Multicomponent synthesis of 4-arylidene-2-phenyl-5(4H)-oxazolones (azlactones) using a mechanochemical approach

Abstract

Background: Mechano heterocyclic chemistry (MCH) is a recent quickly growing technique in the synthesis of heterocycles and draws the attention of heterocyclic chemists towards the uses of grindstone technique in a solvent free green efficient synthesis of many heterocyclic systems. On the other hand, multicomponent approach has opened the door for the rapid and efficient one-step procedures to synthesize a wide range of complex targets. Azlactones have been reported to exhibit a wide range of pharmaceutical properties including immune suppressive, anticancer. Antimicrobial, antitumor, anti-inflammatory and antiviral. It also used as useful synthons in the synthesis of several small molecules, including amino acids and peptides. Results: The present work describes an efficient one step green synthesis of 4-arylidene-2-phenyl-5(4H)-oxazolones (azlactones) via the multi-component synthesis by the mechanochemical grinding of glycine, benzoyl chloride, an aromatic aldehyde and fused sodium acetate in the presence of drops of acetic anhydride. This process is green, simple to handle, step and atom efficient, economical and environmentally friendly, because it does not require a reaction solvent or heating, we introduced the yield economy [YE] as a metric to assess the conversion efficiency of grinding and conventional synthetic reactions of azlactones. The structures of the newly synthesized compounds were elucidated by elemental and spectral analyses. Conclusion: In conclusion, we have developed a simple, efficient and eco-friendly strategy for facile synthesis of azlactones. The key advantages of this strategy, over conventional approach, include its simple, solvent free conditions, as well as its facile work-up, high yield economy and environmental friendliness. It is also successful in achieving three of the green chemistry objectives of a solvent free operation, high atom economy and step efficient. Thus, combining the features of both economic and environmental advantages.