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Synlett 2003(10): 1415-1418
DOI: 10.1055/s-2003-40826
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

First Diels-Alder Reactions of 3-Styrylchromones under Microwave Irradiation

Diana C. G. A. Pintoa, Artur M. S. Silva*a, Lúcia M. P. M. Almeidaa, José R. Carrillob, Angel Díaz-Ortizb, António de la Hoz*b, José A. S. Cavaleiroa
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 Facultad de Químicas, Universidad de Castilla-La Mancha, 13071 - Ciudad Real, Spain
Fax: +34(926)295618; e-Mail: adlh@qino-cr.uclm.es;
Further Information

Publication History

Received 22 April 2003
Publication Date:
24 July 2003 (online)

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Abstract

Microwave irradiation in solvent-free conditions induces Diels-Alder cycloaddition reactions of 3-styrylchromones with N-methyl and N-phenylmaleimide giving 4-aryl-1,3-dioxopyrrolo[3,4-c]-3a,4,11a,11b-tetrahydroxanthones in good yields. This is the first example of [4+2] cycloaddition reactions of 3-styrylchromones.

Key words

Diels-Alder reactions - microwave irradiation - 3-styrylchromones - N-methyl - N-phenylmaleimide

    References

  • 1a Gerwick WH. Lopez A. Van Duyne GD. Clardy J. Ortiz W. Baez A. Tetrahedron Lett.  1986,  27:  1979 
    Google Scholar
  • 1b Gerwick WH. J. Nat. Prod.  1989,  22:  252 
    Google Scholar
  • 2a Price WA. Silva AMS. Cavaleiro JAS. Heterocycles  1993,  36:  2601 
    Google Scholar
  • 2b Pinto DCGA. Silva AMS. Cavaleiro JAS. New J. Chem.  2000,  24:  85 
    Google Scholar
  • 3a Doria G. Romeo C. Forgione A. Sberze P. Tibolla N. Corno ML. Cruzzola G. Cadelli G. Eur. J. Med. Chem.  1979,  14:  347 
    Google Scholar
  • 3b Brion JD, Le Baut G, Zammattio F, Pierre A, Atassi G, and Belachmi L. inventors; Eur. Pat. Appl. EP  454,587. 
  • 4a Pinto DCGA. Silva AMS. Cavaleiro JAS. Levai A. Patonay T. J. Heterocycl. Chem.  1998,  35:  217 
    Google Scholar
  • 4b Pinto DCGA. Silva AMS. Cavaleiro JAS. Foces-Foces C. Llamas-Sainz A. Jagerovic N. Elguero J. Tetrahedron  1999,  55:  10187 
    Google Scholar
  • 4c Pinto DCGA. Silva AMS. Cavaleiro JAS. J. Heterocycl. Chem.  2000,  37:  1629 
    Google Scholar
  • 5a Aziz G. J. Org. Chem.  1962,  27:  2954 
    Google Scholar
  • 5b Elkaschef MA.-F. Abdel-Megeid FME. Mokhtar K.-EM. Gad FA. Acta Chim. Hung.  1975,  84:  319 
    Google Scholar
  • 6a Lechter RM. Yue T.-Y. J. Chem. Res.  1992,  (S) 248, (M) 2078 
    CrossrefGoogle Scholar
  • 6b Lechter RM. Yue T.-Y. J. Chem. Soc., Chem. Commun.  1992,  1310 
    CrossrefGoogle Scholar
  • 6c Kelkar AS. Letcher RM. Cheung K.-K. Chiu K.-F. Brown GD. J. Chem. Soc., Perkin Trans. 1  2000,  3732 
    CrossrefGoogle Scholar
  • 7 Silva AMS. Silva AMG. Tomé AC. Cavaleiro JAS. Eur. J. Org. Chem.  1999,  135 
    CrossrefGoogle Scholar
  • 8a Davies SG. Mobbs BE. Goodwin CJ. J. Chem. Soc., Perkin Trans. 1  1987,  2597 
    Google Scholar
  • 8b Alonso R. Brossi A. Tetrahedron Lett.  1988,  29:  735 
    Google Scholar
  • 8c Sonawane SA. Chavan VP. Shingare MS. Karale BK. Indian J. Heterocycl. Chem.  2002,  12:  65 
    Google Scholar
  • 8d Karale BK. Chavan VP. Hangarge RV. Mane AS. Gill CH. Shingare MS. Indian J. Heterocycl. Chem.  2001,  10:  233 
    Google Scholar
  • 8e Silva AMS. Cavaleiro JAS. Elguero J. Liebigs Ann. Recl.  1997,  2065 
    Google Scholar
  • 8f

