Reductive Cyclization of a Functionalized 1,1′-Bianthraquinone

Abstract

Reductive cyclization of 2,2′-dimethoxymethyl-[1,1′-bianthracene]-9,9′,10,10′-tetrone with Cu powder in concentrated sulfuric acid yields helianthrone with partially reduced side chain.

Key words

ring closure - reduction - cyclization - fused-ring systems

References

• 1 Rahimipour S. Palivan C. Barbosa F. Bilkis I. Koch Y. Weiner L. Fridkin M. Mazur Y. Gescheidt G. J. Am. Chem. Soc.  2003,  125:  1376 
• 2 Siboni G. Amit-Patito I. Weizman E. Waintraub-Porat M. Weitman H. Ehrenberg B. Malik Z. Cancer Lett.  2003,  196:  57 
• 3 Kraus GA. Pratt D. Tossberg J. Carpenter S. Biochem. Biophys. Res. Commun.  1990,  172:  149 
• 4 English DS. Das K. Zenner JM. Zhang W. Kraus GA. Larock RC. Petrich JW. J. Phys. Chem. A  1997,  101:  3235 
• 5 Brockmann H. Fortschr. Chem. Org. Naturst.  1957,  14:  141 
• 6 Brockmann H. Spitzner D. Tetrahedron Lett.  1975,  37 
• 7 Cameron DW. Raverty WD. Aust. J. Chem.  1976,  29:  1523 
• 8 Falk H. Angew. Chem. Int. Ed.  1999,  38:  3134 ; Angew. Chem. 1999, 111, 3306
• 9 Brockmann H. Franssen U. Spitzner D. Augustiniak H. Tetrahedron Lett.  1974,  1991 
• 10a Brockmann H. Eggers H. Chem. Ber.  1958,  91:  81 
• 10b Brockmann H. Eggers H. Chem. Ber.  1958,  91:  547 
• 10c Spitzner D. Angew. Chem.  1977,  89:  55 
• 10d Rodewald G. Arnold R. Griesler J. Steglich W. Angew. Chem.  1977,  89:  56 
• 10e Mazur Y, Bock H, and Lavie D. inventors; Can. Pat. Appl. CA  2029993.  ; Chem. Abstr. 1992, 116, 6343
• 11 Scholl R. Mansfeld J. Ber. Dtsch. Chem. Ges.  1910,  43:  1734 
• 12 Brockmann H. Kluge F. Muxfeldt H. Chem. Ber.  1957,  90:  2302 
• 13 Iio H. Zenfuku K. Tokoroyama T. Tetrahedron Lett.  1995,  36:  5921 
• 14 Scharf HD. Weitz R. Tetrahedron  1979,  35:  2263 
• 16a Fanta PE. Synthesis  1974,  9 
• 16b

  Preparation of Compound 7.
  Activation of Cu-powder: commercially available Cu powder (Merck, Darmstadt, Germany) was treated in glacial acetic acid at r.t. for 10 min. The mixture was filtered and the filter cake washed with H₂O until neutral. The treatment was repeated and the activated Cu was finally washed with acetone and dried in vacuo at r.t. and stored under an atmosphere of argon. Activated Cu powder was introduced into a melt of 6 (10.00 g, 34.9 mmol) in naphthalene (14 g) with stirring. The reaction mixture was kept at 235 °C for 3 h, cooled to r.t. and the crashed cake was extracted with CHCl₃. The filtered solution was concentrated and the residue dissolved in toluene (20 mL). This solution was adsorbed on silica gel. Elution with toluene gave after the fast removing of naphthalene a yellow filtrate which was concentrated to give 6.00 g of crude 7. The crude product was crystallized from hot EtOH to yield 5.00 g (56%), yellow plates, mp 226-227 °C (EtOH). ¹H NMR (300 MHz, CDCl₃): δ = 8.572-8.545 (d, J = 8 Hz, 1 H), 8.344-8.316 (dd, J = 0.9, 7.6 Hz, 1 H), 8.102-8.076 (d, J = 8 Hz, 1 H), 7.999-7.970 (dd, J = 1.0, 7.6 Hz, 1 H), 7.796-7.741 (ddd, J = 1.0, 7.6, 7.3 Hz, 1 H), 7.714-7.659 (ddd, J = 1.0, 7.5, 7.6 Hz, 1 H), 3.40 (s, 2 H, CH ₂ ), 3.17 (s, 3 H, CH ₃ ). ¹³C NMR (75.48 MHz, CDCl₃): δ = 183.85 (s), 183.50 (s), 142.81 (s), 139.94 (s), 134.32 (s), 134.30 (d), 134.08 (d), 133.33 (s), 133.29 (d), 130.75 (s), 127.53 (d), 127.47 (d), 127.12 (d), 72.03 (t), 58.89 (q). MS: m/z (%) = 502 (8)[M]⁺, 470 (100), 409 (30), 383 (20). IR (KBr): 1668 cm^-1 (C=O). UV (EtOH): λ_max (log ε) = 254 nm (4.53), 336 (3.62). Anal. Calcd for C₃₂H₂₂O₆ (502.5): C, 76.48; H, 4.41. Found: C, 76.62; H, 4.39.

