Improvement of the catalytic performance of hybrid nanocomposite based on phosphate-benzimidazole in Knoevenagel condensation

Abstract

In this work, we have developed a simple and very effective experimental strategy for the reaction of Knoevenagel via the condensation of aromatic aldehydes substituted with active methylene compounds in the presence of hybrid nanocomposites xMCl₂-yNaPO₃ (MCl₂ = 2,2′-dibenzimidazolyl butane dichlorhydrates), under ecological conditions. The Phosphate-Benzimidazole hybrid nanocomposite as heterogeneous catalysts has demonstrated a high catalytic activity for the Knoevenagel condensation in ethanol as an ecological solvent. It has several advantages such as light reaction conditions, a simple and ecological working procedure. Meanwhile, xMCl₂-yNaPO₃ can be recovered by simple filtration and this catalytic system having an interesting lifetime (five cycles) with no decrease in activity.

Organic chemistry; Ecological conditions; MCl₂-NaPO₃, Hybrid Nanocomposites, Phosphate, Heterogeneous catalytic.

1. Introduction

Morocco has more than half of the world's phosphate reserves and it is mainly the world's leading exporter. Indeed, Moroccan phosphate is exported to all destinations: Europe, Latin America and Asia [1]. Recently, hybrid phosphate materials have received considerable attention [2]. In the broad sense, hybrids phosphate combine the different properties of phosphate with those of the organic compound such as polymers and organic salts. Nowadays, hybrid materials are increasingly used in many modern technologies and nanotechnologies such as photocatalysis [3], biomedical [4], corrosion inhibition [5], photovoltaics [6] and especially in catalysis [7]. The Knoevenagel condensation reaction between carbonyl compounds (aldehyde or ketones) and active methylene compounds that contain two electron-with drawing groups is very important organic reactions which have been frequently used for the production of fine chemicals and heterocyclic compounds of biological significance [8, 9]. It has been a subject of interest for the production of highly processed chemicals, such as coumarin derivatives [10, 11] fragrances [12] and UV filters in cosmetics [13]. Moreover, synthetic routes too many drugs and therapeutic substances involve production of a key intermediary via Knoevenagel condensation [14, 15, 16]. Furthermore, this reaction is used as a classic test reaction to examine the activity of new solid base catalysts. The protocol of the Knoevenagel condensation reaction of aldehyde with malononitrile was reported using different catalysts such as diamine-functionalized meso polymers [17], amine functionalized, mesoporous zirconia [18], Mg–Al mixed oxide on hexagonal mesoporous silica [19], biguanide-functionalized meso-porous silica [20], acid–base bifunctional mesoporous MCM-41 silica [21], amine-functionalized super paramagnetic nanoparticles [22], chitosan hydrogel [23], acrylic resin immobilized lipase [24], organic–inorganic hybrid silica materials containing imidazoliumand dihydroimidazolium salts [25], IRMOF-3 [26], ZIF-8 [27]. Al-KIT-6-NH₂ [28], Graphene oxide (GO) [29], Zeolitic imidazolate [30], graphene oxide with ethylenediamine [31], DCPD [32] and chitosan [33, 34, 35]. In this paper, the hybrid nanocomposite xMCl₂-yNaPO₃ were prepared with different molar ratios and studied as potential heterogeneous catalysts for the Knoevenagel condensation via the reaction of different aldehydes with active methylene in ethanol at room temperature.

2. Procedure

2.1. Used materials

All chemicals of catalytic reaction were purchased from Merck or Fluka Chemical Companies. The known products were identified by comparison of their melting points and spectral data with those reported in the literature. The thin-layer chromatography (TLC) using silica gel SIL G/UV 254 plates monitored progress of the reactions. Melting points were recorded on a KOFLER hot stage apparatus and are uncorrected. ¹H NMR and ¹³C NMR spectra were recorded on a Brucker 300-MHz spectrometer in DMSO-d₆.

2.2. The organic compound MCl₂

The 2,2′-dibenzimidazolyl butane dichlorhydrates (MCl₂) was synthesized and characterized according to procedure reported in many literatures [36]. This compound is used as an organic source for the synthesis of xMCl₂-yNaPO₃ hybrid nanocomposites.

