1 Introduction

In organic chemistry, one of the most important and useful conversion is the construction of the carbon-carbon bonds. In 1979, Miyaura, Yamada and Suzuki1 published a coupling reaction between boronic acid and an organo-halide catalyzed by a palladium complex. The importance of this coupling is obvious in different areas, from the synthesis of natural product to industrial material.2 Although there are many research groups that have introduced many systems for this synthesis by different catalysis in water, there are many drawbacks in their procedure such as evaluated temperature, the addition of tetra butyl ammonium bromide (TBAB) as phase transfer catalyst and complicated work-up procedure.3,4,5,6,7,8,9,10,11,–12 In general, activation of aryl chloride needs hard reaction conditions and high amount of palladium as a catalyst. The development of benign methods for the synthesis of the Suzuki-Miyaura reaction that use the small amount of catalyst is a subject of continuous interest for synthetic chemists.13,14,15,16,17,18,19,20,21,–22 Especially, for the catalyst which is precious and exhaustive as palladium. There are some reports that have introduced ligand-free Suzuki-Miyaura reactions catalyzed by simple palladium salts such as [Pd(OAc)2], [Pd(dba)2], and PdCl2. There are some drawbacks in their systems, for example, they are inappropriate for low-cost systems and in competition with the ligand assisted-systems, their selectivity is less.

For many years, phosphine-based ligands were the superior ligands for Suzuki-Miyaura reaction, because by changing the attached groups to the phosphorus atom, the properties in steric and electronic features were tuned. But, because of their environmental problems, high costs and sensitivity to air, chemists were encouraged to think about other ligands such as nitrogen-containing ligands, that in contrast to phosphines, have many advantages. In modern inorganic chemistry, Schiff bases are a class of organic-inorganic compounds that are synthesized by the condensation of the carbonyl compound with amino compounds and are used as ligands due to their versatility.23,24,25,26,27,–28 Among many potential organic ligands, Schiff bases are widely employed as ligands in coordination chemistry, in addition, their functionalities are tuned depending on the nature of starting materials. Recently, many researchers recognized the Schiff base ligands as excellent alternatives to phosphines in Suzuki-Miyaura reactions.29,30,–31 In this research, it is described the synthesis and characterization of two different ionic Schiff base ligands: imidazolium and sulfonium salophen type Schiff base ligands as cationic and anionic Schiff base ligands, respectively, (Scheme 1). In addition, the effect of ligands in ligand assisted PdCl2 catalyst in Suzuki-Miyaura reaction is investigated.

Scheme 1
scheme 1

Synthetic procedures of cationic L1 and anionic L2 Schiff base ligands.

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2 Experimental

2.1 Materials and methods

Reagents and starting material were purchased from Merck. 5-Chloromethyl salicylaldehyde and sodium 5-sulfonatosalicylaldehydes were prepared by a method described in refs 33 and 32, respectively. All solvents were used without purification. Infrared (IR) spectra were recorded in the range 400–4000 cm−1 with a Perkin Elmer FT-IR spectrophotometer using KBr pellets. UV–visible spectra were recorded with a PerkinElmer Lambda 25 spectrometer. C, H and N determinations were achieved on a Heraeus CHN-O rapid analyzer, NMR spectra were recorded with a Bruker Avance II-400 and Mass spectra was recorded by 5975C VL MSD with Tripe-Axis Detector spectrometer.

2.2 Synthesis of sodium sulfoniumsalophen Schiff base ligand

In a round bottom flask containing 20 mL of methanol, (0.5 g, 1 mmol) of phenylendiamine and (2.07 g, 2 mmol) of sodium 5-sulfonatosalicylaldehyde was added and then the content was refluxed for 3 h. Then the solvent was evaporated and the yellow-orange product was obtained and dried in air. Anal. Calcd. for C20H14S2O8N2Na2: C, 46.15; H, 2.69; S, 12.30, N, 5.38%. Found: C, 45.60; H,3.07; S,11.50; N,4.97. 1H NMR (δ, ppm, DMSO-d6) 8.42 (s, 2H, OH), 6.86–7.94 (m, 10H, Ar–H), 5.31 (s, 2H, N=CH). ESI-MS: m/z calc. for (520), found 522.

