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DOI: 10.1055/s-2004-835655
3-Nitrochromene Derivatives as 2π Components in 1,3-Dipolar Cycloadditions of Azomethine Ylides
Publikationsverlauf
Publikationsdatum:
08. November 2004 (online)
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Abstract
The 1,3-dipolar cycloaddition of 2-aryl-3-nitrochromenes with various azomethine ylides has been investigated. The structure and stereochemistry of cycloadducts were studied in detail by NMR spectroscopic methods.
Key words
azomethine ylids - chromenes - cycloadditions - pyrroles
- 1
Synthetic Applications of 1,3-Dipolar Cycloaddition Chemistry Toward Heterocycles and Natural Products
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References
General Procedure: A mixture of sarcosine (2.5 equiv) or N-benzyl-glycine (2.5 equiv), paraformaldehyde (6 equiv), and the corresponding 3-nitrochromene derivatives (3a-e, 1 equiv) was heated under reflux in toluene (10 mL for 1 mmol of dipolarophile). The water formed was removed by the aid of a Dean-Stark trap. After completion of the reaction (judged by TLC) the reaction mixture was filtered through a pad of Celite and the solvent was evaporated in vacuo. The residue crystallized from Et2O to give 4a-j. The reaction times and yields (based on the dipolarophiles) are summarized in Table
[1]
. All new compounds afforded correct elemental analyses and spectroscopic data, for example:
2-Methyl-3a-nitro-4-phenyl-benzopirano[3,4-
c
]-pyrrolidine (
4a): 1H NMR (250 MHz, CDCl3): δ = 7.44 (5 H, m, Ph-H), 7.23 (2 H, m, Ar-H), 7.04 (2 H, m, Ar-H), 5.01 (1 H, s, H-4), 4.03 (1 H, t, J = 8.5 Hz, H-9b), 3.62 (1 H, d, J = 11.4 Hz, H-3), 3.50 (1 H, t, J = 8.5 Hz, H-1), 2.85 (1 H, d, J = 11.4 Hz, H-3), 2.71 (1 H, t, J = 8.5 Hz, H-1), 2.41 (3 H, s, NMe). 13C NMR (62.5 MHz, CDCl3): δ = 154.0 (q, C-5a), 134.0 (Ph-1′C), 129.4 (CH, C-7), 128.5 (2 × CH, Ph-2′ and 6′C), 128.3 (CH, C-9), 127.8 (CH, Ph-4′C), 126.8 (2 × CH, Ph-3′ and 5′C), 122.6 (q, C-9a), 122.5 (CH, C-8), 117.6 (CH, C-6), 95.9 (q, C-3a), 80.1 (CH, C-4), 62.8 (CH2), 61.8 (CH2), 43.3 (CH, H-9b), 41.3 (NCH3). IR (KBr): 2976, 2947, 2823, 1535, 1489, 1479, 1452, 1371, 1254, 1238, 1149, 1045, 1024 cm-1.
2-Benzyl-4-(4-chlorophenyl)-3a-nitro-benzopirano[3,4-
c
]-pyrrolidine (
4f): 1H NMR (250 MHz, CDCl3): δ = 7.37-7.23 (8 H, m, Ar-H), 7.21 (1 H, t, J = 7.5 Hz, H-7), 7.16 (2 H, d, J = 8.5 Hz, Ar4-3′ and 5′H), 7.02 (1 H, t, J = 7.5 Hz, H-8), 7.00 (1 H, d, J = 7.5 Hz, H-6), 5.03 (1 H, s, H-4), 3.97 (1 H, t, J = 8.4 Hz, H-9b), 3.71 (1 H, d, J = 12.9 Hz, CH2Ph), 3.57 (1 H, d, J = 12.9 Hz, CH2Ph), 3.46 (1 H, t, J = 8.4 Hz, H-1), 3.41 (1 H, d, J = 11.4 Hz, H-3), 2.87 (1 H, d, J = 11.4 Hz, H-3), 2.86 (1 H, t, J = 8.4 Hz, H-1). 13C NMR (62.5 MHz, CDCl3): δ = 154.0 (q, C-5a), 137.6 (Bn-1′C), 135.5 (q, Ar4-4′C), 132.8 (q, Ar4-1′C), 128.9 (2 × CH), 128.8 (2 × CH), 128.7 (2 × CH), 128.4 (2 × CH), 128.1 (CH, C-9), 127.8 (Bn-4′C), 123.1 (CH, C-8), 122.9 (q, C-9a), 117.8 (CH, C-6), 94.9 (q, C-3a), 79.6 (CH, C-4), 60.7 (CH2), 59.2 (CH2), 59.1 (CH2), 42.6 (CH, H-9b). IR (KBr): 3061, 3025, 2968, 2920, 2824, 1537, 1490, 1455, 1380, 1260, 1233, 1210, 1153, 1092, 1057, 1014 cm-1.
