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Abstract

Ball mill–assisted preparation of nano-bio Calcite (CaCO₃) based on avian shell and its application as a novel, biodegradable, and heterogeneous catalyst with high catalytic activity and reusability in the green and high efficient synthesis of pyrano[4,3-b]pyrans via a condensation reaction of different aromatic aldehydes, malononitrile, and 4-hydroxy-6-methyl-2H-pyran-2-one at 120°C under solvent-free conditions is reported. The reaction proceeds to completion within 5–30 min in 90–98% yield. The nanocatalyst was characterized by X-ray diffraction (XRD), Brunauer–Emmett–Teller (BET), scanning electron microscope (SEM), elemental analysis, and laser particle sizer.

Keywords

biocatalyst green chemistry ball mill–assisted preparation eggshell waste

Introduction

Multicomponent reactions (MCRs) have emerged as efficient and powerful tools in modern synthetic organic chemistry because the synthesis of complex organic molecules from simple and readily available substrates can be achieved in a very fast and efficient manner without the isolation of any intermediate.^1
–3 Therefore, developing new MCRs and improving known MCRs are popular areas of research in current organic chemistry.⁴ One such reaction is the synthesis of pyrans. It is known that many pyran derivatives exhibit a wide spectrum of pharmacological and biological applications such as fungicidal, insecticidal, acaricidal,⁵ antiviral,⁶ antileishmanial, and anticonvulsant activities.⁷ Moreover, they have been shown to exhibit important medicinal properties such as antimicrobial,⁸ antiviral,^9,10 antiproliferative,¹¹ antitumor,¹² and anticancer¹³ activities. In addition, functionalized pyran derivatives have been reported to show promising properties as anti-HIV, antituberculosis, anti-inflammatory, and antifungal agents.^14

–18 According to the best of our knowledge and despite their wide range of pharmacological and industrial applications, the synthesis of pyrano[4,3-b]pyrans has received little attention. Recently, this important class of pyran derivatives was synthesized via one-pot multicomponent condensation reaction of aryl aldehydes, malononitrile, and 4-hydroxy-6-methyl-2H-pyran-2-one in the presence of different reagents such as KF-Al₂O₃,¹⁹ [bmim]BF₄,¹³ piperidine,²⁰ and NH₄Oac.²¹ However, in spite of their potential utility, all of these methods suffer from one or more disadvantages, such as unsatisfactory yields, very prolonged reaction times, and use of organic solvents. In this regard and in continuation of our efforts to develop new, green chemistry methods,^22,23 we decided to explore green synthesis of 2-amino-7-methyl-5-oxo-4-phenyl-4,5-dihydropyrano[4,3-b]pyran-3-carbonitrile derivatives in the presence of nano-calcite (CaCO₃) based on eggshell waste as a novel and green nanocatalyst in solvent-free and thermal conditions.

Chicken eggshell is totally biodegradable, recyclable, and biocompatible with good osteoconductivity²⁴ and consists of more than 90% CaCO₃ that emerged as a novel bone substitute in its natural form.^25,26 For the first time, we report the ultrasonic-assisted preparation of nano-CaCO₃ based on eggshell waste and its application as a heterogeneous catalyst in green synthesis of 2-aminochromenes,²⁷ which in turn has a problem in its industrial use. Further, nanotextured surfaces are prepared using photolithography, plasma etching, micro-contact printing, ultrasonic irradiation, stencil-assisted patterning, and long polymer chemical etching processes that are cost-prohibitive or require special equipment.²⁸ Therefore, a simple, green, and cost-effective process is required to make nanotextured surfaces. In this regard, we decided to report a green, simple, and cheap approach to make nano-CaCO₃ based on chicken eggshell waste by using a convenient ball mill–assisted preparation. The second aim is to investigate its catalytic application in the green synthesis of pyrano[4,3-b]pyran (Scheme 1).

Scheme 1

Synthesis of 2-amino-7-methyl-5-oxo-4-phenyl-4,5-dihydropyrano[4,3-b]pyran-3-carbonitrile derivatives.

