Novel magnetic nanoparticles with ionic liquid tags as a reusable catalyst in the synthesis of polyhydroquinolines

Abstract

In this study, we have introduced {Fe₃O₄@SiO₂@(CH₂)₃Im}C(NO₂)₃ as a novel and heterogeneous reusable catalyst for the four component preparation of polyhydroquinoline derivatives under mild and eco-friendly reaction conditions. The structural confirmation of the novel heterogeneous reusable promoter was fully made using FT-IR, X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), energy-dispersive spectroscopy (EDS) elemental mapping analysis, high resolution transmission electron microscopy (HRTEM), thermogravimetry (TG), derivative thermal gravimetric (DTG), differential thermal (DTA) and vibrating sample magnetometer (VSM) analyses. The nanomagnetic heterogeneous catalyst was successfully applied for the synthesis of polyhydroquinoline derivatives via a four component condensation of a good range of aryl aldehydes, dimedone, ethyl acetoacetate or methyl acetoacetate as a β-ketoester, and ammonium acetate as a nitrogen source under solvent free conditions. Moreover, experimental evidence has demonstrated that {Fe₃O₄@SiO₂@(CH₂)₃Im}C(NO₂)₃ could act as a recoverable nanomagnetic and reusable catalyst without any considerable drop in the yield and the reaction time for at least eight times.

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Introduction

In recent times, the development and expansion of magnetic nanoparticles (MNPs) as versatile supports have been shown to be an influential branch in the field of green chemistry due to the environmentally benign nature of these compounds. For the easy separation of the magnetic materials from the reaction system, numerous attempts were focused on surface modifications in order to construct varied heterogeneous magnetically recoverable promoters for the organic functional transformation.¹ Moreover, using nanomagnetic heterogeneous catalytic systems for the promotion of the reaction supports a high catalytic performance as in the case of the homogeneous catalysts; in addition, the facile and efficient recovery point of view is approved through applying a simple external magnet and these merits led to an increase in their potential applicability.² The chemistry of MNPs has been extensively reviewed.^1–3

On the other hand, the capabilities of ionic liquids as reagents, catalysts, reaction media and proper solvents for different goals in the field of green chemistry have been well documented in the past few years.^4–10 Despite the widespread applications of ionic liquids, investigations have disclosed that in some case, the ionic liquids are at a disadvantage due to their toxic nature.^11,12 Therefore, ongoing studies are needed to overcome the defects connected with conventional, unsafe ionic liquids to replacing them with safer and more productive alternatives. Therefore, the combination of ionic liquids and magnetic nanoparticles (MNPs) as versatile supports for the immobilization of the ionic liquids offers several merits such as an easy synthetic pathway, a large surface area, a high thermal stability, a facile separation from the reaction mixture, and a low toxicity and price.¹³

The synthesis of complex compounds with high atom and step economy, improvement of the effectiveness and plainness in the synthetic pathway, providing easy and straightforward approach to library molecules and diversity-oriented synthesis (DOS) are the principal interest of the one pot multicomponent reactions (MCRs) and this beneficial technical protocol persuaded both academic and industrial chemists to access molecular diversity by this way.^14–17

Recently, due to the varied pharmaceutical and biological applications connected to the polyhydroquinolines structural motif, major attention has been paid to the production of these versatile organic compounds. Substituted 1,4-dihydropyridines are renowned calcium channel modulators, and they can be applied as a treatment for cardiovascular diseases.¹⁸ Some biologically active species base on the 1,4-dihydropyridine moiety are illustrated in Fig. 1.¹⁹

Fig. 1 Biologically active 1,4-dihydropyridines.

Because of the therapeutic applications of the 1,4-dihydropyridine derivatives, synthetic chemists have explored several protocols for their synthesis using different reaction conditions and varied catalytic systems such as Yb(OTf)₃,²⁰ [pyridine-SO₃H]Cl,²¹ [Dsim]HSO₄,²² Triton X-100 in water,²³ TiO₂ NPs,²⁴ SnO₂ NPs,²⁵ silica-bonded imidazolium-sulfonic acid chloride,²⁶ [2-MPyH]OTf,²⁷ SBA-15/SO₃H,²⁸ Ni-nanoparticles,²⁹ IL-HSO₄@SBA-15,³⁰ Baker's yeast,³¹ L-proline,³² and [bmim]BF₄.³³ Although the reported methods offer several merits and provide improvements for the synthesis of the target molecules, many of these protocols need longer reaction times and use harsh reaction conditions, unsafe organic solvents, and drastic workups. Therefore, investigating a new, environmentally compatible catalytic system is still in great demand.

We performed this study in order to explore a new protocol for the production of polyhydroquinoline derivatives and continue our investigations on the knowledge-based design, construction and applications of ionic liquids,³⁴ molten salts,³⁵ nanocatalysts, magnetic nanoparticles (MNPs),³⁶ magnetic nanoparticles with ionic liquid tags,³⁷ and trinitromethane³⁸ for organic functional group transformations. Specifically, we report on the design, synthesis and applicability of a novel nanomagnetically recoverable and reusable promoter catalyst, {Fe₃O₄@SiO₂@(CH₂)₃Im}C(NO₂)₃, for the preparation of polyhydroquinolines through a four component condensation of several aryl aldehydes, dimedone, ethyl acetoacetate or methyl acetoacetate as a β-ketoester, and ammonium acetate as a nitrogen source under mild and solvent free conditions (Schemes 1 and 2).

Scheme 1 Synthesis of polyhydroquinoline derivatives in the presence of {Fe₃O₄@SiO₂@(CH₂)₃Im}C(NO₂)₃.

Scheme 2 Synthetic pathway for the preparation of {Fe₃O₄@SiO₂@(CH₂)₃Im}C(NO₂)₃ as a heterogeneous core–shell catalyst.

Characterization of the novel catalyst

The structural verification of the novel nanomagnetically recoverable and reusable promoter, {Fe₃O₄@SiO₂@(CH₂)₃Im}C(NO₂)₃, was made using FT-IR, X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), elemental mapping, high resolution transmission electron microscopy (HRTEM), thermogravimetry (TG), and vibrating sample magnetometer (VSM) analysis.

As depicted in Fig. 2, the FT-IR spectrum of the novel nanomagnetic heterogeneous core–shell catalyst in comparison with different synthetic pathway compounds from Fe₃O₄@SiO₂ to {Fe₃O₄@SiO₂@(CH₂)₃Im}C(NO₂)₃ was investigated in the range of 400–4000 cm⁻¹. The overall differences in the FT-IR spectra can be used as proof for the preparation of the novel nanomagnetically recoverable and reusable promoter catalyst. According to the FT-IR spectrum, the two peaks at 1394 and 1592 cm⁻¹ can be attributed to the nitro functional groups in the structure of the catalyst. Furthermore, the overlapping of the uncoated hydroxyl groups and N–H stretching mode in the imidazolium ring caused a broad peak in the region of about 2900–3700 cm⁻¹.

