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Synlett 2022; 33(13): 1251-1254
DOI: 10.1055/s-0041-1738382
letter

Facile Synthesis of Benzo[c]chromen-6-ones via Base-Promoted Reaction of 4-Chloro-3-formylcoumarin and α,α-Dicyanoolefins

Abdolali Alizadeh∗
,
Behnaz Farajpour
We gratefully thank Tarbiat Modares University for financial support.
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Abstract

Herein, a chemoselective protocol for the facile and efficient synthesis of substituted benzo[c]chromen-6-ones is presented. The reaction took place under green and mild conditions with group-assisted purification (GAP) by using inexpensive and readily available precursors.

Key words

4-chloro-3-formylcoumarin - α,α-dicyanoolefins - benzo[c]chromen-6-ones - chemoselective reactions - group-assisted purification

Supporting Information



Publication History

Received: 02 February 2022

Accepted after revision: 08 May 2022

Article published online:
12 July 2022

© 2022. Thieme. All rights reserved

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  • 14 Benzo[c]chromen-6-ones 3a–3f; General Procedure Et3N (1 mmol) was added to a mixture of 4-chloro-3-formylcoumarin (1) (1 mmol), and α,α-dicyanoolefin 2 (1 mmol) in EtOH (2 mL). The reaction mixture was magnetically stirred at 80 °C for 6 h (monitored by TLC). The target product 3 was isolated by filtration and washed with EtOH (96%). 6-Oxo-9-phenyl-6H-benzo[c]chromene-8-carbonitrile (3a) White powder; mp = 222–225 °C; 0.21 g; yield: 72%. IR (KBr): 2221 (CN), 1733 (C=O), 1596, 1572, and 1536 (Ar), 1128, 1102, and 1007 (C–O). Anal. Calcd. for C20H11NO2 (297.31): C, 80.80; H, 3.73; N, 4.71. Found: C, 80.82; H, 3.71; N, 4.73. 1H NMR (300 MHz, CDCl3): δ = 7.41 (1 H, td, 3 J HH = 7.8 Hz, 4 J HH = 1.2 Hz, CH2 of coumarin), 7.43 (1 H, dd, 3 J HH = 8.4 Hz, 4 J HH = 1.0 Hz, CH4 of coumarin), 7.55–7.69 (5 H, m, 5 CH of Ph), 7.66 (1 H, t, 3 J HH = 8.0 Hz, 4 J HH = 2.5 Hz, CH3 of coumarin), 8.11 (1 H, d, 3 J HH = 7.9 Hz, CH1 of coumarin), 8.22 (1 H, s, CH10), 8.80 (1 H, s, CH7). MS (EI, 70 eV): m/z (%) = 297 (M+, 100), 269 (23), 240 (34), 213 (15). The solubility of this product was too low for us to record a 13C NMR spectrum. 9-(4-Bromophenyl)-6-oxo-6H-benzo[c]chromene-8-carbonitrile (3b) White powder; mp = 294–297 °C; 0.30 g; yield: 82%. IR (KBr): 2219 (CN), 1736 (C=O), 1595, 1574, 1550, and 1429 (Ar), 1130, 1099, 1074, and 1002 (C–O). Anal. Calcd. for C20H10BrNO2 (376.20): C, 63.85; H, 2.68; N, 3.72. Found: C, 63.84; H, 2.70; N, 3.69. 1H NMR (300 MHz, DMSO-d 6): δ = 7.43 (1 H, t, 3 J HH = 8.3 Hz, CH2 of coumarin), 7.45 (1 H, d, 3 J HH = 8.6 Hz, CH4 of coumarin), 7.66 (1 H, t, 3 J HH = 7.9 Hz, CH3 of coumarin), 7.70 (2 H, d, 3 J HH = 8.5 Hz, 2 CH of Ar), 7.82 (2 H, d, 3 J HH = 8.4 Hz, 2 CH of Ar), 8.54 (1 H, dd, 3 J HH = 8.2 Hz, 4 J HH = 1.1 Hz, CH1 of coumarin), 8.63 (1 H, s, CH10), 8.66 (1 H, s, CH7). 