Cu(0) onto sulfonic acid functionalized silica/carbon composites as bifunctional heterogeneous catalysts for the synthesis of polysubstituted pyridines and nitriles under benign reaction media

Abstract

A series of novel and highly efficient bifunctional heterogeneous catalysts based on Cu(0) onto sulfonic acid functionalized silica/carbon composites derived from silica and inexpensive natural organic materials (starch, glucose, maltose, cellulose and chitosan) were successfully synthesized. The utility of the developed catalysts was explored for the one-pot synthesis of polysubstituted pyridines under solvent-free conditions and for the oxidative transformation of aldehydes to nitriles using aqueous ammonia and H₂O₂. Among the different catalysts screened, Cu(0)–SilC_cell–SO₃H was found to be the most active and selective. The prepared bifunctional composites were characterized by FTIR, TGA and CHNS, while the most active catalyst, Cu(0)–SilC_cell–SO₃H was further characterized by SEM, TEM, XRD, EDX, ICP-AES and XPS analysis. Further, the catalyst can be recovered and reused for atleast six runs without any significant impact on catalytic activity and selectivity. The high catalytic activity, thermal stability, simple recovery, reusability and eco-friendly nature of the catalyst makes the present protocol particularly attractive from the view point of green chemistry.

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Introduction

The challenges of the 21st century require scientific and technological accomplishments that must be developed using sustainable and environmentally benign practices. In this vein, catalysis and green chemistry walk hand in hand in promoting faster and cleaner transformations.^1,2 The designing of one-pot multiple transformations also known as tandem or domino reactions, completely demonstrates the concepts of efficiency, atom economy and waste reduction.³ Thus, the key to attain multicatalytic events in the same reaction vessel involve the use of highly selective heterogeneous catalysts. Following this concept, chemists have designed various heterogeneous multifunctional catalysts with well-defined multisites to avoid unwanted pathways. The active sites in the multifunctional catalysts can be organic, metallic or combination of both, and thus can work independently or synergistically to perform multicatalytic events in the desired reactions.^4,5 The heterogeneous catalysts, for instance Pd–SO₃H/SiO₂, Ir/H-beta zeolite, Pt/H-beta zeolite, Pd–H₃PW₁₂O₄₀/SiO₂ and many others have recently been explored for their multifunctional applications.^5,6 Despite the spectacular success in the field of multifunctional catalysts, there is always much scope available for the improvement at several levels. Among various types of multifunctional catalysts, heterogeneous metal/sulphonated bronsted acid catalysts have attracted considerable interest.⁷ With increasing demands upon our planet's resources, more and more research efforts are being focussed on the preparation of new materials from renewable resources. Thus, sulfonated carbon based composites prepared from biomaterials and silica have been proved to be promising heterogeneous catalysts in the conversion of biomass due to their excellent hydrothermal stability and catalytic activity.^8–10

Composites containing metal NPs have attracted a great deal of attention, due to their unique optical, electrical, and catalytic properties.^6,11,12 Recently, Cu(0) nanoparticles have drawn attention of chemists owing to their inexpensive nature, easy preparation and the ability to replace other noble metals, such as Ag, Au and Pt.¹³ Conversely, the use of Cu(0) nanoparticles is often complicated by the issues related with their oxidation and agglomeration in the absence of stabilizers, thereby diminishing their activity.¹⁴ Recent advances in the design and preparation of Cu(0) nanoparticles confirmed that they can be synthesized through different preparation routes and using acid functionalized supports to give tailored sizes, shapes and distributions, overcoming the main drawbacks of traditional synthetic methodologies.¹⁵ Furthermore, acid functionalized organic/inorganic composites generally exhibit important advantages over traditional catalysts such as: (i) the control of the particle shape by the acidic functional groups located in the polymer chain; (ii) the improvement of catalytic selectivity; (iii) the stabilization of nanoparticles by suppression of their aggregation^16,17 and thus can act as efficient supports for the immobilization of metal nanoparticles. Hence, with the growing interest in the heterogeneous catalysis, it is certain that metal nanoparticles based acid functionalized organic/inorganic composites will continue to be a fast moving topic for next several years.

Pyridine and its derivatives are an important class of N-heterocyclic compounds which have been found to be an integral part of many natural products^18–20 and have shown potent pharmacological properties.²¹ Recently, multicomponent reactions (MCRs) have gained tremendous attention from medicinal and organic chemists. These methods offer rapid and convergent construction of complex molecules without isolation and purification of intermediates, minimizing waste, effort, time, and cost. Thus, several elegant and effective methods based on MCRs have been reported for the synthesis of pyridine derivatives.²²

Further, nitriles are an important class of compounds in organic synthesis, because of their versatility and potential for further transformation into other functional compounds.²³ Representative strategies for the synthesis of nitriles generally involve the use of toxic reagents, high temperature, pressure, and generate large amount of wastes.^24–26 Hence, there is a growing demand for a highly practical nitrile synthesis by employing heterogeneous metal catalysts and using cheap and commercially available starting materials.

