Periodic mesoporous organosilica with ionic-liquid framework supported manganese: an efficient and recyclable nanocatalyst for the unsymmetric Hantzsch reaction

Abstract

An efficient approach for the green and rapid synthesis of biologically active substituted polyhydroquinoline derivatives via unsymmetric Hantzsch reaction using an ionic liquid based periodic mesoporous organosilica supported manganese (Mn@PMO-IL) catalyst under solvent-free conditions is described. This catalyst showed high reactivity and selectivity for the preparation of a set of different derivatives of polyhydroquinolines under moderate reaction conditions and short times. Moreover, the catalyst was also recovered and reused several times without important decrease in reactivity and yields. The nitrogen adsorption–desorption and transmission electron microscopy of the recovered catalyst significantly proved the high stability and durability of the catalyst under applied reaction conditions. Furthermore, compared to the classical methodologies, this method consistently illustrated the advantages of short reaction times, low catalyst loading, high yields, easy separation and purification of the products, and high recoverability and reusability of the catalyst.

---

Introduction

Polyhydroquinolines, as a family of 1,4-dihydropyridine (1,4-DHP) derivatives, are one of the most important groups of nitrogen heterocycles that have attracted considerable interest due to their promising pharmacological and therapeutic activities such as calcium channel blockers, vasodilating, bronchodilating, antiatherosclerotic, antitumor, geroprotective, hepatoprotective, and antidiabetic.^1,2 Moreover, some 1,4-dihydropyridines exhibit other medicinal applications which include platelet antiaggregatory activity,³ neuroprotectant,⁴ cerebral antischemic activity in the treatment of Alzheimer's disease,⁵ and chemosensitizer acting in tumour therapy.⁶ As an example, quinolines having a 1,4-dihydropyridine nucleus are being used as antiasthamatic, antiinflammatory, antibacterial, and tyrosine kinase inhibiting agents.⁷ Furthermore, the dihydropyridine unit has widely been used as a hydride source for reductive amination.⁸ Due to the aforementioned advantages of the polyhydroquinolines in the biological and chemical worlds, to date many strategies have been developed for the synthesis of these compounds. These were firstly prepared by Hantzsch in 1882 ⁹ via cyclocondensation reaction between alkyl acetoacetate, aldehyde and ammonia in acetic acid or by refluxing in alcohol. In recent years, numerous catalysts have been successfully reported for the preparation of these compounds under homogeneous reaction conditions. Some of these developing catalysts include TMS-iodide,¹⁰ Bu₄N⁺HSO₄⁻,¹¹ K₇[PW₁₁CoO₄₀],¹² ionic liquids,¹³ metal triflates,¹⁴ CAN,¹⁵ iodine,¹⁶ PTSA-SDS,¹⁷ tris(pentafluorophenyl)borane,¹⁸ boronic acids,^19,20 HClO₄/SiO₂ ²¹ and BINOL-phosphoric acids.²² Nevertheless, the problems of environmentally harmful, expensive and non-reusable catalysts and product separation limit the use of these homogeneous catalytic systems. To overcome these drawbacks, recently several attempts have been successfully developed for the synthesis of polyhydroquinoline derivatives using efficient and reusable heterogeneous catalysts under appropriate conditions. Some of applied catalysts are silica-supported acids,^23,24 ZnO NPs,²⁵ polymers^26,27 and Ni nanoparticles.²⁸ However, some of the later catalytic methods have disadvantages of high reaction temperature, the use of ecologically suspected organic solvents and longer reaction times. Therefore, the developing reaction conditions in the synthesis of polyhydroquinoline derivatives using efficient and reusable catalysts under green conditions is still the need of the day.

