Zeolite ( ZSM-5 ) as a Highly Efficient and Heterogeneous Catalyst for the Synthesis of β-Enaminones and β-Enamino Esters

Several β-enaminones and β-enaminoesters have been synthesized in high yields from amine and β-diketone in the presence of Zeolite (ZSM-5) as a catalyst. This method is applicable to both cyclic and acyclic ketones with aromatic and aliphatic amines.


Introduction
β-enaminones and β-enamino esters have been used as synthons for the synthesis of a variety of bioactive heterocycles [1][2][3] and pharmaceuticals displaying anti-inflammatory 4 antitumor 5 , antibacterial 6 , anti-epileptic [7][8] , anti-convulsant 9 and other therapeutic properties 10,11 .These compounds also serve as key intermediates in organic synthesis [12][13][14] and their chemistry has undergone a renaissance of interest 15 .The most common and widely employed protocol involves direct condensation of β-dicarbonyl compounds with amines in aromatic hydrocarbon solvents under reflux with azeotropical removal of water 16 .Subsequently the reaction procedure has been modified with the use of several catalysts such a molecular iodine 17 , Bi(TFA) 3 18 , NaAuClO  22 , silica chloride 23 , ceric(IV)ammonium nitrate 24 .Sc(OTf) 3 25 and Yb(OTf) 3 26 .Some other routes to the synthesis of β-Enaminones include condensation of methyl ketones with dimethylformamide dimethylacetals 27 , aminolysis of dithioacetals mediated by copper acetate 28 , reductive cleavage of isoxazoles 29 , cyclization of aminoacids 30 and substitution of the imidoylbenzotriazoles with trimethylsilyl enol ethers 31 .Out of these methods, most of them suffer from various disadvantages such as long reaction time and unspecified yields, use of expensive reagents, tedious work-up and lack of general applicability etc.The reaction has recently been reported to be catalysed by heterogeneous catalysts such as silica sulfuric acid 32 and silica-supported LiHSO 4 33 .
Keeping in view the importance of these compounds, it is desirable to find out more efficient, environmental friendly, cheap and readily available catalysts for synthesis of β-enaminones and β-enamino esters.During the last few years, there has been a spurt in the use of inorganic solid acids, particularly zeolites, in organic reactions [34][35][36] owing to their varied lewis and bronsted acidity, thermal stability, low cost and ease of separation.Prompted by these reports, we herein report a zeolite (ZSM-5) catalysed synthesis of various β-enaminones and β-enamino esters (Scheme 1).

Experimental
All the isolated compounds were characterized by IR, 1 H NMR, mass spectroscopy and melting point.The IR spectra were recorded in the range of 4000-400 cm -1 FT-IR spectrophotometer using KBr disk.Melting points were taken in open capillary tubes and therefore uncorrected.Purity of the compounds was checked on silica gel alumina sheet using n-hexane and ethylacetate as eluent.The visualization of spot was carried out in UV chamber.The 1 H NMR were recorded on Brucker 400 MHz spectrometer in CDCl 3 using TMS as an internal standard.The catalyst ZSM-5 (SAR-100) was purchased from ranbaxy (India) and used as received.

General procedure for the synthesis of β-enaminones and β-enamino esters derivatives
A mixture of amine (1 mmol), β-carbonyl compound (1 mmol) and zeolite (0.04 g) was placed in a 25 mL two-necked round-bottomed flask fitted with a reflux condenser.Ethanol (2 mL) was added to the mixture and the contents were heated under reflux till the completion of the reaction as monitored by TLC.After completion, the reaction was cooled to room temperature, solvent removed under reduced pressure and the crude product isolated with EtOAc (2x10 mL).The combined portions were filtered, dried under vacuum.The crude product was recrystallised from EtOH/H 2 O.

Results and Discussion
First of all, in order to screen the catalytic activity of the catalyst, i.e., ZSM-5, the reaction of aniline (1 mmol) with dimedone (1 mmol) was selected.Various reactions in the presence of different amount of catalyst in ethanol at room temperature and under reflux were carried out in order to optimize the reaction conditions (Table 1).It is clear from the Table 1 that the best results (maximum yields and minimum time) were obtained with 0.04 g of the catalyst in EtOH under reflux.a Isolated yield After optimization of the catalyst concentration and temperature, the reaction was performed in various other solvents (Table 2) in order to study solvents effects.The best results were obtained using EtOH (2 mL) under reflux, though the reaction had also taken place in other solvents but with poor yields (Table 2).The products, after work up and recrystallization, were isolated either as off-white solids (Entry 1-8, Table 3) or as viscous liquids (Entry 9 and 10, Table 3).The products obtained were characterized by 1 H NMR and Mass spectrum, and comparing the data with the literature values.The 1 H NMR spectrum obtained on the product 5,5-dimethyl-3-(phenylamino)cyclohex-2-enone (Table 3, entry 1) is shown in Figure 1.
Table 3   The methyl protons (2x CH 3 ) were observed at δ 1.12, methylene protons (2x CH 2 ) at δ 2.33 and 2.34 as singlets.The sharp singlets at δ 5.59 and 6.01 were assigned to olefinic(=CH) proton and (-NH) proton, respectively.The aromatic protons were obtained as a complex multiplet ranging from δ 7.12 to 7.36.The rest of the products were characterized by comparing the data with the literature values.It has been observed that the presence of electron withdrawing groups leads to slightly decreased yields and prolonged reaction time.
In summary, we have demonstrated that zeolite (ZSM-5) is an efficient, easily available and environmental friendly, heterogeneous catalyst for the synthesis of a number of β-enaminones and β-enamino esters.The catalyst works well with both aromatic and aliphatic amines and the corresponding cyclic or acyclic ketones to afford the desired product in good to excellent yields.

Table 1 .
Effect of catalyst loading and temperature on the reaction of aniline with dimedone

Table 2 .
Study of solvent effects on the reaction of dimedone with aniline in the presence of ZSM-5 a Isolated yields