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Synlett 2013; 24(19): 2559-2562
DOI: 10.1055/s-0033-1339895
DOI: 10.1055/s-0033-1339895
letter
Hydroxylated Polyfunctionalized Benzo[c]coumarins by an Organocatalyzed Tandem 1,4-Conjugate Addition, Decarboxylation and Aromatization Reaction
Further Information
Publication History
Received: 23 July 2013
Accepted after revision: 05 September 2013
Publication Date:
24 October 2013 (online)
![](https://www.thieme-connect.de/media/synlett/201319/lookinside/thumbnails/10.1055-s-0033-1339895-1.jpg)
Abstract
Novel hydroxylated polyfunctionalized benzo[c]coumarins were synthesized by a new one-pot reaction of an unprotected monohydroxy-3-(acetoacetyl)coumarin as an active methylene Michael donor with 4-oxo-4H-chromene-3-carboxylic acid as a Michael acceptor in the presence of a catalytic amount of 4-pyrrolidin-1-ylpyridine. An organobase-catalyzed tandem 1,4-conjugate addition, decarboxylation and aromatization reaction mechanism is proposed.
Supporting Information
- for this article is available online at http://www.thieme-connect.com/ejournals/toc/synlett.
- Supporting Information
-
References
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- 11 8-Acetyl-7-hydroxy-10-(2-hydroxybenzoyl)-6H-benzo[c]chromen-6-ones (3a–d) Carboxylic acid 2 (1.0 g, 5.26 mmol) was added to a soln of the appropriate 3-(acetoacetyl)coumarin 1a–d (5.26 mmol) in CHCl3 (20 mL). A catalytic amount of 4-PPy (0.26 mmol, 0.04 g) was added dropwise, and the mixture was refluxed with stirring for 24 h. Incomplete consumption of the starting materials was observed (TLC), even after an extended reaction time. The solvent was evaporated and the resulting gummy solid was directly purified by column chromatography [silica gel, PE–CH2Cl2 (gradient 3:1 to 2:1 to 1:1 to 0:1)]. Pure fractions were combined and precipitated in PE.
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12
8-Acetyl-7-hydroxy-10-(2-hydroxybenzoyl)-6H-benzo[c]chromen-6-one (3a)
White powder; yield: 1.371 g (70%); mp 197–198 °C. 1H NMR (300.13 MHz, CDCl3): δ = 2.79 (s, 3 H, H-2′), 6.79 (ddd, J = 8.2, 7.2, 1.1 Hz, 1 H, H-5′′′), 7.20–7.10 (m, 2 H, H-2 and H-3′′′), 7.28 (dd, J = 8.2, 1.4 Hz, 1 H, H-6′′′), 7.42 (dd, J = 8.3, 1.1 Hz, 1 H, H-4), 7.58–7.49 (m, 2 H, H-3 and H-4′′′), 7.65 (dd, J = 8.3, 1.3 Hz, 1 H, H-1), 8.19 (s, 1 H, H-9), 11.99 (s, 1 H, 2′′′-OH), 13.24 (s, 1 H, 7-OH). 13C NMR (75.47 MHz, CDCl3): δ = 31.9 (C-2′), 108.0 (C-6a), 116.2 (C-10b), 118.0 (C-4), 118.8 (C-3′′′), 119.3 (C-1′′′), 119.6 (C-5′′′), 124.2 (C-8), 125.4 (C-2), 125.7 (C-10), 127.5 (C-1), 132.4 (C-3), 132.8 (C-6′′′), 137.7 (C-10a), 137.9 (C-4′′′), 138.3 (C-9), 151.0 (C-4a), 163.6 (C-2′′′), 163.8 (C-7), 165.3 (C-6), 196.2 (C-1′), 202.3 (C-1′′). HRMS (ESI+): m/z calcd for [C22H14O6 + Na]+: 397.0688; found: 397.0688. - 13 8-Acetyl-3,7-dihydroxy-10-(2-hydroxybenzoyl)-6H-benzo[c]chromen-6-one (3b) White-yellowish powder; yield: 0.920 g (45%); mp 279–280 °C. 1H NMR [300.13 MHz, DMSO-d 6–CDCl3 (1:2)]: δ = 2.72 (s, 3 H, H-2′), 6.64 (dd, J = 9.0, 2.5 Hz, 1 H, H-2), 6.76–6.85 (m, 2 H, H-4 and H-5′′′), 7.07 (dd, J = 8.5, 1.0 Hz, 1 H, H-3′′′), 7.32 (dd, J = 8.0, 1.7 Hz, 1 H, H-6′′′), 7.39 (d, J = 9.0 Hz, 1 H, H-1), 7.55 (ddd, J = 8.5, 7.2, 1.7 Hz, 1 H, H-4′′′), 8.05 (s, 1 H, H-9), 10.34 (s, 1 H, 3-OH), 11.98 (s, 1 H, 2′′′-OH), 13.30 (s, 1 H, 7-OH). 13C NMR [75.47 MHz, DMSO-d 6–CDCl3 (1:2)]: δ = 31.2 (C-2′), 103.1 (C-4), 106.0 (C-6a), 107.3 (C-10b), 113.8 (C-2), 117.9 (C-3′′′), 119.1 (C-5′′′), 119.5 (C-1′′′), 121.7 (C-8), 124.6 (C-10), 128.3 (C-1), 132.4 (C-6′′′), 137.0 and 137.3 (C-4′′′ and C-9), 138.1 (C-10a), 152.3 (C-4a), 161.3 (C-3), 162.2 (C-2′′′), 163.3 (C-7), 164.8 (C-6), 195.4 (C-1′), 201.4 (C-1′′). HRMS (ESI+): m/z calcd for [C22H14O7 + Na]+: 413.0637; found: 413.0622.
