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

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.

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

References

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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.

9

Sandulache, A.; Silva, A. M. S.; Pinto, D. C. G. A.; Cavaleiro, J. A. S. unpublished results.

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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).