- Email: [email protected]
Ultrasonic accelerated Knoevenagel condensation by magnetically recoverable MgFe2O4 nanocatalyst: A rapid and green synthesis of coumarins under solvent-free conditions
Accepted Manuscript Short communication Ultrasonic Accelerated Knoevenagel Condensation by Magnetically Recoverable MgFe Green Synthesis of Coumarins under Solvent-Free Conditions
2
O
4
Nanocatalyst: a Rapid and
Javad Safaei Ghomi, Zeinab Akbarzadeh PII: DOI: Reference:
S1350-4177(17)30286-9 http://dx.doi.org/10.1016/j.ultsonch.2017.06.022 ULTSON 3745
To appear in:
Ultrasonics Sonochemistry
Received Date: Revised Date: Accepted Date:
23 April 2017 24 June 2017 25 June 2017
Please cite this article as: J.S. Ghomi, Z. Akbarzadeh, Ultrasonic Accelerated Knoevenagel Condensation by Magnetically Recoverable MgFe 2 O 4
Nanocatalyst: a Rapid and Green Synthesis of Coumarins under Solvent-Free Conditions
10.1016/j.ultsonch.2017.06.022
, Ultrasonics Sonochemistry (2017), doi: http://dx.doi.org/
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Ultrasonic Accelerated Knoevenagel Condensation by Magnetically Recoverable MgFe2O4 Nanocatalyst: a Rapid and Green Synthesis of Coumarins under Solvent-Free Conditions
Javad Safaei Ghomi* and Zeinab Akbarzadeh Department of Organic Chemistry, Faculty of Chemistry, University of Kashan, Kashan, 51167, I. R. Iran Corresponding Author Tel.: +98 31 55912385; fax: +98 31 55552935;
*
E-mail:
[email protected]
Abstract The novel and green procedure to synthesis of 3-substituted coumarins was performed through the Knoevenagel condensation between various salicylaldehydes and 1,3- dicarbonyl compounds by MgFe2O4 nanoparticles as an efficient catalyst under solvent-free condition using ultrasound irradiation. The nano catalyst was easily recovered by an external magnet and reused for several times without significant loss of its catalytic performance. Compare to the previous works, this progressive protocol have advantages such as simple workup, high yields of coumarins, solvent free condition, environmentally benign and short reaction times.
Keywords: Coumarin, Knoevenagel, Ultrasonic, MgFe2O4 Nanoparticles, Solvent-free
1
Introduction At the recent years, many investigations have been focused on increasing the efficiency of organic catalytic synthesis because of their applicable importance. One of the progressive strategies which have recently attracted considerable attention is the usage of ultrasound condition with heterogeneous catalyst. The ultrasonic condition increases the rate of organic transformations at mild condition that otherwise need strict conditions of pressure and temperature [1-3]. Ultrasonic irradiation is frequently used to facilitate numerous synthetically reactions by way of the creation, growth and implosive collapse of bubbles in a liquid [4]. Bubble collapse initiated by cavitation creates high pressures, intense local heating and very short lifetimes. Cavitation serves as a means of concentrating the dispread energy of sound [5,6]. Compared to conventional heating which provides thermal energy in the macro system, ultrasound irradiation is able to activate many reactions by providing the activation energy in micro environment [7,8]. Moreover high yields of products, low reaction times, minimization of side products [9,10], nontoxic and environmentally friendly solvent [11,12], saving money and energy are other advantages of ultrasound irradiation. Magnetic nanoparticles are broadly applied in many fields such as catalysis in chemical synthesis, biomedicine, biotechnology, environmental remediation [13-16]. Magnetic nanocatalysts is easily separated from reaction blend using an external magnet which provides a facile separation of catalyst from reactants without filtration. Thus important advantages of these nanomaterials are easy recovery, reusability for several times and environmentally mild [17]. Coumarins represent biological and pharmacological activities such as antimicrobial, anticoagulant, antibacterial, fungicidal and pesticidal [18-22]. Also, coumarin and their derivatives constitute pharmacologically active products and structural components of 2
