Results and Discussions
In continuation of our synthesis towards biologically important heterocycles,23 we report herein, a simple, mild and efficient synthesis of densely substituted indeno[1,2-b]pyridines by the multi- component reaction of 1,3-indandione, aldehydes, propiophenone or 2-phenylacetophenone and ammonium acetate in excellent yields employing ceric ammonium nitrate (CAN) (10 mol%) as a catalyst at room temperature (25-30 °C)(Scheme 1).
Scheme 1. Synthesis of fully substituted indenopyridine at room temperature (25-30 °C).
Initially, we explored the four component reaction of 1,3-indandione (1 mmol), propiophenone (1 mmol), 4-nitrobenzaldehyde (1 mmol) and ammonium acetate (1.3 mmol). All these four components were first mixed and stirred at room temperature (25-30 °C) in ethanol (5 mL) which resulted in isolation of only 30% of the desired product. To enhance the yields and reduce the reaction time, several metal catalysts were examined. Using FeCl3.6H2O (15 mol%) as a catalyst, the reaction proceeded smoothly to afford the desired product in good yields (75%, Table 1, entry 3). On the other hand, InCl3, RuCl3 and VO(acac)2 gave intermediate yields (Table 1, entries 5-7). Surprisingly, using ceric ammonium nitrate (CAN) (10 mol%, Table 1, entry 9) as catalyst in ethanol best result both in terms of yields and reaction time was obtained. Ethanol (5 mL) proved to be a much better solvent in terms of yields than all the other tested solvents including CH2Cl2, THF, MeCN and even H2O (Table 1, entries 10-13) which afforded the desired products in moderate yields. Therefore, the optimized conditions for the indeno[1,2- b]pyridines synthesis consist of the combination of 1,3-indandione (1 mmol), propiophenone (1 mmol), benzaldehydes (1 mmol), ammonium acetate (1.3 mmol), ceric ammonium nitrate (CAN) (10 mol%) and EtOH (5 mL) at room temperature (25-30 °C) (Table 1, entry 9).