Fig. 2 FT-IR spectrum of the novel nanomagnetic heterogeneous catalyst in comparison with different stepwise synthetic pathway materials.

By comparison, for the investigation of the purity and the phase of the applied materials for the synthesis of the catalyst, the X-ray diffraction patterns (XRD) were obtained for the different stepwise prepared materials (Fig. 3). From the XRD patterns, it can be deduced that the addition of each layer to the surface of the Fe₃O₄ nanoparticles lead to a change compared with the previous stage, which is an indication of the synthesis of the novel nanomagnetic core–shell catalyst. The X-ray diffraction pattern of the prepared catalyst confirmed that it has a crystalline nature with diffraction lines at 2θ = 13.35°, 16.30° and 24.90°. In another study, according to the Scherrer equation,

D = Kλ/(β cos θ) (1)

where λ is the X-ray wavelength, K is the Scherrer constant, β is the peak width at half maximum and θ is the Bragg diffraction angle, the 2θ value, peak width, particle size and interplanar distance, were extracted from the XRD data (Table 1).

Fig. 3 XRD pattern of the new catalyst and comparison with the different stepwise synthesized intermediates.

Table 1 XRD extracted data related to a novel nanomagnetic catalyst

Entry	2θ	Peak width [FWHM] (degree)	Size [nm]	Inter planar distance [nm]
1	13.35	0.68	11.76	0.662439
2	16.30	0.64	12.54	0.543152
3	24.90	0.80	10.17	0.357164

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In another assay, for the investigation of the size and morphology of the novel catalyst, field emission scanning electron microscopy (FESEM) images were obtained (Fig. 4a–c). As the recorded FESEM images show, the size of the catalyst particles is in the nanometer scale.

Fig. 4 (a and b) Field emission scanning electron microscopy (FESEM) images of {Fe₃O₄@SiO₂@(CH₂)₃Im}C(NO₂)₃ as a new nanomagnetic core–shell catalyst. Inset (c) expansion of image (b).

Moreover, in order to explore the elemental composition of the catalyst {Fe₃O₄@SiO₂@(CH₂)₃Im}C(NO₂)₃, energy-dispersive spectroscopy (EDS) elemental mapping analysis was conducted (Fig. 5a–g). Examination of the SEM-EDS mapping images, which are shown in Fig. 5b–g, proved the presence of Si, Fe, N, O, and C in the catalyst. As shown in Fig. 5b–f, the elements were distributed well in the catalyst surface.

Fig. 5 (a) SEM image and SEM-EDS elemental mapping images of (b) silicon (red), (c) iron (green), (d) nitrogen (blue), (e) oxygen (cyan), (f) carbon (purple) and (g) overlapping of Si, Fe, N, O, and C in {Fe₃O₄@SiO₂@(CH₂)₃Im}C(NO₂)₃.

The data from energy dispersive X-ray (EDX) analysis of the new heterogeneous catalyst showed all the predicted elements in the structure of the catalyst, namely, iron, silicon, oxygen, carbon, and nitrogen, as indicated in Fig. 6. Moreover, SEM-coupled EDX data for the catalyst revealed C (0.53), N (0.27), Fe (93.56), O (4.64) and Si (0.99).

Fig. 6 Energy dispersive X-ray (EDX) spectrum of the new heterogeneous catalyst.

High resolution transmission electron microscopy (HRTEM) images of {Fe₃O₄@SiO₂@(CH₂)₃Im}C(NO₂)₃ were recorded and illustrated to obtain structural information of the catalyst in more detail. As depicted in Fig. 8a and b, all the nanoparticles presented well-defined uniform spherical shapes, highly dispersed by the ionic liquid tags over the Fe₃O₄NPs after sonication in ethanol. As shown in the HRTEM images (Fig. 8a–c), amorphous silica coating layers over the crystalline nanoparticles of Fe₃O₄NPs are clearly seen at low or high magnification of the HRTEM. According to Fig. 8c, the thickness of the silica shell (@SiO₂@(CH₂)₃Im}C(NO₂)₃) is around 2 to 3 nm with an interplanar crystalline spacing value of the Fe₃O₄NPs around 0.50 nm (Fig. 7). Moreover, it is worth mentioning that the images from both the FESEM and HRTEM analyses are in good agreement with the XRD extracted data.

Fig. 7 Average of crystalline distance layer of the Fe₃O₄NPs in {Fe₃O₄@SiO₂@(CH₂)₃Im}C(NO₂)₃.

Fig. 8 HRTEM images of the {Fe₃O₄@SiO₂@(CH₂)₃Im}C(NO₂)₃ (a and b) and magnified HRTEM images of one nanoparticle (c).

In order to investigate the thermal stability of the novel nanomagnetic catalyst, thermal gravimetric (TG), derivative thermal gravimetric (DTG), and differential thermal (DTA) analyses were conducted (Fig. 9). From these studies, it could be inferred that the main weight loss upon heating from ambient temperature to about 100 °C can be attributed to the evaporation of the physically adsorbed water and other organic solvents used during the catalyst preparation. Weight loss at around 210 °C is due to thermal decomposition of the ionic tag of the catalyst. Finally, decomposition of the catalyst occurred between 300 and 550 °C. Moreover, the study of the DTA analysis diagram revealed that it is downward and exothermic.

Fig. 9 Thermal gravimetric (TG), derivative thermal gravimetric (DTG), and differential thermal (DTA) analyses of the novel core–shell catalyst.

In order to study the magnetic properties of the new catalyst, vibrating sample magnetometer (VSM) analysis of the catalyst was compared with that of nanomagnetic Fe₃O₄ (Fig. 10). By investigation of the obtained magnetization curves, it was observed that the saturation of {Fe₃O₄@SiO₂@(CH₂)₃Im}C(NO₂)₃ as a catalyst reduced from 52.42 emu g⁻¹ for Fe₃O₄ nanoparticles to 37.48 emu g⁻¹. This decrease can be related to surface modification of the Fe₃O₄ nanoparticles during the preparation of the catalyst.

Fig. 10 VSM magnetization curves of the catalyst compared with Fe₃O₄ nanoparticles.

