An introduction to the synthesis of nitroanilines and nitropyridines via three component ring transformation

Nitro compounds show great importance in chemistry, biology and material sciences. Among them, nitropyridines and nitroanilines are widely used as useful intermediates for synthesis of biologically active compounds of pharmaceutical and agrochemical importance. Hence, we reported a powerful method for synthesis of various kinds of nitro compounds by using a three component ring transformation (TCRT) of dinitropyridone 1 with ketones in the presence of less nucleophilic ammonium acetate (NH₄OAc) as nitrogen source.

When pyridone 1 was reacted with aromatic ketone in the presence of ammonium acetate, 6-arylated 3-nitropyriines 2 were formed besides diazabicyclo compounds 3. This method was also applicable to cycloalkanones and α,β-unsaturated ketones to afford cycloalka[b]pyridines 4 and 6-alkynylated/alkenylated pyridines 5, respectively. It was found to be possible to use aldehydes as the substrate, what led to 3,5-disubstituted pyridines 6.

On the other hand, when aliphatic ketones were employed as the substrate, two kinds of ring transformation proceeded. Namely, 2,6-disubstituted 4-nitroanilines 8 were formed in addition to nitropyridines 7. This protocol was successful applied to synthesis of N,N,2,6-tetrasubstituted nitroanilines 9 upon treatment of dinitropyridone 1 with ketone and amine in the presence of acetic acid.