THE MONOGRAPH CHAPTERS

These cover the following topics (a) theoretical methods, with emphasis on the utility of such methods (b) molecular dimensions, as determined by X-ray, electron diffraction and microwave spectra (c) molecular spectra, covering NMR, IR, UV, mass and photoelectron spectra (d) thermodynamic aspects, such as stability, ring strain, aromaticity, shape and conformation of saturated and partially saturated rings (e) tautomerism, including prototopic and ring-chain (/) betaine and other unusual structures. 

These consider ring syntheses from non-heterocyclic compounds first, followed by transformation of other heterocyclics. Syntheses in which no new heterocyclic ring is formed are dealt with primarily in the appropriate reactivity section, but with cross-referencing when necessary. Ring syntheses from acyclic precursors are dealt with as logically as possible according to the number and nature of the new ring bonds formed in the process. 

Fused benzene rings are treated as substituents. Thus quinoline, for example, is considered as a substituted pyridine, albeit a very special and important one, and treated alongside other substituted pyridines in the discussion of its structure, reactivity and synthesis. Reactions of quinoline at positions 1-4 are considered as reactions at ring atoms, whilst reactions at positions 5-8 are regarded as reactions of the substituent . 

The applications sections of monograph chapters provide access to important compounds used in medicine or industry, to industrially important sources of compounds, and to key natural products. 

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Details of bond lengths and bond angles for all the X-ray structures of heterocyclic compounds through 1970 are listed in Physical Methods in Heterocyclic Chemistry , volume 5. This compilation contains many examples for five-membered rings containing two heteroatoms, particularly pyrazoles, imidazoles, Isoxazoles, oxazoles, isothlazoles, thlazoles, 1,2-dlthloles and 1,3-dlthloles. Further examples of more recent measurements on these heterocyclic compounds can be found in the monograph chapters. 

Heterocyclics of all sizes, as long as they are unsaturated, can serve as dipolarophiles and add to external 1,3-dipoles. Examples involving small rings are not numerous. Thiirene oxides add 1,3-dipoles, such as di azomethane, with subsequent loss of the sulfur moiety (Section 5.06.3.8). As one would expect, unsaturated large heterocyclics readily provide the two-atom component for 1,3-dipolar cycloadditions. Examples are found in the monograph chapters, such as those on azepines and thiepines (Sections 5.16.3.8.1 and 5.17.2.4.4). 

This is a rather substantial area of chemistry of the six-membered heterocyclic compounds and one in which, while a few general trends are discernible, there is also an enormous diversity of behaviour depending on the ring system. Consequently, there can be no detailed discussion in this chapter, and the reader is referred to the monograph chapters for information on individual ring systems. 

The use of classical condensation reactions is important. Thus, the Dieckmann reaction (equation 38) and the Thorpe-Ziegler cyclization (equation 39) have been used for almost a century for the preparation of a wide range of monocyclic and benzo-fused heterocycles. The aldol condensation and related reactions have also been fairly widely exploited, especially for the synthesis of 4-quinolones (the Camps reaction, e.g. equation 40), and various extensions of this general approach are described in the monograph chapters. 

Reactions involving the [4 + 1 + 1] principle, an example of which is shown in equation (136), are rather uncommon and of strictly limited utility [3 + 2 + 1] and [2 + 2 + 2] processes, on th,e other hand, are well known. Representative [3 + 2+1] three-bond formation processes are given in equations (137)—(141), from which it can be seen that the common situation is where ammonia, a substituted amine or formamide constitutes the one-atom fragment. Many [2 + 2 + 2] atom fragment syntheses are known and some are familiar reactions. Thus, the cobalt(I)-catalyzed condensation of nitriles and isocyanates with alkynes gives pyridines and 2-pyridones, often in excellent yield (e.g. equation 142), while the cyclotrimerizations of nitriles, imidates, isocyanates, etc., are well established procedures for the synthesis of 1,3,5-triazine derivatives (e.g. equation 143). Further representative examples are given in equations (144)-(147), and the reader is referred to the monograph chapters for full discussion of these and other [2 + 2 + 2] processes. Examination of the... 

Three general chapters on structure, reactivity, and synthesis precede the monograph chapters in each of Parts 2 to 5 of CHEC. The purpose is to introduce each family of ring systems and to emphasize the logical correlations within them, and so to help in the understanding of known reactions and in the prediction of new ones. These 12 general chapters thus provide an overview of the whole subject of heterocyclic chemistry and they should be of particular interest to students and teachers. These general chapters also appeared in the 1985 version of the Handbook of Heterocyclic Chemistry and it is planned that they will appear in a new revised version of the Handbook. 

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