Introduction

Important factors associated with the development of greener processes are atom economy, efficiency, elimination of toxic intermediates/products and generation of as minimum waste as possible. In this sense, multicomponent reactions (MCRs) have emerged as an interesting tool that allows for the straightforward synthesis of intricate molecules in a one-pot fashion without the isolation and purification of intermediates, therefore leading to lower costs, time and energy consumption. Additionally, MCRs are modular and convergent in nature and also an important source of molecular diversity. The Hantzsch three-component reaction is the best-known multicomponent reaction, because os the their potent biological activities, affording dihydropyridine which have been employed therapeutically as the commercially available drugs nifedipine and nimodipine.

The synthesis of 1,4-dihydropyridines using heterogeneous catalysis have been reported employing many types of compounds, and thinking about green chemistry, the zeolites, in particular, have received increasing attention owing to their efficiency and selectivity in organic transformations, as consequence of attractive properties, ie tunable acidity and pore size; still, an important feature of such materials is the possibility of inserting additional metals into their framework.

Objective

The application of an ultra-stable (US) Y zeolite as a green catalyst in the synthesis of a series of 1,4-dihydropyridines under microwave irradiation.

Methodology

In a sealed tube, a mixture of diketone or b-ketoester (1.0 mol), aldehyde (0.5 mol) and ammonium acetate or p-toluidine (1.25 mol) was carried out with the zeolite catalyst USY (50 mg) at 0.5 mL of ethanol, heated to 110^oC (300 W) in an oil bath or under microwave irradiation (300 W) for the time required for product formation. The progress of the synthesis was verified by TLC. After completing the time proposed in the optimization of the reaction, the reaction mixture was diluted with ethanol (5-6 mL) and the catalyst was separated by centrifugation, along 3 processes followed by washing of the mixture composed of the desired product diluted in ethanol and the heterogeneous catalyst, this solvent being eliminated by vacuum, resulting in a solid that was purified by column chromatography using hexane / ethyl acetate as eluent.

For the catalyst recycling study, the zeolite was separated from the reaction mixture and washed several times with ethanol followed by centrifugations for 5 min at 5000 W. At the end of each washing process, the zeolite was placed in the kiln to remove the remaining ethanol and then weighed to be reused. In all cycles the catalyst was practically fully recovered, that is, in all syntheses it was possible to use approximately 50 mg of USY zeolite.

Results and discussion

We initiated our study using dimedone, benzaldehyde, ammonium acetate in ethanol as solvent and evaluating different catalysts and diferent times. The USY zeolite showed to be the most suitable for the studied MCR, providing desired product in 96% yield. Looking for a more efficient protocol, microwave (MW) irradiation was tested, and for our delight, the desired product was still obtained with yhis catalyst. We then evaluated the catalyst loading using diferente quantities (mg) of the USY zeolite under MW irradiation for diferente times, and the best result was using 50 mg for 20 min. For the catalyst recycling study, the USY zeolite was separated from the reaction mixture and washed 4-5 times with ethanol followed by centrifugations for 5 min at 5000 W, and then reused. As shown in Fig. 1, the yield was still very good (> 90%) up to the 4 th cycle.

The zeolites using in this work were characterized by XRD, SEM analyses and N₂ sorption measurements. The XRD diffractograms of the zeolites in their protonic form confirmed its respective type and the crystalline structures of each material that we have called "confinement effects", which make the catalytic environment more conducive to solvation and reactivity. EDX, on the other hand, helped us to observe the differences of zeolite usy in relation to the others by having appropriate values ​​of external surface area and microporous volume associated with its crystalline arrangement. The high stability of the USY zeolite as a catalyst is demonstrated by the XRD diffractogram and the adsorbed pyridine DRIFTS spectrum, which did not change when made with the zeolite before and after being used in reaction. The analyzes show that the FAU structure, the specific surface area and acidic properties of the USY zeolite are practically preserved after the reaction. Through the analyzes carried out, a large number of acidic sites with a Brønsted nature are observed, which is an important factor in terms of their better catalytic behavior, evidenced also by the low Si / Al ratio.

The scope and limitation of this method using different aldehydes and dimedone or ethyl acetoacetate was made for studied it. Aromatic aldehydes containing electron donating and withdrawing groups, aliphatic aldehydes and heteroaromatic aldehydes have been successfully employed, providing good to excellent isolated yields. In addition, we tested this protocol in the synthesis of acridinediones using para-toluidine instead of ammonium acetate, also providing the desired product.

Conclusion

In conclusion, the USY zeolite, which has been fully characterized in order to better understand its catalytic stability and its role as a heterogeneous catalyst, can be used as a green catalyst in the synthesis of a series of 1,4-dihydropyridines under microwave irradiation , providing excellent performance even after simple recovery and reuse. The best catalytic behavior of the USY zeolite was attributed to its microporous structure and to its textural and acidic properties. Using this porous material in the optimized reaction conditions, 21 compounds were prepared in isolated yields of 64-96%.