Condensation of Chromone-3-carboxaldehyde with Phenylacetic Acids: An Efficient Synthesis of (E)-3-Styrylchromones

Abstract

An efficient and diastereoselective synthetic method for preparing (E)-3-styrylchromones has been developed by the reaction of chromone-3-carboxaldehyde with phenylacetic acids in the presence of potassium tert-butoxide under classical heating conditions or microwave irradiation. The Knoevenagel-type reaction followed by a decarboxylation was faster under microwave conditions.

chromone-3-carboxaldehyde - phenylacetic acids - condensation - microwave irradiation - (E)-3-styrylchromones

References

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11

(E)-3-Styrylchromones 3a,b,d were shown to possess spectroscopic and analytical data identical to those previously reported.¹⁰

12

Physical Data of ( E )-4′-Trifluoromethyl-3-styrylchromone (3c): Mp 206-207 °C. ¹H NMR (300.13 MHz, CDCl₃): δ = 7.02 (d, 1 H, J = 16.3 Hz, H-α), 7.45 (t, 1 H, J = 7.8, 8.0 Hz, H-6), 7.49 (d, 1 H, J = 7.8 Hz, H-8), 7.60 (m, 4 H, H-2′,3′,5′,6′), 7.69 (dt, 1 H, J = 7.8, 7.8, 1.6 Hz, H-7), 7.76 (d, 1 H, J = 16.3 Hz, H-β), 8.13 (s, 1 H, H-2), 8.30 (dd, 1 H, J = 8.0, 1.6 Hz, H-5). ¹³C NMR (75.47 MHz, CDCl₃): δ = 118.1 (C-8), 121.2 (C-3), 121.7 (C-α), 124.1 (C-10), 124.2 (q, J = 271.8 Hz, CF₃), 125.5 (C-6), 126.3 (C-5), 125.6 (q, J = 3.9 Hz, C-3′,5′), 126.7 (C-2′,6′), 129.4 (q, J = 32.5 Hz, C-4′), 130.4 (C-β), 133.8 (C-7), 140.9 (C-1′), 154.0 (C-2), 155.7 (C-9), 176.6 (C-4). ¹⁹F NMR (300.13 MHz, CDCl₃; ref. C₆F₆): δ = -85.5 (s, CF ₃). Anal. Calcd for C₁₈H₁₁O₂F₃: C, 68.36; H, 3.51. Found: C, 68.04; H, 3.22.

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14

Typical Experimental Procedure under Classical Heating Conditions: A mixture of chromone-3-carboxaldehyde (1, 0.10 g, 5.74 × 10^-1 mmol), the appropriate phenylacetic acid 2a-g (0.39 g, 2.87 mmol) and tert-BuOK (0.10 g, 8.61 × 10^-1 mmol) in dry pyridine (15 mL) was refluxed until complete disappearance of 1. After that period the contents were cooled to r.t. and poured over H₂O and ice. The mixture was acidified at pH 2 with a solution of HCl. The pale yellow precipitate was separated by filtration washed with H₂O and purified by thin layer chromatography with a 7:3 mixture of CH₂Cl₂-light petroleum ether as eluent. The obtained residue was crystallised from EtOH giving 3-styrylchromones 3a-g in good yields (Table [3] ).