The 2,2′-dibenzimidazolyl butane dichlorhydrates: Blue solid, Yield: 83 %, FT-IR (KBr pellet, cm⁻¹): 3330 (N-H), 3085 ((=C-H)Ar), 1628 (C=N), 1563 (N-H₂), 1512 (C=C), 1459 (CH₂/Met), 750 ((=C-H) Ar) cm⁻¹. Raman (cm⁻¹): 3080 (N-H), 2740 (NH₂⁺Cl⁻), 1629 (C=N), 1512 (C=C/Ar), 1450 (CH₂/Met), 750 ((=C-H)Ar) cm⁻¹. The ¹H NMR (300 MHz, D₂O, ppm): 1.9 (q,4H), 3.1 (t,3H), 7.43–7.56 (m,8H) ppm. The ¹³C NMR (100 MHz, D₂O, ppm): 25.56, 113.45, 125.98, 130.38, and 153.05 ppm. ESI-MS: [M + H]⁺, 291 g/mol, [M-H]⁺, 289 g/mol.

2.3. Development of xMCl₂-yNaPO₃ hybrid nanocomposites catalysts

The xMCl₂-yNaPO₃ hybrid nanocomposites were prepared by soft chemistry route under ambient conditions. The synthesis was done by ion exchange process between the benzimidazole derivative cations and the sodium metaphosphates anions. To study the morphological and structural properties of hybrid materials, five molar ratios have been synthesized, by changing the phosphate content (Table 1).

Table 1.

Synthesis of hybrid nanocomposites xMCl₂-yNaPO₃.

Samples	Variables
	(NaPO3)/(MCl2) molar ratios	NaPO3 (mol)	MCl2 (mol)	T (◦C)	t (min)
MCl2	-	0	0.01	25	5
NaPO3 + MCl2(R1)	1:1	0.01	0.01	25	6
NaPO3 + MCl2(R2)	2:1	0.02	0.01	25	6
NaPO3 + MCl2(R3)	3:1	0.03	0.01	25	6
NaPO3 + MCl2(R4)	4:1	0.04	0.01	25	6
NaPO3 + MCl2(R5)	5:1	0.05	0.01	25	6

The preparation of hybrid materials is realized by ion exchanges between MCl₂ cations and NaPO₃ anions. The molecular structure of xMCl₂-yNaPO₃ hybrid nanocomposites catalysts is given in Figure 1. The synthesized hybrid nanocomposites catalysts are characterized using various analyses such as: Fourier transform infrared (FTIR) (Figure S1-(a)) and Raman spectroscopy (Figure S1-(b)), the UV-visible spectroscopy (Figure S2), X-ray diffraction (XRD) (Figure S3), transmission electron microscope (TEM) and energy dispersive X-ray spectroscopy (EDX) (Figure S4), respectively [37]. According to the five molar ratios (R₁, R_2, R₃, R₄ and R₅) of the synthesized hybrid nanocomposites (xMCl₂-yNaPO₃), we have tested all these catalysts and we have chosen the best catalyst R₂ to study the optimal conditions for the Knoevenagel condensation. Then, we have generalized the optimal conditions for the other catalysts (R₁, R₃, R₄ and R₅).

Figure 1.

Molecular structure of xMCl₂-yNaPO₃ hybrid nanocomposites catalysts [37].

The characterization data for the hybrids catalysts have been given in the supplemental information (Figure S1 - S4).

2.4. Typical procedure for the Knoevenagel reaction

The carbonyl compound (1 mmol), active methylene (1 mmol), R₂ (1MCl₂-2NaPO₃) heterogeneous catalyst (6 mg) and ethanol (3 mL) were mixed. The reaction mixture was stirred at room temperature for appropriate time (Table 2). The completion of the reaction was monitored by thin-layer chromatography (TLC) using n-hexane–EtOAc (5:1) as eluent. Then, the reaction mixture was diluted with 5 mL of hot ethanol and the catalyst was separated by simple filtration and the filtrate was evaporated. The products (3a-j) obtained is recrystallized from ethanol. The products prepared 3 are known compounds [32, 38, 39, 40] and were confirmed by comparing the ¹H and ¹³C NMR data with authentic samples reported in the literature.

