A Mild and Efficient Synthesis of Novel Isoxazolyl‐Benzo[d]Pyrazino[2,1‐b] [1,3]Oxazoles

Abstract

Synthesis of novel 2‐3‐methyl‐5‐[(E)‐2‐aryl‐1‐ethenyl]‐4‐isoxazolyl‐4,10a‐diaryl‐1,10a‐dihydro‐2H‐benzo[d]pyrazino[2,1‐b][1,3]oxazoles 5 were simply achieved by the reaction of 2‐[3‐methyl‐5‐[(E)‐2‐aryl‐1‐ethenyl]‐4‐isoxazolyl(2‐oxo‐2‐arylethyl)amino]‐1‐aryl‐1‐ethanones 3 with o‐aminophenol 4 in the presence of CAN catalyst. The intermediates, 2‐[3‐methyl‐5‐[(E)‐2‐aryl‐1‐ethenyl]‐4‐isoxazolyl(2‐oxo‐2‐arylethyl)amino]‐1‐aryl‐1‐ethanones 3, were prepared by the reaction of 4‐amino‐3‐methyl‐5‐styrylisoxazole 1, with phenacylbromides 2 in ethanol in the presence of K2CO3. The structures of the newly synthesized compounds 3a, 3b, 3c, 3d, 3e, 3f, 3g, 3h, 3i, 3j, 3k, 3l and 5a, 5b, 5c, 5d, 5e, 5f, 5g, 5h, 5i, 5j, 5k, 5l have been confirmed by analytical and spectral data.

A Green Protocol for One‐Pot Pseudo Five‐Component Synthesis of a New Series of Bis‐Betti Bases Via Mannich‐Type Reaction

“…Decreasing (5 mol %) or increasing (15 and 20 mol %) the ratio of p-TSA at 90 °C under solvent-free conditions did not improve the product yield (Table 1, entries 10-12). When the reaction mixture was examined in the presence of various catalysts such as formic acid and guanidine hydrochloride at 90 °C under solvent-free conditions for 1.5 h, the product 4 a was furnished in 58 and 71 % yields, respectively (Table 1, entries [13][14]. Therefore, the entry 7 of Table 1 offered the optimum reaction condition for the one-pot synthesis of bis-Betti base derivative 4 a under solvent free conditions.…”

“…Characterization data of all compounds, FT-IR, 1 H-NMR, 13 C-NMR spectra and Mass data of the products can be found in the Supporting Information.…”

“…The synthetic routes for the synthesis of this scaffold have been reviewed. [5][6][7][8] Moreover, bis-aminomethylnaphthols (bis-Betti bases) have been synthesized using by the reaction of various types of dihydroxynaphthalens such as 2,6-dihydroxynaphthalene and 2,3-dihydroxynaphthalene with aldehydes and amines, [9][10][11][12][13] the reaction of diamines such as 2,6-diaminopyridine, piperazine and p-phenylenediamine with naphthols and aldehydes, [14][15] and the reaction of dialdehydes such as terephthaldehyde and isophthalaldehyde with naphthols and amines [16][17] and reduction of bisdihydrooxazine structures. [18] The Betti reaction produces racemic and nonracemic aminoalkylnaphthol ligands.…”

Synthesis, Characterization, and Anti‐inflammatory Activity of Novel Isoxazolyl‐4‐(2‐oxo‐2,3‐dihydro‐1H‐3‐indolyl)pyrrole‐3‐carboxylates

“…Based on the significance of pharmacological profile of isoxazole derivatives, and as a sequel to our work on the synthesis of biologically important isoxazolyl heterocycles with potent anticancer activity, we herein, describe the green route for synthesis of novel isoxazolyl‐4‐(2‐oxo‐2,3‐dihydro‐1 H ‐3‐indolyl)pyrrole‐3‐carboxylates.…”