Dr. Charles Sell, PhD, has recently retired from Givaudan after thirty-six years in the fragrance industry. His work has covered all aspects of synthetic organic chemistry as applied to the fragrance industry, from discovery of novel materials through process R&D to improvement of established chemical manufacturing processes. His interest in the design of novel fragrance ingredients, coupled with a long-standing interest in the chemistry of living organisms, led to a deepened investigation into olfaction.

• Preface xiIntroduction xiii1 The Structure of Matter 1The Route to the Atomic Theory 1The Atomic Theory, Atomic Number, and Atomic Weight 4Atomic Structure 7Isotopes 8The Electronic Structure of Atoms 9Electronic Structure of Transition Metals 11Hybridisation of Orbitals 11Chemical Bonding, Ions, Cations, Anions, and Molecules 12Review Questions 162 Carbon 1 – Hydrocarbons 17Ethane: Conformational Isomers 17Alkanes: Structural Isomers 20Alkenes: Geometric Isomers 22Alkynes 26Cyclic Structures 26Polycyclic Structures 28Greek Letters 30Aromatic Rings 31Stereoisomerism 33Rules for Hydrocarbon Nomenclature 36Quick Rules for Isomers 37Stereoisomers 37Review Questions 383 Carbon 2 – Heteroatoms 39Hydrogen Bonding 39Alcohols 40Phenols 43Ethers 44Aldehydes 45Ketones 46Carboxylic Acids 47Esters 49Acid Anhydrides and Chlorides 50Acetals and Ketals 50Peroxy Compounds 52Nitrogen–Amines and Ammonium Salts 53Nitrogen–Imines, Schiff’s Bases, and Enamines 54Nitrogen–Amides/Peptides 55Nitrogen–Nitriles 56Nitrogen–Nitro Compounds 57Sulfur 58Heterocyclic Compounds 60Review Question 664 States of Matter 67Solids 67Liquids 71Gases 71Phase Changes 71Two‐Phase Systems 73Solubility 74Surfactants 75Emulsions 79Micelles 81Detergency 81Bilayers 82Colloids 84Review Questions 845 Separation and Purification 85Distillation 85Sublimation 93Crystallisation 93Solvent Extraction 94Recent Developments in Commercial Extraction of Natural FragranceIngredients 95Chromatography 96Paper Chromatography 98Thin Layer Chromatography 98Column Chromatography 99High Performance Liquid Chromatography 100Gas Chromatography 100Review Questions 1056 Analysis 107Physical Methods of Analysis 108Density 108Melting Point 108Boiling Point 108Refractive Index 109Optical Rotation 109Flashpoint 109Viscosity 109Colour 109Chemical Methods of Analysis 110Titration 110Acid Content 111Base Content 111Peroxide Content 111Ester Value 111Aldehyde/Ketone Content 112Phenol Content 112Chemical Oxygen Demand (COD) 112Water Content 112Atomic Absorption 113Spectroscopic Methods of Analysis 113Ultraviolet (UV) 114Infrared (IR) 118Nuclear Magnetic Resonance (NMR) 120Mass Spectrometry (MS) 124Gas Chromatography–Mass Spectrometry (GC–MS) 127Eugenol as an Example of Spectroscopic Techniques 127Quality Control 131Review Questions 1327 Chemical Reactivity 133The Three Laws of Thermodynamics 133Free Energy 135Chemical Reactions 136The Principle of Microscopic Reversibility and Chemical Equilibrium 137Reaction Profiles 138Catalysts 140Types of Organic Reactions 140Review Questions 1458 Chemistry and Perfume 1: Acid/Base Reactions 147Acids and Bases 147Strong and Weak 149pH 150Electrophiles and Nucleophiles 152Esterification and Ester Hydrolysis 154The Aldol Reaction and Aldol Condensation 155Acetals and Ketals 158Schiff’s Bases and Enamines 160Nitriles 161Alcohol Dehydration 162Acid‐Catalysed Addition to Olefins 163The Michael Reaction 164The Grignard Reaction 165The Friedel–Crafts Reaction 167Electrophilic Substitutions