Synlett 2010(13): 1931-1934  
DOI: 10.1055/s-0030-1258502
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

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

Flavio S. Emerya,d, Maria do Carmo F. R. Pintoa, Carlos A. de Simoneb,c, Valéria R. S. Maltab, Eufrânio N. da Silva Júnior*a, Antonio V. Pintoa
a Núcleo de Pesquisas de Produtos Naturais, UFRJ, 21944-971, Rio de Janeiro, RJ, Brazil
Fax: +55(21)25626512; e-Mail: [email protected];
b Instituto de Química e Biotecnologia, UFAL, 57072-970, Tabuleiro do Martins, Maceió, Al, Brazil
c Departamento de Física e Informática, Instituto de Física, USP, 13560-160, São Carlos, SP, Brazil
d Faculdade de Ciências Farmacêuticas, USP, 14040-903, Ribeirão Preto, SP, Brazil
Further Information

Publication History

Received 31 March 2010
Publication Date:
16 July 2010 (online)

Abstract

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

    References and Notes

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  • 4b da Silva Júnior EN. Souza MCBV. Pinto AV. Pinto MCFR. Ferreira VF. Menna-Barreto RFS. Silva RSF. Teixeira DV. de Simone CA. de Castro SL. Eur J. Med. Chem.  2008,  1774 
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  • 5b Pinto AV. Pinto CN. Pinto MCFR. Emery FS. de Moura KCG. Carvalho CEM. Brinn IM. Heterocycles  1998,  45:  2491 
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  • 5d da Silva Júnior EN. de Simone CA. de Souza ACB. Pinto CN. Guimarães TT. Pinto MCFR. Pinto AV. Tetrahedron Lett.  2009,  50:  1550 
  • 6 da Silva Júnior EN. de Moura MABF. Pinto AV. Pinto MCFR. de Souza MCBV. Araújo AJ. Pessoa C. Costa-Lotufo LV. Montenegro RC. de Moraes MO. Ferreira VF. Goulart MOF. J. Braz. Chem. Soc.  2009,  20:  635 
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  • 10a

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

  • 10b Otwinowski Z. Minor W. Methods Enzymol.  1997,  276:  307 
  • 10c Sheldrick GM. SHELXL-97: Program for Crystal Structures Analysis   University of Göttingen; Göttingen / Germany: 1997. 
  • 10d Sheldrick GM. SHELXS-97: Program for Crystal Structure Resolution   University of Göttingen; Göttingen / Germany: 1997. 
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9

A orange crystal (0.086 × 0.150 × 0.240) mm³ 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 Collect¹0a software, as well as Scalepack¹0b 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) 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 F² 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 Uiso(H) = 1.5 Ueq (C-methyl) or 1.2 Ueq(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:+44 1223 336 033 or e-mail: [email protected]).

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) ų; Z: 2; density(calcd): 1.367 mg/m³; absorption coefficient: 0.088 mm; F(000): 460; crystal size: (0.086 × 0.150 × 0.240) mm³; 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 F²; data/restraints/parameters: 4219/2/365; goodness-of-fit on F²: 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.

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. 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): λmax (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. 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): λmax (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. 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): λmax (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).