Rogelio Jiménez

Synthesis of demethylated nidulol via an intramolecular Michael reaction

An expeditious synthesis of 5,7-dihydroxy-6-methylphthalide from open-chain precursors is described. The key intermediates, synthons 3 and 4, were readily obtained from accessible materials and were further transformed to a common precursor, a five-membered lactone derivative, via an intramolecular Michael addition. Lactone 2 was aromatised to the phthalide system under basic conditions. The process thus constitutes a formal synthesis of the phthalide framework.

Intramolecular H-bonding interaction in angular 3-π-EWG substituted imidazo[1,2-a]pyridines contributes to conformational preference

BackgroundThe proton at position 5 of imidazo[1,2-a]pyridines substituted with an angular electron withdrawing group (EWG) at position 3, shows an unusual downfield chemical shift, which is usually explained in terms of a peri effect. However usage of this term is sometimes confusing. In this investigation, it is proposed that the aforementioned shift is in fact a combination of several factors: Anisotropy, long-distance mesomerism and an attractive intramolecular interaction of the electrostatic hydrogen bond type.ResultsTheoretical calculations were performed aimed to obtain evidence of the existence of an intramolecular non-bonding interaction between H-5 and the oxygen atom of the EWG. Results derived from conformational and vibrational analysis at the DFT B3LYP/6-311++G(d,p) level of theory, the determination of Bond Critical Points derived from AIM theory, and the measurement of some geometrical parameters, support the hypothesis that the higher stability of the prevailing conformation in these molecules (that in which the oxygen of the EWG is oriented towards H-5) has its origin in an intramolecular interaction.ConclusionComputational calculations predicted correctly the conformational preferences in angular 3-π-EWG-substituted imidazo[1,2-a]pyridines. The existence of an electrostatic hydrogen bond between H-5 and the oxygen atom of the π-EWG was supported by several parameters, including X-ray crystallography. The existence of such structural array evidently impacts the H-5 chemical shift.

AN UNEXPECTED PREFERRED CROWDED CONFORMATION IN 1-ARYL-2-(3- METHYL-1,2,4-TRIAZOL-4-YL)ETHANOL DERIVATIVES

A sterically crowded conformation in solution for l-aryl-2-(3-methyl-l,2,4-triazol-4-yl)ethanol derivatives 3 is suggested from spectroscopic data. The X-ray difraction analysis of structures 3a and 3d confirms such preferred structural array giving the unexpected synclinal conformation in the solid state. Bond distances between the triazole methyl hydrogen atoms and the center of the aromatic ring are in good agreement with those previously reported in the literature to explain this type of structural arrangement.