Background

Recently, the applications of nanoparticles (NPs) in catalysis have attracted considerable attention because of their improved efficiency and facile reaction conditions [1, 2]. These materials have enormously large and highly reactive surface area, so these materials exhibit some unique properties in comparison to bulk materials. Because of individual property of silica-based NPs compared to others, it has been well studied. Silica NPs are easily prepared in room temperature, and their sizes can be easily tuned. On the other hand, silica NPs are stable in organic solvent and are environmentally friendly materials [3–12].

The ultrasonic irradiation is applicable to a broad range of practical syntheses. Some advantages of ultrasound procedure are short reaction times, mild reaction conditions, formation of purer products, and waste minimization. Ultrasonic irradiation can also be used to influence selectivity and yields of reactions [13–15]. Despite the vast advantages of this technique, the use of ultrasound in the synthesis of organic compounds is not fully developed. To develop the application of ultrasound in organic reaction, herein, we wish to describe the reaction of indoles with aldehydes in the presence of a catalytic amount of native silica gel nanoparticles under ultrasonic irradiation (Scheme 1).

Scheme 1
scheme 1

Reaction of indoles with aldehydes in the presence of a catalytic amount of native silica gel nanoparticles.

Full size image

Bis(indolyl)methanes, indole, and their derivatives are known as important intermediates in organic synthesis and pharmaceutical chemistry, and exhibit various physiological properties [16]. Bis(indolyl)methanes are found in cruciferous plants and are known to promote beneficial estrogen metabolism [17] and induce apoptosis in human cancer cells. Therefore, there is great interest in the synthesis of these compounds [18–21]. Synthetically, the reaction of indole with aldehydes or ketones produces azafulvenium salts that react further with a second indole molecule to form bis(indol-3-yl)methanes [22]. In recent years, syntheses of this class of molecules under mild conditions have been reported, with promoters such as montmorillonite clay K-10 [23, 24], trichloro-1,3,5-triazine [25], AlPW12O40[26], sodium dodecyl sulfate [27], ZrCl4[28], I2[29], In(OTf)3/ionic liquid [30], CuBr2[31], MW/Lewis acids (FeCl3, BiCl3, InCl3, ZnCl2, CoCl2) [32], NaHSO4 and Amberlyst-15 [33], silica sulfuric acid [34], metal hydrogen sulfates [35], NaHSO4/ionic liquid [36], CAN [37], NBS [38], and Ph3CCl [39]. However, most of the existing methods involve toxic metal ions and solvents, have high costs, use corrosive reagents, and have cumbersome work-up procedures. Consequently, new procedures that address these drawbacks are desirable.

Methods

Materials and apparatus

All chemicals were purchased from Nanostructured & Amorphous Materials, Inc. (nano SiO2 15 nm; TX, USA), Sigma-Aldrich Co. (MO, USA), or Merck & Co., Inc (NJ, USA) chemical companies and used without further purification. Products were characterized by comparing their spectral (IR, 1HNMR, and TLC) and physical data (m.p. and b.p.) with those of authentic samples. Infrared spectra were recorded on a WQF-510 FTIR spectrometer (Rayleigh Instruments Ltd., Essex, England). 1H NMR spectra were recorded with a DRX-500 AVANCE spectrometer (Bruker Corporation, MA, USA) at 500 MHz (1H) in CDCl3 or DMSO-d6 as the solvent and tetramethyl silaneas internal reference. Melting points were measured with Electrothermal 9300 (Electrothermal, Essex, UK). Soltec Sonica Mod 3200 ETH ultrasonic cleaner bath (Soltec S.r.l., Milan, Italy) was used for ultrasonic irradiation. The reaction vessel placed inside the ultrasonic bath contained water.

General procedure

A mixture of indole (1 mmol), aldehyde (2 mmol), and silica NPs (20 mol%) was mixed and added some drop of diethyl ether to it. Further, the reaction mass was irradiated under ultrasonic irradiation at 80°C for appropriate time (Table 1). The progress of reaction was monitored by TLC. After the completion of reaction, the colored product obtained was recrystallized from ethanol and filtered to get the pure product.

Table 1 Synthesis of bis (indolyl)methanes by the reaction of indole with aldehydes in the presence of silica NPs in solvent-free condition
Full size table

Results and discussion

The methodology developed is simple with high to excellent yields. We first compared the catalyst effect on different solvents for synthesis of bis(indol-3-yl)methanes using native silica NPs, and the results are summarized in Table 2.

Table 2 Optimization of solvent effect on the model reaction
Full size table

In a typical experiment, the reaction of indole and benzaldehyde in solvent or solvent-free condition was carried in the presence of silica NPs to afford the corresponding bis(indol-3-yl)methanes. We kept the catalyst concentration constant and used different solvents like dichloromethane, chloroform, toluene acetonitrile, THF, ethanol, and acetonitrile which afforded lower yields. We have also studied the sonochemical effect on model reaction using different solvents. In all cases, the experimental results show that the yields of the products are very low under sonication. Using lower amount of catalyst resulted in lower yields, while higher amount of catalyst did not affect the reaction times and yields, and in the absence of catalyst, the yield of the product was not found. The best results were obtained using 20 mol% of catalyst (Table 2, entry 7). Based on the results of this study, it seems that the reaction times and yields will improve in the solvent-free condition under ultrasound irradiation. The obtained results are summarized in Table 2, entries 1 to 7. These results suggest that the absence of solvent is the best condition for synthesis of bis(indol-3-yl)methanes. Furthermore, the effect of catalyst load on reaction time and yield is explored in Table 3.

Table 3 Screening of catalyst concentration on model reaction
Full size table

The best result is obtained with 20 mol% of the catalyst. After optimizing the conditions, the generality of this method was examined by the reaction of several substituted aryl aldehydes with indole. The results are shown in Table 1. The products were isolated and identified by melting point, NMR, and IR (Scheme 1).

Conclusion

Silica NPs in solvent-free condition were found to be selective and effective catalysts in green synthesis of bis(indolyl)methanes under ultrasonic irradiation. This catalyst provides clean conversion; greater selectivity and easy work-up make this protocol practical and economically attractive.