Categories: Synthesis of N-Heterocycles > benzo-fused N-Heterocycles >
Synthesis of quinoxalinones
Benzimidazoles and quinoxalin-2(1H)-ones were synthesized by treatment of 2-(N-Boc-amino)phenylisocyanide with carboxylic acids and glyoxylic acids, respectively via two-component coupling, deprotection, and intermolecular cyclization.
Z.-Z. Chen, Y. Tang, L. Zuo, D.-Y. Tang, J. Zhang, Z.-G. Xu, Synlett, 2014, 25, 2518-2520.
Efficient reactions of α-keto acids with 2-aminobenzamides, 2-aminobenzenethiols, benzene-1,2-diamines, and 2-aminophenols provide quinazolinones, benzothiazoles, quinoxalinones, and benzoxazinones under catalyst-free conditions, using water as the solvent. Products can be easily purified through filtration and washing with ethanol (or crystallized).
J. Huang, W. Chen, J. Liang, Q. Yan, Y. Fan, M.-W. Chen, Y. Peng, J. Org. Chem., 2021, 86, 14866-14882.
A photoredox-catalyzed direct arylation of quinoxalin-2-(1H)-ones using diaryliodonium triflates as convenient, stable, and cheap aryl sources provides efficient access to a wide variety of pharmaceutically important 3-arylquinoxalin-2-(1H)-ones. This operationally simple method offers mild conditions, broad scope, scalability, and high functional group tolerance.
R. K. Samanta, P. Meher, S. Murarka, J. Org. Chem., 2022, 87, 10947-10957.
The combination of tert-butyl hypochlorite, tetrabutylammonium iodide and tetrabutylammonium chloride as oxidation system enables the transformation of ethyl 2-(N-arylcarbamoyl)-2-iminoacetates into the corresponding quinoxalinones in high yield. Oxygen exhibits a beneficial effect on the reaction.
D. Li, Y. Li, W. Yu, Synthesis, 2017, 49, 4283-4291.
Whereas the cyclocondensation of 2-aminothiophenols with 1,2-biselectrophiles such as ethyl glyoxalate and diethyl oxalate in aqueous medium leads to the formation of benzothiazole-2-carboxylates via a 5-endo-trig process contrary to Baldwin’s rule, the reaction of 2-aminophenols/anilines produced the corresponding benzazine-3-ones or benzazine-2,3-diones via a 6-exo-trig process in compliance with Baldwin’s rule.
T. M. Dhameliya, S. S. Chourasiya, E. Mishra, P. S: Hadhavar, P. V. Bharatam, A. K. Chakraborti, J. Org. Chem., 2017, 82, 10077-10091.
An efficient, photoredox-catalyst-free radical alkylation of quinoxalin-2(1H)-ones with photoexcited 4-alkyl-1,4-dihydropyridines (R-DHPs) as alkyl radical precursors and acetoxybenziodoxole (BI-OAc) as an electron acceptor offers benign reaction conditions and good functional group compatibility.
X.-K. He, J. Lu, A.-J. Zhang, Q.-Q. Zhang, G.-Y. Xu, J. Xuan, Org. Lett., 2020, 22, 5984-5989.
A tandem nitrosation/cyclization reaction of N-aryl cyanoacetamides with tert-butyl nitrite provides quinoxalin-2-ones in good yields with good functional group tolerance. The dehydrogenative N-incorporation is achieved through a sequence of nitrosation, tautomerization, and cyclization.
F. Wang, B.-L. Hu, L. Liu, H.-Y. Tu, X.-G. Zhang, J. Org. Chem., 2017, 82, 11247-11252.
A facile and effective alkoxylation of quinoxalin-2(1H)-ones with primary or secondary alcohols via cross-dehydrogenative coupling under catalyst-free conditions provides 3-alkoxylquinoxalin-2(1H)-ones in very good yields in the presence of PhI(OTFA)2 as oxidant.
Q. Yang, X. Han, J. Zhao, H.-Y. Zhang, Y. Zhang, J. Org. Chem., 2019, 84, 11417-11424.
An efficient visible-light-induced C(sp2)-H/N-H cross-dehydrogenative coupling (CDC)-amination with both primary and secondary aliphatic amines allows the direct formation of 3-aminoquinoxalin-2(1H)-ones. Preliminary mechanistic studies reveal that the reaction proceeds through a radical process.
W. Wei, L. Wang, P. Bao, Y. Shao, H. Yue, D. Yang, X. Yang, X. Zhao, H. Wang, Org. Lett., 2018, 20, 7125-7130.
An efficient visible-light-induced decarboxylative coupling reaction of N-protected α-amino acids with heterocycles provides aminoalkylated heterocycles in good yields. Attractive features of this process include the generation of aminomethyl radical by an inexpensive organic photocatalyst under transition-metal-free conditions.
Y. Li, C. Dai, S. Xie, P. Liu, P. Sun, Org. Lett., 2021, 23, 5906-5910.
A metal-free cross-dehydrogenative coupling between quinoxalinones and amines in the presence of catalytic iodine and aqueous tert-butyl hydroperoxide as the terminal oxidant provides 3-aminoquinoxalinones in good yields in dioxane as solvent. The reaction is highly versatile and exhibits good functional group tolerance with a range of primary and secondary amines.
A. Gupta, M. S. Deshmuk, N. Jain, J. Org. Chem., 2017, 82, 4748-4792.
The use of trifluoromethyl thianthrenium salts enables high-yielding and scalable trifluoromethylation reactions under visible light irradiation. A free radical homolytic process is involved in this reaction, generating a key trifluoromethyl radical intermediate.
Y. Li, X. Liang, K. Niu, J. Gu, F. Liu, Q. Xia, Q. Wang, W. Zhang, Org. Lett., 2022, 24, 5918-5923.