Pd@L-asparagine–EDTA–chitosan: a highly effective and reusable bio-based and biodegradable catalyst for the Heck cross-coupling reaction under mild conditions

Abstract

In this research, a novel supramolecular Pd(II) catalyst supported on chitosan grafted by L-asparagine and an EDTA linker, named Pd@ASP–EDTA–CS, was prepared for the first time. The structure of the obtained multifunctional Pd@ASP–EDTA–CS nanocomposite was appropriately characterized by various spectroscopic, microscopic, and analytical techniques, including FTIR, EDX, XRD, FESEM, TGA, DRS, and BET. The Pd@ASP–EDTA–CS nanomaterial was successfully employed, as a heterogeneous catalytic system, in the Heck cross-coupling reaction (HCR) to afford various valuable biologically-active cinnamic acid derivatives in good to excellent yields. Different aryl halides containing I, Br and even Cl were used in HCR with various acrylates for the synthesis of corresponding cinnamic acid ester derivatives. The catalyst shows a variety of advantages including high catalytic activity, excellent thermal stability, easy recovery by simple filtration, more than five cycles of reusability with no significant decrease in its efficacy, biodegradability, and excellent results in the HCR using low-loaded Pd on the support. In addition, no leaching of Pd into the reaction medium and the final products was observed.

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1. Introduction

Among different organic transformations, Heck cross-coupling reaction (HCR), also known as Mizoroki–Heck reaction,^1–5 has received significant interest in recent years due to its ability to form C–C bonds. Indeed, this reaction has emerged as an efficient replacement, working under extensively mild conditions, for the Grignard reagents and subsequent required organic transformations to construct C=C bonds. Green chemistry (GC) has significant effects on the improvement of human civilization.^6–9 For this reason, developing chemical reactions according to the GC metrics in terms of the use of well-dispersed heterogeneous, bio-based, and biodegradable catalytic systems is vital.^10–13 Therefore, they have had a impressive and critical role in chemical synthesis to make a revolution in synthetic organic chemistry. Due to the different applications of HCR in the organic synthesis and manufacturing of important products such as agrochemicals¹⁴ and active pharmaceutical ingredients (APIs),¹⁵ the progress to develop effective approaches for HCR especially in the pharmaceutical industry is fundamental.^16–20 Definitely, catalytic systems have played a key role in this reaction; consequently, the preparation of useful and applicable catalysts in this field is very important. Recently, various heterogeneous Pd catalysts have been used in the HCR and other cross-coupling reactions, which have shown more advantages compared to homogeneous counterparts such as precluding the addition of different ligands, no Pd leaching in the final products, easy recycling and separation of overpriced Pd from the reaction medium, and reasonable application in industrial sectors.^21–37 Subsequently, from the greenness, cost-effectiveness, and safety point of view, it is essential to develop simple and effective procedures for the HCR by means of heterogeneous Pd catalysts.^31,38–46

Heterogeneous metal catalysts are normally produced through the chelation of metal nanoparticles (NPs) on suitable solid supports and can simplify the separation and recovery of both catalysts and desired products from the reaction medium.^34,47–50 As a result, to design and produce an effective catalyst, the selection of an appropriate biopolymeric support, which has various merits including ecologically benign nature, the use of harmless metals, and reproducibility, is the focal point of GC in the 21st century.^51–54 In recent decades, natural polymers have received extensive consideration as outstanding supports for sustainable chemistry^{23,46,55–59} since they possess both free amine and OH functional groups simultaneously and are capable of reacting with both nucleophiles and electrophiles through ion pairs and hydrogen bonding.^53,60 Commonly, biopolymers have no destructive impact on the environment as they are biodegradable and obtained from renewable resources.^61–63 According to the industrial need for clean and green chemical procedures, the use of bio-based heterogeneous catalysts has been increased dramatically.^64–67 Recently, chitosan has been used in different catalytic systems, as a biodegradable and biocompatible natural polymer support,^23,68–76 as well as food and pharmaceutical products.⁷⁷ Indeed, ethylenediaminetetraacetic acid (EDTA) has been utilized as an ion exchange and chelating agent for several metal ions in many preceding publications.^78–80 However, this compound has a good capacity to act as a low-cost and nontoxic crosslinker for creating strong bonds with organic compounds having nucleophilic centers.^81–83 Recently, EDTA has been used as a linker to produce different organic or inorganic polymeric supports such as chitosan–EDTA–cellulose network,^84,85L-asparagine–EDTA–amide silica-coated MNPs, chitosan–EDTA,⁸⁶ and diamide–diacid-bridged PMO.⁸⁷

