. 7.4 Cis–Trans Isomerism in Alkenes
    6. 7.5 Alkene Stereochemistry and the E,Z Designation
    7. 7.6 Stability of Alkenes
    8. 7.7 Electrophilic Addition Reactions of Alkenes
    9. 7.8 Orientation of Electrophilic Additions: Markovnikov’s Rule
    10. 7.9 Carbocation Structure and Stability
    11. 7.10 The Hammond Postulate
    12. 7.11 Evidence for the Mechanism of Electrophilic Additions: Carbocation Rearrangements
    13. Chemistry Matters—Bioprospecting: Hunting for Natural Products
    14. Key Terms
    15. Summary
    16. Additional Problems
  9. 8 Alkenes: Reactions and Synthesis
    1. Why This Chapter?
    2. 8.1 Preparing Alkenes: A Preview of Elimination Reactions
    3. 8.2 Halogenation of Alkenes: Addition of X2
    4. 8.3 Halohydrins from Alkenes: Addition of HO-X
    5. 8.4 Hydration of Alkenes: Addition of H2O by Oxymercuration
    6. 8.5 Hydration of Alkenes: Addition of H2O by Hydroboration
    7. 8.6 Reduction of Alkenes: Hydrogenation
    8. 8.7 Oxidation of Alkenes: Epoxidation and Hydroxylation
    9. 8.8 Oxidation of Alkenes: Cleavage to Carbonyl Compounds
    10. 8.9 Addition of Carbenes to Alkenes: Cyclopropane Synthesis
    11. 8.10 Radical Additions to Alkenes: Chain-Growth Polymers
    12. 8.11 Biological Additions of Radicals to Alkenes
    13. 8.12 Reaction Stereochemistry: Addition of H2O to an Achiral Alkene
    14. 8.13 Reaction Stereochemistry: Addition of H2O to a Chiral Alkene
    15. Chemistry Matters—Terpenes: Naturally Occurring Alkenes
    16. Key Terms
    17. Summary
    18. Summary of Reactions
    19. Additional Problems
  10. 9 Alkynes: An Introduction to Organic Synthesis
    1. Why This Chapter?
    2. 9.1 Naming Alkynes
    3. 9.2 Preparation of Alkynes: Elimination Reactions of Dihalides
    4. 9.3 Reactions of Alkynes: Addition of HX and X2
    5. 9.4 Hydration of Alkynes
    6. 9.5 Reduction of Alkynes
    7. 9.6 Oxidative Cleavage of Alkynes
    8. 9.7 Alkyne Acidity: Formation of Acetylide Anions
    9. 9.8 Alkylation of Acetylide Anions
    10. 9.9 An Introduction to Organic Synthesis
    11. Chemistry Matters—The Art of Organic Synthesis
    12. Key Terms
    13. Summary
    14. Summary of Reactions
    15. Additional Problems
  11. 10 Organohalides
    1. Why This Chapter?
    2. 10.1 Names and Structures of Alkyl Halides
    3. 10.2 Preparing Alkyl Halides from Alkanes: Radical Halogenation
    4. 10.3 Preparing Alkyl Halides from Alkenes: Allylic Bromination
    5. 10.4 Stability of the Allyl Radical: Resonance Revisited
    6. 10.5 Preparing Alkyl Halides from Alcohols
    7. 10.6 Reactions of Alkyl Halides: Grignard Reagents
    8. 10.7 Organometallic Coupling Reactions
    9. 10.8 Oxidation and Reduction in Organic Chemistry
    10. Chemistry Matters—Naturally Occurring Organohalides
    11. Key Terms
    12. Summary
    13. Summary of Reactions
    14. Additional Problems
  12. 11 Reactions of Alkyl Halides: Nucleophilic Substitutions and Eliminations
    1. Why This Chapter?
    2. 11.1 The Discovery of Nucleophilic Substitution Reactions
    3. 11.2 The SN2 Reaction
    4. 11.3 Characteristics of the SN2 Reaction
    5. 11.4 The SN1 Reaction
    6. 11.5 Characteristics of the SN1 Reaction
    7. 11.6 Biological Substitution Reactions
    8. 11.7 Elimination Reactions: Zaitsev’s Rule
    9. 11.8 The E2 Reaction and the Deuterium Isotope Effect
    10. 11.9 The E2 Reaction and Cyclohexane Conformation
    11. 11.10 The E1 and E1cB Reactions
    12. 11.11 Biological Elimination Reactions
    13. 11.12 A Summary of Reactivity: SN1, SN2, E1, E1cB, and E2