Herein, we have synthesized novel and sustainable bifunctional heterogeneous catalysts based on Cu(0) NPs onto sulfonic acid functionalized silica/carbon composites [Cu(0)–SilC–SO₃H]. The developed catalyst has been efficiently utilized for the one-pot synthesis of polysubstituted pyridines via nucleophilic addition/intermolecular cyclization under solvent-free conditions. Further, to explore the wider applicability of the developed catalyst, we have used Cu(0)–SilC–SO₃H for the oxidative transformation of aldehydes to nitriles using aqueous ammonia and H₂O₂ at 100 °C. In both these reactions, excellent results were obtained. To the best of our knowledge, the use of copper nanoparticles onto sulfonic acid functionalized silica/carbon composites as catalysts for the one-pot synthesis of polysubstituted pyridines and for the oxidative synthesis of nitriles from aldehydes has not been previously reported in the literature.

Results and discussion

Characterization of Cu(0) onto sulfonic acid functionalized silica/carbon composites [Cu(0)–SilC–SO₃H]

The preparation procedure of Cu(0)–SilC–SO₃H is represented in Scheme 1. Initially, silica/carbon composites were prepared by the partial carbonization of biomaterials (starch, glucose, maltose, cellulose and chitosan) in the presence of silica followed by sulfonation using sulfonic acid.²⁷ This step was followed by the immobilization of Cu(0) nanoparticles onto the surface of sulfonated silica/carbon composites by in situ reduction of copper chloride with NaBH₄. The prepared Cu(0)–SilC–SO₃H composites were characterized by FTIR, TGA and CHNS, while the most active catalyst, Cu(0)–SilC_cell–SO₃H was further characterized by SEM, TEM, XRD, EDX, ICP-AES and XPS analysis.

Scheme 1 General procedure for the synthesis of Cu(0)–SilC–SO₃H.

The surface chemical structure of Cu(0)–SilC–SO₃H was characterized by FTIR spectroscopy. The FTIR spectrum showed bands in the region of 1639–1648 cm⁻¹ which were assigned to aromatic C=C stretching modes in polycyclic aromatic rings. The absorption bands in the range of 1402–1406 cm⁻¹ and 1100–1106 cm⁻¹ were observed due to the asymmetric and symmetric stretching modes of SO₂ group, indicating the successful incorporation of SO₃H groups into the carbon framework. Further, the broad bands ranging from 3401–3412 cm⁻¹ were due to the phenolic –OH groups present in the aromatic rings. The Cu(0) based sulfonated silica/carbon composites prepared from different natural organic compounds (Cu(0)–SilC_star–SO₃H from starch, Cu(0)–SilC_glu–SO₃H from glucose; Cu(0)–SilC_mal–SO₃H from maltose, Cu(0)–SilC_cell–SO₃H from cellulose and Cu(0)–SilC_chit–SO₃H from chitosan) showed almost similar FTIR spectra. The major absorption frequencies are shown in Table 1 and the FTIR spectra of Cu(0)–SilC_cell–SO₃H is shown in Fig. 1.

Table 1 Major absorption frequencies in FTIR (υ_max in cm⁻¹) of Cu(0)–SilC–SO₃H^a

Entry	Catalyst	C=C	SO2 asym.	Str. sym.	–OH
a FTIR was recorded on Perkin-Elmer FTIR spectrophotometer using KBr discs.
1	Cu(0)–SilCstar–SO3H	1646	1404	1104	3410
2	Cu(0)–SilCglu–SO3H	1639	1402	1100	3401
3	Cu(0)–SilCmal–SO3H	1643	1406	1105	3405
4	Cu(0)–SilCcell–SO3H	1645	1403	1102	3406
5	Cu(0)–SilCchit–SO3H	1648	1406	1106	3412

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Fig. 1 FTIR spectrum of Cu(0)–SilC_cell–SO₃H.

The thermal stability of Cu(0)–SilC–SO₃H was examined by TGA in the temperature range of 30 to 800 °C under a static atmosphere of nitrogen. The major weight losses of different Cu(0)–SilC–SO₃H catalysts are represented in Table 2. The TGA curve of Cu(0)–SilC_cell–SO₃H (Fig. 2) showed an initial weight loss below 110 °C which can be ascribed to the evaporation of water and solvent molecules present in the composite. The second weight loss appeared between 310–350 °C, which may be attributed to the decomposition of sulfonic acid moieties present in Cu(0)–SilC_cell–SO₃H. Further weight loss from 350 to 800 °C was attributed to the bulk pyrolysis of silica/cellulose skeleton.

Table 2 Thermogravimetric analysis representing major weight losses in Cu(0)–SilC–SO₃H^a

Entry	Catalyst	Loss of residual solvent (°C)	Loss of organic functionality (°C)
a Thermal analysis was carried out at a heating rate of 10 °C min^−1.
1	Cu(0)–SilCstar–SO3H	100	325–800
2	Cu(0)–SilCglu–SO3H	100	318–670
3	Cu(0)–SilCmal–SO3H	110	315–670
4	Cu(0)–SilCcell–SO3H	108	320–800
5	Cu(0)–SilCchit–SO3H	105	322–800

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Fig. 2 TGA curve of Cu(0)–SilC_cell–SO₃H.

