Kranthi Kumar Gangu,
Suresh Maddila,
Surya Narayana Maddila and
Sreekantha B. Jonnalagadda*
School of Chemistry & Physics, University of KwaZulu-Natal, Westville Campus, Chiltern Hills, Durban-4000, South Africa. E-mail: jonnalagaddas@ukzn.ac.za; Fax: +27 31 2603091; Tel: +27 31 2607325
First published on 3rd January 2017
The co-precipitation method using a surface modifier, glutamic acid was employed in the design of iron doped calcium oxalates (Fe-CaOx). Fe-CaOx with diverse iron loading (0.5–3.0 mmol) were prepared and their phase purity and surface features were examined by X-ray powder diffraction (XRD), Fourier transform infrared (FT-IR), electron microscopy (SEM, TEM), energy dispersive X-ray (EDX), Inductively Coupled Plasma-Optical Emission Spectroscopy (ICP-OES), N2-sorption, thermal and fluorescent analysis. The Fe-CaOx materials proved excellent as catalysts in the one-pot syntheses of eight 2,4-dihydro pyrano[2,3-c]pyrazole derivatives via four component condensation of aromatic aldehydes, malononitrile, hydrazine hydrate and dimethyl acetylenedicarboxylate in ethanol with impressive yields (92–98%) in short reaction times (<20 min). The 2.0 mmol loaded iron in Fe-CaOx showed the finest catalytic performance with 98% yield in 10 min compared to other loadings. The stability, ease of separation, and reusability for up to six cycles of Fe-CaOx make it an environmentally friendly and cost-effective viable choice for the value-added organic transformations.
The ability to hold the adsorbed substances firmly and thereby activate the reactants is the advantageous characteristic of transition metals.16,17 The incorporation of transition metals into the solid support lattices is common practice to enhance their activity and to improve cost-effectiveness. Relative to other expensive choices, iron is the most possible candidate for doping due to its low cost, abundance, non-toxic and environmentally benign nature.18 The partial loading of iron in the place of Ca2+ in CaOx can give rise to material with improved activity. Besides the chemical composition, the physical features attained by the catalysts such as morphology, size etc. are known to play a key role in their activity.19–21 The controlled morphology and growth of crystals with ideal physical features is prime initiative to augment the catalytic activity. Literature survey reveals that many biological proteins, amino acids, surfactants, polymeric compounds have shown significant influence on crystal growth and morphology of several materials of interest under diverse synthetic conditions.22–25
Multi-component reaction (MCR), where all reactants (more than two) placed in one vessel and make the reaction conditions viable for developing bonds between the reactants to give a single product is an eco-compatible synthetic technique and which is replacing many traditional tardy processes. The MCR is a worthwhile approach for the preparation of varied organic scaffolds with introduction of diverse precursor elements.26–28 Heterocyclic systems are prevalent in nature and possess unique characteristics to design varied physiological and pharmacologically active substrates.29 Heterocyclic compounds are integral parts of the medicinal chemistry and have played a pragmatic role as precursor materials in the synthesis of drugs possessing antimalarial, antiulcer, diuretic, anthelmintic, antidepressants, anticancer, antineoplastic and antipsychotic activities.30–33 The wide range of physico-chemical and biological properties instilled in the heterocyclic compounds open new vistas in the scheming of novel pharmaceutical materials with impressive bioactivities. Among heterocycles, pyrazoles in general and pyranopyrazoles in particular possess salient pharmaceutical and biological characteristics with wide adoption in the field of medicinal chemistry, which necessitates competent procedures for their syntheses.34–38 Literature shows that Zonouz et al. have prepared the pyrano[2,3-c]pyrazole derivatives with different substituted aldehydes under reflux at 60 °C with 64–78% yields and reaction time of 2.5 h.39 Zou et al. have synthesized pyrano[2,3-c]pyrazoles moieties using ethyl acetoacetate in the place of dimethyl acetylenedicarboxylate reactant and reported products with 72–85% of yield in 2.5–5.0 h reaction time at 50 °C.40 Tamaddon and Alizadeh reported the synthesis of dihydropyrano[2,3-c]pyrazoles compounds, with combination of aryl aldehyde, malononitrile, ethyl acetoacetate and hydrazine hydrate in water at 50–60 °C by using cocamidopropyl betaine (CAPB), a zwitterionic biodegradable surfactant as catalyst with yields of 88–96%.41 Soleimani et al. have synthesized different pyranopyrazole derivatives at 70 °C by using nanostructured Fe3O4@SiO2 as catalyst with 83–94% yield in 20–40 min reaction time.42 In earlier work, we have reported the efficacy use of some heterogeneous catalysts and their activity in selective synthesis of heterocyclic compounds with excellent yields.43–46
In the present study, a series of novel Fe-CaOx materials were prepared by co-precipitation method using glutamic acid as crystal growth modifier. The efficacies of the materials as heterogeneous catalyst for the synthesis of pyranopyrazole moieties through four-component one-pot reaction were investigated. The effect of varied Fe doping, morphological and textural features on their activity was probed.
