Heterocyclic reactivity

Nevertheless, the puzzling fact to be explained is that the harder ring nitrogen prefers the softer electrophilic center and that this preference is more pronounced than the one observed for the amino nitrogen. Much remains to be done to explain ambident heterocyclic reactivity it was shown recently by comparison between Photoelectrons Spectroscopy and kinetic data that not only the frontier densities but also the relative symmetries of nucleophilic occupied orbitals and electrophilic unoccupied orbitals must be taken into consideration (308). 

Figure 8.2 Structures of some other heterocyclic reactive dye systems...

Heterocyclic reactive groups, 9 320—321 Heterocyclics. See also Heterocyclic compounds... 

Fluorine and chlorine are the only important choices for the labile substituents on a heterocyclic reactive system but numerous other leaving groups have been patented, mostly as substituent on an s-triazine ring. These include sulpho, cyano, thiocyanato, azido and trichloromethyl [26], as well as more elaborate groupings (Figure 7.2). Such derivatives are... 

Aspects of the chemistry of compounds belonging to more than 20 systems covered by this chapter have been reported, but the chemistry of only a few of these systems has been studied in detail. Chief among these are the 1,2,3-selenadiazoles, which have generated wide interest owing to their ready conversion into selenium heterocycles, reactive intermediates, and nitrogen- and selenium-free products, and the 1,2,5-selenadiazoles and 1,2,3,5-diselenadiazole systems in which interest stems from their use in the synthesis of potentially useful conducting materials. Compounds belonging to several new systems have been synthesized. 

Table 2.7 Heterocyclic reactive systems and dyeing temperature...

It is generally observed that a C—H bond which is antiperiplanar to a lone pair of electrons (65) is weakened and susceptible to removal by electrophilic or free-radical oxidizing agents. This provides an explanation for the ready hydroperoxidation of aliphatic ethers, both cyclic and acyclic, by atmospheric oxygen. These considerations, however, go beyond the special area of six-membered heterocyclic reactivity presently considered. 

Attention has been paid to heterocyclic reactivity since the very beginning of applications of quantum chemistry to problems in organic chemistry.1,2i 125,126 Numerous papers 127-137 reported HMO and VB calculations of 77-electron densities and bond orders for models... 

Keywords Diheteropentalene systems, 5, 5-Fused heterocycles aromaticity, 5, 5-Fused heterocycles reactivity, Ring syntheses... 

In this section, we concentrate on the influence of steric effects on heterocyclic reactivity, but we do not treat reactions of substituents bonded to heteroaromatics, except in special cases of ambident reactivity (ring vs. substituent) modified by steric effects. 

The method can clearly measure not only the effect of a substituent upon the reactivity of benzene as outlined above, but also the reactivity of a different aromatic system, by placing it instead of the substituted benzene in, for example, Eq. (5.2). This method was introduced by Taylor (62JCS4881), who used, however, a different reaction, the pyrolysis of 1-arylethyl acetates (described below) This was the first application to the determination of heterocyclic reactivities. 

This technique has been used in the majority of studies of heterocycle reactivity for the advantageous reasons described above, yet it is less familiar to the majority of chemists. A full description is therefore given here. 

Electron-excessive N,S-heterocycles, reactivity, structure, synthesis 85CRV341. 

This chapter describes the structures of aromatic heterocycles and gives a brief summary of some physical properties. The treatment we use is the valence-bond description, which we believe is appropriate for the understanding of all heterocyclic reactivity, perhaps save some very subtle effects, and is certainly sufficient for a general textbook on the subject. The more fundamental, molecular-orbital description of aromatic systems is less relevant to the day-to-day interpretation of heterocyclic reactivity, though it is necessary in some cases to utilise frontier orbital considerations, however such situations do not fall within the scope of this book. 