After characterizing the nanomagnetic catalyst, the applicability of the catalyst was explored for the synthesis of polyhydroquinoline derivatives through a four component condensation of several aryl aldehydes, dimedone, ethyl acetoacetate or methyl acetoacetate as β-ketoester, and ammonium acetate as a nitrogen source. In order to achieve the optimized reaction conditions, the condensation of 4-chlorobenzaldehyde, dimedone, ethylacetoacetate, and ammonium acetate was chosen as a test reaction. The resulting data for the optimization of temperatures, catalyst loadings, and solvents showed that the best results were acquired when the reaction was carried out under solvent-free conditions in the presence of 7 mg of {Fe₃O₄@SiO₂@(CH₂)₃Im}C(NO₂)₃ as a catalyst at 80 °C (Table 2, entry 4). The data for the optimization of the reaction conditions are included in Table 2.

Table 2 Optimization of the reaction conditions for the synthesis of polyhydroquinolines^a

Entry	Solvent	Load of catalyst (mg)	Temperature (°C)	Time (min)	Yield^b (%)
a Reaction conditions: 4-chlorobenzaldehyde (1 mmol, 0.144 g), dimedone (1 mmol, 0.140 g), ethyl acetoacetate (1 mmol, 0.130 g), and ammonium acetate (3 mmol, 0.231 g).b Isolated yield.
1	—	10	100	15	93
2	—	10	80	16	92
3	—	10	60	25	85
4	—	7	80	18	92
5	—	4	80	22	87
6	—	—	80	60	54
7	EtOAc	7	Reflux	80	55
8	n-Hexane	7	Reflux	70	35
9	CH3CN	7	Reflux	80	60
10	EtOH	7	Reflux	90	90
11	H2O	7	Reflux	90	78

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After evaluation of the appropriate reaction conditions, we studied the scope and productivity of this process for the synthesis of biologically active target molecules in the presence of {Fe₃O₄@SiO₂@(CH₂)₃Im}C(NO₂)₃ as a heterogeneous recoverable catalyst. Thus, polyhydroquinoline derivatives were prepared via a four component reaction of a wide range of aromatic aldehydes bearing electron-withdrawing and electron-releasing groups, ethyl acetoacetate or methyl acetoacetate, dimedone, and ammonium acetate under solvent free conditions. The results are displayed in Table 3.

Table 3 Synthesis of polyhydroquinolines in the presence of {Fe₃O₄@SiO₂@(CH₂)₃Im}C(NO₂)₃^a

Product	X	Y	Time (min)	Yield^b (%)	Mp (°C) found [Lit]^ref.
a Reaction conditions: aromatic aldehyde (1 mmol), dimedone (1 mmol, 0.140 g), ethyl acetoacetate or methyl acetoacetate (1 mmol), and ammonium acetate (3 mmol, 0.231 g).b Isolated yields.
1a	4-Cl	OEt	18	92	243–245 [242–244]^36c
1b	H	OEt	19	91	224–226 [224–226]^36c
1c	2,4-Cl2	OEt	16	93	244–246 [242–244]^36c
1d	4-OMe	OEt	18	90	255–257 [255–257]^36c
1e	3-Br	OEt	18	91	206–208 [229–231]^26
1f	2-Cl	OEt	20	94	207–209 [208–209]^39
1g	4-Me	OEt	17	90	263–265 [263–265]^36c
1h	3,4-(OMe)2	OEt	16	92	205–207 [204–206]^36c
1i	4-F	OEt	18	90	193–195 [193–195]^36c
1j	4-NO2	OEt	22	88	242–243 [241–242]^36c
1k	2-OMe	OEt	14	92	249–251 [248–250]^41
1l	3-OEt-4-OH	OEt	15	95	195–196 [190–192]^36c
1m	3-OH	OEt	17	93	231–234 [230–232]^36c
1n	4-Cl	OMe	18	89	257–258 [219–222]^40
1o	H	OMe	17	90	259–261 [257–259]^26
1p	4-Br	OMe	19	90	261–263 [263–264]^42
1q	2,4-Cl	OMe	22	91	251–253 [250–252]^42
1r	4-OMe	OMe	18	91	254–257 [256–259]^26
1s	4-OH	OMe	17	92	297–298 [232–234]^26
1t	4-Me	OMe	17	90	270–273 [283–285]^23

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One of the excellent merits of nanomagnetic heterogeneous core–shell catalysts is the possibility of recycling and the ease of separating them from the reaction mixture in a catalyzed system after completion of the reaction. In order to demonstrate the reusability of our catalyst, the reaction of benzaldehyde, dimedone, ethyl acetoacetate, and ammonium acetate was preferred as a model process. After each run, hot ethanol was added to the reaction mixture to dissolve the crude product. Then, the nanomagnetic catalyst was separated from the reaction mixture by applying an external magnet. The catalyst was reused for the next run after washing it with ethanol and drying. As depicted in Fig. 11, the catalytic activity of {Fe₃O₄@SiO₂@(CH₂)₃Im}C(NO₂)₃ was conserved for eight consecutive runs without any discernible reduction.

Fig. 11 Reusability test of {Fe₃O₄@SiO₂@(CH₂)₃Im}C(NO₂)₃ as a novel nanomagnetic catalyst.

Finally, the catalytic activity of {Fe₃O₄@SiO₂@(CH₂)₃Im}C(NO₂)₃ was compared with some previously investigated recoverable catalysts (Table 4). As depicted, it can be deduced that the previously reported methods suffer from different drawbacks such as elevated temperatures, use of organic solvents and/or transition metal catalysts, activation by sonication irradiation, longer reaction times, or harsh reaction conditions.

Table 4 Catalytic activity of the nanomagnetic catalyst in this work compared with some other recoverable catalysts for the synthesis of compound 1b

Entry	Reaction conditions	Time (min)	Yield (%)	Lit.
1	[TBA]2[W6O19] (7 mol%), solvent-free, 110 °C	20	93	43
2	Trifluoroethanol (TFE), 70 °C	180	98	44
3	Fe3O4-SA-PPCA (10 mg), EtOH, 50 °C	120	97	45
4	Mn@PMO-IL (1 mol%), solvent-free, 80 °C	20	95	46
5	Co3O4–CNTs (0.03 g), EtOH, 50 °C, sonication	15	97	47
6	Nafion-H®, PEG 400–water (60 : 40), 50 °C	90	96	48
7	(bzacen)MnCl (2.5 mol%), EtOH, reflux	20	90	49
8	Nano-Fe3O4 (5 mol%), solvent-free, 50 °C	6	89	50
9	Nanocat Fe–Ce (100 mg), EtOH, r.t.	20	95	51
10	Hf(NPf2)4 (1 mol%), C10F18, 60 °C	180	95	52
This work	{Fe3O4@SiO2@(CH2)3Im}C(NO2)3 (7 mg), solvent-free, 80 °C	19	91	—

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A suggested mechanistic pathway for the synthesis of polyhydroquinoline derivatives is portrayed in Fig. 12, where initially the in situ generated NH₃ formed from ammonium acetate reacts with activated β-ketoester to yield the corresponding intermediate 2. On the other hand, in the presence of the novel nanomagnetic catalyst, dimedone is converted to its enol form, which performs a nucleophilic addition to the activated aryl aldehyde, providing the corresponding Knoevenagel adduct 3. Then, the reaction between these two intermediates generates intermediate 4. Tautomerization of 4 led to the formation of derivative 5, which suffers an intramolecular nucleophilic attack of the amino group to the activated carbonyl group providing intermediate 6. Finally, dehydration of this intermediate formed the desired target molecules 1a–t.