The amount of sulfonic acid groups grafted onto the surface of Cu(0) based sulfonated silica/carbon composites was determined by CHNS analysis (Table 3). The results indicated that Cu(0)–SilC_star–SO₃H contained 0.89 wt%, Cu(0)–SilC_glu–SO₃H contained 0.81 wt%, Cu(0)–SilC_mal–SO₃H contained 0.58 wt%, Cu(0)–SilC_cell–SO₃H contained 1.2 wt% and Cu(0)–SilC_cell–SO₃H contained 0.98 wt% of sulfur, equivalent to SO₃H loading of 0.28, 0.25, 0.18, 0.32 and 0.30 mmole per gram of the catalyst. Further, the acid densities and the amount of C, H and S present in Cu(0)–SilC–SO₃H as determined by elemental analysis is also presented in Table 3. Among the different Cu(0)–SilC–SO₃H catalysts, Cu(0)–SilC_cell–SO₃H exhibited the highest SO₃H density. The most active Cu(0)–SilC_cell–SO₃H was further characterized by SEM, TEM, XRD, EDX and XPS analysis.

Table 3 Acid densities and amount of C, H and S present in Cu(0)–SilC–SO₃H^a

Entry	Catalyst	–SO3H (mmol g^−1)	S (wt%)	C (wt%)	H (wt%)
a Determined by elemental analysis.
1	Cu(0)–SilCstar–SO3H	0.28	0.89	18.2	1.2
2	Cu(0)–SilCglu–SO3H	0.25	0.81	19.1	1.3
3	Cu(0)–SilCmal–SO3H	0.18	0.58	20.4	1.7
4	Cu(0)–SilCcell–SO3H	0.32	1.2	19.6	1.5
5	Cu(0)–SilCchit–SO3H	0.30	0.98	21.5	1.6

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The shape and surface morphology of the catalyst was investigated by scanning electron microscopy (Fig. 3). The SEM micrographs of Cu(0)–SilC_cell–SO₃H showed floccules like structure with quasi spherical morphology. On the other hand, the surface of the composite was non-smooth depicting its amorphous nature and thus resulted in an increase in its surface area.

Fig. 3 SEM images of Cu(0)–SilC_cell–SO₃H.

To provide more accurate information on the particle size and fine structure of Cu(0)–SilC_cell–SO₃H, transmission electron microscopy (TEM) was carried out. TEM micrographs revealed the uniform formation of Cu(0) nanoflowers onto the surface of sulfonated SilC_cell material (Fig. 4a). The sulfonated carbon material appears as light grey particles over which black coloured Cu(0) nanorods combined to form nanoflowers, which can be easily visualised (Fig. 4b). The average diameter of the Cu(0) nanorods as determined from TEM analysis was found to be 28 nm (Fig. 4c).

Fig. 4 TEM images of Cu(0)–SilC_cell–SO₃H.

The XRD pattern of Cu(0)–SilC_Cell–SO₃H exhibited diffraction peaks corresponding to face-centered cubic (fcc) Cu.²⁸ Fig. 5 showed three reflection patterns at 2θ = 43.4, 50.5, and 74.2° which can be indexed as [111], [200] and [220] planes of copper. All the diffraction peak values along with the d-spacings match those in standard XRD data for copper (JCPDS 04-0836).²⁸ These results indicated that copper metal in Cu(0)–SilC_cell–SO₃H was present in Cu(0) state and no peaks of impurity were detected. In addition, a broad diffraction peak at 2θ = 15–29° was attributed to the reflection patterns of amorphous carbon composed of polycyclic aromatic carbon sheets oriented in a random manner.²⁹

Fig. 5 XRD pattern of Cu(0)–SilC_cell–SO₃H.

The elemental composition of Cu(0)–SilC_cell–SO₃H was determined by energy dispersive X-ray (EDX) analysis. The EDX spectrum, displayed in Fig. 6, clearly reveals the presence of C, Si, O, S and Cu present in Cu(0)–SilC_cell–SO₃H. Further, the weight percentage of Cu in Cu(0)–SilC_cell–SO₃H was determined by inductively coupled plasma atomic emission spectroscopy (ICP-AES). The results indicated that Cu content loaded onto Cu(0)–SilC_cell–SO₃H was 3.2 wt%.

Fig. 6 EDX of Cu(0)–SilC_cell–SO₃H.

The electron properties of the species formed on the surface of Cu(0)–SilC_cell–SO₃H, such as the oxidation state, and the binding energy of the core electron of the copper metal were analyzed using XPS. Fig. 7a showed the overall survey spectrum of Cu(0)–SilC_cell–SO₃H in which peaks corresponding to carbon 1s (284.9 eV), oxygen 1s (532.2 eV), silica 2p (105.3 eV) and copper 2p (932.7 eV) are clearly observed. In addition, the survey spectrum of the catalyst showed a singlet at around 168 eV for sulphur 2p, which is associated with SO₃H groups.³⁰ Fig. 7b showed the typical Cu(0) absorptions at 932.7 and 952.1 eV for 2p_3/2 and 2p_5/2 respectively, which are consistent with the literature values for Cu(0).³¹

Fig. 7 XPS of Cu(0)–SilC_cell–SO₃H; overall survey spectrum (a), Cu 2p core level spectrum (b).

