Nucleophilic substitution structure affecting electrophilicity

Of course, the presence of the nitrogen atoms as part of the ring structure, as well as exocyclic, will affect not only dissociation behavior, but overall chemical reactivity. The course of electrophilic and nucleophilic substitution reactions will be determined by the presence of these nitrogen atoms. For example, the two heterocyclic nitrogen atoms in pyrimidines result in an electron distribution about the ring which makes C-5 electron rich relative to the other carbon atoms and thus most susceptible to electrophilic addition. 

While the alkoxymetallation process has typically been affected by highly electrophilic metal salts, high-valent metal species generated by an oxidative addition have also been used to activate alkynes through the formation of 7r-complexes. In such cases, the metal-carbon emerging from the attack of an oxygen nucleophile may enter a reaction manifold that leads to an additional C-G bond formation rather than a simple protic quench. This approach, pioneered by Arcadi and Cacci, has proved to be a powerful strategy for the synthesis of structurally diverse substituted... 

The chemical properties of pyridine are those we would expect on the basis of its structure. The ring undergoes the substitution, both electrophilic and nucleophilic, typical of aromatic rings our interest will lie chiefly in the way the nitrogen atom affects these reactions. 

No gas-phase reactions of electrophilic substitution have been known so far, while the formation of the transition state structure of Eq. (5.9) in solution is greatly (often decisively) affected by medium factors, the specific solvation and the nucleophilic catalysis. Even though the true structure of a transition state of the Se2 reaction is much more complicated than XXIV, this structure correctly reflects the stereochemistry of substitution at the tetrahedral carbon atom, namely, the retention of configuration of the carbon atom bonds observed experimentally in most Se2 reactions (the Se2 rule. Ref. [1]). 

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