Moreover, asparagine is one of the 20 amino acids found in human cells and it is essential for maintaining balance in the central nervous system.⁴³L-Asparagine was the first isolated amino acid from plants about 220 years ago.⁸⁸ Its cubic structure was demonstrated as well in 1802.⁸⁹ The N : C ratio of 2 : 4 in asparagine made it a good source of nitrogen in living creatures.⁹⁰ Due to the presence of acidic and basic sites, abundance in nature, and cost-effectiveness, L-asparagine is a proper candidate, which acts as an available and biocompatible precursor for preparation of simple or complex bifunctional organocatalytic systems.^91,92 On the other hand, according to the literature survey, cinnamic acid (CA) and its derivatives are in the focus of attention of medicine, pharmaceuticals, perfumeries, and cosmetic industries.^93–99 Cinnamic acid derivatives (CADs) are naturally found in fruits, vegetables, and flowers, and CA is an important intermediate for the production of the famous shikimic acid, which is the essential precursor for the synthesis of (−)-oseltamivir (Tamiflu®, an antiviral drug).^100,101 Both acid and ester forms (methyl, ethyl, and benzyl) exist in different essential oils, resins, and balsams. Although there are natural sources for CADs, various chemical and biochemical approaches have been invented for their synthesis including the Perkin reaction,¹⁰² enzymatic method,¹⁰³ Knoevenagel condensation accelerated by MW irradiation¹⁰⁴ or promoted by tetraalkylammonium halides,¹⁰⁵ the use of phosphorous oxychloride,¹⁰⁶ or DDQ under ultrasonic conditions,¹⁰⁷ Claisen–Schmidt condensation, and HCR.¹⁰⁸ Among these procedures, green HCR catalyzed by biopolymeric-based catalysts has been performed recently.^61–63 Finally, based on the applicable experiences in our research group in terms of green catalysis and biopolymers, we decided to design novel bio-based catalysts for the HCR. In continuation of our interest to develop novel and more efficient supramolecular catalytic systems for different organic transformations,^87,109,110 we herein report the synthesis and characterization of a new Pd(II) supported on the biopolymeric chitosan support. The Pd@ASP–EDTA–CS catalyst was prepared by grafting of L-asparagine using the EDTA dianhydride (EDTADA) onto the chitosan backbone biopolymer, followed by chelation of Pd(II) (Scheme 1). The Pd@ASP–EDTA–CS nanocomposite was investigated to promote and improve HCR efficiently at a lower temperature and shorter reaction time to afford corresponding CADs in good to excellent yields.

Scheme 1 Schematic representation for the synthesis of Pd@ASP–EDTA–CS nanocatalyst (1).