On the other hand, organic functionalized ordered mesoporous silicas with tailored porosity on several length scales are of interest for a variety applications in areas of adsorption, chromatography, catalysis, sensor technology, and gas storage due to their large specific surface area and uniform pore size with high coverage of introduced functional groups.^29,30 Among different types of organic containing mesoporous silicas, periodic mesoporous organosilicas (PMOs), which are synthesized by the simultaneous use of a soft template and a hydrolysable bis-silane condensing around the template,³¹ have mostly progressed the field of material science research. The unique properties of PMOs such as tuneable chemophysical properties, high loading of uniform distribution of organic functional groups in their framework and superior thermal stability make them attractive candidate for a wide range of applications in catalysis, electronic, support and adsorption chemistry.³² In the last decades, ionic liquids (ILs) have attracted rising interest with a various range of applications in different areas of chemistry because of their significant properties such as extremely low volatility, low melting point, high chemical and thermal stability and high ionic conductivity.³³ However, in spite of the remarkable utility of these compounds, their widespread applications in process chemistry is still restricted because many of them are very expensive.³⁴ Moreover, due to high viscosity of ionic liquids only a small amount of them (called diffusion layer) participates in the chemical process.³⁵ To overcome these limitations, the concept of supported ionic liquids has been recently developed. Especially, silica supported ionic liquids has been successfully developed and applied in several chemical transformations as an effective support for transition metal catalysts. Along this regard, more recently we have prepared a novel periodic mesoporous organosilica with alkyl imidazolium ionic liquid framework (PMO-IL) and studied its application as effective support for the immobilization and stabilization of a set of different transition metals (M@PMO-IL). The prepared metal containing PMO-IL nanomaterials were then successfully applied as powerful and highly reusable catalysts in a number of organic reactions such as aerobic oxidation of alcohols and carbon–carbon bond coupling processes.^36,37 In continuation of our study on applications of metal supported PMO-IL, herein the catalytic application of a manganese containing ionic liquid-based periodic mesoporous organosilica (MnPMO-IL) material is investigated in the synthesis of polyhydroquinoline derivatives. This was achieved by the one-pot condensation of aldehydes (aromatic, aliphatic, unsaturated and heterocyclic), 5,5-dimethyl-1,3-cyclohexanedione (dimedone) or 1,3-cyclohexanedione, β-dicarbonyl and ammonium acetate in the presence of Mn@PMO-IL nanocatalyst under solvent free conditions (Scheme 1). Moreover the reactivity, reusability and stability of the catalyst during reaction process have also been studied in detail.

Scheme 1 Preparation of the Mn@PMO-IL nanocatalyst and its application in synthesis of polyhydroquinolines.

Results and discussion

The PMO-IL nanomaterial was first prepared by hydrolysis and co-condensation of 1,3-bis(3-trimethoxysilylpropyl) imidazolium iodide and tetramethoxysilane in the presence of Pluronic P123 under acidic conditions.³⁷ The PMO-IL nanomaterial was then reacted with a sub-stoichiometric amount of manganese acetate in DMSO solvent, according to our recently reported procedure, to produce the Mn@PMO-IL nanocatalyst (Scheme 1).³⁸ This catalyst was then characterized with some techniques such as infrared (IR) spectroscopy, thermal gravimetric analysis (TGA), powder X-ray diffraction (PXRD), transmission electron microscopy (TEM) and energy dispersive X-ray (EDX) spectroscopy. The IR spectrum of the Mn@PMO-IL was performed to investigate the presence of organic functional groups in the material framework (Fig. 1). This showed bands at 1147, 1073 and 952 cm⁻¹ corresponding to asymmetric and symmetric vibrations of Si–O–Si bonds.^36c The strong and broad signal cleared about 3300 cm⁻¹ is attributed to O–H bonds of siloxane groups. The bands observed at 2933 and 2859 cm⁻¹ are assigned to C–H stretching of aliphatic moieties. Moreover, the signals cleared at 1563 and 1635 cm⁻¹ are, respectively, attributed to C=C and C=N stretching vibrations of imidazolium ring.^36c,36e These observations successfully confirm victorious incorporation of alkyl imidazolium ionic liquid groups in the material framework.

Fig. 1 IR spectrum of the Mn@PMO-IL nanocatalyst.

Thermal gravimetric analysis (TGA) of the Mn@PMO-IL was performed to investigate the thermal stability of the material (Fig. 2). This analysis illustrated a weight loss of 6.64% in the temperature below 120 °C corresponding to removal of water. A very small weight loss (2.28%) between 120 and 280 °C is attributed to elimination of surfactant template remained from extraction process. The third weight loss (18.35%) from 280 to 800 °C is related to removal of ionic liquid functional groups located in the material framework. This data successfully proves the successful incorporation of organic functional moieties in the solid network and confirms high thermal stability of the material.

Fig. 2 Thermal gravimetric analysis (TGA) of the Mn@PMO-IL nanocatalyst.

The PXRD analysis of the material demonstrated a single high intensity peak at 2θ 0.7–1.3 which indexed as the d100 reflection and matches with the 2-dimensional hexagonal materials having long range periodicity (Fig. 3). This significantly proves the presence of uniform mesostructure with high regularity. The transmission electron microscopy (TEM) image of the Mn@PMO-IL was in good agreement with PXRD analysis and successfully confirmed a two dimensional hexagonal structure with high regularity for the material (Fig. 4). Furthermore, this image together with PXRD analysis proved the high stability of the material structure after immobilization of manganese species onto/into the mesopores.