    Sandulache A.; Silva, A. M. S.; Pinto, D. C. G. A.; Almeida, L. M. P. M.; Cavaleiro, J. A. S. New J. Chem. submitted for publication.
  • 10 Microwaves in Organic Synthesis   Loupy A. Wiley; Weinheim: 2002. 
    Google Scholar
  • 11 De la Hoz A. Díaz-Ortiz A. Moreno A. Langa F. Eur. J. Org. Chem.  2000,  3659 
    CrossrefGoogle Scholar
  • 12 Lacova M. Gasparova R. Loos D. Liptay T. Pronayova N. Molecules  2000,  5:  167 
    CrossrefGoogle Scholar
9

Sandulache, A.; Silva, A. M. S.; Pinto, D. C. G. A.; Cavaleiro, J. A. S. unpublished results.

13

Typical Experimental Procedure: A mixture of N-methyl-maleimide and the appropriate 3-styrylchromone (1 or 5) (4:1 mole ratio) was irradiated at atmospheric pressure in a focused microwave reactor (Prolabo MX350) at 270 W for 30 min (final temperature 160 °C). The crude products were purified by flash chromatography on silica gel (Merck type 60, 230-400 mesh), using a 2:1 mixture of hexane:ethyl acetate.

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Typical Experimental Procedure: A mixture of the appropriate 3-styrylchromone (1 or 5) and N-phenylmaleimide (1:3 mole ratio) was irradiated at atmospheric pressure in a focused microwave reactor (Prolabo MX350) at 270 W for 30 min (final temperature 200 °C, except for 4′-ethoxy-2-styrylchromones 1c or 5c which was 160 °C). The crude products were purified by flash chromatography on silica gel (Merck type 60, 230-400 mesh); using a 4:1 mixture of hexane:EtOAc the endo cycloadducts were collected while the exo cycloadducts were eluted with a 2:1 mixture of hexane:EtOAc.

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Selected Physical Data: 4-(4-chlorophenyl)-2-methyl-1,3-dioxopyrrolo[3,4-c]-3a,4,11a,11b-tetrahydroxanthone 2b: 1H NMR (300.13 MHz, CDCl3): δ = 2.98 (s, 3 H, 2-CH 3), 3.43 (d broad, 1 H, J = 8.6 Hz, H-3a), 3.81 (t, 1 H, J = 8.6 Hz, H-11b), 4.60 (d broad, 1 H, J = 7.0 Hz, H-4), 5.33 (ddd, 1 H, J = 8.6, 3.0 and 0.9 Hz, H-11a), 7.02 (dd, 1 H, J = 8.0 and 0.8 Hz, H-10), 7.06 (ddd, 1 H, J = 7.9, 7.3 and 0.8 Hz, H-8), 7.14 (d, 2 H, J = 8.4 Hz, H-3′,5′), 7.31 (d, 2 H, J = 8.4 Hz, H-2′,6′), 7.34 (ddd, 1 H, J = 7.0, 3.0 and 0.6 Hz, H-5), 7.51 (ddd, 1 H, J = 8.0, 7.3 and 1.7 Hz, H-9), 7.91 (dd, 1 H, J = 7.9 and 1.7 Hz, H-7). 13C NMR (75.47 MHz, CDCl3): δ = 25.3 (2-CH3), 38.5 (C-4), 43.3 (C-11b), 44.7 (C-3a), 70.9 (C-11a), 118.1 (C-10), 120.3 (C-6a), 122.3 (C-8), 127.5 (C-7), 128.3 (C-2′,6′), 129.3 (C-3′,5′), 133.1 (C-5a), 133.5 (C-4′), 136.1 (C-5), 136.4 (C-1′), 136.5 (C-9), 160.1 (C-10a), 173.5 (C-1), 176.8 (C-3), 178.8 (C-6). EI-MS: m/z (rel. int.) = 393 (100) [M+ ], 307 (50), 281 (60), 268 (43), 247 (7), 215 (14), 197 (27), 188 (25), 152 (45), 136 (11), 121 (64), 92 (20), 77 (11), 63 (14).

