8 TUTORIAL CHEMISTRY TEXTS RS.C Heterocyclic Chemistry by MALCOLM SAINSBURY
Preface This book provides a concise,yet thorough,introduction to the vast sub- ject of heterocyclic chemistry by dealing only with those compounds con- taining a single heteroatom.By restricting g the discussion to these,the most important classes of heterocycles,a balanced treatment is possible allowing the student to rapidly understand the importance of heterocyclic compounds in general to mankind and at the same time stimulating an ents. The contents of the book are carefully designed to meet the needs of undergraduate students in the 2nd year of a degree course in Chemistry or Biochemistry and are based upon the author's own lectures given to students at Bath.Although prim arily an undergraduate text,the e main principles that govern heterocyclic chemistry as a whole are addressed in this book,providing a sure foundation for those wishing to widen their interest in heterocyclic chemistry in later years. Malcolm Sainsbury Bath
Preface This book provides a concise, yet thorough, introduction to the vast subject of heterocyclic chemistry by dealing only with those compounds containing a single heteroatom. By restricting the discussion to these, the most important classes of heterocycles, a balanced treatment is possible, allowing the student to rapidly understand the importance of heterocyclic compounds in general to mankind and at the same time stimulating an interest in the challenges this chemistry presents. The contents of the book are carefully designed to meet the needs of undergraduate students in the 2nd year of a degree course in Chemistry or Biochemistry and are based upon the author’s own lectures given to students at Bath. Although primarily an undergraduate text, the main principles that govern heterocyclic chemistry as a whole are addressed in this book, providing a sure foundation for those wishing to widen their interest in heterocyclic chemistry in later years. Malcolm Sainsbury Bath
Contents Introduction to Heterocyclic Chemistry 1 1.1 Coverage 12 nclature Importance to Life and Industry 1.4 General Principles 46 Pyridine 18 2.1 Resonance Description 2.2 Electrophilic Substitution 189 Pyridine N-Oxides 22 Nucleophilic Substitution 2.5 Lithiation e 2.6 Methods of Synthesis 28 2.7 Commonly Encountered Pyridine Derivatives 2.8 Reduc ed Pyridine 36 3 Benzopyridines 42 3.1 Introduction 42 3.2 Quinoline 3.3 Isoquinoline 50 4 Pyrylium Salts,Pyrans and Pyrones 58 4.1 Introduction 4.2 Pyrylium Salts 58
Contents I Introduction to Heterocyclic Chemistry 1.1 Coverage 1.2 Nomenclature 1.3 Importance to Life and Industry 1.4 General Principles 2 Pyridine 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 Resonance Description Electrophilic Substitution Pyridine N-Oxides Nucleophilic Substitution Lit hiat ion Methods of Synthesis Commonly Encountered Pyridine Derivatives Reduced Pyridines 3 Benropyridines 3.1 Introduction 3.2 Quinoline 3.3 Isoquinoline 4 Pyrylium Salts, Pyrans and Pyrones 4.1 Introduction 4.2 Pyrylium Salts i 18 18 19 22 23 28 28 29 36 42 42 43 50 58 58 59 V
vi Contents 4.3 Pyran-2-ones(a-Pyrones) 61 44 45 Pyran-4-ones(-Pyrones Reduced Pyrans 5 4.6 Saccharides and Carbohydrates 65 Benzopyrylium Salts,Coumarins, Chrom n es,Flavonoids and Related Compounds 68 51 Structural Types and Nomenclature 5.2 Coumarins 5.3 Chromones(Benzopyran-4-ones) 80D 6 Five-membered Heterocycles containing One Heteroatom:Pyrrole,Furan and Thiophene 77 6.1 Pyrrole 6.2 Furan 6.3 Thiophene 91 Benzo[b]pyrrole,Benzo[b]furan and Benzo[b]thiophene 97 7.1 Indole(Benzo[blpyrrole) 7.2 Benzo[b]furan and Benzo[b]thiophene 110 8 Four-membered Heterocycles containing a Single Nitrogen,Oxygen or Sulfur Atom 115 Azete,Azetine and Azetidine 115 Oxetene and Oxetane 121 8.3 Thietene and Thietane 122 Answers to Problems 125 Subject Index 141
vi Contents 4.3 Pyran-2-ones (a-Pyrones) 4.4 Pyran-4-ones (y-Pyrones) 4.5 Reduced Pyrans 4.6 Saccharides and Carbohydrates 61 63 65 65 5 Benropyrylium Salts, Coumarins, Chromones, Flavonoids and Related Compounds 68 5.1 Structural Types and Nomenclature 5.2 Coumarins 5.3 Chromones (Benzopyran-4-ones) 68 70 72 6 Five-membered Heterocycles containing One Heteroatom: Pyrrole, Furan and Thiophene 77 6.1 Pyrrole 6.2 Furan 6.3 Thiophene 77 85 91 7 Benzo[b]pyrrole, Benzo[b]furan and Benzo[&]thiophene 97 7.1 Indole (Benzo[b]pyrrole) 7.2 Benzo[b]furan and Benzo[b]thiophene 97 110 8 Four-membered Heterocycles containing a Single Nitrogen, Oxygen or Sulfur Atom 115 8.1 Azete, Azetine and Azetidine 8.2 Oxetene and Oxetane 8.3 Thietene and Thietane 115 121 122 Answers to Problems 125 Subject Index 141
1 Introduction to Heterocyclic Chemistry Aims By the end of this chapter you should understand: Why heterocyclic chemistry is so important to mankind The names of a few commonly encountered heterocyclic com- pounds Some of the major factors that govern the shape and stability of heterocyclic compounds 1.1 Coverage The subject of heterocyclic chemistry is vast,so in this book the focus is on the more common four-,five-and six-membered systems contain- ing one heteroatom.Little attempt is made to extend the coverage to knowledge will need to consult more advanced works.Fortunately,there is a very wide choice;excellent texts include Heterocyclic Chemistry by Gilchrist'and Heterocyclic Chemistry by Joule and Mills.2 In addition, there are many authoritative mplaions that dealhery 1.2 Nomenclature Students will be familiar with carbocyclic compounds,such as cyclo hexane and benzene,that are built from rings of carbon atoms.If one or more of the carbon atoms is replaced by another element,the prod- uct is a heterocycle.Multiple replacements are commonplace,and the elements involved need not be the same.The most common are oxygen
I Introduction to Heterocyclic Chemistry 1.1 Coverage The subject of heterocyclic chemistry is vast, so in this book the focus is on the more common four-, five- and six-membered systems containing one heteroatom. Little attempt is made to extend the coverage to more complex heterocycles, so that students interested in extending their knowledge will need to consult more advanced works. Fortunately, there is a very wide choice; excellent texts include Heterocyclic Chemistry by Gilchrist' and Heterocyclic Chemistry by Joule and Mills.2 In addition, there are many authoritative compilations that deal with heterocyclic chemistry in much more depth? I .2 Nomenclature ~~ ~~ Students will be familiar with carbocyclic compounds, such as cyclohexane and benzene, that are built from rings of carbon atoms. If one or more of the carbon atoms is replaced by another element, the product is a heterocycle. Multiple replacements are commonplace, and the elements involved need not be the same. The most common are oxygen, I