Results and Discussion

Characterization of Eggshell Nanocatalyst

Chemical Composition of Eggshell Powder

For the present study, we prepared nano-CaCO₃ by using the ball mill treatment on washed, cleaned, and dried eggshell for 4 h. The nanocatalyst was characterized by X-ray diffraction (XRD), elemental analysis, and field emission scanning electron microscope (FESEM). Elemental analysis of nanocatalyst shows a high level of Ca (39.22%), O (46.86%), and C (13%) with small amounts of Mg (0.62%), K (0.19%), Na (0.09%), and P (0.02%). Thus, the waste eggshell can be considered from a chemical viewpoint as a pure relatively natural carbonate-based material.

XRD Analysis

XRD pattern of the nano eggshell powder with 2θ = 29.4° are indicating that CaCO₃ is a major phase of the waste eggshell (Figure 1).²⁸ It was found that the nano eggshell generated the nanocrystalline CaCO₃ with a crystallite size less than 100 nm (Figure 1).

Figure 1.

XRD Pattern of nano-CaCO₃.

Scanning Electron Microscope (SEM)

FESEM images of raw eggshell and nano-CaCO₃ were compared in Figure 2. SEM images study showed an increase in porosity of nano-CaCO₃ due to the downsizing of the powder during ball mill treatment. The comparison of the mesoporous nature of the nanocatalyst to low porosity of untreated eggshell proves the essential effect of ball mill treatment on catalytic activity of biocatalyst in the reaction process (Table 1). This effect is due to the larger contact area because of many distributed pores and pits over the entire eggshell surface (Figure 2).

Figure 2.

SEM Images of (a) nano-CaCO₃ and (b) raw eggshell.

Table 1.

BET Surface Area (S _BET) and Average Particle Size of Eggshell Powder and Pure CaCO₃.

Entry	Sample	Milling Time	Surface Area^a (m² g⁻¹)	Average Particle Size^b (µm)	Time	Yield (%)
1	NESP	4 h	4.0351	3	10 min	94
2	Eggshell	2 h	0.3265	15	35 min	86
3	Eggshell	30 min	0.0236	35	1 h	65
4	CaCO₃	—	0.0145	49	2 h	30
5	CaCO₃	2 h	0.1633	27	2 h	55
6	CaCO₃	4 h	2.1531	19	2 h	76

^aDetermined by N₂ adsorption analysis.

^bDetermined by laser particle sizer.

Particle Size and BET Surface Area Analysis

In the following, we tried to explore the effect of average particle size and surface area of the prepared catalyst with different ball milling time on its catalytic activity during the reaction process. The BET surface area analysis showed a higher surface area of 4.0351 m² g⁻¹ with the average particle size of 3 µm for eggshell with ball milling time of 4 h. As shown in Table 1, the catalytic activity increases with the decrease in particle size, which in turn decreases the reaction time and increases the product yield of the reaction due to downsizing of the CaCO₃ crystals as a result of the increase in ball milling time. The highest yield (94%) and shortest reaction time (10 min) were achieved for nano-CaCO₃ with 4 h of the ball milling time. This proves the essential effect of ball mill treatment on the catalytic activity of eggshell powder as a mild and efficient catalyst in the reaction (Table 1).

Comparison of Catalytic Activity of Nanocatalyst and CaCO₃

In addition, a comparative reaction was carried on to show the excellence of nano-bio CaCO₃ than that of commercially available calcium carbonate treated in different ball milling time (Table 1, entries 4–6). As shown in Table 1, the catalytic activity of commercially available CaCO₃ was increased with ball milling time because of downsizing the powder in ball mill treatment. However, compared with CaCO₃ nanocatalyst, the reaction time was very long and the product yield was low. It is due to natural average porosity of eggshell product which increases with ball mill treatment. Since, the catalytic activity of the catalysts agreed well with the specific surface area and catalyst particle size, it is logical that mesoporous CaCO₃-derived avian shell with downsized crystals can catalyze the reaction more effectively than commercially available CaCO₃with larger particle size and low porosity.