Fe-CaOx with four doping levels of iron was prepared by co-precipitation method. Initially, the stock solutions of precursors of 0.5 M of CaCl2, 0.2 M of Na2C2O4 and 0.5 M of Fe(NO3)3·9H2O were prepared. In a typical preparation, 5.0 mmol (10 mL of 0.5 M) of CaCl2 and 2.0 mmol (0.330 g) of glutamic acid were mixed with 50.0 mL water with continuous stirring. To that solution, 5.0 mmol (25 mL of 0.2 M) of Na2C2O4 was added slowly from burette and the resultant mixture was further stirred for 30 min. A solution containing requisite amount of iron precursor was added drop by drop to the mixture and stirring was continued for another 3 h. The reaction mixture was left overnight (12 h) to facilitate the crystallisation and the resultant crystalline material was harvested by centrifugation followed by several washings with millipore water. Repeating the exercise, total four materials namely, 0.5 mmol Fe-CaOx/glu (0.5 Fe-CaOx/glu), 1.0 mmol Fe-CaOx/glu (1.0 Fe-CaOx/glu), 2.0 mmol Fe-CaOx/glu (2.0 Fe-CaOx/glu) and 3.0 mmol Fe-CaOx/glu (3.0 Fe-CaOx/glu) were synthesised. The collected samples were calcined at 350 °C over 3 h under air flow. For comparison, un-doped CaOx in presence and absence of glutamic acid (glu) was prepared following the same procedure and designated as CaOx/glu and CaOx, respectively. The calculated chemical compositions of the samples and obtained yields are summarised in Table 1. The materials were further analysed to confirm their characteristics.
Sample | CaCl2 (mmol) | Na2C2O4 (mmol) | Fe(NO3)3·9H2O | Glutamic acid (mmol) | Yield (%) |
---|---|---|---|---|---|
CaOx | 5.0 | 5.0 | — | — | 79 |
CaOx/glu | 5.0 | 5.0 | — | 2.0 | 85 |
0.5 Fe-CaOx/glu | 5.0 | 5.0 | 0.5 mmol (1.0 mL of 0.5 M iron sol.) | 2.0 | 84 |
1.0 Fe-CaOx/glu | 5.0 | 5.0 | 1.0 mmol (2.0 mL of 0.5 M iron sol.) | 2.0 | 87 |
2.0 Fe-CaOx/glu | 5.0 | 5.0 | 2.0 mmol (4.0 mL of 0.5 M iron sol.) | 2.0 | 94 |
3.0 Fe-CaOx/glu | 5.0 | 5.0 | 3.0 mmol (6.0 mL of 0.5 M iron sol.) | 2.0 | 92 |
Fig. 1 XRD patterns (a) CaOx (b) CaOx/glu (c) 0.5 Fe-CaOx/glu (d) 1.0 Fe-CaOx/glu (e) 2.0 Fe-CaOx/glu (f) 3.0 Fe-CaOx/glu. |
The crystallinity was tested using X'Pert High score plus software after successive profile fit treatments, which indicates that the degree of crystallinity of the material decreases with increase in doping of Fe in CaOx. The control sample without the glutamic acid (Fig. 1a) recorded high degree of crystallinity (62 ± 4.2%), but when glutamic acid used (Fig. 1b), the crystallinity dropped to 51 ± 3.5% and the trend continued with increased Fe in the samples (Fig. 1c–f). The results show that introduction of glutamic acid as crystal growth modifier has worked well towards the control of nucleation. The crystallite size was determined by the Scherrer's formula using (020) reflection as reference and the resultant calculations showed that the crystallite size reduced in presence of glu to 32–38 ± 4 nm, relative to the control sample (CaOx) with crystallite size of 52 ± 2.6 nm. The XRD studies also reveal that the glutamic acid concentration inhibits crystal growth and influence morphological features, but not altering the thermodynamically stable COM phase.
