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Synlett 2016; 27(05): 782-788
DOI: 10.1055/s-0035-1560383
letter
© Georg Thieme Verlag Stuttgart · New York

Unusual Acid- and Base-Catalyzed C–N Bond Formation Approach through Reaction of Chromonyl Meldrum’s Acid and Nitrogen Binucleophiles

Saeed Balalaie*
a   Peptide Chemistry Research Center, K. N. Toosi University of Technology, P.O. Box 15875-4416 Tehran, Iran   Email: balalaie@kntu.ac.ir
b   Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
,
Hamid Reza Bijanzadeh
a   Peptide Chemistry Research Center, K. N. Toosi University of Technology, P.O. Box 15875-4416 Tehran, Iran   Email: balalaie@kntu.ac.ir
,
Saber Mehrparvar
a   Peptide Chemistry Research Center, K. N. Toosi University of Technology, P.O. Box 15875-4416 Tehran, Iran   Email: balalaie@kntu.ac.ir
,
Frank Rominger
c   Organisch-Chemisches Institut der Universitaet Heidelberg, Im Neuenheimer Feld 270, 69120 Heidelberg, Germany
› Author Affiliations
Further Information

Publication History

Received: 22 August 2015

Accepted after revision: 20 October 2015

Publication Date:
30 November 2015 (online)

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Abstract

Reaction of chromonyl Meldrum’s acid and N-substituted 2-aminobenzamides was studied in the presence of acidic and basic catalysts. The use of methanesulfonic acid as a catalyst in this reaction led to the synthesis of chromonyl quinazolinones through employing Meldrum’s acid as a carbon leaving group. However, in the presence of basic catalyst, this reaction gave functionalized 2-pyridones.

Keywords

chromonyl Meldrum’s acid - binucleophile - acid catalysis - base catalysis - chromonyl quinazolinines - domino Michael–elimination–cyclization reaction - functionalized 2-pyridones

Supporting Information

    Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0035-1560383. Copies of 1H NMR, 13C NMR for compound 3a and 1H NMR, 13C NMR, IR, HRMS spectra for compounds 7a–n and 8a–d, and X-ray crystal data for compounds 7c and 7k are included.
  • Supporting Information
 

