Catalytic activity of the nanoporous MCM-41 surface for the Paal–Knorr pyrrole cyclocondensation

2.1 Characterization of MCM-41

A small-angle powder XRD pattern of MCM-41 is presented in Fig. 1. The XRD pattern of MCM-41 shows four reflections: a very intense peak (1 0 0) and three additional high-order peaks (1 1 0), (2 0 0), and (2 1 0) with lower intensities. This pattern is characteristic of a hexagonal pore structure.

Fig. 1:

Small-angle powder XRD pattern of MCM-41.

Nitrogen sorption isotherms at 77 K for the prepared sample are presented in Fig. 2. The isotherm can be classified as type IV according to the IUPAC convention, and is typical of mesoporous materials [42].

Fig. 2:

N₂ adsorption–desorption isotherm of MCM-41.

2.2 Catalyst screening of various mineral oxides

Initially, we examined the condensation of hexane-2,5-dione (1.2 mmol) with 4-bromoaniline (1 mmol) to evaluate the efficiency of various mineral oxides as catalysts (Table 1). The reaction was screened under solvent-free conditions at room temperature within 1 h.

Table 1

Catalyst screening of various mineral oxides for the synthesis of 1j under neat conditions at room temperature within 1 h.

Entry	Catalyst, g	Time, min	Conversion, %a
1	–	60	38
2	MCM-41-HTb (0.02)	60	60
3	MCM-41-HT (0.04)	60	65
4	MCM-41-HT (0.06)	60	61
5	SiO2 (0.04)	60	42
6	TiO2 anatase (0.04)	60	41
7	Al2O3 neutral (0.04)	60	15
8	Al2O3 acidic (0.04)	60	18
9	Al2O3 basic (0.04)	60	10
10	ZnO (0.04)	60	16
11	Fe3O4 (0.04)	60	22

^aGas chromatography assay (%).

^bMCM-41 prepared using a hydrothermal method.

Among these solid surfaces, Fe₃O₄, ZnO, and basic, neutral, and acidic Al₂O₃ showed poor catalytic activities (Table 1, entries 7–11). TiO₂ and SiO₂ gave moderate yields, whereas MCM-41 catalyzed the reaction to afford the desired product in good yield.

2.3 Catalyst screening of various MCM-41 materials

Various MCM-41 surfaces prepared using the conventional hydrothermal method and microwave heating were tested for the same reaction (Table 2). The reaction in the presence of various MCM-41 materials resulted in 57–65 % yield of product. However, a 10–18 % decrease was observed for the sample prepared using microwaves at 480 W for 20 min (Table 2, entry 8). Porosimetry data showed that the catalyst had a high surface area in the range of 1054–1275 m² g⁻¹. Nevertheless, it seems that the yield of product is a function of the surface area of the catalyst, and below 1100 m² g⁻¹, a notable decrease in the catalytic activity is observed (Table 2, entries 1–8).

Table 2

Catalytic effect of various MCM-41 materials on the synthesis of 1j under neat conditions.

Entry	Catalyst	BET surface area, m2 g–1	Conversion, %a
1	MCM-41-HTb	1275	65
2	MCM-41-360 W-20 minc	1151	60
3	MCM-41-360 W-40 minc	1137	58
4	MCM-41-360 W-60 minc	1129	57
5	MCM-41-360 W-90 minc	1119	57
6	MCM-41-300 W-20 minc	1119	57
7	MCM-41-420 W-20 minc	1177	60
8	MCM-41-480 W-20 minc	1054	47

^aGas chromatography assay (%).

^bMCM-41 prepared using a hydrothermal method.

^cMCM-41 prepared using microwave heating.

2.4 Optimization of the model reaction

To investigate the role of mesoporous MCM-41, the same reaction was carried out in the absence or presence of a catalyst at different temperatures. In the absence of MCM-41 under ambient (i.e., room temperature) and thermal conditions (i.e., 50 °C and 70 °C), the uncatalyzed reaction afforded the product 1j in 38 %, 70 %, and 82 % yield, respectively (Table 3, entries 1–3). When the same reaction was catalyzed by MCM-41, the reaction yield sharply increased under various conditions (Table 3, entries 4–6); e.g., in the presence of MCM-41 as a catalyst, the product 1j was obtained in 65 % yield (instead of 38 %) at room temperature. Accordingly, the MCM-41 catalyzed reaction at 70 °C after 1 h exhibited the highest conversion rate and afforded the product 1j quantitatively (Table 3, entry 6).

