Heteroatom Chemistry Volume 23, Number 4, 2012 Four-Component Synthesis of Disubstituted 1,3,4-Oxadiazole Derivatives from Cinnamaldehyde, an Aromatic Carboxylic Acid, a Secondary Amine, and N -Isocyaniminotriphenylphosphorane Ali Ramazani, 1 Robabe Kalhor, 1 Aram Rezaei, 2 and Zahra Karimi 1 1 Chemistry Department, Zanjan University, Zanjan, Iran 2 Young Researchers Club, Zanjan Branch, Islamic Azad University, Zanjan, Iran Received 21 April 2011; revised 23 October 2011, 13 January 2012 ABSTRACT: The iminium intermediate generated by the reaction between a secondary amine and cinnamaldehyde was reacted with N-isocyanimino- triphenylphosphorane in the presence of benzoic acid derivatives to form the corresponding iminophospho- rane intermediate, whose intramolecular aza-Wittig reaction led to disubstituted 1,3,4-oxadiazole deriva- tives. The syntheses were completed under neutral conditions at room temperature to give excellent yields. C  2012 Wiley Periodicals, Inc. Heteroatom Chem 23:315–321, 2012; View this article online at wileyonlineli- brary.com. DOI 10.1002/hc.21013 INTRODUCTION 1,3,4-Oxadiadoles have attracted interest in medici- nal chemistry as surrogates of carboxylic acid. They are an important class of heterocyclic compounds that have a wide range of pharmaceutical and Correspondence to: Ali Ramazani; e-mail: aliramazani@ gmail.com. c  2012 Wiley Periodicals, Inc. biological activities such as antimicrobial, antifun- gal, antimalarial, analgesic, hypoglycemic, and an- tihypertensive anti-Inflammatory [1–5]. The multi- component condensation reactions give advantages to other reactions. In recent years, several tech- niques have been reported for the preparation of CNNPPh 3 4 [6,7]. There are various methods for the use of 4 in the synthesis of metal complexes. How- ever, the application of 4 in the synthesis of organic compounds is uncommon. Today, most isocyanide- based multicomponent reactions (IMCRs) chemistry relates to the traditional reactions of Passerini and Ugi. Indeed, the wide number of various scaffolds now available mainly builds on these two IMCRs and their combination with other kinds of reactions [8–31]. In recent years, the intramolecular version of the aza-Wittig type reaction has attracted much at- tention because of its high potential for the synthesis of a wide variety of nitrogen hetrocycles [32]. Lately, we have established a one-pot technique to syn- thesize organophosphorus compounds [32–41]. Not many reliable simple examples have been reported for the single-step synthesis of 1,3,4-oxadiazoles, es- pecially from easily available carboxylic acids and acid hydrazides [42]. In this paper, we report an effi- cient synthetic method for the preparation of disub- stituted 1,3,4-oxadiazole derivatives using CNNPPh 3 4 chemistry [27] (Scheme 1). 315