Rehab
Tahseen alhayo
a,
Ghufran Sh.
Jassim
b,
Hasanain Amer
Naji
c,
A. H.
Shather
d,
Israa Habeeb
Naser
e,
Luay Ali
Khaleel
f and
Haider Abdulkareem
Almashhadani
*g
aAl-Farahidi University, College of dentistry, Baghdad, Iraq
bDepartment of Chemistry, College of Science, University of Anbar, Anbar, Iraq
cFaculty of Pharmacy, Al-Turath University College, Baghdad, Iraq
dDepartment of Computer Engineering Technology Al Kitab University,Altun Kopru, Kirkuk 00964, Iraq
eMedical Laboratories Techniques Department / AL-Mustaqbal University College, 51001 Hillah, Babil, Iraq
fCollage of Dentistry, National University of Science and Technology, Dhi Qar, Iraq
gChemistry Department, College of Science, University of Baghdad, Baghdad, Iraq. E-mail: haider.200690@gmail.com; h_r200690@yahoo.com
First published on 8th November 2023
In this research, we present a post-synthetic method for synthesizing a novel nanomagnetic Cu(II) Schiff base complex and investigate its efficiency in catalytic organic conversion reactions. Various spectroscopic analyses were employed to characterize the physiochemical characteristics of the resulting nanocomposite. The experimental results successfully demonstrate the catalytic application of the prepared Cu-complex in the preparation of pyrano[2,3-c]pyrazole heterocycles. This synthesis involved a one-pot three-component condensation reaction, wherein hydrazine hydrate, ethyl acetoacetate, malononitrile, and aromatic aldehydes were combined under reflux conditions using water as the solvent. Notably, the heterogenized complex exhibited exceptional catalytic performance, achieving remarkable conversion rates and selectivity, all accomplished using only 12 mg of the catalyst. Furthermore, thorough stability assessments of this catalyst were conducted through reusability and hot filtration tests, which confirmed its non-leaching properties and demonstrated excellent results over the course of five consecutive runs.
The pyrano[2,3-c]pyrazoles synthesis involves diverse strategies, such as multicomponent reactions, cyclization reactions, or condensation reactions, which allow for the introduction of different functional groups and substitution patterns.2–5 One commonly employed strategy involves the condensation reaction between pyrazole derivatives and α,β-unsaturated carbonyl compounds, such as α,β-unsaturated ketones or aldehydes, under acidic or basic conditions.6 Another synthetic approach involves the cyclization of α,β-unsaturated ketones with hydrazine derivatives, followed by oxidative cyclization or ring-closing reactions using suitable reagents or catalysts. On the other hand, multicomponent reactions, such as the one-pot condensation of α,β-unsaturated carbonyl compounds, hydrazine derivatives, and active methylene compounds such as malononitrile, have been employed as the most efficient and simple method for this synthesis.7 In this regard, several catalytic methods have been employed for these reactions. One notable approach involves the use of Lewis acid catalysts, such as Zn, Fe and Cu complexes, which promote the generation and condensation of pyrazolone and α,β-unsaturated carbonyl intermediates, facilitating the cyclization process and resulting in the selective production of the fused pyrano[2,3-c]pyrazole rings at enhanced reaction rates.8–10 The use of catalytic methods provides several advantages, including increased reaction rates, improved yields, and enhanced control over regioselectivity and stereoselectivity, making them valuable tools in these transformations.