    14. Chemistry Matters—Green Chemistry
    15. Key Terms
    16. Summary
    17. Summary of Reactions
    18. Additional Problems
  13. 12 Structure Determination: Mass Spectrometry and Infrared Spectroscopy
    1. Why This Chapter?
    2. 12.1 Mass Spectrometry of Small Molecules: Magnetic-Sector Instruments
    3. 12.2 Interpreting Mass Spectra
    4. 12.3 Mass Spectrometry of Some Common Functional Groups
    5. 12.4 Mass Spectrometry in Biological Chemistry: Time-of-Flight (TOF) Instruments
    6. 12.5 Spectroscopy and the Electromagnetic Spectrum
    7. 12.6 Infrared Spectroscopy
    8. 12.7 Interpreting Infrared Spectra
    9. 12.8 Infrared Spectra of Some Common Functional Groups
    10. Chemistry Matters—X-Ray Crystallography
    11. Key Terms
    12. Summary
    13. Additional Problems
  14. 13 Structure Determination: Nuclear Magnetic Resonance Spectroscopy
    1. Why This Chapter?
    2. 13.1 Nuclear Magnetic Resonance Spectroscopy
    3. 13.2 The Nature of NMR Absorptions
    4. 13.3 Chemical Shifts
    5. 13.4 Chemical Shifts in 1H NMR Spectroscopy
    6. 13.5 Integration of 1H NMR Absorptions: Proton Counting
    7. 13.6 Spin–Spin Splitting in 1H NMR Spectra
    8. 13.7 1H NMR Spectroscopy and Proton Equivalence
    9. 13.8 More Complex Spin–Spin Splitting Patterns
    10. 13.9 Uses of 1H NMR Spectroscopy
    11. 13.10 13C NMR Spectroscopy: Signal Averaging and FT–NMR
    12. 13.11 Characteristics of 13C NMR Spectroscopy
    13. 13.12 DEPT 13C NMR Spectroscopy
    14. 13.13 Uses of 13C NMR Spectroscopy
    15. Chemistry Matters—Magnetic Resonance Imaging (MRI)
    16. Key Terms
    17. Summary
    18. Additional Problems
  15. 14 Conjugated Compounds and Ultraviolet Spectroscopy
    1. Why This Chapter?
    2. 14.1 Stability of Conjugated Dienes: Molecular Orbital Theory
    3. 14.2 Electrophilic Additions to Conjugated Dienes: Allylic Carbocations
    4. 14.3 Kinetic versus Thermodynamic Control of Reactions
    5. 14.4 The Diels–Alder Cycloaddition Reaction
    6. 14.5 Characteristics of the Diels–Alder Reaction
    7. 14.6 Diene Polymers: Natural and Synthetic Rubbers
    8. 14.7 Ultraviolet Spectroscopy
    9. 14.8 Interpreting Ultraviolet Spectra: The Effect of Conjugation
    10. 14.9 Conjugation, Color, and the Chemistry of Vision
    11. Chemistry Matters—Photolithography
    12. Key Terms
    13. Summary
    14. Summary of Reactions
    15. Additional Problems
  16. 15 Benzene and Aromaticity
    1. Why This Chapter?
    2. 15.1 Naming Aromatic Compounds
    3. 15.2 Structure and Stability of Benzene
    4. 15.3 Aromaticity and the Hückel 4n + 2 Rule
    5. 15.4 Aromatic Ions
    6. 15.5 Aromatic Heterocycles: Pyridine and Pyrrole
    7. 15.6 Polycyclic Aromatic Compounds
    8. 15.7 Spectroscopy of Aromatic Compounds
    9. Chemistry Matters—Aspirin, NSAIDs, and COX-2 Inhibitors
    10. Key Terms
    11. Summary
    12. Additional Problems
  17. 16 Chemistry of Benzene: Electrophilic Aromatic Substitution
    1. Why This Chapter?
    2. 16.1 Electrophilic Aromatic Substitution Reactions: Bromination
    3. 16.2 Other Aromatic Substitutions
    4. 16.3 Alkylation and Acylation of Aromatic Rings: The Friedel–Crafts Reaction
    5. 16.4 Substituent Effects in Electrophilic Substitutions
    6. 16.5 Trisubstituted Benzenes: Additivity of Effects
    7. 16.6 Nucleophilic Aromatic Substitution
    8. 16.7 Benzyne
    9. 16.8 Oxidation of Aromatic Compounds
    10. 16.9 Reduction of Aromatic Compounds
    11. 16.10 Synthesis of Polysubstituted Benzenes