13C NMR (75 MHz, DMSO-d 6): δ = 110.73 (C8), 116.65 (CN), 117.32 (C6a), 117.47 (CH4 of coumarin), 120.49 (C ipso –Br), 123.50 (C10), 124.34 (CH2 of coumarin), 125.05 (C10b), 125.12 (CH1 of coumarin), 131.23 (2CH of Ar), 131.77 (2 CH of Ar), 132.61 (CH3 of coumarin), 135.83 (CH7 and C of Ar), 138.13 (C10b), 148.30 (C9), 151.69 (C4a), 158.74 (CO2). MS (EI, 70 eV): m/z (%) = 377 (M+, 100), 349 (14), 296 (28), 267 (25), 240 (61), 213 (29). Crystal data for 3b (C20H10BrNO2; CCDC 2092628): M W = 376.20, monoclinic, P 1 21/c 1, a = 7.8474(16) Å, b = 14.652(3) Å, c = 13.751(3) Å, α = 90, β = 103.77(3), γ = 90, V = 1535.6(6)Å3, Z = 4, D calc = 1.627 mg/m3, F (000) = 752, crystal dimension 0.30 × 0.10 × 0.10 mm, Mo Kα radiation (λ = 0.71073 Å), 2.063 ≤ 2θ ≤ 24.997, intensity data were collected at 290.0 K with a Bruker APEX area-detector diffractometer by employing the ω/2θ scanning technique, in the range of –9 ≤ h ≤ 9, –17 ≤ k ≤ 17, –15 ≤ l ≤ 16; the structure was solved by a direct method, all non-hydrogen atoms were positioned and anisotropic thermal parameters were refined from 2567 observed reflections with R (into) = 0.0992 by a full-matrix least-squares technique converged to R1 = 0.0388, and wR2 = 0.1013 [I > 2σ(I)]. 9-(2-Chlorophenyl)-6-oxo-6H-benzo[c]chromene-8-carbonitrile (3c) White powder; mp = 260–261 °C; 0.25 g; yield: 76%. IR (KBr): 2223 (CN), 1736 (C=O), 1594, 1559, 1483, and 1400 (Ar), 1134, 1104, and 1016 (C–O). Anal. Calcd. for C20H10ClNO2 (331.75): C, 72.41; H, 3.04; N, 4.22. Found: C, 72.43; H, 3.05; N, 4.20. 1H NMR (300 MHz, DMSO-d 6): δ = 7.41 (1 H, t, 3 J HH = 7.7 Hz, CH2 of coumarin), 7.47 (1 H, d, 3 J HH = 8.3 Hz, CH4 of coumarin), 7.55–7.62 (3 H, m, 3 CH of Ar), 7.66 (1 H, t, 3 J HH = 7.3 Hz, CH3 of coumarin), 7.72 (1 H, dd, 3 J HH = 6.5 Hz, 3 J HH = 1.1 Hz, CH of Ar), 8.53 (1 H, d, 3 J HH = 8.0 Hz, CH1 of coumarin), 8.66 (1 H, s, CH10), 8.74 (1 H, s, CH7). 13C NMR (75 MHz, DMSO-d 6): δ = 112.49 (C8), 116.54 (CN), 117.42 (C6a), 120.93 (CH4 of coumarin), 125.05 (CH2 of coumarin), 127.71 (C10), 129.50 (C10b), 129.77 (CH1 of coumarin), 131.22 (CH of Ar), 131.44 (CH of Ar), 132.68 (CH3 of coumarin), 132.49 (CH7), 132.68 (C of Ar), 134.72 (CH of Ar), 134.79 (C ipso –Cl), 138.06 (C10b), 147.35 (C9), 151.67 (C4a), 158.66 (CO2). MS (EI, 70 eV): m/z (%) = 331 (M+, 100), 303 (47), 267 (51), 239 (82), 212 (35). 9-(4-Chlorophenyl)-6-oxo-6H-benzo[c]chromene-8-carbonitrile (3d) White powder; mp = 285–289 °C; 0.26 g; yield: 79%. IR (KBr): 2220 (CN), 1736 (C=O), 1594, 1574, 1472, and 1429 (Ar), 1122, 1094, and 1004 (C–O). Anal. Calcd. for C20H10ClNO2 (331.75): C, 72.41; H, 3.04; N, 4.22. Found: C, 72.39; H, 3.02; N, 4.21. 