2. Experimental

2.1. General information

EDTA (MW = 292.24 g mol⁻¹), and L-asparagine (MW = 132.12 g mol⁻¹) were purchased from Merck and used without further purification. Acrylic acid and the corresponding esters, aryl halides, and PdCl₂ were purchased from international chemical companies including Sigma-Aldrich and Sumchun. Chitosan (MW = 190–300 kDa, medium molecular weight, 75–85% deacetylation degree) was obtained from Across Company. Analytical TLC experiments were accomplished using Merck Kieselgel 60 F-254 Al-plates and then visualized by UV light and iodine vapor. An Electrothermal 9100 apparatus was used for measuring the melting points of the products. The functional groups of the samples were identified by FTIR spectroscopy (1720-X PerkinElmer) in the range of 600–4000 cm⁻¹ using KBr discs. The morphology of the Pd@ASP–EDTA–CS catalyst was examined by FESEM (KYKY EM8000) and TEM (Philips EM 208S) techniques, and the related elements of the catalyst were demonstrated by SEM mapping. For more consideration, the X-ray diffraction pattern and energy-dispersive X-ray spectroscopy of the catalyst were studied by XRD (Bruker D8, Germany) and EDX (Bruker, Germany) techniques, respectively. The TGA curves of the catalyst were recorded by a Bahr Company STA 504 instrument, while the Brunauer–Emmett–Teller (BET) test was performed by a Micromeritics ASAP 2020. The ¹H NMR spectra of the isolated products were recorded at 500 MHz using a Varian-INOVA spectrometer in DMSO-d₆ at ambient temperature (see ESI†).

2.2. General procedure for the preparation of EDTA dianhydride (EDTADA)

EDTA (10.0 g, 34 mmol), pyridine (16 mL) and acetic anhydride (14 mL) were added into a 100 mL round bottom flask equipped with a condenser and a magnetic stirrer. The reaction was mixed at 65–70 °C for 24 h under N₂ atmosphere. After the completion of the reaction, the resulting product was filtered and washed with acetic anhydride (5.0 mL) and dry diethyl ether (10 mL) to afford a white powder. The final product was dried by a rotary evaporator under vacuum at 40–50 °C until a fine and dry white powder was obtained (yield 90–92%, mp: 189–191 °C) (Scheme 1).^111,112

2.3. Preparation of L-asparagine–EDTA monoanhydride (ASP–MAEDTA)

The prepared EDTADA (0.256 g, 1 mmol) was added into a two-neck round-bottom flask equipped with a condenser and a magnetic stirrer. Then, 3 mL dry toluene was added under Ar atmosphere. After that, exactly one equivalent of L-asparagine (0.132 g, 1.0 mmol) was gradually added over 60 min to react with only one anhydride functioinal group of the EDTADA. Finally, the mixture was refluxed under continuous stirring for 18 h. The desired intermediate (I) was filtered and dried under vacuum at 60 °C to afford a creamy white powder (0.386 g, yield = 98.8%).^84,85

2.4. Preparation of the L-asparagine–ETDA grafted on chitosan

In a double-neck round-bottom flask containing dry toluene (10 mL), intermediate (I) (0.35 g) and chitosan (0.7 g) were added. Then, the mixture was stirred and heated at 60–70 °C under Ar atmosphere for 18 h. After the completion of reaction, the mixture was cooled down to r.t. and the suspension was filtered and dried under vacuum to afford 0.49 g of the desired intermediate (II) (Scheme 1).

2.5. Synthesis of the Pd@ASP–EDTA–CS catalyst (1)

PdCl₂ (24.5 mg) was added to the mixture of intermediate (II) (0.49 g) and EtOH (3.0 mL), and the suspension was refluxed for 18 h. After cooling of the mixture to ambient temperature, the prepared catalyst (I) was filtered and washed under vacuum with EtOH and then dried in an oven at 70 °C to afford the final catalyst (0.35 g) (Scheme 1).

2.6. General procedure for the synthesis of cinnamic acid derivatives in the HCR catalyzed by Pd@ASP–EDTA–CS catalyst (1)

A mixture of aryl halides (3a–e, 2.0 mmol), active alkenes (4a–d, 3.0 mmol), potassium carbonate (2.0 mmol) and catalyst 1 (4.0 mg) were added into a three-neck round-bottom flask containing a proper solvent, DMF or CH₃CN (3.0 mL), followed by heating and stirring for an appropriate time under Ar atmosphere, as designated in Table 2. After the completion of the reaction, as monitored by TLC [eluent n-hexane : EtOAc = 5 : 1], and cooling the reaction mixture to r.t., the catalyst 1 was filtered. Then, the solvent was recovered under reduced pressure, and a mixture of CHCl₃ (5 mL) and water (5 mL) was added to the reaction flask followed by stirring for 30 min. Next, the mixture was transferred to a decanter and settled for 0.5 h. The mixture was decanted to separate the undesired salts and materials. Afterward, the water content of the organic layer was removed by utilizing dry Na₂SO₄. After that, the organic phase was recycled under vacuum to afford the final products. Finally, the crude product was recrystallized from EtOH to obtain the pure corresponding product (see ESI†).