    12. Chemistry Matters—Combinatorial Chemistry
    13. Key Terms
    14. Summary
    15. Summary of Reactions
    16. Additional Problems
  18. 17 Alcohols and Phenols
    1. Why This Chapter?
    2. 17.1 Naming Alcohols and Phenols
    3. 17.2 Properties of Alcohols and Phenols
    4. 17.3 Preparation of Alcohols: A Review
    5. 17.4 Alcohols from Carbonyl Compounds: Reduction
    6. 17.5 Alcohols from Carbonyl Compounds: Grignard Reaction
    7. 17.6 Reactions of Alcohols
    8. 17.7 Oxidation of Alcohols
    9. 17.8 Protection of Alcohols
    10. 17.9 Phenols and Their Uses
    11. 17.10 Reactions of Phenols
    12. 17.11 Spectroscopy of Alcohols and Phenols
    13. Chemistry Matters—Ethanol: Chemical, Drug, and Poison
    14. Key Terms
    15. Summary
    16. Summary of Reactions
    17. Additional Problems
  19. 18 Ethers and Epoxides; Thiols and Sulfides
    1. Why This Chapter?
    2. 18.1 Names and Properties of Ethers
    3. 18.2 Preparing Ethers
    4. 18.3 Reactions of Ethers: Acidic Cleavage
    5. 18.4 Cyclic Ethers: Epoxides
    6. 18.5 Reactions of Epoxides: Ring-Opening
    7. 18.6 Crown Ethers
    8. 18.7 Thiols and Sulfides
    9. 18.8 Spectroscopy of Ethers
    10. Chemistry Matters—Epoxy Resins and Adhesives
    11. Key Terms
    12. Summary
    13. Summary of Reactions
    14. Additional Problems
    15. Preview of Carbonyl Chemistry
  20. 19 Aldehydes and Ketones: Nucleophilic Addition Reactions
    1. Why This Chapter?
    2. 19.1 Naming Aldehydes and Ketones
    3. 19.2 Preparing Aldehydes and Ketones
    4. 19.3 Oxidation of Aldehydes and Ketones
    5. 19.4 Nucleophilic Addition Reactions of Aldehydes and Ketones
    6. 19.5 Nucleophilic Addition of H2O: Hydration
    7. 19.6 Nucleophilic Addition of HCN: Cyanohydrin Formation
    8. 19.7 Nucleophilic Addition of Hydride and Grignard Reagents: Alcohol Formation
    9. 19.8 Nucleophilic Addition of Amines: Imine and Enamine Formation
    10. 19.9 Nucleophilic Addition of Hydrazine: The Wolff–Kishner Reaction
    11. 19.10 Nucleophilic Addition of Alcohols: Acetal Formation
    12. 19.11 Nucleophilic Addition of Phosphorus Ylides: The Wittig Reaction
    13. 19.12 Biological Reductions
    14. 19.13 Conjugate Nucleophilic Addition to α,β‑Unsaturated Aldehydes and Ketones
    15. 19.14 Spectroscopy of Aldehydes and Ketones
    16. Chemistry Matters—Enantioselective Synthesis
    17. Key Terms
    18. Summary
    19. Summary of Reactions
    20. Additional Problems
  21. 20 Carboxylic Acids and Nitriles
    1. Why This Chapter?
    2. 20.1 Naming Carboxylic Acids and Nitriles
    3. 20.2 Structure and Properties of Carboxylic Acids
    4. 20.3 Biological Acids and the Henderson–Hasselbalch Equation
    5. 20.4 Substituent Effects on Acidity
    6. 20.5 Preparing Carboxylic Acids
    7. 20.6 Reactions of Carboxylic Acids: An Overview
    8. 20.7 Chemistry of Nitriles
    9. 20.8 Spectroscopy of Carboxylic Acids and Nitriles
    10. Chemistry Matters—Vitamin C
    11. Key Terms
    12. Summary
    13. Summary of Reactions
    14. Additional Problems
  22. 21 Carboxylic Acid Derivatives: Nucleophilic Acyl Substitution Reactions
    1. Why This Chapter?
    2. 21.1 Naming Carboxylic Acid Derivatives
    3. 21.2 Nucleophilic Acyl Substitution Reactions
    4. 21.3 Reactions of Carboxylic Acids
    5. 21.4 Chemistry of Acid Halides
    6. 21.5 Chemistry of Acid Anhydrides
    7. 21.6 Chemistry of Esters
    8. 21.7 Chemistry of Amides
    9. 21.8 Chemistry of Thioesters and Acyl Phosphates: Biological Carboxylic Acid Derivatives
