Reactions of biacetyl (¼ butane-2,3-dione) with (N-isocyanimino)triphenylphosphorane in the presence of aromatic carboxylic acids proceed smoothly at room temperature and under neutral conditions to afford 3-(5-aryl-1,3,4-oxadiazol-2-yl)-3-hydroxybutan-2-one derivatives in high yields.
Introduction. -Due to the atom economy, convergent character, and simplicity of one-pot procedures, multi-component condensation reactions (MCRs) have an advantageous position among other reactions. The development of novel MCRs is receiving growing interest from industrial-chemistry research groups and represents a challenge for organic chemists [1] [2]. The drive toward the ideal synthesis embracing step count, ideally just one, and yield, ideally 100%, has been pursued intensively since scientists began to construct molecules. Of course, there are many other factors that affect these two aspects of synthesis, including cost, starting material availability, safety, environmental concerns, and overall ease of the process, including workup and purification [3]. The nature of the synthesis project also plays a role. Complexmolecule total synthesis is often driven by step count, while showcasing innovative chemistry. Traditional structureÀactivity relationship (SAR) evaluations in medicinal chemistry typically involve the preparation of an advanced intermediate that can be analogued readily to introduce the molecular diversity necessary to prepare a collection, or library, of structurally related compounds. One strategy that potentially meets the goals of total synthesis and library production is multicomponent reaction (MCR) chemistry, in which three or more starting materials are brought together in a highly convergent approach to rapidly build up molecular structure and complexity [4].
1,3,4-Oxadiazoles have attracted interest in medicinal chemistry as surrogates of carboxylic acids, esters, and carboxamides. They are an important class of heterocyclic compounds that have a wide range of pharmaceutical and biological activities including antimicrobial, antifungal, anti-inflammatory, and antihypertensive properties [5 -9].
Several methods have been reported in the literature for the synthesis of 1,3,4oxadiazoles. These protocols are multistep in nature [10 -16]. The most general method involves the cyclization of diacylhydrazides with a variety of reagents, such as SOCl 2 , POCl 3 , or H 2 SO 4 , usually under harsh reaction conditions. Few reliable and