2.5 Evaluation of the reaction scope

To expand the generality of this novel catalytic method, various aromatic primary amines were tested under the optimized conditions and the results are summarized in Table 4, indicating that both electron-donating (such as methoxy, methyl, and dimethyl) and electron-withdrawing (such as bromo, chloro, dichloro, and nitro) substituents on the aromatic ring of aniline underwent smooth reaction with hexane-2,5-dione giving excellent conversions in most cases. However, an extended reaction time is observed for nitro-substituted aniline derivatives (Table 4, entries 1g–1i) having a negative influence on the reaction rate.

Table 4

Solvent-free synthesis of N-substituted pyrroles catalyzed by MCM-41 at 70 °C.

Entry	Ar	Time, h	Conversion, %a	Yield, %b	M.p., °C
1a	4-Methoxyphenyl	1	100	95	56–57
1b	Phenyl	1	100	93	48–50
1c	4-Methylphenyl	1	100	94	44–45
1d	3-Methylphenyl	1	100	93	Oil
1e	2-Methylphenyl	1	97	91	Oil
1f	2,5-Dimethylphenyl	1	100	92	Oil
1g	4-Nitrophenyl	1/4	11/35	7/29	142–144
1h	3-Nitrophenyl	1/4	54/88	48/80	85
1i	2-Nitrophenyl	4	4	–	–
1j	4-Bromophenyl	1	100	94	75
1k	4-Chlorophenyl	1	100	93	55–57
1l	3,4-Dichlorophenyl	4	96	88	Oil
1m	Cyclohexyl	1	100	73	Oil
1n	tert-Butyl	4c	–	–	–
1o	iso-Propyl	4c	100	72	Oil

^aGas chromatography assay (%).

^bYields refer to those of pure isolated products.

^cThe reaction was carried out at 30 °C.

For comparison, the reactions with sterically more demanding primary aliphatic amines were also studied (Table 4, entries 1m–1o). In particular, with Ar = R = tert-butyl, no reaction was observed under these conditions.

2.6 Reusability of the catalyst

The feasibility of repeated use of MCM-41 was also examined. The recovery of the catalyst was very easy. After completion of the reaction, ethanol was added to the reaction mixture. The catalyst was simply filtered from the resulting mixture, and dried at 120 °C under reduced pressure for 2 h. The reused catalyst was stable under the reaction conditions, and its activity in terms of yields slightly decreased with increasing number of cycles of the reaction (conversion for six subsequent runs: 100 %– 100 %–100 %–99 %–95 %–92 %).

4.1 Materials and methods

Sodium silicate solution (7.5–8.5 % Na₂O, 25.5–28.5 % SiO₂, Merck-105621) and cetyltrimethylammonium bromide (96 %, Fluka-52370) were used for the preparation of MCM-41 without additional purification. All mineral oxides were available commercially. All other chemicals (H₂SO₄, HCl, and organic solvents) were of analytical quality, and water was purified in an SG Water purification system (Barsbüttel, Germany).

All of the products were characterized by a comparison of their spectroscopic data with those of authentic samples [38–40, 44].

The powder XRD pattern was recorded at room temperature from 1° to 10° in 2θ by using a D8 Advance instrument (Bruker AXS GmbH, Karlsruhe, Germany) with CuK_α radiation (λ = 0.15406 nm).

The N₂ adsorption/desorption analyses were performed on a BELSORP-miniII instrument at 77 K (BEL Japan). MCM-41 was degassed at 120 °C for 1.5 h under inert gas flow prior to analysis. Specific surface area, total pore volume, and pore diameter of samples were obtained by the Brunauer–Emmett–Teller (BET) method using BELSORP analysis software.