numerous natural compounds [23]. Coumarins are commonly prepared by methods containing Perkin [24], Pechmann [25], Reformatsky [26], Wittig [27] and Knoevenagel [28] reactions. The Knoevenagel condensation are generally catalyzed by bases [29] including pyridine, piperidine, sodium ethoxide and ammonia. Previously, a procedure for the synthesis of different coumarins via Knoevenagel condensation using P(RNCH2CH2)3N (R=Me, i-Pr) as a catalyst under solvent-free conditions had been reported by Kisanga et al [30]. Following, several groups have performed similar methods for the preparation of substituted coumarins using various catalysts [31]. For example in recent years metal oxides nanoparticles have been applied in Knoevenagel reaction to production of coumarins [32]. However, some of the reported methods tolerate some drawbacks such as long reaction times, harsh reaction conditions, use of toxic catalyst, difficulty in separation of catalyst from reaction mixture and non-reusable catalyst. Therefore, to avoid these limitations, the development of an eco-friendly and green procedure using efficient, easily available catalyst with high catalytic activity and short reaction times for the preparation of coumarins is still favored. The demand for environmentally benign method with heterogeneous and reusable catalyst, promoted us to promote a safe alternate way for the synthesis of coumarins. In the ongoing work, we used the ultrasonic irradiation and Magnetic nanoparticles to perform Knoevenagel condensation of o-hydroxy benzaldehyde and 1,3- dicarbonyl compound in more effective and convenient condition. A magnetically separable MgFe2O4 nanoparticles was synthesized and characterized and applied as an efficient catalyst in the solvent-free preparation of 3-substituted coumarins by the Knoevenagel condensation under ultrasonic irradiation. The advantages of this green approach are moderate reaction condition, simply remove of the nano MgFe2O4 by applying an external magnet, recoverability of the nano-catalyst and also light catalyst loading.
3
2. Experimental 2.1. Materials and Apparatus All required chemicals were prepared commercially from companies (Sigma-Aldrich and Merck). They were used without further purification. The ultrasonic irradiation was applied in reactions using a multiwave ultrasonic generator
(Sonicator
3200;
Bandelin,
MS
73,
Germany),
equipped
by
a
converter/transducer and titanium oscillator (horn), 12.5mm diameter, operating at 20 kHz with a maximum power output of 200 W. The ultrasonic generator automatically attuned the power level. Melting points of products were determined by Electro thermal 9200. All IR spectra were recorded by means of FT-IR Magna spectrometer 550 Nicolet using KBr plates. EIMS (70 eV) was performed by Finnigan-MAT-8430 mass spectrometer in m/z. NMR spectra were attained in DMSO-d 6 as solvent and are reported as parts per million (ppm) downfield from TMS as an internal standard. The NMR spectra were obtained on a Bruker Avance-400 MHz spectrometer. Brunauer Emmett Teller (BET) method for surface area measurement was determined by nitrogen adsorption measurement using an automated gas adsorption analyzer (Tristar 3000, Micromeritics). Powder XRD of MgFe2O4 nanoparticles was attained by a Philips diffractometer of X’pert Company. Microscopic morphology of the nanoparticles was visualized by SEM (MIRA 3 TESCAN). Energy-dispersive X-ray spectroscopy (EDX) of the nanoparticles imagined by a Sigma ZEISS, Oxford Instruments Field Emission.
2.2. Preparation of MgFe2O4 nanoparticles
4
In a typical synthesis, MgSO4, Fe(NO3)3·9H2O, NaCl and NaOH with the molar ratio 1:2:10:8 were mixed and poured in an agate mortar for 30 min. The reaction was begun during the mixing by releasing of heat. In continues, a mushy mixture was formed and its color was changed from colorless to light red (∼1 min) and finally brown (∼10 min). The reaction mixture was then placed in a quartz crucible, inserted into a quartz tube, annealed at 700 °C for 1 h, and subsequently cooled to room temperature. Samples were collected, washed several times with distilled water, and dried at 120 ºC overnight in a drying oven [33].