Heterogeneous magnetic catalysts are a promising class of materials in catalysis due to their unique combination of magnetic properties and catalytic functionality.11–15 These catalysts offer advantages such as enhanced catalyst recovery, recyclability, and improved reaction kinetics.15–18 Compared to traditional catalysts, heterogeneous magnetic catalysts simplify catalyst recovery, reduce costs, and minimize environmental impact.19,20 Additionally, their recyclability ensures long-term viability and economic feasibility, making them an attractive option in catalysis applications.21 The active regions located on the surface of the magnetic core or attached functional coatings enable a wide range of an extensive variety of catalytic reactions.22
In this regard; heterogeneous Schiff base catalysts are crucial in organic synthesis, promoting diverse and efficient chemical transformations.23,24 These catalysts consist of immobilized Schiff base ligands on solid supports, offering advantages such as enhanced catalytic activity, improved selectivity, and recyclability.25–27 They are compatible with a wide range of substrates, enabling the synthesis of various organic compounds with high yields and purity.28 The tunable and robust nature of these catalysts allows for the development of new synthetic methods and exploration of complex transformations.29,30 Overall, heterogeneous Schiff base catalysts play a vital role in advancing organic synthesis, providing efficient and environmentally friendly routes to valuable organic molecules.31
Overall, the unique combination of magnetic properties and catalytic efficiency of Schiff base complexes holds great promise for catalysis applications, opening new avenues for efficient and sustainable chemical transformations. Now, in this paper, a Schiff base complex of copper immobilized on magnetic Fe3O4 nanoparticles [Fe3O4@SiO2-Schiff base-Cu(II)] was successfully fabricated as a novel and efficient magnetically recoverable nanocatalyst for the multicomponent synthesis of pyrano[2,3-c]pyrazoles.
Fig. 1 FTIR spectrum of (a) Fe3O4, (b) Fe3O4@SiO2, (c) Fe3O4@SiO2-diamine and (d) [Fe3O4@SiO2-Schiff base-Cu(II)] complex. |
The X-ray diffraction (XRD) analysis was conducted to examine the structural properties of the [Fe3O4@SiO2-Schiff base-Cu(II)] complex (Fig. 2). The XRD pattern displayed the characteristic peaks of crystalline structure of Fe3O4 (JCPDS file no 19-0629) at 2θ = 30.15°, 35.65°, 43.33, 53.89°, 57.31°, 62.89° and 74.33° that are related to planes (220), (311), (400), (422), (511), and (440), (533), respectively.36 The results show that the post synthetic modification process did not change the crystalline structure of the final magnetic nanoparticles and it was remained intact. The presence of an amorphous SiO2 layer can be confirmed by a broad peak at 2θ = 24.29°. The prepared catalyst exhibited some additional diffraction peaks at 2θ = 24.29°, 31.37°, 39.33° and 40.61 which could be due to the addition of [Schiff base-Cu(II)] complex on Fe3O4@SiO2 surface.
The thermal stability of the [Fe3O4@SiO2-Schiff base-Cu(II)] complex was investigated using TGA and DSC analysis (Fig. 3). The weight loss observed below 200 °C is due to the removal of organic solvents and moisture that were adsorbed.37 Furthermore, a weight loss of approximately 23% was occurred at 200–470 °C, indicating the separation and breakdown of the Schiff base organic groups from the nanocomposite surface through pyrolysis. This process was characterized by a noticeable endothermic peak in the DSC analysis. The nanocomposite demonstrated stability up to around 200 °C, thanks to the inherent thermal stability of the Schiff base design. Consequently, it can be easily employed in organic reactions and high-temperature conditions.
The elemental composition of the [Fe3O4@SiO2-Schiff base-Cu(II)] complex was examined through EDAX analysis (Fig. 4). This analysis confirmed the presence of distinct peaks corresponding to the Fe, Si, and O elements, which is consistent with the TGA results indicating that over 60% of the sample consists of inorganic materials, including the Fe3O4 support and SiO2 shell surrounding its surface. Furthermore, the observation of peaks for C and N provides further confirmation of the synthesis of the Schiff base layer derived from the prepared ligand. Lastly, the presence of Cu in the sample confirms the successful bonding of electron-donor atoms to copper ions and the formation of the desired catalyst. The results clearly demonstrate the successful preparation of the designed composite using the post-synthetic modification method.
Furthermore, the EDS mapping images clearly illustrate the even distribution of the [Schiff base-Cu(II)] complex across the Fe3O4@SiO2 surface (Fig. 5). The significant percentages of Fe, O, and Si elements indicate their prominent presence in the composite material. On the other hand, the presence of carbon and nitrogen elements can be attributed to the successful incorporation of the Schiff base ligand, which shows a homogeneous distribution within the composite structure. The close alignment between the distribution patterns of copper and nitrogen reinforces the evidence of effective coordination between N atoms and copper ions within the catalyst. Collectively, the EDS mapping analysis provides comprehensive visual evidence of the uniform distribution and elemental composition of the [Fe3O4@SiO2-Schiff base-Cu(II)] complex.
