Vicarious nucleophilic amination of nitroquinolines with 4-amino-1,2,4-triazole

Abstract

3-, 5-, 6-, 7- and 8-Nitroquinolines react with 4-amino-1,2,4-triazole in basic medium (potassium tert-butoxide-dimethyl sulfoxide) giving amino products of the vicarious nucleophilic substitution (VNS) of hydrogen, predominantly at ortho position to the nitro group, except 8-nitroquinoline, which reacts at para position. Additionally, furazano[3,4-f]- and furazano[3,4-h]quinoline were obtained in the case of 5- and 8- nitroquinoline, respectively. 2-Nitroquinoline was aminated to 2-quinolino(1,2,4-triazol-4-yl)amine in these conditions.Key words: nitroquinolines, vicarious nucleophilic substitution (VNS), 4-amino-1,2,4-triazole.

8-Hydroxy-5-nitroquinoline as a C-nucleophilic reagent in the reaction of C, C-coupling with quinazoline

“…These positions of molecule 1 are characterized by increased electrophilic properties. Taking into account the absence of steric hindrances to the formation of a stable C-C bond at the C 6 position of nitroxaline, it can be assumed that this electrophilic center is the most active when interacting with nucleophiles, which is confirmed by data from the literature [4][5][6].…”

“…The lowest unoccupied molecular orbital (LUMO, Fig. 1b) are localized on the nitrogen atoms of the nitro group, C 6 and C 8 atoms of nitroxaline. These positions of molecule 1 are characterized by increased electrophilic properties.…”

“…The reaction of amination of nitroquinolines with trimethylhydrazinium iodide occured in a solution of anhydrous DMSO in the presence of potassium tert-butylate [5]. Vicarious amination of nitroquinolones with 4-amino-1,2,4-triazole was carried out under similar conditions and occured at the C 6 atom of nitroquinolone [6]. It was known that 5-nitro-8-hydroxyquinoline 1 reacted with formaldehyde in the presence of amines, to form 7-substituted aminomethyl derivatives of 5-nitroquinoline-8-ol 2 [7] (Scheme 1).…”

Electrophilic and Nucleophilic Aromatic Substitutions are Mechanistically Similar with Opposite Polarity

“…Nevertheless, at low temperatures, ammonia adds to active nitroarenes such as 2,4‐dinitrochlorobenzene to form σ H adducts that, upon oxidation, produces 3‐chloro‐4,6‐dinitroaniline (Scheme 2). [8] At higher temperatures, the slower ipso substitution of chlorine dominates.…”

“…Similarly, α‐chlorocarbanions generated by deprotonation of alkyl chloroacetates enter VNS with nitrobenzene, whereas carbanion of dimethyl chloromalonate is a weak nucleophile unable to react with nitrobenzene, but it reacts with more electrophilic 5‐nitrothiazole, etc [24] . Such weak nucleophile as ammonia forms long lived σ H adducts with m ‐dinitrobenzene and 2,4‐dinitrochlorobenzene so oxidative amination proceeds, [8] whereas similar amination does not proceed with nitrobenzene and chloronitrobenzene.…”