in Aromatic Molecules 168Review Questions 1709 Oxidation and Reduction Reactions 171Review Questions 18510 Perfume Structure 187Notes, Chords, and Discords 187Ingredients 187Odour Families and Top, Middle, and Base Notes 188Persistence/Tenacity 191Threshold 192Impact 192Radiance/Bloom 193Physical and Chemical Factors 194Review Questions 19611 Chemistry in Consumer Goods 197Introduction 197Acids in Consumer Goods 198Bases in Consumer Goods 199Nucleophiles in Consumer Goods 200Oxidants in Consumer Goods 201Reductants in Consumer Goods 202Surfactants in Consumer Goods 204Chelating Agents in Consumer Goods 205Photoactive Agents in Consumer Goods 206Antibacterial Agents in Consumer Goods 207Other Reactive Ingredients in Consumer Goods 208Types of Consumer Goods 209Fine Fragrance 209Cosmetics and Toiletries 210Personal Wash 210Laundry 211Household 212Review Questions 21412 The Chemistry of Living Organisms 215Molecular Recognition 215Classes of Natural Chemicals 218Carbohydrates 218Nucleic Acids 221Lipids 223Proteins 225Toxicity and Product Safety 230Review Questions 23913 The Mechanism of Olfaction 243The Role of Olfaction in Biology 243The Organs Used in Olfaction 244The Process of Olfaction 246Transport to the Receptors 246The Receptor Event 247The Combinatorial Nature of Olfaction 249The Perception of Odour 252Review Questions 25614 Natural Fragrance Ingredients 257Why Does Nature Produce Odorous Chemicals? 257Basic Principles of Biosynthesis: Enzymes and Cofactors 258General Pattern of Biosynthesis of Secondary Metabolites 261Polyketide Biosynthesis 262Lipid Biosynthesis 263The Shikimic Acid Pathway 265Terpenoids 267Degradation Products 277Malodours 279Review Questions 28115 Synthetic Fragrance Ingredients 283Why the Industry Uses Synthetic Fragrance Ingredients? 283The Economics of Fragrance Ingredient Manufacture 284Production of Fragrance Ingredients from Polyketides and Shikimates 288Terpenoid Production 290Production of Fragrance Ingredients from Petrochemicals 302What Is Required of a Fragrance Ingredient? 320How Novel Fragrance Ingredients Are Designed? 322Review Questions 32616 Chemical Information 329How New Chemical Information Is Generated and Published? 329Patents 329Reviews and Books 331Abstracts 331How to Find Chemical Information? 33317 Towards a Sustainable Future 335What Is Sustainability? 335Commercial Feasibility 337Safety in Use 337Natural Fragrance Ingredients 340Synthetic Fragrance Ingredients 341Synthetic Fragrance Ingredients A: Use of By‐Products 341Synthetic Fragrance Ingredients B: Environmental Impact 342Synthetic Fragrance Ingredients C: Biotechnology 344Synthetic Fragrance Ingredients D: Finding the Balance 345The Symrise Route 347The Takasago Route 347The BASF Route 348Menthol Sustainability 349Pro‐fragrances 351Social and Health Factors 353Understanding Olfaction 353Malodour Management 354Health and Well‐Being 355Information 356Conclusion 356Answers to Review Questions 357Glossary 371Bibliography 379Index 381

Dr. Charles Sell, PhD, has recently retired from Givaudan after thirty-six years in the fragrance industry. His work has covered all aspects of synthetic organic chemistry as applied to the fragrance industry, from discovery of novel materials through process R&D to improvement of established chemical manufacturing processes. His interest in the design of novel fragrance ingredients, coupled with a long-standing interest in the chemistry of living organisms, led to a deepened investigation into olfaction.

