Efficient Synthesis of Quinoxaline Derivatives by Selective Modification of 3‐Chloro‐6‐fluoroquinoxalin‐2(1H)‐one 4‐Oxide

Abstract

The readily available and polyfunctionalized 3‐chloro‐6‐fluoroquinoxalin‐2(1H)‐one 4‐oxide, derived from the efficient one‐step annulation reaction of 1,1,2‐trichloro‐2‐nitroethene with 4‐fluoroaniline, was selectively modified at the chloronitrone and the amide units, leading to more than 30 new quinoxaline derivatives with a unique substitution pattern in good to excellent yields. In addition, the electronic properties of the versatile starting compound were computed by means of density functional theory, which gave a reasonable explanation for its unique reactivity. The antimalarial activity of all hitherto unknown compounds has been investigated.

Synthesis and Reactivity of 3‐Halo‐4,5‐dihydroisoxazoles: An Overview

“…On the other hand, Zapol'skii and co‐workers [43] reported an alternative possibility to generate chloronitrile oxide in situ by treatment of 1,1,2‐trichloro‐2‐nitroethene with powdered sodium hydroxide in anhydrous solvents at 60 °C, followed by rapid and spontaneous release of chloride ion, chloridric acid and CO 2 (Scheme 2f). The aforementioned nitrated precursor is easily accessible through nitration of the inexpensive solvent trichloroethene with concentrated HNO 3 [43–45] …”

Part II: nitroalkenes in the synthesis of heterocyclic compounds

“…Further reactions of 106 with nucleophiles and electrophiles were also investigated by the same group. 70 Dihydroquinoxalinones 109 were synthesized via a consecutive anti-Michael addition-amidation reaction of o-phenylenediamine 99 (R ¼ H) with b-nitroacrylates 108 under uncatalysed reaction conditions (Scheme 28). 71 According to the authors nding, the best yield was obtained when 1.25 equivalents of diamine reacted with 1 equivalent of nitroalkene in EtOAc for two hours at room temperature.…”

Synthesis, Biological Evaluation and Structure-Activity Relationships of New Quinoxaline Derivatives as Anti-Plasmodium falciparum Agents

“…Over the last years, our group has been working on the development and synthesis of new quinoxaline derivatives. As a result of this line of research, the activities of quinoxaline 1,4-di- N -oxide derivatives against Mycobacterium tuberculosis [6,7,8,9,10,11,12,13], Trypanosoma cruzi [14,15], Leishmania amazonensis [16], L. infantum [17], P. falciparum [16,17,18,19,20,21,22,23] and different tumor cells [24,25,26] have been reported. The presence of two N -oxides is associated with a significant increase in some biological properties, such as anticancer [27] or antioxidant [28] activity.…”