- 14 8-Acetyl-4,7-dihydroxy-10-(2-hydroxybenzoyl)-6H-benzo[c]chromen-6-one (3c) White-yellowish powder; yield: 1.091 g (53%); mp 272–273 °C. 1H NMR [300.13 MHz, DMSO-d 6–CDCl3 (1:2)]: δ = 2.74 (s, 3 H, H-2′), 6.80 (ddd, J = 8.1, 7.3, 1.1 Hz, 1 H, H-5′′′), 6.93–7.12 (m, 4 H, H-1, H-2, H-3 and H-3′′′), 7.32 (dd, J = 8.1, 1.7 Hz, 1 H, H-6′′′), 7.54 (ddd, J = 8.7, 7.3, 1.7 Hz, 1 H, H-4′′′), 8.07 (s, 1 H, H-9), 10.28 (s, 1 H, 4-OH), 11.68 (s, 1 H, 2′′′-OH), 13.33 (s, 1 H, 7-OH). 13C NMR [75.47 MHz, DMSO-d 6–CDCl3 (1:2)]: δ = 31.3 (C-2′), 107.7 (C-6a), 116.7 (C-10b), 116.9 (C-1), 117.9 (C-3′′′), 118.3 (C-3), 119.2 (C-5′′′), 119.6 (C-1′′′), 123.3 (C-8), 124.5 (C-2), 126.1 (C-10), 132.5 (C-6′′′), 137.0 (C-4′′′), 137.6 (C-9), 139.5 (C-10a), 145.64 (C-4 and C-4a), 162.0 (C-2′′′), 162.9 (C-7), 164.5 (C-6), 195.5 (C-1′), 201.1 (C-1′′). HRMS (ESI+): m/z calcd for [C22H14O7 + Na]+: 413.0637; found: 413.0617.
- 15 8-Acetyl-2,7-dihydroxy-10-(2-hydroxybenzoyl)-6H-benzo[c]chromen-6-one (3d) White-yellowish powder; yield: 0.474 g (23%); mp 134–135 °C. 1H NMR [300.13 MHz, DMSO-d 6–CDCl3 (1:2)]: δ = 2.72 (s, 3 H, H-2′), 6.84 (t, J = 7.8 Hz, 1 H, H-5′′′), 7.02 (dd, J = 8.9, 2.7 Hz, 1 H, H-3), 7.06–7.10 (m, 2 H, H-1 and H-3′′′), 7.30 (d, J = 8.9 Hz, 1 H, H-4), 7.36 (d, J = 7.8 Hz, 1 H, H-6′′′), 7.53–7.61 (m, 1 H, H-4′′′), 8.04 (s, 1 H, H-9), 9.78 (s, 1 H, 2-OH), 11.70 (s, 1 H, 2′′′-OH), 13.33 (s, 1 H, 7-OH). 13C NMR [75.47 MHz, DMSO-d 6–CDCl3 (1:2)]: δ = 31.3 (C-2′), 107.7 (C-6a), 112.0 (C-1), 116.3 (C-10b), 117.9 (C-3′′′), 118.3 (C-4), 119.1 (C-5′′′), 120.0 (C-1′′′), 120.3 (C-3), 123.3 (C-8), 126.2 (C-10), 132.6 (C-6′′′), 136.9 and 137.0 (C-4′′′ and C-9), 137.1 (C-10a), 143.6 (C-4a), 154.1 (C-2), 162.1 (C-2′′′), 162.9 (C-7), 165.0 (C-6), 195.4 (C-1′), 200.6 (C-1′′). HRMS (ESI+): m/z calcd for [C22H14O7 + Na]+: 413.0637; found: 413.0627.