2.3 Synthesis of imidazolium salophen chloride Schiff base

a) Preparation of methyl-imidazoliume-salicylaldehyde chloride: In a round bottom flask, 5-chloromethyl salicylaldehyde (0.907 g, 0.0074 mol) and 1-methyl-imidazole (0.61 g, 0.0074 mol) were stirred in 25 mL of acetonitrile for 3 h at room temperature. After filtration, the product was dried under vacuum. M.p.: 64 °C, Anal. Calcd. for C12H13O2N2Cl: C, 57.02; H, 5.18; N,11.08% Found: C, 55.92; H, 4.89; N, 10.92. 1HNMR (δ, ppm, MeOD): (8.47, 1H, CHO), (7.50, 1H, CH), (6.25, 6.07, 6.03, 3H, aromatic), (5.40, CH2, methylene), (5.38, 5.33, 2H, ethylene), (3.37, CH3, methyl).

b) Synthesis of the imidazoliumsalophen chloride Schiff base ligand: In a round bottom flask, methyl-imidazole-salicylaldehyde (1.5 g, 0.0059 mol) and phenylendiamine (0.178 g, 0.0029 mol) were refluxed in methanol for 3 h. Then the solvent was removed under reduced pressure. The product was purified by diethyl ether and n-hexane. Anal. Calcd. for C30H30Cl2N6O2: C,62; H, 5.23; N,14.54%, Found: C,59.90; H,4.93; N,13.90. 1H NMR (δ, ppm, DMSO-d6): 9.45 (s, 2H, OH), 6.81–7.72 (m, 16H, aromatic), 5.43 (s, 4H, methylene), 5.16 (s, 2H, ethylene), 3.89 (s, 6H). ESI-MS: m/z calcd. for (577), found 577.6.

2.4 General protocol for Suzuki-Miyaura reaction

A mixture of phenylboronic acid (1 mol, 0.12 g), 4-bromotoluene (1 mol, 0.17 g), PdCl2 (0.5 mol%) and ligand (5 mol%) and K2CO3 (2 mol%) was refluxed in 20 mL of MeOH for 2 h. Then the reaction was diluted with distilled water (20 mL) and extracted with diethyl ether (3×20 mL). The organic phase was separated and evaporated. The product was purified by column chromatography, authenticated by 1H-NMR and by comparison of their melting point with those reported in the literature.

2.5 Catalytic reaction

The water-soluble ligands L1 and ligand L2 were synthesized as described previously. Then their effect was investigated in the catalytic Suzuki-Miyaura condensation reaction in the presence of PdCl2. In order to optimize the reaction conditions, the phenylboronic acid and 4-bromotoluene was chosen as a model substrate and different reaction conditions such as temperature, solvent, and mol% of PdCl2 in assistance of ligands L1 and ligand L2 were investigated. For determination of the efficient solvent, the effect of different organic solvents was investigated in the Suzuki-Miyaura reaction (Scheme 2) and the data was shown that the methanol was efficient solvent. The effect of temperature was considered and optimized on 65 °C. The amount of 5 mol% of ligand L2 is employed in the presence of the minimum amount of PdCl2. The results showed that in the absence of the ligand the yield of the reaction decreased significantly.

Scheme 2
scheme 2

Suzuki-Miyaura reaction.