Synthesis of Pyrano[4,3-b]pyran Derivatives

The green synthesis of pyrano[4,3-b]pyran derivatives was performed using the condensation reaction of 4-chlorobenzaldehydes (1 mmol), 4-hydroxy-6-methyl-2H-pyran-2-one (1 mmol), and malononitrile (1.2 mmol) in the presence of catalytic amount of nano eggshell powder (0.1 g) under solvent-free conditions. Without the addition of a catalyst, no pyrano[4,3-b]pyrans was formed even after 10 h under the reaction conditions.

Optimization of Reaction Conditions

To develop optimum conditions, the effect of temperature on the rate of the reaction was studied for the preparation of pyrano[4,3-b]pyrans. At 120°C, the reactions proceeded to completion very rapidly. A decrease in temperature leads to decreasing product yields and rate of the reaction. Next, the optimum amount of nanocatalyst was evaluated in the range of 0.02–0.2 g (Figure 3). The highest yield was obtained with 0.1 g of the catalyst. A further increase in the amount of catalyst up to 0.2 g did not have any significant effect on the product yield or the reaction time (Figure 3).

Figure 3.

Optimization of catalyst amount.

The generality of this reaction was examined using different aldehydes (Table 2). In all cases, the reactions gave the corresponding products in good to excellent yields (90–98%) and in very short reaction times (5–30 min). This method offers significant improvements with regard to the scope of the transformation, simplicity, and green aspects by avoiding expensive, hazardous, or corrosive catalysts (Table 2).

Table 2.

Nano-CaCO₃-Catalyzed Synthesis of 2-amino-7-methyl-5-oxo-4-phenyl-4H,5H-pyrano[4,3-b]pyran-3-carbonitrile Derivatives.

Entry	Ar	Time (min)	Yield (%)^a
1	C₆H₅	10	90
2	4-Cl-C₆H₄	10	94
3	3-NO₂-C₆H₄	10	95
4	2,4-Cl₂-C₆H₄	25	93
5	4-Br-C₆H₄	25	92
6	2-OH-C₆H₄	5	96
7	4-OH-C₆H₄	5	98
8	4-CH₃O-C₆H₄	10	94
9	3-Br-C₆H₄	30	93
10	4-(CH₃)₂N-C₆H₄	20	91

^aYield refers to isolated pure product.

The reusability of the catalyst was examined in the synthesis of pyrano[4,3-b]pyran derivatives. The catalyst was recovered after each run, washed three times with hot EtOH, dried in an oven at 120°C, and tested for its activity in subsequent runs. It was found that the catalyst could be reused four times without the loss of its catalytic activity.

Experimental

Materials and Instruments

All chemicals were of analytical grade, purchased from Merck, and used as received. Melting points were determined on a Gallenkamp melting point apparatus and are uncorrected. NMR spectra were recorded at 400.2 (¹H) and 100.64 (¹³C) MHz on Bruker DRX-400.2 Avance spectrometer at 400.2 and 125.77 MHz, respectively. IR spectra were obtained with MATSON 1000 FT-IR spectrophotometer. XRD with a D8 Bruker diffractometer (40 kV and 40 mA) and Cu_Kα radiation (λ = 0.154 nm) was used to analyze the crystal structure of the milled powders. The XRD patterns were recorded in the 2θ range of 20–80° with the step size of 0.01°. The mean size and size distribution of the eggshell powder were measured using a dynamic laser light scattering (DLS) apparatus (FRITSCH Analysette 22 NanoTec Laser Particle Sizer). The chemical composition of the catalyst was determined using X-ray fluorescence (XRF) Microanalyser (Unisantis XMF-104, Germany) with 40 kV, 300 mA, and Mo radiation. The morphology of the cross section of the film was examined with an FESEM after being fractured in liquid nitrogen. Dried samples were coated with gold ions using an ion coater at 150 s. Surface structure was visualized using an FESEM (Hitachi S4160) using a 15 kV accelerating voltage. The milling was carried out in a planetary ball mill using hardened chromium steel vial (250 mL) at room temperature under argon atmosphere. It was performed using hardened chromium steel vial (250 mL). The ball-to-powder weight ratio and the rotation speed of the vial were 10:1 and 350 rpm, respectively.

