Synthetic Utilization of Polynitroaromatic Compounds. 6. Remarkable Regioselectivity in Nucleophilic Displacement of Aromatic Nitro Groups with Amines

Abstract

5,7-Dinitroquinazoline-4-ones undergo nucleophilic displacement of a nitro group with N-, S-, and O-nucleophiles. In contrast to previously studied dinitro-substituted benzoannulated five- and seven-membered heterocycles (where a high degree of selectivity was observed), these quinazolines mostly yield mixtures of regioisomeric substitution products. At the same time, primary and secondary amines react selectively to afford 5-aminoquinazolones (peri-substitution). A similar effect is observed for some other polynitroaromatic compounds with adjacent nitro and carbonyl groups. This phenomenon is attributed to a stabilization of the intermediate peri-sigma-complex by intramolecular hydrogen bond N(+)-H...O double bond C.

Concerted Nucleophilic Aromatic Substitution Reactions

“…Nucleophilic displacement of nitro groups, in 5,7‐dinitroquinazoline‐4‐one 51 , by methylamine as nucleophile, was reported by Goel et al . Their computational study built upon a previous experimental study that had shown that the nitro group in the peri ‐position to the carbonyl was regioselectively displaced over the nitro group in the para ‐position, affording 52 in 85 % yield (Scheme ). In that experimental paper, the authors had proposed the reaction to occur via a σ‐intermediate, but evidence for this complex was not presented.…”

Regioselective Copper(I)‐Catalyzed Ullmann Amination of Halopyridyl Carboxylates using Sodium Azide: A Route for Aminopyridyl Carboxylates and their Transformation to Pyrido[2, 3‐d]pyrimidin‐4(1H)‐ones

“…Further, an attempt has been made to build some nitrogen‐containing heterocyclic motifs by using the synthesized ortho‐functionalized aminopyridines as the starting material (Scheme ). Treatment of 2‐aminonicotinic acid (2a) with acetic anhydride gave compound 10 which was further utilized to afford 2‐methyl‐3‐phenylpyrido[2, 3‐d]pyrimidin‐4(3H)‐one 11 by the treatment of aniline in ethanol (Scheme ) …”

Regioselective nucleophilic aromatic substitution reactions of 5,7-dinitroquinazoline-4-one and 5,7-dinitroquinazoline-4-thione with methylamine: a mechanistic consideration

“…A similar type of hydrogen bonding is not possible in the corresponding para-s-complex due to the absence of carbonyl oxygen in the vicinity of the para-position. 6 Despite the importance of amine-substituted quinazolines and the pharmacological significance of their production, the underlying mechanism of substituting the nitro group of 5,7-dinitroquinazoline-4-one with methylamine still remains to be understood. Either of the two distinct mechanistic pathways (depicted in Schemes 1 and 2), i.e., a two-step addition-elimination process via a zwitterionic intermediate para/peri-s-complex (A/B) or a one-step concerted mechanism via a transition state (TS1/TS2) can be followed during the nucleophilic aromatic substitution of the nitro group of 5,7-dinitroquinazoline-4-one.…”