The morphology of the [Fe3O4@SiO2-Schiff base-Cu(II)] complex was examined using scanning electron microscopy (SEM). The SEM analysis, as depicted in Fig. 6, clearly demonstrated the uniform spherical shape of the resulting nanocomposite, characterized by a rough surface texture. A notable observation was made when comparing these particles to the uncoated Fe3O4 counterparts, revealing a noticeable increase in size. This size increment strongly indicates the presence of SiO2 and [Schiff base-Cu(II)] shells that envelop the Fe3O4 particles. Remarkably, the SEM analysis revealed no significant agglomeration in the sample, signifying the successful distribution and stability of the nanocomposite.
The structure and size of the [Fe3O4@SiO2-Schiff base-Cu(II)] complex were analyzed using HR-TEM (Fig. 7). The particles exhibited a nearly spherical shape and demonstrated a high level of crystallinity. Their sizes ranged from 25 to 32 nm. They were surrounded by an amorphous layer, which contributed to their irregular shape. This shape suggested that the Fe3O4 nanoparticles were well-dispersed, likely due to their small size and interaction with the grafted layers. In certain areas, some aggregation was observed, possibly attributed to the magnetic property of nanoparticles. These results confirm the successful formation of the desired complex on the surface of the modified magnetic nanoparticles.
Through BET analysis, the [Fe3O4@SiO2-Schiff base-Cu(II)] complex was examined to determine its isotherm type, surface area and pore characteristics (Fig. 8). The measured values were 27.2 nm, 39.59 m2 g−1, and 0.041 cm3 g−1 for mean pore diameter, surface area, and total pore volume, respectively. The nanocomposite displayed a type IV isotherm and exhibited a mesoporous structure, evident from its average pore volume. Comparing these results with previous research, it can be inferred that the modification with [Schiff base-Cu(II)] complex led to a reduction in the BET characteristics of Fe3O4@SiO2. These surface characteristics of the [Fe3O4@SiO2-Schiff base-Cu(II)] complex provide ample reaction sites for direct interaction with organic reactants, resulting in an improved catalytic capacity.
The magnetic characteristics of the synthesized magnetic nanoparticles were evaluated using a vibration sample magnetometer (VSM). Fig. 9 provides a clear depiction of the saturation magnetization (Ms) values obtained for (a) Fe3O4, (b) Fe3O4@SiO2, (c) Fe3O4@SiO2-diamine, and (d) [Fe3O4@SiO2-Schiff base-Cu(II)] complex, which were determined as 74, 53, 33, and 24 emu g−1, respectively. The introduction of an amorphous SiO2 layer on the surface resulted in a notable decrease in the Ms value of Fe3O4 due to the non-magnetic nature silica. The difference in Ms values between Fe3O4@SiO2 and Fe3O4@SiO2-diamine indicated the bonding of a significant quantity of 3,4-diaminobenzoic acid groups to the surface of the Fe3O4 nanoparticles modified with silica. Moreover, the subsequent formation of organic functional groups (Schiff base) could diminish the surface moments of individual particles, leading to an overall reduction in magnetism. This decline in magnetic properties verifies the binding of iron nanoparticles to the [SiO2-Schiff base-Cu(II)] complex and validates its successful synthesis. Despite the lower Ms value of [Fe3O4@SiO2-Schiff base-Cu(II)] compared to pure Fe3O4, it remains adequate for effective magnetic separation, facilitating quicker removal from crude solutions.
