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Synlett 2016; 27(03): 465-470
DOI: 10.1055/s-0035-1560829
DOI: 10.1055/s-0035-1560829
letter
Actions of Bisnucleophiles on (E)-3-[3-(2-Hydroxyaryl)-3-oxoprop-1-en-1-yl]chromones: Versatile Transformations into Oxygen- and Nitrogen-Containing Heterocycles
Further Information
Publication History
Received: 11 August 2015
Accepted after revision: 04 October 2015
Publication Date:
05 November 2015 (online)
![](https://www.thieme-connect.de/media/synlett/201603/lookinside/thumbnails/st-2015-d0631-l_10-1055_s-0035-1560829-1.jpg)
Abstract
The transformations of (E)-3-[3-(2-hydroxyaryl)-3-oxoprop-1-en-1-yl]chromones in the presence of methylhydrazine and aromatic bisnucleophiles are described. The reactions generally lead to chromone ring transformation via pyrone ring-opening and heterocyclization to give novel diazoles and (Z)-3-aminomethylenechromanones, respectively. Piperazine catalyzes chromanone ring closure of the starting substrate to afford chromone–chromanone dyads.
Key words
chromones - α,β-unsaturated carbonyl systems - Michael additions - bisnucleophiles - X-ray diffraction - heterocycles - 2D NMRSupporting Information
- Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0035-1560829.
- Supporting Information
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References and Notes
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- 18 Transformations of (E)-3-[3-(2-Hydroxyaryl)-3-oxoprop-1-en-1-yl]chromones 1a,b; General procedure Methylhydrazine, phenylenediamine, 2-aminophenol or piperazine (2 mmol) was added to a stirred solution of (E)-3-[3-(2-hydroxyaryl)-3-oxoprop-1-en-1-yl]chromone 1a,b (1 mmol) in THF (20 mL) at r.t., and the resulting mixture was allowed to stir overnight. After removal of the solvent under reduced pressure, the obtained resinous material was subjected to column chromatography. The product was recrystallized from a mixture of hexane–dichloromethane (1:1) by slow evaporation of the solvent at 6 °C to afford 2a,b, 3aa,ab or 4a,b. Good-quality single crystals suitable for X-ray analysis were only obtained for products 2a, 3aa and 4a,b.
- 19 2,2′-(1′,2-Dimethyl-3,4-dihydro-1′H,2H-[3,4′-bispyrazole]-3′,5-diyl)diphenol (2a) Yield: 0.20 g (57%); M r = 348.41 g/mol; colorless crystals; mp 205–206 °C. 1H NMR (300 MHz, CDCl3): δ = 2.88 (s, 3 H, 1-N-CH 3), 2.98 (dd, J = 18.0, 14.0 Hz, 1 H, H-4[A]), 3.69 (dd, J = 18.0, 10.0 Hz, 1 H, H-4[M]), 3.95 (s, 3 H, 1′-N-CH 3), 4.40 (dd, J = 14.0, 10.0 Hz, 1 H, H-3[X]), 6.83–6.94 (m, 2 H, H-5′′, H-5′′′), 6.97–7.14 (m, 3 H, H-3′′, H-3′′′, H-6′′), 7.20–7.28 (m, 2 H, H-4′′, H-4′′′), 7.47 (dd, J = 7.8, 1.6 Hz, 1 H, H-6′′′), 7.61 (s, 1 H, H-5′), 10.73 (s, 1 H, 2′′′-OH), 10.97 (s, 1 H, 2′′-OH). 13C NMR (75 MHz, CDCl3): δ = 39.1 (1′-N-CH3), 42.1 and 42.2 (1-N-CH3 and C-4), 63.8 (C-3), 116.1 (C-1′′), 116.5 (C-3′′), 117.2 (C-1′′′), 117.3 (C-3′′′), 118.3 (C-4′), 119.1 (C-5′′), 119.2 (C-5′′′), 127.2 (C-6′′), 127.3 (C-6′′′), 129.1 (C-4′′), 130.4 (C-4′′′), 130.5 (C-5′), 147.9 (C-3′), 153.1 (C-5), 155.7 (C-2′′′), 157.6 (C-2′′). HRMS (ESI): m/z [M + H]+ calcd for C20H21N4O2: 349.1665; found: 349.1668.