2.3. General procedure for the preparation of 3-substituted coumarins under Ultrasonic irradiation A mixture of o-hydroxy benzaldehyde (2 mmol), 1,3- dicarbonyl compound (3 mmol) and MgFe2O4 nano-powder (4 mol%) as catalyst was sonicated at 20 KHz frequency and 35 W power and 45°C, for desired times (monitored by TLC). After the completion of reaction, the mixture was cooled to room temperature. Afterward 5 mL ethanol was added to the mixture and MgFe2O4 nanoparticles was separated magnetically by an external magnet, washed with acetone to remove the residual product and dried for reuse. Finally the residue was recrystallized from ethanol to obtain the crude product. 3. Results and discussion 3.1. Structural analysis of MgFe2O4 nanocatalyst The XRD pattern of MgFe2O4 nanoparticles is depicted in Fig.1. This figure reveals high phase purity of the nanocatalyst and has perfect agreement with the reported XRD pattern for nano MgFe2O4 (JCPDS No. 71-1232). Average crystalline size of the MgFe2O4 nanoparticles was calculated to be 25-30 nm that was obtained from FWHM Scherrer’s formula. 5
By the scanning electron microscopy (SEM) image, morphology and particle size of MgFe2O4 nanoparticles is confirmed (Fig.2). As indicated in Fig.2 the size of particles diameters is in the range of nanometers. The average diameters of the nano MgFe2O4 is obtained about 25-30 nm by BET surface area 35-40 m2/g.
The elemental compositions of the MgFe2O4 nanoparticles were demonstrated by EDX. Energy Dispersive Spectroscopy (Fig.3) confirmed the presence of O, Fe and Mg in the nanocatalyst.
3.2. Synthesis of coumarins catalyzed by MgFe2O4 Coumarin derivatives has been prepared from the Knoevenagel condensation of salicylaldehydes and 1,3- dicarbonyl compounds catalyzed by nano MgFe2O4 at 45°C under ultrasound irradiation as drawn in Scheme 1.
The effect of experimental factors comprising type and amount of catalyst and solvent were investigated to find the best condition for this reaction and the results are listed in Table 1. The examination of solvent was demonstrated that solvent-free is the best condition for the Knoevenagel condensation of o-hydroxy benzaldehydes and 1,3- dicarbonyl compounds (Table 1, entry 6). Comparison of this entry with the entries 7-9 of Table 1 (various catalyst containing nano CuO, nano ZnO and nano MgO) reveals that the MgFe2O4 nanoparticles is the most efficient catalyst for the sonochemically synthesis of 3-substituted coumarins. The optimized quantity of MgFe2O4 nanocatalyst for this synthesis is 4 mol% (Table 1, entry 11).