2.7. Spectral data of the selected products

2.7.1. Cinnamic acid (5a). White crystals, m.p. = 132–133 °C; FTIR (KBr, cm⁻¹) ν = 3450, 2928, 1694, 1670, 1562, 1441, 1096; ¹H NMR (500 MHz, DMSO-d₆) δ (ppm) = 12.40 (S, 1H), 7.59 (d, J = 16.0 Hz, 1H), 7.71–7.63 (m, 2H), 7.44–7.32 (m, 3H), 6.52 (d, J = 16.0 Hz, 1H).

3. Results and discussion

3.1. Characterization of Pd@ASP–EDTA–CS nanocatalyst (1)

The overall procedure for the synthesis of Pd@ASP–EDTA–CS catalyst (1) has been summarized in Scheme 1. The catalyst was characterized using different spectroscopic, microscopic and analytical techniques including Fourier transform infrared (FTIR) spectroscopy, energy-dispersive X-ray (EDX) spectroscopy, field emission scanning electron microscopy (FESEM), X-ray powder diffraction (XRD), thermogravimetric analysis (TGA), Brunauer–Emmett–Teller (BET) surface area analysis, and differential reflectance spectroscopy (DRS).

3.1.1. Fourier transform infrared (FTIR) analysis. FTIR spectroscopy was employed to determine the functional groups and structure of EDTADA (a), L-asparagine (b) chitosan (c), and the Pd@ASP–EDTA–CS catalyst (1). The results are illustrated in the overlay spectra in Fig. 1. In the FTIR spectra, the observed bands at 3400–3600 are attributed to the hydroxyl and amine groups, and the vibration double bands of the C=O groups in EDTA dianhydride stands at 1810 and 1760, respectively, which is displaced by amidic and acidic groups at 1675 cm⁻¹ and 1733 cm⁻¹, respectively. The sp³ C–H bands are shown at 2900–3000 cm⁻¹, and the absorbance bands at 1200–1400 cm⁻¹ are assigned to the bending of –NH groups. The C–O stretching bands are located at about 1100 cm⁻¹.

Fig. 1 FTIR spectra of the Pd@ASP–EDTA–CS catalyst (1).

3.1.2. Energy dispersive X-ray spectroscopy (EDX) analysis. Chemical composition and elemental analysis of the Pd@ASP–EDTA–CS (1) was carried out using energy-dispersive X-ray spectroscopy (EDX). The EDX spectrum of the catalyst is depicted in Fig. 2. In addition, the EDX analysis showed the well-defined peaks related to C, O, N, Cl, and Pd in the structure of Pd@ASP–EDTA–CS (1) with the percentages of 44.63, 36.64, 11.04, 3.23, and 4.46, respectively.

Fig. 2 EDS spectrum of the Pd@ASP–EDTA–CS nanocatalyst (1).

3.1.3. Field emmision scanning electron microscopy (FESEM) analysis. The morphology and texture of the Pd@ASP–EDTA–CS (1) were specified by FESEM analysis, and the related photographs are presented in Fig. 3. According to these FESEM photographs, the size and surface shape of the catalyst are well observed, which proves that the particles have special layered morphology, the mythological figure of the Persian legend of Rostam and Sohrab, which shows the black and white combat from the top view in the first image with defined pores and without agglomeration.

Fig. 3 FESEM images of the Pd@ASP–EDTA–CS nanocatalyst (1).

3.1.4. Differential reflectance spectroscopy (DRS) of the catalyst (1) and its components. By comparing the DRS of the catalyst (1) and its components, it can be implied that the structure of the catalyst consists of bands, which are found in the precursors (Fig. 4a). Through more investigation, by carrying out the Excel adjustments on the secondary axis for the catalyst, more obvious points of the combination are shown (Fig. 4b).