FT-IR spectroscopic method was used to analyse the vibrational frequencies of COM phases. The presence of hydroxyl group, metal to oxygen bond and carboxylic group absorption bands confirm the COM phase formation (Fig. 2). Absence of any glutamic acid related peaks reveal that glu was involved in the crystal growth inhibition, and does not bind to the surfaces of COM crystals. The FT-IR spectra also reveal that added glutamic acid is suited to retain the more stable COM phase with crystal growth inhibition, but hampering the formation of less stable COD and COT phases.
Fig. 2 XRD patterns (a) CaOx (b) CaOx/glu (c) 0.5 Fe-CaOx/glu (d) 1.0 Fe-CaOx/glu (e) 2.0 Fe-CaOx/glu (f) 3.0 Fe-CaOx/glu. |
The hydroxyl absorption bands appeared at 3337 and 3433 cm−1 respectively correspond to symmetric and asymmetric O–H stretching vibrations, whereas 3254 and 3058 cm−1 correspond to stretching vibrations of O–H–O. The peaks at 1610 (asymmetric) and 1317 cm−1 (symmetric) stretching vibrations are from the carboxylic group. The peaks at 662 and 517 cm−1 are related to the bending (rocking) vibrational frequencies of the same group. The absorption peak at 781 cm−1 represents the existence of metal to oxygen bond.49,50
The materials with different concentrations of Fe, from 0.5 Fe-CaOx/glu to 3.0 Fe-CaOx/glu, (Fig. 4) exhibited identical morphology with no significant changes, but particles showed some differences in their shape. The TEM micrograph of 0.5 Fe-CaOx/glu (Fig. 5a) shows particles with needle-like ends, which changed to irregular sharped ends with 1.0 Fe-CaOx/glu (Fig. 5b). While the 2.0 Fe-CaOx/glu (Fig. 5c) exhibited hexagonal shaped particles with semi ellipsoid shapes and particle size 108–238 nm, the 3.0 Fe-CaOx/glu (Fig. 5d) showed an over dispersion of iron particles with their hexagonal shapes deteriorated and particle size remaining unaltered. With increase in iron content, the distortions in the shape of COM particles were noticed. The elemental analysis conducted using EDX and ICP-OES confirmed the presence of iron and its anticipated increment in wt% from sample 0.5 to 3.0 Fe-CaOx, authenticate the synthetic procedure employed (Fig. 5).
Fig. 4 SEM micrographs of (a) 0.5 Fe-CaOx/glu (b) 1.0 Fe-CaOx/glu (c) 2.0 Fe-CaOx/glu (d) 3.0 Fe-CaOx/glu. |
Fig. 5 TEM micrographs of (a) 0.5 Fe-CaOx/glu (b) 1.0 Fe-CaOx/glu (c) 2.0 Fe-CaOx/glu (d) 3.0 Fe-CaOx/glu; elemental analysis by EDX and ICP-OES. |
The textural properties of the materials were measured with N2 adsorption isotherm at 77 K. The observed isotherms are related to the type IV and the amount of probe N2 gas adsorbed varied with samples (Fig. 7). The BET-specific surface area was measured and the value increased from control to highest dopant loaded sample (Table 2). The CaOx (control) recorded low BET-surface of 9.93 m2 g−1, whereas high iron containing 3.0 Fe-CaOx/glu possessed high BET-surface area (93.22 m2 g−1). The pore volume also increased in the same trend as BET-surface area. As the dopant concentration increased, the number of additional adsorptive sites increase and thereby the surface area also improve. Pore size is in mesoporous range with high value for CaOx/glu sample and low for the 3.0 Fe-CaOx. The increased surface area and pore volume with dopant concentration divulges that the dopant replaces the calcium ions in its crystal lattice, but creates more pores of lesser size without blocking the existing pores.