    10. 21.9 Polyamides and Polyesters: Step-Growth Polymers
    11. 21.10 Spectroscopy of Carboxylic Acid Derivatives
    12. Chemistry Matters—β-Lactam Antibiotics
    13. Key Terms
    14. Summary
    15. Summary of Reactions
    16. Additional Problems
  23. 22 Carbonyl Alpha-Substitution Reactions
    1. Why This Chapter?
    2. 22.1 Keto–Enol Tautomerism
    3. 22.2 Reactivity of Enols: α-Substitution Reactions
    4. 22.3 Alpha Halogenation of Aldehydes and Ketones
    5. 22.4 Alpha Bromination of Carboxylic Acids
    6. 22.5 Acidity of Alpha Hydrogen Atoms: Enolate Ion Formation
    7. 22.6 Reactivity of Enolate Ions
    8. 22.7 Alkylation of Enolate Ions
    9. Chemistry Matters—Barbiturates
    10. Key Terms
    11. Summary
    12. Summary of Reactions
    13. Additional Problems
  24. 23 Carbonyl Condensation Reactions
    1. Why This Chapter?
    2. 23.1 Carbonyl Condensations: The Aldol Reaction
    3. 23.2 Carbonyl Condensations versus Alpha Substitutions
    4. 23.3 Dehydration of Aldol Products: Synthesis of Enones
    5. 23.4 Using Aldol Reactions in Synthesis
    6. 23.5 Mixed Aldol Reactions
    7. 23.6 Intramolecular Aldol Reactions
    8. 23.7 The Claisen Condensation Reaction
    9. 23.8 Mixed Claisen Condensations
    10. 23.9 Intramolecular Claisen Condensations: The Dieckmann Cyclization
    11. 23.10 Conjugate Carbonyl Additions: The Michael Reaction
    12. 23.11 Carbonyl Condensations with Enamines: The Stork Enamine Reaction
    13. 23.12 The Robinson Annulation Reaction
    14. 23.13 Some Biological Carbonyl Condensation Reactions
    15. Chemistry Matters—A Prologue to Metabolism
    16. Key Terms
    17. Summary
    18. Summary of Reactions
    19. Additional Problems
  25. 24 Amines and Heterocycles
    1. Why This Chapter?
    2. 24.1 Naming Amines
    3. 24.2 Structure and Properties of Amines
    4. 24.3 Basicity of Amines
    5. 24.4 Basicity of Arylamines
    6. 24.5 Biological Amines and the Henderson–Hasselbalch Equation
    7. 24.6 Synthesis of Amines
    8. 24.7 Reactions of Amines
    9. 24.8 Reactions of Arylamines
    10. 24.9 Heterocyclic Amines
    11. 24.10 Spectroscopy of Amines
    12. Chemistry Matters—Green Chemistry II: Ionic Liquids
    13. Key Terms
    14. Summary
    15. Summary of Reactions
    16. Additional Problems
  26. 25 Biomolecules: Carbohydrates
    1. Why This Chapter?
    2. 25.1 Classification of Carbohydrates
    3. 25.2 Representing Carbohydrate Stereochemistry: Fischer Projections
    4. 25.3 D,L Sugars
    5. 25.4 Configurations of the Aldoses
    6. 25.5 Cyclic Structures of Monosaccharides: Anomers
    7. 25.6 Reactions of Monosaccharides
    8. 25.7 The Eight Essential Monosaccharides
    9. 25.8 Disaccharides
    10. 25.9 Polysaccharides and Their Synthesis
    11. 25.10 Some Other Important Carbohydrates
    12. Chemistry Matters—Sweetness
    13. Key Terms
    14. Summary
    15. Summary of Reactions
    16. Additional Problems
  27. 26 Biomolecules: Amino Acids, Peptides, and Proteins
    1. Why This Chapter?
    2. 26.1 Structures of Amino Acids
    3. 26.2 Amino Acids and the Henderson–Hasselbalch Equation: Isoelectric Points
    4. 26.3 Synthesis of Amino Acids
    5. 26.4 Peptides and Proteins
    6. 26.5 Amino Acid Analysis of Peptides
    7. 26.6 Peptide Sequencing: The Edman Degradation
    8. 26.7 Peptide Synthesis
    9. 26.8 Automated Peptide Synthesis: The Merrifield Solid-Phase Method
    10. 26.9 Protein Structure
    11. 26.10 Enzymes and Coenzymes
    12. 26.11 How Do Enzymes Work? Citrate Synthase