15

Physical Data of 3-Styrylchromones 3e-f
(E)-2′-Chloro-3-styrylchromone (3e): Mp 125.1-125.4 °C. ¹H NMR (300.13 MHz, CDCl₃): δ = 7.03 (dd, 1 H, J = 16.4, 0.5 Hz, H-α), 7.21 (ddd, 1 H, J = 7.5, 7.6, 1.8 Hz, H-5′), 7.28 (ddd, 1 H, J = 7.5, 7.7, 1.5 Hz, H-4′), 7.39 (dd, 1 H, J = 7.7 and 1.5 Hz, H-6′), 7.44 (ddd, 1 H, J = 7.6, 7.8, 0.9 Hz, H-6), 7.49 (dd, 1 H, J = 8.2, 0.9 Hz, H-8), 7.69 (ddd, 1 H, J = 7.6, 8.2, 1.7 Hz, H-7), 7.70 (dd, 1 H, J = 7.5, 1.8 Hz, H-3′), 7.92 (d, 1 H, J = 16.4 Hz, H-β), 8.19 (d, 1 H, J = 0.5 Hz, H-2), 8.32 (dd, 1 H, J = 7.8, 1.7 Hz, H-5). ¹³C NMR (75.47 MHz, CDCl₃): δ = 118.1 (C-8), 121.5 (C-α), 121.8 (C-3), 124.1 (C-10), 125.4 (C-6), 126.3 (C-5), 126.6 (C-3′), 126.9 (C-4′), 127.3 (C-β), 128.9 (C-5′), 129.8 (C-6′), 133.5 (C-2′), 133.6 (C-7), 135.4 (C-1′), 153.2 (C-2), 155.9 (C-9), 176.5 (C-4). Anal. Calcd for C₁₇H₁₁O₂Cl: C, 72.22; H, 3.92. Found: C, 71.99; H, 3.63.
(E)-2′-Trifluoromethyl-3-styrylchromone (3f): Mp 137.2-137.5 °C. ¹H NMR (300.13 MHz, CDCl₃): δ = 7.03 (d, 1 H, J = 16.1 Hz, H-α), 7.37 (t, 1 H, J = 7.6, 7.6 Hz, H-4′), 7.44 (dt, 1 H, J = 7.5, 7.5, 1.0 Hz, H-6), 7.49 (dd, 1 H, J = 8.4, 1.0 Hz, H-8), 7.80 (d, 1 H, J = 8.0 Hz, H-3′), 7.87 (dq, 1 H, J = 16.1, 2.4 Hz, H-β), 8.17 (dd, 1 H, J = 0.6 Hz, H-2). ¹³C NMR (75.47 MHz, CDCl₃): δ = 118.1 (C-8), 122.5 (C-3), 122.5 (q, J = 273.9 Hz, CF₃), 123.0 (C-α), 124.1 (C-10), 125.4 (C-6), 125.9 (q, 1 H, J = 5.7 Hz, C-β), 126.3 (C-5), 127.0 (q, J = 2.2 Hz, C-3′), 127.1 (C-6′), 127.5 (C-4′), 127.6 (q, J = 29.8, C-2′), 131.9 (C-5′), 133.7 (C-7), 136.3 (q, J = 1.7 Hz, C-1′), 153.3 (C-2), 155.9 (C-9), 176.5 (C-4).
¹⁹F NMR (300.13 MHz, CDCl₃; ref. C₆F₆): δ = -82.9 (s, CF ₃). Anal. Calcd for C₁₈H₁₁O₂F₃: C, 68.36; H, 3.51. Found: C, 68.66; H, 3.53.
(E)-2′-Nitro-3-styrylchromone (3g): Mp 194-195 °C. ¹H NMR (300.13 MHz, CDCl₃): δ = 7.08 (dd, 1 H, J = 16.3, 0.7 Hz, H-α), 7.43 (ddd, 1 H, J = 7.8, 7.7, 1.4 Hz, H-4′), 7.45 (ddd, 1 H, J = 7.7, 7.8, 1.0 Hz, H-6), 7.50 (dd, 1 H, J = 7.9, 1.0 Hz, H-8), 7.63 (ddd, 1 H, J = 7.7, 7.9, 1.4 Hz, H-5′), 7.70 (ddd, 1 H, J = 7.7, 7.9, 1.7 Hz, H-7), 7.79 (dd, 1 H, J = 8.0, 1.4 Hz, H-6′), 7.91 (d, 1 H, J = 16.3 Hz, H-β), 7.98 (dd, 1 H, J = 8.0, 1.4 Hz, H-3′), 8.22 (d, 1 H, J = 0.7 Hz, H-2), 8.31 (dd, 1 H, J = 7.8, 1.7 Hz, H-5). ¹³C NMR (75.47 MHz, CDCl₃): δ = 118.2 (C-8), 121.5 (C-3), 124.0 (C-α and C-10), 124.8 (C-3′), 125.5 (C-6), 126.0 (C-β), 126.3 (C-5′), 128.3 (C-4′), 128.6 (C-6′), 133.0 (C-1′), 133.2 (C-5), 133.8 (C-7), 147.9 (C-2), 153.4 (C-2′), 156.0 (C-9), 176.3 (C-4). Anal. Calcd for C₁₇H₁₁O₄N: C, 69.62; H, 3.78; N, 4.78. Found: C, 69.57; H, 3.79; N, 4.75.

16

Typical Experimental Procedure under Microwave Irradiation: A mixture of chromone-3-carboxaldehyde (1, 0.10 g, 5.74 × 10^-1 mmol), the appropriate phenylacetic acid 2a-g (0.39 g, 2.87 mmol) and tert-BuOK (0.10 g, 8.61 × 10^-1 mmol) in dry pyridine (15 mL) was irradiated in a 100 mL PFA sealed vessel of a high-pressure rotor segment in an Ethos SYNTH microwave (Milestone Inc.), at a maximum temperature of 180 °C for 1 h (800 W of power). After that period the contents were cooled to r.t. and poured over H₂O and ice. The mixture was acidified at pH 2 with a solution of HCl. The pale yellow precipitate was separated by filtration washed with H₂O and purified by thin layer chromatography with a 7:3 mixture of CH₂Cl₂-light petroleum ether as eluent. The obtained residue was crystallised from EtOH giving 3-styrylchromones 3a-g in good yields (3a, 86.2%; 3b, 79.9%; 3c, 90.9%; 3d, 56.0%; 3e, 90.3%; 3f, 94.1%; 3g, 80.2%).

17 Gribble GW. Kelly WJ. Tetrahedron Lett.  1985,  26:  3779