6
In continues the Knovenogel reaction was carried out under different powers of ultrasound irradiation in order to detect the proper power of ultrasonic irradiation for this reaction as shown in Table 2. As can be seen this reaction is effectively proceed by 4 mol % of MgFe2O4 nanocatalyst with the power 35 W of ultrasonic irradiation. Essentially the main role of ultrasound irradiation is enhancement number of active cavitation bubbles and size of the individual bubbles. Both of which are expected to result in higher maximum collapse temperature and accelerated the synthesis of coumarin derivatives by knoevenagel reaction. Various substituted coumarins were prepared by nano MgFe2O4 using the obtained optimized condition. Comparison of heating and ultrasound methods demonstrates that ultrasonic approach is very effective for these synthesis as presented in Table3. As a result of this table, when the coumarin derivatives were synthesized under heating method, they were produced in lower yields at higher reaction times, but performing these reactions under sonication condition created excellent yields of coumarins at short times. Therefore, ultrasonic method is more environmentally benignly because of its basic green chemistry conception. These consequences can be attributed to the shock wave and microjet generated by the cavitation. During the ultrasonic irradiation, MgFe2O4 nanoparticles is dispersed in the reaction and provides more sites for the construction of cavity over its surface following the number of A reasonable mechanism for the preparation of coumarin derivatives by the nano MgFe2O4 is illustrated in Scheme 2. At first, a complex was formed between the O from the carbonyl group of salicylaldehyde and Mg from nanocatalyst. Afterward this complex react with active methylene provided by ethyl acetoacetate. Subsequently transesterification reaction is occurred in this intermediate and finally dehydration lead to creating 3-acetylcoumarin. These steps is efficiently carried out on the high nanoparticle surface and also by the cavitation effect of ultrasound irradiation. Based on this mechanism, it is highly probable that the carbonyl groups of salicylaldehydes and 1,3-dicarbonyl compounds have been activated, by coordination of carbonyl oxygen and MgFe2O4 nanoparticles. Thus the significant roles of MgFe2O4 nanocatalyst are activation of carbonyl groups and efficient development of the reaction on its high surface area.
2
O
4
Nanocatalyst: a Rapid and
Javad Safaei Ghomi, Zeinab Akbarzadeh PII: DOI: Reference:
S1350-4177(17)30286-9 http://dx.doi.org/10.1016/j.ultsonch.2017.06.022 ULTSON 3745
To appear in:
Ultrasonics Sonochemistry
Received Date: Revised Date: Accepted Date:
23 April 2017 24 June 2017 25 June 2017
Please cite this article as: J.S. Ghomi, Z. Akbarzadeh, Ultrasonic Accelerated Knoevenagel Condensation by Magnetically Recoverable MgFe 2 O 4
Nanocatalyst: a Rapid and Green Synthesis of Coumarins under Solvent-Free Conditions
10.1016/j.ultsonch.2017.06.022
, Ultrasonics Sonochemistry (2017), doi: http://dx.doi.org/
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Ultrasonic Accelerated Knoevenagel Condensation by Magnetically Recoverable MgFe2O4 Nanocatalyst: a Rapid and Green Synthesis of Coumarins under Solvent-Free Conditions
Javad Safaei Ghomi* and Zeinab Akbarzadeh Department of Organic Chemistry, Faculty of Chemistry, University of Kashan, Kashan, 51167, I. R. Iran Corresponding Author Tel.: +98 31 55912385; fax: +98 31 55552935;
*
E-mail:
[email protected]
Abstract The novel and green procedure to synthesis of 3-substituted coumarins was performed through the Knoevenagel condensation between various salicylaldehydes and 1,3- dicarbonyl compounds by MgFe2O4 nanoparticles as an efficient catalyst under solvent-free condition using ultrasound irradiation. The nano catalyst was easily recovered by an external magnet and reused for several times without significant loss of its catalytic performance. Compare to the previous works, this progressive protocol have advantages such as simple workup, high yields of coumarins, solvent free condition, environmentally benign and short reaction times.
