Organic Chemistry Heterocyclic Compounds Lec.5 PDF

Organic Chemistry III Heterocyclic Compounds Reactions of pyridine II | Lec.5 Organic Chemistry | Heterocyclic Compounds Contents : Nucleophilic substitution in pyridine 3 Organic Chemistry | Heterocyclic Compounds Nucleophilic substitution in pyridine: Here, as in electrophilic substitution, the py...

Organic Chemistry III Heterocyclic Compounds Reactions of pyridine II | Lec.5 Organic Chemistry | Heterocyclic Compounds Contents : Nucleophilic substitution in pyridine 3 Organic Chemistry | Heterocyclic Compounds Nucleophilic substitution in pyridine: Here, as in electrophilic substitution, the pyridine ring resembles a benzene ring that contains strongly electron-withdrawing groups. Nucleophilic substitution takes place readily, particularly at the 2- and 4positions. For example: Organic Chemistry | Heterocyclic Compounds The reactivity of pyridine toward nucleophilic substitution is so great that even the powerfully basic hydride ion, H-, can be displaced. Two important examples of this reaction are amination by sodium amide (Chichibabin reaction), and alkylation or arylation by organolithium compounds. Organic Chemistry | Heterocyclic Compounds Organic Chemistry | Heterocyclic Compounds As it has been seen, nucleophilic aromatic substitution can take place by a mechanism that is quite analogous to the mechanism for electrophilic substitution. Reaction proceeds by two steps; the rate of the first step, formation of a charged particle, determines the rate of the overall reaction. In electrophilic substitution, the intermediate is positively charged; in nucleophilic substitution, the intermediate is negatively charged. Organic Chemistry | Heterocyclic Compounds The ability of the ring to accommodate the charge determines the stability of the intermediate and of the transition state leading to it, and hence determines the rate of the reaction. Nucleophilic attack at the 4-position yields a carbanion that is a hybrid of structures I, II, and III: Organic Chemistry | Heterocyclic Compounds Attack at the 3-position yields a carbanion that is a hybrid of structures IV, V, and VI: Organic Chemistry | Heterocyclic Compounds (As before, attack at the 2-position resembles attack at the 4position.) All these structures are more stable than the corresponding ones for attack on a benzene derivative, because of electron withdrawal by the nitrogen atom. Structure III is especially stable, since the negative charge is located on the atom that can best accommodate it, the electronegative nitrogen atom. Organic Chemistry | Heterocyclic Compounds It is reasonable, therefore, that nucleophilic substitution occurs more rapidly on the pyridine ring than on the benzene ring, and more rapidly at the 2- and 4-positions than at the 3-position. The same electronegativity of nitrogen that makes pyridine unreactive toward electrophilic substitution makes pyridine highly reactive toward nucleophilic substitution.