Nitropyridines, their synthesis and reactions

Reaction of pyridine and substituted pyridines with N2O5 in an organic solvent gives the N-nitropyridinium ion. When this is reacted with SO2/HSO3- in water, 3-nitropyridine is obtained (77 % yield). With substituted pyridines the method gives good yields for 4-substituted and moderate yields for 3-substituted pyridines. The reaction mechanism is not an electrophilic aromatic substitution but one in which the nitro group migrates from the 1-position to the 3-position by a [1,5] sigmatropic shift. From 3-nitropyridine, 5-nitropyridine-2-sulfonic acid is formed in a two step reaction. From this, a series of 2-substituted-5-nitropyridines has been synthesized. 3-Nitropyridine and 4-substituted-3-nitropyridines have been substituted with ammonia and amines by the vicarious nucleophilic substitution (VNS) method with ammonia and amines and by the oxidative substitution method in the position para to the nitro group. High regioselectivities and yields have been obtained in both cases to afford a series of 4-substituted-2-alkylamino-5-nitropyridines. The VNS method has also been used in alkylation reactions with 3-nitropyridines to form dichloromethyl-and alkoxycarbomethyl-β-nitropyridines. From the appropriate substituted nitropyridines imidazopyridines and azaindoles have been formed.