Keywords: Coumarin, Knoevenagel, Ultrasonic, MgFe2O4 Nanoparticles, Solvent-free
1
Introduction At the recent years, many investigations have been focused on increasing the efficiency of organic catalytic synthesis because of their applicable importance. One of the progressive strategies which have recently attracted considerable attention is the usage of ultrasound condition with heterogeneous catalyst. The ultrasonic condition increases the rate of organic transformations at mild condition that otherwise need strict conditions of pressure and temperature [1-3]. Ultrasonic irradiation is frequently used to facilitate numerous synthetically reactions by way of the creation, growth and implosive collapse of bubbles in a liquid [4]. Bubble collapse initiated by cavitation creates high pressures, intense local heating and very short lifetimes. Cavitation serves as a means of concentrating the dispread energy of sound [5,6]. Compared to conventional heating which provides thermal energy in the macro system, ultrasound irradiation is able to activate many reactions by providing the activation energy in micro environment [7,8]. Moreover high yields of products, low reaction times, minimization of side products [9,10], nontoxic and environmentally friendly solvent [11,12], saving money and energy are other advantages of ultrasound irradiation. Magnetic nanoparticles are broadly applied in many fields such as catalysis in chemical synthesis, biomedicine, biotechnology, environmental remediation [13-16]. Magnetic nanocatalysts is easily separated from reaction blend using an external magnet which provides a facile separation of catalyst from reactants without filtration. Thus important advantages of these nanomaterials are easy recovery, reusability for several times and environmentally mild [17]. Coumarins represent biological and pharmacological activities such as antimicrobial, anticoagulant, antibacterial, fungicidal and pesticidal [18-22]. Also, coumarin and their derivatives constitute pharmacologically active products and structural components of 2
numerous natural compounds [23]. Coumarins are commonly prepared by methods containing Perkin [24], Pechmann [25], Reformatsky [26], Wittig [27] and Knoevenagel [28] reactions. The Knoevenagel condensation are generally catalyzed by bases [29] including pyridine, piperidine, sodium ethoxide and ammonia. Previously, a procedure for the synthesis of different coumarins via Knoevenagel condensation using P(RNCH2CH2)3N (R=Me, i-Pr) as a catalyst under solvent-free conditions had been reported by Kisanga et al [30]. Following, several groups have performed similar methods for the preparation of substituted coumarins using various catalysts [31]. For example in recent years metal oxides nanoparticles have been applied in Knoevenagel reaction to production of coumarins [32]. However, some of the reported methods tolerate some drawbacks such as long reaction times, harsh reaction conditions, use of toxic catalyst, difficulty in separation of catalyst from reaction mixture and non-reusable catalyst. Therefore, to avoid these limitations, the development of an eco-friendly and green procedure using efficient, easily available catalyst with high catalytic activity and short reaction times for the preparation of coumarins is still favored. The demand for environmentally benign method with heterogeneous and reusable catalyst, promoted us to promote a safe alternate way for the synthesis of coumarins. In the ongoing work, we used the ultrasonic irradiation and Magnetic nanoparticles to perform Knoevenagel condensation of o-hydroxy benzaldehyde and 1,3- dicarbonyl compound in more effective and convenient condition. A magnetically separable MgFe2O4 nanoparticles was synthesized and characterized and applied as an efficient catalyst in the solvent-free preparation of 3-substituted coumarins by the Knoevenagel condensation under ultrasonic irradiation. The advantages of this green approach are moderate reaction condition, simply remove of the nano MgFe2O4 by applying an external magnet, recoverability of the nano-catalyst and also light catalyst loading.
3
2. Experimental 2.1. Materials and Apparatus All required chemicals were prepared commercially from companies (Sigma-Aldrich and Merck). They were used without further purification. The ultrasonic irradiation was applied in reactions using a multiwave ultrasonic generator
(Sonicator
3200;
Bandelin,
MS
73,
Germany),
equipped
by
a
converter/transducer and titanium oscillator (horn), 12.5mm diameter, operating at 20 kHz with a maximum power output of 200 W. The ultrasonic generator automatically attuned the power level. Melting points of products were determined by Electro thermal 9200. All IR spectra were recorded by means of FT-IR Magna spectrometer 550 Nicolet using KBr plates. EIMS (70 eV) was performed by Finnigan-MAT-8430 mass spectrometer in m/z. NMR spectra were attained in DMSO-d 6 as solvent and are reported as parts per million (ppm) downfield from TMS as an internal standard. The NMR spectra were obtained on a Bruker Avance-400 MHz spectrometer. Brunauer Emmett Teller (BET) method for surface area measurement was determined by nitrogen adsorption measurement using an automated gas adsorption analyzer (Tristar 3000, Micromeritics). Powder XRD of MgFe2O4 nanoparticles was attained by a Philips diffractometer of X’pert Company. Microscopic morphology of the nanoparticles was visualized by SEM (MIRA 3 TESCAN). Energy-dispersive X-ray spectroscopy (EDX) of the nanoparticles imagined by a Sigma ZEISS, Oxford Instruments Field Emission.
