o-Nitroaryloxiranyl Aryl Ketones as Versatile Reagents for the Facile Synthesis of 2-Arylquinolines and Quinolin-4-ones

Abstract

Quinolines and quinolin-4-ones, which are a frequent motif in biologically active molecules, can be prepared from readily available o-nitroaryloxiranyl aryl ketones. The two-stage synthesis of 2-arylquinolines involves the regioselective opening of the oxirane ring with hydrobromic acid or, in some cases, hydrochloric acid to afford 2-halo-3-hydroxy-3-(o-nitroaryl)-1-arylpropan-1-ones and sodium dithionite-mediated intramolecular reductive cyclization. At the same time, o-nitrophenyloxiranyl aryl ketones without other substituents in the 2-nitrophenyl fragment, when exposed to hydrochloric acid in a one-step reaction, form 6-chloro-1,3-dihydroxy-2-arylquinolin-4-ones. The cis-isomer of o-nitrophenyloxiranyl phenyl ketone, when exposed to hydrobromic acid, forms a mixture of 1,3-dihydroxy-2-phenylquinolin-4-one and 6-bromo-1,3-dihydroxy-2-phenylquinolin-4-one, from which a two-component solid solution was isolated in a ratio of the corresponding quinolinones of 0.95:0.05. The cascade processes of quinolin-4-one formation occur without the participation of an external reducing agent, but all functional groups in the molecule, namely the nitro group, oxirane ring, and carbonyl group, are involved in them.

Keywords

o-Nitroaryloxiranyl aryl ketones - Oxirane ring opening - Intramolecular reductive cyclization - 2-Arylquinolines - 2-Arylquinolin-4-ones - Two-component solid solution

