The Structure of Heterocyclic Compounds

Most chemical compounds consist of molecules. The classification of such chemical compounds is based on the structure of these molecules, which is defined by the type and number of atoms as well as by the covalent bonding within them. There are two main types of structure  

Cyclic compounds in which the ring is made up of atoms of one element only are called isocyclic compounds. If the ring consists of C-atoms only, then we speak of a carbocyclic compound, e.g.  

Cyclic compounds with at least two different atoms in the ring (as ring atoms or members of the ring) are known as heterocyclic compounds. The ring itself is called a heterocycle. If the ring contains no C-atom, then we speak of an inorganic heterocycle, e.g.  

If at least one ring atom is a C-atom, then the molecule is an organic heterocyclic compound. In this case, all the ring atoms which are not carbon are called heteroatoms, e.g.  

The Chemistry of Heterocycles, Second Edition. By Theophil Eicher and Siegfried Hauptmann Copyright 2003 Wiley-VCH Verlag GmbH Co. KGaA ISBN 3-527-30720-6 

---

Bertinotti, F., G. Giacomello, and A. M. Liquori. 1956. The Structure of Heterocyclic Compounds Containing Nitrogen. I. Crystal and Molecular Structure of s-Tetrazine. Acta Cryst. 9, 510. 

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. 

The Chemistry of Heterocyclic Compounds has been published since 1950 under the initial editorship of Arnold Weissberger, and later, until his death in 1984, under the joint editorship of Arnold Weissberger and Edward C. Taylor. In 1997, Peter Wipf joined Prof. Taylor as editor. This series attempts to make the extraordinarily complex and diverse held of heterocyclic chemistry as organized and readily accessible as possible. Each volume has traditionally dealt with syntheses, reactions, properties, structure, physical chemistry, and utility of compounds belonging to a specihc ring system or class (e.g., pyridines, thiophenes, pyrimidines, three-membered ring systems). This series has become the basic reference collection for information on heterocyclic compounds. 

Zuckerman et al. have extensively utilized this method in heterocyclic tin(II) chemistry 100). In some cases, this synthesis may also be performed with tin(II) chloride, the starting hydrochloride being coordinated by the addition of an amine 120). Free 171) and metal-bound tin(II) chloride 172) have been treated analogously with trimethyltin hydroxide to yield amorphous powders of the composition Sn(OH)2 and (CO)5MSn(OH)2 (M = Cr, W) and ClSnMe3. Unfortunately, no direct information on the structure of these compounds is available. 

The foregoing examples show that the nucleophilic attack to nitroarenes at the o>T/ o-position followed by cyclization is a general method for the synthesis of various heterocycles. When nucleophiles have an electrophilic center, heterocyclic compounds are obtained in one step. Ono and coworkers have used the anion derived from ethyl isocyanoacetate as the reactive anion for the preparation of heterocyclic compounds. The carbanion reacts with various nitroarenes to give isoindoles or pyrimidines depending on the structure of nitroarenes (Eqs. 9.56 and 9.57).89 The synthesis of pyrroles is discussed in detail in Chapter 10. 

Clearly, in view of a diversity in the types of heterocyclic compounds, one may hardly expect that all the manifestations of their aromaticity (antiaromaticity) could be rationalized in terms of some simple regularities. We shall therefore attempt to trace certain characteristic trends in the dependence of the aromaticity on the type of heteroatoms, their number and positions in the molecular structure. Our reasoning will be based on the nature of the aromaticity criteria and of the electron count rules. Then turning to individual compounds, we shall add details to the picture. 

In Chapter 11 of Part A, the mechanistic classification of 1,3-dipolar cycloadditions as a type of concerted cycloadditions was developed. Dipolar cycloaddition reactions are useful both for the synthesis of heterocyclic compounds and for carbon-carbon bond formation. Table 6.2 lists some of the types of molecules that are capable of dipolar cycloaddition. These molecules, which are called 1,3-dipoles, have n-electron systems that are isoelectronic with allyl anion, consisting of two filled and one empty orbital. Each molecule has at least one charge-separated resonance structure with opposite charges in a... 

Much work has been devoted to [2 + 3] cycloadditions both in the synthesis of and in reactions of this kind of heterocycle. Dimroth rearrangement is another feature which has been explored widely. X-ray structural analysis was extensively used alongside physico-chemical methods to elucidate the structure of novel compounds. 

This article is an attempt to provide a guide to the nomenclature of heterocyclic compounds. The various systems available will be described, and problems associated with their use will be discussed. Where appropriate, the advantages and disadvantages of particular systems will be mentioned. In the interests of precision and conciseness, nomenclature rules themselves are not framed in a readily digestible form they are meant not for reading, but for reference. It is hoped that the following text will be more readily assimilable, and, in conjunction with the original rules (the most relevant of which are provided here as an Appendix), will enable the reader to name the majority of heterocyclic molecules. However, it is beyond the scope of the article to cover all possible heterocyclic structures in cases where the text proves inadequate, reference to the rules themselves will be necessary. 

---