Synthesis, biological evaluation, and computational studies of novel fused six-membered O-containing heterocycles as potential acetylcholinesterase inhibitors

Two-Step Sequence Multicomponent Synthesis/Reductive Rearrangement of 2-Acyl-2,3-dihydrofurans for Modular Assembly of Annulated 4H-Pyrans

Heterocycles of synthetic and natural origin are a well-established class of compounds representing a broad range of organic molecules that constitute over 60% of drugs and agrochemicals in the market or research pipeline. Considering the vast abundance of these structural motifs, the development of chemical processes providing easy access to novel complex target molecules by introducing environmentally benign conditions with the main focus on improving the cost-effectiveness of the chemical transformation is highly demanding and challenging. Accordingly, sonochemistry appears to be an excellent alternative and a highly feasible environmentally benign energy input that has recently received considerable and steadily increasing interest in organic synthesis. However, the involvement of transition-metal-catalyst(s) in a chemical process often triggers an unintended impact on the greenness or sustainability of the transformation. Consequently, enormous efforts have been devoted to developing metal-free routes for assembling various heterocycles of medicinal interest, particularly under ultrasound irradiation. The present review article aims to demonstrate a brief overview of the current progress accomplished in the ultrasound-assisted synthesis of pharmaceutically relevant diverse heterocycles using transition-metal-free catalysis.

https://pubs.rsc.org/en/content/articlepdf/2022/ra/d2ra02063g

Ultrasound-assisted transition-metal-free catalysis: a sustainable route towards the synthesis of bioactive heterocycles

Electron impact mass spectra of 1,3,5-triarylpentane-1,5-diones are reported. All compounds studied show a tendency to eliminate a water molecule and also the elements of [H3O] before fragmentation to smaller ions. The [H3O] loss proceeds via loss of water to form a pyran ion, which subsequently eliminates a hydrogen atom to form the stable pyrillium cation. Copyright © 2002 John Wiley & Sons, Ltd.

Mass spectra of 1,3,5-triarylpentane-1, 5-diones: formation and decomposition of pyrilium cation from the molecular ion.

The oxidation of 3-aryl-1H-benzo[f]chromenes with Koser’s reagent in methanol afforded a series of benzoflavylium tosylates. This reaction is the first example of the use of polyvalent iodine compounds to access arene-condensed pyrylium salts.

Oxidation of 3-aryl-1 H -benzo[ f ]chromenes with Koser’s reagent – synthesis of benzoflavylium tosylates

Data on the chemistry of monocyclic, unsaturated, six-membered, oxygen-containing heterocycles, viz., 4H-pyrans, are correlated and systematized for the first time. The methods for their synthesis, their transformations, and spectroscopic data for them are discussed. The interest in these compounds, which has increased recently, is due to the fact that they are convenient starting compounds for the preparation of important classes of heterocycles such as pyrylium salts and saturated 1,5-diketones. The recyclization of the former and the cyclization of the latter lead to a great diversity of heterocycles that contain various elements (oxygen, nitrogen, sulfur, phosphorus, etc.) in five-, six-, and seven-membered rings and various substituents, including heteroaromatic and heteroorganic substituents. The preparation of 4H-pyrans is realized via three principal pathways: by condensation of carbonyl compounds, by cyclization of saturated 1,5-diketones, and by synthesis on the basis of pyrylium salts. The transformations of 4H-pyrans examined in the review include dehydroaromatization or acidic disproportionation, which lead to pyrylium salts, hydration to give saturated 1,5-diketones, reactions with the participation of the double bonds of the pyran ring, recyclization to give aromatic compounds, and the preparation of radicals and ion radicals. It was shown that 4H-pyrans are used for the solution of theoretical problems, as, for example, in the study of the mechanism of hydride transfer.

O. V. Drygina

Papers

4H-pyrans (review)