Unusual Double ‘O/N to N/O’ Recyclization of 5-Alkyl-7,8-dimethoxy-2-arylbenzo[d]pyrrolo[3,2-b]pyrylium Perchlorates into 5-Alkyl-7,8-dimethoxy-2-arylfuro[2,3-c]isoquinolines

Abstract

Novel unusual double recyclization of both pyrrole and pyrylium cores of 5-alkyl-7,8-dimethoxy-2-phenylbenzo[d]pyrrolo[3,2-b]pyrylium perchlorate by nucleophiles is described, which regardless of the nucleophile (ammonium carbamate, triethylamine, sodium acetate, HCl in methanol), results in 5-alkyl-7,8-dimethoxy-2-phenylfuro[2,3-c]isoquinoline. The structure of 5-methyl-7,8-dimethoxy-2-phenylfuro[2,3-c]isoquinoline was established from X-ray diffraction analysis.

recyclization - pyrylium salt - isoquinoline - ANRORC reaction - nucleophile

References

<A NAME="RD01805ST-1">1</A>

Currently at the Department of Chemistry, University of Durham, Durham DH1 3LE, UK.

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<A NAME="RD01805ST-8">8</A>

General Procedure for the Reaction of Perchlorates 1a-c with Nucleophiles. To the solution of ammonium carbamate (50 mmol) in MeOH (50 mL) 5-alkyl-7,8-dimethoxy-2-arylben-zo[d]pyrrolo[3,2-b]pyrylium perchlorate (1a-c, 5 mmol) [5] was added and the mixture was refluxed for 2 h. MeOH was removed in vacuo and H₂O (50 mL) was added to the residue. After stirring for 20 min, the product was filtered off, washed with H₂O and dried to afford compounds 2a, 2b, or 2c in 50%, 47% and 43% yields, respectively.
7,8-Dimethoxy-5-methyl-2-phenylfuro[2,3- c ]iso-quinoline ( 2a): colorless needles, mp 199-200 °C (from MeCN). ¹H NMR (500 MHz, DMSO-d ₆): δ = 2.88 (s, 3 H, CH₃), 3.96 (s, 3 H, 7-OMe), 4.07 (s, 3 H, 8-OMe), 7.34 (t, 1 H, J = 7.8 Hz, C4′-H), 7.40 (s, 1 H, C6-H), 7.47 (t, J = 7.8 Hz, 2 H, C3′ and C5′-H), 7.56 (s, 1 H, C9-H), 7.69 (s, 1 H, C1-H), 7.91 (d, J = 7.8 Hz, 2 H, C2′ and C6′-H). MS (EI): m/z (%) = 319 (100) [M⁺]. Anal. Calcd for C₂₀H₁₇NO₃: H, 75.22; H, 5.37; N, 4.39. Found: C, 75.32; H, 5.31; N, 4.45.
7,8-Dimethoxy-5-ethyl-2-phenylfuro[2,3- c ]isoquinoline ( 2b): colorless needles, mp 173-174 °C (from 2-PrOH). ¹H NMR (500 MHz, DMSO-d ₆): δ = 1.40 (t, J = 7.5 Hz, 3 H, CH₃,), 3.30 (q, J = 7.5 Hz, 2 H, CH₂), 3.96 (s, 3 H, 7-OMe), 4.02 (s, 3 H, 8-OMe), 7.40 (t, 1 H, J = 7.8 Hz, C4′-H), 7.52 (t, J = 7.8 Hz, 2 H, C3′ and C5′-H), 7.54 (c, 1 H, C6-H), 7.71 (c, 1 H, C9-H), 7.91 (d, J = 7.8 Hz, 2 H, C2′ and C6′-H), 7.96 (c, 1 H, C1-H). MS (EI): m/z (%) = 333 (100) [M⁺]. Anal. Calcd for C₂₁H₁₉NO₃: C, 75.66; H, 5.74; N, 4.20. Found: C, 75.48; H, 5.65; N, 4.31.
7,8-Dimethoxy-5-methyl-2-(4-bromophenyl)furo[2,3- c ]isoquinoline ( 2c): colorless needles, mp 212-213 °C (from 2-PrOH). ¹H NMR (500 MHz, DMSO-d ₆): δ = 2.89 (s, 3 H, CH₃), 3.96 (s, 3 H, 7-OMe), 4.01 (s, 3 H, 8-OCH₃), 7.49 (s, 1 H, C6-H), 7.67 (s, 1 H, C9-H), 7.73 (d, J = 8.5 Hz, 2 H, C2′ and C6′-H), 7.82 (d, J = 8.5 Hz, 2 H, C3′ and C5′-H), 8.00 (s, 1 H, C1-H). MS (EI): m/z (%) = 397 (98, ⁷⁹Br) [M⁺], 399 (100, ⁸¹Br) [M⁺]. Anal. Calcd for C₂₀H₁₆BrNO₃: C, 60.32; H, 4.05; Br, 20.06; N, 3.52. Found: C, 60.48; H, 4.18; Br, 20.23; N, 3.38.