1H NMR (300 MHz, DMSO-d 6): δ = 7.44 (1 H, t, 3 J HH = 7.8 Hz, CH2 of coumarin), 7.45 (1 H, d, 3 J HH = 8.7 Hz, CH4 of coumarin), 7.67 (1 H, t, 3 J HH = 8.9 Hz, CH3 of coumarin), 7.69 (2 H, d, 3 J HH = 8.0 Hz, 2 CH of Ar), 7.78 (2 H, d, 3 J HH = 7.8 Hz, 2 CH of Ar), 8.56 (1 H, d, 3 J HH = 7.2 Hz, CH1 of coumarin), 8.64 (1 H, s, CH10), 8.67 (1 H, s, CH7). MS (EI, 70 eV): m/z (%) = 332 (M+, 100), 303 (59), 267 (27), 240 (72), 213 (19). The solubility of this product was too low for us to record a 13C NMR spectrum. 9-(3,4-Dimethoxyphenyl)-6-oxo-6H-benzo[c]chromene-8-carbonitrile (3e) White powder; mp = 245–248 °C; 0.27 g; yield: 77%. IR (KBr): 2217 (CN), 1735 (C=O), 1596, 1522, 1473, and 1430 (Ar), 1146, 1104, and 1024 (C–O). Anal. Calcd. for C22H15NO4 (357.36): C, 73.94; H, 4.23; N, 3.92. Found: C, 73.95; H, 4.21; N, 3.93. 1H NMR (300 MHz, DMSO-d 6): δ = 3.86 (3 H, s, OCH3), 3.88 (3 H, s, OCH3), 7.18 (1 H, d, 3 J HH = 8.3 Hz, CH of Ar), 7.34 (1 H, d, 3 J HH = 8.3 Hz, CH of Ar), 7.37 (1 H, s, CH of Ar), 7.45 (1 H, t, 3 J HH = 7.7 Hz, CH2 of coumarin), 7.47 (1 H, d, 3 J HH = 8.3 Hz, CH4 of coumarin), 7.67 (1 H, t, 3 J HH = 8.8 Hz, CH3 of coumarin), 8.60 (1 H, d, 3 J HH = 8.7 Hz, CH1 of coumarin), 8.62 (1 H, s, CH10), 8.66 (1 H, s, CH7). 13C NMR (75 MHz, DMSO-d 6): δ = 55.72 (OCH3), 55.94 (OCH3), 110.62 (C8), 111.66 (CH of Ar), 112.67 (CH of Ar), 112.71 (CH of Ar), 116.67 (CN), 117.42 (C6a), 117.77 (CH4 of coumarin), 119.62 (C10), 121.86 (CH2 of coumarin), 123.86 (C10b), 125.01 (CH1 of coumarin), 128.82 (CH3 of coumarin), 132.57 (C of Ar), 135.91 (CH7), 137.84 (C10b), 148.66 (C9), 150.07 (C ipso –OCH3), 150.07 (C ipso –OCH3), 151.60 (C4a), 158.79 (CO2). MS (EI, 70 eV): m/z (%) = 357 (M+, 2), 331 (12), 191 (30), 103 (66), 76 (100), 50 (100). 9-(4-Methylphenyl)-6-oxo-6H-chromene-8-carbonitrile (3f) White powder; mp = 262–264 °C; 0.22 g; yield: 73%. IR (KBr): 2224 (CN), 1733 (C=O), 1664, 1593, 1572, and 1427 (Ar), 1162, 1120, and 1102 (C–O). Anal. Calcd. for C21H13NO2 (311.33): C, 81.01; H, 4.21; N, 4.50. Found: C, 81.02; H, 4.23; N, 4.47. 1H NMR (300 MHz, CDCl3): δ = 2.47 (3 H, s, CH3), 7.38 (2 H, d, 3 J HH = 8.2 Hz, 2 CH of Ar), 7.39 (1 H, t, CH2 of coumarin), 7.40 (1 H, dd, 3 J HH = 8.2 Hz, 4 J HH = 1.5 Hz, CH4 of coumarin), 7.58 (2 H, d, 3 J HH = 8.2 Hz, 2 CH of Ar), 7.59 (1 H, td, 3 J HH = 8.6 Hz, 4 J HH = 1.6 Hz, CH3 of coumarin), 8.09 (1 H, dd, 3 J HH = 8.2 Hz, 4 J HH = 1.4 Hz, CH1 of coumarin), 8.19 (1 H, s, CH10), 8.73 (1 H, s, CH7). MS (EI, 70 eV): m/z (%) = 311 (M+, 100), 283 (34), 255 (26), 226 (22), 113 (21), 83 (24). The solubility of this product was too low for us to record a 13C NMR spectrum.