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2.5.1 Effect of the mol% of Palladium chloride on the reaction

In order to gauge the performance of our ligand system, we decided to employ the minimum amount of palladium chloride in the presence of ligands system. Three mol% of palladium chloride were employed and the results were showed that by using the 0.5 mol% of palladium chloride, high yield was achieved (Table 1). The Suzuki–Miyaura coupling of aryl halides has been reported by many research groups that employed different mol% of Pd-catalyzed systems from the minimum amount of 0.1 mol% to a large amount of Pd complexes. For example, Buchwald and co-workers had reported high quantities of catalyst (2–3 mol%).34 Rao, Gyandshwar Kumar and co-workers proposed 2 mol% of Pd-catalyst for this coupling.35 Pankaj Nehra and co-workers used the ionic Schiff base complexes in Suzuki–Miyaura coupling, by using 0.1% mol catalyst in the presence of K2CO3 in coupling of I, Br aryls with the yields 70–89%.36 Whaghmode and Borhade investigated the Pd-Salen complexes as catalysts in Suzuki reaction of aryl iodides and aryl bromides in 1:1 DMF: water ratio, Na2CO3 as base 0.5 mol% Pd-Salen complex at 90 °C.37, 38 They found that the Suzuki reaction of aryl iodides and bromides give excellent yields (37–100%) of products in short reaction times (10–60 min). Anindita Dewan and co-workers introduced some catalytic system based on Pd complex of tetradentate Schiff base ligands that efficiently converts the aryl bromides up to 95%.39 Some other research work have been provided in the reference section in which they used Schiff base Pd- complexes to convert aryl iodides or aryl bromides with moderate to high yields.40,41,–42 In comparison to these reports, the efficiency of our system is appreciable and this system showed medium to high efficiency with respect to catalyst amount usage and reaction conditions.

Table 1 Suzuki-Miyaura condensation of phenylboronic acid and 4-bromotoluene in methanol, at reflux conditions by using 5 mol% of ligand L2.
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2.5.2 Effect of solvent

Despite the fact that literature presented a protocol for the Suzuki-Miyaura reaction in different media, the preparation of the ligand as pre-catalyst for complexation with Palladium is not a simple and benign reaction.43,44,–45 The effect of different solvents such as methanol, ethanol, acetonitrile, acetone, THF/H2O and carbon tetrachloride were studied on the model reaction at room temperature. The results are given in Table 2.

Table 2 Effect of the solvent on the model reaction of the Suzuki-Miyaura condensation in the presence of ligand L2.
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Among these solvents, methanol was found to have better results than the aprotic or non-polar solvents.

2.5.3 Effect of the ligands on the reaction

The model reaction of phenylboronic acid and 4-bromotoluene was selected for the Suzuki-Miyaura reaction in this presented catalyst system. By using the L1 and L2 ligands in the present methodology, the applied mol% of PdCl2 and reaction time were reduced in high yield of the reaction. As it is observed in Table 3, although L1 and L2 ligands enhanced the yield of the reaction, the ligand L2 was more effective than the ligand L1. The mechanism of the ligand-assisted Suzuki-Miyaura reaction was given in ref 30 in a similar to many other pieces of research (Scheme 3). It has been mentioned that the role of the ligand in the ligand assisted Suzuki-Miyaura reaction is not straightforward and this mechanism has been given on the computational studies. The catalytic cycles involve the steps of: in situ generation of the L-Pd(0), transmetallation involving the exchange of halide for an aryl group and, reductive elimination of diaryl from Pd(II) species. By considering this mechanism, it could be suggested that additives which accelerate these steps can improve the performance of the catalytic system. The effect of the ligands could be remarkable in step 1 of the catalytic cycle. The ionic character of the catalysts providing an efficient media for oxidative addition of R-X on ligand assisted Pd- catalyst system. At this step, the ligand L2 could accelerate this step by the counter ion Na+. It could be proposed that the separation of the X- (halide) from the substrate could be easier by interaction of Na+ by using ligand L2 while, the Cl-(counter ion of the imidazolium moiety) of the ligand L1 competes with the R-X in coordinating to PdCl2 in step 1, thus decreases the activity of the PdCl2. So the ligand L2 should be more effective than ligand L1.

