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Synlett 2004(15): 2717-2720  
DOI: 10.1055/s-2004-835660
LETTER
© Georg Thieme Verlag Stuttgart · New York

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

Vera L. M. Silvaa, Artur M. S. Silva*a, Diana C. G. A. Pintoa, José A. S. Cavaleiroa, Tamás Patonayb
a Department of Chemistry, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal
Fax: +351(234)370084; e-Mail: arturs@dq.ua.pt;
b Department of Organic Chemistry, University of Debrecen, P. O. Box 20, 4010 Debrecen, Hungary
Fax: +36(52)453836; e-Mail: tpatonay@puma.unideb.hu;
Further Information

Publication History

Received 20 September 2004
Publication Date:
10 November 2004 (online)

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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.

Key words

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

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

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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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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] ).

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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.

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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%).