1 3 J IRAN CHEM SOC DOI 10.1007/s13738-016-0849-3 ORIGINAL PAPER Synthesis and anti-brucella activity of some new 1,3,4-oxadiazole derivatives containing a ferrocene unit Ali Reza Kazemizadeh 1 · Nahid Shajari 1 · Reza Shapouri 2 · Neda Adibpour 3 · Reza Teimuri-Mofrad 4 Received: 24 November 2015 / Accepted: 21 March 2016 © Iranian Chemical Society 2016 ring. 1,3,4-Oxadiazoles are biological important het- erocycles [1]. These compounds have anti-fungal [2, 3], anti-bacterial [4], anti-inflammatory [5], anti-HIV [6], herbicidal [7], and pesticidal activities [8]. Several meth- ods have been reported in the literature for the synthesis of 1,3,4-oxadiazoles [9–14]. In recent years, a one-pot method for the synthesis of 1,3,4-oxadiazole derivatives from (isocyanoimino)triphenylphosphorane has been reported [15–24]. Brucella spp. is obligate intracellular gram-negative bacteria that primarily infect animals, especially domes- tic livestock, but can be transmitted to humans. Brucel- losis is a zoonotic worldwide disease that is endemic in the Middle East [25–29]. Brucella abortus is a major source of morbidity in humans and domestic animals. Brucella infects host macrophage cells and proliferates inside of them. For successful treatment, high penetra- tion rate antibiotics should be used to get into the cell cytoplasm, as well as the infected macrophage [25–29]. Treatment for brucellosis remains eristic and needs long- term therapy with at least two antibacterial agents such as tetracyclines, rifampin, trimethoprim, sulfamethoxa- zole, and gentamicin. Also drug resistance of Brucella to some antibiotics such as rifampin and streptomycin has been reported [26, 30, 31]. Thus, investigating the new antibacterial agents against Brucella seems important. In connection with our interest for the synthesis of hetero- cycles [32–35], we report the synthesis and evaluation of anti-brucella activity of some new ferrocenyl-containing 1,3,4-oxadiazole derivatives (5) in in vitro and in vivo assays. The products (5a–e) were synthesized via a four- component reaction between cinnamic acid derivatives or 3-phenyl-2-propynoic acid (1), (N-isocyanimino)tri- phenylphosphorane, (2), ferrocenecarbaldehyde (3), and dibenzylamine (4) (Scheme 1; Table 1). Abstract An isocyanide-based multicomponent reaction between cinnamic acid derivatives or 3-phenyl-2-propynoic acid, (N-isocyanimino)triphenylphosphorane, ferrocenecar- baldehyde, and dibenzylamine has been reported in excel- lent yields for the preparation of some new ferrocenyl- containing 1,3,4-oxadiazole derivatives. The anti-brucella activities of the products are investigated in in vitro and in vivo assays. Keywords Isocyanide-based multicomponent reaction · (N-isocyanimino)triphenylphosphorane · Ferrocene · Anti- brucella activity Introduction 1,3,4-Oxadiazoles are heterocyclic compounds with one oxygen atom and two nitrogen atoms in a five membered * Ali Reza Kazemizadeh alirezakazemizadeh@yahoo.com 1 Research Laboratory of MCR, Department of Chemistry, Zanjan Branch, Islamic Azad University, PO Box 49195-467, Zanjan, Iran 2 Department of Microbiology, Zanjan Branch, Islamic Azad University, PO Box 49195-467, Zanjan, Iran 3 Department of Medicinal Chemistry, School of Pharmacy, Zanjan University of Medical Sciences, 45139-56184 Zanjan, Iran 4 Organic Synthesis Research Laboratory, Department of Organic and Biochemistry, Faculty of Chemistry, University of Tabriz, 51664 Tabriz, Iran