Table 2.

Optimization of the reaction conditions.^a

Entry	Catalyst	Amount (g)	Solvent (3 ml)	Time (min)	Yieldb (%)
1	–	–	EtOH	180	54
2	MCl2c	0.01	EtOH	–	–
3	R1 (1MCl2-1NaPO3)	0.01	EtOH	10	74
4	R2 (1MCl2-2NaPO3)	0.01	EtOH	4	90
5	R3 (1MCl2-3NaPO3)	0.01	EtOH	6	91
6	R4 (1MCl2-4NaPO3)	0.01	EtOH	6	91
7	R5 (1MCl2-5NaPO3)	0.01	EtOH	10	83
8	R2 (1MCl2-2NaPO3)	0.01	MeOH	3	90
9	R2 (1MCl2-2NaPO3)	0.01	CH3CN	15	70
10	R2 (1MCl2-2NaPO3)	0.01	THF	10	81
11	R2 (1MCl2-2NaPO3)	0.001	EtOH	10	77
12	R2 (1MCl2-2NaPO3)	0.002	EtOH	7	81
13	R2 (1MCl2-2NaPO3)	0.003	EtOH	7	83
14	R2 (1MCl2-2NaPO3)	0.004	EtOH	7	90
15	R2 (1MCl2-2NaPO3)	0.005	EtOH	5	92
16	R2 (1MCl2-2NaPO3)	0.006	EtOH	3	95
17	R2 (1MCl2-2NaPO3)	0.007	EtOH	3	93
18	R2 (1MCl2-2NaPO3)	0.008	EtOH	3	93
19	R2 (1MCl2-2NaPO3)	0.009	EtOH	3	91
20	R2 (1MCl2-2NaPO3)	0.01	EtOH	3	91

^aReaction conditions: p-chlorobenzaldehyde 1a (1 mmol), malonitrile 2a (1 mmol), catalyst, 3 ml solvent, at room temperature.

^bIsolated yield.

^cMCl₂ is soluble in solvent organic.

2.5. The spectral data of product (3a-j)

2-(4-chlorophenylmethylene) malononitrile (3a):

Colorless solid, mp 158–159 °C; ¹H NMR (Figure S5) (300 MHz, DMSO-d_6, δ, ppm) 7.67 (d, 2H, J = 8.7 Hz), 7.92 (d, 2H, J = 8.7 Hz), 8.49 (s, 1H, C=CH). ¹³C NMR (Figure S6) (75 MHz, DMSO-d_6, δ, ppm) 160.5, 139.5, 132.5, 131.6, 130.1, 114.4, 113.4, 82.7.

Methyl-3-(4-chlorophenyl)-2-cyanoacrylate (3b):

White solid, mp 120–121 °C; ¹H NMR (Figure S7) (300 MHz, DMSO-d_6, δ, ppm) 3.84 (t, 3H, OCH₃), 7.65 (d, 2H, J = 8.4 Hz, ArH), 8.04 (d, 2H, J = 8.4 Hz, ArH), 8.38 (s, 1H, C=CH). ¹³C NMR (Figure S8) (75 MHz, DMSO-d_6, δ, ppm) 162.5, 154.2, 138.5, 132.5, 130.6, 129.9, 115.8, 103.4, 53.8.

Ethyl-3-(4-chlorophenyl)-2-cyanoacrylate (3c):

Colorless solid, mp 89–90 °C; ¹H NMR (Figure S9) (300 MHz, DMSO-d_6, δ, ppm) 1.28 (t, 3H, J = 7.2 Hz, CH₃), 4.29 (q, 2H, J = 7.2 Hz, CH₂), 7.61 (d, 2H, J = 8.7 Hz, ArH), 8.00 (d, 2H, J = 8.7 Hz, ArH), 8.33 (s, 1H, C=CH). ¹³C NMR (Figure S10) (75 MHz, DMSO-d_6, δ, ppm) 162.0, 154.0, 138.5, 132.8, 130.5, 129.8, 115.7, 103.5, 62.9, 14.3.

