Methylisoquinoline-Based Three-Component Condensation Reactions Involving Chromone-3-carboxaldehydes: One-Pot Synthesis of a New Class of Chromenopyridoisoquinolines

Abstract

The synthesis of a new class of compounds, the chromenopyridoisoquinolines, in good yields by a one-pot three-component reaction of chromone-3-carboxaldehydes with the methylisoquinoline acetylenedicarboxylate zwitterion is described.

Key words

chromenopyridoisoquinolines - multicomponent reactions - isoquinoline - chromone-3-carboxaldehydes - acetylenedicarboxylate

References and Notes

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All melting points were determined on a Büchi apparatus and are uncorrected. The ^¹H NMR and ^¹³C NMR spectra were recorded on a Bruker AM300 spectrometer in CDCl₃ with TMS as internal standard. All coupling constants are given in Hz and chemical shifts are given in ppm.
Typical Experimental Procedure for the Preparation of 3a: DMAD (1.0 mmol) was added to a stirred solution of chromone-3-carboxaldehyde 1a (1.0 mmol) and isoquinoline (1.0 mmol) in DME (20 mL) at r.t. and the reaction mixture was stirred for 12 h. Distillation of the solvent in vacuo followed by column chromatography using petroleum ether-EtOAc (3:1) as eluent afforded the chromenopyridoisoquinoline 3a (Scheme  [¹] ). Yield: 54%; yellow crystals; mp 206-207 ˚C (EtOH). IR (KBr): 1728, 1704, 1665, 1607 cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 1.82 (d, J = 0.8 Hz, 3 H, 6-Me), 3.85 (s, 3 H, 8-COOMe), 3.90 (s, 3 H, 9-COOMe), 5.14 (s, 1 H, 15b-H), 5.54 (s, 1 H, 9a-H), 5.71 (br s, 1 H, 5-H), 6.52 (br d, J = 7.9 Hz, 1 H,
1-H), [¹8] 7.03 (ddd, J = 7.9, 7.6, 1.1 Hz, 1 H, 2-H), 7.04 (br d, J = 7.6 Hz, 1 H, 4-H), 7.04 (br d, J = 8.4 Hz, 1 H, 11-H), 7.11 (ddd, J = 7.9, 7.2, 1.0 Hz, 1 H, 13-H), 7.27 (td, J = 7.6, 1.0 Hz, 1 H, C-3), 7.56 (ddd, J = 8.4, 7.2, 1.7 Hz, 1 H, 12-H), 7.83 (ddd, J = 7.9, 1.7, 0.4 Hz, 1 H, 14-H), 9.97 (d, J = 0.4 Hz, 1 H, CHO). ^¹³C NMR (75 MHz, CDCl₃): δ = 20.7 (6-Me), 52.6 (9-Me), 53.3 (8-Me), 61.5 (C-15b), 68.6 (C-5a), 72.3 (C-9a), 108.7 (C-5), 118.3 (C-9), 118.4 (C-11), 121.1 (C-14a), 122.8 (C-13), 124.0 (C-4), 124.8 (C-15c), 125.8
(C-2), 127.2 (C-14), 128.5 (C-1), 129.2 (C-3), 131.1 (C-4a), 137.1 (C-12), 137.5 (C-6), 141.9 (C-8), 160.5 (C-10a), 164.9 (8-C=O), 166.1 (9-C=O), 186.1 (C=O), 197.3 (C=O). MS (LCMS): m/z (%) = 460 (100) [M⁺ + 1]. Anal. Calcd for C₂₆H₂₁NO₇ (459.45): C, 67.97; H, 4.61; N, 3.05. Found: C, 67.86; H, 4.73; N, 2.98.

18

The multiplicities and chemical shifts of the aromatic protons have been confirmed after simulation with program SpinWorks, version 2.2.0, available from
ftp://davinci.chem.umanitoba.ca.