Fig. 3 Powder X-ray diffraction (PXRD) of Mn@PMO-IL.

Fig. 4 Transmission electron microscopy (TEM) image of Mn@PMO-IL.

Energy-dispersive X-ray (EDX) spectroscopy showed the presence of C, O, Si, Cl and Mn in the Mn@PMO-IL nanocatalyst (Fig. 5). The elemental distribution mapping of this analysis shows signals of carbon : oxygen : silicon : chlorine : manganese in the ratio of 34.2 : 44.9 : 16.7 : 1.3 : 1.9 wt%, respectively. This confirms successful incorporation of expected elements in the material network. It is also important to note that the X-ray photoelectron spectroscopy (XPS) of the catalyst showed peaks at binding energies of 654.2 and 642.6 eV for the Mn 2p_1/2 and Mn 2p_3/2, respectively, confirming that Mn species are strongly bound to electronegative atoms and may be they are as Mn(III).³⁸

Fig. 5 Energy dispersive X-ray (EDX) spectroscopy of the Mn@PMO-IL.

Effect of catalyst loading, solvent and temperature in the synthesis of polyhydroquinolines

After characterization, the catalytic activity of Mn@PMO-IL in the synthesis of polyhydroquinolines under different reaction conditions was investigated. For comparison of the results between solvent and solvent-free conditions, the solvent effect in the condensation of dimedone (1 mmol), benzaldehyde (1 mmol), ethylacetoacetate (1 mmol) and ammonium acetate (1 mmol) in the presence of Mn@PMO-IL (1 mol%), as a test model, was studied. As shown in Table 1, among the applied solvents such as ethanol, methanol, water, chloroform and a solvent-free system, the best result was obtained after 20 min under solvent-free conditions in excellent yield (Table 1, entries 1–5). With this optimistic result in hand, we then investigated the best reaction conditions by using different amounts of catalyst. An increase in the quantity of Mn@PMO-IL from 0.35 to 1 mol% also increased the product yield from 35% to 95% (Table 1, entries 5–7).

Table 1 Catalytic activity evaluation and the effect of temperature and solvent in the synthesis of polyhydroquinolines^a

Entry	Mn@PMO-IL (mol%)	Temp. (°C)	Solvent	Time (min)	Yield^b (%)
a Reaction conditions: dimedone (1 mmol), benzaldehyde (1 mmol), ethylacetoacetate (1 mmol), ammonium acetate (1 mmol) and catalyst (1 mol%).b Isolated yields.
1	1	Reflux	Ethanol	30	53
2	1	Reflux	Methanol	30	48
3	1	Reflux	Water	30	45
4	1	Reflux	Chloroform	30	38
5	1	80	—	20	95
6	0.7	80	—	20	67
7	0.35	80	—	20	35
8	None	80	—	120	Trace
9	1	60	—	20	53
10	1	45	—	20	30
11	PMO-IL	80	—	60	25
12	Mn(OAc)3·2H2O	80	—	20	95

---

It is also important to note, in the absence of catalyst at 120 min under the same conditions as before, only a trace amount of product was obtained (Table 1, entry 8). Furthermore, by using PMO-IL instead of Mn@PMO-IL as catalyst, the rate of the model reaction was significantly decreased and a lower yield of product was obtained after 60 min (Table 1, entry 11). On the other hand, applying of Mn(OAc)₃·2H₂O as catalyst gave excellent yield of the product (Table 1, entry 12), however, this is not recoverable and reusable for the next runs. These observations show that the reaction cycle is mainly catalyzed by manganese species immobilized on the PMO-IL nanostructure. Accordingly, in all further reactions, 1 mol% of the Mn@PMO-IL catalyst was used because of satisfactory yield of the product in reasonably short time.

Our study also showed that the reaction was also effected by the amount of heat and the best result was observed at 80 °C (Table 1, entry 5 vs. entries 9, 10). In another study, the reaction was performed using different quantities of reagents. This showed that the best result is obtained with a 1 : 1:1 : 1 ratio of dimedone, benzaldehyde, ethyl acetoacetate and ammonium acetate, respectively.

