Catalyst-Free Synthesis of N-(1,7-Dioxotetrahydropyrazolo[1,2-a]pyrazol-2-yl)benzamide Derivatives by 1,3-Dipolar Cycloaddition and Rearrangement

Abstract

N-(1,7-Dioxotetrahydropyrazolo[1,2-a]pyrazol-2-yl)-benzamide derivatives, a novel class of compounds, were synthesized by 1,3-dipolar cycloaddition of azomethine imines with azlactones and subsequent rearrangement. The reaction can be completed rapidly under mild conditions without a catalyst.

Key words

cycloadditions - azomethine imines - azlactones - heterocycles - bicyclic compounds

• References


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• 10 N-(1,7-Dioxotetrahydro-1H,5H-pyrazolo[1,2-a]pyrazol-2-yl)benzamides 3a–p; General Procedure Azomethine imine 1 (1.2 equiv, 0.24 mmol), azlactone 2 (0.2 mmol), and CH₂Cl₂ (0.5 mL) were added to a small tube containing a magnetic stirrer, and the mixture were stirred at r.t. for 2–6 h. The crude product was purified by column chromatography [silica gel, EtOAc–PE (1:1)]. N-(3,5-Dioxo-1,2-diphenyltetrahydro-1H,5H-pyrazolo[1,2-a]pyrazol-2-yl)benzamide (3a) White solid; yield: 74.8 mg (91%); mp 191–192 °C; IR (KBr): 3418, 3059, 2929, 2850, 1785, 1676, 1575, 1298, 918, 711 cm^–1; ¹H NMR (400 MHz, CDCl₃): δ = 7.48 (dd, J = 15.3, 7.2 Hz, 5 H), 7.41–7.34 (m, 8 H), 7.24–7.19 (m, 2 H), 6.71 (s, 1 H), 4.77 (s, 1 H), 3.41 (s, 1 H), 3.00–2.81 (m, 3 H); ¹³C NMR (101 MHz, CDCl₃): δ = 165.73, 165.00, 161.93, 135.68, 133.48, 131.83, 131.57, 131.03, 129.47, 128.90, 128.76, 128.71, 128.52, 127.38, 126.86, 126.57, 71.04, 50.17, 35.99; HRMS (ESI): m/z [M + Na]⁺ calcd for C₂₅H₂₁NaN₃O₃: 434.1475; found: 434.1468. N-[1-(4-Methoxyphenyl)-3,5-dioxo-2-phenyltetrahydro-1H,5H-pyrazolo[1,2-a]pyrazol-2-yl]benzamide (3b) White solid; yield: 61.5 mg (70%); mp 159–160 °C; IR (KBr): 3413, 3061, 2932, 1783, 1713, 1597, 1503, 1267, 1173, 1045, 916, 835, 716 cm^–1; ¹H NMR (400 MHz, CDCl₃): δ = 7.54 (d, J = 8.4 Hz, 2 H), 7.45 (t, J = 6.9 Hz, 3 H), 7.38–7.33 (m, 5 H), 7.13 (d, J = 8.7 Hz, 2 H), 6.87 (d, J = 8.8 Hz, 2 H), 6.75 (s, 1 H), 4.68 (s, 1 H), 3.78 (s, 3 H), 3.39 (s, 1 H), 2.99–2.84 (m, 3 H); ¹³C NMR (101 MHz, CDCl₃): δ = 190.77, 165.57, 165.10, 160.22, 135.65, 133.49, 131.91, 131.82, 128.68, 128.59, 128.52, 126.90, 126.56, 122.56, 114.28, 114.24, 70.86, 55.52, 55.02, 35.69; HRMS (ESI): m/z [M + Na]⁺ calcd for C₂₆H₂₃NaN₃O₄: 464.1581; found: 