Experimental Design-Based Response Surface Methodology Optimization for Synthesis of β-Mercapto Carbonyl Derivatives as Antimycobacterial Drugs Catalyzed by Calcium Pyrophosphate

A simple protocol for the efficient preparation of β-mercapto carbonyl derivatives as antimycobacterial drugs has been achieved via Thia-Michael reaction between chalcones derivatives and thiols in the presence of calcium pyrophosphate as a heterogeneous catalyst under mild reaction conditions. The central composite design was used to design an experimental program to provide data to model the effects of various factors on reaction yield . The variables chosen were catalyst weight , reaction time , and solvent volume . The mathematical relationship of reaction yield on the three significant independent variables can be approximated by a nonlinear polynomial model. Predicted values were found to be in good agreement with experimental values. The optimum reaction conditions for reaction model (chalcone and thiophenol) obtained by response surface were applied to other substrates. This procedure provides several advantages such as high yield, clean product formation, and short reaction time. 1. Introduction Tuberculosis is the second most common cause of death from infectious disease. Roughly one-third of the world’s population has been infected with Mycobacterium tuberculosis, and new infections occur at a rate of one per second. In 2007 there were an estimated 13.7 million chronic active cases, and in 2010 there were 8.8 million new cases and 1.45 million deaths. 0.35 million of these deaths occur in those coinfected with HIV [1]. The needs of newly developed antimycobacterial drugs are required for the control of tuberculosis in the present time. In the discovery of new antimycobacterial drugs, the emergence of multidrug-resistant and extensively drug-resistant strains of Mycobacterium has encouraged the researchers to intensify the efforts to discover novel drugs [2]. Recently, the Czech authors showed that the 1,3-diphenyl-3-arylsulfenylpropan-1-one derivatives presented an antimycobacterial activity [3]. Thia-Michael reaction is a convenient route for synthesis of these β-mercapto carbonyl derivatives [4]. Traditionally, this reaction is catalyzed by strong bases [5] such as alkali metal alkoxides, hydroxides, and amines. However the use of either strongly acidic or basic conditions frequently leads to the formation of undesirable side products owing to competing reactions, such as polymerization, self-condensation, and rearrangements. The development of solid basic catalysts which could replace the liquid bases currently used in industrial processes is a major field of today’s catalysis research [6]. In this paper we report a mild and convenient