Fig. 12 Suggested catalytic mechanism for the synthesis of target molecules.

Conclusion

In this study, the design and synthesis of a novel and heterogeneous reusable catalyst, {Fe₃O₄@SiO₂@(CH₂)₃Im}C(NO₂)₃, has been reported. The structure of this catalyst was fully characterized using FT-IR, X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), high resolution transmission electron microscopy (HRTEM), thermogravimetry (TG), and derivative thermal gravimetric (DTG), differential thermal (DTA), and vibrating sample magnetometer (VSM) analyses. The catalytic performance of {Fe₃O₄@SiO₂@(CH₂)₃Im}C(NO₂)₃ was successfully explored in the four component preparation of polyhydroquinoline derivatives under mild and eco-friendly reaction conditions. The encouraging advantages of this study are the eco-friendly and mild reaction conditions, easy separation and reusability of the catalyst, short reaction times with high products yields, and an easy work-up.

Experimental

General

Solvents and reagents were purchased from Sigma-Aldrich, Alfa Aesar, and Merck and were used without further purification. Melting points were obtained with an Amstrad/electrothermal apparatus. ¹H NMR (400 MHz) and ¹H NMR (300 MHz) spectra were obtained on a Bruker Avance 400 and Bruker Avance 300 NMR spectrometers, respectively, in proton coupled mode using deuterated DMSO as a solvent unless otherwise stated. ¹³C NMR (101 MHz) spectra were acquired on a Bruker Avance 400 NMR spectrometer in the proton decoupled mode at 20 °C in deuterated DMSO as a solvent unless otherwise stated. Chemical shifts are given in δ (parts per million) and the coupling constants (J) in hertz. ¹⁹F NMR (282 MHz) spectra were obtained on a Bruker Avance 300 NMR spectrometer in the proton coupled mode. Infrared spectra were acquired with an FT-IR 4100 LE (JASCO, Pike Miracle ATR) spectrometer. HRTEM was carried out on a high resolution transmission electron microscope JEOL JEM-2010 equipped with an X-ray detector OXFORD INCA Energy TEM 100 for microanalysis (EDS). The acquisition of the images was performed using a GATAN ORIUS SC600 digital camera mounted on-axis, integrated with the program GATAN Digital Micrograph 1.80.70 for GMS 1.8.0. Field emission scanning electron microscopy (FESEM) images were recorded on a Merlin VP Compact from Zeiss equipped with an EDS microanalysis system Quantax 400 from Bruker. The resolution was 0.8 nm at 15 kV and 1.6 nm at 1 kV. Field emission equipment is able to work at much reduced voltages (from 0.02 kV to 30 kV) allowing the observation of beam sensitive samples without damaging them and minimizing the charging effects. Scanning electron microscopy (SEM) studies were performed on a Hitachi S3000N, equipped with an X-ray detector Bruker XFlash 3001 for microanalysis (EDS) and mapping. The scanning microscope is able to work in the variable pressure mode for the observation of nonconductive specimens without coating with any conductive material. Low-resolution mass spectra (EI) were obtained at 70 eV with an Agilent 5973 Network spectrometer, with fragment ions m/z reported with relative intensities (%) in parentheses. HRMS analyses were carried out on an Agilent 7200 Q-TOF spectrometer. Magnetic measurements were performed using vibration sample magnetometry VSM (MDK Co. Kashan, Iran) analysis. TG-DTA analyses were carried out on a METTLER TOLEDO equipment (model TGA/SDTA851 and /SF/1100 TG-DTA). X-ray diffraction (XRD) analysis was performed using a Bruker D8-Advance apparatus with a Göbel mirror (non-planar samples) equipped with a high temperature chamber (up to 900 °C), a KRISTALLOFLEX K 760-80F X-ray generator (power: 3000 W, voltage: 20–60 kV and current: 5–80 mA), and a tube of RX with copper anode. Preparative thin-layer chromatography was carried on laboratory made TLC glass plates with silica gel 60 PF254 (Merck). Column chromatography was performed using silica gel 60 of 40–60 microns (hexane/EtOAc as eluent).

Synthetic procedures

General procedure for the preparation of novel silica-coated magnetic nanoparticles with ionic liquid tags (Scheme 2)

First, the Fe₃O₄ nanoparticles were synthesized according to a previously reported method.⁵³ Then, the surface of the Fe₃O₄ nanoparticles was modified with a layer of SiO₂ by treating with tetraethyl orthosilicate (TEOS) to form compound B. In the next step, silanization of Fe₃O₄@SiO₂ (B) by reaction with 3-chloropropyltrimethoxysilane in refluxing toluene afforded compound C. Subsequently, 6 mmol (0.408 g) of imidazole were added to compound C dispersed in toluene. The resulting mixture was refluxed for 12 h. Finally, trinitromethane (6 mmol, 0.906 g) was added to compound D in toluene and the reaction mixture was stirred for 12 h in refluxing toluene to form {Fe₃O₄@SiO₂@(CH₂)₃Im}C(NO₂)₃ (E) as a reusable nanomagnetic core–shell catalyst with an ionic tag (Scheme 2).

General procedure for the synthesis of polyhydroquinolines as target molecules (Scheme 1)

To a round bottom flask containing a mixture of aromatic aldehyde (1 mmol), dimedone (1 mmol, 0.14 g), ethyl acetoacetate or methyl acetoacetate as a β-ketoester (1 mmol), and ammonium acetate as a nitrogen source (3 mmol, 0.23 g), 7 mg of {Fe₃O₄@SiO₂@(CH₂)₃Im}C(NO₂)₃ were added as a MNPs@IL catalyst. Then, the reaction mixture was stirred at 80 °C for adequate time under solvent-free conditions (Table 3). After completion of the reactions, as monitored by TLC (n-hexane/ethyl acetate), the reaction mixture was cooled to ambient temperature. Afterwards, in order to separate and recover the catalyst, hot ethanol was added to the mixture to dissolve the desired products and unreacted starting materials. The catalyst was insoluble in hot ethanol and easily separated from the reaction mixture by utilizing an external magnet. Finally, the target products were recrystallized from ethanol with high to excellent yields (Table 3).

