br Acknowledgments br Introduction Dihydropyridines DHPs are a


1,4-Dihydropyridines (1,4-DHPs) are a class of highly important molecular skeletons abundant in natural products. They are key intermediates of nitrogen-containing polycyclic hydrocarbons and widely used in pharmaceutical agents [1,2]. In view of their high significance, great effort has been made to develop new methods to synthesize 1,4-DHPs, among which, the Hantzsch reaction utilizing an amine, an aldehyde, and two 1,3-dicarbonyl compounds to synthesize 1,4-DHPs is the most classic approach. However, this approach has some obvious disadvantages such as harsh reaction conditions, excessive use of volatile organic solvents and high reaction temperature [3]. Later, chemists developed several alternate and efficient methods for the synthesis of 1,4-DHPs, which include the promotion of microwave [4], polymer [5], TMSCl [6], Lewis HZ-1157 Supplier [7], Brønsted acid [8], solid acid [9], base [10], biocatalysts [11] and organocatalysts [12]. Although the known methodologies have convenient protocols with good to high yields, the reported methods still suffered from drawbacks, such as prolonged reaction times, high temperature and the use of non-recyclable catalysts. Thus, it is essential to develop a simple, efficient and green method for the synthesis of 1,4-DHPs.
In the recent years, green chemistry using environment-friend reagents and conditions is one of the most fascinating developments in synthesis of widely used organic compounds. Ultrasound has been used to accelerate the chemical reactions proceed via the formation and adiabatic collapse of transient cavitation bubbles. The ultrasonic effect induces very high local pressure and temperatures inside the bubbles and enhances mass transfer and turbulent flow in the liquid [13]. Ultrasound has been utilized to accelerate a number of synthetically useful reactions, especially in heterocyclic chemistry [13].
Ionic liquids (ILs) technology has been widely used as another new and environment-friend approach toward modern synthetic chemistry and has attracting advantages such as extremely low vapor pressure, excellent thermal stability, reusability, and talent to dissolve many organic and inorganic substrates [14]. 1-Carboxymethyl-3-methylimidazolium tetrafluoroborate ([CMMIM]BF4) is a Brønsted acidic ionic liquid and has been proofed to be excellent catalysts to some organic synthesis, which clearly indicate its advantages such as benign to environment, easy to be recycled and homogeneous to reaction, such as synthesis of Fischer indole [15], synthesis of 3,4-dihydropyrimidin-2-(1H)-ones [16], Mannich reaction [17]. Besides, solvent-free organic synthesis as a green synthetic approach has received considerable attention because they are operationally simple, often involve nontoxic materials, and proceed in excellent yield with high selectivity [18]. Toward the development of clean chemical processes [19], we report a novel and environment-friend procedure for the solvent-free preparation of 4-substituted 1,4-dihydropiridine-3,5-dicarboxylates in the presence of [CMMIM]BF4 as an efficient and versatile catalyst under ultrasonic irradiation (Scheme 1).


Results and discussion
For the solvent-free synthesis of the dimethyl 4-phenyl-1,4-dihydropiridine-3,5-dicarboxylate (4a), ultrasound promotion, ionic liquid catalyzation are the two most important parameters. To optimize, the preliminary reaction was sonicated under various sets of conditions at 25–30°C catalyzed by benzaldehyde (1a, 1mmol), methyl propiolate (2, 2mmol), ammonium carbonate (1mmol) and 5mol% [CMMIM]BF4 as catalyst (Table 1). The effect of the ultrasound power intensity on the product yield was also investigated by increasing the irradiation power from 150 to 350W. It can be seen from Table 1 that increase of ultrasonic power led to relatively higher yield and shorter reaction time, which peaked at 300W. Then the yield decreased slightly with increasing ultrasound power intensity >300W. Therefore, 300W of ultrasonic irradiation was sufficient to push the reaction forward. The best yield for 4a was obtained at 15min at room temperature with 300W ultrasonic irradiation. The possible explanation for the positive association of between yield and irradiation power is that the increase in the acoustic power could increase the number of active cavitation bubbles and the size of the individual bubbles, both of which are expected to result in higher maximum collapse temperature and accelerated respective reaction. However, when ultrasonic intensity exceeded the optimal value (>300W), excessive number of gas bubbles exist in the solution, which adversely exhibits scattering effect on the sound waves and lowers the level of energy focused on the reaction vessel. Additionally, the coalescence of the cavities in the presence of large number of cavities may promote the formation of a large cavity which collapses less violently. Consistent with previous studies, increase in the operating intensity beyond the optimum will lead to the decrease of the utilization efficiency of ultrasound and the reaction yield [21,22].