- 20 2-[3′-(2-Hydroxyphenyl)-1′,2-dimethyl-3,4-dihydro-1′H,2H-[3,4′-bispyrazol]-5-yl]-4-methoxyphenol (2b) Yield: 0.19 g (50%); M r = 378.43 g/mol; white solid; mp 182–183 °C. 1H NMR (300 MHz, CDCl3): δ = 2.87 (s, 3 H, 1-N-CH 3), 2.97 (dd, J = 18.0, 14.0 Hz, 1 H, H-4[A]), 3.65 (dd, J = 18.0, 10.0 Hz, 1 H, H-4[M]), 3.74 (s, 3 H, 5′′-OCH 3), 3.95 (s, 3 H, 1′-N-CH 3), 4.42 (dd, J = 14.0, 10.0 Hz, 1 H, H-3[X]), 6.62 (d, J = 2.9 Hz, 1 H, H-6′′), 6.81–6.95 (m, 3 H, H-4′′, H-3′′, H-5′′′), 7.06 (dd, J = 8.2, 1.2 Hz, 1 H, H-3′′′), 7.20–7.27 (m, 1 H, H-4′′′), 7.47 (dd, J = 7.8, 1.6 Hz, 1 H, H-6′′′), 7.61 (s, 1 H, H-5′), 10.56 (br s, 2 H, 2′′′-OH and 2′′-OH). 13C NMR (75 MHz, CDCl3): δ = 39.2 (1′-N-CH3), 42.1 and 42.3 (1-N-CH3 and C-4), 55.9 (5′′-O-CH3), 63.9 (C-3), 112.2 (C-6′′), 116.3 (C-4′′), 117.1 (C-3′′), 117.3 (C-1′′′), 117.4 (C-3′′′), 118.4 (C-5′′′), 119.4 (C-4′), 127.3 (C-6′′′), 129.2 (C-4′′′), 130.7 (C-5′), 148.0 (C-3′), 151.9 (C-5′′), 152.3 (C-1′′), 152.9 (C-5), 155.8 and 156.0 (C-2′′ and C-2′′′). HRMS (ESI): m/z [M + Na]+ calcd for C21H22N4O3Na: 401.1590; found: 401.1581.
- 21 (Z)-3-{[(2-Aminophenyl)amino]methylene}-2-[2-(2-hydroxyphenyl)-2-oxoethyl]chroman-4-one (3aa) Yield: 0.27 g (68%), M r = 400.43 g/mol; orange crystals; mp 140–141 °C. 1H NMR (300 MHz, CDCl3): δ = 3.43 (dd, J = 16.4, 7.0 Hz, 1 H, H-1′[AB]), 3.69 (dd, J = 16.4, 6.2 Hz, 1 H, H-1′[AB]), 3.70 (s, 2 H, 2′′′′-NH 2), 5.73 (dd, J = 7.0, 6.2 Hz, 1 H, H-2[X]), 6.76–6.91 (m, 4 H, H-5′′′, H-3′′′, H-4′′′′, H-6′′′′), 6.93–7.12 (m, 4 H, H-8, H-6, H-3′′′′, H-5′′′′), 7.38–7.54 (m, 4 H, H-7, H-4′′′, H-1′′, H-6′′′), 7.97 (dd, J = 7.7, 1.3 Hz, 1 H, H-5), 11.80 (d, J = 12.0 Hz, 1 H, 1′′-NH), 12.18 (s, 1 H, 2′′′-OH). 13C NMR (75 MHz, CDCl3): δ = 44.3 (C-1′), 75.3 (C-2), 103.8 (C-3), 117.4 (C-3′′′′), 117.9 (C-6′′′′), 118.1 (C-4′′′′), 118.6 (C-8), 119.1 (C-5′′′), 119.5 (C-1′′′), 120.1 (C-3′′′), 121.9 (C-6), 122.8 (C-10), 125.6 (C-5′′′′), 126.5 (C-5), 128.2 (C-1′′′′), 130.1 (C-6′′′), 134.6 (C-7), 136.9 (C-4′′′), 137.2 (C-2′′′′), 144.5 (C-1′′), 157.3 (C-9), 162.6 (C-2′′′), 181.6 (C-4), 203.3 (C-2′). HRMS (ESI): m/z [M + Na]+ calcd for C24H20N2O4Na: 423.1321; found: 423.1318.