To demonstrate the generality of this method, we next investigated the scope of this reaction under the optimized conditions (Mn@PMO-IL 1 mol%, solvent-free, 80 °C). As shown in Table 2, this method was equally effective irrespective of the nature and positions of the substituents attached to the phenyl ring of the aromatic aldehyde. All strongly activating (4c, 4f, 4g, 4k, 4l, 4p, 4s, 4u), weakly activating (4h, 4n, 4x), weakly deactivating (4d, 4m, 4r, 4t), and strongly deactivating (4b, 4j, 4v) substrates gave products with nearly equal ease. As shown, benzaldehyde substrates containing activating substituents such as OH (Table 2, entries 6, 12 and 19), CH₃O (Table 2, entry 21) and CH₃ (Table 2, entries 8, 14 and 23) furnished high yields of corresponding coupling adducts. Benzaldehyde (Table 2, entries 1, 5, 9 and 23) also gave satisfactory yields of related products. Moreover, other aldehyde substrates containing deactivating substituents such as NO₂ (Table 2, entries 2, 10 and 22) and Cl (Table 2, entries 4, 13, 18 and 20) delivered high yields of corresponding coupling products. In addition, the aliphatic aldehydes such as butanal (Table 2, entry 15) afforded a 55% yield in 100 min. Also acid-sensitive substrates such as cinnamaldehyde proceeded well to give the corresponding polyhydroquinoline without any side product (entry 17). Furthermore, the procedure worked well for heterocyclic aldehydes (Table 2, entries 3, 7, 11 and 16). These observations strongly confirm high efficiency and powerful activity of the present catalyst for a broad range of aldehydes to produce different derivatives of polyhydroquinolines which are important and applicable in drug chemistry.

Table 2 Synthesis of polyhydroquinoline derivatives in the presence of Mn@PMO-IL catalyst^a

Entry	R1	R2	R3	Compounds	Time (min)	Yield^b (%)	Mp (°C)
							Found	Reported
a All products were characterized by ^1H NMR, ^13C NMR and IR spectroscopies and compared with the reports in the literature.^15,26,28,39,40b Isolated yields.
1	C6H5	H	OEt	4a	20	90	241–242	240–241
2	4-NO2C6H4	H	OEt	4b	25	90	203–205	204–205
3	2-Thienyl	H	OEt	4c	15	92	232–233	233–234
4	4-ClC6H4	H	OEt	4d	20	87	234–236	234–235
5	C6H5	H	Me	4e	45	80	227–230	229–230
6	3-HOC6H4	H	Me	4f	35	87	244–246	—
7	2-Furyl	H	OMe	4g	20	95	212–216	—
8	4-CH3C6H4	H	OMe	4h	20	89	218–220	—
9	C6H5	Me	OEt	4i	20	95	202–204	203–204
10	4-NO2C6H4	Me	OEt	4j	20	88	243–245	244–246
11	2-Thienyl	Me	OEt	4k	20	90	239–241	237–239
12	3-HOC6H4	Me	OEt	4l	20	92	220–222	218–220
13	2-ClC6H4	Me	OEt	4m	20	92	207–209	206–208
14	4-CH3C6H4	Me	OEt	4n	20	88	260–262	261–263
15	CH3CH2CH2	Me	OEt	4o	100	55	147–149	147–148
16	2-Furyl	Me	OEt	4p	20	92	247–248	246–248
17	C6H5–CH=CH	Me	OEt	4q	28	87	204–206	205–207
18	2,4-Cl2C6H3	Me	OEt	4r	20	85	240–243	241–244
19	3-CH3O-4-HOC6H4	Me	OEt	4s	20	91	202–204	200–202
20	4-ClC6H4	Me	OMe	4t	20	85	219–222	220–222
21	4-CH3OC6H4	Me	OMe	4u	20	87	258–260	259–261
22	3-NO2C6H4	Me	OMe	4v	20	85	232–234	234–236
23	C6H5	Me	OMe	4w	20	90	209–211	212–214
24	4-CH3C6H4	Me	OMe	4x	20	86	268–271	270–274

---

Since the reusability of the catalysts is an important benefit and makes them useful for commercial applications, in the next study the recovery and reusability of Mn@PMO-IL were investigated. For this, the reaction of dimedone, benzaldehyde, ethylacetoacetate and ammonium acetate in the presence of 1 mol% catalyst was selected as a test model. To achieve the reaction efficiency of recovered catalyst, after completion of the reaction, the obtained mixture was filtered and washed completely with ethanol to give the catalyst. The recovered catalyst was dried and then used again in the same reaction that led to the yield of 94%. The more investigations showed that the catalyst could be recovered and reused, under the same conditions of the fresh run, for at least five times without any considerable loss in activity (Fig. 6A). Also, re-activity of the catalyst was investigated (Fig. 6B). To do this, Mn@PMO-IL was added to a mixture of dimedone, benzaldehyde, ethylacetoacetate and ammonium acetate and the reaction mixture was heated in 80 °C. After completion of the reaction, monitored by TLC, the fresh amounts of starting materials were added to the previous reaction mixture in the flask and stirring and heating were carried out to complete the second cycle. These cycles were occurred to ten times without noticeable decrease in yield of the reactions (Fig. 6B). These observations significantly prove high recoverability, reusability, reactivity and stability of the present catalyst under applied reaction conditions.