2-(phenylmethylene) malononitrile (3d):

Colorless solid, mp 80–81 °C; ¹H NMR (Figure S11) (300 MHz, DMSO-d_6, δ, ppm) 7.57–7.70 (m, 3H, ArH), 7.59 (d, 2H, J = 7.2 Hz, ArH), 8.50 (s, 1H, C=CH). ¹³C NMR (Figure S12) (75 MHz, DMSO-d_6, δ, ppm) 155.7, 134.8, 131.7, 131.6, 130.9, 129.9, 114.6, 113.5, 82.0.

Methyl-2-cyano-3-phenylacrylate (3e):

White solid, mp 84–85 °C; ¹H NMR (Figure S13) (300 MHz, DMSO-d_6, δ, ppm) 3.84 (t, 3H, CH₃), 7.54–7.65 (m, 3H, ArH), 8.03 (d, 2H, J = 8.4 Hz, ArH), 8.38 (s, 1H, C=CH). ¹³C NMR (Figure S14) (75 MHz, DMSO-d_6, δ, ppm) 162.8, 155.6, 133.9, 131.7, 131.6, 129.8, 115.0, 102.8, 53.8.

2-(p-tolylmethylene) malononitrile (3f):

White solid, mp 118–119 °C; ¹H NMR (Figure S15) (300 MHz, DMSO-d_6, δ, ppm) 2.37 (s, 3H), 7.38 (d, J = 8.4 Hz, 2H), 7.82 (d, J = 8.4 Hz, 2H), 8.39 (s, 1H, C=CH). ¹³C NMR (Figure S16) (75 MHz, DMSO-d_6, δ, ppm) 161.6, 146.1, 131.1, 130.5, 129.1, 114.8, 113.8, 80.3, 21.5.

Ethyl-2-cyano-3-p-tolylacrylate (3g):

White solid, mp 91–92 °C; ¹H NMR (Figure S17) (300 MHz, DMSO-d_6, δ, ppm) 1.31 (t, J = 7.2 Hz, 3H), 2.37 (s, 3H), 4.34 (q, J = 7.4 Hz, 2H), 7.79 (d, J = 7.7 Hz, 2H), 7.90 (d, J = 7.2 Hz, 2H), 8.05 (s, 1H). ¹³C NMR (Figure S18) (75 MHz, DMSO-d_6, δ, ppm) 163.0, 155.5, 144.9, 131.4, 130.4, 129.1, 116.2, 101.2, 63.1, 14.3, 21.3.

2-(4-nitrophenylmethylene) malononitrile (3h):

Yellow solid, mp 161–162 °C; ¹H NMR (Figure S19) (300 MHz, DMSO-d_6, δ, ppm) 8.11 (d, J = 8.7 Hz, 2H), 8.29 (d, J = 8.7 Hz, 2H), 8.67 (s, 1H, C=CH). ¹³C NMR (Figure S20) (75 MHz, DMSO-d_6, δ, ppm) 159.7, 150.1, 137.1, 131.9, 124.8, 114.0, 112.9, 82.4.

Methyl-2-cyano-3-(4-nitrophenyl) acrylate (3i):

Yellow solid, mp 172–173 °C; ¹H NMR (Figure S21) (300 MHz, DMSO-d_6, δ, ppm) 3.88 (s, 3H, CH₃), 8.19 (d, 2H, J = 7.1 Hz, ArH), 8.34 (d, 2H, J = 7.1 Hz, ArH), 8.48 (s, 1H, C=CH). ¹³C NMR (Figure S22) (75 MHz, DMSO-d_6, δ, ppm) 162.1, 153.1, 149.8, 137.6, 132.1, 131.0, 124.4, 115.1, 107.0, 53.9.

