Cover
Dedication
Preface
Acknowledgments
Chapter 1: Some Biologically Important Heterocycles of Nature
1. 1.1 Vitamins
2. 1.2 Antibiotics and Tetrapyrroles
3. References
Chapter 2: Orbitals and Aromaticity; Chemical Reactivity
1. References
Chapter 3: A Prelude to Synthesis
1. References
Chapter 4: π‐Deficient Heterocycles: Some Physical Properties
1. References
Chapter 5: π‐Deficient Heterocycles: De Novo Syntheses
1. 5.1 De Novo Syntheses, Pyrimidines
2. 5.2 Fused‐Ring Systems, Quinolines
3. References
Chapter 6: π‐Deficient Heterocycles: Introduction of New Substituents: Nucleophilic Substitution
1. References
Chapter 7: π‐Deficient Heterocycles: Introduction of New Substituents: Heterocyclic N‐Oxides
1. 7.1 Further Reactions of N‐Oxides
2. References
Chapter 8: π‐Deficient Heterocycles: Introduction of New Substituents: Quinolines and Isoquinolines
1. References
Chapter 9: π‐Deficient Heterocycles: Manipulation of Existing Substituents
1. 9.1 Summary
2. References
Chapter 10: π‐Excessive Heterocycles: General Properties
1. References
Chapter 11: π‐Excessive Heterocycles: De Novo Syntheses
1. 11.1 Synthesis of 1,3‐Azoles
2. 11.2 Synthesis of 1,2‐Azoles
3. 11.3 Fischer Indole Synthesis
4. References
Chapter 12: π‐Excessive Heterocycles: Introduction of New Substituents
1. References
Chapter 13: Ring Transformations of π‐Excessive Heterocycles: Diels‐Alder Reactions
1. References
Chapter 14: Heterocycles as Synthons
1. References
Chapter 15: 1,3‐Dipolar Cycloadditions—An Overview
1. References
Chapter 16: Back to Basics
1. References
Chapter 17: A Brief Synopsis
Index
End User License Agreement

List of Illustrations