Catalytic testing for the synthesis of polysubstituted pyridines

The catalytic activity of Cu(0)–SilC–SO₃H was studied for the synthesis of polysubstituted pyridines via one-pot condensation of aldehydes, ethyl acetoacetate, malononitrile and amines at 100 °C under solvent-free conditions. To select the appropriate Cu(0) based sulfonic acid functionalized silica/carbon composite, benzaldehyde, malononitrile, ethyl acetoacetate and aniline were selected as the model substrates and the reaction was carried out in the presence of Cu(0)–SilC_star–SO₃H, Cu(0)–SilC_glu–SO₃H, Cu(0)–SilC_mal–SO₃H, Cu(0)–SilC_cell–SO₃H and Cu(0)–SilC_chit–SO₃H at 100 °C under solvent-free conditions (Table 4). It was found that among the different catalysts screened, Cu(0)–SilC_cell–SO₃H was the most effective catalyst in terms of reaction time and yield (entry 4, Table 4). Thus, out of various natural organic compounds (starch, glucose, maltose, cellulose and chitosan), cellulose could be the best choice for the preparation of Cu(0) based sulfonated silica/carbon composite. The high catalytic activity of Cu(0)–SilC_cell–SO₃H might be due to the fact that cellulose acts as a nanoreactor for metal nanoparticles³² and as a result it stabilizes the metal nanoparticles more effectively. The intra-chain hydrogen bonding between hydroxyl groups and oxygen of the adjoining ring molecules stabilizes the linkage and results in the linear configuration of the cellulose chain. It also contains microfibrils with up to 30 nm width that are three dimensionally connected to each other. The metal nanoparticles can be stabilized in the cavities of those microfibrils via oxygen–metal electrostatic interaction, which make cellulose an effective support for the metal nanoparticles stabilization.³²

Table 4 Effect of the Cu(0)–SilC–SO₃H on the synthesis of polysubstituted pyridines and nitriles

Entry	Catalyst	Pyridines^a		Nitriles^b
		Time (h)	Yield^c (%)	Time (h)	Yield^d (%)
a Reaction conditions: benzaldehyde (1 mmol), malononitrile (1 mmol), ethyl acetoacetate (1 mmol), aniline (1 mmol) and catalyst (0.13 mol% Cu) at 100 °C under solvent-free conditions.b Reaction conditions: benzaldehyde (1 mmol), 25% NH3(aq.) (5 mL), 30% H2O2 (0.1 mL, 2 mmol) and catalyst (0.19 mol% Cu) at 100 °C.c Isolated yields.d Column chromatography yields.
1	Cu(0)–SilCstar–SO3H	3.5	90	4.5	91
2	Cu(0)–SilCglu–SO3H	4	82	5	86
3	Cu(0)–SilCmal–SO3H	5	80	5	85
4	Cu(0)–SilCcell–SO3H	2.5	92	3.5	93
5	Cu(0)–SilCchit–SO3H	3	90	4	92

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Further, to select the appropriate catalyst amount, the model reaction was also examined by varying the catalyst amounts such as 0.05 g (0.06 mol% Cu), 0.1 g (0.13 mol% Cu), 0.15 g (0.19 mol% Cu) and 0.2 g (0.26 mol% Cu). It was found that 0.1 g (0.13 mol% Cu) of Cu(0)–SilC_cell–SO₃H was sufficient to get the optimum product yield, while further increase in the catalyst amount did not increase the yield significantly (entries 8, 10, 11, 12, Table 5). Furthermore, to optimize the reaction conditions with respect to different solvents and reaction temperature, the model reaction was examined in different solvents such as ethanol, methanol, acetonitrile, water, toluene as well as under solvent-free conditions. It was found that higher product yield was obtained when the reaction was carried out under solvent-free conditions in comparison to liquid phase conditions (Table 5). The maximum catalytic activity under solvent-free conditions may be attributed to the good dispersion of active reagent sites which facilitates better contact between reactants and the catalyst.³³ However, due to the absence of any solvent (as medium), there is no dilution effect and the heat needed for energy of activation is directly available to the reactant molecules. Further, to select the optimum reaction temperature, the model reaction was carried out under solvent-free conditions at 80, 90, 100 and 120 °C, and 100 °C was choosen as the optimum reaction temperature in view of the product yield and reaction time (entry 8, Table 5).

Table 5 Effect of different solvents, temperature and catalyst amount on Cu(0)–SilC_cell–SO₃H catalyzed one-pot synthesis of polysubstituted pyridines^a

Entry	Solvent	Temp. (°C)	Catalyst (g)	Time (h)	Yield^b (%)
a Reaction conditions: benzaldehyde (1 mmol), malononitrile (1 mmol), ethyl acetoacetate (1 mmol) and aniline (1 mmol) at 100 °C under solvent-free conditions.b Isolated yield.c Column chromatography yields.
1	Ethanol	Reflux	0.1	4	86
2	Methanol	Reflux	0.1	5	80
3	Acetonitrile	Reflux	0.1	7.5	45^c
4	Water	Reflux	0.1	7.5	55^c
5	Toluene	Reflux	0.1	10	35^c
6	Solvent-free	80	0.1	3.5	85
7	Solvent-free	90	0.1	3.25	88
8	Solvent-free	100	0.1	2.5	92
9	Solvent-free	120	0.1	2.5	92
10	Solvent-free	100	0.05	4	70
11	Solvent-free	100	0.15	2.5	92
12	Solvent-free	100	0.2	2.5	92