Fig. 4 (a) DRS of the Pd@ASP–EDTA–CS catalyst (1) and its components. (b) Intensified DRS of Pd@ASP–EDTA–CS catalyst (1).

3.1.5. X-ray diffraction (XRD) analysis of the catalyst (1). The XRD pattern of Pd@ASP–EDTA–CS (1) is shown in (Fig. 5). The observed peaks were compared with the standard reference patterns of EDTA (card no. JCPDS, 00-033-1672), chitosan (card no. JCPDS, 00-039-1834), L-asparagine (card no. JCPDS, 00-031-1542), and PdCl₂ (card no. JCPDS, 00-001-0228). The sharp peaks in the pattern demonstrate the presence of crystalline regions in the structure of catalyst 1 as well as the combination of several peaks after the grafting of L-asparagine onto the chitosan backbone by the EDTA linker and subsequent chelation of Pd(II).

Fig. 5 XRD pattern of the Pd@ASP–EDTA–CS catalyst (1).

3.1.6. Thermogravimetric analysis (TGA) and BET of the catalyst (1). The thermal stability of Pd@ASP–EDTA–CS nanocomposite (1) was investigated under air atmosphere in the temperature range of 50–1000 °C (Fig. 6a). The initial mass loss for the catalyst 1 are about 3 wt% (below 100 °C) and 40 wt% (at about 200–330 °C), which represent the removal of water or organic solvents and degradation of peripheral L-asparagine moieties, respectively. The catalyst (1) displays another stage for mass loss over the temperature range of TGA, and the total weight loss of the catalyst reaches about 85%, which clearly demonstrates the effect of organic units grafted onto the surface of chitosan chains. The stability of the catalyst is about 200 °C (Fig. 6b). After the first two steps, including the removal of water or organic solvents and the degradation of the L-asparagine moieties, the high weight loss (about 45%) at 330–650 °C can be attributed to the decomposition of the EDTA and chitosan moieties that remain in the catalyst structure. These results also indicate that EDTA and L-asparagine have been successfully grafted onto the chitosan polymeric surface. The effect of chelated Pd nanoparticles on the biopolymeric support caused an increase in the thermal stability of the catalyst in comparison to the pristine chitosan, as seen from the TGA results.¹¹³

Fig. 6 (a) TGA and (b) DTA curves of the Pd@ASP–EDTA–CS catalyst (1).

In addition, the porosity of the Pd@ASP–EDTA–CS catalyst (1) was examined through the physisorption of N₂ at 77 K. The illustrative curve of the catalyst displays a type III nitrogen gas sorption isotherm, which indicates that there are plentiful microspores in the supramolecular biopolymeric-based catalyst 1. The results demonstrated that the specific surface area of catalyst 1 is 9.1004 m² g⁻¹. The BJH adsorption cumulative volume of the pores between 17.000 Å and 3000.000 Å width was 0.011020 cm³ g⁻¹, the BJH adsorption average pore width (4V/A) was 73.681 Å, the BJH desorption average pore width (4V/A) was 95.458 Å, and the adsorption average pore width (4V/A by BET) was 18.4597 Å. The N₂ adsorption–desorption isotherm and BJH pore volume of the catalyst are shown in Fig. 7a and b.

Fig. 7 (a) The N₂ adsorption–desorption isotherm of the Pd@ASP–EDTA–CS catalyst (1) and (b) the pore width of the Pd@ASP–EDTA–CS catalyst (1).