Chapter 1
1. Figure 1.1 Some naturally occurring heterocycles.
2. Figure 1.2 Naturally occurring heterocycles.
3. Figure 1.3 Heterocyclic vitamins.
4. Schema 1.1
5. Figure 1.4 Heterocyclic vitamins.
6. Figure 1.5 Antibiotics and and tetrapyrroles.
Chapter 2
1. Figure 2.1 Properties of aromatic heterocylics, orbitals.
2. Figure 2.2 Trends in resonance energy.
3. Figure 2.3 π‐Deficient heterocycles.
4. Figure 2.4 π‐Excessive heterocycles.
Chapter 3
1. Scheme 3.1 Why heterocycles?
2. Scheme 3.2 A laboratory analogy.
3. Figure 3.1 Common bond‐forming reactions.
4. Figure 3.2 Some remarkable transformations.
Chapter 4
1. Figure 4.1 π‐Deficient heterocycles: Solubility and tautomerization.
2. Figure 4.2 π‐Deficient heterocycles: basicity.
Chapter 5
1. Figure 5.1 Synthesis of π‐deficient heterocycles.
2. Scheme 5.1 Synthesis of π‐deficient heterocycles: pyridines.
3. Scheme 5.2 Synthesis of π‐deficient heterocycles: pyridines.
4. Figure 5.2 Synthesis of π‐deficient heterocycles: pyridines.
5. Figure 5.3 Synthesis of π‐deficient heterocycles: pyrimidines.
6. Scheme 5.3 Synthesis of π‐deficient heterocycles: quinolines.
7. Scheme 5.4 Synthesis of π‐deficient heterocycles: isoquinolines.
8. Scheme 5.5 Synthesis of π‐deficient heterocycles: isoquinolines.
Chapter 6
1. Figure 6.1 Introducing new substituents.
2. Figure 6.2 Introducing new substituents.
3. Scheme 6.1
4. Scheme 6.2 Nucleophilic displacement: potential complications.
5. Figure 6.3 Orbital requirements for fragmentation.
6. Scheme 6.3
7. Figure 6.4 A complication of a different sort.
8. Scheme 6.4 Nucleophilic displacement: a second complication.
9. Figure 6.5 Elimination‐addition: a competing mechanism.
10. Figure 6.6 Unequivocal generation of 3,4‐pyridyne.
Chapter 7
1. Figure 7.1 Introducing new substituents.
2. Figure 7.2 Pyridine N‐oxides.
3. Figure 7.3 Pyridine N‐oxides.
4. Figure 7.4 Pyridine N‐oxides, reduction.
5. Figure 7.5 A novel activating agent.
6. Figure 7.6 For weaker nucleophiles, activation is crucial.
7. Figure 7.7 Planning a synthesis of ricinine.
8. Figure 7.8 Synthesis of ricinine: tactical considerations.
9. Figure 7.9 Strategic considerations in the synthesis of ricinine.
10. Figure 7.10 Ricinine synthesis: a potential end game.
11. Scheme 7.1 Synthesis of ricinine: putting it all together.
12. Figure 7.11 Action of Ac₂O on N‐oxides.
13. Figure 7.12 Action of Ac₂O on N‐oxides.
14. Figure 7.13 Related transformations.
15. Figure 7.14 Synthesis of 2‐chloromethylpyridine.
16. Figure 7.15 Further reactions with sulfonyl chlorides.
17. Figure 7.16 Multiple Boekelheide rearrangements.
18. Figure 7.17 Rules for Ac₂O arrangements.
19. Scheme 7.2 Application of the Beokelheide rearrangement to the synthesis of muscopyridine.
20. Figure 7.18 Cycloaddition routes to N‐oxides.
21. Figure 7.19 Cycloaddition routes to N‐oxides.
22. Figure 7.20 Cycloaddition routes to N‐oxides.
Chapter 8
1. Figure 8.1 Claisen’s synthesis of benzoyl cyanide.
2. Figure 8.2 Formation of a Reissert compound from quinoline.
3. Figure 8.3 Pyridine does not form a Reissert compound.
4. Figure 8.4 Chemistry of Reissert derivatives.
5. Scheme 8.1
6. Scheme 8.2 Aklylation of Reissert derivatives.
7. Scheme 8.3 Aklylation of Reissert derivatives.
8. Scheme 8.4 Aporphine ‐ the final steps.
9. Figure 8.5 Chemistry of Reissert derivatives.
10. Scheme 8.5 Chemistry of Reissert derivatives.
11. Figure 8.6 Chemistry of Reissert derivatives.