• Preface xiIntroduction xiii1 The Structure of Matter 1The Route to the Atomic Theory 1The Atomic Theory, Atomic Number, and Atomic Weight 4Atomic Structure 7Isotopes 8The Electronic Structure of Atoms 9Electronic Structure of Transition Metals 11Hybridisation of Orbitals 11Chemical Bonding, Ions, Cations, Anions, and Molecules 12Review Questions 162 Carbon 1 – Hydrocarbons 17Ethane: Conformational Isomers 17Alkanes: Structural Isomers 20Alkenes: Geometric Isomers 22Alkynes 26Cyclic Structures 26Polycyclic Structures 28Greek Letters 30Aromatic Rings 31Stereoisomerism 33Rules for Hydrocarbon Nomenclature 36Quick Rules for Isomers 37Stereoisomers 37Review Questions 383 Carbon 2 – Heteroatoms 39Hydrogen Bonding 39Alcohols 40Phenols 43Ethers 44Aldehydes 45Ketones 46Carboxylic Acids 47Esters 49Acid Anhydrides and Chlorides 50Acetals and Ketals 50Peroxy Compounds 52Nitrogen–Amines and Ammonium Salts 53Nitrogen–Imines, Schiff’s Bases, and Enamines 54Nitrogen–Amides/Peptides 55Nitrogen–Nitriles 56Nitrogen–Nitro Compounds 57Sulfur 58Heterocyclic Compounds 60Review Question 664 States of Matter 67Solids 67Liquids 71Gases 71Phase Changes 71Two‐Phase Systems 73Solubility 74Surfactants 75Emulsions 79Micelles 81Detergency 81Bilayers 82Colloids 84Review Questions 845 Separation and Purification 85Distillation 85Sublimation 93Crystallisation 93Solvent Extraction 94Recent Developments in Commercial Extraction of Natural FragranceIngredients 95Chromatography 96Paper Chromatography 98Thin Layer Chromatography 98Column Chromatography 99High Performance Liquid Chromatography 100Gas Chromatography 100Review Questions 1056 Analysis 107Physical Methods of Analysis 108Density 108Melting Point 108Boiling Point 108Refractive Index 109Optical Rotation 109Flashpoint 109Viscosity 109Colour 109Chemical Methods of Analysis 110Titration 110Acid Content 111Base Content 111Peroxide Content 111Ester Value 111Aldehyde/Ketone Content 112Phenol Content 112Chemical Oxygen Demand (COD) 112Water Content 112Atomic Absorption 113Spectroscopic Methods of Analysis 113Ultraviolet (UV) 114Infrared (IR) 118Nuclear Magnetic Resonance (NMR) 120Mass Spectrometry (MS) 124Gas Chromatography–Mass Spectrometry (GC–MS) 127Eugenol as an Example of Spectroscopic Techniques 127Quality Control 131Review Questions 1327 Chemical Reactivity 133The Three Laws of Thermodynamics 133Free Energy 135Chemical Reactions 136The Principle of Microscopic Reversibility and Chemical Equilibrium 137Reaction Profiles 138Catalysts 140Types of Organic Reactions 140Review Questions 1458 Chemistry and Perfume 1: Acid/Base Reactions 147Acids and Bases 147Strong and Weak 149pH 150Electrophiles and Nucleophiles 152Esterification and Ester Hydrolysis 154The Aldol Reaction and Aldol Condensation 155Acetals and Ketals 158Schiff’s Bases and Enamines 160Nitriles 161Alcohol Dehydration 162Acid‐Catalysed Addition to Olefins 163The Michael Reaction 164The Grignard Reaction 165The Friedel–Crafts Reaction 167Electrophilic Substitutions in Aromatic Molecules 168Review Questions 1709 Oxidation and Reduction Reactions 171Review Questions 18510 Perfume Structure 187Notes, Chords, and Discords 187Ingredients 187Odour Families and Top, Middle, and Base Notes 188Persistence/Tenacity 191Threshold 192Impact 192Radiance/Bloom 193Physical and Chemical Factors 194Review Questions 19611 Chemistry in Consumer Goods 197Introduction 197Acids in Consumer Goods 198Bases in Consumer Goods 199Nucleophiles in Consumer Goods 200Oxidants in Consumer Goods 201Reductants in Consumer Goods 202Surfactants in Consumer Goods 204Chelating Agents in Consumer Goods 205Photoactive Agents in Consumer Goods 206Antibacterial Agents in Consumer Goods 207Other Reactive Ingredients in Consumer Goods 208Types of Consumer Goods 209Fine Fragrance 209Cosmetics and Toiletries 210Personal Wash 210Laundry 211Household 212Review Questions 21412 The Chemistry of Living Organisms 215Molecular Recognition 215Classes of Natural Chemicals 218Carbohydrates 218Nucleic Acids 221Lipids 223Proteins 225Toxicity and Product Safety 230Review Questions 23913 The Mechanism of Olfaction 243The Role of Olfaction in Biology 243The Organs Used in Olfaction 244The Process of Olfaction 246Transport to the Receptors 246The Receptor Event 247The Combinatorial Nature of Olfaction 249The Perception of Odour 252Review Questions 25614 Natural Fragrance Ingredients 257Why Does Nature Produce Odorous Chemicals? 