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Selected Physical Data: 2,4-diphenyl-1,3-dioxo-pyrrolo[3,4-c]-3a,4,11a,11b-tetrahydroxanthone 3a: 1H NMR (300.13 MHz, CDCl3): δ = 3.61 (ddd, 1 H, J = 8.5, 1.2 and 0.8 Hz, H-3a), 3.93 (t, 1 H, J = 8.5 Hz, H-11b), 4.73 (d broad, 1 H, J = 6.7 Hz, H-4), 5.43 (ddd, 1 H, J = 8.5, 2.5 and 1.2 Hz, H-11a), 7.04 (dd, 1 H, J = 7.8 and 1.0 Hz, H-10), 7.10 (ddd, 1 H, J = 7.7, 7.5 and 1.0 Hz, H-8), 7.20-7.29 (m, 4 H, H-2′,6′,2′′,6′′), 7.31-7.48 (m, 7 H, H-5,3′,4′,5′,3′′,4′′,5′′), 7.52 (ddd, 1 H, J = 7.8, 7.5 and 1.8 Hz, H-9), 7.99 (dd, 1 H, J = 7.7 and 1.8 Hz, H-7). 13C NMR (75.47 MHz, CDCl3): δ = 38.5 (C-4), 43.2 (C-11b), 45.5 (C-3a), 70.7 (C-11a), 118.2 (C-10), 121.1 (C-6a), 122.6 (C-8), 126.3 (C-2′′,6′′), 127.3 (C-2′,6′), 127.8 e/ou 127.9 (C-7,4′), 128.8 (C-4′′), 129.3 (C-3′,5′), 129.4 (C-3′′,5′′), 131.7 (C-1′′), 132.7 (C-5a), 136.5 (C-9), 137.1 (C-5), 138.5 (C-1′), 160.3 (C-10a), 172.8 (C-1), 175.7 (C-3), 180.1 (C-6). EI-MS: m/z (rel. int.) = 421 (68) [M+ ], 330 (14), 301 (9), 273 (100), 247 (36), 215 (13), 197 (55), 183 (22), 171 (25), 152 (75), 139 (16), 131 (32), 121 (77), 110 (32), 103 (21), 91 (65), 77 (72), 64 (43).

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Selected Physical Data: 2,4-diphenyl-1,3-dioxo-pyrrolo[3,4-c]-3a,4,11a,11b-tetrahydroxanthone 4a: 1H NMR (300.13 MHz, CDCl3): δ = 3.53 (dt, 1 H, J = 3.1 and 2.3 Hz, H-4), 3.58 (dd, 1 H, J = 8.5 and 3.1 Hz, H-11b), 4.42 (ddd, 1 H, J = 8.5, 3.1 and 2.3 Hz, H-3a), 5.28 (dt, 1 H, J = 3.1 and 1.3 Hz, H-11a), 5.81 (dt, 1 H, J = 2.3 and 1.3 Hz, H-5), 6.87 (dd, 1 H, J = 8.4 and 0.9 Hz, H-10), 7.10 (ddd, 1 H, J = 7.7, 7.5 and 0.9 Hz, H-8), 7.31-7.43 (m, 8 H, H-2′,3′,4′,5′,6′,2′′,4′′,6′′), 7.47-7.54 (m, 3 H, H-9,3′′,5′′), 7.96 (dd, 1 H, J = 7.7 and 1.7 Hz, H-7). 13C NMR (75.47 MHz, CDCl3): δ = 40.1 (C-3a), 44.3 (C-11b), 47.9 (C-4), 73.0 (C-11a), 118.1 (C-10), 119.5 (C-5), 119.9 (C-6a), 122.6 (C-8), 126.4 (C-2′,4′,6′), 127.6 (C-7), 128.4 (C-2′′,6′′), 128.3 (C-3′,5′), 128.7 (C-4′′), 129.2 (C-3′′,5′′), 131.8 (C-1′′), 135.5 (C-5a), 136.8 (C-9), 138.8 (C-1′), 159.5 (C-10a), 173.2 (C-1), 174.3 (C-3), 190.7 (C-6). EI-MS: m/z (rel. int.) = 421 (6) [M+ ], 301 (17), 273 (4), 154 (100), 120 (20), 92 (23), 77 (6), 64 (6).