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

Seung-Hye Yang; Seohyun Jo; Dongyun Shin

doi:10.1055/s-0036-1588798

Synlett, Inhaltsverzeichnis

Synlett 2017; 28(13): 1614-1619
DOI: 10.1055/s-0036-1588798

letter

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

Autor*innen

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

Abstract

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This paper is dedicated to Professor Young-Ger Suh on the occasion of his 65^th 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.

Key words

2-quinolone - Lewis acid - intramolecular - cyclization - oxidation

Volltext

Referenzen

References and Notes
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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.