    13. Chemistry Matters—The Protein Data Bank
    14. Key Terms
    15. Summary
    16. Summary of Reactions
    17. Additional Problems
  28. 27 Biomolecules: Lipids
    1. Why This Chapter?
    2. 27.1 Waxes, Fats, and Oils
    3. 27.2 Soap
    4. 27.3 Phospholipids
    5. 27.4 Prostaglandins and Other Eicosanoids
    6. 27.5 Terpenoids
    7. 27.6 Steroids
    8. 27.7 Biosynthesis of Steroids
    9. Chemistry Matters—Saturated Fats, Cholesterol, and Heart Disease
    10. Key Terms
    11. Summary
    12. Additional Problems
  29. 28 Biomolecules: Nucleic Acids
    1. Why This Chapter?
    2. 28.1 Nucleotides and Nucleic Acids
    3. 28.2 Base Pairing in DNA
    4. 28.3 Replication of DNA
    5. 28.4 Transcription of DNA
    6. 28.5 Translation of RNA: Protein Biosynthesis
    7. 28.6 DNA Sequencing
    8. 28.7 DNA Synthesis
    9. 28.8 The Polymerase Chain Reaction
    10. Chemistry Matters—DNA Fingerprinting
    11. Key Terms
    12. Summary
    13. Additional Problems
  30. 29 The Organic Chemistry of Metabolic Pathways
    1. Why This Chapter?
    2. 29.1 An Overview of Metabolism and Biochemical Energy
    3. 29.2 Catabolism of Triacylglycerols: The Fate of Glycerol
    4. 29.3 Catabolism of Triacylglycerols: β-Oxidation
    5. 29.4 Biosynthesis of Fatty Acids
    6. 29.5 Catabolism of Carbohydrates: Glycolysis
    7. 29.6 Conversion of Pyruvate to Acetyl CoA
    8. 29.7 The Citric Acid Cycle
    9. 29.8 Carbohydrate Biosynthesis: Gluconeogenesis
    10. 29.9 Catabolism of Proteins: Deamination
    11. 29.10 Some Conclusions about Biological Chemistry
    12. Chemistry Matters—Statin Drugs
    13. Key Terms
    14. Summary
    15. Additional Problems
  31. 30 Orbitals and Organic Chemistry: Pericyclic Reactions
    1. Why This Chapter?
    2. 30.1 Molecular Orbitals of Conjugated Pi Systems
    3. 30.2 Electrocyclic Reactions
    4. 30.3 Stereochemistry of Thermal Electrocyclic Reactions
    5. 30.4 Photochemical Electrocyclic Reactions
    6. 30.5 Cycloaddition Reactions
    7. 30.6 Stereochemistry of Cycloadditions
    8. 30.7 Sigmatropic Rearrangements
    9. 30.8 Some Examples of Sigmatropic Rearrangements
    10. 30.9 A Summary of Rules for Pericyclic Reactions
    11. Chemistry Matters—Vitamin D, the Sunshine Vitamin
    12. Key Terms
    13. Summary
    14. Additional Problems
  32. 31 Synthetic Polymers
    1. Why This Chapter?
    2. 31.1 Chain-Growth Polymers
    3. 31.2 Stereochemistry of Polymerization: Ziegler–Natta Catalysts
    4. 31.3 Copolymers
    5. 31.4 Step-Growth Polymers
    6. 31.5 Olefin Metathesis Polymerization
    7. 31.6 Intramolecular Olefin Metathesis
    8. 31.7 Polymer Structure and Physical Properties
    9. Chemistry Matters—Degradable Polymers
    10. Key Terms
    11. Summary
    12. Additional Problems
  33. A | Nomenclature of Polyfunctional Organic Compounds
  34. B | Acidity Constants for Some Organic Compounds
  35. C | Glossary
  36. D | Periodic Table
  37. Answer Key
    1. Chapter 1
    2. Chapter 2
    3. Chapter 3
    4. Chapter 4
    5. Chapter 5
    6. Chapter 6
    7. Chapter 7
    8. Chapter 8
    9. Chapter 9
    10. Chapter 10
    11. Chapter 11
    12. Chapter 12
    13. Chapter 13
    14. Chapter 14
    15. Chapter 15
    16. Chapter 16
    17. Chapter 17
    18. Chapter 18
    19. Chapter 19
    20. Chapter 20
    21. Chapter 21
    22. Chapter 22
    23. Chapter 23
    24. Chapter 24
    25. Chapter 25
    26. Chapter 26
    27. Chapter 27
    28. Chapter 28
    29. Chapter 29
    30. Chapter 30
    31. Chapter 31
  38. Index