Ethyl-2-cyano-3-(4-nitrophenyl) acrylate (3j):

Yellow solid, mp 168–169 °C; ¹H NMR (Figure S23) (300 MHz, DMSO-d_6, δ, ppm) 1.28 (t, 3H, J = 7.2 Hz, CH₃), 4.29 (q, 2H, J = 7.2 Hz, CH₂), 7.62 (d, 2H, J = 8.4 Hz, ArH), 8.02 (d, 2H, J = 8.4 Hz, ArH), 8.30 (s, 1H, C=CH). ¹³C NMR (Figure S24) (75 MHz, DMSO-d_6, δ, ppm) 162.0, 154.0, 138.4, 132.8, 130.6, 129.9, 115.8, 103.6, 62.9, 14.4.

All the ¹H NMR and ¹³C NMR spectra of the products (3a-j) have been listed in the supplemental information (Figure S5 - S24).

3. Results and discussion

3.1. Catalytic studies

To quantify the catalytic performance of the catalyst R₂ (1MCl₂-2NaPO₃), a model reaction between p-chlorobenzaldehyde 1a and malonitrile 2a was carried out in 3mL of ethanol at room temperature (Scheme 1). Initially, the model reaction was catalyzed by xMCl₂-yNaPO₃ nanocomposite hybrids catalysts with different molar ratios of phosphate: MCl₂, R₁, R₂, R₃, R₄ and R₅ (Table 1). The results are summarized in Table 2.

Scheme 1.

The condensation reaction between 4-chlorobenzaldehyde and malononitrile.

In the absence of catalyst, the reaction gave only 54 % yield of the product after 180 min (Table 2, entry 1). The best catalyst was R₂ (1MCl₂-2NaPO₃) because the product 2-(4-chlorobenzylidene) malononitrile 3a was obtained in 90 % yields within 4 min (Table 2, entry 4). So, the R₂ (1MCl₂-2NaPO₃) was selected as the catalyst for Knoevenagel condensation reaction and further studies were done using R₂ as a heterogeneous catalyst.

Secondly, the role of solvent in the reaction was examined with 0.01 g of catalyst R₂ (1MCl₂-2NaPO₃). The reaction proceeded quickly in ethanol, methanol and protic solvents (Table 2, entries 4 and 8). In an aprotic solvent like: THF and CH₃CN, the reaction gave an average conversion (Table 2, entries 9 and 10). Indeed, the Ethanol was selected as the best solvent for this reaction. To examine the effect of the catalyst amount, the reaction between p-chlorobenzaldehyde 1a and malonitrile 2a in the presence of the catalyst R₂ (1MCl₂-2NaPO₃) was considered. The study proceeded by conducting the reaction by varying the molar ratios of nanocomposite hybrids catalysts. The results of the study is given in Table 2 (entries 11–20).

According to the results, we optimized the amount of catalyst for the Knoevenagel reaction and it was selected as 0.006 g of R₂ (1MCl₂-2NaPO₃) with respect to the substrates (Table 2, entry 16). Finally, the catalytic activity of the catalyst can be generalized comprehensively, by conducting the Knoevenagel reaction with a diverse set of substrates (Scheme 2). All the products were characterized by ¹H and ¹³C NMR spectroscopy and melting point determinations. The details are listed in Table 3. From these results, we can recommend the R₂ (1MCl₂-2NaPO₃) as a good heterogeneous catalyst for Knoevenagel reaction and it gave goods to excellent conversion for all the sets of substrates under consideration at short reaction times (3–30 min).

Scheme 2.

The condensation reaction between aromatic aldehydes and ethylcyanoacetate or methyl cyanoacetate or malononitrile.

Table 3.

The Knoevenagel condensation reactions of various aromatic aldehydes and ethylcyanoacetate or methylcyanoacetate or malononitrile catalyzed by R₂ (1MCl₂-2NaPO₃).

Entry	Ar	X	Time (min)	Yielda %	M.p (°C)
					Found	Reported
3a	4-Cl	CN	3	95	158–159	159-160 [38]
3b	4-Cl	CO2Me	10	90	120–121	120-121 [32]
3c	4-Cl	CO2Et	10	91	89–90	89-90 [38]
3d	H	CN	20	89	80–81	80-81 [38]
3e	H	CO2Me	25	85	84–85	83.9–85.4 [40]
3f	4-Me	CN	10	93	118–119	118-120 [39]
3g	4-Me	CO2Et	30	90	91–92	90-91 [39]
3h	4-NO2	CN	3	98	161–162	160-161 [39]
3i	4-NO2	CO2Me	15	93	172–173	172-173 [32]
3j	4-NO2	CO2Et	25	96	168–169	168-169 [32]

^aIsolated yields.

