Aqueous One-Pot Synthesis of Pyrazoles, Pyrimidines and Isoxazoles Promoted by Microwave Irradiation

Abstract

Microwave irradiation promotes the conversion of enaminoketones formed in situ into a variety of heterocycles by reaction with the appropriate bidentate nucleophile. The advantages of the method over previous approaches are short reaction times and facile purification by precipitation of the products in aqueous media. Moreover the convenient one-pot procedure makes these syntheses particularly suitable for library production. Organic reactions in aqueous media have become of great interest as water is not only more environmentally friendly, but also because organic reactions in water often display unique reactivity and selectivity.

Controlled Microwave Heating in Modern Organic Synthesis

“…[141] The reaction proceeds with initial formation of an enaminoketone as the key intermediate from the 1,3-diketone and DMFDMA precursors, followed by a tandem addition-elimination/cyclodehydration step. Remarkably, the authors were able to perform the multicomponent condensation by heating all three building blocks together with a small amount of acetic acid (2.6 equiv) in water at 220 8C for 1 minute!…”

“…[5,143] Molteni et al have successfully used other bidentate nucleophiles such as amidines and hydroxylamine for the synthesis of related heterocycles. [141] Numerous reports of the use of DMFDMA as a building block for the rapid synthesis of a large variety of heterocyclic ring systems by MAOS have also appeared. [144][145][146][147] The Bohlmann-Rahtz synthesis of trisubstituted pyridines from b-aminocrotonates and an ethynyl ketone has found application in the preparation of a variety of heterocycles containing this structural motif.…”

New Strategies for the Synthesis of Pyrimidine Derivatives

“…[22] This microwave-promoted reaction proceeds via in situ enaminoketone formation by its condensation with amidinium chlorides 23.…”

Efficient and Selective Acetylation of Biomolecules with 1-Acetylimidazole Catalyzed by Er(OTf)_3.

“…Nevertheless, in the last decade, the possible use of aqueous environments for the chemical synthesis has directed the studies towards the development of catalysts resistant to moisture. Moreover in recent times, microwave (MW) irradiation as an alternative source of heating has been proposed in many reactions performed in water such as Mannich reactions,]9,10] substitution reactions, [11,12] epoxides opening, [13,14] Diels-Alder cycloadditions, [15,16] heterocycle synthesis, [17,18] carbonylation reactions, [19][20][21] and carbon-carbon coupling reactions [22][23][24]. Microwave-assisted organic reaction offers several advantages over conventional heating including homogeneous and rapid heating, remarkable accelerations in reactions as a result of the heating rate producing high yields and lower quantities of side-products.…”