3.2. Optimization of conditions in the HCR reaction using Pd@ASP–EDTA–CS catalyst (1)

In our preliminary experiments, the catalytic activity of the as-prepared catalyst 1 was evaluated in the synthesis of cinnamic acid derivatives (5) through the Heck cross-coupling reaction between different halobenzenes and various active alkenes. For this purpose, the reaction conditions were optimized using certain mixtures of iodobenzene (3a, 2.0 mmol), methyl acrylate (4b, 3.0 mmol), and K₂CO₃ (2.0 mmol) as the model reaction. In a systematic screening, the reaction conditions were investigated precisely by considering several crucial variables such as catalyst loading, reaction time, solvent, and reaction temperature, as given in Table 1. Primarily, in the absence of any catalyst, the progress of the model reaction even after a long reaction time at r.t. or under reflux conditions was not detected (entries 1, 2). On the other hand, no detectable yield for the model reaction in the presence of Pd@ASP–EDTA–CS catalyst (1) without using K₂CO₃ base was obsereved (entries 3, 4). A trace amount of the desired product, methyl cinnamate (5b), was obtained by simultaneous using of the catalyst 1 and K₂CO₃ under solvent-free conditions (entry 5). Interestingly, when the catalyst and base in proper solvents such as DMF and CH₃CN were used the best yeilds of the desired product were obtained (entries 6, 7). On the other hand, the model reaction in toluene afforded only a trace amount of the desired product (entry 8). The same result was acquired for H₂O (entry 9). Furthermore, the model reactions in the presence of EDTA, L-asparagine, EDTA–ASP, and the support (ASP–EDTA–CS) were separately investigated without using any Pd(II) species, but there were no yields of the desired product 5b (entries 10–15). While the catalyst amount used in these experiments was just 4.0 mg, other quantities less than 4.0 mg afforded lower reaction yields. Indeed, the utilized catalytic amount was dramatically lower than that of optimized conditions since the quantity of loaded PdCl₂ on the catalyst 1 was 4.46%. Therefore, the total employed Pd, as an expensive metal, based on the mass of aryl halides was about 0.1%.

Table 1 Optimization of the conditions for HCR in the model reaction of iodobenzene (3a) and methyl acrylate (4b) to afford methyl cinnamate (5b) under different conditions in the presence of Pd@ASP–EDTA–CS catalyst (1)^a

Entry	Catalyst	Base	Solvent	Temp. (°C)	Time (h)	Yield^b (%)
a Reaction conditions: aryl halide (3a, 2.0 mmol), alkene (4b, 3.0 mmol), K2CO3 (2.0 mmol), Pd@ASP–EDTA–CS (1, 4.0 mg), and solvent (3.0 mL) unless otherwise stated. b Isolated yield.
1	—	K2CO3	DMF	r.t	48	N.R
2	—	K2CO3	DMF	Reflux	48	N.R
3	Pd@ASP–ETDA–CS	—	DMF	Reflux	48	N.R
4	Pd@ASP–ETDA–CS	—	CH3CN	Reflux	48	N.R
5	Pd@ASP–ETDA–CS	—	Solvent-free	80	24	Trace
6	Pd@ASP–ETDA–CS	K2CO3	DMF	90	14–20	78–90
7	Pd@ASP–ETDA–CS	K2CO3	CH 3 CN	80	16–20	75–90
8	Pd@ASP–ETDA–CS	K2CO3	Toluene	105	36	Trace
9	Pd@ASP–ETDA–CS	K2CO3	H2O	105	36	Trace
10	ASP–ETDA	K2CO3	DMF	130	36	N.R
11	ASP–ETDA–CS	K2CO3	DMF	130	36	N.R
12	ASP–ETDA	K2CO3	CH3CN	80	36	N.R
13	ASP–ETDA–CS	K2CO3	CH3CN	80	36	N.R
14	L-Asparagine	K2CO3	DMF	130	36	N.R
15	EDTA	K2CO3	DMF	130	36	N.R

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According to the optimization experiments for the model reaction, the impact of various solvents and the amount of utilized catalyst on the yield of desired product 5b is illustrated in Fig. 8. The model reaction was investigated in different solvents such as CH₃CN, toluene, water, and DMF using catalyst (1) with different loadings (in mg). Based on the obtained results summarized in Table 1 and Fig. 8, the optimum reaction conditions were found to be 4.0 mg catalyst loading in DMF or CH₃CN solvents at 80–90 °C.