Publikationsverlauf

Eingereicht: 16. August 2025

Angenommen nach Revision: 17. September 2025

Artikel online veröffentlicht:
23. Oktober 2025

• References

• 1 Manske RH. Chem Rev 1942; 30: 113
• 2a Kuzmina OM, Steib AK, Markiewich JT, Flubacher D, Knochel P. Angew Chem Int Ed 2013; 52: 4945
• 2b Larionov OV, Stephens D, Mfuh A, Chavez G. Org Lett 2014; 16: 864
• 2c Kuzmina OM, Steib AK, Flubacher D, Knochel P. J Am Chem Soc 2012; 18: 4818
• 3 Liu KM, Lian LY, Duan XF. Chem Commun 2015; 51: 1124
• 4a Berman AM, Lewis JC, Bergman RG, Ellman JA. J Am Chem Soc 2008; 130: 14926
• 4b Berman AM, Bergman RG, Ellman JA. J Org Chem 2010; 75: 7863
• 4c Campeau L-C, Stuart DR, Leclerc J-P. et al. J Am Chem Soc 2009; 131: 3291
• 5a Cao L, Zhao H, Guan R, Jiang H, Dixneuf PH, Zhang M. Nat Commun 2021; 12: 4206
• 5b Ren X, Han S, Gao X. et al. Tetrahedron Lett 2018; 59: 1065
• 5c Singh PP, Aithagani SK, Yadav M, Singh VP, Vishwakarma RA. J Org Chem 2013; 78: 2639
• 5d Deb A, Manna S, Maji A, Dutta U, Maiti D. Eur J Org Chem 2015; 5251
• 6a Mierde HV, Van Der Voort P, De Vos D, Verport F. J Org Chem 2008; 1625
• 6b Wang R, Fan H, Zhao W, Li F. Org Lett 2016; 18: 3558
• 6c Parua S, Sikari R, Sinha S, Das S, Chakraborty G, Paul ND. Org Biomol Chem 2018; 16: 274
• 6d Xu J, Chen Q, Luo Z, Tang X, Zhao J. RSC Adv 2019; 9: 28764
• 7a Hao Z, Zhou X, Ma Z. et al. J Org Chem 2022; 87: 12596
• 7b Chetia S, Sarmah S, Dutta A, Sarma D, Eur J. Org Chem 2023; 26: e202300390
• 7c Mondal S, Chakraborty S, Khanra S. et al. J Org Chem 2024; 89: 5250
• 8a Tan D-W, Li H-X, Zhu D-L. et al. Org Lett 2018; 20: 608
• 8b Martinez R, Ramon DJ, Yus M. Tetrahedron 2006; 62: 8982
• 9 Rubio-Presa R, Suarez-Pantiga S, Pedrosa MR, Sanz R. Adv Synth Catal 2018; 360: 2216
• 10a Anand N, Koley S, Ramulu JB, Singh MSH. Org Biomol Chem 2015; 13: 9570
• 10b Martinez R, Ramon DJ, Yus M. J Org Chem 2008; 73: 9778
• 10c Ding Y, Guo T, Li Z. et al. Angew Chem Int Ed 2022; 61: e202206284
• 11 Li X, Xing Q, Li P, Zhao J, Li F. Eur J Org Chem 2017; 618
• 12a Ji X, Huang H, Li Y, Chen H, Jiang H. Angew Chem Int Ed 2012; 51: 7292
• 12b Liu Y, Hu Y, Cao Z. et al. Adv Synth Catal 2018; 360: 2691
• 13 Wang P, Wang X, Niu X, Zhu L, Yao X. Chem Commun 2020; 56: 4840
• 14a Narasimhamurthy KH, Chandrappa S, Kumar KSS. Chem Lett 2013; 42: 1073
• 14b Ma Y, Zhou C, Xiao F, Mao G, Deng G-J. J Org Chem 2023; 88: 2952
• 15 Lee SY, Cheon C-H. J Org Chem 2018; 83: 13036
• 16 Okuma K, Seto J. Phosph Sulfur Silicon 2010; 185: 1014
• 17 Okuma K, Yasuda T, Shioji K, Yokomori Y. Bull Chem Soc Jpn 1824; 2017: 9
• 18 Lee SY, Jeon J, Cheon C-H. J Org Chem 2018; 83: 5177
• 19 Chen X, Qui S, Wang S, Wang H, Zhai H. Org Biomol Chem 2017; 15: 6349
• 20a Liu F, Yu L, Lv S, Yao J, Liu J, Jia X. Adv Synth Catal 2016; 358: 459
• 20b Sangu K, Fuchibe K, Akitama T. Org Lett 2004; 6: 353
• 20c Hill MD, Movassaghi M. Synthesis 2007; 1115
• 21 Mamedova VL, Mamedova SV, Korshin DE, Gavrilova EL, Mamedov VA. Russ Chem Rev 2025; 94: RCR5167
• 22 Shi D, Rong L, Wang J. et al. J Chem Res(S) 2003; 342
• 23 Shi D, Rong L, Shi C. et al. Synthesis 2005; 0717
• 24 Sandelier MJ, DeShong P. Org Lett 2007; 17: 3209
• 25 Sudhapriya N, Nandakumar A, Perumal PT. RSC Adv 2014; 4: 58476
• 26a Mamedov VA, Mamedova VL, Syakaev VV. et al. Tetrahedron 2017; 73: 5082
• 26b Mamedov VA, Mamedova VL, Khikmatova GZ. et al. RSC Adv 2016; 6: 27885
• 27a Mamedova VL, Khikmatova GZ, Korshin DE, Mamedova SV, Gavrilova EL, Mamedov VA. Russ Chem Rev 2022; 91: RCR5049
• 27b Charushin VN, Verbitskiy EV, Chupakhin ON. et al. Russ Chem Rev 2024; 93: RCR5125 (348)
• 28 Arndt F, Eistert B, Partale W. Chem Ber 1928; 61: 1107
• 29 Bamberger E, Busdorf H, Szolayski B. Chem Ber 1899; 32: 210
• 30a Huse H, Whiteley M. Chem Rev 2011; 111: 152-159
• 30b Beniddir MA, Bogdan EL, Iorga BI. et al. J Nat Prod 2014; 77: 1117
• 31 Cheng G, Hao H, Dai M, Liu Z, Yuan Z. Eur J Med Chem 2013; 66: 555
• 32 Venturella P, Bellino A, Piozzi F, Marino ML. Heterocycles 1976; 4: 1089
• 33 Spence TWM, Tennant G. J Chem Soc 1971; 3712
• 34 Fayzullin RR, Shteingolts SA, Lodochnikova OA, Mamedova VL, Korshin DE, Mamedov VA. CrystEngComm 2019; 21: 1587
• 35 Mamedov VA, Mamedova VL, Khikmatova GZ. et al. Rus Chem Bul Int Ed 2019; 68: 1020
• 36 Das S, Sinha S, Samanta D. et al. J Org Chem 2019; 84: 10160
• 37a Xu X, Ai Y, Wang R, Liu L, Yang J, Li F. J Catal 2021; 395: 340
• 37b Liu Y-T, Wei Y, Huang Z-H, Liu Y. Org Biomol Chem 2021; 19: 659
• 38 Xie J, Huang H, Xu Y, Li R, Chen J, Ye X. RSC Adv 2020; 10: 8586
• 39 Xu T, Shao Y, Dai L, Yu S, Cheng T, Chen J. J Org Chem 2019; 84: 13604
• 40 Mahato S, Mukherjee A, Santra S, Zyryanov GV, Majee A. Org Biomol Chem 2019; 17: 7907
• 41 Naruto H, Togo H. Synthesis 2020; 52: 1122
• 42 Xu J-X, Pan N-L, Chen J-X, Zhao J-W. J Org Chem 2021; 86: 10747
• 43 Li C, Li J, An Y, Peng J, Wu W, Jiang H. J Org Chem 2016; 8: 12189
• 44 Gomes CMM, Kouznetsov VV, Sortino MA, Alvarez SL, Zacchino SA. Bioorg Med Chem 2008; 16: 7908
• 45 Varma PP, Sherigara BS, Mahadevan KM, Hulical V. Synth Commun 2010; 40: 2220
• 46 Khan D, Kushwaha P, Parveen I, Maurya N, Shaily. Curr Org Chem 2025; 29: 213