17.6 • Reactions of Alcohols

We’ve already seen several reactions of alcohols—their conversion into alkyl halides and tosylates in Section 10.5 and their dehydration to give alkenes in Section 8.1—albeit without mechanistic details. Let’s now look at those details.

Conversion of Alcohols into Alkyl Halides

Tertiary alcohols react with either HCl or HBr at 0 °C by an SN1 mechanism through a carbocation intermediate. Primary and secondary alcohols are much more resistant to acid, however, and are best converted into halides by treatment with either SOCl2 or PBr3 through an SN2 mechanism.

The reaction of a tertiary alcohol with HX takes place by an SN1 mechanism when acid protonates the hydroxyl oxygen atom. Water is expelled to generate a carbocation, and the cation reacts with nucleophilic halide ion to give the alkyl halide product.

Tertiary alcohol is protonated by hydrogen chloride or hydrogen bromide, water leaves forming carbocation (S N 1 mechanism), which reacts with halide to form an alkyl chloride or bromide.

The reactions of primary and secondary alcohols with SOCl2 and PBr3 take place by SN2 mechanisms. Hydroxide ion itself is too poor a leaving group to be displaced by nucleophiles in SN2 reactions, but reaction of an alcohol with SOCl2 or PBr3 converts the –OH into a much better leaving group, either a chlorosulfite (–OSOCl) or a dibromophosphite (–OPBr2), which is readily expelled by backside nucleophilic substitution.