This chapter describes in general terms the types of reactivity found in the typical six- and five-membered aromatic heterocycles. We discuss electrophilic addition (to nitrogen) and electrophilic, nucleophilic and radical substitution chemistry. This chapter also has discussion of orf/to-quinodimethanes, in the heterocyclic context. Organometallic derivatives of heterocycles, and transition metal (especially palladium)-catalysed chemistry of heterocycles, are so important that we deal with these aspects separately, in Chapter 4. Emphasis on the typical chemistry of individual heterocyclic systems is to be found in the summary chapters (7, 10, 13, 15, 19 and 23), and a more detailed examination of typical heterocyclic reactivity and many more examples for particular heterocyclic systems are to be found in the chapters - Pyridines Reactions and Synthesis , etc. 

The study of aromatic heterocyclic reactivity can be said to have begun with the results of electrophilic substitution processes - these were traditionally the means for the introduction of substitutents onto het-erocylic rings. To a considerable extent, that methodology has been superseded, especially for the introduction of carbon substituents, by methods relying on the formation of organometallic nucleophiles (4.1) and on palladium-catalysed processes (4.2). Nonetheless, the reaction of heterocycles with electrophilic reagents is still extremely useful in many cases, particularly for electron-rich, five-membered heterocycles. 

Some illustrative and self-explanatory examples are shown below. For a discussion of the heterocyclic reactivity involved in the examples shown, the reader should consult the relevant ring-system chapter. 

We have maintained the principal aim of the earlier editions - to teach the fundamentals of heterocyclic reactivity and synthesis in a way that is understandable by undergraduate students. However, in recognition of the level at which much heterocyclic chemistry is now normally taught, we include more advanced and current material, which makes the book appropriate both for post-graduate level courses, and as a reference text for those involved in heterocyclic chemistry in the work place. 

The main body of factual material is to be found in chapters entitled Reactions and synthesis of... a particular heterocyclic system. Didactic material is to be found partly in advanced general discussions of heterocyclic reactivity and synthesis (Chapters 3, 4 and 6), and partly in six short summary chapters (such as Typical Reactivity of Pyridines, Quinolines and Isoquinolines Chapter 7), which aim to capture the essence of that typical reactivity in very concise resumes. These last are therefore suitable as an introduction to the chemistry of that heterocyclic system, but they are insufficient in themselves and should lead the reader to the fuller discussions in the Reactions and Synthesis of. .. chapters. They will also serve the undergraduate student as a revision summary of the typical chemistry of that system. 

Pyrimidine (1) is the trivial name for 1,3-diazine two me/a-oriented CH units in benzene have been replaced by nitrogen atoms. Quinazoline (2) is benzo-fused pyrimidine and is defined by the fusion nomenclature as benzo[if]pyrimidine, alternatively as 1,3-diazanaphthalene by the replacement nomenclature. Perimidine (3) is the trivial name for the pen -naphtho-fused pyrimidine system. It may be called (fusion names) l//-benzo[f/e]quinazoline or l//-naphtho[l,8-r/e]pyrimidine, or alternatively l//-l,3-diazaphenalene by the replacement nomenclature. However, the three trivial names are all system names accepted by lUPAC and approved as parents for further fusion name formation the benzo- and naphtho-pyrimidine names are therefore not used. In principle, additional rings can be fused onto the benzo or naphtho moiety in either quinazoline or perimidine without any profound alteration in heterocyclic reactivity. Aceperimidylene (4) and aceperimidine (5) are the trivial names for two cyclopenteno and cyclopentano fused perimidines. 

Due to the presence of two electronegative oxygen rings, the pyrazine and quinoxaline rings are poor substrates for electrophilic aromatic substrates. These nitrogen atoms do increase the heterocycles reactivity toward nucleophilic aromatic reaction. This reaction is usually done starting... 

We have maintained the principal aim of the earlier editions - to teach the fundamentals of heterocyclic reactivity and synthesis in a way which is understandable by undergraduate students. However in addition, and in recognition of... 

We have added exercises, with solutions given in an appendix at the end of the book, designed to help the reader to understand, learn and apply the principles of heterocyclic reactivity. We believe that this departure considerably improves the usefulness of the book as an instrument for the teaching of heterocyclic chemistry. References have not been given for the exercises, though all are real examples culled from the literature. 

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