12. Scheme 8.6 Chemistry of Reissert derivatives.
13. Figure 8.7 A very selective reduction.
14. Figure 8.8 Chemistry of Reissert derivatives.
15. Figure 8.9 Some selective reductions employing Reissert derivatives.
16. Figure 8.10 Chemistry of Reissert derivatives.
Chapter 9
1. Figure 9.1 Manipulation of existing substituents: acidic alkyl groups.
2. Figure 9.2 Manipulation of existing substituents: active methylene chemistry.
3. Figure 9.3 Active methylene chemistry.
4. Figure 9.4 Mechanism of the Mannich reaction.
5. Figure 9.5 Synthesis of L‐699,392.
6. Figure 9.6 Manipulation of existing substituents: vinylpyridines.
7. Figure 9.7 1,4‐Dihydropyridines as latent 1,5‐dicarbonyl compounds.
8. Figure 9.8 Synthetic utility of vinyl pyridines.
9. Scheme 9.1 Vinyl pyridines as bis annulation reagents.
10. Scheme 9.2
11. Scheme 9.3 Vinyl pyridines as bis annulation reagents.
12. Figure 9.9 Manipulation of existing substituents.
13. Figure 9.10 Manipulation of existing substituents.
14. Figure 9.11 Variants of the Hammick reaction.
15. Figure 9.12 Manipulation of existing substituents.
16. Figure 9.13 Manipulation of existing substituents.
17. Scheme 9.4 Putting it all together: synthesis of quinine.
Chapter 10
1. Figure 10.1 π‐Excessive heterocycles: general properties
2. Figure 10.2 π‐Excessive heterocycles: general properties
3. Figure 10.3 π‐Excessive heterocycles: general properties
4. Figure 10.4 π‐Excessive heterocycles: general properties.
5. Figure 10.5 C‐2 versus C‐3 electrophilic aromatic substitution.
Chapter 11
1. Figure 11.1 Synthesis of π‐excessive heterocycles.
2. Figure 11.2 De Novo synthesis.
3. Figure 11.3 De Novo synthesis.
4. Figure 11.4 Mechanism of pyrrole synthesis.
5. Scheme 11.1 De Novo synthesis.
6. Scheme 11.2
7. Scheme 11.3 De Novo synthesis.
8. Scheme 11.4 Knorr pyrrole synthesis.
9. Scheme 11.5 Knorr pyrrole synthesis.
10. Figure 11.5 De Novo synthesis.
11. Figure 11.6 Interrupted Feist‐Benary reaction.
12. Scheme 11.6 De Novo synthesis.
13. Scheme 11.7
14. Scheme 11.8 De Novo synthesis.
15. Scheme 11.9
16. Figure 11.7 De Novo synthesis.
17. Scheme 11.10
18. Figure 11.8 De Novo synthesis.
19. Figure 11.9 De Novo synthesis.
20. Figure 11.10 De Novo synthesis.
21. Figure 11.11 De Novo synthesis.
22. Figure 11.12 De Novo synthesis.
23. Figure 11.13 De Novo synthesis.
24. Figure 11.14 De Novo synthesis.
25. Figure 11.15 De Novo synthesis.
Chapter 12
1. Figure 12.1 Synthesis of π‐excessive heterocycles.
2. Figure 12.2 Generation of acetyl nitrate.
3. Figure 12.3 Introduction of new substituents.
4. Figure 12.4 Introduction of new substituents.
5. Scheme 12.1 Introduction of new substituents.
6. Scheme 12.2 Introduction of new substituents.
7. Figure 12.5 Introduction of new substituents.
8. Figure 12.6 Conditions for Mannich condensations.
9. Scheme 12.3
10. Scheme 12.4 Putting it all together.
11. Figure 12.7 Lithiation of anisole.
12. Figure 12.8 Lithiation of methyl vinyl ether.
13. Figure 21.9 Lithiation of π‐excessive heterocycles.
14. Scheme 12.5
Chapter 13
1. Figure 13.1 Ring transformation of π‐excessive heterocycles: Diels‐Alder reactions.
2. Figure 13.2 Energy diagram for Diels‐Alder reaction of furan.
3. Figure 13.3 Ring transformation of π‐excessive heterocycles: Diels‐Alder reactions.
4. Figure 13.4 Ring transformation of π‐excessive heterocycles: Diels‐Alder reactions.