15

Preparation of Compound 6.
To a solution of 5 (18.00 g, 53.6 mmol) in toluene (700 mL) was added with stirring a freshly prepared solution of NaOMe [Na (4.00 g, 173 mmol) and MeOH (200 mL)] at r.t. The red reaction mixture was diluted with H₂O after 3 h, the organic phase was separated, washed with H₂O until neutral, dried (Na₂SO₄), and filtered over Al₂O₃ (neutral). Elution with toluene gave a yellow filtrate, which was concentrated to yield 10.00 g (65%) of yellow crystals, mp 180 °C.
¹H NMR (300 MHz, CDCl₃): δ = 8.30-7.70 (m, 5 H), 4.75 (s, 2 H, CH ₂ ), 3.61 (s, 3 H, OMe). Anal. Calcd for C₁₆H₁₁O₃Cl (286.7): Cl, 12.4. Found: Cl, 12.62.

17

Preparation of Compounds 10 and 11.
To the dark brown solution of 7 (1.01 g, 20 mmol) in concd H₂SO₄ (60 mL) at -5 °C was added Cu powder (5 g) with stirring in the dark. Soon, the solution became green. The reaction mixture was poured on ice (200 g) after 5 min. The precipitate was filtered off, washed with H₂O until neutral and dissolved in CHCl₃. The organic solution was dried (Na₂SO₄) and concentrated, and the brown residue (1.00 g) was dissolved in benzene (50 mL). The crude product was chromatographed on silica gel in the dark to avoid photocyclization. Elution with benzene gave 0.150 g (18%) 10 (eluted first) and 0.100 g (11%) 11.
Compound 10: red needles, mp >240 °C. ¹H NMR (300 MHz, CDCl₃): δ = 8.84 (d, J = 7.6 Hz, 2 H), 8.47 (d, J = 8 Hz, 2 H), 7.96 (dd, J = 8.2, 7.8 Hz, 4 H), 7.57 (dd, J = 8.2, 6.9 Hz, 2 H), 7.39 (dd, J = 7.5, 7.0 Hz, 2 H), 5.06 and 4.52 (AB, J _AB = 12.0 Hz, 4 H, -CH ₂ -O-). ¹³C NMR (75.48 MHz, CDCl₃): δ = 184.1 (s), 141.8 (s), 137.1 (s), 133.1 (d), 132.4 (s), 131.9 (d), 131.7 (s), 131.0 (s), 130.0 (d), 129.7 (d), 129.1 (d), 129.0 (s), 128.0 (d), 127.5 (s), 70.61 (t). MS: m/z (%) = 424 (51)[M]⁺, 395 (20), 236 (35), 28 (100). UV (EtOH): λ_max (log ε) = 457 nm (3.75), 353 (3.46), 316 (3.39), 236 (4.19). Anal. Calcd for C₃₁H₂₀O₃ (424.4): C, 84.89; H, 3.80. Found: C, 84.48; H, 3.77.
Compound 11: red needles, mp >240 °C. ¹H NMR (300 MHz, CDCl₃): δ = 8.85-7.33 (m, 12 H), 5.05 and 4.50 (AB, J _AB = 12 Hz, 2 H, -CH ₂ -O-), 3.13 (s, 3 H, OMe), 2.63 (s, 3 H, Me). MS: m/z (%) = 440 (60)[M]⁺, 407 (60), 28 (100). Anal. Calcd for C₃₀H₁₆O₃ (440.5): C, 84.53; H, 4.58. Found: C, 84.70; H, 4.43.