Quinoxalines XV. Convenient Synthesis and Structural Study of Pyrazolo[1,5-a]quinoxalines

Abstract

A series of aryloxymethylquinoxaline oximes, hitherto unknown and synthesized from the corresponding aldehydes, afforded in only one step pyrazolo[1,5-a]quinoxalines in the presence of acetic anhydride at high temperatures. A formal [3,5]-sigmatropic rearrangement was proposed as the mechanistic rationale for this unprecedented transformation. Saponification with potassium hydroxide furnished the free phenol derivatives which were studied by NMR spectroscopy and accompanying theoretical DFT calculations, establishing intramolecular hydrogen bonding and the spatial magnetic properties. Additionally, mass spectrometric fragmentation was investigated by B/E-linked scans and collision-induced dissociation experiments. The fragmentation pattern devoted a new gas phase rearrangement process, which proved to be unique and characteristic for pyrazolo[1,5-a]quinoxalines.

Quantification and Visualization of the Anisotropy Effect in NMR Spectroscopy by Through-Space NMR Shieldings

“…Further was our approach [1] employed to quantify the electronic structure of ring-closed push-pull allenes [88]: besides polar and carbene-like also carbone-like canonical structures could be identified. And, when studying the local aromaticity of pyrazolo[1,5-a]quinoxalines with the same approach [1], the preferred conjugation via the NdN]C link and much less via the N]CdC]CdC connection could be readily identified [89].…”

Spatial magnetic properties subject to lone pair and π electron delocalization in benzenoid and quinoid structures. Are quinoid tautomers really nonaromatic?

“…Thus, TSNMRS not only help to identify aromaticity, but also to visualize the size of the extended conjugation in such systems as well. In consideration of the results so far, it can be ascertained that comparable stability of nonaromatic, quinoid tautomers results from remarkable extended π conjugation 49 and intramolecular hydrogen bonding. On the other hand, both effects operate independently-the spatial magnetic properties of the enol form 4b do not change without the intramolecular hydrogen bonding in 4c (Figure 4) which is of substantial magnitude with respect to the stability of this tautomer.…”

Oximes of six-membered heterocyclic compounds with two and three heteroatoms. II.* Reactions and biological activity (review)

“…As a result of an intramolecular Diels-Alder reaction 1,2,4-triazine ketoxime 56 is converted into the oxime derivative benzo[b]furo[2,3-b]pyrazine 57 [30]. The 1H-pyrazolo[3,4-b]quinazoline system 59 is obtained (with yields of 62-86%) from the quinoxaline oximes 58 and hydrazine derivatives in an acidic medium [79,80]. Cyclization of the oximes 60 in acetic anhydride in the presence of sodium acetate leads to pyrazolo[1,5-a]quinoxalines 61 with yields of 41-58% [80].…”

“…The 1H-pyrazolo[3,4-b]quinazoline system 59 is obtained (with yields of 62-86%) from the quinoxaline oximes 58 and hydrazine derivatives in an acidic medium [79,80]. Cyclization of the oximes 60 in acetic anhydride in the presence of sodium acetate leads to pyrazolo[1,5-a]quinoxalines 61 with yields of 41-58% [80]. …”