Nano-SiO₂ catalyzed synthesis of β-enaminones under solvent free conditions

Abstract

Nano-SiO₂ efficiently catalyzed the synthesis of β-enaminones using direct condensation of various (cyclic and acyclic) β-diketones with aromatic and aliphatic amines under solvent-free conditions. This eco-friendly catalyst can be recovered and reused without significant loss of activity. This methodology provides a simple synthetic route to enaminones in excellent yields at room temperature.

Graphical abstract

Introduction

Enaminones are versatile, readily obtainable reagents and their chemistry has received considerable attention in recent years [1, 2]. β-Enaminones are useful synthones for the synthesis of various pharmaceuticals and bioactive heterocycles [3], including anticonvulsant, anti-inflammatory, and antitumor agents. The conventional method for the synthesis of enaminones is the azeotropic removal of water by refluxing an amine with 1,3-diketones in aromatic solvents [4]. Recently, some other methods applied various catalysts such as NaAuCl₄ [5], SiO₂/NaHSO₄ [3], PPA-SiO₂ [6], zirconium(IV) chloride [7], Bi(TFA)₃ [8], Cu-np [9], H₃PW₁₂O₄₀ [10], (bromodimethyl)sulfonium bromide [11], silica supported Fe(HSO₄)₃ [12], trichloroacetic acid [13], AlPO₄ [14], VO(acac)₂ [2], silica-supported sulfuric acid [15], and SiO₂/HClO₄ [16]. Despite efficiency of the published methods, some of these procedures suffer from disadvantages such as long reaction times, use of toxic organic solvent, use of expensive and non-reusable catalyst and high temperature reaction. Therefore, there is much room for the development of new protocols to overcome these problems. Use of heterogeneous solid catalysts in organic synthesis and industrial reactions is interesting due to their selectivity, recyclability, operational simplicity, and minimal waste disposal [17]. Recently, nano-SiO₂ has been found to be an efficient, cheap, noncorrosive and reusable solid catalyst for a variety of organic synthesis like preparation of 2-aryloxazines, 2-aryltetrahydropyrimidines [18], α-aminophosphonates [19], and oxidation of alcohols [20].

Herein, we report a simple and convenient method for the synthesis of β-enaminones by condensation of various amines with β-dicarbonyls in the presence of catalytic amounts nano-SiO₂ as a reusable and eco-friendly catalyst at room temperature under solvent free conditions (Scheme 1).

Results and discussion

In this work, we initially showed the effect of the catalyst for the preparation of 4-(phenylamino)-pent-3-en-2-one. Acetylacetone (1 mmol) was treated with aniline (1 mmol) in the absence and presence of different amounts of nano-SiO₂ at room temperature for 60 min under solvent-free conditions (Table 1). As it is clear from this table, the best result was obtained when the reaction was carried out in the presence of 10 mol% of nano-SiO₂ (Table 1, entry 3). Use of higher amount of catalyst (20–30 mol%) neither improves the yield nor the reaction time further.

Table 1 Synthesis of β-enaminones in different amount of nano-SiO₂

To explore the scope and limitation of this reaction, we synthesized different substituted β-enaminones using condensation of β-dicarbonyls with various amines (aliphatic and aromatic) in the presence of nano-SiO₂ under solvent-free conditions at room temperature (Table 2). As indicated in this table, the reactions of aniline with cyclic and acyclic β-diketones under optimal reaction conditions afforded β-enaminones in excellent yields (Table 2, entries 1–4). Similarly anilines possessing both electron-donating and electron-withdrawing groups reacted with various β-dicarbonyls to afford excellent yields of the desired β-enaminones (Table 2, entries 5–11). In the same conditions, cyclic and acyclic aliphatic amines such as morpholine and benzylamine successfully condensed with β-dicarbonyls to produce the corresponding β-enaminones in excellent yields and short reaction times (Table 2, entries 12–17). In the case of ethylenediamine when 2 mmol of β-dicarbonyls was used the expected products were produced in excellent yields (Table 2, entries 18, 19).

Table 2 Synthesis of β-enaminones using nano-SiO₂ (10 mol%) under solvent-free conditions

The recyclability of the catalyst was also studied for the reaction of acetyl acetone with aniline. After the completion of the reaction, the catalyst was filtered off, washed with ethyl acetate, dried, and reused as such for subsequent experiments under the same reaction conditions. The results in Table 3 clearly established the recyclability and reusability of the catalyst without significant loss of activity.

Table 3 Reusability of the catalyst for synthesis of enaminones

Mechanistically, it is well established that the activation of the carbonyl groups of the diketones with the silanol groups of the nano-SiO₂ can facilitate the nucleophilic attack of the amine to generate the imine intermediate [9]. Subsequent tautomerisation of resulting imine forms the corresponding β-enaminones as shown in Scheme 2.

To show the advantages and limitation of the present method the synthesis of 3-(p-tolylamino)-5,5-dimethylcyclohex-2-enone was compared with some of those reported in the literature using other solid catalysts (Table 4).

Table 4 Comparison of the results for the synthesis of 3-(p-tolylamino)-5,5-dimethylcyclohex-2-enone using nano-SiO₂ with other catalysts

As it is evident from Table 4, nano-SiO₂ is an effective, reusable, and commercially available this purpose, leading to β-enaminone at ambient temperature with high yield and low catalyst loading.

Conclusion

We have demonstrated a green protocol for the preparation of β-enaminones using commercially available nano-SiO₂ as a heterogeneous catalyst. The major advantages of our method are solvent-free conditions, easy recovery and reuse of catalyst, short reaction time, excellent yield, easy work up, cost-effective use of cheap and commercially available catalyst.

Experimental

Nano-SiO₂ was purchased from Plasmachem Company. The structure of the products was characterized by spectral data (¹H NMR and ¹³C NMR) and physical properties and comparison with authentic samples.

General procedure for the preparation of β-enaminones using nano-SiO₂

A mixture of β-dicarbonyl (1 mmol), amine (1 mmol), and 0.006 g nano-SiO₂ (10 mol%) was stirred at room temperature without solvent. The progress of the reaction was monitored by TLC. After completion of the reaction, 10 cm³ ethyl acetate was added to the mixture and filtered off. The residue was washed with ethyl acetate and catalyst was recovered. The filtrate was evaporated and product was collected. In the case of ethylenediamine, under optimal reaction conditions two equivalents of β-diketone was used (Table 2, entries 18, 19).

Recycling of the catalysts

To a mixture of acetyl acetone (30 mmol) and aniline (30 mmol), 0.18 g nano-SiO₂ was added in one lot and the resulting mixture was stirred at room temperature for 60 min. After completion of the reaction, ethyl acetate was added to the mixture and the catalyst was filtered off, washed with ethyl acetate, dried, and reused as such for subsequent experiments under same reaction conditions (Table 3).