Synlett 2013; 24(19): 2559-2562
DOI: 10.1055/s-0033-1339895
letter
© Georg Thieme Verlag Stuttgart · New York

Hydroxylated Polyfunctionalized Benzo[c]coumarins by an Organocatalyzed Tandem 1,4-Conjugate Addition, Decarboxylation and Aromatization Reaction

Oualid Talhi
a  Department of Chemistry & QOPNA, University of Aveiro, 3810-193 Aveiro, Portugal   Fax: +351(234)370084   Email: artur.silva@ua.pt
,
Malika Makhloufi-Chebli
b  Département de Chimie, UMMTO, Faculté des Sciences, 15000 Tizi ouzou, Algeria
,
Diana C. G. A. Pinto
a  Department of Chemistry & QOPNA, University of Aveiro, 3810-193 Aveiro, Portugal   Fax: +351(234)370084   Email: artur.silva@ua.pt
,
Maamar Hamdi*
c  Département de Chimie, USTHB, BP32 El alia, Bab ezzouar, 16111 Alger, Algeria   Fax: +213(21)247311   Email: prhamdi@gmail.com
,
Artur M. S. Silva*
a  Department of Chemistry & QOPNA, University of Aveiro, 3810-193 Aveiro, Portugal   Fax: +351(234)370084   Email: artur.silva@ua.pt
› Author Affiliations
Further Information

Publication History

Received: 23 July 2013

Accepted after revision: 05 September 2013

Publication Date:
24 October 2013 (online)


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

 
  • References

  • 1 Murray DH, Méndez J, Brown SA. The Natural Coumarins: Occurrence, Chemistry and Biochemistry . Wiley; Chichester: 1982
    • 3a Kostova I. Mini-Rev. Med. Chem. 2006; 6: 365
    • 3b Lin HC, Tsai SH, Chen CS, Chang YC, Lee CM, Lai ZY, Lin CM. Biochem. Pharmacol. 2008; 75: 1416
    • 3c Yuce B, Danis O, Ogan A, Sener G, Bulut M, Yarat A. Arzneim. Forsch. 2009; 59: 129
  • 4 Kontogiorgis C, Hadjipavlou-Litina D. J. Med. Chem. 2005; 48: 6400
    • 5a Harvey RG, Cortez C, Ananthanarayan TP, Schmolka SJ. J. Org. Chem. 1988; 53: 3936
    • 5b Wang C.-J, Hsieh Y.-J, Chu C.-Y, Lin Y.-L, Tseng T.-H. Cancer Lett. 2002; 183: 163
    • 5c Musa MA, Cooperwood JS, Khan MO. Curr. Med. Chem. 2008; 15: 2664
  • 6 Schönberg A, Latif N. J. Am. Chem. Soc. 1954; 76: 6208
    • 7a Sashidhara K, Rosaiah JN, Kumar A, Bhatia G, Khanna AK. Bioorg. Med. Chem. Lett. 2010; 20: 3065
    • 7b Sun W, Cama LD, Birzin ET, Warrier S, Locco L, Mosley R, Hammond ML, Rohrer SP. Bioorg. Med. Chem. Lett. 2006; 16: 1468
    • 7c Cudaj J, Podlech J. Tetrahedron Lett. 2010; 51: 3092
    • 7d Lubbe M, Appel B, Flemming A, Fischer C, Langer P. Tetrahedron 2006; 62: 11755
    • 8a Rodríguez-Domínguez JC, Kirsch G. Synthesis 2006; 1895
    • 8b Rajitha B, Kumar VN, Someshwar P, Madhav JV, Reddy PN, Reddy YT. ARKIVOK 2006; (xii): 23
    • 8c Karami B, Kiani M. Catal. Commun. 2011; 14: 62
    • 8d Daru J, Stirling A. J. Org. Chem. 2011; 76: 8749
    • 8e Iaroshenko VO, Savych I, Villinger A, Sosnovskikh VY, Langer P. Org. Biomol. Chem. 2012; 10: 9344
    • 9a Boutemeur-Kheddis B, Hamdi M, Sellier N, Silva AM. S. J. Heterocycl. Chem. 2000; 38: 227
    • 9b Hamdi M, Cottet S, Tedeschi C, Spéziale V. J. Heterocycl. Chem. 1997; 34: 1821
    • 9c Elligsen G, Vercruysse K, Spéziale V, Hamdi M, Fery-Forgues S. Acta Chem. Scand. 1997; 51: 521
    • 9d Boutemeur-Kheddis B, Bendaas A, Hamdi M, Sakellariou R, Spéziale V. Org. Prep. Proced. Int. 1994; 26: 360
    • 9e Hamdi M, Spéziale V, Jaud J. Z. Kristallogr. 1994; 209: 495
    • 9f Makhloufi-Chebli M, Hamdi SM, Hamdi M, Rabahi A, Silva AM. S. J. Mol. Liq. 2013; 181: 89
  • 10 Makhloufi-Chebli M, Hamdi M, Silva AM. S, Balegroune F. J. Soc. Alger. Chim. 2008; 18: 91
  • 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 1ad (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.
  • 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.