To show the efficiency and capability of the present protocol of our catalyst with some reported catalysts for the Knoevenagel reactions, summarized results in Table 4, we observed that R₂ (1MCl₂-2NaPO₃) is an efficient catalyst with respect to the reaction time, a simple work-up protocol, the excellent yields of products and using green solvent.

Table 4.

Comparison of the catalytic efficiency of R₂ (1MCl₂-2NaPO₃) with that of reported catalysts in the Knoevenagel condensation.

Entry	Catalyst	Conditions	Yielda % (Refs.)
1	Fe3O4 MNPs-OSO3H	10 mg, 3 ml H2O, reflux, 10–145 min	80-97 [41]
2	Clay A, PC-A	100 mg, 3 ml EtOH/H2O, 40 °C, 5–120 min	21-98 [42]
3	[MML-PDO][OAc]	10 mol%, 1 ml H2O, r.t, 7–600 min	95-99 [43]
4	Na2Ca(HPO4)2	6 mg, 3 ml EtOH, r.t, 10–65 min	82-97 [44]
5	DCPD	10 mg, 3 ml EtOH, r.t, 10 min	84-96 [32]
6	R2 (1MCl2-2NaPO3)	6 mg, 3 ml EtOH, r.t, 3–30 min	85-98 (Present work)

^aIsolated yield.

3.2. Reusability studies of the catalyst

In addition, the reusability of the catalyst was also studied. Indeed, the catalyst can be removed from the reaction mixture by simple filtration. It was washed thoroughly and dried. The reuse of the R₂ (1MCl₂-2NaPO₃) as a heterogeneous catalyst for Knoevenagel reaction was studied by conducting the model reaction in the presence of recycled catalyst for five cycles. The results are given in Figure 2. It is clear that the recycled catalyst can be used for subsequent reactions without much loss of the catalytic activity. The catalyst has retained its form and characteristics after the completion of the reaction. Furthermore, it has all the advantages of solid phase catalysts as an operational simplicity, filterability, ability to regenerate and reuse. There was no considerable loss in the activity after recycling.

Figure 2.

Recycling of R₂ (1MCl₂-2NaPO₃) in the preparation of 3a.

3.3. Mechanism for the Knoevenagel condensation transformation

In this context, we will present a suggestion of Knoevenagel condensation mechanism by using a new heterogeneous catalyst R₂ (1MCl₂-2NaPO₃) in Scheme 3. The mechanism has already been planned [44]. First, a basic site removes a proton from the active methylene grouping of acidic nature, forming a carbanion. Then, a nucleophile attack occurs on the carbon atom of the carbonyl group of the aldehyde substituted that its oxygen is activated to give rise to an intermediate (I). Thus, turns into an alkene (3a-j) by dehydration.

Scheme 3.

Suggested transformation mechanism for the Knoevenagel condensation in the presence of R₂ (1MCl₂-2NaPO₃).

4. Conclusion

In summary, we have demonstrated that the MCl₂-NaPO₃ hybrid nanocomposite is a new heterogeneous catalyst, very efficient and reusable for the Knoevenagel condensation. It would be perfectly suited to green chemistry, sustainability and environmental security. This procedure has several advantages such as excellent yields with very short times and the catalyst can be recycled five times without any significant loss of its catalytic activity.

Declarations

Author contribution statement

Zakaria Benzekri: Conceived and designed the experiments; Performed the experiments; Wrote the paper.

Halima El aadad: Performed the experiments; Wrote the paper.

Sarra Sibous, Houda Serrar: Analyzed and interpreted the data.

Said Boukhris: Contributed reagents, materials, analysis tools or data; Wrote the paper.

Abdelkrim Chahine, Abdelaziz Souizi: Contributed reagents, materials, analysis tools or data.

Funding statement

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Competing interest statement

The authors declare no conflict of interest.

Additional information

No additional information is available for this paper.

Appendix A. Supplementary data

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