Pyridine‐N‐oxide as an intermediate for the preparation of 2‐ and 4‐substituted pyridines

Abstract

A description is given of methods for the preparation of 4‐, 2,4‐ and 3,4‐substituted pyridines, e.g. 4‐aminopyridine. the N‐oxide of pyridine or derivatives of pyridine is used as an intermediate to make e pyridine nucleus accessible for substitution in positions 2 and 4.

A Convenient Synthesis of Gimeracil

“…The starting material 2,4-dimethoxypyridine (4) could be prepared from 2,4-dichloropyridine by nucleophilic substitution of the chlorine atoms with freshly prepared sodium methoxide in N-methyl-2-pyrrolidone under a nitrogen atmosphere. 11 2,4-dimethoxypyridine (4) was first chlorinated at both C-3 and C-5 positions to afford 3,5-dichloro-2,4-dimethoxypyridine (5) in 88% yield, with N-chlorosuccinimide (NCS) as the chlorination reagent. Selective monochlorination at the C-5 position using NCS was attempted, but the regioselectivity was poor.…”

Cyclization of substituted 3,4-diaminopyridines into 1H-[1,2,3]triazolo[4,5-c]pyridine 2-oxide derivatives during the nitration process

“…Its elemental composition was C 5 H 3 N 5 O 3 . The above findings led us to assign the structure of 4-nitro-1H- [1,2,3]triazolo [4,5-c]pyridine 2-oxide (II) to the obtained compound. Tautomeric N-hydroxy structure IIa is also possible (Scheme 1).…”

“…We showed previously that nitration of 3,4-bis-(formylamino)pyridine (I) with a mixture of nitric and sulfuric acids leads to the formation of 4-nitro-1H- [1,2,3]triazolo [4,5-c]pyridine 2-oxide (II) [1]. In the present work we performed a more detailed study on this reaction, using various substituted 3,4-diaminopyridine derivatives as substrates.…”

“…The reduction of nitro compound II with iron in acetic acid under the conditions described in [3] gave 1H- [1,2,3]triazolo [4,5-c]pyridin-4-amine (V) whose IR and 1 H NMR spectra were identical to those of an authentic sample of V prepared from 4-chloro-1H- [1,2,3]triazolo [4,5-c]pyridine [4].…”

“…In the present work we performed a more detailed study on this reaction, using various substituted 3,4-diaminopyridine derivatives as substrates. We found that the reactions of 3,4-bis(acetylamino)pyridine (III) and 3,4-diaminopyridine (IV) with excess nitric acid (d = 1.5 g/cm 3 ) in concentrated sulfuric acid at 60°C [1] afforded the same product which decomposed with explosion on heating above 225°C. The presence of strong absorption bands at 1310, 1365, and 1540 cm -1 in the IR spectrum of this compound indicated that its molecule contains a nitro group and an N-oxide moiety.…”