Convenient Synthesis of Pyrazolo[4′,3′:5,6]pyrano[4,3-c][1,2]oxazoles via Intramolecular Nitrile Oxide Cycloaddition

Abstract

A simple and efficient synthetic route to the novel 3a,4-dihydro-3H,7H- and 4H,7H-pyrazolo[4′,3′:5,6]pyrano[4,3-c][1,2]oxazole ring systems from 3-(prop-2-en-1-yloxy)- or 3-(prop-2-yn-1-yloxy)-1H-pyrazole-4-carbaldehyde oximes has been developed by employing the intramolecular nitrile oxide cycloaddition (INOC) reaction as the key step. The configuration of intermediate aldoximes was unambiguously determined using NOESY experimental data and comparison of the magnitudes of 1JCH coupling constants of the iminyl moiety, which were greater by approximately 13 Hz for the predominant syn isomer. The structures of the obtained heterocyclic products were confirmed by detailed 1H, 13C and 15N NMR spectroscopic experiments and HRMS measurements.

Synthesis and Characterization of Novel Heterocyclic Chalcones from 1-Phenyl-1H-pyrazol-3-ol

“…As expected, the 1 H, 13 C and 15 N NMR chemical shifts and the relevant correlations in the two-dimensional NMR spectra of these two isomeric 1,2-oxazoles were highly similar. The unambiguous formation of 1,2-oxazole (isoxazole) moiety was easily deduced from 1 H-15 N HMBC spectral data, as it clearly showed a distinct longrange correlation between the isoxazole methine 4′-H proton and nitrogen N-2′, which resonated at δ −18.6 and −19.6 ppm for compounds 15 and 14, respectively, and this is in good agreement with the data reported in the literature [69]. The 2 Hz optimized 1 H- 15 N HMBC spectra hinted in favor of these structures.…”

Special Issue “Recent Advances in the Synthesis, Functionalization and Applications of Pyrazole-Type Compounds II”

“…Pyrazolo [4 ,3 :5,6]pyrano [4,3-c] [1,2]oxazoles with various substituents at C-3 or C-7 were synthetized. Through extensive NMR spectroscopic studies carried out using standard and advanced methods, the authors unambiguously confirmed the predomination of the syn-isomer of intermediate aldoximes [9]. Bearing in mind the remarkable biological activities of both pyrazole and thiazole scaffolds, Y. N. Mabkhot and coworkers developed a convenient synthesis of novel pyrazolo [5,1-b]thiazole-based heterocycles.…”

Pyrazole-based lamellarin O analogues: synthesis, biological evaluation and structure–activity relationships

“…[29][30][31] Replacement of the central pyrrole to pyrazole is expected to change e.g., the energy of the highest occupied molecular orbital (HOMO) which is associated with increased metabolic stability. 32 In continuation of our previous works devoted to synthesis and investigation of pyrazole derivatives, [33][34][35][36][37][38][39][40][41] in this study we ought to synthesize and investigate various functionalized pyrazole derivatives of lamellarin O. The goal was based on the scaffold hopping of the pyrrole ring in natural lamellarin O to its pyrazole counterpart.…”

“…In continuation of our previous works devoted to synthesis and investigation of pyrazole derivatives, 33–41 in this study we ought to synthesize and investigate various functionalized pyrazole derivatives of lamellarin O. The goal was based on the scaffold hopping of the pyrrole ring in natural lamellarin O to its pyrazole counterpart.…”