- 22 (Z)-2-[2-(2-Hydroxyphenyl)-2-oxoethyl]-3-{[(2-hydroxyphenyl)amino]methylene}chroman-4-one (3ab) Yield: 0.27 g (76%); M r = 401.41 g/mol; yellow solid; mp 140–141 °C. 1H NMR (300 MHz, CDCl3): δ = 3.38 (dd, J = 16.2, 6.6 Hz, 1 H, H-1′[AB]), 3.71 (dd, J = 16.2, 6.6 Hz, 1 H, H-1′[AB]), 5.74 (t, J = 6.6 Hz, 1 H, H-2[X]), 6.75–6.99 (m, 6 H, H-4′′′′, H-6′′′′, H-5′′′′, H-3′′′, H-5′′′, H-8), 7.03–7.17 (m, 2 H, H-6, H-3′′′′), 7.35–7.57 (m, 4 H, H-7, H-4′′′, H-6′′′, H-1′′), 8.01 (dd, J = 7.8, 1.7 Hz, 1 H, H-5), 11.99 (d, J = 12.0 Hz, 1 H, 1′′-NH), 12.11 (s, 1 H, 2′′′-OH). 13C NMR (75 MHz, CDCl3): δ = 44.4 (C-1′), 75.6 (C-2), 103.9 (C-3), 114.6 (C-3′′′′), 116.2 (C-6′′′′), 118.1 (C-4′′′′), 118.6 (C-8), 119.0 (C-5′′′), 119.6 (C-1′′′), 121.3 (C-3′′′), 121.8 (C-6), 122.9 (C-10), 124.3 (C-5′′′′), 126.6 (C-5), 128.5 (C-1′′′′), 130.1 (C-6′′′), 134.5 (C-7), 136.7 (C-4′′′), 141.8 (C-1′′), 145.5 (C-2′′′′), 157.5 (C-9), 162.7 (C-2′′′), 181.4 (C-4), 203.2 (C-2′). HRMS (ESI): m/z [M + Na]+ calcd for C24H19NO5Na: 424.1161; found: 424.1131.
- 23 3-(4-Oxochroman-2-yl)-4H-chromen-4-one (4a) Yield: 0.18 g (61%); M r = 292.29 g/mol; colorless crystals; mp 195–196 °C. 1H NMR (300 MHz, CDCl3): δ = 2.89 (dd, J = 16.9, 13.0 Hz, 1 H, H-3′[AB]), 3.25 (dd, J = 16.9, 3.0 Hz, 1 H, H-3′[AB]), 5.72 (ddd, J = 13.0, 3.0, 1.0 Hz, 1 H, H-2′[X]), 7.02–7.13 (m, 2 H, H-8′, H-6′), 7.40–7.57 (m, 3 H, H-6, H-8, H-7′), 7.72 (ddd, J = 8.7, 7.1, 1.7 Hz, 1 H, H-7), 7.95 (ddd, J = 8.6, 4.9, 3.6 Hz, 1 H, H-5′), 8.20–8.28 (m, 1 H, H-5), 8.24 (d, J = 1.0 Hz, 1 H, H-2). 13C NMR (75 MHz, CDCl3): δ = 42.8 (C-3′), 73.0 (C-2′), 117.9 (C-8′), 118.2 (C-8), 121.1 (C-10′), 122.0 (C-6′), 122.9 (C-3), 123.8 (C-10), 125.5 (C-6), 125.9 (C-5), 127.3 (C-5′), 134.1 (C-7), 136.1 (C-7′), 153.3 (C-2), 156.3 (C-9), 161.2 (C-9′), 175.7 (C-4), 191.3 (C-4′). HRMS (ESI): m/z [M + Na]+ calcd for C18H12O4Na: 315.0633; found: 315.0636.