257Basic Principles of Biosynthesis: Enzymes and Cofactors 258General Pattern of Biosynthesis of Secondary Metabolites 261Polyketide Biosynthesis 262Lipid Biosynthesis 263The Shikimic Acid Pathway 265Terpenoids 267Degradation Products 277Malodours 279Review Questions 28115 Synthetic Fragrance Ingredients 283Why the Industry Uses Synthetic Fragrance Ingredients? 283The Economics of Fragrance Ingredient Manufacture 284Production of Fragrance Ingredients from Polyketides and Shikimates 288Terpenoid Production 290Production of Fragrance Ingredients from Petrochemicals 302What Is Required of a Fragrance Ingredient? 320How Novel Fragrance Ingredients Are Designed? 322Review Questions 32616 Chemical Information 329How New Chemical Information Is Generated and Published? 329Patents 329Reviews and Books 331Abstracts 331How to Find Chemical Information? 33317 Towards a Sustainable Future 335What Is Sustainability? 335Commercial Feasibility 337Safety in Use 337Natural Fragrance Ingredients 340Synthetic Fragrance Ingredients 341Synthetic Fragrance Ingredients A: Use of By‐Products 341Synthetic Fragrance Ingredients B: Environmental Impact 342Synthetic Fragrance Ingredients C: Biotechnology 344Synthetic Fragrance Ingredients D: Finding the Balance 345The Symrise Route 347The Takasago Route 347The BASF Route 348Menthol Sustainability 349Pro‐fragrances 351Social and Health Factors 353Understanding Olfaction 353Malodour Management 354Health and Well‐Being 355Information 356Conclusion 356Answers to Review Questions 357Glossary 371Bibliography 379Index 381

Dr. Charles Sell, PhD, has recently retired from Givaudan after thirty-six years in the fragrance industry. His work has covered all aspects of synthetic organic chemistry as applied to the fragrance industry, from discovery of novel materials through process R&D to improvement of established chemical manufacturing processes. His interest in the design of novel fragrance ingredients, coupled with a long-standing interest in the chemistry of living organisms, led to a deepened investigation into olfaction.

• Preface xiIntroduction xiii1 The Structure of Matter 1The Route to the Atomic Theory 1The Atomic Theory, Atomic Number, and Atomic Weight 4Atomic Structure 7Isotopes 8The Electronic Structure of Atoms 9Electronic Structure of Transition Metals 11Hybridisation of Orbitals 11Chemical Bonding, Ions, Cations, Anions, and Molecules 12Review Questions 162 Carbon 1 – Hydrocarbons 17Ethane: Conformational Isomers 17Alkanes: Structural Isomers 20Alkenes: Geometric Isomers 22Alkynes 26Cyclic Structures 26Polycyclic Structures 28Greek Letters 30Aromatic Rings 31Stereoisomerism 33Rules for Hydrocarbon Nomenclature 36Quick Rules for Isomers 37Stereoisomers 37Review Questions 383 Carbon 2 – Heteroatoms 39Hydrogen Bonding 39Alcohols 40Phenols 43Ethers 44Aldehydes 45Ketones 46Carboxylic Acids 47Esters 49Acid Anhydrides and Chlorides 50Acetals and Ketals 50Peroxy Compounds 52Nitrogen–Amines and Ammonium Salts 53Nitrogen–Imines, Schiff’s Bases, and Enamines 54Nitrogen–Amides/Peptides 55Nitrogen–Nitriles 56Nitrogen–Nitro Compounds 57Sulfur 58Heterocyclic Compounds 60Review Question 664 States of Matter 67Solids 67Liquids 71Gases 71Phase Changes 71Two‐Phase Systems 73Solubility 74Surfactants 75Emulsions 79Micelles 81Detergency 81Bilayers 82Colloids 84Review Questions 845 Separation and Purification 85Distillation 85Sublimation 93Crystallisation 93Solvent Extraction 94Recent Developments in Commercial Extraction of Natural FragranceIngredients 95Chromatography 96Paper Chromatography 98Thin Layer Chromatography 98Column Chromatography 99High Performance Liquid Chromatography 100Gas Chromatography 100Review Questions 1056 Analysis 107Physical Methods of Analysis 108Density 108Melting Point 108Boiling Point 108Refractive Index 109Optical Rotation 109Flashpoint 109Viscosity 109Colour 109Chemical Methods of Analysis 