Fig. 6 (A) Reusability and (B) re-activity of the Mn@PMO-IL nanocatalyst in the synthesis of 4i.

The recovered catalyst after third reaction cycle was analyzed by transmission electron microscopy and nitrogen adsorption–desorption experiment. The nitrogen adsorption–desorption analysis showed a type IV isotherm with H1 hysteresis loop and high intensity in relative pressure of 0.4–0.6 (Fig. 7). The BET surface area and mean pore volume of this material was found to be 435 m² g⁻¹ and 8.54 cm³ g⁻¹, respectively. Moreover, the BJH calculations also illustrated a peak with high intensity and mean pore diameter of 6 nm confirming the presence of uniform pores in the meso-range (Fig. 7). The TEM image of this material was in good agreement with nitrogen sorption data and significantly illustrated a uniform and regular mesopores which is characteristics of two dimensional hexagonal structures (Fig. 8). These observations strongly confirm high stability and recoverability of the Mn-nanocatalyst under applied reaction conditions. The high activity, recoverability and stability of the present catalytic system may be attributed to ionic liquid nature of the PMO-IL as well as uniform mesoporous channels of the material, which effectively immobilize the active Mn species and protect them against leaching and deactivation.

Fig. 7 Nitrogen adsorption–desorption (top) and BJH pore size distribution (bottom) isotherms of recovered Mn@PMO-IL after third reaction cycle.

Fig. 8 TEM image of recovered Mn@PMO-IL catalyst after third reaction cycle.

A proposed mechanism for the Mn@PMO-IL nanocatalyst catalyzed synthesis of polyhydroquinolines is presented in Scheme 2. The role of catalyst is shown in steps 1 and 5 where it catalyzes the Knoevenagel type coupling of aldehydes with active methylene compounds and in steps 3 and 6 where it catalyzes the Michael type addition of intermediates 5, 6 or 7, 8 to give product 4. The formation of acridinedione 9 is possible when 5 reacts with 7,⁴¹ since this possibility is discarded due to non-formation of intermediates 5 and 6.⁴² A literature survey also adjusts with absence of acridinediones as a by-product during present reaction.^10–28

Scheme 2 Plausible mechanism of catalytic synthesis of polyhydroquinolines using Mn@PMO-IL.

Experimental

Synthetic procedures, materials and methods

Chemicals were purchased from Merck, Fluka and Aldrich chemical companies. Melting points were determined using a Barnstead Electrothermal (BI 9300) apparatus and are uncorrected. IR spectra were obtained using a FT-IR JASCO-680 spectrometer instrument. NMR spectra were taken with a Bruker 400 MHz Ultrashield spectrometer at 400 MHz (¹H) and 100 MHz (¹³C) using CDCl₃ or DMSO-d₆ as the solvent with TMS as the internal standard. TEM image was taken on a FEI Tecnai 12 BioTWIN microscope operated at 120 kV. The thermal gravimetric analysis (TGA) was measured by NETZSCH STA 409 PC/PG from room temperature to 800 °C.

Preparation of manganese supported ionic liquid based periodic meoporous organosilica (Mn@PMO-IL) catalyst

To do this, firstly the PMO-IL nanomaterial was prepared according to our previous reported procedure.³⁷ Then Mn(OAc)₃·2H₂O (0.5 mmol) was added to a monodispersed solution of PMO-IL material (1 g, 1.0 mmol IL per g) in DMSO (4.5 mL) under argon atmosphere. The mixture was first stirred at 50 °C for 6 h and then at 100 °C for 2 h. After that, the reaction solution was cooled to room temperature and the resulting mixture was filtered and washed completely with ethanol to remove unsupported Mn(OAc)₃·2H₂O. The final material was obtained after drying by evacuation at 60 °C for 12 h and denoted as Mn@PMO-IL.³⁸