- 24 3-(6-Methoxy-4-oxochroman-2-yl)-4H-chromen-4-one (4b) Yield: 0.14 g (43%); M r = 322.31 g/mol; colorless crystals; mp 195–196 °C. 1H NMR (300 MHz, CDCl3): δ = 2.85 (dd, J = 17.0, 13.1 Hz, 1 H, H-3′[AB]), 3.24 (dd, J = 17.0, 2.9 Hz, 1 H, H-3′[AB]), 3.83 (s, 3 H, 6′-OCH 3), 5.67 (ddd, J = 13.1, 2.9, 1.0 Hz, 1 H, H-2′[X]), 7.00 (d, J = 9.0 Hz, 1 H, H-8′), 7.13 (dd, J = 9.0, 3.2 Hz, 1 H, H-7′), 7.37 (d, J = 3.1 Hz, 1 H, H-5′), 7.40–7.52 (m, 2 H, H-6, H-8), 7.72 (ddd, J = 8.6, 7.2, 1.7 Hz, 1 H, H-7), 8.21–8.28 (m, 1 H, H-5), 8.24 (d, J = 1.0 Hz, 1 H, H-2). 13C NMR (75 MHz, CDCl3): δ = 42.7 (C-3′), 55.8 (6′-OCH3) 73.1 (C-2′), 107.6 (C-5′), 118.2 (C-8), 119.2 (C-8′), 121.0 (C-10′), 123.0 (C-3), 123.8 (C-10), 125.2 (C-7′), 125.5 (C-6), 125.9 (C-5), 134.0 (C-7), 153.3 (C-2), 154.5 (C-6′), 155.8 (C-9′), 156.3 (C-9), 175.7 (C-4), 191.5 (C-4′). HRMS (ESI): m/z [M + Na]+ calcd for C19H14O5Na: 345.0739; found: 345.0748.
- 25 Crystal data for compound 2a (CCDC 1404991): C20H20N4O2, M = 348.40, triclinic, space group Pī, Z = 2, a = 8.7610(13) Å, b = 9.9194(16) Å, c = 11.871(2) Å, α = 66.580(7)°, β = 70.069(7)°, γ = 74.993(7)°, V = 880.8(3) Å3, μ(Mo-Kα) = 0.088 mm–1, D c = 1.314 g cm–3, colorless block, crystal size = 0.22 × 0.16 × 0.10 mm3. Of a total of 19322 reflections collected, 4753 were independent (R int = 0.0413). Final R1 = 0.0467 [I > 2σ(I)] and wR2 = 0.1267 (all data). Data completeness to θ = 25.24°, 99.9%.
- 26 Crystal data for compound 3aa (CCDC 1404990): C24H20N2O4, M = 400.42, monoclinic, space group P21/n, Z = 4, a = 14.9755(11) Å, b = 4.7510(3) Å, c = 26.6395(16) Å, β = 93.664(5)°, V = 1891.5(2) Å3, μ(Mo-Kα) = 0.097 mm–1, D c = 1.406 g cm–3, orange plate, crystal size of 0.22 × 0.12 × 0.03 mm3. Of a total of 15482 reflections collected, 4999 were independent (R int = 0.0475). Final R1 = 0.0505 [I > 2σ(I)] and wR2 = 0.1233 (all data). Data completeness to θ = 25.24°, 99.6%.
- 27 Crystal data for compound 4b (CCDC 1404989): C19H14O5, M = 322.30, triclinic, space group Pī, Z = 2, a = 8.4108(9) Å, b = 8.5434(9) Å, c = 10.6878(11) Å, α = 83.293(3)°, β = 72.084(3)°, γ = 82.141(3)°, V = 721.61(13) Å3, μ(Mo-Kα) = 0.108 mm–1, D c = 1.483 g cm–3, colorless plate, crystal size of 0.16 × 0.12 × 0.07 mm3. Of a total of 13854 reflections collected, 2640 were independent (R int = 0.0256). Final R1 = 0.0553 [I > 2σ(I)] and wR2 = 0.1356 (all data). Data completeness to θ = 25.24°, 99.6%.