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.

Starting from easily accessible 2‐chloro‐3‐(cyclopentyloxy)‐7‐fluoroquinoxaline 1‐oxide, 12 new biologically promising aroylquinoxaline N‐oxides were synthesized through carbene‐catalyzed aroylation of the chloro nitrone unit with different aromatic aldehydes in the presence of 1,3‐dimethylimidazolium iodide as the carbene precursor. The optimized reaction conditions tolerated a broad bandwidth of aldehydes and allowed the synthesis of the corresponding ketones in yields up to 87 %. Studies of their biological activities resulted in interesting specific cytotoxic effects against tumor cell lines.

A selection of 2‐chloro‐substituted O‐alkylquinoxaline N‐oxides, easily accessible by the one‐step annulation reaction of 4‐fluoroaniline with 1,1,2‐trichloro‐2‐nitroethylene and subsequent O‐alkylation, was arylated at the chloronitrone unit in yields up to 96 %. This first efficient Pd‐catalyzed Suzuki–Miyaura reaction of chloroquinoxaline N‐oxides with arylboronic acids led to new 2‐arylquinoxaline N‐oxides. The scope and limitations of this arylation reaction were investigated, and the role of some sterically demanding boronic acids in the cross‐coupling reaction was evaluated by means of DFT calculations. Additionally, the Pd‐catalyzed C‐arylation of the amide unit of selected quinoxalinone derivatives was accomplished.

Eur. J. Org. Chem. 2013, 36, 8185-8196, http

Temperature. -The newly synthesized aroylquinoxaline N-oxides (III) are screened for their antimicrobial activity as well as their cytotoxicity. Although no antimicrobial potency is found, several products show cytotoxic effects. The reaction fails for 4-nitrobenzaldehyde as substrate (not shown). -(MAICHROWSKI, J.; BHASIN, A.; SASSE, F.; KAUFMANN*, D. E.; Eur.