General procedure for the preparation of polyhydroquinolines

In a round-bottomed flask the aldehyde (1 mmol), 1,3-cyclohexanedione derivatives (1 mmol), ammonium acetate (1 mmol), β-dicarbonyl (1 mmol) and Mn@PMO-IL nanocatalyst (1 mol%) were mixed thoroughly. The flask was heated at 80 °C with concomitant stirring. After completion of the reaction confirmed by TLC (eluent : EtOAc : n-hexane), hot ethanol (5 mL) was added and the obtained solution was filtered and completely washed with ethanol. The solvent was then evaporated and the crude products were recrystallized in ethanol and gave pure crystals in 80–95% yields based on the starting aldehyde. The products were characterized by IR, ¹H NMR, ¹³C NMR and via comparison of their melting points with the reported ones. Spectroscopic data of new compounds are as following:

2-Methyl-3-acetyl-5-oxo-4-(3-hydroxyphenyl)-1,4,5,6,7,8-hexahydroquinoline (4f)

Mp: 244–246 °C; R_f = 0.31 (n-hexane : ethyl acetate = 3 : 1); IR (KBr): 3417, 3255, 3202, 2960, 1665, 1613, 1478, 1222 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ (ppm): 1.91–2.15 (m, 2H), 2.18 (s, 3H), 2.25 (t, J = 11.2 Hz, 2H), 2.41 (s, 3H), 2.46 (t, J = 7.9 Hz, 2H), 5.24 (s, 1H), 7.08–7.30 (m, 4H), 9.11 (s, 1H); ¹³C NMR (100 MHz) δ (ppm): 18.79, 26.24, 29.13, 29.88, 31.95, 35.22, 50.24, 109.86, 113.09, 127.05, 127.58, 129.26, 131.14, 131.46, 142.74,144.55, 149.44, 193.78, 197.91; Anal. calcd for C₁₈H₁₉NO₃: C, 72.71; H, 6.44; N, 4.71; O, 16.14; found: C 72.62, H 6.37, N 4.80.

2-Methyl-5-oxo-4-(2-furyl)-1,4,5,6,7,8-hexahydroquinoline-3-carboxylic acid methyl ester (4g)

Mp: 212–216 °C; R_f = 0.40 (n-hexane : ethyl acetate = 3 : 1); IR (KBr): 3285, 3079, 2944, 1698, 1649, 1608, 1483, 1220 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ (ppm): 0.91–1.15 (m, 2H), 1.93 (t, J = 6.5 Hz, 2H), 2.26 (s, 3H), 2.51 (t, J = 4.0 Hz, 2H), 3.60 (s, 3H), 5.06 (s, 1H), 5.79–5.83 (m, 1H), 6.19–6.25 (m, 1H), 7.32–7.40 (m, 1H), 9.25 (s, 1H); ¹³C NMR (100 MHz) δ (ppm):18.16, 20.78, 26.11, 29.35, 36.58, 50.78, 100.24, 104.0, 107.71, 109.43, 141.18, 146.03, 152.26, 158.29, 167.09, 194.42; Anal. calcd for C₁₆H₁₇NO₄: C, 66.89; H, 5.96; N, 4.88; O, 22.27; found: C 66.78, H 5.89, N 4.95.

2-Methyl-5-oxo-4-(4-methylphenyl)-1,4,5,6,7,8-hexahydroquinoline-3-carboxylic acid methyl ester (4h)

Mp: 218–220 °C; R_f = 0.33 (n-hexane : ethyl acetate = 3 : 1); IR (KBr): 3286, 2960, 1716, 1671, 1605, 1379, 1225 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ (ppm): 1.70–1.92 (m, 2H), 2.18 (t, J = 4.2 Hz, 2H), 2.26 (s, 3H), 2.28 (s, 3H), 2.47 (t, J = 7.7 Hz, 2H), 3.52 (s, 3H), 4.87 (s, 1H), 6.97 (d, J = 7.8 Hz, 2H),7.02 (q, J = 7.93 Hz, 2H), 9.13 (s, 1H); ¹³C NMR (100 MHz) δ (ppm):18.14, 20.52, 26.08, 31.64, 34.90, 50.60, 103.24, 111.23, 111.26, 112.58, 127.09, 128.45, 134.53, 144.74, 145.03, 151.16, 167.38, 194.61; Anal. calcd for C₁₉H₂₁NO₃: C, 73.29; H, 6.80; N, 4.50; O, 15.41; found: C 73.19, H 6.72, N 4.57.

General procedure for the recovery of Mn@PMO-IL nanocatalyst in the polyhydroquinolines synthesis

In a flask containing benzaldehyde (1 mmol), ethylacetoacetate (1 mmol), dimedone (1 mmol) and ammonium acetate (1 mmol) 1 mol% of Mn@PMO-IL nanocatalyst was added and the mixture was stirred at 80 °C. After completion of the reaction, the mixture was added to hot ethanol and the obtained solution was hotly filtered and completely was washed with ethanol. The catalyst was then recovered and reused at the same conditions as the first run for at least 5 reaction cycles and delivered corresponding product in high yield and selectivity.