Spectral data

Ethyl 4-(4-chlorophenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate: (1a)^36c

Melting point: 243–245 °C; FT-IR (KBr): ν(cm⁻¹) = 3277, 3207, 3078, 2967, 1706, 1648, 1605, 1489, 1382, 1214; ¹H NMR (400 MHz) δ 9.08 (br. s, 1H), 7.22 (s, 2H), 7.14 (s, 2H), 4.82 (s, 1H), 3.95 (m, 2H), 2.45 (d, J = 17.0, 1H), 2.35–2.25 (m with s at 2.27, 4H), 2.15 (d, J = 15.5, 1H), 1.96 (d, J = 15.5, 1H), 1.10 (br. s, 3H), 0.99 (s, 3H), 0.81 (s, 3H); ¹³C NMR (101 MHz) δ 194.7, 167.1, 150.0, 147.0, 145.8, 130.6, 129.7, 128.1, 110.1, 103.5, 59.5, 50.6, 36.0, 32.5, 29.5, 26.8, 18.7, 14.5; MS (EI) m/z (%): 375 (M⁺ + 2, 5), 373 (M⁺, 14), 262.1 (100), 234 (20); TOF-HRMS (EI): m/z (M)⁺ calcd for C₂₁H₂₄ClNO₃ 373.1445; found 373.1428.

Ethyl 2,7,7-trimethyl-5-oxo-4-phenyl-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate: (1b)^36c

Melting point: 224–226 °C; FT-IR (KBr): ν(cm⁻¹) = 3289, 3216, 3081, 2962, 1701, 1614, 1485, 1382, 1212; ¹H NMR (400 MHz) δ 9.03 (br. s, 1H), 7.15 (s, 4H), 7.05 (s, 1H), 4.85 (s, 1H), 3.96 (m, 2H), 2.41 (d, J = 17.0, 1H), 2.35–2.20 (m with s at 2.27, 4H), 2.15 (d, J = 16.0, 1H), 1.96 (d, J = 16.0, 1H), 1.11 (s, 3H), 1.00 (s, 3H), 0.83 (s, 3H); ¹³C NMR (101 MHz) δ 194.7, 167.3, 149.9, 148.1, 145.4, 128.1, 127.9, 126.1, 110.4, 104.1, 59.5, 50.7, 36.3, 32.6, 29.6, 26.9, 18.7, 14.6; MS (EI) m/z (%): 339 (M⁺, 13), 262 (100), 234 (20); TOF-HRMS (EI): m/z (M)⁺ calcd for C₂₁H₂₅NO₃ 339.1834; found 339.1863.

Ethyl 4-(2,4-dichlorophenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate: (1c)^36c

Melting point: 244–246 °C; FT-IR (KBr): ν(cm⁻¹) = 3283, 3208, 3078, 2958, 1706, 1648, 1610, 1495; ¹H NMR (400 MHz) δ 9.11 (s, 1H), 7.33 (s, 1H), 7.27 (s, 2H), 5.14 (s, 1H), 3.93 (m, 2H), 2.41 (d, J = 17.1, 1H), 2.30–2.20 (m with s at 2.24, 4H), 2.13 (d, J = 16.1, 1H), 1.91 (d, J = 16.0, 1H), 1.07 (t, J = 6.8, 3H), 0.99 (s, 3H), 0.83 (s, 3H); ¹³C NMR (101 MHz) δ 194.3, 167.0, 150.3, 145.9, 144.7, 133.3, 133.2, 131.2, 128.6, 127.3, 109.7, 103.2, 59.5, 50.6, 35.2, 32.4, 29.5, 26.8, 18.7, 14.5; MS (EI) m/z (%): 411 (M⁺ + 4, 1), 409 (M⁺ + 2, 5), 407 (M⁺, 9), 372 (14), 262 (100), 234 (19); TOF-HRMS (EI): m/z (M)⁺ calcd for C₂₁H₂₃Cl₂NO₃ 407.1055; found 407.1062.

Ethyl 4-(4-methoxyphenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate: (1d)^36c

melting point: 255–257 °C; FT-IR (KBr): ν(cm⁻¹) = 3277, 3202, 3078, 2957, 1701, 1649, 1606, 1496; ¹H NMR (400 MHz) δ 8.99 (s, 1H), 7.04 (d, J = 8.2, 2H), 6.73 (d, J = 8.2, 2H), 4.78 (s, 1H), 3.96 (q, J = 6.9, 2H), 3.66 (s, 3H), 2.40 (d, J = 17.0, 1H), 2.35–2.20 (m with s at 2.26, 4H), 2.15 (d, J = 16.0, 1H), 1.96 (d, J = 16.0, 1H), 1.13 (t, J = 6.9, 3H), 1.00 (s, 3H), 0.84 (s, 3H); ¹³C NMR (101 MHz) δ 194.7, 167.4, 157.7, 149.6, 145.0, 140.5, 128.8, 113.5, 110.6, 104.4, 59.4, 55.3, 50.7, 35.4, 32.5, 29.6, 26.9, 18.7, 14.6; MS (EI) m/z (%): 369 (M⁺, 33), 340 (13), 296 (11), 262 (100), 234 (21); TOF-HRMS (EI): m/z (M)⁺ calcd for C₂₂H₂₇NO₄ 369.1940; found 369.1950.

Ethyl 4-(3-bromophenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate: (1e)²⁶

Melting point: 206–208 °C; FT-IR (KBr): ν(cm⁻¹) = 3273, 3073, 2958, 1702, 1604, 1489, 1380, 1211, 1071, 769; ¹H NMR (400 MHz) δ 9.12 (s, 1H), 7.32–7.22 (m, 2H), 7.20–7.08 (m, 2H), 4.82 (s, 1H), 4.05–3.90 (m, 2H), 2.42 (d, J = 17.2, 1H), 2.38–2.25 (m with s at 2.29, 4H), 2.17 (d, J = 16.2, 1H), 1.99 (d, J = 15.8, 1H), 1.12 (t, J = 6.8, 3H), 1.00 (s, 3H), 0.85 (s, 3H); ¹³C NMR (101 MHz) δ 194.7, 167.0, 150.7, 150.3, 146.0, 130.8, 130.5, 129.0, 127.0, 121.5, 109.9, 103.4, 59.6, 50.6, 36.5, 32.6, 29.5, 26.8, 18.8, 14.5; MS (EI) m/z (%): 419 (M⁺ + 2, 6), 417 (M⁺, 6), 262 (100), 234 (23); TOF-HRMS (EI): m/z (M)⁺ calcd for C₂₁H₂₄BrNO₃ 417.0940; found 417.0933.