Fig. 9 The VSM analyses of (a) Fe3O4, (b) Fe3O4@SiO2, (c) Fe3O4@SiO2-diamine and (d) [Fe3O4@SiO2-Schiff base-Cu(II)] complex. |
Entry | Catalyst | Catalyst amount (mg) | Solvent | Temperature (°C) | Time (min) | Yielda,b (%) |
---|---|---|---|---|---|---|
a Conditions: ethyl acetoacetate (1 mmol), hydrazine hydrate (1 mmol), benzaldehyde (1 mmol), malononitrile (1 mmol) and (1 mmol), catalyst (mg) and solvent (3 mL). b Isolated yield. | ||||||
1 | [Fe3O4@SiO2-Schiff base-Cu(II)] complex | 5 | EtOH | Reflux | 10 | 68 |
2 | [Fe3O4@SiO2-Schiff base-Cu(II)] complex | 5 | MeOH | Reflux | 10 | 65 |
3 | [Fe3O4@SiO2-Schiff base-Cu(II)] complex | 5 | Water | Reflux | 10 | 73 |
4 | [Fe3O4@SiO2-Schiff base-Cu(II)] complex | 5 | PEG-400 | 100 | 10 | 70 |
5 | [Fe3O4@SiO2-Schiff base-Cu(II)] complex | 5 | Solvent-free | 100 | 10 | 58 |
6 | [Fe3O4@SiO2-Schiff base-Cu(II)] complex | 7 | EtOH | Reflux | 10 | 81 |
7 | [Fe3O4@SiO2-Schiff base-Cu(II)] complex | 9 | EtOH | Reflux | 10 | 93 |
8 | [Fe3O4@SiO2-Schiff base-Cu(II)] complex | 12 | EtOH | Reflux | 10 | 98 |
9 | [Fe3O4@SiO2-Schiff base-Cu(II)] complex | 14 | EtOH | Reflux | 10 | 98 |
10 | [Fe3O4@SiO2-Schiff base-Cu(II)] complex | 12 | EtOH | Reflux | 30 | 98 |
11 | [Fe3O4@SiO2-Schiff base-Cu(II)] complex | 12 | EtOH | 45 | 10 | 47 |
12 | [Fe3O4@SiO2-Schiff base-Cu(II)] complex | 12 | EtOH | 25 | 10 | Trace |
13 | Catalyst free | — | EtOH | Reflux | 12 h | Trace |
14 | Fe3O4 | 12 | EtOH | Reflux | 60 | 25 |
15 | Fe3O4@SiO2 | 12 | EtOH | Reflux | 60 | 21 |
16 | Fe3O4@SiO2-diamine | 12 | EtOH | Reflux | 60 | 33 |
17 | Fe3O4@SiO2-Schiff base | 12 | EtOH | Reflux | 60 | 47 |
In next step, we explored the wide applicability and versatility of this method by utilizing the prescribed reaction conditions to examine a diverse range of aromatic and heteroaromatic aldehydes. This comprehensive set of aldehydes included various electron-donating and electron-withdrawing groups, such as halogens, nitro, methoxy, hydroxyl, and amino functionalities. The experimental results showcased exceptional yields of the desired pyrano[2,3-c]pyrazoles products, demonstrating the effectiveness of the approach (Table 2). Interestingly, we observed that the electron-withdrawing groups significantly influenced both the reaction rate and yield, leading to the most favorable outcomes. This finding suggests that electronic and hindrance effects play a decisive role in reaction progress. Additionally, we successfully transformed heterocyclic carbaldehydes into the target products, achieving impressive yields within remarkably short reaction times. This remarkable efficiency highlights the potential of this method for synthesizing pyrano[2,3-c]pyrazoles from a wide range of substrates, including those with complex and heterocyclic structures. Finally, an investigation into scaling up reactions was ultimately conducted using 15 mmol of benzaldehyde as the model substrate. This endeavor yielded the corresponding product in an excellent yield, effectively confirming the method's scalability and applicability.