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After optimizing the reaction conditions, the substrate scope with respect to various aldehydes and aromatic amines was examined and a wide range of pyridine derivatives were prepared. The results are summarized in Table 6. Among various aromatic aldehydes studied, aldehyde possessing electron-withdrawing group such as –NO₂ gave higher yields (product 5g, Table 6) compared to those possessing electron-donating groups (–OCH₃, –CH₃) (products 5b, 5c, Table 6). It is pertinent to mention that the positions of these substituents had an apparent effect on the reaction. When aromatic aldehyde bearing ortho substituted electron withdrawing group (–NO₂) was used, a comparatively lower yield was obtained (product 5f, Table 6). Moreover, the reaction with heteroaromatic aldehyde also proceeded well and gave the corresponding product in good yield (product 5i, Table 6). Among various substituted aromatic amines, the anilines with electron-withdrawing as well as electron donating groups also worked well and gave good yields (product 5j–5o, Table 6). Therefore, the present methodology offers wider substrate scope for the synthesis of polysubstituted pyridines under the optimized reaction conditions.

Table 6 Cu(0)–SilC_cell–SO₃H catalyzed one-pot synthesis of polysubstituted pyridines in solvent-free conditions^a,b

a Reaction conditions: aldehyde (1 mmol), malononitrile (1 mmol), ethyl acetoacetate (1 mmol) and amine (1 mmol) and Cu(0)–SilC_cell–SO₃H (0.1 g, 0.13 mol% Cu) at 100 °C under solvent-free conditions.b Isolated yield.

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The mechanisms of Bronsted acid catalysis as well as the synergism between metal and Bronsted acid in the field of organic synthesis have been discussed in detail in the comprehensive review by Rueping et al.^24,34 Accordingly, a probable mechanism has been proposed (Scheme 2) for the synthesis of polysubstituted pyridines catalyzed by the bifunctional Cu(0)–SilC_cell–SO₃H. Initially, aromatic aldehyde and malononitrile undergo Knoevenagel condensation to give I. Then, the Michael addition of ethyl acetoacetate to intermediate I gave intermediate II. Subsequently, aromatic amine reacts with II to form intermediate III. An intramolecular cyclization of III (via loss of H₂O molecule) followed by isomerization to give intermediate IV. Finally oxidative aromatization of IV in the presence of catalyst gave the final product V. Overall, four new bonds were formed in a one-pot process to give the polysubstituted pyridines.

Scheme 2 Plausible mechanism for the Cu(0)–SilC_cell–SO₃H catalyzed one-pot synthesis of polysubstituted pyridines.

Catalytic testing for the synthesis of nitriles

Motivated by the impressive performance of Cu(0)–SilC_cell–SO₃H for the synthesis of polysubstituted pyridines, we further explored the catalytic activity of the Cu(0)–SilC–SO₃H composites for the synthesis of nitriles. Initially, to optimize the reaction conditions for the synthesis of nitriles, benzaldehyde was choosen as the test substrate and the reaction was carried out in the presence of different catalysts using H₂O₂ in aqueous ammonia at 100 °C (Table 4). Again, it was found that Cu(0)–SilC_cell–SO₃H derived from cellulose showed the best results in terms of time and yield (entry 4, Table 4). Further, the effect of catalyst amount on the test reaction was also examined by varying the catalyst amounts and the results inferred that the 0.15 g (0.19 mol% Cu) of Cu(0)–SilC_cell–SO₃H was the sufficient amount required to get the optimum product yield.

Furthermore, to optimize the reaction conditions with respect to different oxidants and reaction temperature, the reaction with test substrate was carried out under different set of conditions to obtain the best possible combination. The effect of various oxidants such as molecular oxygen (O₂), hydrogen peroxide (H₂O₂) and TBHP in aqueous ammonia at temperatures ranging from R.T. to 120 °C was explored with test substrate (Table 7). Initially, when the reaction was carried out in the absence of any oxidant at 100 °C, no product formation took place (entry 1, Table 7). Further, when the reaction was carried out in the presence of different oxidants, it was observed that molecular oxygen (O₂) gave the poorest yield (entry 2, Table 7) and the best results were obtained with H₂O₂ in terms of time and yield (entry 3, Table 7). Although, good results were obtained with TBHP as well, however, it has led to decrease in selectivity of the product formation (entry 4, Table 7). The decrease in yield in case of TBHP as oxidant may be due to the interaction of the developed catalyst with tert-butyl alcohol, a by-product formed from the decomposition of TBHP which leads to decrease in activity of the catalyst. However, such kind of catalyst deactivation or catalyst poisoning is limited using H₂O₂ as oxidant and hence results in better conversion than TBHP.³⁵

Table 7 Effect of different oxidants and temperature on Cu(0)–SilC_cell–SO₃H catalyzed oxidative synthesis of nitriles in aqueous ammonia at 100 °C^a

Entry	Oxidant	Temperature (°C)	Time (h)	Yield^b (%)
a Reaction conditions: benzaldehyde (1 mmol), 25% NH3(aq.) (5 mL), 30% H2O2 (0.1 mL, 2 mmol) and Cu(0)–SilCcell–SO3H (0.15 g, 0.19 mol% Cu) at 100 °C.b Column chromatography yields.c No reaction.
1	—	100	5	NR^c
2	O2	100	5	30
3	H2O2	100	3.5	93
4	TBHP	100	3.5	80
5	H2O2	R.T.	5	45
6	H2O2	60	4.5	85
7	H2O2	80	4.0	90
8	H2O2	120	3.5	93