  • References and Notes

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  • 12 General Procedure for the Synthesis of 3, 7, and 8 Typical Procedure for 3 To a solution of 3-formylchromone (1; 1 mmol, 174 mg) in EtOH–H2O (4 mL; 1:1) was added Meldrum’s acid (2; 1 mmol, 144 mg), and the mixture was stirred for 3 h at ambient temperature. The precipitate formed was isolated by filtration. 2,2-Dimethyl-5-[(4-oxo-4H-chromen-3-yl)methylene]-1,3-dioxane-4,6-dione (3a) Yellow powder. 1H NMR (300 MHz, DMSO-d 6): δ = 1.78 (s, 6 H, 2 CH3), 7.56 (t, 1 H, J = 7.6 Hz, HAr), 7.73 (d, 1 H, J = 8.4 Hz, HAr), 7.87 (t, 1 H, J = 7.5 Hz, HAr), 8.10 (d, 1 H, J = 7.5 Hz, HAr), 8.26 (s, 1 H, =CH), 9.31 [s, 1 H, (CO2)2C=CH]. 13C NMR (75 MHz, DMSO-d 6): δ = 27.0, 104.9, 117.9, 118.0, 118.7, 123.1, 125.7, 126.7, 135.1, 145.5, 155.1, 159.8, 162.0, 162.2, 173.3. General Procedure for 7 To a solution of isatoic anhydride (4; 1 mmol, 163 mg) in EtOH (4 mL) was added the primary amine, aryl hydrazine, or aryl hydrazide 5a–h (1 mmol), and the mixture was heated for 1 h at 70 °C. This mixture was used for the synthesis of 7a–n or 8a–d without purification. To a solution of product 6a–h (1 mmol) in EtOH (10 mL) was added product 3 (1 mmol), and methanesulfonic acid (20 mol%, 20 mg), and the mixture was heated for 12 h at 70 °C. The reaction reached completion as indicated by TLC (EtOAc–n-hexane, 1:3), and the precipitate was filtered. The precipitate was washed with MeOH, and the resulting powder was pure product 7a–n (yields 48–84%). 2-(4-Oxo-4H-chromen-3-yl)-3-phenethyl-2,3-dihydroquinazolin-4(1H)-one (7c) Yellow powder, 285 mg (72%), mp 228–230 °C. IR (KBr): ν = 3327, 1724, 1632 cm–1. 1H NMR (300 MHz, DMSO-d 6): δ = 2.88 (dt, 2 H, J = 15.0, 6.6 Hz, CH2Ph), 3.10–3.14 (m, 1 H, CHPh), 4.05–4.09 (m, 1 H, CHN), 5.97 (s, 1 H, CH), 6.68 (t, 1 H, J = 7.1 Hz, HAr), 6.75 (d, 1 H, J = 7.9 Hz, HAr), 6.92 (s, 1 H, NH), 7.16 (d, 1 H, J = 6.6 Hz, HAr), 7.19–7.23 (m, 5 H, HAr), 7.45 (t, 1 H, J = 7.2 Hz, HAr), 7.53 (d, 1 H, J = 6.6 Hz, HAr), 7.68–7.77 (m, 2 H, HAr), 7.97 (s, 1 H, =CH), 8.04 (d, 1 H, J = 7.6 Hz, HAr). 13C NMR (75 MHz, DMSO-d 6): δ = 33.8, 46.2, 64.3, 114.8, 114.9, 117.5, 118.4, 121.4, 123.1, 124.9, 125.7, 126.1, 127.4, 128.3, 128.7, 133.1, 134.5, 138.9, 146.0, 153.2, 155.7, 162.1, 176.1. ESI-HRMS: m/z calcd for C25H21N2O3 [M + H]+: 397.1545; found: 397.1545. Colorless crystal (polyhedron), dimensions 0.270 × 0.150 × 0.130 mm3, crystal system monoclinic, space group C2/c, Z = 8, a = 21.6199(9) Å, b = 15.8126(7) Å, c = 12.0816(5) Å, α = 90°, β = 95.9595(18)°, γ = 90°, V = 4108.0(3) Å3, ρ = 1.282 g cm–3, T = 200(2) K, θmax = 25.661°, radiation Mo Kα, λ = 0.71073 Å, 0.5° ω scans with CCD area detector, covering the asymmetric unit in reciprocal space with a mean redundancy of 4.29 and a completeness of 98.6% to a resolution of 0.83 Å, 17018 reflections measured, 3847 unique [R(int) = 0.0280], 2992 observed [I > 2σ(I)], intensities were corrected for Lorentz and polarization effects, an empirical absorption correction was applied using SADABS based on the Laue symmetry of the reciprocal space, μ = 0.09 mm–1, Tmin = 0.89, Tmax = 0.96, structure refined against F2 with a full-matrix least-squares algorithm using the SHELXL (Version 2014-3) software, 275 parameters refined, hydrogen atoms were treated using appropriate riding models, except H6 at N6, which was refined isotropically, goodness of fit 1.03 for observed reflections, final residual values R1(F) = 0.038, wR(F 2) = 0.090 for observed reflections, residual electron density –0.17 to 0.18 eÅ–3. CCDC 1057685 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif. General Procedure for the Synthesis of 8 To a solution of chromonyl Meldrum’s acid (3, 1 mmol) in EtOH (10 mL) was added product 6 (1 mmol) and K2CO3 (30 mol%, 50 mg), and the mixture was heated at 70 °C for 12 h, monitoring progress of reaction by TLC (eluent: EtOAc–n-hexane, 1:3). The EtOH was removed under vacuum, and further purification was carried out using preparative TLC (n-hexane–EtOAc, 2:1). The products were obtained as yellow oils. N-Benzyl-2-[5-(2-hydroxybenzoyl)-2-oxopyridin-1(2H)-yl]benzamide (8b) Yellow oil; 314 mg (74%). IR (KBr): ν = 3263, 1677, 1658 cm–1. 1H NMR (300 MHz, DMSO-d 6): δ = 4.31 (dd, 1 H, J = 15.0, 8.0 Hz, CH2), 4.35 (dd, 1 H, J = 15.0, 6.0 Hz, CH2), 6.53 (d, 1 H, J = 9.5 Hz, HAr), 6.88 (t, 1 H, J = 9.5 Hz, HAr), 6.94 (d, 1 H, J = 7.8 Hz, HAr), 7.18–7.30 (m, 5 H, HAr), 7.35 (t, 1 H, J = 7.4 Hz, HAr), 7.44 (d, 1 H, J = 7.4 Hz, HAr), 7.55–7.67 (m, 3 H, HAr), 7.85 (d, 1 H, J = 2.5 Hz, HAr), 7.89 (dd, 1 H, J = 8.7, 2.5 Hz, HAr), 9.00 (t, 1 H, J = 5.9 Hz, NH), 10.29 (s, 1 H, OH). 13C NMR (75 MHz, DMSO-d 6): δ = 54.9, 116.3, 116.6, 116.7, 119.2, 119.4, 124.4, 124.5, 126.7, 127.0, 128.2, 128.4, 129.3, 129.9, 131.2, 132.8, 134.2, 138.1, 139.1, 139.2, 146.4, 155.8, 156.0, 161.3, 165.9, 191.6. ESI-MS: m/z = 425.0 [M + H]+. Anal. Calcd. for C26H20N2O4: C, 73.57; H, 4.75; N, 6.60. Found: C, 73.49; H, 4.79; N, 6.64.