Month 2019 Bis-thiourea Derivatives and Their Utility in Synthesis of Mono-heterocyclic, Bis-heterocyclic, and Fused Heterocyclic Systems Kamal M. Dawood* Chemistry Department, Faculty of Science, Cairo University, Giza 12613, Egypt *E-mail: dr_dawood@yahoo.com; kmdawood@sci.cu.edu.eg Received October 9, 2018 DOI 10.1002/jhet.3540 Published online 00 Month 2019 in Wiley Online Library (wileyonlinelibrary.com). Bis-thiourea derivatives have distinguished synthetic potentialities. They are interesting substrates for construction of various classes of heterocycles, such as thiazoles, thiadiazoles, imidazoles, bis-thiazoles, bis-thiadiazoles, and fused heterocyclic systems. The current review is concerned on disclosing the synthetic and research applications of bis-thioureas that were reported in the literature during the last decade. J. Heterocyclic Chem., 00, 00 (2019). Contents 1 Introduction 1 2 Synthetic Routes to Bis-Thioureas 2 2.1 2,5-Dithiobiureas 2 2.2 Alkylene-bis-thioureas 3 2.3 Arylene-bis-thioureas 4 3 Reactions of Bis-Thioureas 10 3.1 Reaction of Bis-thioureas with α-Halo Carbonyl Compounds 10 3.2 Reaction of Bis-thioureas with Hydrazonoyl Halides 12 3.3 Reaction of Bis-thioureas with Ethenecarbonitriles 12 3.4 Reaction of bis-thioureas with acetylenedicarboxylates 14 3.5 Oxidative Desulfurization Reactions of Bis-thioureas 15 3.6 Thermal degradation of bis-thioureas 18 4 Conclusions 19 References and Notes 19 1. INTRODUCTION Substituted thiourea derivatives have attracted much attention as drug candidates against several diseases, because of their broad potential pharmacological activities [1]. Thiourea derivatives were reported to be non-nucleoside inhibitors of the reverse transcriptase enzyme of the human immunodeficiency virus [2,3]. Some thiourea scaffolds were approved by the Food and Drug Administration as commercial drugs for treatment of diseases (Fig. 1). For example, thioacetazone (also known as amithiozone) and thiocarlide are oral antibiotics for treatment of tuberculosis [4], and ambazone is an oral antiseptic and antineoplastic drug [5]. In addition, some commercially available drugs employed thioureas in their synthesis. Examples are thiopental and thiamylal, which are sedative/hypnotic drugs [6]; pramipexole is a central nervous system drug for treating Parkinson’s disease [7]. Thiouracils are antithyroid drugs, and famotidine is used to treat and prevent ulcers in the stomach and intestines (Fig. 1) [8]. Bis-thiourea derivatives were reported as key precursors for synthesis of broad heterocyclic systems of potential © 2019 Wiley Periodicals, Inc.