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Further, to select the optimum reaction temperature, the reaction with test substrate was carried out in aqueous ammonia at R.T., 60, 80, 100 and 120 °C, and 100 °C was choosen to be the optimum reaction temperature in view of the product yield and reaction time (entry 3, Table 7). At room temperature, the yield of the product obtained was very poor, while the reaction at 60 and 80 °C was little slow, and at 120 °C, no significant improvement in yield was observed (entries 5–8, Table 7). With an optimized reaction conditions, we then prepared various substituted aryl nitriles to explore the substrate scope. As shown in Table 8, a variety of substituted aldehydes bearing either electron-withdrawing or electron-donating groups were oxidatively transformed into corresponding nitriles using H₂O₂ in aqueous ammonia at 100 °C. Various functional groups such as methoxy, methyl, bromo, chloro and nitro at ortho, meta or para position in arylaldehyde were tolerated fairly well and afforded the desired products in moderate to high yields (products 2b–2h, Table 8). Further, thiophene-2-aldehyde and naphthyl-1-aldehyde were also successfully employed and corresponding nitriles were obtained in good yields (products 2i–2j).

Table 8 Cu(0)–SilC_cell–SO₃H catalyzed oxidative synthesis of nitriles using H₂O₂ in aqueous ammonia at 100 °C^a,b

a Reaction conditions: aldehyde (1 mmol), 25% NH₃(aq.) (5 mL), 30% H₂O₂ (0.1 mL, 2 mmol) and Cu(0)–SilC_cell–SO₃H (0.15 g, 0.19 mol% Cu) at 100 °C.b Column chromatography yields.

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A cyclic mechanism has been proposed (Scheme 3), which involves the electrophilic activation of aldehyde by Cu(0)–SilC_cell–SO₃H followed by the nucleophilic attack of aqueous ammonia to form an aldimine (I). This step is followed by the activation of H₂O₂ by co-ordinating with Cu(0) to form Cu(I) imine complex (II). Then, the activated oxygen of the co-ordinated H₂O₂ abstracts hydrogen from the imine to give the final product ‘III’ and an intermediate ‘IV’. Intermediate ‘IV’ then loses molecule of water and Cu(0) is regenerated.

Scheme 3 Plausible mechanism for the Cu(0)–SilC_cell–SO₃H catalyzed oxidative synthesis of nitriles.

Recyclability and heterogeneity

In sustainable organic synthesis, the recyclability is an important parameter. In order to investigate this parameter, we carried out the recyclability studies of Cu(0)–SilC_cell–SO₃H in case of 5a, Table 6 and 2a, Table 8. After completion of the reaction, the catalyst was recovered by simple filteration, washed with distilled water, dried and reused for subsequent runs. The results shown in Fig. 8 clearly demonstrate that the catalyst is recyclable upto 6^th run without significant loss of activity. The heterogeneity of Cu(0)–SilC_cell–SO₃H was further tested by the hot filtration test to check any possibility of leaching of Cu(0) metal from the catalyst surface. The reaction in case of 2a, Table 8 has been carried out in the presence of Cu(0)–SilC_cell–SO₃H, until the conversion was 45% (1 h) after which the catalyst was filtered off at the reaction temperature. The reaction was then continued further under same set of conditions without the catalyst and found that no significant conversion was observed. The ICP-AES analysis of the used Cu(0)–SilC_cell–SO₃H after 6^th run showed negligible loss of Cu metal from the surface of Cu(0)–SilC_cell–SO₃H. Further, the amount of SO₃H in the used catalyst after 6th run was determined by elemental analysis, showed 0.27 mmol g⁻¹ of SO₃H compared to 0.32 mmol g⁻¹ in the fresh catalyst. Furthermore, the XPS analysis of the recovered catalyst after six consecutive runs was also carried out, where no change of oxidation state of Cu(0) has been confirmed (Fig. S1, see ESI†). Thus, it can be concluded that the catalyst is heterogeneous in nature and Cu(0) nanoparticles are efficiently stabilized over the support.

Fig. 8 Recyclability of Cu(0)–SilC_cell–SO₃H: reaction conditions [pyridines]: benzaldehyde (1 mmol), malononitrile (1 mmol), ethyl acetoacetate (1 mmol) and aniline (1 mmol), Cu(0)–SilC_cell–SO₃H (0.1 g. 0.13 mol% Cu) at 100 °C under solvent-free condition for 2.5 h; [nitriles]: benzaldehyde (1 mmol), 25% NH₃(aq.) (5 mL), 30% H₂O₂ (0.1 mL, 2 mmol) and Cu(0)–SilC_cell–SO₃H (0.15 g, 0.19 mol% Cu) at 100 °C in 3.5 h.

