Indian Journal of Chemistry Vol. 49B, May 2010, pp. 547-553 An efficient synthesis of some substituted piperidin-4-one thiosemicarbazone derivatives as potential anticonvulsant under microwave irradiation Sameer Rastogi* & Harshita Rastogi Department of Pharmacy, Sunder Deep Pharmacy College, NH-24, Sunder Deep Nagar, Dasna, Ghaziabad 201 001, India E-mail: samrastogi_1982@yahoo.com Received 21 August 2008; accepted (revised) 30 December 2009 Microwave assisted organic reaction enhancement (MORE) is a simple, clean, fast, efficient, economic and environment friendly method for the synthesis of 2, 6-diaryl-3-methyl-4-piperidones by condensation of ethyl methyl ketone, benzaldehyde, substituted aromatic aldehydes and ammonium acetate. Thiosemicarbazone derivatives of 2, 6-diaryl- 3-methyl-4-piperidones have been synthesized by reaction with thiosemicarbazide. Using microwave irradiation, all the reaction could be completed in very short duration (4-7 min) with considerable increase in the yields (53.2-80.8%). All the synthesized compounds have been evaluated for their anticonvulsant activity by maximal electroshock method. Compounds 1b, 3b and 6b have been found to exhibit excellent anticonvulsant activity. Keywords: Anticonvulsant, piperidine-4-one, thiosemicarbazone In the recent years, microwave assisted organic reactions have emerged as a new tool in organic synthesis. Important advantages of this technique include highly accelerated rate of the reaction, reduction in reaction time with an improvement in the yield and quality of product. Moreover, the technique is considered as an important approach towards ‘Green Chemistry’ because of its eco-friendly nature. Conventional methods of organic synthesis usually need longer heating time, elaborate and tedious apparatus set-up, which result in higher cost of process and the excessive use of solvents/reagents leads to environmental pollution 1 . Microwave-assisted reactions in solvent or solvent-free conditions have gained popularity because of rapid reaction rate, cleaner reactions and ease of manipulation 2 . Among the wide variety of heterocycles that have been explored for developing pharmaceutically important molecules, piperidin-4-ones exhibit various biological activities like analgesic, antihypertensive, central nervous system depressant, antiviral, bactericidal and fungicidal activities 3-7 . However, little is known about piperidin-4-ones substituted with thiosemicarbazone moiety possessing potential pharmacological activity. This work was undertaken with a view to explore the possibility of anticonvulsant activity in the piperidin- 4-one nucleus. During our synthetic studies, it was observed that the synthesis of thiosemicarbazone derivatives of 2,6- diaryl-3-methyl-4-piperidones required a reaction time of 12-16 hr while the yields were always poor (<50%). Therefore, it was felt worthwhile to study these reactions under microwave irradiation with the aim of decreasing the reaction time and increasing the yield. The new microwave procedures were developed by considering two important parameters: minimum reaction time and maximum yield of the pure product. This was achieved by carrying out each reaction in two major ways. Firstly, optimization of the microwave power (intensity) was performed by conducting the reactions at different microwave powers/intensities (160, 350 and 500W) setting for a fixed time of five minutes. The microwave intensity giving the maximum yield was selected for optimizing the reaction time (Table I). Each time, the product was isolated, the yield and quality of the product was compared with the one obtained by conventional method. Finally, by using the optimized microwave intensity and time, each reaction was repeated at least three times and the products were compared with the conventional products by studying their melting point, mixed melting point, TLC, Co- TLC and IR spectra. Experimental Section All the chemicals used were obtained from S.D. Fine Chem. Ltd., Mumbai and E-Merck Ltd., Mumbai while the reagents and solvents were of analytical