2.2. Preparation of MgFe2O4 nanoparticles
4
In a typical synthesis, MgSO4, Fe(NO3)3·9H2O, NaCl and NaOH with the molar ratio 1:2:10:8 were mixed and poured in an agate mortar for 30 min. The reaction was begun during the mixing by releasing of heat. In continues, a mushy mixture was formed and its color was changed from colorless to light red (∼1 min) and finally brown (∼10 min). The reaction mixture was then placed in a quartz crucible, inserted into a quartz tube, annealed at 700 °C for 1 h, and subsequently cooled to room temperature. Samples were collected, washed several times with distilled water, and dried at 120 ºC overnight in a drying oven [33].
2.3. General procedure for the preparation of 3-substituted coumarins under Ultrasonic irradiation A mixture of o-hydroxy benzaldehyde (2 mmol), 1,3- dicarbonyl compound (3 mmol) and MgFe2O4 nano-powder (4 mol%) as catalyst was sonicated at 20 KHz frequency and 35 W power and 45°C, for desired times (monitored by TLC). After the completion of reaction, the mixture was cooled to room temperature. Afterward 5 mL ethanol was added to the mixture and MgFe2O4 nanoparticles was separated magnetically by an external magnet, washed with acetone to remove the residual product and dried for reuse. Finally the residue was recrystallized from ethanol to obtain the crude product. 3. Results and discussion 3.1. Structural analysis of MgFe2O4 nanocatalyst The XRD pattern of MgFe2O4 nanoparticles is depicted in Fig.1. This figure reveals high phase purity of the nanocatalyst and has perfect agreement with the reported XRD pattern for nano MgFe2O4 (JCPDS No. 71-1232). Average crystalline size of the MgFe2O4 nanoparticles was calculated to be 25-30 nm that was obtained from FWHM Scherrer’s formula. 5
By the scanning electron microscopy (SEM) image, morphology and particle size of MgFe2O4 nanoparticles is confirmed (Fig.2). As indicated in Fig.2 the size of particles diameters is in the range of nanometers. The average diameters of the nano MgFe2O4 is obtained about 25-30 nm by BET surface area 35-40 m2/g.
The elemental compositions of the MgFe2O4 nanoparticles were demonstrated by EDX. Energy Dispersive Spectroscopy (Fig.3) confirmed the presence of O, Fe and Mg in the nanocatalyst.
3.2. Synthesis of coumarins catalyzed by MgFe2O4 Coumarin derivatives has been prepared from the Knoevenagel condensation of salicylaldehydes and 1,3- dicarbonyl compounds catalyzed by nano MgFe2O4 at 45°C under ultrasound irradiation as drawn in Scheme 1.
The effect of experimental factors comprising type and amount of catalyst and solvent were investigated to find the best condition for this reaction and the results are listed in Table 1. The examination of solvent was demonstrated that solvent-free is the best condition for the Knoevenagel condensation of o-hydroxy benzaldehydes and 1,3- dicarbonyl compounds (Table 1, entry 6). Comparison of this entry with the entries 7-9 of Table 1 (various catalyst containing nano CuO, nano ZnO and nano MgO) reveals that the MgFe2O4 nanoparticles is the most efficient catalyst for the sonochemically synthesis of 3-substituted coumarins. The optimized quantity of MgFe2O4 nanocatalyst for this synthesis is 4 mol% (Table 1, entry 11).
6