HETEROCYCLES, Vol. 57, No. 6, 2002, pp. 1017 - 1032, Received, 1st February, 2002 SYNTHESIS OF 3-SUBSTITUTED 5-ARYLIDENE-1-METHYL-2- THIOHYDANTOINS UNDER MICROWAVE IRRADIATION Ahmed I. Khodair † and John Nielsen* Department of Chemistry, Technical University of Denmark, Kemitorvet, Building 207, DK-2800 Kgs. Lyngby, Denmark, E-mail: jni@kemi.dtu.dk Abstract - A mono-modal microwave oven was used to expedite the synthesis of small libraries of 3-substituted 1-methyl-2-thiohydantoins and 3-substituted 5-arylidene-1-methyl-2-thiohydantoins. In comparison with the traditional reflux methods, similar or higher yields were obtained. INTRODUCTION The pioneering reports on the use of microwave irradiation as thermal source to carry out organic reactions were published in 1986. 1,2 In 1989, the first review dealing with microwave heating in organic synthesis appeared. 3 Since then a rapidly increasing number of reports and reviews have been published demonstrating that a large variety of organic reactions can be conducted safely in microwave ovens leading to reduction in reaction times of up to three orders of magnitude. 4,5 These reports also include solid-phase reactions and the generation of combinatorial libraries. 6 The timesaving ability together with the very short response times and the minimization of thermal decomposition of products are the main advantages of microwave heating. In our efforts to generate combinatorial libraries of potentially biologically active compounds using expeditious parallel synthesis, we have been interested in a series of heterocyclic compounds. Among these are the substituted thiohydantoins whereof several 5-arylidene-2-thiohydantoins have shown potent activity against herpes simplex virus (HSV), 7 human immunodeficiency virus (HIV) 8 and the leukemia sub-panel. 9 In addition, certain other series of hydantoin derivatives showed interesting activities, including antiviral, 10 anti-inflammatory, 11 anticonvulsant, 12 antidepressant, 13 and platelet inhibitor ฀ On leave from Department of Chemistry, Faculty of Education, Tanta University, Kafer EL-Sheikh, Egypt