Conclusions

We have described the catalytic application of a manganese containing ionic liquid-based ordered mesoporous organosilica (Mn@PMO-IL) in the unsymmetric Hantzsch reaction. The reaction system was significantly affected by catalyst loading, reaction temperature and solvent. The catalyst illustrated high efficiency and reactivity for the synthesis of substituted polyhydroquinoline derivatives using a variety of activated and deactivated aldehyde, 1,3-cyclohexanedione derivatives, ammonium acetate and β-dicarbonyls under solvent-free conditions. In addition, the catalyst could be recovered and reused at least five times with no decrease in its activity and selectivity. Also, investigation of the re-activity of the catalyst showed that the repeating cycles could be occurred to ten times without noticeable decrease in times and yields of the reactions. Therefore, the attractive features of this protocol are simple procedure, short reaction times, high yields, simple workup, reusability and re-activity of the catalyst and simple purification of the products.

Acknowledgements

The authors thank the Yasouj University and the Iran National Science Foundation (INSF) for supporting this work.

Notes and references

1. (a) F. Bossert, H. Meyer and E. Wehinger, Angew. Chem., Int. Ed., 1981, 20, 762–769; (b) H. Nakayama and Y. Kasoaka, Heterocycles, 1996, 42, 901–909.
2. (a) T. Godfraid, R. Miller and M. Wibo, Pharmocol. Rev., 1986, 38, 321–416; (b) A. Sausins and G. Duburs, Heterocycles, 1988, 27, 269–289; (c) P. P. Mager, R. A. Coburn, A. J. Solo, D. J. Triggle and H. Rothe, Drug Des. Discovery, 1992, 8, 273–289; (d) R. Mannhold, B. Jablonka, W. Viogdt, K. Schoenafinger and K. Schravan, Eur. J. Med. Chem., 1992, 27, 229–235.
3. R. G. Bretzel, C. C. Bollen, E. Maeser and K. F. Federlin, Am. J. Kidney Dis., 1993, 21, 53–64.
4. V. Klusa, Drugs Future, 1995, 20, 135–138.
5. R. G. Bretzel, C. C. Bollen, E. Maeser and K. F. Federlin, Drugs Future, 1992, 17, 465–468.
6. R. Boer and V. Gekeler, Drugs Future, 1995, 20, 499–509.
7. (a) Y. L. Chen, K. C. Fang, J. Y. Sheu, S. L. Hsu and C. C. Tzeng, J. Med. Chem., 2001, 44, 2374–2377; (b) G. Roma, M. D. Braccio, G. Grossi and M. Chia, Eur. J. Med. Chem., 2000, 35, 1021–1035; (c) M. P. Maguire, K. R. Sheets, K. McVety, A. P. Spada and A. Zilberstein, J. Med. Chem., 1994, 37, 2129–2137.
8. T. Itoh, K. Nagata, M. Miyazaki, H. Ishikawa, A. Kurihara and A. Ohsawa, Tetrahedron, 2004, 60, 6649–6655.
9. A. Hantzsch, Justus Liebigs Ann. Chem., 1882, 215, 1–82.
10. G. Sabitha, G. S. K. K. Reddy, C. S. Reddy and J. S. Yadav, Tetrahedron Lett., 2003, 44, 4129–4131.
11. N. Tewari, N. Dwivedi and R. P. Tripathi, Tetrahedron Lett., 2004, 45, 9011–9014.
12. M. M. Heravi, K. Bakhtiari, N. M. Javadi, F. F. Bamoharram, M. Saeedi and H. O. Oskooie, J. Mol. Catal. A: Chem., 2007, 264, 50–52.
13. S. J. Ji, Z. Q. Jiang, J. Lu and T. P. Loh, Synlett, 2004, 831–835.
14. L. M. Wang, J. Sheng, L. Zhang, J. W. Han, Z. Fan, H. Tian and C. T. Qian, Tetrahedron, 2005, 61, 1539–1543.
15. S. Ko and C. F. Yao, Tetrahedron Lett., 2006, 62, 7293–7299.