Primary or secondary alcohol reacts with thionyl chloride to form chlorosulfite which forms alkyl chloride. The alcohol reacts with phosphorus tribromide to form dibromo phosphite. This leads to alkyl bromide.

Conversion of Alcohols into Tosylates

Alcohols react with p-toluenesulfonyl chloride (tosyl chloride, p-TosCl) in pyridine solution to yield alkyl tosylates, ROTos (Section 11.1). Only the O–H bond of the alcohol is broken in this reaction; the C–O bond remains intact, so no change of configuration occurs if the oxygen is attached to a chirality center. The resultant alkyl tosylates behave much like alkyl halides, undergoing both SN1 and SN2 substitution reactions.

An alcohol reacts with para-toluenesulfonylchloride in the presence of pyridine to form a tosylate (R O T o S) and pyridine dot hydrogen chloride.

One of the most important reasons for using tosylates in SN2 reactions is stereochemical. The SN2 reaction of an alcohol with an alkyl halide proceeds with two inversions of configuration—one to make the halide from the alcohol and one to substitute the halide—and yields a product with the same stereochemistry as the starting alcohol. The SN2 reaction of an alcohol with a tosylate, however, proceeds with only one inversion and yields a product of opposite stereochemistry to the starting alcohol. Figure 17.6 shows a series of reactions on the R enantiomer of 2-octanol that illustrates these stereochemical relationships.

(R)-2-octanol reacts with phosphorus tribromide to form (S)-2-bromooctane. This reacts with sodium ethoxide forming ethyl (R)-1-methylheptyl ether. (R)-2-octanol reacts with para-tosylchloride to form (R)-1-methylheptyl tosylate that forms ethyl (S)-1-methylheptyl ether.
Figure 17.6 Stereochemical consequences of SN2 reactions on derivatives of (R)-2-octanol. Substitution through the halide gives a product with the same stereochemistry as the starting alcohol; substitution through the tosylate gives a product with opposite stereochemistry to the starting alcohol.
Problem 17-12

How would you carry out the following transformation, a step used in the commercial synthesis of (S)-ibuprofen?

Structure of (1R)-1-(4-isobutylphenyl)ethanol separated from structure of (2S)-2-(4-isobutylphenyl)propanenitrile by two reaction arrows.

Dehydration of Alcohols to Yield Alkenes

A third important reaction of alcohols, both in the laboratory and in biological pathways, is their dehydration to give alkenes. Because of the usefulness of the reaction, a number of methods have been devised for carrying out dehydrations. One method that works particularly well for tertiary alcohols is the acid-catalyzed reaction discussed in Section 8.1. For example, treatment of 1-methylcyclohexanol with warm, aqueous sulfuric acid in a solvent such as tetrahydrofuran results in loss of water and formation of 1-methylcyclohexene.

1-methylcyclohexanol reacts with hydronium ion, tetrahydrofuran at 50 degree celsius to form 1-methylcyclohexene with 91 percent yield.

Acid-catalyzed dehydrations usually follow Zaitsev’s rule (Section 11.7) and yield the more stable alkene as the major product. Thus, 2-methyl-2-butanol gives primarily 2-methyl-2-butene (trisubstituted double bond) rather than 2-methyl-1-butene (disubstituted double bond).

2-methyl-2-butanol reacts with hydronium ion, tetrahydrofuran at 25 degree Celsius to form 2-methyl-2-butene (trisubstituted) as the major product and 2-methyl-1-butene (disubstituted) as the minor product.

This reaction is an E1 process (Section 11.10) and occurs by the three-step mechanism shown in Figure 17.7 on the next page. Protonation of the alcohol oxygen is followed by unimolecular loss of water to generate a carbocation intermediate and final loss of a proton from the neighboring carbon atom to complete the process. As with most E1 reactions, tertiary alcohols react fastest because they lead to stabilized, tertiary carbocation intermediates. Secondary alcohols can be made to react, but the conditions are severe (75% H2SO4, 100 °C) and sensitive molecules don’t survive.

