Ultrasound-assisted and Efficient Multicomponent Synthesis of 4H-Pyran Derivatives Catalyzed by LiOH.H

AIMS AND

objectivesIt is well established that 4H-pyran derivatives hold a significant position in synthetic organic chemistry due to their diverse biological and pharmacological properties. This work aims to introduce a novel synthetic pathway for highly functionalized 4H-pyran derivatives, achieved through a 1,4-Michael addition followed by a cascade cyclization. This reaction is catalyzed by LiOH·H MATERIALS AND

methodsIn this study, lithium hydroxide monohydrate (LiOH·H2O) was used as the catalyst. To explore environmentally friendly methods, two novel approaches utilizing pure water were investigated (Method 1 and Method 2). The first method involves the use of alkylidene reagents malononitrile and ethyl acetoacetate in an aqueous medium. The second method features a multi-component cyclocondensation of aromatic aldehydes, malononitrile, and ethyl acetoacetate, activated by ultrasound waves and conducted in pure water. The impact of various substituents on the formation of 4H-pyrans, including both electron-poor and electron-rich aromatic aldehydes, was also evaluated.

resultsMost products were obtained in high yield and as very pure crystals with distinct colors. Generally, aromatic aldehydes with electron-withdrawing groups (Cl) exhibited greater reactivity than those with electron-donating groups (OMe). This trend is clearly demonstrated when comparing entries 3 and 4 with entries 5 and 6 in Tables.

conclusionCompared to other procedures, this method is simple, fast, eco-compatible since it uses water as a solvent. In addition, the products are obtained in good yields in the pure state after simple recrystallization without the need for other purification techniques, such as column chromatography. These factors make this novel approach highly attractive for the synthesis of 4H-pyrans.