A straightforward synthesis of some fused aza-arenesvia nucleophilic displacement of a ring hydrogen atom in nitroarenes by aromatic hydrazone anions

Abstract

6-Nitroquinoline 6 undergoes direct cyclocondensation with aromatic aldehyde hydrazones 9 in the presence of sodium hydride in DMF at low temperature, giving the corresponding 3-aryl-1H-pyrazolo[3,4-f]quinolines 10 and/or 3-aryl[1,2,4]triazino[6,5-f]quinolines 11 in low to moderate yield. With aromatic keto hydrazones 7, 3,3-disubstituted 2,3-dihydro[1,2,4]triazino[6,5-f]quinoline-4-oxides 8 are obtained in moderate to good yield. The mode of cyclocondensation is considerably dependent on the electronic nature of a ring substituent of the aromatic hydrazones; electron-donating substituents favor the formation of 11, while electron-withdrawing substituents work favorably for the formation of 10. Monocyclic nitroarenes 15 react similarly with 4-nitrobenzaldehyde hydrazone 9a to give another type of cyclocondensation product, 3-aryl-1H-indazoles 16, in moderate yield. In contrast, nucleophilic substitution of a ring hydrogen atom takes place with 4-methylbenzaldehyde hydrazone 9f to yield N-arylated hydrazone 22b, which, however, fails to cyclize to 16 under the conditions employed. The reaction has been suggested to proceed through the initial attack of a hydrazone anion on the position adjacent to the nitro group, followed by migration of an ipso hydrogen atom to the nitro group in the Meisenheimer intermediate 18. The resulting N²-arylated hydrazone anion would undergo ring closure via either addition to the nitroso group or displacement of this moiety, eventually leading to the fused aza-arenes 8, 10/11, 13 or 16.