Fig. 8 Investigation of the optimized loading of the Pd@ASP–EDTA–CS catalyst (1) in different solvents for HCR to afford 5b.

After the abovementioned experimetns, the scope of the reaction was expanded using aryl halides having electron-withdrawing groups (EWG) under the optimized conditions. The results are summarized in Table 2. As expected, by using this novel heterogeneous catalytic system, the obtained yields for aryl halides containing EWG were poor (entries 4, 5, 9, 10, 14, 15, 19 and 20).

Table 2 Synthesis of different derivatives of cinnamic acid (5a–l) through HCR catalyzed by the Pd@ASP–EDTA–CS catalyst (1) under the optimized conditions^a

Entry	Ar–X	Alkene	Product	Time (h)	Temp. (°C)	Yield^b (%)	m.p. (°C)	m.p. (°C) (Lit.)
a Reaction conditions: aryl halide (3a–e, 2.0 mmol), alkene (4a–d, 3.0 mmol), K2CO3 (2.0 mmol), Pd@ASP–EDTA–CS (1, 4.0 mg), and solvent (3.0 mL). b Isolated yield.
1				14	80	85	131–132	133 (ref. 120)
2				20	80	75	131–132	133
3				40	80	20	—	133
4				48	80	Trace	—	212
5				48	80	Trace	—	224–226 (ref. 121)
6				17	80	90	33–35	34–38 (ref. 122)
7				19	80	80	33–35	34–38
8				36	80	20	33–35	34–38
9				48	80	Trace	—	34–38
10				48	80	Trace	—	34–38
11				14	80	85	Liquid	(6.5–7.5)^123
12				20	80	76	Liquid	6.5–7.5
13				36	80	20	Liquid	6.5–7.5
14				48	80	Trace	—	—
15				48	80	Trace	—	—
16				16	80	85	Liquid^99	B.P.: 271
17				20	80	80	Liquid	B.P.: 271
18				36	80	20	Liquid	B.P.: 271
19				48	80	Trace	—	—
20				48	80	Trace	—	—

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3.3. The proposed mechanism for the synthesis of cinnamic acid derivatives in the presence of catalyst 1

According to the XRD pattern, the oxidation state of palladium in the Pd@ASP–EDTA–CS catalyst (1) is (II). Moreover, the active catalytic sites in HCR generally contain Pd(0) species. Therefore, the reduction of Pd(II) in catalyst 1 to its activated form, Pd(0), occurs smoothly in DMF and CH₃CN as oxidizable solvents.^114–116 Hence, the oxidative addition of the Pd(0) species to aryl halide 3a–e affords intermediate (I), and then coordination insertion between intermediate (I) and alkene 4a–d gives intermediate (II). Afterward, the migratory insertion of hydrogen, followed by C–C bond rotation, generates intermediate (III), which produces the desired product 5a–l and intermediate (IV) through syn-β-hydride elimination. Finally, the activated form of the catalyst 1 is recovered by the reductive elimination of HI using K₂CO₃ base (Scheme 2).^117–119

Scheme 2 The proposed mechanism for the synthesis of cinnamic acid derivatives 5 using aryl halides and active alkenes in the presence of catalyst 1.

3.4. Reusability of the Pd@ASP–EDTA–CS catalyst (1)

One of the vital parameters in heterogeneous catalytic processes is the reusability of catalyst. For the evaluation of this parameter, the model reaction was examined using the recycled catalyst for five consecutive runs. At the end of each run, the utilized catalyst 1 was removed by a simple filtration, followed by washing with EtOH, drying at 70 °C, and reused in the next model reaction. The obtained results are summarized in Fig. 9. Considering the results of isolated yields for the model reaction, the catalytic activity of the catalyst after five runs shows a slight decrease, which exhibits the proper conservation of the catalytic activity after recycling.

Fig. 9 Reusability of the catalyst 1 in the model reaction to afford methyl cinnamate (5b).

