Organic Chemistry Heterocyclic Compounds Lec. 4 - PDF

Organic Chemistry III Heterocyclic Compounds Reactions of pyridine | Lec.4 Organic Chemistry | Heterocyclic Compounds Contents : Reactions of pyridine 3 Electrophilic substitution in pyridine 4 Questions 13 Organic Chemistry | Heterocyclic Compounds Reactions of pyridine: The chemical properties of...

Organic Chemistry III Heterocyclic Compounds Reactions of pyridine | Lec.4 Organic Chemistry | Heterocyclic Compounds Contents : Reactions of pyridine 3 Electrophilic substitution in pyridine 4 Questions 13 Organic Chemistry | Heterocyclic Compounds Reactions of pyridine: The chemical properties of pyridine are those as would be expect on the basis of its electronic structure. The ring undergoes the substitution, both electrophilic and nucleophilic, typical of aromatic rings; the interest will lie chiefly in the way the nitrogen atom affects these reactions. There is another set of reactions in which pyridine acts as a base or nucleophile; these reactions involve nitrogen directly and are due to its unshared pair of electrons. Organic Chemistry | Heterocyclic Compounds Electrophilic substitution in pyridine: Toward electrophilic substitution, pyridine resembles a highly deactivated benzene derivative. It undergoes nitration, sulfonation, and halogenation only under very vigorous conditions but does not undergo the Friedel-Crafts reaction at all. Substitution occurs chiefly at the 3- (or β-) position: Organic Chemistry | Heterocyclic Compounds Organic Chemistry | Heterocyclic Compounds Accounting the reactivity and orientation on the usual basis of stability of the intermediate carbonium ion. Attacking at the 4-position yields a carbonium ion that is a hybrid of structures I, II, and III: Organic Chemistry | Heterocyclic Compounds Whereas attacking at the 3-position yields an ion that is a hybrid of structures IV, V, and VI: Organic Chemistry | Heterocyclic Compounds Attack at the 2-position resembles attack at the 4-position just as ortho attack resembles para attack in the benzene series (H.W). Organic Chemistry | Heterocyclic Compounds All these structures are less stable than the corresponding ones for attack on benzene, because of electron withdrawal by the nitrogen atom. As a result, pyridine undergoes substitution more slowly than benzene. Of these structures, III is especially unstable, since in it the electronegative nitrogen atom has only a sextet of electrons. As a result, attack at the 4-position (or 2-position) is especially slow, and substitution occurs predominantly at the 3-position. Organic Chemistry | Heterocyclic Compounds It is important to see the difference between substitution in pyridine and substitution in pyrrole. In the case of pyrrole, a structure in which nitrogen bears a positive charge is especially stable since every atom has an octet of electrons; nitrogen accommodates the positive charge simply by sharing four pairs of electrons: Organic Chemistry | Heterocyclic Compounds Organic Chemistry | Heterocyclic Compounds In the case of pyridine, a structure in which nitrogen bears a positive charge (III) is especially unstable since nitrogen has only a sextet of electrons; nitrogen shares electrons readily, but as an electronegative atom it resists the removal of electrons: Organic Chemistry | Heterocyclic Compounds Questions: Q.1: 2-Aminopyridine can be nitrated or sultonated under much milder conditions than pyridine itself; substitution occurs chiefly at the 5-position. Account for these facts. Organic Chemistry | Heterocyclic Compounds Q.2: Because of the difficulty of nitrating pyridine, 3aminopyridine is most conveniently made via nicotinic acid. Outline the synthesis of 3-aminopyridi- ne from β-picoline.