Silica-ZnCl2: An Efficient Catalyst for the Synthesis of 4-Methylcoumarins

Silica-ZnCl2 has been found to be an efficient and eco-friendly catalyst for the synthesis of substituted 4-methylcoumarins from ethyl acetoacetate and substituted phenols under “neat” conditions in an oil bath at 80°C. The experimental procedure is simple, includes shorter reaction times (15–65？min), compatible with sensitive functional groups, and results in excellent yield of the products. 1. Introduction Since long time, the use of solid phase technique has been considered to be the method of choice for application in a large number of diverse and interesting chemical manipulations. Reactions involving solid-supported catalysts encompass advantages like easy work up of the reaction by filtration of solid-supported reagent, increased reactivity, higher yields of the product, and recyclability of the reagent for subsequent reaction [1]. The utility of the solid-supported reactions has been acknowledged in the synthesis of several chemical libraries. A large number of solid-supported reagents like SiO2-SO3H [2], PPA-SiO2 [3], and HClO4-SiO2 [4] have been developed over the period of time and have been used in many chemical reactions. In our laboratory we have developed many silica-based reagents [5], which fascinated us for the development of other solid-supported reagents. ZnCl2, being an inexpensive and easily available catalyst, has been demonstrated in chemical reactions as a Lewis acid catalyst [6]. Although it is a user choice catalyst, it is very hygroscopic accompanied with its nonusability. Therefore, we have prepared a silica-ZnCl2 reagent by Paul’s method [7] which can find application as a user-friendly catalyst. To check its applicability, we wanted to use this catalyst in the preparation of biologically important molecules, whose synthetic preparation can be improved. Hence, we chose the synthesis of substituted coumarins which have a long list of applications. Coumarins are found to have varied bioactivities including inhibition of platelet aggregation [8], inhibition of steroid 5a-reductase [9], inhibition of HIV-1 protease [10], and antibacterial [11] and anticancer [12] activities. Suitably substituted coumarins have various applications in food additives, pharmaceutical, perfume, and cosmetic industries [13]. Moreover, 7-hydroxy-4-methylcoumarin derivatives have also been used in the synthesis of dendrimers [14]. Since coumarins have become one of the prime molecules of investigation, several groups have started synthesizing molecules with similar moieties for further applications. Coumarins can be synthesized using several