Heterocyclic Chemistry At A Glance

John A. Joule, Keith Mills

• Publisher: Wiley
• Year: 2012
• Print ISBN: 9780470971215, 9780470971222
• eBook ISBN: 9781118380192
• Edition: 2
• Topic: Scienze fisiche
• Subtopic: Chimica organica

This expanded second edition provides a concise overview of the main principles and reactions of heterocyclic chemistry for undergraduate students studying chemistry and related courses. Using a successful and student-friendly "at a glance" approach, this book helps the student grasp the essence of heterocyclic chemistry, ensuring that they can confidently use that knowledge when required. The chapters are thoroughly revised and updated with references to books and reviews; extra examples and student exercises with answers online; and color diagrams that emphasize exactly what is happening in the reaction chemistry depicted.

Chapter 1

Heterocyclic Nomenclature

A selection of the structures, names and standard numbering of the more common heteroaromatic systems and some common non-aromatic heterocycles, are shown in this chapter. The aromatic heterocycles are grouped into those with six-membered rings and those with five-membered rings. The names of six-membered aromatic heterocycles that contain nitrogen generally end in ‘ine’, though note that ‘purine’ is the name for a very important bicyclic system which, has both a six- and a five-membered nitrogen-containing heterocycle. Five-membered heterocycles containing nitrogen generally end with ‘ole’. Note the use of italic ‘H’ in a name such as ‘9H-purine’ to designate the location of an N-hydrogen in a system in which, by tautomerism, the hydrogen could reside on another nitrogen (e.g. N-7 in the case of purine). Names such as ‘pyridine’, ‘pyrrole’ and ‘thiophene’ are the original, and now standard, names for these heterocycles; names such as ‘1,2,4-triazine’ for a six-membered ring with three nitrogens located as indicated by the numbers, are more logically systematic.

A detailed discussion of the systematic rules for naming polycyclic systems in which several aromatic or heteroaromatic rings are fused together, is beyond the scope of this book, however, two simple examples will serve to illustrate the principles. In the name ‘pyrrolo[2,3-b]pyridine’, the numbers signify the positions of the first named heterocycle, numbered as if it were a separate entity, which are the points of ring fusion; the italic letter, ‘b’ in this case, designates the side of the second named heterocycle to which the other ring is fused, the lettering deriving from the numbering of that heterocycle as a separate entity, that is, side a is between atoms 1 and 2, side b is that between atoms 2 and 3, and so on. Actually, this particular heterocycle is more often referred to as ‘7-azaindole’ – note the use of the prefix ‘aza’ to denote the replacement of a ring carbon by nitrogen. Similarly, ‘5-azaindole’ is systematically called ‘pyrrolo[3,2-c]pyridine’ – note that the order of the numbers ‘3,2-’ arises because the first atom of the pyrrole encountered in counting round from the pyridine nitrogen to determine the side of fusion, and thus the label ‘c’, is C-3 of the pyrrole unit. The numbering of a bi- or polycyclic system as a whole is generated from a series of rules concerned with the orientation of the rings and the positions of the nitrogen(s), but we do not deal with these here – the overall numbering for these two systems is shown for two substituted examples.

A device that is useful in discussions of reactivity is the designation of positions as ‘α’, ‘β’ or ‘γ’. For example, the 2- and the 6-positions in pyridine are equivalent in reactivity terms, so to make discussion of such reactivity clearer, each of these positions is referred to as an ‘α-position’. Comparable use of α and β is made in describing reactivity in five-membered systems. These useful designations are shown on some of the structures. Note that carbons at angular positions do not have a separate number but are designated using the number of the preceding atom followed by ‘a’ – as illustrated for quinoline.

Six-Membered Aromatic Heterocycles

Five-Membered Aromatic Heterocycles

Non-Aromatic Heterocycles

Small-Ring Heterocycles

Chapter 2

Structures of Heteroaromatic Compounds

Structures of Benzene and Naphthalene

We start our consideration of heteroaromatic structures by recalling the prototypical structures of aromatic hydrocarbons such as benzene and naphthalene. Hückel's rule states that aromaticity is associated with fully conjugated cyclic systems of 4n+2 π-electrons, that is with 2, 6, 10, 14 and so on, π-electrons, with 6π-electron monocyclic compounds being by far the commonest. Thus, benzene has a cyclic arrangement of six π-electrons comprising a conjugated molecular orbital system that is thermodynamically much more stable than a corresponding non-cyclically conjugated system – this additional stabilisation is called ‘resonance energy’ and has a value of about 152 kJ mol¹ for benzene. Compared with alkenes, this results in a much diminished tendency to react with electrophiles by addition and a greater tendency to react by substitution of hydrogen. Addition reactions would lead to products in which a substantial proportion of the resonance energy had been lost. As we shall remind ourselves in Chapter 3, electrophilic substitution is the prototypical reaction of benzene.

In benzene, the geometry of the ring, with angles of 120°, fits precisely the geometry of a planar trigonally hybridised carbon atom, and allows the assembly of a σ-skeleton of six sp² hybridised carbon atoms in a strainless planar ring. Each carbon then has one extra electron, which occupies an atomic p orbital orthogonal to the plane of the ring. The p orbitals interact sideways to generate the π-molecular orbitals associated with the aromatic system.

We shall represent the stabilising delocalisation of aromatic molecules by drawing ‘mesomeric structures’, thus benzene is represented as a ‘resonance hybrid’ of the two extreme forms. These have no existence in their own right, but are ‘resonance contributors’ to the ‘real’ structure. The use of mesomeric structures is particularly useful in representing the polarisation inherent in many heterocycles and, especially, for representing the delocalisation of charge in reaction intermediates. We shall find them invaluable in helping to understand heteroaromatic reactivity and regioselectivity.

Naphthalene, with ten carbons and ten orthogonal p orbitals, has an aromatic system with ten π-electrons. Naphthalene is represented by three mesomeric structures and has a resonance energy of about 255 kJ mol^-1, substantially less than twice that of benzene.

Structures of Pyridines and Pyridiniums

The structure of pyridine is completely analogous to that of benzene, being related through replacement of CH by N. The key differences a...

Table of contents

• Cover
• Other Titles Available in the Chemistry at a Glance series:
• Title Page
• Copyright
• Biography
• Abbreviations
• Introduction to Second Edition
• Chapter 1: Heterocyclic Nomenclature
• Chapter 2: Structures of Heteroaromatic Compounds
• Chapter 3: Common Reaction Types in Heterocyclic Chemistry
• Chapter 4: Palladium in Heterocyclic Chemistry
• Chapter 5: Pyridines
• Chapter 6: Diazines
• Chapter 7: Quinolines and Isoquinolines
• Chapter 8: Pyryliums, Benzopyryliums, Pyrones and Benzopyrones
• Chapter 9: Pyrroles
• Chapter 10: Indoles
• Chapter 11: Furans and Thiophenes
• Chapter 12: 1,2-Azoles and 1,3-Azoles
• Chapter 13: Purines
• Chapter 14: Heterocycles with More than Two Heteroatoms: Higher Azoles (5-Membered) and Higher Azines (6-Membered)
• Chapter 15: Heterocycles with Ring-Junction Nitrogen (Bridgehead Nitrogen)
• Chapter 16: Non-Aromatic Heterocycles
• Chapter 17: Heterocycles in Nature
• Chapter 18: Heterocycles in Medicine
• Chapter 19: Applications and Occurrences of Heterocycles in Everyday Life
• Index