Pyridines typical reactivity

The formal replacement of a CH in benzene by N leads to far-reaching changes in typical reactivity pyridines are much less susceptible to electrophilic substitution than benzene and much more susceptible to nucleophilic attack. However, pyridine undergoes a range of simple electrophilic additions, some reversible, some forming isolable products, each involving donation of the nitrogen lone pair to an electrophile, and thence the formation of pyridinium salts which, of course, do not have a counterpart in benzene chemistry at all. The ready donation of the pyridine lone pair in this way does not destroy the aromatic... 

Electrophilic nitration and bromination of pyridine iV-oxides can be controlled to give 4-substituted products by way of attack on the free A-oxide. ° Under conditions where the A-oxide is 0-protonated, substitution follows the typical pyridine/pyridinium reactivity pattern thus, in fuming sulfuric acid, bromination shows P-regioselectivity. Mercuration takes place at the a-position, however mercuric-catalysed sulfonation produces the 3-sulfonic acid. ... 

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. 

This chapter describes in general terms the types of reactivity found in the typical six-and five-membered aromatic heterocycles. In addition to discussions of classical substitution chemistry, considerable space is devoted to radical substitution, metallation and palladium-catalysed reactions, since these areas have become very important in heterocyclic manipulations. In order to gain a proper appreciation of their importance in the heterocyclic context we provide an introduction to these topics, since they are only poorly covered in general organic text-books. Emphasis on the typical chemistry of individual heterocyclic systems is to be found in the summary/revision chapters (4, 7, 10, 12, 16, and 20) 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. For the advanced student, it is recommended that this present chapter should be read in its entirety before moving on to the later chapters, and that the introductory summary/revision chapters, like Typical reactivity of pyridines, quinolines and isoquinolines should be read before the more detailed discussions. 

There is another important factor in the low reactivity of pyridine derivatives toward electrophilic substitution. The —N=CH— unit is basic because the electron pair on nitrogen is not part of the aromatic n system. The nitrogen is protonated or complexed with a Lewis acid under many of the conditions typical of electrophilic substitution reactions. The formal positive charge present at nitrogen in such species further reduces the reactivity toward electrophiles. 

Compared with monocyclic aromatic hydrocarbons and the five-membered azaarenes, the pathways used for the degradation of pyridines are less uniform, and this is consistent with the differences in electronic structure and thereby their chemical reactivity. For pyridines, both hydroxylation and dioxygenation that is typical of aromatic compounds have been observed, although these are often accompanied by reduction of one or more of the double bonds in the pyridine ring. Examples are used to illustrate the metabolic possibilities. 

While our discussion will mainly focus on sifica, other oxide materials can also be used, and they need to be characterized with the same rigorous approach. For example, in the case of meso- and microporous materials such as zeolites, SBA-15, or MCM materials, the pore size, pore distribution, surface composition, and the inner and outer surface areas need to be measured since they can affect the grafting step (and the chemistry thereafter) [5-7]. Some oxides such as alumina or silica-alumina contain Lewis acid centres/sites, which can also participate in the reactivity of the support and the grafted species. These sites need to be characterized and quantified this is typically carried out by using molecular probes (Lewis bases) such as pyridine [8,9],... 

Collections of fundamental and thermodynamic data can be found in an earlier review [158] and in standard resources [13, 14]. However, due to the reactivity of iodine there are many less common or more reactive forms of iodine that have been less well characterized. For example, a blue 12 cation, a brown I3+, or a green I5+ cation are formed in concentrated sulfuric acid and 1+ is stabilized in donor environments such as pyridine [159]. So-called hypervalent iodine reagents have been developed as a versatile oxidation tool in organic synthesis and often iodine derivatives are employed as electron transfer catalysts. Some fundamental thermodynamic data and typical applications of iodine are summarized in Scheme 5. 

The above types of catalysis function by stabilizing the transition state of the reaction without changing the mechanism. Catalysts may also involve a different reaction, pathway. A typical example is nucleophilic catalysis in an acyl transfer or hydrolytic reaction. The hydrolysis of acetic anhydride is greatly enhanced by pyridine because of the rapid formation of the highly reactive acetylpyridinium ion (equation 2.12). For nucleophilic catalysis to be efficient, the nucleophile... 

Heteroaromatic amines can oxidize to the corresponding N-oxide, which are typically stable enough to be isolated and detected as degradation products. The N-oxide functionality typically increases the reactivity of the aromatic ring. For example, the N-oxide functionality in pyridine N-oxide facilitates both electrophilic and nucleophilic substitution at the alpha and gamma positions (57). 

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