Comparison of Cu(0)–SilC_cell–SO₃H with other catalysts

In order to demonstrate the role of Cu(0)–SilC_cell–SO₃H as bifunctional catalyst for the one-pot multicomponent synthesis of polysubstituted pyridines and for the oxidative synthesis of nitriles, we performed some control experiments in case of 5a and 2a (Table 6 and 8) and the results are summarized in Table 9. Initially, no reactions took place when they were carried out in the absence of catalyst (entry 1, Table 9). Further, reactions in the presence of non-sulfonated silica/cellulose catalyst (SilC_cell), again gave the poor results and the corresponding products were obtained in traces (entry 2, Table 9). However, when we carried out the reactions in the presence of sulfonated silica/cellulose (SilC_cell–SO₃H), it has led to significant increase in the yields (entry 3, Table 9). But, since the yields obtained with SilC_cell–SO₃H were not satisfactory, we performed the reactions in the presence of Cu(0) immobilized non-sulfonated silica/cellulose [Cu(0)–SilC_cell] which had also led to increase in the yield of polysubstituted pyridines and nitriles up to 70% and 75% respectively (entry 4, Table 9) which implies that both Cu(0) nanoparticles and SO₃H Bronsted acid sites are playing active role in catalysing the reaction. So, in order to investigate the dual role of the catalyst, we performed the desired reactions in the presence of Cu(0)–SilC_cell–SO₃H. As expected, the combined use of Cu(0) nanoparticles and SilC_cell–SO₃H gave excellent results and the corresponding products were obtained in 92% and 93% yields (entry 5, Table 9).

Table 9 Control experiments for the comparison of activity of Cu(0)–SilC_cell–SO₃H with other catalysts

Entry	Catalyst	Pyridines^a		Nitriles^b
		Time (h)	Yield^c (%)	Time (h)	Yield^d (%)
a Reaction conditions: benzaldehyde (1 mmol), malononitrile (1 mmol), ethyl acetoacetate (1 mmol) and aniline (1 mmol) and catalyst (0.1 g for entries 2 and 3; 0.13 mol% Cu for entries 4 and 5) at 100 °C under solvent-free conditions.b Reaction conditions: benzaldehyde (1 mmol), 25% NH3(aq.) (5 mL), 30% H2O2 (0.1 mL, 2 mmol) and catalyst (0.15 g for entries 2 and 3; 0.19 mol% Cu for entries 4 and 5).c Isolated Yield.d Column chromatography yields.e No reaction.
1	No catalyst	2.5	NR^e	3.5	NR^e
2	SilCcell	2.5	Traces	3.5	Traces
3	SilCcell–SO3H	2.5	65	3.5	60
4	Cu(0)–SilCcell	2.5	70	3.5	75
5	Cu(0)–SilCcell–SO3H	2.5	92	3.5	93

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Further, in order to study the merits of the current protocol for the synthesis of polysubstituted pyridines and nitriles, a comparison of the efficacy of Cu(0)–SilC_cell–SO₃H with some of the reported catalytic systems in the literature was done. The results presented in Table 10 clearly depicts that the present method comparatively affords a truly green process using benign reaction media along with higher product yields in shorter reaction time. Further, it is noteworthy to mention here that Cu(0)–SilC_cell–SO₃H with lower catalyst loading exhibits high activity in the synthesis of polysubstituted pyridines and nitriles under the same reaction conditions along with the added advantages of catalyst recovery and reusability. In addition, the greenness of our protocol is also evaluated by employing the applications of green chemistry metrics (E-factor). The comparison of E-factor with several other catalyst systems explained the improved greenness of the present protocol (Table S1, see ESI†).

Table 10 Comparison of the catalytic activity of Cu(0)–SilC_cell–SO₃H with reported catalytic systems for the synthesis of polysubstituted pyridines and nitriles

Reaction	Catalyst	Reaction Conditions	Time (h)	Yield (%)	Reference
a Reaction conditions: benzaldehyde (1 mmol), malononitrile (1 mmol), ethyl acetoacetate (1 mmol) and aniline (1 mmol).b Reaction conditions: benzaldehyde (1 mmol).c Isolated yield.d Column chromatography yield.
Pyridines^a	FeCl3 (Homogeneous)	EtOH, 70 °C, Catalyst (5 mol%)	6	75	36
	SnCl2·2H2O (homogeneous)	H2O, 60 °C, Catalyst (10 mol%)	8	82	37
	Cu(0)–SilCcell–SO3H (heterogeneous)	Solvent-free, 100 °C, catalyst (0.1 g, 0.13 mol% Cu)	2.5	92^c	Present work
Nitriles^b	Cu(OTf)2/Bipy (homogeneous)	OH-TEMPO, NH3 (aq), NaOH, MeCN, 25 °C, Catalyst (10 mol%)	16	95	38
	Polymer-PhI(OAc)2 (heterogeneous)	Sodium dodecylsulfate (SDS), aq NH4OAc, 70 °C, catalyst (1.0 g, 2 mmol)	4	90	39
	Cu(0)–SilCcell–SO3H (heterogeneous)	NH3 (aq), H2O2, 100 °C, Catalyst (0.15 g, 0.19 mol% Cu)	3.5	93^d	Present work

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Conclusion

In conclusion, we have developed bifunctional Cu(0) based sulfonic acid functionalized silica/carbon composites and their catalytic activities have been evaluated for the one-pot synthesis of polysubstituted pyridines and for the oxidative transformation of aldehydes to nitriles. The bifunctional composite derived from cellulose was found to be most active and selective under benign reaction media. Further, the developed catalyst is recyclable upto 6 consecutive runs without significant loss in activity, and exhibits good compatibility with a broad range of functional groups. Meanwhile, this protocol may complement the existing approaches to afford the synthesis of polysubstituted pyridines and nitriles, which are utilized as the key intermediates in the synthesis of drugs and pharmaceuticals.

