Complex Diazaazulenones from the Reaction of ortho-Naphthoquinones with Ammonium Acetate

Abstract

Complex diazaazulenones compounds were obtained from ortho-naphthoquinones by reaction with ammonium acetate.

Key words

lapachones - heterocycles - diazaazulenone - X-ray crystallography

References and Notes

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• 10a

  Enraf-Nonius (1997-2000). COLLECT. Nonius B. V., Delft, The Netherlands.

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• 10c Sheldrick GM. SHELXL-97: Program for Crystal Structures Analysis   University of Göttingen; Göttingen / Germany: 1997. 
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9

A orange crystal (0.086 × 0.150 × 0.240) mm^³ of compound 9 was selected for X-ray diffraction. Intensity data were collected at r.t. (T = 298K) using a diffractometer Kappa CCD of Enraf Nonius with MoKα monochromatic radiation (λ = 0.71073 Å) and using the Collect^¹0a software, as well as Scalepack^¹0b for cell refinement. The compound 9 was measured a total of 4349 reflections to a maximum 2θ of 27.42˚. No significant absorption effect (µ = 0.088 mm^-¹) for compound 9 was revealed, so no absorption correction was applied. The crystal structure for compound 9 was solved by direct methods and refined anisotropically with full matrix least square on F^² using SHELXL-97 program.^¹0c H atoms attached to C atoms were located on stereochemical grounds placed (C-H = 0.93-0.98 Å) and refined as riding with U_iso(H) = 1.5 U_eq (C-methyl) or 1.2 U_eq(other) times the value of the equivalent isotropic displacement parameter of atoms to which they are bonded. The software used were: data collection: COLLECT;^¹0a cell refinement: HKL SCALEPACK;^¹0b data reduction: HKL DENZO and SCALEPACK.^¹0b The program (s)used to solve structure: SHELXS-97.^¹0d The program (s)used to refine structure: SHELXL-97.^¹0c molecular graphics: ORTEP-3, software used to prepare material for publication: WinGX.^¹0e Crystallographic data for compounds 9 have been deposited with the Cambridge Crystallographic Data Center as Supplementary Publication No. CCDC 739857. Copies of the data can be obtained, free of charge, on application to CCDC, 12 Union Road, Cambridge CH21EZ, UK (fax:[phone] or e-mail: [e-mail]).

11

Crystal Data and Structure Refinement for Compound 9
Empirical formula: C₂₈H₂₄N₂O₃; formula weight: 436.49; temperature: 295 (2) K; wavelength: 0.71073 Å; crystal system: monoclinic; space group: Pn; unit cell dimensions: a = 5.32360 (10) Å, b = 9.9426 (3) Å, β = 95.6930 (10)˚, c = 20.1385 (7) Å; volume: 1060.68 (5) Å^³; Z: 2; density(calcd): 1.367 mg/m^³; absorption coefficient: 0.088 mm^-¹; F(000): 460; crystal size: (0.086 × 0.150 × 0.240) mm^³; θ range for data collection: 2.29-27.42˚; index ranges: -6 £ h £ 6, -12 £ k £ 11, -26£ l £ 25; reflections collected: 4349; independent reflections: 4219 [R(int) = 0.060]; completeness to θ = 27.42˚: 98.7%; absorption correction: none; refinement method: full-matrix least-squares on F^²; data/restraints/parameters: 4219/2/365; goodness-of-fit on F^²: 1.077; final R indices [I > 2σ(I)]: R1 = 0.0562, wR2 = 0.1403; R indices (all data): R1 = 0.0803, wR2 = 0.1662; largest diff. peak and hole: 0.305 and -0.343 e Å^-³.