Ethyl 4-(2-chlorophenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate: (1f)³⁹

Melting point: 207–209 °C; FT-IR (KBr): ν(cm⁻¹) = 3277, 3210, 3073, 2957, 1701, 1649, 1606, 1496, 1380; ¹H NMR (400 MHz) δ 9.07 (s, 1H), 7.28 (d, J = 6.8, 1H), 7.24–7.12 (m, 2H), 7.06 (t, J = 7.0, 1H), 5.18 (s, 1H), 3.98–3.87 (m, 2H), 2.41 (d, J = 17.0, 1H), 2.32–2.20 (m with s at 2.24, 4H), 2.13 (d, J = 16.1, 1H), 1.91 (d, J = 16.1, 1H), 1.07 (t, J = 7.1, 3H), 1.00 (s, 3H), 0.84 (s, 3H); ¹³C NMR (101 MHz) δ 194.3, 167.2, 150.1, 145.6, 145.4, 132.4, 131.9, 129.4, 127.7, 127.1, 110.0, 103.7, 59.4, 50.7, 35.4, 32.4, 29.6, 26.8, 18.6, 14.5; MS (EI) m/z (%): 375 (M⁺ + 2, 7), 373 (M⁺, 22), 338 (39), 262 (100), 234 (48); TOF-HRMS (EI): m/z (M)⁺ calcd for C₂₁H₂₄ClNO₃ 373.1445; found 373.1457.

Ethyl 2,7,7-trimethyl-5-oxo-4-(p-tolyl)-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate: (1g)^36c

Melting point: 263–265 °C; FT-IR (KBr): ν(cm⁻¹) = 3276, 3208, 3078, 2958, 1702, 1648, 1606, 1493, 1282; ¹H NMR (400 MHz) δ 8.99 (s, 1H), 7.15–6.90 (m, 4H), 4.79 (s, 1H), 3.95 (m, 2H), 2.39 (d, J = 17.1, 1H), 2.36–2.10 (m with 2 s at 2.25 and 2.18, 8H), 1.95 (d, J = 16.0, 1H), 1.12 (s, 3H), 0.99 (s, 3H), 0.83 (s, 3H); ¹³C NMR (101 MHz) δ 194.7, 167.3, 149.8, 145.2 (2c), 135.0, 128.7, 127.8, 110.5, 104.2, 59.4, 50.7, 35.8, 32.6, 29.6, 26.9, 21.0, 18.7, 14.6; MS (EI) m/z (%): 353 (M⁺, 18), 262 (100), 234 (18); TOF-HRMS (EI): m/z (M)⁺ calcd for C₂₂H₂₇NO₃ 353.1991; found 353.2005.

Ethyl 4-(3,4-dimethoxyphenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate: (1h)^36c

Melting point: 205–207 °C; FT-IR (KBr): ν(cm⁻¹) = 3280, 3213, 3081, 2941, 1696, 1605, 1514; ¹H NMR (300 MHz, EtOH-d₆) δ 6.80 (d, J = 1.2 Hz, 1H), 6.72–6.53 (m, 2H), 4.83 (s, 1H), 3.94 (q, J = 7.1, 2H), 3.66 (s, 3H), 3.63 (s, 3H), 2.35 (d, J = 17.0 Hz, 1H), 2.29–2.19 (m with s at 2.26, 4H), 2.13 (d, J = 16.4 Hz, 1H), 1.98 (d, J = 16.4 Hz, 1H), 1.09 (t, J = 7.1 Hz, 3H), 0.97 (s, 3H), 0.82 (s, 3H); ¹³C NMR (101 MHz) δ 194.7, 167.3, 149.7, 148.3, 147.3, 144.9, 140.8, 119.6, 112.0, 111.8, 110.4, 104.2, 59.4, 55.7, 55.6, 50.6, 35.5, 32.5, 29.6, 26.8, 18.6, 14.6; MS (EI) m/z (%): 399 (M⁺, 33), 370 (10), 262 (100), 234 (21); TOF-HRMS (EI): m/z (M)⁺ calcd for C₂₃H₂₉NO₅ 399.2046; found 399.2056.

Ethyl 4-(4-fluorophenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate: (1i)^36c

Melting point: 193–195 °C; FT-IR (KBr): ν(cm⁻¹) = 3291, 3219, 3078, 2959, 1702, 1607, 1487, 1382, 1212, 853, 531; ¹H NMR (400 MHz) δ 9.06 (s, 1H), 7.14 (m, 2H), 6.99 (m, 2H), 4.83 (s, 1H), 3.96 (m, 2H), 2.40 (d, J = 17.1, 1H), 2.34–2.20 (m with s at 2.28, 4H), 2.15 (d, J = 15.8, 1H), 1.96 (d, J = 15.9, 1H), 1.10 (s, 3H), 0.99 (s, 3H), 0.82 (s, 3H); ¹³C NMR (101 MHz) δ 194.7, 167.2, 160.8 (d, J = 241.2), 149.9, 145.6, 144.3, 129.6 (d, J = 8.0), 114.8 (d, J = 21.0), 110.4, 103.9, 59.5, 50.6, 35.7, 32.6, 29.5, 26.9, 18.7, 14.6; MS (EI) m/z (%): 357 (M⁺, 21), 262 (100), 234 (22); ¹⁹F NMR (282 MHz, DMSO) δ −115.39; TOF-HRMS (EI): m/z (M)⁺ calcd for C₂₁H₂₄FNO₃ 357.1740; found 357.1746.

Ethyl 2,7,7-trimethyl-4-(4-nitrophenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate: (1j)^36c

Melting point: 242–243 °C; FT-IR (KBr): ν(cm⁻¹) = 3274, 3189, 3076, 2966, 1703, 1649, 1609, 1493, 1349, 1215; ¹H NMR (400 MHz) δ 9.22 (s, 1H), 8.09 (d, J = 8.5, 2H), 7.41 (d, J = 8.5, 2H), 4.96 (s, 1H), 3.96 (q, J = 6.9, 2H), 2.43 (d, J = 17.1, 1H), 2.35–2.25 (m with s at 2.31, 4H), 2.18 (d, J = 16.2, 1H), 1.97 (d, J = 16.2, 1H), 1.10 (t, J = 7.0, 3H), 1.00 (s, 3H), 0.81 (s, 3H); ¹³C NMR (101 MHz) δ 194.7, 166.8, 155.4, 150.5, 146.6, 146.1, 129.2, 123.6, 109.5, 102.8, 59.7, 50.5, 37.1, 32.6, 29.4, 26.9, 18.8, 14.5; MS (EI) m/z (%): 384 (M⁺, 15), 262 (100), 234 (22); TOF-HRMS (EI): m/z (M)⁺ calcd for C₂₁H₂₄N₂O₅ 384.1685; found 384.1692.

