ZnCl₂-Catalyzed Intramolecular Cyclization Reaction of 2-Aminochalcones Using Polymer-Supported Selenium Reagent: Synthesis of 2-Phenyl-4-quinolones and 2-Phenyl-2,3-dihydroquinolin-4(1H)-one

Abstract

A new and efficient method for the synthesis of 2-phenyl-4-quinolones and 2-phenyl-2,3-dihydroquinolin-4(1H)-ones is described. The reaction involves ZnCl₂-mediated polystyrene-supported selenium-induced intramolecular cyclization of 2-amino­chalcones and subsequent traceless or functionalizing cleavage of selenium linker.

Key words

polystyrene-supported selenium reagent - intramolecular cyclization - zinc chloride - 2-phenyl-4-quinolones - 2-phenyl-2 - 3-dihydroquinolin-4(1H)-one

References and Notes

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16

Benzeneselenenyl bromide was prepared by the reaction of diphenyldiselenide (1.0 equiv) and bromine (1.0 equiv) in CH₂Cl₂ at r.t. for 1 hour.

17

General Procedure for Obtaining 4-Quinolone 4 via Route A
An oven-dried 50 mL round-bottomed flask was charged with a suspension of the swollen polystyrene-supported selenenyl bromide (Br: 0.99 mmol/g) resin (1.0 g) in dry CH₂Cl₂ (20 mL). ZnCl₂ (40 mol%) was added. After stirring for 0.5 hour at r.t., substituted 2-aminochalcone 5 (5.0 mmol) was added, and the reaction was stirred for another 12 hours. The resin 3 was collected by filtration, washed with H₂O (4 × 20 mL), THF-H₂O (v/v = 3:1; 2 × 20 mL), THF (2 × 15 mL), MeOH (2 × 15 mL) and CH₂Cl₂ (2 × 15 mL) and dried in vacuo. To a flask containing the suspension of the swollen resin 3 in THF (20 mL) was added 30% H₂O₂ aq (1.0 mL), and the mixture was stirred for 1 hour at 0 ˚C, followed by 20 min at r.t. After the reaction, the mixture was filtered, and the resin was washed with CH₂Cl₂ (2 × 20 mL). The filtrate was washed with H₂O (2 × 10 mL), dried over MgSO₄, and evaporated to dryness in vacuo.
1-Benzyl-2-phenyl-4-quinolone (4a) ^¹H NMR (500 MHz, CDCl₃): δ = 8.53 (1 H, d, J = 7.8 Hz), 7.56 (1 H, m), 7.45-7.26 (10 H, m), 6.98 (2 H, d, J = 7.3 Hz), 6.56 (1 H, s), 5.33 (2 H, s). ^¹³C NMR (125 MHz, CDCl₃): δ = 176.81, 155.64, 140.94, 135.98, 135.21, 132.57, 129.74, 128.98, 128.64, 128.01, 127.64, 126.65, 126.49, 125.34, 125.22, 124.09, 117.30, 112.59, 52.36. IR (KBr): ν_max = 1608, 1486, 763 cm^-¹. HRMS: m/z calcd for C₂₂H₁₈NO [M + H]⁺: 312.1388; found: 312.1385.

18

General Procedure for the Preparation of 2-Phenyl-2,3-dihydroquinolin-4 (1 H )-one (9)
An oven-dried schlenk tube was charged with a suspension of the swollen resin 7 (0.5 g) in dry toluene (10 mL) under nitrogen atmosphere, and tributyltin hydride (0.291 g, 1.0 mmol) or allyltributylstannane (0.331 g, 1.0 mmol) and 2,2′-azobisisobutyronitrile (AIBN, 0.082 g, 0.5 mmol) were added after which the reaction mixture was heated to 90 ˚C for 2 hours. After cooling, the suspension was poured into a fritted funnel, and the resin was washed with CH₂Cl₂ (2 × 10 mL). The filtrate was then concentrated and 10% HCl (5 mL) was added, and the resulting solution was washed with hexanes (3 × 10 mL). The aqueous phase was then neutralized with 10% NaOH and extracted with Et₂O (2 × 10 mL). The combined organic layers were washed with brine (10 mL), dried over MgSO₄, and concentrated to afford the product 9.
1-Acetyl-2-phenyl-2,3-dihydroquinolin-4 (1 H )-one (9a) ^¹H NMR (400 MHz, CDCl₃): δ = 2.43 (3 H, s), 3.22-3.28 (1 H, m), 3.35-3.40 (1 H, m), 6.47 (1 H, br), 7.15-7.22 (7 H, m), 7.44-7.48 (1 H, m), 7.93 (1 H, d, J = 7.6 Hz). ^¹³C NMR (100 MHz, CDCl₃): δ = 193.1, 170.0, 141.7, 137.9, 134.3, 128.5, 127.5, 127.2, 126.7, 126.0, 125.4, 125.0, 54.6, 42.5, 23.3. IR (film): ν_max = 1693, 1682, 1663, 1601, 1461, 694 cm^-¹. HRMS: m/z calcd for C₁₇H₁₅NO₂: 265.1103; found: 265.1100.