Table 3 Suzuki-Miyaura condensation of phenylboronic acid and 4-boromotoluene in methanol, at reflux conditions.
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Scheme 3
scheme 3

Pd catalysis mechanism in Suzuki-Miyaura coupling.

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2.5.4 Effect of temperature

The effect of temperature on the Suzuki-Miyaura was considered on the methanol in the presence of ligands L1 and L2 (Table 4). Results showed that yield% was enhanced by increasing the temperature to 65 °C. Considering technical limitations, the lower temperature for the reaction is one of the main concerns of synthesis in chemistry. The number of literature that reports the Suzuki-Miyaura condensation in high temperature and even long reaction time is enormous.46,47,48,49,50,51,–52 The refluxed temperature of methanol is 65 °C, so the optimized reaction temperature in the mixture of Methanol/H2O was set at 65 °C and the obtained results were acceptable.

Table 4 Effect of temperature on the model reaction of the Suzuki-Miyaura condensation in the presence of ligand L2 in methanol.
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2.5.5 Effect of aryl halides on the condensation with boronic acid

In this protocol, a series of aryl halides bearing electron-donating or withdrawing substituents are applied that provided substituted biphenyls. Although this method is effective for both aryl halides with donating or withdrawing electron, the yields in the reaction of aryl halides containing electron-donating substituents were comparatively better than the yields by the reaction of aryl halides bearing electron-withdrawing groups. Moreover, the nature of halides on aryl halides was the important factor for the reactivity and the yield of the Suzuki-Miyaura condensation. Aryl halides containing I and Br atoms showed good to excellent yield than aryl halides with F- and Cl-, because those are better-leaving groups (Table 5).

Table 5 Suzuki Coupling of different Aryl Bromides.
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Although calculated turnover numbers are not very good in comparison with other turnover numbers reported in the Suzuki-Miyaurareactions53 considering the benign reaction conditions, easy workup and short reaction time proposed in this paper, and introducing a new Schiff base compound as a capable promoter catalyst for Suzuki-Miyaura reaction is outstanding (Table 6).

Table 6 Reported turnover frequencies for Suzuki-Miyaura reaction.
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2.6 Characterization of the reaction products

After completion of the reaction, the reaction was diluted with distilled water. The extraction of the organic phase was done with diethyl ether. The extracted phase was evaporated and purified by column chromatography. The melting point of the products was compared with the melting points that were reported in the literature and the 1H NMR confirmed the products.

2.6.1 NMR spectra of the products

1HNMR spectra of the products were exactly according to the reports in the literature.

4-methyl-biphenyl. 1H NMR (CDCl3), 7.68–7.65 (m, 2H), 7.59–7.57 (m, 2H), 7.52–7.48 (m, 2H), 7.42–7.38 (m, 1H), 7.34–7.32 (m, 2H), 2.47 (s, 3H).

4-methoxybiphenyl. 1H NMR (CDCl3), 7.68–7.65 (m, 2H), 7.59–7.57 (m, 2H), 7.52–7.48 (m, 2H), 7.42–7.38 (m, 1H), 7.34–7.32 (m, 2H), 2.47 (s, 3H).

4-phenylbenzonitrile. 1H NMR (DMSO), 7.22–7.20 (m, 2H), 7.07–7.10 (m, 2H), 7.22 (s, 1H), 6.95–6.98 (m, 2H).

4-aminobiphenyl. 1H NMR (CDCl3), 6.46 (s, 2H), 6.50–6.52 (m, 2H), 7.39–7.42 (m, 2H), 7.48–7.53 (m, 2H), 7.59–7.63 (m, 2H), 7.25 (s, 1H).

4-Phenylacetophenone.1HNMR (CDCl3) δ 7.85 (d, 2 H), 7.63 (d, 2 H), 7.58 (d, 2 H), 7.40–7.37 (m, 3 H), 2.63 (s, 3 H).