A laboratory microwave oven MW 3100 (Landgraf Laborsysteme HLL GmbH, Langenhagen, Germany) equipped with a magnetic stirrer operating at 2450 MHz was used for syntheses of MCM-41 samples. In order to prepare MCM-41 under microwave conditions, the top of the reaction vessel (placed inside the microwave chamber) was attached to a water-cooled reflux condenser, located outside of the microwave chamber, for reflux purpose. The temperature inside the vessel was monitored using a Precision Temperature Logger EBI-2 T Type 311 (possessing an external probe) from ebro^® Electronic GmbH and Co KG, Ingolstadt, Germany.

4.2 Preparation of MCM-41 using a hydrothermal method (MCM-41-HT)

MCM-41 was prepared through hydrothermal treatment by following a similar methodology according to Gonçalves and co-workers [41]. The following solutions were used: (A) a solution of 9.9 g sodium silicate in 30 mL deionized water; (B) a suspension of 8.12 g of cetyltrimethylammonium bromide in 80 mL deionized water.

In a typical experiment, solution A was added dropwise to a rapidly stirred suspension B. After 1-h stirring at ambient temperature, the obtained pH was 12.0. The pH was adjusted to 10.0 using dilute sulfuric acid (2 m) within 1 h.

The mixture was then autoclaved at 373 K for 2 days in Teflon-lined stainless steel reaction vessels. The solid product was recovered by filtration and washed with deionized water, until the filtrate had the final pH 7.0. The white precipitate was dried at 373 K under vacuum and calcined at 813 K for 6 h to remove the surfactant leading to MCM-41-HT.

4.3 Preparation of MCM-41 using microwave heating

In this procedure, after adjusting the pH of the suspension to 10.0 (as mentioned above), antifoam SILFAR^® S184 (0.2 g) was added to the obtained suspension and stirred for a further 1 h. The resulting mixture was loaded into the microwave vessel. The vessel was then inserted into the microwave chamber (equipped with a water-cooled reflux condenser), and the reaction was carried out maintaining the power at 300, 360, 420, and 480 W (50 %, 60 %, 70 %, and 80 % of maximum power, respectively) for an appropriate time (recorded temperature during irradiation was 96.5 °C). The solid product was recovered by filtration and washed with deionized water, until the filtrate had the final pH 7.0. The white precipitate was dried at 373 K under vacuum and calcined at 813 K for 6 h to remove the surfactant leading to MCM-41 prepared by microwave irradiation.

4.4 General procedure for Paal–Knorr pyrrole cyclocondensation

In a typical reaction, primary aromatic amine (1 mmol), hexane-2,5-dione (1.2 mmol), and MCM-41 (0.04 g) were stirred at 70 °C for the appropriate reaction time. After completion of the reaction (monitored by TLC or GC), ethanol (2 mL) was added to the reaction mixture, and the catalyst was recovered by filtration. The organic medium was removed with a rotary evaporator under reduced pressure to afford the product 1. The crude product was passed through a short column of neutral alumina [eluted with ethyl acetate–hexane (3:7)] to give the pure product.

4.5 Selected spectroscopic data

N-(4′-Bromophenyl)-2,5-dimethylpyrrole (1j): M.p. 75 °C. – ¹H NMR (500 MHz, CDCl₃): δ = 7.60 (d, 2H), 7.15 (d, 2H), 5.90 (s, 2H), 2.05 (s, 6H). – ¹³C NMR (125 MHz, CDCl₃): δ = 138.0, 132.2, 129.8, 128.6, 121.5, 106.0, 12.9. – MS (EI): m/z (rel. intensity, %) = 251 (80) [M]⁺, 250 (100), 249 (78), 169 (30), 154 (30), 129 (20).

N-(4′-Chlorophenyl)-2,5-dimethylpyrrole (1k): M.p. 55– 57 °C. – ¹H NMR (500 MHz, CDCl₃): δ = 7.42 (d, 2H), 7.14 (d, 2H), 5.90 (s, 1H), 2.02 (s, 6H). – ¹³C NMR (125 MHz, CDCl₃): δ = 137.5, 133.5, 129.5, 129.4, 128.5, 106.1, 12.9. – MS (EI): m/z (rel. intensity, %) = 206 (80), 205 (100) [M]⁺, 191 (10), 170 (25), 155 (25), 130 (20), 111 (10).