16. S. Ko, M. N. V. Sastry, C. Lin and C. F. Yao, Tetrahedron Lett., 2005, 46, 5771–5774.
17. A. Kumar and R. A. Maurya, Synlett, 2008, 883–885.
18. S. Chandrasekhar, Y. S. Rao, L. Sreelakshmi, B. Mahipal and C. R. Reddy, Synthesis, 2008, 1737–1741.
19. R. Sridhar and P. T. Perumal, Tetrahedron, 2005, 61, 2465–2470.
20. A. Debache, R. Boulcina, A. Belfaitah, S. Rhouati and B. Carboni, Synlett, 2008, 509–512.
21. M. Maheswara, V. Siddaiah, G. L. V. Damu and C. V. Rao, ARKIVOC, 2006, 2, 201–206.
22. C. G. Evans and J. E. Gestwicki, Org. Lett., 2009, 11, 2957–2959.
23. M. Maheswara, V. Siddaiah, Y. K. Rao, Y. Tzeng and C. Sridhar, J. Mol. Catal. A: Chem., 2006, 260, 179–180.
24. R. Gupta, S. Paul and A. Loupy, Synthesis, 2007, 2835–2838.
25. M. Z. Kassaee, H. Masrouri and F. Movahedi, Monatsh. Chem., 2010, 141, 317–322.
26. J. G. Brietenbucher and G. Figliozzi, Tetrahedron Lett., 2000, 41, 4311–4314.
27. A. Dondoni, A. Massi, E. Minghini and V. Bertolasi, Tetrahedron, 2004, 60, 2311–2326.
28. B. S. Sapkal, K. F. Shelke, B. B. Shingate and M. S. Shingare, Tetrahedron Lett., 2009, 50, 1754–1756.
29. F. Hoffmann, M. Corneluis, J. Morell and M. Froba, Angew. Chem., Int. Ed., 2006, 45, 3216–3251.
30. X. S. Zhao, G. Q. Lu and H. Y. Zhu, 24th Australia and New Zealand Chemical Engineering Conference and Exhibition, 1996, vol. 4, p. 39.
31. (a) S. Fujita and S. Inagaki, Chem. Mater., 2008, 20, 891; (b) S. E. Hankari, B. Motos-Prez, P. Hesemann, A. Bouhaouss and J. J. E. Moreau, Chem. Commun., 2011, 47, 6704–6706.
32. (a) Q. Yang, J. Liu, L. Zhang and C. Li, J. Mater. Chem., 2009, 19, 1945–1955; (b) F. Hoffmann and M. Fröba, Chem. Soc. Rev., 2011, 40, 608–620; (c) M. S. Moorthy, S. S. Park, D. Fuping, S. H. Hong, M. Selvaraj and C. S. Ha, J. Mater. Chem., 2012, 22, 9100–9108.
33. H. Olivier-Bourbigou, L. Magna and D. Morvan, Appl. Catal., A, 2010, 373, 1–56.
34. D. B. Zhao, Y. C. Liao and Z. D. Zhang, Clean: Soil, Air, Water, 2007, 35, 42–48.
35. A. Riisager, R. Fehrmann, S. Flicker, R. van Hal, M. Haumann and P. Wasserscheid, Angew. Chem., Int. Ed., 2005, 44, 815–819.
36. (a) B. Karimi, D. Elhamifar, J. H. Clark and A. J. Hunt, Chem.–Eur. J., 2010, 16, 8047–8053; (b) B. Karimi, D. Elhamifar, J. H. Clark and A. J. Hunt, Org. Biomol. Chem., 2011, 9, 7420–7426; (c) B. Karimi, D. Elhamifar, O. Yari, M. Khorasani, H. Vali, J. H. Clark and A. J. Hunt, Chem.–Eur. J., 2012, 18, 13520–13530; (d) D. Elhamifar, F. Hosseinpoor, B. Karimi and S. Hajati, Microporous Mesoporous Mater., 2015, 204, 269–275; (e) D. Elhamifar, B. Karimi, A. Moradi and J. Rastegar, ChemPlusChem, 2014, 79, 1147–1152.
37. D. Elhamifar, B. Karimi, J. Rastegar and M. H. Banakar, ChemCatChem, 2013, 5, 2418–2424.
38. D. Elhamifar and A. Shábani, Chem.–Eur. J., 2014, 20, 3212–3217.
39. A. Khojastenezhad, F. Moeinpour and A. Davoodnia, Chin. Chem. Lett., 2011, 22, 807–810.
40. L. M. Wang, J. Sheng, L. Zhang, J. W. Han, Z. Y. Fan and H. Tian, Tetrahedron, 2005, 61, 1539–1543.
41. G. W. Wang and C. B. Miao, Green Chem., 2006, 8, 1080–1085.
42. K. A. Undale, T. S. Shaikh, D. S. Gaikwad and D. M. Pore, C. R. Chimie, 2011, 14, 511–515.

---