Entry | Aldehyde | Product | Time (min) | Yielda,b (%) | Melting point (°C) | |
---|---|---|---|---|---|---|
Measured | Literature | |||||
a Isolated yield. b Conditions: ethyl acetoacetate (1 mmol), hydrazine hydrate (1 mmol) arylaldehyde (1 mmol), malononitrile (1 mmol), [Fe3O4@SiO2-Schiff base-Cu(II)] (12 mg) in water solvent (3 mL) at reflux conditions. | ||||||
1 | 10 | 98 | 243–245 | 243–-245 (ref. 38) | ||
2 | 12 | 98 | 234–236 | 234–236 (ref. 38) | ||
3 | 15 | 96 | 230–231 | 229–230 (ref. 39) | ||
4 | 20 | 94 | 238–240 | 237–240 (ref. 40) | ||
5 | 30 | 93 | 195–197 | 196–198 (ref. 40) | ||
6 | 15 | 97 | 181–183 | 180–182 (ref. 38) | ||
7 | 25 | 96 | 221–222 | 221–222 (ref. 41) | ||
8 | 20 | 95 | 207–209 | 207–209 (ref. 38) | ||
9 | 35 | 94 | 172–174 | 172–174 (ref. 42) | ||
10 | 30 | 91 | 209–211 | 209–211 (ref. 38) | ||
11 | 45 | 88 | 246–248 | 246–248 (ref. 43) | ||
12 | 55 | 90 | 235–237 | 235–237 (ref. 41) | ||
13 | 35 | 92 | 221–223 | 222–224 (ref. 38) | ||
14 | 70 | 87 | 209–211 | 209–211 (ref. 44) | ||
15 | 70 | 87 | 227–228 | 227–228 (ref. 41) | ||
16 | 20 | 87 | 182–184 | 182–183 (ref. 45) | ||
17 | 75 | 88 | 218–220 | 218–219 (ref. 41) | ||
18 | 10 | 99 | 250–251 | 250–251 (ref. 46) | ||
19 | 45 | 90 | 229–231 | 228–230 (ref. 47) | ||
20 | 75 | 89 | 214–215 | 215–216 (ref. 41) | ||
21 | 65 | 86 | 223–224 | 222–224 (ref. 47) |
Scheme 2 presents a proposed mechanism for [Fe3O4@SiO2-Schiff base-Cu(II)] complex catalyzed the synthesis of pyrano[2,3-c]pyrazoles.48 The initial step involves the Cu-catalyzed cyclocondensation of a beta-keto ester and hydrazine hydrate, resulting in the formation of a five-membered N-heterocycle referred to as a pyrazalone intermediate. This pyrazalone intermediate demonstrates the presence of two resonance structures (II, III). Concurrently, Cu also facilitates the Knoevenagel condensation of aryl malononitrile and aldehydes. Subsequently, the pyrazalone intermediate engages in a Michael reaction with the β-aryl-α-cyanoacrylate compound generated from the Knoevenagel condensation. Subsequent to this, a Thorpe–Ziegler type cyclization takes place, result in the production of the corresponding pyrano[2,3-c]pyrazoles heterocycles.
Scheme 2 Suggested reaction pathway for the synthesis of pyrano[2,3-c]pyrazoles facilitated by the catalytic properties of the [Fe3O4@SiO2-Schiff base-Cu(II)] complex. |
Entry | Catalyst | Time (min) | Yield (%) | Refa |
---|---|---|---|---|
a Isolated yield. | ||||
1 | Mg–Al hydrotalcite | 60 | 87 | 49 |
2 | ZnO NPs | 60 | 94 | 50 |
3 | Thiamine hydrochloride | 15 | 91 | 51 |
4 | ZnS NPs | 8 | 92 | 52 |
5 | RuIII@CMC/Fe3O4 | 30 | 93 | 39 |
6 | Fe3O4@SiO2/Si(OEt)(CH2)3NH/CC/EDA/Cu(OAc)2 | 6 | 86 | 53 |
7 | Fe3O4@SiO2/Si(OEt)(CH2)3@melamine@TC@Cu(OAc)2 | 7 | 92 | 54 |
8 | [Fe3O4@SiO2-Schiff base-Cu(II)] complex | 10 | 98 | This work |
Footnote |
† Electronic supplementary information (ESI) available. See DOI: https://doi.org/10.1039/d3na00906h |
This journal is © The Royal Society of Chemistry 2023 |