Catalyst Preparation

Empty chicken eggshells were collected from the household and washed with warm tap water. The adhering membrane was separated manually. Then the eggshells were washed with distilled water and dried at 120°C for 1 h and were milled in a planetary ball mill for 4 h. The resulting material was denominated as nano-CaCO₃.

General Procedure for the Synthesis of Pyrano[4,3-b]pyrans

A mixture of 4-chlorobenzaldehyde (0.14 g, 1 mmol), malononitrile (0.07 g, 1 mmol), and 4-hydroxy-6-methyl-2H-pyran-2-one (0.126 g, 1 mmol) in solvent-free condition at 120°C was stirred thoroughly in the presence of a catalytic amount of nano-CaCO₃ (0.1 g) to afford the corresponding pyrano[4,3-b]pyran in excellent yields. After completion of the reaction (TLC), hot EtOH (5 mL) was added to the reaction mixture and stirred for 5 min. Then the solid catalyst was filtered from the soluble products and washed with hot EtOH (5 mL). After cooling, the crude products were precipitated. Pure pyrano[4,3-b]pyrans were obtained in high yields without any more purification. All compounds were known in the literature^13,19
–21 and the NMR and IR spectra of the products were in agreement with earlier data.^13,19
–21

Spectra data of 2-amino-7-methyl-5-oxo-4-(4-chlorophenyl)-4H,5H-pyrano[4,3-b]pyran-3-carbonitrile (Table 2, entry 2): Pale yellow crystals, mp 227–229°C (lit. 10; 228–230°C); IR (KBr, cm⁻¹): 3383, 3324, 3195, 2201, 1710, 1674, 1645, 1597, 1488, 1445, 1414, 1384, 1261, 1141, 1092, 1015, 981, 854, 830, 807, 777, 511; ¹H NMR (400.2 MHz, dimethyl sulfoxide [DMSO], δ/ppm): 2.23 (s, 3H, CH₃), 4.33 (s, 1H, CH), 6.29 (s, 1H, =CH), 7.23 (d, 2H, J = 8.4 Hz, ArH), 7.26 (s, 2H, NH₂), 7.38 (d, 2H, J = 8.4 Hz, ArH); ¹³C NMR (100.64 MHz, DMSO, δ/ppm): 19.8, 36.2, 57.9, 98.4, 100.7, 119.6, 128.8, 129.9, 132.1, 143.0, 158.5, 158.7, 161.8, 163.6.

Conclusion

In summary, easy and rapid ball mill–assisted preparation of nano-CaCO₃-based eggshell waste has been explored. Also, a green, rapid, and highly efficient protocol for the one-pot synthesis of pyrano[4,3-b]pyran has been described under thermal solvent-free conditions using inexpensive and green bioactive catalyst. The nano-CaCO₃ was reused several times without any loss of its catalytic activity and reusability. This green catalyst is a natural, heterogeneous, and biocompatible nanocatalyst that can catalyze the organic transformation and reduce environmental problems. Thus, eggshell can be considered as a powerful green agent suited for the organic synthesis.

Footnotes

Acknowledgment

The support of the Graduate University of Advanced Technology and the Iran National Science Foundation (INSF) is gratefully acknowledged (project 91004279).

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The authors received financial support from the Iran National Science Foundation (INSF).

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Ball Mill–assisted Preparation of Nano-CaCO 3 as a Novel and Green Catalyst–based Eggshell Waste

Abstract

Keywords

Introduction

Results and Discussion

Characterization of Eggshell Nanocatalyst

Chemical Composition of Eggshell Powder

XRD Analysis

Scanning Electron Microscope (SEM)

Particle Size and BET Surface Area Analysis

Comparison of Catalytic Activity of Nanocatalyst and CaCO3

Synthesis of Pyrano[4,3-b]pyran Derivatives

Optimization of Reaction Conditions

Experimental

Materials and Instruments

Catalyst Preparation

General Procedure for the Synthesis of Pyrano[4,3-b]pyrans

Conclusion

Footnotes

Acknowledgment

Declaration of Conflicting Interests

Funding

References

Comparison of Catalytic Activity of Nanocatalyst and CaCO₃