Experimental

General

All the chemicals and solvents used were purchased from Aldrich Chemical Company or Merck. The ¹H and ¹³C NMR data were recorded in CDCl₃ on Bruker Avance III (400 MHz and 100 MHz) and mass spectral data on Bruker Esquires 3000 (ESI†). The FTIR spectra were recorded on Perkin-Elmer FTIR spectrophotometer. TGA was recorded on Linsesis STA PT-1000 make thermal analyzer. CHNS analysis was recorded on ThermoFinnigan FLASH EA 1112 series. SEM images were recorded using FEG SEM JSM-7600F. Transmission Electron Micrographs (TEM) were recorded on Philips CM-200. X-ray diffractograms (XRD) were recorded in 2 theta range of 10–80° on a Bruker AXSDB X-ray diffractometer using Cu Kα radiations. EDX analysis was carried out using OXFORD X-MAX JSM-7600 and the amount of metal in catalyst was determined by ICP-AES analysis using ARCOS from M/s Spectro, Germany. XPS spectra of the catalyst were recorded on a KRATOS ESCA model AXIS 165 (Resolution).

General procedure for the preparation of Cu(0)–SilC–SO₃H

Initially, silica/carbon composites were prepared by the partial carbonization of biomaterials (starch, glucose, maltose, cellulose and chitosan) in the presence of silica followed by sulfonation using sulfonic acid.²⁷ Typically, silica (2 g, K100, 0.063–0.200 mm) and natural organic compound (2.4 g, glucose, maltose, cellulose, chitosan or starch) in the ratio of 1 : 1.2 in a round-bottom flask (100 mL) were dried at 80 °C for 6 h, followed by incomplete carbonization at 250 °C under nitrogen atmosphere for 10 h. These were then sulfonated using concentrated sulfuric acid (15 mL, >96 wt%) on heating at 150 °C for 6 h under N₂ atmosphere. The composite material obtained was then washed repeatedly with hot distilled water (>80 °C) until sulfate anions were no longer detected in the filtered water. Sulfonated carbon/silica composites were finally dried in an oven at 100 °C for 2 h. For the preparation of Cu(0)–SilC–SO₃H, a mixture of aqueous CuCl₂ solution (0.134 g, 1.0 mmol, 3 mL) was added to sulfonated silica/carbon composite (1 g) in ethanol (10 mL) and the reaction mixture was stirred at room temperature for 6 h. After that, aqueous solution of NaBH₄ (1.2 mmol, 5 mL) was added slowly to the above reaction mixture during 8 h. Finally, the mixture was filtered, and the residue was successively washed with H₂O (3 × 5 mL) and ethanol (3 × 5 mL), and dried under vacuum at room temperature.

General procedure for the synthesis of polysubstituted pyridines

To a mixture of aldehyde (1 mmol), ethyl acetoacetate (1 mmol), malononitrile (1 mmol), and amine (1 mmol) in a round-bottom flask (25 mL), Cu(0)–SilC_cell–SO₃H (0.1 g, 0.13 mol% Cu) was added, and the reaction mixture was stirred under solvent-free conditions at 100 °C for an appropriate time (Table 6). After completion of the reaction (monitored by TLC), the reaction mixture was diluted with ethyl acetate and the catalyst was filtered off. The organic layer was washed with water (3 × 10 mL) followed by brine solution (2 × 10 mL) and dried over anhyd. Na₂SO₄. Finally, the product was obtained after removal of the solvent under reduced pressure followed by crystallization with EtOAc-pet. ether. The recovered catalyst was washed with EtOAc (3 × 10 mL) followed by double distilled water (3 × 10 mL) and dried. It was then reused for subsequent reactions.

General procedure for the oxidative synthesis of nitriles from aldehydes

To a mixture of aldehyde (1 mmol), 25% aq. NH₃ (5 mL) and 30% H₂O₂ (0.1 mL, 2 mmol) in a round-bottom flask (25 mL), Cu(0)–SilC_cell–SO₃H (0.15 g, 0.19 mol% Cu) was added, and the reaction mixture was stirred at 100 °C for an appropriate time (Table 8). After completion of the reaction (monitored by TLC), the reaction mixture was diluted with ethyl acetate and the catalyst was filtered off. The organic layer was washed with water (3 × 10 mL) followed by brine solution (2 × 10 mL) and dried over anhyd. Na₂SO₄. Finally, the product was obtained after removal of the solvent under reduced pressure followed by passing through column of silica gel and elution with EtOAc-pet. ether. The recovered catalyst was washed with EtOAc (3 × 10 mL) followed by double distilled water (3 × 10 mL) which was dried and reused for subsequent reactions.

Acknowledgements

We gratefully acknowledge the Head, SAIF, IIT Bombay for SEM, TEM, EDX, CHNS and ICP-AES studies; SAIF, Punjab University Chandigarh for XRD; IICT, Hyderabad for XPS analysis. Financial assistance from UGC, New Delhi (SRF to one of the authors, MB and major research project, F 41-281/2012 SR) is gratefully acknowledged.

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Footnote

† Electronic supplementary information (ESI) available: Spectral details of all the products listed in Tables 6 and 8 and copies of spectras of ¹H, D₂O and ¹³C of selected products. See DOI: 10.1039/c6ra19840f

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