Synthesis of 4‐Hetarylisoxazoles from Amino Acid‐Derived Halogenoximes and Push‐Pull Enamines

Abstract

An approach to 4‐hetarylisoxazole‐derived amines and other related 3,4‐disubstituted isoxazoles which relies on [3+2] cycloaddition of amino acid‐derived halogenoximes and push‐pull enamines is described. The target products are obtained at gram scale in up to 81 % overall yield. The efficiency of the method is affected by the electronic properties of the enamine component at the key step.

Organocatalyzed Three-Component Synthesis of Isoxazol-5(4H)-ones under Aqueous Conditions

“…1 H NMR (300 MHz, DMSO-d6): δ 1.38 (t, J = 6.9 Hz, 3H, CH3), 2.27 (s, 3H, CH3), 4.42 (q, J = 6.9 Hz, 2H, OCH2), 7.12 (d, J = 9.0 Hz, 2H, Ar-H), 7.82 (s, 1H, H-vinyl), 8.51 (d, J = 8.7 Hz, 2H, Ar-H); 13 C NMR (75 MHz, DMSO-d6) δ 11.7, 14.9, 64.4, 115.4, 126.1, 137.4, 151.6, 162.7, 164.1, 169.1. 4-(4-Ethylbenzylidene)-3-methylisoxazol-5(4H)-one (4d). 1 H NMR (300 MHz, DMSO-d6): δ 1.23 (t, J = 7.5, 3H, CH3), 2.30 (s, 3H, CH3), 2.72 (q, J = 7.5 Hz, 2H, CH2-), 7.45 (d, J = 8.1 Hz, 2H, Ar-H), 7.93 (s, 1H, H-vinyl), 8.39 (d, J = 8.1 Hz, 2H, Ar-H); 13 C NMR (75 MHz, DMSO-d6): δ 11. 8,15.4,28.9,118.1,128.9,130.8,134.5,151.6,152.1,162.7,168.5;Anal.…”

“…. 1 H NMR (300 MHz, DMSO-d6): δ 1.39 (t, J = 6.9, 3H, CH3), 2.22 (s, 3H, CH3), 4.09 (q, J = 6.6 Hz, 2H, CH2-), 6.95 (d, J = 7.2, 2H, Ar-H), 7.82 (d, J = 8.4, 2H), 7.66 (s, 1H, H-vinyl), 7.81 (d, J = 8.4, 2H, Ar-H), 8.47 (s,1H, Ar-H), 10.66 (s, 1H, OH); 13 C NMR (75 MHz, DMSO-d6): δ 11.6, 14.9, 64.3, 114.0, 116.2, 118.0, 125.5, 131.9, 147.1, 152.1, 154.5, 162.6, 169.4. 8, 56.5, 60.9, 112.5, 117.6, 128.4, 143.4, 152.2, 152.9, 162.7, 168.9.…”

“…. 1 H NMR (300 MHz, DMSO-d6): δ 2.39 (s, 3H, CH3), 8.12 (s, 1H, ArCH═), 9.51 (s, 1H, H of indole ring), 7.30-7.36 (m, 2H, Ar-H), 7.58-7.63 (m, 2H, Ar-H), 12.80 (s, N-H); 13 C NMR (75 MHz,109.3,113.1,113.6,119.2,123.0,124.4,128.4,136.8,138.9,140.8,162.1,170.8.…”

“…. 1 H NMR (300 MHz, DMSO-d6): δ 2.25 (s, 3H, CH3), 7. 4H,2H,7.82 (dd,J = 3.6,11.4 Hz,1H,8.15 (dd,J = 3.6,11.7 Hz,1H,.…”

“…1 Derivatives of this attractive five-membered heterocyclic ring are found in various natural and medicinal products. 1 Isoxazol-5(4H)-ones, on the other hand, have widely been shown antibacterial, antifungal, androgen receptor antagonist, tyrosinase inhibitory, SIRT1 inhibitory, anti-obesity, anti-HIV, antioxidant, anticancer, fungicide and insecticide properties activities. 2 As reported, the compounds have been studied in photovoltaic cells, 3 monochromatic terahertz difference frequency, 4 and laser dyes.…”