Figure 17.7 MECHANISM
Mechanism for the acid-catalyzed dehydration of a tertiary alcohol to yield an alkene. The process is an E1 reaction and involves a carbocation intermediate.
Three-step mechanism: 1-methylcyclohexanol is protonated by hydronium, water leaves forming tertiary carbocation, deprotonation of adjacent carbon by water results in formation of double bond, produces 1-methylcyclohexene.

To circumvent the need for strong acid and allow the dehydration of secondary alcohols in a gentler way, reagents have been developed that are effective under mild, basic conditions. One such reagent, phosphorus oxychloride (POCl3) in the basic amine solvent pyridine, is often able to effect the dehydration of secondary and tertiary alcohols at 0 °C.

1-methylcyclohexanol reacts with phosphorus oxychloride and pyridine at 0 degree Celsius to form 1-methylcyclohexene with 96 percent yield.

Alcohol dehydrations carried out with POCl3 in pyridine take place by an E2 mechanism, as shown in Figure 17.8. Because hydroxide ion is a poor leaving group (Section 11.3), direct E2 elimination of water from an alcohol does not occur. On reaction with POCl3, however, the –OH group is converted into a dichlorophosphate (–OPOCl2), which is a good leaving group and is readily eliminated. Pyridine is both the reaction solvent and the base that removes a neighboring proton in the E2 elimination step.

Figure 17.8 MECHANISM
Mechanism for the dehydration of secondary and tertiary alcohols by reaction with POCl3 in pyridine. The reaction is an E2 process.
Two-step mechanism: cyclohexanol oxygen attacks P O Cl 3, chlorine leaves. Pyradine deprotonates adjacent carbon, electrons force O P O Cl 2 to leave, forming cyclohexene.

As noted in Section 11.11, biological dehydrations are also common and usually occur by an E1cB mechanism on a substrate in which the –OH group is two carbons away from a carbonyl group. One example occurs in the biosynthesis of the aromatic amino acid tyrosine. A base (:B) first abstracts a proton from the carbon adjacent to the carbonyl group, and the anion intermediate then expels the –OH group with simultaneous protonation by an acid (HA) to form water.

A base reacts with 5-dehydroquinate to form an anion intermediate. This is followed by the release of water to form 5-dehydroshikimate. This further forms tyrosine.
Problem 17-13
What product(s) would you expect from dehydration of the following alcohols with POCl3 in pyridine? Indicate the major product in each case.
(a)
Chemical structure of 2-methylpentan-3-ol.
(b)
Cyclohexane with hydroxyl (wedge) and hydrogen (dash). On adjacent carbon clockwise, hydrogen (wedge) and methyl (dash).
(c)
Cyclohexane with hydroxyl (wedge) and hydrogen (dash). On adjacent carbon clockwise, methyl (wedge) and hydrogen (dash).
(d)
Chemical structure of 2,3-dimethylpentan-3-ol.
(e)
Chemical structure of 2-methylpentan-2-ol.

Conversion of Alcohols into Esters

Alcohols react with carboxylic acids to give esters, a reaction that is common in both the laboratory and living organisms. In the laboratory, the reaction can be carried out in a single step if a strong acid is used as catalyst. More frequently, though, the reactivity of the carboxylic acid is enhanced by first converting it into a carboxylic acid chloride, which then reacts with the alcohol.

Benzoic acid reacts with methanol, hydrogen chloride, heat to form methyl benzoate. It reacts with thionyl chloride to form benzoyl chloride. Benzoyl chloride reacts with methanol to form methyl benzoate.

In living organisms, a similar process occurs, though a thioester or acyl adenosyl phosphate acts as substrate rather than a carboxylic acid chloride. We’ll look at the mechanisms of these reactions in Chapter 21.

A thioester reacts with alcohol, R O H to form an ester. An acyl adenosyl phosphate reacts with alcohol, R O H to form an ester.
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