<A NAME="RD01805ST-9">9</A>

Melting points were determined on a Kofler hot-stage apparatus and were uncorrected. The ¹H NMR spectra were obtained on a Bruker DRX500 (500.13 MHz) spectrometer using dimethylsulfoxide-d ₆ as a solvent. Chemical shifts (δ) are in ppm and J values are in Hz. Mass spectra (EIMS) were determined with FINNIGAN MAT; INCOS 50 mass spectrometer operating at ionization potential of 70 eV.

<A NAME="RD01805ST-10">10</A>

The crystals of 2a are monoclinic, C₂₀H₁₇NO₃, at 20 °C a = 9.892 (2), b = 12.452(3), c = 12.971 (3) Å, β = 94.25(2)°, V = 1593.4 (6) ų, M _r = 159.67, Z = 4, space group P2₁/n, d _calc = 1.331 g cm^-3, µ(Mo-K_α) = 0.090 mm^-1, F(000) = 672. Unit cell dimensions and intensity of 2850 reflections (2686 unique, R _int = 0.035) were measured using automatic four-circle ‘Siemens P3/PC’ diffractometer (graphite-monochromated Mo-K_α radiation, 2θ/θ-scan, 2θ_max = 50°). The structure was solved by direct method using SHELX97 software [Sheldrick, G. M. SHELX97, PC Version. A system of computer programs for the crystal structure solution and refinement, Rev. 2, 1998]. The positions of the hydrogen atoms were located from difference maps of electron density and refined using riding model with U_iso = nU_eq of non-hydrogen atom bonded with hydrogen atom given (n = 1.5 for methyl groups and n = 1.2 for remaining H atoms). The structure was refined by full-matrix least squares method using anisotropic thermal parameters for all non-hydrogen atoms. Final divergence factors are wR2 = 0.155 for 3001 reflections (R1 = 0.052 for 1827 reflections with F > 4σ(F), S = 0.971). The full tables of the atomic coordinates, bond lengths and bond angles have been deposited at the Cambridge Crystallographic Data Centre, CCDC No 198113.

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<A NAME="RD01805ST-12">12</A>

When appropriate amounts of Et3N or NaOAc or HCl were used instead of ammonium carbamate, compounds 2a-c were isolated in similar yields to that for the reaction with ammonium carbamate. In the case of HCl, pyrylium salt (1a-c) was dissolved in concd aq HCl (10 mL per 1 g of 1a-c) on heating, the solution was refluxed for 2 h, cooled down and acidified with aq NaHCO₃ until neutral or slightly basic reaction. The precipitate was filtered off, washed with H₂O and dried to afford compounds 2a-c in somewhat lower yields (30-35%).

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<A NAME="RD01805ST-14">14</A>

Tao, Y. T.; Bogza, S. L.; Perepichka, I. F., manuscript in preparation.

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