12

Melting points were obtained on Thomas Hoover and are uncorrected. Analytical grade solvents were used. Column chromatography was performed on silica gel (Acros Organics 0.035-0.070 mm, pore diameter ca 6 nm). Infrared spectra were recorded on a Perkin-Elmer FT-IR spectrometer. ^¹H and ^¹³C NMR were recorded at r.t. using a Varian Gemini 200, in the solvents indicated, with TMS as internal standard. Chemical shifts (δ) are given in ppm. Electron-impact mass spectra (70 eV) were obtained using a VG Autospec apparatus (Micromass, Manchester, UK). The main fragments were described as a relation between atomic mass units and the charge (m/e) and the relative abundance in percentage of the base peak intensity. Lapachol(1) was extracted from the hardwood Tabebuia sp. (Tecoma) and purified by a series of recrystallizations with the appropriate solvent.^¹³a β-lapachone (2) was obtained by acid cyclization from lapachol (1) by Hooker’s methodology.^¹³b General Procedure for the Synthesis of the Compounds 8-10 To 1.0 mmol of β-lapachone (2) or nor-β-lapachone (3) in a solution of glacial AcOH (10.0 mL), was added NH₄OAc (14.4 mmol), followed by reflux for 2.5 h. After cooling, the reaction medium was poured in H₂O, and the solid residue was filtered under vacuum, washed with water for neutralization and soon after the solid was chromatographed in a silica gel column starting with hexane as eluent. In preparing 8, the compound was found in a polarity corresponding to 2.5% of the EtOAc-hexane gradient. In obtention of 9, the compound was chromatographed in the EtOAc-hexane gradient corresponding to 3.5%. Compound 10 was obtained in the EtOAc-hexane gradient corresponding to 3.5%. The orange solids were recrystallized in a mixture of hexane-acetone (1:1).
Spectroscopic Data of Compound 8 Orange crystals; mp 244-245 ˚C; yield 11.2%. IR (KBr): 3064, 2963, 2924, 2851, 1665, 1629, 1499, 1388, 1284, 1172, 1074, 1062, 1020, 870, 759, 703 cm^-¹. ^¹H NMR (200 MHz, CDCl₃): δ = 9.4 (dd, 1 H), 8.8 (dd, 1 H), 8.1 (dd, 2 H), 7.6 (m, 4 H), 3.8 (s, 2 H), 3.3 (s, 2 H), 1.6 (s, 12 H). ^¹³C NMR (50 MHz, CDCl₃): δ = 160.8, 159.5, 153.6, 144.2, 133.5, 131.3, 129.0, 127.2, 126.4, 125.7, 125.3, 123.2, 122.7, 122.2, 120.1, 108.4, 107.4, 86.2, 85.7, 47.7, 45.1, 29.6, 28.4, 28.2. UV (EtOH): λ_max (log ε) = 373.0 (4.09), 328.5 (4.29), 315.5 (4.27), 264.5 (4.36), 228.0 (4.49), 205.5 (4.40) nm. MS (70 eV): m/z (%) = 437 (33), 436 (100), 421 (15), 393 (8,0), 341 (8,0), 325 (20), 297 (6), 218 (5).
Spectroscopic Data of Compound 9 Orange crystals; mp 265-268 ˚C; yield 11.2 (%). IR (KBr): 3074, 3058, 2976, 2928, 2856, 1663, 1630, 1601, 1531, 1460, 1385, 1276, 1250, 1117, 1069, 867, 752, 710 cm^-¹. ^¹H NMR (200 MHz, CDCl₃): δ = 9.3 (dd, 1 H), 8.4 (dd, 1 H), 8.1 (m, 2 H), 7.6 (m, 4 H), 3.6 (s, 2 H), 3.4 (s, 2 H), 1.6 (s, 12 H). ^¹³C NMR (50 MHz, CDCl₃): δ = 161.3, 158.8, 154.5, 148.8, 139.7, 131.4, 131.0, 129.6, 128.2, 127.2, 126.6, 125.0, 124.0, 123.2, 122.5, 120.3, 109.7, 108.1, 88.3, 86.0, 45.3, 41.8, 28.4, 28.2. UV (EtOH): λ_max (log ε) = 373.0 (3.99), 328.5 (4.19), 315.5 (1.32), 265.0 (1.62), 228.5 (2.21), 203.0 (2.03) nm. MS (70 eV): m/z (%) = 436 (100), 421 (34), 393 (10,6), 341 (8.7), 325 (42), 297 (10), 218 (9), 140 (11), 41 (22).
Spectroscopic Data of Compound 10 Orange crystals; mp 243-245 ˚C; yield 10%. IR (KBr): 3094, 2973, 2920, 2850, 1667, 1611, 1597, 1584, 1529, 1459, 1446, 1365, 1348, 1316, 1282, 1255, 1158, 1117, 1087, 760, 720, 701 cm^-¹. ^¹H NMR (200 MHz, CDCl₃): δ = 9.0 (d, 1 H), 8.3 (d, 1 H), 8.1 (m, 2 H), 7.6 (m, 4 H), 3.3 (t, 2 H), 3.1 (t, 2 H), 2.0 (m, 4 H), 1.6 (s, 12 H). ^¹³C NMR (50 MHz, CDCl₃): δ = 168.2, 155.2, 147.8, 147.2, 141.5, 130.7, 129.6, 129.6, 126.5, 125.8, 125.4, 125.0, 123.9, 123.0, 122.8, 121.7, 121.3, 109.5, 106.9, 76.8, 74.7, 32.2, 31.7, 26.6, 26.3, 22.8, 18.4. UV (EtOH): λ_max (log ε) = 364 (4.01), 306 (4.62), 230 (4.67) nm. MS (70 eV): m/z (%) = 464 (5), 408 (2), 352 (2), 44 (13), 40 (100).