Ethyl 4-(2-methoxyphenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate: (1k)⁴¹

Melting point: 249–251 °C; FT-IR (KBr): ν(cm⁻¹) = 3284, 3078, 2964, 1689, 1623, 1611, 1488, 1361, 1215, 751; ¹H NMR (300 MHz, EtOH-d₆) δ 7.15 (d, J = 7.0, 1H), 6.93 (t, J = 7.4, 1H), 6.79–6.56 (m, 2H), 5.06 (s, 1H), 3.87 (q, J = 7.0, 2H), 3.65 (s, 3H), 2.32 (d, J = 17.0, 1H), 2.26–2.15 (m with s at 2.18, 4H), 2.14–1.97 (m, 1H), 1.91 (d, J = 16.4, 1H), 1.10–0.90 (m, 6H), 0.80 (s, 3H); ¹³C NMR (101 MHz) δ 193.8, 167.3, 157.1, 149.9, 144.1, 134.9, 130.5, 126.9, 119.4, 111.0, 108.6, 102.9, 58.7, 55.1, 50.4, 32.8, 32.0, 29.3, 26.2, 18.0, 14.1; MS (EI) m/z (%): 369 (M⁺, 61), 340 (37), 262 (100), 234 (31); TOF-HRMS (EI): m/z (M)⁺ calcd for C₂₂H₂₇NO₄ 369.1940; found 369.1946.

Ethyl 4-(3-ethoxy-4-hydroxyphenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate: (1l)^36c

Melting point: 195–196 °C; FT-IR (KBr): ν(cm⁻¹) = 3443, 3282, 3200, 3079, 2959, 1657, 1616, 1493, 1381; ¹H NMR (300 MHz, EtOH-d₆) δ 6.74 (s, 1H), 6.52 (s, 2H), 4.79 (s, 1H), 4.02–3.81 (m, 4H), 2.33 (d, J = 17.0, 1H), 2.28–2.18 (m with s at 2.25, 4H), 2.12 (d, J = 16.5, 1H), 1.98 (d, J = 16.4, 1H), 1.27 (t, J = 7.0, 3H), 1.08 (t, J = 7.1, 3H), 0.96 (s, 3H), 0.81 (s, 3H); ¹³C NMR (101 MHz) δ 194.8, 167.4, 149.6, 146.2, 145.3, 144.8, 139.4, 120.1, 115.4, 113.9, 110.6, 104.5, 64.2, 59.4, 50.7, 35.4, 32.5, 29.6, 26.8, 18.7, 15.2, 14.6; MS (EI) m/z (%): 399 (M⁺, 30), 370 (11), 262 (100), 234 (19); TOF-HRMS (EI): m/z (M)⁺ calcd for C₂₃H₂₉NO₅ 399.2046; found 399.2048.

Ethyl 4-(3-hydroxyphenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate: (1m)^36c

Melting point: 231–234 °C; FT-IR (KBr): ν(cm⁻¹) = 3463, 3291, 2961, 1669, 1620, 1487, 1381, 1277, 1216; ¹H NMR (400 MHz) δ 9.05 (s, 1H), 9.00 (s, 1H), 6.94 (t, J = 7.7, 1H), 6.59–6.56 (m, 2H), 6.45 (d, J = 7.3, 1H), 4.78 (s, 1H), 3.98 (q, J = 7.0, 2H), 2.40 (d, J = 17.0, 1H), 2.32–2.25 (m with s at 2.27, 4H), 2.16 (d, J = 16.1, 1H), 1.99 (d, J = 16.1, 1H), 1.14 (t, J = 7.1, 3H), 1.00 (s, 3H), 0.87 (s, 3H); ¹³C NMR (101 MHz) δ 194.7, 167.4, 157.3, 149.9, 149.4, 145.1, 128.9, 118.6, 115.0, 113.1, 110.4, 104.1, 59.5, 50.8, 36.1, 32.5, 29.6, 27.0, 18.7, 14.6; MS (EI) m/z (%): 355 (M⁺, 13), 262 (100), 234 (20); TOF-HRMS (EI): m/z (M)⁺ calcd for C₂₁H₂₅NO₄ 355.1784; found 355.1792.

Methyl 4-(4-chlorophenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate: (1n)⁴⁰

Melting point: 257–258 °C; FT-IR (KBr): ν(cm⁻¹) = 3288, 3198, 3076, 1682, 1606, 1492, 1226; ¹H NMR (400 MHz) δ 9.12 (s, 1H), 7.23 (br. d, J = 6.6, 2H), 7.13 (br. d, J = 6.4, 2H), 4.83 (s, 1H), 3.51 (s, 3H), 2.40 (d, J = 17.0, 1H), 2.35–2.20 (m with s at 2.28, 4H), 2.16 (d, J = 16.0, 1H), 1.96 (d, J = 15.7, 1H), 0.99 (s, 3H), 0.81 (s, 3H); ¹³C NMR (101 MHz) δ 194.7, 167.6, 150.0, 146.8, 146.1, 130.7, 129.6, 128.2, 110.1, 103.2, 51.1, 50.6, 35.8, 32.6, 29.5, 26.8, 18.8; MS (EI) m/z (%): 361 (M⁺ + 2, 4), 359 (M⁺, 11), 248 (100); TOF-HRMS (EI): m/z (M)⁺ calcd for C₂₀H₂₂ClNO₃ 359.1288; found 359.1275.

Methyl 2,7,7-trimethyl-5-oxo-4-phenyl-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate: (1o)²⁶

Melting point: 259–261 °C; FT-IR (KBr): ν(cm⁻¹) = 3278, 3202, 3079, 2986, 1709, 1607, 1789, 1309; ¹H NMR (300 MHz, EtOH-d₆) δ 7.13 (d, J = 7.3, 2H), 7.02 (t, J = 7.4, 2H), 6.92 (t, J = 7.1, 1H), 4.89 (s, 1H), 3.53 (s, 3H), 2.34 (d, J = 17.0, 1H), 2.28–2.18 (m with s at 2.26, 4H), 2.12 (d, J = 16.5, 1H), 1.97 (d, J = 16.5, 1H), 0.96 (s, 3H), 0.79 (s, 3H); ¹³C NMR (101 MHz) δ 194.7, 167.7, 149.9, 147.9, 145.7, 128.2, 127.7, 126.1, 110.4, 103.6, 51.1, 50.7, 36.0, 32.6, 29.6, 26.8, 18.7; MS (EI) m/z (%): 325 (M⁺, 11), 248 (100); TOF-HRMS (EI): m/z (M)⁺ calcd for C₂₀H₂₃NO₃ 325.1678; found 325.1673.

