Síntesis de derivados de flavonoides y cromonas y exploración de nuevas aplicaciones de la química de radicales para la síntesis de compuestos heterocíclicos nitrogenados

Abstract

In this work, different methodologies for the preparation of oxime derivatives of flavonoids and chromones by reacting the latter with hydroxylamines were evaluated: O- (2-bromo-allyl) hydroxylamine [2] and O- (2-bromobenzyl) hydroxylamine [3] , which were prepared following the protocol Gabriel synthesis (15, 16). Different methodologies were designed to synthesize tested oxime ethers from the reaction of nitrogen of hydroxylamine with carbon in position 4 of the core-benzo-pyrone  flavone and chromone. Based on the methodologies described above various reaction conditions, the formation of an intermediate dichlorinated for subsequent conversion to oxime using dry solvents with bases at reflux or using bases in heating in an oil bath were evaluated, obtaining best results when using dry pyridine in an oil bath at 140 ° C and hydroxylamines in the form of hydrochlorides, with a short duration and with better yields than those reported. Using this methodology oxime ethers they were obtained: 2-phenyl-4H-chromen-4-O-methyl oxime [10a], 2-phenyl-4H-chromen-4-O-benzyl oxime [the 9th], 2-phenyl- 4H-chromen-4-O- (2-bromo-allyl) oxime [4a] and 2-phenyl-4H-chromen-4-O- (2-bromobenzyl) oxime [the 5th] with yields of 54%, 70%, 72% and 74% respectively, which were monitored by gas chromatography-mass spectrometry (GC-MS) and characterized by nuclear magnetic resonance (NMR) hydrogen (1 H) and carbon (APT) and also by two-dimensional experiments such as COSY 1H -1 H (proton-proton correlation), HSQC (heteronuclear single quantum correlation) and HMBC (heteronuclear multiple bond correlation). Importantly, the compounds 2, 3, 4a and 5a are not reported in the literature, being new compounds synthesized in high yields.