5. Figure 13.5 Ring transformation of π‐excessive heterocycles: Diels‐Alder reactions.
6. Figure 13.6 Ring transformation of π‐excessive heterocycles: Diels‐Alder reactions.
7. Figure 13.7 Ring transformation of π‐excessive heterocycles: Diels‐Alder reactions.
8. Scheme 13.1 Ring transformation of π‐excessive heterocycles: Diels‐Alder reactions.
9. Scheme 13.2 Ring transformation of π‐excessive heterocycles: Diels‐Alder reactions.
10. Figure 13.8 Ring transformation of π‐excessive heterocycles: Diels‐Alder reactions.
11. Scheme 13.3 Ring transformation of π‐excessive heterocycles: Diels‐Alder reactions.
12. Figure 13.9 Ring transformation of π‐excessive heterocycles: Diels‐Alder reactions.
13. Scheme 13.4 A novel synthesis of pyridoxine.
14. Figure 13.10 Ring transformation of π‐excessive heterocycles: Diels‐Alder reactions.
15. Figure 13.11 Ring transformation of π‐excessive heterocycles: Diels‐Alder reactions.
16. Scheme 13.5
17. Scheme 13.6 Ring transformation of π‐excessive heterocycles: Diels‐Alder reactions.
Chapter 14
1. Figure 14.1 Heterocycles as synthons
2. Scheme 14.1 Furan as a synthon.
3. Scheme 14.2 Furan as a synthon.
4. Scheme 14.3 Furan as a synthon.
5. Scheme 14.4 Putting it all together.
6. Scheme 14.5 Furan as a synthon.
7. Scheme 14.6 Furan as a synthon.
8. Figure 14.2 Heterocycles as a synthon.
9. Figure 14.3 Thiophene as a synthon.
10. Scheme 14.7 Thiophene as a synthon.
11. Scheme 14.8 Thiophene as a synthon.
12. Scheme 14.9 Thiophene as a synthon.
13. Scheme 14.10 Woodward’s synthesis of colchicine.
14. Figure 14.4 Heterocycles as synthons.
15. Scheme 14.11 Isoxazole as a synthon.
16. Scheme 14.12 Isoxazole as a synthon.
17. Scheme 14.13 Isoxazole as a synthon.
18. Scheme 14.14 Isoxazole as a synthon.
19. Scheme 14.15 Isoxazole as a synthon.
20. Figure 14.5 Isoxazole as a synthon.
21. Scheme 14.16 Isoxazole as a synthon.
22. Figure 14.6 Heterocycles as synthons.
23. Scheme 14.17 Pyrazoles as a synthon.
Chapter 15
1. Figure 15.1 Synthesis and reactions of 1,3‐dipoles.
2. Figure 15.2 Synthesis and reactions of 1,3‐dipoles.
3. Figure 15.3 Synthesis and reactions of 1,3‐dipoles.
4. Figure 15.4 Synthesis and reactions of 1,3‐dipoles.
5. Figure 15.5 Synthesis and reactions of 1,3‐dipoles.
6. Scheme 15.1
7. Figure 15.6 Synthesis and reactions of 1,3‐dipoles.
8. Figure 15.7 Synthesis and reactions of 1,3‐dipoles.
9. Figure 15.8 Nitrile oxides.
10. Scheme 15.2 Nitrile oxides.
11. Figure 15.9 Synthesis and reactions of 1,3‐dipoles.
12. Figure 15.10 Synthesis and reactions of 1,3‐dipoles.
13. Scheme 15.3
14. Figure 15.11 Synthesis and reactions of 1,3‐dipoles.
15. Scheme 15.4 Synthesis and reactions of 1,3‐dipoles.
16. Figure 15.12 Synthesis and reactions of 1,3‐dipoles.
17. Figure 15.13 Synthesis and reactions of 1,3‐dipoles.
18. Figure 15.14 Synthesis and reactions of 1,3‐dipoles.
19. Figure 15.15 Synthesis and reactions of 1,3‐dipoles.
20. Figure 15.16 Synthesis and reactions of 1,3‐dipoles.
21. Scheme 15.5 Synthesis and reactions of 1,3‐dipoles.
22. Scheme 15.6 Synthesis and reactions of 1,3‐dipoles.
Chapter 16
1. Figure 16.1 Back to basics.
2. Figure 16.2 Nitriles and amidines.
3. Figure 16.3 Nitriles and amidines.
4. Figure 16.4 Nitriles and amidines.
5. Scheme 16.1 Complex transformations.
6. Scheme 16.2 Mechanisms are good practice.

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^* Vitaku, E.; Smith, D. T.; Njardarson, J.T. J. Med. Chem. 2014, 57, 10257-10274.