Sample | BET-surface area (m2 g−1) | Pore volume (cm3 g−1) | Pore size (nm) | Average crystallite size (nm) from XRD |
---|---|---|---|---|
CaOx | 9.9 ± 1.2 | 0.03 ± 0.005 | 17.5 ± 1.14 | 52 ± 2.6 |
CaOx/glu | 13.5 ± 0.9 | 0.05 ± 0.003 | 19.3 ± 1.01 | 32 ± 3.1 |
0.5 Fe-CaOx/glu | 31.3 ± 1.8 | 0.09 ± 0.002 | 13.5 ± 1.94 | 36 ± 5.3 |
1.0 Fe-CaOx/glu | 46.3 ± 3.3 | 0.12 ± 0.003 | 12.3 ± 2.01 | 34 ± 2.8 |
2.0 Fe-CaOx/glu | 49.2 ± 2.0 | 0.13 ± 0.002 | 12.7 ± 1.05 | 33 ± 3.3 |
3.0 Fe-CaOx/glu | 93.2 ± 2.1 | 0.14 ± 0.001 | 6.9 ± 1.98 | 38 ± 4.2 |
Fig. 8 shows the fluorescent spectra of CaOx crystals with different iron doping. When samples were excited at 250 nm, the emission maximum was exhibited at 756 nm. The emission intensity diminished with increase in doping of iron. The decrease in fluorescence intensity is reveals that the Fe is substituted in some of the places of Ca2+ ions in crystal structure and this confirms the entry of iron into the lattice of CaOx. Relative to the un-doped CaOx, the doped iron decreases the fluorescence efficiency of the sample through ion–ion interactions and energy transfer processes. The doped iron in the crystal structure quenches the fluorescence intensity of CaOx crystals by weakening of the interactions between Ca2+ and oxalate ions.
Fig. 8 Fluorescent spectra of (a) un-doped CaOx (b) 1.0 Fe-CaOx/glu (c) 2.0 Fe-CaOx/glu (d) 3.0 Fe-CaOx/glu. |
Scheme 1 Typical reaction ((1) 3-fluoro benzaldehyde, (2) malanonitrile, (3) hydrazine hydrate, (4) dimethyl acetylenedicarboxylate). |
To establish the need of catalyst, the un-catalysed title reaction was conducted under similar reaction conditions. The reaction took 2.5 h to produce the final product with 60% yield. Initially, when NaOH, Na2CO3, pyridine, AcOH, or Al2O3 were employed as catalysts, no significant improvement was found either in the reaction time or yield (Table 3, entries 2–5). The addition of CaOx/glu reduced the reaction time, but produced the low yields (Table 3, entry 6). Thereafter, the reaction was examined with different Fe-CaOx/glu samples (0.5 Fe-CaOx/glu, 1.0 Fe-CaOx/glu, 2.0 Fe-CaOx/glu, 3.0 Fe-CaOx/glu) to compare their efficacy in getting better yields of pyrano[2,3-c]pyrazole in shorter reaction times. When 0.5 Fe-CaOx/glu was employed as catalyst, the reaction was finished in 15 min with yield of 89%, whereas 1.0 Fe-CaOx/glu gave 93% yield in 15 min. When 2.0 Fe-CaOx/glu was used as catalyst, the reaction was completed in 10 min and recorded 98% yield. Surprisingly, the use of 3.0 Fe-CaOx/glu resulted in lower yield (90%) and longer reaction time (20 min) (Table 3, entry 9). The higher amount of iron in 3.0 Fe-CaOx might have hindered the creation of active catalytic sites due over dispersion of iron on the surfaces of CaOx as evidenced from the TEM micrograph (Fig. 4d). The change in basic structural orientation of CaOx crystals under higher Fe conditions could be the likely the reason behind the poor catalytic performance of 3.0 Fe-CaOx/glu. The optimally Fe doped sample, (2.0 Fe-CaOx/glu) facilitated completing the reaction in excellent yields and shorter reaction time.