General Procedure: The corresponding 3-nitrochromene derivatives (3a-e, 10 mmol) were dissolved in dry toluene (50 mL) and ethyl (4-chlorobenzylideneamino)acetate (2.47 g, 11 mmol) or methyl 2-(4-chlorobenzylideneamino)-3-phenyl-propionate (3.32 g, 11 mmol), silver acetate (2.50 g, 15 mmol), and Et3N (1.11 g, 1.6 mL, 11 mmol) was added. The reaction mixture was stirred at r.t. for 12 h. After the completion of the reaction (judged by TLC) aq NH4Cl solution (25 mL) was added to the reaction mixture and this was washed with H2O (2 × 20 mL) and brine (20 mL). The organic layer was dried over MgSO4, evaporated and the residue was trituated with Et2O. The crystallized product was collected to yield a white powder, which could be recrystallized from EtOH to give 6a-j. The reaction times and yields (based on the dipolarophiles) are summarized in Table
[2]
. Selected data for representative examples:
Ethyl 3-(4-chlorophenyl)-3a-nitro-4-phenyl-benzopirano[3,4-
c
]-pyrrolidine-1-carboxylate (
6a): 1H NMR (250 MHz, CDCl3): δ = 7.51 (d, 1 H, J = 7.6 Hz, H-9), 7.35 (2 H, d, J = 8.7 Hz, Ar3-3′ and 5′H), 7.27 (2 H, d, J = 8.7 Hz, Ar3-2′ and 6′H), 7.12 (7 H, m, Ar-H), 6.77 (d, 1 H, J = 7.5 Hz, H-6), 5.48 (1 H, s, H-4), 4.88 (1 H, br m, H-3), 4.74 (1 H, d, J = 3.6 Hz, H-9b), 4.43 (2 H, q, J = 7.1 Hz, OCH2), 4.05 (1 H, br s, H-1), 2.99 (1 H, br s, H-2), 1.41 (3 H, t, J = 7.1 Hz, CH2CH3). 13C NMR (62.5 MHz, CDCl3): δ = 171.8 (q, C=O), 149.7 (q, C-5a), 135.4 (q, Ar3-4′C), 134.7 (q, Ar3-1′C), 129.1 (2 × CH, Ar3-2′ and 6′C), 129.0 (CH, C-7), 128.9 (CH, C-9), 128.8 (CH, Ar4-1′C), 128.5 (2 × CH, Ar3-3′ and 5′C), 128.4 (q, C-9a), 128.3 (2 × CH, Ar4-2′ and 6′C), 128.2 (2 × CH, Ar4-3′ and 5′C), 124.8 (CH, Ar4-4′C), 123.2 (CH, C-8), 118.2 (CH, C-6), 96.4 (q, C-3a), 75.5 (CH, C-4), 69.4 (CH, C-3), 68.3 (CH, C-1), 62.2 (CH2), 45.6 (CH, H-9b), 14.3 (CH3). IR (KBr): 3334, 2979, 1733, 1586, 1540, 1487, 1453, 1368, 1298, 1228, 1212, 1114, 1094, 1015 cm-1.
Methyl 1-benzyl-3,4-
bis
-(4-chlorophenyl)-3a-nitro-benzopirano[3,4-
c
]-pyrrolidine-1-carboxylate (
6f): 1H NMR (250 MHz, CDCl3): δ = 7.76 (1 H, dd, J = 1.7 and 7.8 Hz, H-9), 7.35 (2 H, d, J = 8.6 Hz, Ar3-3′ and 5′H), 7.27 (2 H, d, J = 8.6 Hz, Ar3-2′ and 6′H), 7.15 (4 H, m, Bn-H and H-7), 7.14 (2 H, d, J = 8.5 Hz, Ar4-3′ and 5′H), 7.10 (1 H, dt, J = 1.7 and 7.8 Hz, H-8), 7.05 (2 H, d, J = 8.5 Hz, Ar4-2′ and 6′H), 6.96 (2 H, m, Bn-H), 6.76 (1 H, dd, J = 1.7 and 7.8 Hz, H-6), 5.55 (1 H, s, H-4), 5.10 (1 H, s, H-9b), 5.09 (1 H, d, J = 7.8 Hz, H-3), 3.78 (3 H, s, OMe), 2.94 (1 H, br d, J = 7.8 Hz, H-2), 2.81 (1 H, d, J = 13.7 Hz, α-CH2), 2.37 (1 H, d, J = 13.7 Hz, β-CH2). 13C NMR (125 MHz, CDCl3): δ = 174.4 (q, C=O), 152.1 (q, C-5a), 136.0 (q, Bn-1′C), 135.4 (q, Ar3-4′C), 134.9 (q, Ar4-4′C), 133.3 (q, Ar3-1′C), 132.9 (q, Ar4-1′C), 130.6 (CH, C-9), 129.9 (2 × CH, Bn-2′ and 6′C), 129.6 (2 × CH, Ar4-2′ and 6′C), 129.3 (CH, C-7), 129.2 (2 × CH, Ar3-3′ and 5′C), 128.5 (2 × CH, Bn-3′ and 5′C), 128.3 (2 × CH, Ar4-3′ and 5′C), 128.1 (2 × CH, Ar3-2′ and 6′C), 127.0 (CH, Bn-4′C), 123.1 (CH, C-8), 122.2 (q, C-9a), 118.7 (CH, C-6), 98.5 (q, C-3a), 77.0 (CH, C-4), 72.2 (q, C-1), 67.4 (CH, C-3), 52.7 (OCH3), 49.8 (CH, C-9b), 42.2 (CH2). IR (KBr): 3341, 3031, 1751, 1601, 1542, 1491, 1456, 1436, 1239, 1208, 1130, 1111, 1096, 1079, 1042, 1014, 1006 cm-1.