3.5. Leaching test of Pd in the reaction medium (hot filtration test)

Finally, to check the leaching of Pd(0) species into the reaction medium, the model Heck reaction was heated, and the catalyst 1 was removed from the hot reaction mixture after 3 h by filtration. After that, the reaction continued without any catalyst. Although the reaction mixture was heated under the optimized conditions for about 36 h, the progress stopped at the previous level and the reaction did not proceed on increasing the reaction time either. These findings confirmed the heterogeneous nature of the catalyst 1 as there was no leaching of Pd or observing re-precipitation of the catalyst.

3.6. Comparison of the catalytic activity of the Pd@ASP–EDTA–CS catalyst (1) with other catalytic systems

In order to compare the efficacy of Pd@ASP–EDTA–CS catalyst (1) with other catalytic systems for the application in the HCR, several parameters including the catalyst loading as well as reaction conditions, required time, and yield of the desired product 5b were taken into consideration and the results are summarized in Table 3. It can be seen that Pd@ASP–EDTA–CS heterogeneous catalyst (1) shows higher efficiency than previously reported catalytic systems for the HCR.

Table 3 The comparison of the obtained results for the HCR using catalyst 1 and other catalytic systems

Entry	Catalyst	Reaction conditions	Catalyst amount	Time (h)	Yield (%)	Reference
1	Trifunctional N,N,O-terdentate amido/pyridyl carboxylate Pd(II) complexes	DMF/145 °C/base	0.01 mol%	20	3–92	124
2	Trifunctional N,N,O-terdentate amido/pyridyl carboxylate Pd(II) complexes	DMF/145 °C/Na2CO3	0.01 mol%	20	92	124
3	Pd(OAc)2	NMP/135 °C/NaOAc//UV-VIS	0.05 mol%	44	80	125
4	CMH–Pd(0)	DMF/120 °C/Et3N	50 mg	6	90	126
5	NHC–Pd/IL@SiO2	NMP/140 °C/NaOAc	0.01 mol%	24	94	127
6	Pd(quinoline-8-carboxylate)2	DMF/130 °C/K2CO3	0.01 mol%	30	39–94	128
7	OCMCS–Pd	DMF/140 °C/Et3N	0.02 mmol	12	89–98	129
8	Pd@ASP–EDTA–CS	DMF/90 °C/K2CO3	4.0 mg	16	90	This work
9	Pd@ASP–EDTA–CS	CH3CN/80 °C/K2CO3	4.0 mg	18	90	This work

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4. Conclusion

In summary, a novel and thermally stable green heterogeneous supramolecular catalytic system has been introduced using both chitosan and L-asparagine amino acid, as naturally-occurring resources, grafted by EDTA to produce a natural bio-based support for chelation of Pd(II) species onto the backbone of the modified chitosan with high dispersion. In covering the green metrics, the quantity of catalyst 1, compared to other HCRs, was very competitive and cost-effective. On the other hand, the complete recovery of organic solvents has lessened the related impact on the environment. The catalyst demonstrated a highly efficient, easy, and sustainable application in the HCR, and the final yields were good to excellent. The recovery of the catalyst was performed by easy filtration at the end of the reaction cycles, and the catalytic activity showed only a slight decrease after five consecutive reaction runs without the leaching of the Pd species in the reaction medium and also the final products. Hence, the abovementioned advantages of the catalyst make it a suitable candidate for the pharmaceutical and fine chemicals industrial sectors.

Author contributions

Mohammad Dohendou: methodology, investigation, writing – original draft & editing, formal analysis, data curation; Mohammad G. Dekamin: conceptualization, funding acquisition; supervision, project administration; resources; writing – review & editing, resources; Danial Namaki: methodology, investigation, data curation.

Conflicts of interest

There are no conflicts to declare.

Acknowledgements

We are grateful for the financial support from The Research Council of Iran University of Science and Technology (IUST), Tehran, Iran (Grant No. 160/22061). We would also like to acknowledge the support of the Iran Nanotechnology Initiative Council (INIC).

Notes and references

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Footnote

† Electronic supplementary information (ESI) available. See DOI: https://doi.org/10.1039/d3na00058c

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