Methyl 4-(4-bromophenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate: (1p)⁴²

Melting point: 261–263 °C; FT-IR (KBr): ν(cm⁻¹) = 3291, 3202, 3078, 2958, 1683, 1606, 1492, 1382, 1332, 1227; ¹H NMR (300 MHz, EtOH-d₆) δ 7.17 (d, J = 8.3, 2H), 7.05 (d, J = 8.3, 2H), 4.85 (s, 1H), 3.47 (s, 3H), 2.34 (d, J = 17.0, 1H), 2.30–2.19 (m with s at 2.27, 4H), 2.12 (d, J = 16.4, 1H), 1.98 (d, J = 16.6, 1H), 0.96 (s, 3H), 0.79 (s, 3H); ¹³C NMR (101 MHz) δ 194.7, 167.5, 150.1, 147.2, 146.1, 131.1, 130.0, 119.2, 110.0, 103.1, 51.2, 50.6, 35.6, 32.6, 29.5, 26.9, 18.8; MS (EI) m/z (%): 405 (M⁺ + 2, 7), 403 (M⁺, 7), 248 (100); TOF-HRMS (EI): m/z (M)⁺ calcd for C₂₀H₂₂BrNO₃ 403.0783; found 403.0674.

Methyl 4-(2,4-dichlorophenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate: (1q)⁴²

Melting point: 251–253 °C; FT-IR (KBr): ν(cm⁻¹) = 3416, 3263, 1378, 2957, 1710, 1650, 1588, 1493, 1216; ¹H NMR (300 MHz, EtOH-d₆) δ 7.21 (d, J = 8.3, 1H), 7.09 (d, J = 1.8, 1H), 7.01 (dd, J = 8.3, 1.7, 1H), 5.19 (s, 1H), 3.43 (s, 3H), 2.35 (d, J = 17.0, 1H), 2.30–2.15 (m with s at 2.21, 4H), 2.10 (d, J = 16.4, 1H), 1.93 (d, J = 16.3, 1H), 0.97 (s, 3H), 0.83 (s, 3H); ¹³C NMR (101 MHz) δ 194.4, 167.5, 150.3, 146.0, 144.9, 133.2, 132.9, 131.2, 128.6, 127.4, 109.9, 100.5, 50.9, 50.6, 35.0, 32.5, 29.5, 26.8, 18.6; MS (EI) m/z (%): 397 (M⁺ + 4, 1), 395 (M⁺ + 2, 5), 393 (M⁺, 7), 358 (15), 248 (100); TOF-HRMS (EI): m/z (M)⁺ calcd for C₂₀H₂₁Cl₂NO₃ 393.0898; found 393.0910.

Methyl 4-(4-methoxyphenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate: (1r)²⁶

Melting point: 254–257 °C; FT-IR (KBr): ν(cm⁻¹) = 3188, 3067, 2961, 1705, 1649, 1605, 1498; ¹¹H NMR (300 MHz, EtOH-d₆) δ 7.03 (d, J = 8.1, 2H), 6.58 (d, J = 8.1, 2H), 4.82 (s, 1H), 3.59 (s, 3H), 3.46 (s, 3H), 2.33 (d, J = 17.0, 1H), 2.28–2.16 (m with s at 2.25, 4H), 2.12 (d, J = 16.5, 1H), 1.97 (d, J = 16.5, 1H), 0.96 (s, 3H), 0.80 (s, 3H); ¹³C NMR (101 MHz) δ 194.7, 167.8, 157.7, 149.6, 145.4, 140.3, 128.6, 113.6, 110.7, 104.0, 55.3, 51.1, 50.7, 35.2, 32.6, 29.6, 26.9, 18.7; MS (EI) m/z (%): 355.2 (M⁺, 26), 248.1 (100); TOF-HRMS (EI): m/z (M)⁺ calcd for C₂₁H₂₅NO₄ 355.1784; found 355.1788.

Methyl 4-(4-hydroxyphenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate: (1s)²⁶

Melting point: 297–298 °C; FT-IR (KBr): ν(cm⁻¹) = 3400, 3276, 3199, 2960, 1687, 1611, 1487, 1380, 1222, 1168, 768; ¹H NMR (300 MHz, EtOH-d₆) δ 6.93 (d, J = 8.1 Hz, 2H), 6.49 (d, J = 8.1 Hz, 2H), 4.79 (s, 1H), 3.47 (s, 3H), 2.33 (d, J = 17.0 Hz, 1H), 2.22 (m with s at 2.25, 4H), 2.11 (d, J = 16.5 Hz, 1H), 1.97 (d, J = 16.5 Hz, 1H), 0.96 (s, 3H), 0.80 (s, 3H); ¹³C NMR (101 MHz) δ 194.3, 167.5, 155.2, 149.1, 144.7, 138.2, 128.1, 114.5, 110.4, 103.7, 50.6, 50.3, 34.5, 32.1, 29.1, 26.4, 18.2; MS (EI) m/z (%): 341 (M⁺, 23), 248 (100); TOF-HRMS (EI): m/z (M)⁺ calcd for C₂₀H₂₃NO₄ 341.1627; found 341.1628.

Methyl 2,7,7-trimethyl-5-oxo-4-(p-tolyl)-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate: (1t)²³

Melting point: 270–273 °C; FT-IR (KBr): ν(cm⁻¹) = 3191, 3072, 2958, 1686, 1644, 1503, 1491, 1227; ¹H NMR (300 MHz, EtOH-d₆) δ 7.01 (d, J = 7.8, 2H), 6.83 (d, J = 7.6, 2H), 4.84 (s, 1H), 3.47 (s, 3H), 2.33 (d, J = 16.7, 1H), 2.27–2.19 (m with s at 2.25, 4H), 2.15–1.90 (m with s at 2.11, 5H), 0.96 (s, 3H), 0.80 (s, 3H); ¹³C NMR (101 MHz) δ 194.7, 167.8, 149.7, 145.5, 145.0, 135.0, 128.8, 127.6, 110.5, 103.8, 51.0, 50.7, 35.6, 32.5, 29.6, 26.9, 21.0, 18.7; MS (EI) m/z (%): 339 (M⁺, 15), 248 (100); TOF-HRMS (EI): m/z (M)⁺ calcd for C₂₁H₂₅NO₃ 339.1834; found 339.1834.

Acknowledgements

We thank the Bu-Ali Sina University, the Iran National Science Foundation (INSF) (Allameh Tabataba'i's Award, Grant Number BN093), the University of Alicante (VIGROB-173), and the Spanish Ministerio de Economía y Competitividad (CTQ2015-66624-P) for financial support to our research groups.

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Footnote

† Electronic supplementary information (ESI) available. See DOI: 10.1039/c6ra16459e

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