464.1573. N-[1-(4-Fluorophenyl)-3,5-dioxo-2-phenyltetrahydro-1H,5H-pyrazolo[1,2-a]pyrazol-2-yl]benzamide (3d) White solid; yield: 72.6 mg (85%); mp 195–196 °C; IR (KBr): 3414, 3074, 2922, 2851, 1796, 1714, 1644, 1515, 1292, 1222, 1034, 918, 706 cm^–1; ¹H NMR (400 MHz, CDCl₃): δ = 7.48 (dd, J = 18.5, 7.5 Hz, 5 H), 7.44–7.33 (m, 6 H), 7.25 (d, J = 3.1 Hz, 1 H), 7.05 (t, J = 8.5 Hz, 2 H), 6.67 (s, 1 H), 4.82 (s, 1 H), 3.35 (s, 1 H), 3.01–2.88 (m, 3 H); ¹³C NMR (101 MHz, CDCl₃): δ = 166.67, 165.88, 164.86, 164.39, 136.09, 133.29, 132.03, 129.33, 128.98, 128.93, 128.64, 128.53, 127.84, 127.25, 126.86, 126.41, 71.10, 35.71, 29.67; HRMS (ESI): m/z [M + Na]⁺ calcd for C₂₅H₂₀FN₃NaO₃: 452.1381; found: 452.1377. N-[1-(2-Furyl)-3,5-dioxo-2-phenyltetrahydro-1H,5H-pyrazolo[1,2-a]pyrazol-2-yl]benzamide (3l) White solid; yield: 55.2 mg (69%); mp 166–168 °C; IR (KBr): 3424, 2932, 1783, 1713, 1666, 1502, 1314, 904, 730 cm^–1; ¹H NMR (400 MHz, CDCl₃): δ = 7.83 (d, J = 7.1 Hz, 2 H), 7.48–7.31 (m, 10 H), 6.52 (dd, J = 3.2, 0.5 Hz, 1 H), 6.29 (dd, J = 3.3, 1.9 Hz, 1 H), 5.90 (s, 1 H), 3.39–3.34 (m, 1 H), 2.94 (ddd, J = 16.1, 10.9, 9.0 Hz, 1 H), 2.80–2.65 (m, 2 H); ¹³C NMR (101 MHz, CDCl₃): δ = 166.05, 165.50, 163.88, 147.86, 143.87, 135.51, 133.24, 131.71, 128.93, 128.74, 128.39, 126.79, 126.56, 113.92, 110.33, 69.23, 46.41, 35.05; HRMS (ESI): m/z [M + Na]⁺ calcd for C₂₃H₁₉NaN₃O₄: 424.1268; found: 424.1261. N-(1-Cyclohexyl-3,5-dioxo-2-phenyltetrahydro-1H,5H-pyrazolo[1,2-a]pyrazol-2-yl)benzamide (3m) White solid; yield: 35.5 mg (91%); mp 141–143 °C; IR (KBr): 3424, 2920, 1713, 1561, 1444, 1279, 1045, 815, 730 cm^–1; ¹H NMR (400 MHz, CDCl₃): δ = 7.80 (d, J = 7.1 Hz, 2 H), 7.65 (d, J = 7.3 Hz, 2 H), 7.55 (t, J = 8.0 Hz, 1 H), 7.44 (d, J = 12.3 Hz, 4 H), 7.37 (t, J = 6.7 Hz, 1 H), 6.70 (s, 1 H), 3.79 (t, J = 8.1 Hz, 1 H), 3.49 (d, J = 7.5 Hz, 1 H), 3.09 (dd, J = 14.8, 6.9 Hz, 1 H), 2.99–2.91 (m, 1 H), 2.71 (dd, J = 16.4, 6.3 Hz, 1 H), 1.99 (d, J = 11.9 Hz, 1 H), 1.79 (d, J = 16.9 Hz, 2 H), 1.66–1.54 (m, 3 H), 1.20–1.06 (m, 5 H); ¹³C NMR (101 MHz, CDCl₃): δ = 166.70, 165.12, 162.50, 138.27, 132.95, 132.24, 129.03, 128.88, 128.80, 127.11, 126.39, 76.06, 69.93, 56.20, 38.88, 35.96, 31.89, 29.89, 25.56; HRMS (ESI): m/z [M + Na]⁺ calcd for C₂₅H₂₇NaN₃O₃: 440.1945; found: 440.1950.

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