A facile synthesis of pyrano[2,3‐d:6,5‐d′]dipyrimidines via microwave‐assisted multicomponent reactions catalyzed by β‐cyclodextrin

Abstract

A facile three‐component reaction of aromatic aldehyde, 2,2‐dimethyl‐1,3‐dioxane‐4,6‐dione, and 6‐amino‐1,3‐dimethyluracil was developed for the first time using β‐cyclodextrin (β‐CD) as a macrocyclic host for aldehyde and an efficient catalyst that leads to a batch of novel pyrano[2,3‐d:6,5‐d′]dipyrimidines (4a‐k). The synthesis was accomplished with the aid of microwave irradiations in solvent‐free conditions. The product obtained was in contrast to the previous report in which a similar reaction resulted in a mixture of benzylidenepyrimidine and bisaminopyrimidine analogs in the presence of triethylbenzylammonium chloride in an aqueous medium. The formation of the pyrano[2,3‐d:6,5‐d′]dipyrimidines may be in virtue of the property of β‐CD to construct new CC and CX (where X = heteroatom) bonds. Reusability of the catalyst up to three runs without any noteworthy change in catalytic activity is one of the main features of the reaction. Other noteworthy features are good to excellent yields, eco‐friendly procedure, non‐column chromatographic purification, and mild conditions.

Furo, Pyrano, and Pyrido[2,3‐d]Pyrimidines: A Comprehensive Review of Synthesis and Medicinal Applications

“…Avvadukkam et al . (2021) [72] devised a facile three‐step reaction process using β ‐cyclodextrin as a macrocyclic host for aromatic aldehyde and an effective catalyst for the synthesis of novel pyrano[2,3‐ d :6,5‐ d ′] dipyrimidines 48 . The reaction involved the combination of aromatic aldehyde 2 , 2,2‐dimethyl‐1,3‐dioxane‐4,6‐dione 46 , and 6‐amino‐1,3‐dimethyluracil 47 under solvent‐free microwave irradiation.…”

Recent advancements in the multicomponent synthesis of heterocycles integrated with a pyrano[2,3-d]pyrimidine core

“…Ammonium acetate enabled the condensation steps in this technique. Avvadukkam et al 121 have identied the synthesis of dihydro-2H-pyranodipyrimidine-tetraones 49a-k under catalytic conditions of b-cyclodextrin (b-CD) as a supramolecular macrocyclic host. Thus, one-pot multicomponent reactions of aryl aldehydes with Meldrum's acid, and 6-amino-1,3-dimethyluracil catalyzed by b-cyclodextrin under microwave irradiation conditions yielded the corresponding pyranodipyrimidines 49a-k (Scheme 28).…”