Entry | Catalyst | Reaction time (min) | Yield (%) |
---|---|---|---|
a Reaction conditions: 3-fluoro benzaldehyde (1.0 mmol), malononitrile (1.0 mmol), hydrazine hydrate (1.0 mmol), dimethyl acetylenedicarboxylic acid (1.0 mmol), catalyst (20 mg) and ethanol (5.0 mL) were refluxed at 50 °C. Isolated yields. | |||
1 | Without catalyst | 150 | 60 |
2 | NaOH | 110 | 63 |
3 | Na2CO3 | 110 | 68 |
4 | AcOH | 95 | 71 |
5 | Al2O3 | 80 | 70 |
6 | CaOx/glu | 50 | 79 |
7 | 0.5 Fe-CaOx/glu | 15 | 89 |
8 | 1.0 Fe-CaOx/glu | 15 | 93 |
9 | 2.0 Fe-CaOx/glu | 10 | 98 |
10 | 3.0 Fe-CaOx/glu | 20 | 90 |
After selecting the appropriate catalyst among the four, the requirement of amount of catalyst (2.0 Fe-CaOx/glu) to ease the organic reaction was investigated by varying it from 10 to 50 mg (Table S1†). A perusal of the results indicate that while amount <20 mg took longer time and lower yields, the increase in amount does not enhance the yield or reduce the reaction time. Further, to examine the efficacy of 2.0 Fe-CaOx/glu as catalyst, a series of reactions were conducted using five different substituted aldehydes under optimized conditions. All the reactions gave the respective pyrano[2,3-c]pyrazole moieties in good to excellent yields (91–98%) (Table 4).
Entry | Aldehyde | Product | Yield (%) | Time (min)/mp |
---|---|---|---|---|
a Reaction conditions: substituted benzaldehyde (1.0 mmol), malononitrile (1.0 mmol), hydrazine hydrate (1.0 mmol), dimethyl acetylenedicarboxylate (1.0 mmol) 2.0 Fe-CaOx/glu and ethanol (5.0 mL) were refluxed at 50 °C.b Isolated yields. | ||||
1 | 94 | 10/236–237 °C | ||
2 | 95 | 15/245–247 °C | ||
3 | 91 | 15/213–215 °C | ||
4 | 96 | 10/217–218 °C | ||
5 | 93 | 10/258–260 °C | ||
6 | 92 | 15/198–200 °C | ||
7 | 94 | 15/221–223 °C |
Based the experimental results and identified products, a plausible reaction mechanism is proposed in Scheme 2. The catalyst initiates the formation of benzylidine malononitrile intermediate (3) through the Knoevenagel condensation of aldehyde (1) and malononitrile (2), while hydrazine hydrate (4) combine with dimethyl acetylenedicarboxylate (5) to give pyrazolone intermediate (6). The Michael addition between (3) and (6) followed by cyclization on the catalyst surface produces the desired pyranopyrazole moiety selectively.
The reusability was investigated for 2.0 Fe-CaOx/glu with title reaction (Scheme 1) to estimate the feasibility to use the catalyst for the successive reactions. The filtered and separated catalyst was dried under vacuum for 1 h at 60 °C and tested for the recyclability. The catalytic performance was not altered in terms of reaction time and yields up to six cycles. After the sixth cycle, the depletion in the reaction time and product yields has been started.
Footnote |
† Electronic supplementary information (ESI) available. See DOI: 10.1039/c6ra25372e |
This journal is © The Royal Society of Chemistry 2017 |