110Titration 110Acid Content 111Base Content 111Peroxide Content 111Ester Value 111Aldehyde/Ketone Content 112Phenol Content 112Chemical Oxygen Demand (COD) 112Water Content 112Atomic Absorption 113Spectroscopic Methods of Analysis 113Ultraviolet (UV) 114Infrared (IR) 118Nuclear Magnetic Resonance (NMR) 120Mass Spectrometry (MS) 124Gas Chromatography–Mass Spectrometry (GC–MS) 127Eugenol as an Example of Spectroscopic Techniques 127Quality Control 131Review Questions 1327 Chemical Reactivity 133The Three Laws of Thermodynamics 133Free Energy 135Chemical Reactions 136The Principle of Microscopic Reversibility and Chemical Equilibrium 137Reaction Profiles 138Catalysts 140Types of Organic Reactions 140Review Questions 1458 Chemistry and Perfume 1: Acid/Base Reactions 147Acids and Bases 147Strong and Weak 149pH 150Electrophiles and Nucleophiles 152Esterification and Ester Hydrolysis 154The Aldol Reaction and Aldol Condensation 155Acetals and Ketals 158Schiff’s Bases and Enamines 160Nitriles 161Alcohol Dehydration 162Acid‐Catalysed Addition to Olefins 163The Michael Reaction 164The Grignard Reaction 165The Friedel–Crafts Reaction 167Electrophilic Substitutions in Aromatic Molecules 168Review Questions 1709 Oxidation and Reduction Reactions 171Review Questions 18510 Perfume Structure 187Notes, Chords, and Discords 187Ingredients 187Odour Families and Top, Middle, and Base Notes 188Persistence/Tenacity 191Threshold 192Impact 192Radiance/Bloom 193Physical and Chemical Factors 194Review Questions 19611 Chemistry in Consumer Goods 197Introduction 197Acids in Consumer Goods 198Bases in Consumer Goods 199Nucleophiles in Consumer Goods 200Oxidants in Consumer Goods 201Reductants in Consumer Goods 202Surfactants in Consumer Goods 204Chelating Agents in Consumer Goods 205Photoactive Agents in Consumer Goods 206Antibacterial Agents in Consumer Goods 207Other Reactive Ingredients in Consumer Goods 208Types of Consumer Goods 209Fine Fragrance 209Cosmetics and Toiletries 210Personal Wash 210Laundry 211Household 212Review Questions 21412 The Chemistry of Living Organisms 215Molecular Recognition 215Classes of Natural Chemicals 218Carbohydrates 218Nucleic Acids 221Lipids 223Proteins 225Toxicity and Product Safety 230Review Questions 23913 The Mechanism of Olfaction 243The Role of Olfaction in Biology 243The Organs Used in Olfaction 244The Process of Olfaction 246Transport to the Receptors 246The Receptor Event 247The Combinatorial Nature of Olfaction 249The Perception of Odour 252Review Questions 25614 Natural Fragrance Ingredients 257Why Does Nature Produce Odorous Chemicals? 257Basic Principles of Biosynthesis: Enzymes and Cofactors 258General Pattern of Biosynthesis of Secondary Metabolites 261Polyketide Biosynthesis 262Lipid Biosynthesis 263The Shikimic Acid Pathway 265Terpenoids 267Degradation Products 277Malodours 279Review Questions 28115 Synthetic Fragrance Ingredients 283Why the Industry Uses Synthetic Fragrance Ingredients? 283The Economics of Fragrance Ingredient Manufacture 284Production of Fragrance Ingredients from Polyketides and Shikimates 288Terpenoid Production 290Production of Fragrance Ingredients from Petrochemicals 302What Is Required of a Fragrance Ingredient? 320How Novel Fragrance Ingredients Are Designed? 322Review Questions 32616 Chemical Information 329How New Chemical Information Is Generated and Published? 329Patents 329Reviews and Books 331Abstracts 331How to Find Chemical Information? 33317 Towards a Sustainable Future 335What Is Sustainability? 335Commercial Feasibility 337Safety in Use 337Natural Fragrance Ingredients 340Synthetic Fragrance Ingredients 341Synthetic Fragrance Ingredients A: Use of By‐Products 341Synthetic Fragrance Ingredients B: Environmental Impact 342Synthetic Fragrance Ingredients C: Biotechnology 344Synthetic Fragrance Ingredients D: Finding the Balance 345The Symrise Route 347The Takasago Route 347The BASF Route 348Menthol Sustainability 349Pro‐fragrances 351Social and Health Factors 353Understanding Olfaction 353Malodour Management 354Health and Well‐Being 355Information 356Conclusion 356Answers to Review Questions 357Glossary 371Bibliography 379Index 381