General Procedure for the Preparation of Compounds 8: The corresponding 3-nitrochromene (3, 0.80 mmol) and 6,7-dimethoxy-(2-methoxycarbonylmethyl)-3,4-dihydro-isoquinolinium bromide (0.29 g, 0.85 mmol) was dissolved in dry MeOH (10 mL) and Et3N (0.14 mL, 0.10 g, 1.00 mmol) was added under argon atmosphere. The reaction mixture was stirred at r.t. for 24 h. The solvent was removed in vacuo, the residue was suspended in Et2O (20 mL). The ethereal solution was washed with H2O (10 mL) and brine (5 mL), dried over MgSO4 and evaporated in vacuo to yield a white solid, which was recrystallized from EtOH to give 8a,b,d. The reaction times and yields are summarized in Table
[4]
. Selected data for representative example:
Methyl 8,9-dimethoxy-6a-nitro-6-(4-methoxyphenyl)-6a,6b,11,12,14,14a-hexahydro-6
H
-chromeno[3′,4′:3,4]pyrrolidino[2,1-
a
]isoquinoline-14-carboxylate (
8b): 1H NMR (500 MHz, CDCl3): δ = 7.18 (1 H, t, J = 7.5 Hz, H-3), 7.06 (1 H, d, J = 7.5 Hz, H-1), 6.93 (1 H, d, J = 7.5 Hz, H-4), 6.90 (1 H, t, J = 7.5 Hz, H-2), 6.85 (2 H, d, J = 8.2 Hz, Ar6-2′ and 6′H), 6.51 (1 H, s, H-10), 6.46 (2 H, d, J = 8.2 Hz, Ar6-3′ and 5′H), 6.10 (1 H, s, H-7), 5.77 (1 H, s, H-6), 4.86 (1 H, s, H-6b), 4.12 (1 H, d, J = 11.3 Hz, H-14a), 4.11 (1 H, d, J = 11.3 Hz, H-14), 3.83 (3 H, s, OMe), 3.70 (3 H, s, OMe), 3.36 (3 H, s, OMe), 3.32 (3 H, s, OMe), 3.18 (1 H, m, H-11), 3.01 (1 H, m, H-12), 2.70 (1 H, m, H-12), 2.62 (1 H, m, H-11). 13C NMR (125 MHz, CDCl3): δ = 170.4 (q, C=O), 159.6 (q, Ar6-4′C), 153.6 (q, C-4a), 147.8 (q, C-9), 146.7 (q, C-8), 129.9 (2 × CH, Ar6-2′ and 6′C), 129.4 (CH, C-1), 128.8 (CH, C-3), 128.0 (q, Ar6-1′C), 127.5 (q, C-10a), 127.4 (C-14b), 123.4 (C-6c), 120.5 (CH, C-2), 116.2 (CH, C-4), 113.2 (C-10), 112.9 (2 × CH, Ar6-3′ and 5′C), 109.8 (CH, C-7), 90.4 (q, C-6a), 75.8 (CH, C-6), 67.7 (CH, C-14), 65.7 (C-6b), 55.8 (OMe), 55.2 (OMe), 54.6 (OMe), 51.7 (OMe), 47.2 (CH, C-14a), 46.8 (C-12), 29.7 (C-11). IR (KBr): 2990, 2945, 2913, 2835, 1749, 1612, 1585, 1552, 1519, 1490, 1459, 1437, 1353, 1249, 1212, 1193, 1150, 1117, 1076, 1042, 1021 cm-1.