3 Results and Discussion

3.1 Synthesis of ligands

S1 and S2 were prepared as described elsewhere.32,56 The synthesis of ionic Schiff base ligands of the L1 and ligand L2 were carried out by condensation reaction of the prepared (cationic and/or anionic) salicylaldehyde and phenylendiamine in methanol in refluxed condition (Scheme 1). The synthesized compounds were characterized via different spectral and analytical methods.

3.1.1 IR spectra

In the FT-IR Spectra of S1 and S2, a characteristic band was seen at 1650 and 1660 cm−1 for C=O bonds of aldehydic group, respectively. The absorption of the O-H bond for these aldehydes was exhibited at the region 3500–3600 cm−1. In the FT-IR spectra of the L1 and L2 these aldehydic carbonyl bands disappeared and a new band appeared in each spectrum of the L1 and L2, at 1630 and 1620 cm−1, respectively, due to new imine (C=N) bond formation during the condensation reaction of aldehydes and phenylendiamine. The absorptions of the O-H bonds for Schiff base ligands appeared at 3430–3455 cm−1

3.1.2 NMR spectra

The 1H-NMR spectrum of ligand L1 and ligand L2 gives useful information for approval of the structures. For the L1, the peaks in the region of the 9.5–11.0 ppm are related to imine-amine tatomerization due to the interaction of the proton of phenol with the imine nitrogen. The resonances of the iminic protons were also observed in the region of 8.3–9.4 ppm. L1 has three phenyl groups and two imidazole rings and is expected to have multiple signals in the aromatic region. In the 1H-NMR spectrum, in region 6.81–7.72 ppm multiple resonances are observed. The resonances at 5.43 and 5.39 ppm are related to the 4H of the methylene groups. The resonance at 3.89 ppm is related to the 6H of the two methyl groups of the imidazole rings.

The broad resonance at 9.12 ppm is related to the OH protons. The resonance at 8.50 ppm is related to the 2H from the two imine groups. In similar to the ligand L1, the ligand L2 has multiple signals in the aromatic region because of the three phenyl groups, so the resonances at region 6.86–8.00 ppm are related to the protons of the aromatic rings. The observed sharp resonance at 8.55 ppm and the broad resonance at 9.00–9.25 ppm are attributed to the iminic and phenolic protons of L2, respectively, The 1H-NMR spectrums of ligand L1 and ligand L2 are shown in Figure 1 and Figure 2, respectively. The 13C-NMR of the ligand L1 and ligand L2 are given in Figure 3 and Figure 4, respectively. For Ligand L1the 14 resonances of 35.88, 51.26, 58.45, 117.33 117.87 121.84, 122.02, 122.08, 123.79, 123.91, 136.16, 136.41, 161.43 and 166.30 ppm were observed. These resonances are completely consistent with the 14 kind carbons in the ligand L1that confirm the structure of the L1 ligand. The low resonances of 35.81 ppm, 51.26 ppm are related to the carbon of methyl on imidazole and methylen of benzylic carbon. Whereas, the resonance in 161.43 ppm and 166.30 ppm are attributed to the Carbon-Nitrogen bond (C=N) and phenolic carbon (C-OH), respectively. The other resonances are for aromatic carbons in phenyl and imidazole rings. For L2 ligand the resonances of 115.64, 117.27 120.16, 123.10, 127.96, 134.39, 134.80, 143.39, 156.96 and 165.96 ppm that finally attributed to the 10 kind carbons in the L2 ligand are observed. In this ligand, the last two resonances (156.96 and 165.96 ppm) are with respect to the carbon of imin (-C=N) and carbon of phenol (C-OH), respectively, and the other resonances are related to the aromatic carbons.

Figure 1
figure 1

1H-NMR of ligand L1.

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Figure 2
figure 2

1H-NMR of ligand L2.

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Figure 3
figure 3

13C-NMR of ligand L1.

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Figure 4
figure 4

13C-NMR of ligand L2.

