A Synthesis of Novel Dioxapropellanes from the Knoevenagel Adducts of Acenaphthoquinone and 3-Oxo-3-arylpropionitriles in Aqueous Methanol

Abstract

A highly chemoselective and regioselective method for the synthesis of dioxopropellanes developed by reaction of the Knoevenagel adducts of acenaphthoquinone (and ninhydrin) and malononitrile, with 3-oxo-3-arylpropionitriles in 70% aqueous MeOH at room temperature, is reported.

Key words

dioxapropellane - acenaphthoquinone - chemoselective - ­regioselective

• References and Notes

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• 19 Typical Procedure for the Preparation of 3a–f To a stirred solution of 3-oxo-3-arylpropionitrile 2 and Et₃N (0.101 g, 1 mmol) in MeOH–H₂O (2:1, 6 mL) was added the adduct of acenaphthoquinone and malononitrile or ethyl cyanoacetate 1 (1 mmol) at r.t. After completion of the reaction (about 30–120 min, TLC (n-hexane–EtOAc, 2:1) monitoring), the solvent was evaporated under vacuum, and the crude product was purified by flash column chromatography on silica gel using EtOAc–n-hexane (1:2) as eluent (for compounds 3a–d) and was washed with MeOH (for compounds 3e–h) to afford the pure product.
• 20 Ethyl 8-Amino-10-cyano-11-phenyl-6b,9a-(epoxyetheno)-acenaphtho[1,2-b]furan-9-carboxylate (3e) Colorless solid; yield 0.40 g (95%), mp 213–216 °C. ¹H NMR (500.1 MHz, DMSO-d ₆): δ = 1.42 (3 H, br, CH₃), 4.25 (2 H, br, OCH₂), 7.48–7.50 (4 H, m, 4 Ar–H), 7.68–7.73 (3 H, m, 3 ArH), 7.82–7.92 (5 H, m, 3 ArH, NH₂), 8.02 (1 H, d, ³ J = 7.4 Hz, ArH). ¹³C NMR (125.7 MHz, DMSO-d ₆): δ = 14.4 (Me), 58.7 (CCN), 59.8 (OCH₂) 70.8(C), 77.7 (CCN), 90.1 (OCO), 116.0 (CN), 120.4 (CH), 120.8 (CH), 124.5 (CH), 125.6 (C), 126.4 (CH), 126.8 (2 CH), 127.6 (2 CH), 129.0 (2 CH), 129.1 (CH), 131.5 (C), 134.8 (C), 135.8 (C), 141.2 (C), 165.0 (CO₂Et), 165.2 (CNH₂), 165.9 (CO). IR (KBr): ν_max = 3397 and 3294 (NH₂), 2208 (CN), 1688 (C=O), 1628 (OC=C), 1540, 1430 (C=C_Ar) cm^–1. MS (EI): m/z (%) = 422 (10) [M⁺], 366 (25), 343 (45), 264 (50), 236 (30), 210 (25), 183 (17), 149 (60), 105 (100), 77 (90), 51 (40). Anal. Calcd (%) for C₂₆H₁₈N₂O₄ (422.13): C, 73.92; H, 4.30; N, 6.63. Found: C, 74.12; H, 4.40; N, 6.72. X-ray Crystal-Structure Determination of 3e The X-ray diffraction measurement was carried out on a STOE IPDS 2T diffractometer with graphite-monochromated Mo Kα radiation. The single crystal suitable for X-ray analysis was obtained from DMSO solution and mounted on a glass fiber. Compound 3e crystallized in the triclinic system with the P-1 space group. For the unit cell a = 9.167(18) Å, b = 11.425(2) Å, c = 11.630(2) Å, α = 69.01(3)°, β = 70.11(3)°, γ = 82.22(3)°, Z = 2, cell volume = 1069.3(4) ų. Orientation matrixes for data collection were obtained by least-square refinement of the diffraction data from 3053 reflections. Diffraction data were collected in a series of ω scans in 1° oscillations and integrated using the Stoe X-AREA software package.²³ Numerical absorption correction was applied using X-Red32 software. The structure was solved by direct methods and subsequent difference Fourier maps and then refined on F² to final R1 = 0.0591 and wR2 (all data) = 0.1535 by a full-matrix least-squares procedure using anisotropic displacement parameters. Atomic factors are from the International Tables for X-ray crystallography. All nonhydrogen atoms were refined with anisotropic displacement parameters. Hydrogen atoms were placed in ideal positions and refined as riding atoms with relative isotropic displacement parameters. All refinements were performed using the X-STEP32, SHELXL-2014 and WinGX-2013.3 programs.²⁴ CCDC-1525132 contains the supplementary crystallographic data for compound 3e in this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.
• 21 Typical Procedure for the Preparation of Compound 10a–d To a stirred solution of 3-oxo-3-arylpropionitrile 2 and Et₃N (0.101 g, 1 mmol) in MeOH–H₂O (2:1, 6 mL) was added the adduct of ninhydrin and malononitrile 9 (0.208 g, 1 mmol) at r.t. After completion of the reaction (about 30–120 min, TLC (n-hexane–EtOAc, 2:1) monitoring), the solvent was evaporated under vacuum, and the crude product was crystallized from CH₂Cl₂–n-hexane.
• 22 2-Amino-4-oxo-10-phenyl-4a,5-dihydro-4H-8b,3a-(epoxy­etheno)indeno[1,2-b]furan-3,11-dicarbonitrile (10a) Orange solid; yield 0.32 g (91%), mp 205–208 °C. ¹H NMR (500.1 MHz, DMSO-d ₆): δ = 7.57 (2 H, t, ³ J = 8.5 Hz, 2 ArH), 7.62 (1 H, t,³ J = 8.0 Hz, ArH), 7.85–7.88 (3 H, m, 3 ArH), 7.99 (1 H, d, ³ J = 7.5 Hz, ArH), 8.04 (1 H, t, ³ J = 7.5 Hz, ArH), 8.09 (1 H, d, ³ J = 8.0 Hz, ArH), 8.17 (2 H, s, NH₂). ¹³C NMR (75.0 MHz, DMSO-d ₆): δ = 52.3 (CCN), 55.9 (C), 69.3 (CCN), 85.3 (OCO), 115.3, 116.8 (2 CN), 120.4 (C), 125.8 (CH), 126.5 (CH), 126.8 (C), 128.2 (2 CH), 130.3 (CH), 134.0 (CH), 134.2 (CH), 136.2 (CH), 138.8 (CH), 143.5 (C), 167.1 (CO), 167.6 (CNH₂), 202.1 (C=O). IR (KBr): ν_max = 3447 and 3335 (NH₂), 2202 (CN), 1725 (C=O), 1662 (OC=C), 1600, 1430 (C=C_Ar) cm^–1. MS (EI): m/z (%) = 353 (25) [M⁺], 341 (65), 249 (32), 205 (47), 149 (33), 105 (100), 77 (82), 51 (70). Anal. Calcd (%) for C₂₁H₁₁N₃O₃ (353.08): C, 71.39; H, 3.14; N, 11.89. Found: C, 71.62; H, 3.28; N, 11.97.
• 23 X-AREA: Program for the Acquisition and Analysis of Data, Version 1.30. Stoe & Cie GmbH; Darmstadt: 2005

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