2-Bromopyridine displacement reactions

Intramolecular nucleophilic displacement of the bromo group by an azine-nitrogen occurs in the cyclization of A-2-quinaldyl-2-bromo-pyridinium bromide (248) to give the naphthoimidazopyridinium ring system. The reaction of 2-bromopyridine and pyridine 1-oxide yields l-(2-pyridoxy)pyridinium bromide (249) which readily undergoes an intramolecular nucleophilic substitution in which departure of hydrogen as a proton presumably facilitates the formation of 250 by loss of the JV-oxypyridyl moiety. 

The relative reactivities with respect to nucleophilic SAE displacement increase in the order Cl < Br < I < F. The relative reactivities of nucleophiles are illustrated by the reactions of 2-bromopyridine replacement by the following groups occurs under the conditions given (an indicates that the product spontaneously tautomerizes) ... 

There is a far from complete set of comparisons of relative reactivities" in nucleophilic displacement of halide. From a study of reactions of bromo-A-methyl-tetrazoles, -triazoles and -imidazoles with piperidine, it seems that the presence of two doubly bonded nitrogens is necessary to overcome electron release from the singly bonded nitrogen to approach the reactivity of 2-bromopyridine. ... 

In some, apparently straightforward, displacements, more detailed mechanistic study reveals the operation of alternative mechanisms. For example the reaction of either 3- or 4-bromopyridine with secondary amines in the presence of sodamide/ sodium t-butoxide, produces the same mixture of 3- and 4-dialkylaminopyridines this proceeds via an elimination process (Sn(EA) - Substitution Nucleophilic Elimination Addition) and the intermediacy of 3,4-didehydropyridine (3,4-pyr-idyne)." That no 2-aminated pyridine is produced shows a greater difficulty in generating 2,3-pyridyne, it can however be formed by reaction of 3-bromo-2-chloropyridines with butyllithium" or via the reaction of 3-trimethylsilyl-2-trifluoromethanesulfonyloxypyridine with fluoride." ... 

Studies related to the nucleophilic displacement in halo N-hetero-cycles indicate that the imidoyl character determines the mobility of the halo group ( ). For example, the rate of reaction of 2-bromoquinoline (V) with methoxide ion is about 80 times faster than that of 2-bromopyridine (VI). Apparently, in the benzo derivatives, the aromatic character of the ring with the heteroatom is reduced, thereby increasing the imidoyl character and thus enhancing the rate. 

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