Synlett 2017; 28(13): 1614-1619
DOI: 10.1055/s-0036-1588798
letter
© Georg Thieme Verlag Stuttgart · New York

AlCl3-Mediated Synthesis of 4-Aryl-2-quinolone-3-carboxylates

Seung-Hye Yang ◊
College of Pharmacy, Gachon University, 191 Hambakmoe-ro, Yeonsu-gu, Incheon 21936, South Korea   Email: dyshin@gachon.ac.kr
,
Seohyun Jo ◊
College of Pharmacy, Gachon University, 191 Hambakmoe-ro, Yeonsu-gu, Incheon 21936, South Korea   Email: dyshin@gachon.ac.kr
,
Dongyun Shin*
College of Pharmacy, Gachon University, 191 Hambakmoe-ro, Yeonsu-gu, Incheon 21936, South Korea   Email: dyshin@gachon.ac.kr
› Author Affiliations
Supported by: Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2015R1D1A1A01056620)
Supported by: Bio & Medical Technology Development Program through the National Research Foundation of Korea (NRF) (NRF-2014M3A9B6069338)
Further Information

Publication History

Received: 18 February 2017

Accepted after revision: 27 March 2017

Publication Date:
02 May 2017 (online)


This paper is dedicated to Professor Young-Ger Suh on the occasion of his 65th birthday
These two authors contributed equally to this work

Abstract

4-Aryl-2-quinolones are important skeletons from both chemical and medicinal viewpoints. We herein report the development of an efficient synthetic method for 3-substituted 4-aryl-2-quinolones. The key reaction in this process involves an AlCl3-mediated intramolecular cyclization of substituted 2-(carbamoyl)-3-phenylacrylates, with optimized reaction conditions of 2.0 equivalents of AlCl3, nitrobenzene, 80 °C, and 3 hours. The chemical yields of cyclization were found to be sensitive to all reaction conditions.

 
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  • 26 Synthesis of 2aB AlCl3 (1.81 mL, 1 M solution in nitrobenzene) was slowly added to a solution of 4aB (300 mg, 0.906 mmol) in dry nitrobenzene (5 mL) at 0 °C. The reaction mixture was warmed to 80 °C and stirred for 3 h. After cooling, the reaction mixture poured into ice-water and diluted with EtOAc. The organic layer was separated and washed with sat. NaHCO3, H2O and brine, dried over anhydrous MgSO4, and filtered. After evaporation of volatile solvents under reduced pressure, the residue was purified by silica gel column chromatography to afford the desired product 3aB; 283 mg (95%), white solid. 1H NMR (600 MHz, CDCl3): δ = 8.93 (s, 1 H), 7.31 (t, J = 7.3 Hz, 2 H), 7.20 (q, J = 7.32 Hz, 12.3 Hz, 1 H), 7.15 (m, 2 H), 6.97 (dd, J = 2.5, 7.3 Hz, 1 H), 6.88 (q, J = 4.8, 7.3 Hz, 1 H), 6.82 (m, 1 H), 4.65 (d, J = 4.6 Hz, 1 H), 4.11 (m, 2 H), 3.82 (d, J = 4.9Hz, 1 H), 1.10 (q, J = 5.0, 7.1 Hz, 3 H) ppm. 13C NMR (150 MHz, CDCl3): δ = 168.2, 166.8, 137.7, 136.2, 133.5, 129.2, 128.5, 124.8, 123.9, 115.9, 61.7, 54.9, 44.9, 14.0 ppm. HRMS (ESI-TOF): m/z [M + H]+ calcd for C18H19ClNO3: 330.0891; found: 330.0895 The mixture of DDQ (257 mg, 1.14 mmol) and 3aB (250 mg, 0.760 mmol) in benzene (5 mL) was stirred for 3 h. The reaction mixture was diluted with water and extracted with EtOAc. The organic layer was washed with sat. NaHCO3, H2O and brine, dried over anhydrous MgSO4, and filtered. After evaporation of volatile solvents under reduced pressure, the residue was purified by silica gel column chromatography to afford the desired product 2aB; 236 mg (95%), white solid. 1H NMR (600 MHz, CDCl3): δ = 9.23 (s, 1 H), 7.56 (d, J = 8.5 Hz, 2 H), 7.33 (t, J = 8.0 Hz, 2 H), 7.12 (t, J = 7.4 Hz, 1 H), 4.26 (q, J = 7.1 Hz, 2 H), 3.47 (s, 2 H), 1.33 (t, J = 7.2 Hz, 3 H) ppm. 13C NMR (151 MHz, CDCl3): δ = 170.0, 162.9, 137.5, 129.0, 124.6, 120.1, 62.0, 41.5, 14.1 ppm. HRMS (ESI-TOF): m/z [M + H]+ calcd for C18H15ClNO3: 328.0735; found: 328.0732.