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3.1.3 UV-visible spectra

Since ligand L1 and ligand L2 are water-soluble, the UV-visible of them were recorded in H2O. The UV-visible spectrum of the L2 showed two bands at 200 and 225 for \( \pi\to{\mathop{\pi}\limits^{*}} \) and 385 nm and \( n\to{\mathop{\pi}\limits^{*}} \) transitions, respectively, while for L1 these two bands are seen at 220 and 364 nm, respectively. The UV-visible spectra are shown in (Figure 5).

Figure 5
figure 5

UV–visible spectra of Ligand L1 and ligand L2.

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3.1.4 Mass spectrometry

For further characterization of the ligands (L1 and L2), the mass spectrometry was also used. Mass spectrometric data of L1 approved the structure of the ligand. In mass spectrometry, in some cases, the ion-molecule shows very low intensity or in rare cases it is not seen.57 In addition, the molecular ion is seen in lower or higher m/z than the original molecule with losing or abstracting of one or more protons.58 The molecular weight of ligand L1 (C30H30Cl2N6O2) is 577, and the molecular ion of the L1 with M/z+ = 577.6 is observed in the spectrum at (Figure 6). There are some main signals with the m/z of 480, 300, 284, 224, 183, 132 and 82. Although there are many picks with low abundance, it is focused on the indicator picks that confirm the structure. The pick at m/z 480 is related to the molecular ion by losing of one methyl imidazole ring (C25H23Cl2N4O2). As a consequence, the signal at m/z 300 is related to the residual molecular ion without another methyl imidazole ring with the other chlorine counter ion plus one hydroxyl group (C20H16N2O) and, the loss of another hydroxyl group gives the signal at m/z 284. The signal at m/z = 132 is related to the phenylendiamine and a signal at m/z = 82 is related to methyl imidazole group. For ligand L2, mass spectrometric data shows the molecular weight of ligand L2 (C20H14N2Na2O8S2) at M+2(522), and the exact mass of the ligand L2 is 520. The spectrum is shown in (Figure 7). There are some main signals at m/z of 497, 474,397, 313,299, 285,194, 119, 108, 77 and 43 that determine the structure of the ligand. Signals at m/z 497 and 474 are related to the molecular ions by losing one and two Na. The m/z = 397 is related to the molecular ion by loss of one of the sulfonyl group. The pick at m/z =  299 is related to the residual molecular ion without another sulfonyl group and one of the hydroxyl group. This fragment would be a radical cation with one oxygen atom (C20H15N2O+). Signals at m/z = 285 are related to (C20H16N2) and the m/z = 194 is related to the residual molecular ion by losing of (C6H5CH+2) group. At the m/z = 108, there is a signal which is related to the phenylendiamine (C6H8N2). The picks at m/z = 77 and 43 are related to the phenyl group and allyl group of the aromatic ring.

Figure 6
figure 6

Mass spectra of ligand L1.

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Figure 7
figure 7

Mass spectra of ligand L2.

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4 Conclusions

In this study, two active catalyst system for Suzuki-Miyaura coupling of aryl halides based on ionic Schiff base ligands, which are easily prepared have been developed. A comparison of catalytic activity of PdCl2 in the presence of these two ligands have been made and was found that the catalyst in the presence of anionic Schiff base ligand was more effective. The effect of different parameters on the rate and yield of the reaction has been considered and the optimized system has been introduced. The Suzuki-Miyaura reaction can be carried out by the Palladium Chloride lonely, but because of the value and costliness of the Palladium, a way to save the precious catalyst by introducing the Schiff base ligand have been presented. Thus, the simplicity in synthetic route for preparation of the ionic Schiff base ligands in this research, using low amount of catalyst (0.5 mol%) as well as medial to high yields and moderate reaction conditions for the Suzuki-Miyaura coupling of aryl bromides and iodides can be introduced as the advantages of the titled catalytic system in this research.