A novel ionic liquid-supported Schiff base ligand applied in the Pd-catalyzed Suzuki–Miyaura coupling reaction

A series of novel ionic liquid-supported Schiff bases have been prepared from the condensation of aromatic aldehydes with the ionic liquid 1-(2-aminoethyl)-3-methylimidazolium hexafluorophosphate. The as-prepared ionic liquid-supported salicyladehyde Schiff base L3 was further investigated as a ligand for the Pd-catalyzed Suzuki-Miyaura coupling reaction under air in ethanol solution, giving biaryls in good to excellent yields. The PdCl 2 /ligand L3 catalytic system could be reused at least 5 times without losing its activity.


Introduction
Transition-metal-catalyzed cross-coupling is a versatile and highly useful transformation, which yields a variety of organic compounds.2][3][4] In the past few years, many attempts have been made to develop effective palladium complexes, which can act as highly active catalysts for this homogeneous reaction.Among them, various forms of ligands such as phosphorous ligands, 5-8 P, O-based ligands, [9][10] bis(thiourea) ligands, 11 thiosemicarbazone, 12 etc.were used to stabilize the catalytic palladium species.Although these catalysts often have higher activities in such transformations, however, most of them are expensive, not easy available, require air-free handling to prevent the oxidation, and exist the main drawback of these catalysts is the necessity of their separation from the reaction mixture at the end of the reaction.
4][15] The capacity of ILs to solvate both polar and nonpolar species allows the dissolution of a wide range of organic, inorganic, and organometallic compounds favoring the formation of a homogeneous catalytic system.However, many palladium (II)-catalyzed coupling reactions are carried out in ILs in the presence of bulky phosphine ligands, [16][17][18] which are sensitive to both oxygen and moisture, and lead to catalyst decomposition.0][21][22] Most recently, much more attention has been focused on the synthesis of functionalized ionic liquids (FILs), via incorporation of additional functional groups such as amine, amide, nitrile, ether, alcohol, acid, urea or thiourea, etc. as a part of the cation and/or anion for task specific purposes.6 We have been interested in the use of functionalized ionic liquid-supported Schiff base, since Schiff base palladium(II) compounds are excellent candidates as N, O-bidentate ligands in catalysis owing to their desirable coordinating ability with palladium.In this paper, we wish to report the use of ionic liquid-supported Schiff base as the palladium (II) ligand to demonstrate their suitability in palladium-catalyzed Suzuki-Miyaura cross-coupling reactions.

Results and Discussion
The ligands L1-L6 of ionic liquid supported Schiff base were readily prepared by the condensation of aromatic aldehydes with the functionalized ionic liquid 1-(2-aminoethyl)-3methylimidazolium hexafluorophosphate (Scheme 1).To evaluate the activity of the catalyst formed in situ from ligand L1-L6 and PdCl2 in Suzuki-Miyaura reaction, the coupling reaction of 4-iodoanisole with phenylboronic acid has been chosen as a model reaction (Table 1).It can be seen that when using L3 as ligand, the reaction proceeded much faster and the product obtained with higher yields than other ligands (Table 1, entry 3). a Reaction conditions: 4-indoanisole (1.0 mmol), phenylboronic acid (1.2 mmol), PdCl2 (0.5mol%), Ligand (0.5mol%), C2H5OH (10mL), K2CO3 (2mmol), at reflux under air.b Isolated yields Encouraged by this result, we further investigated the effect of base, solvent and temperatures on the Suzuki-Miyaura reaction when using L3 as ligand under the same condition mentioned above.The results were listed in Table 2. Using K2CO3 as a base, the reaction gave good yield of the desired product (Table 2, entry 1).Several commonly used solvents were tested.The nonpolar solvent cyclohexane and protic solvent H2O was found not to be effective (Table 2, entries 9 and 12), and polar solvents, such as EtOH, DMF and CH3CN, were preferred for this reaction and the EtOH (Table 2, entries 1-8 and 13) was the best choice.The reaction temperature has dramatic effect on the reaction, when the reaction carried out at 50C, the yield decreased to 88% from 98% (Table 2, entry 13).In addition, the reactions were performed in air and without degassing the solvent prior to use.After having established the optimized coupling reaction conditions, the scope of the reaction and efficiencies of the ligand L3 were evaluated by investigating the coupling of various substituted aryl halides and substituted aryl boronic acid (Scheme 2).
The results were shown in Table 3.As shown in Table 3, the aryl iodides produced good yields in shortest times irrespective of the substituents on aryl halides and aryl boronic acid (Table 3, entries 1-11).Aryl bromides with different substituents also gave good yields in the coupling reaction except o-nitrobromobenzene due to the steric effect (Table 3, entries 12-19).However, aryl chloride gave a poor yield under the same optimized reaction conditions (Table 3, entry 20).One of the main aims of our study was to investigate the reuse and recycling the catalyst.Finally, we explored the reusability of the PdCl2/ligand L3 catalytic system using the reaction of 4-iodoanisole and phenylboronic acid as the model reaction.After the completion of the reaction, the reaction mixture was diluted with Et2O and decanted, the remained catalyst was washed with Et2O for several times and reused directly under the similar conditions mentioned above.The results listed in Table 4 and showed the catalytic system could be reused up to 5 runs while retaining the catalytic activity.

Conclusions
We have demonstrated the PdCl2/ligand L3 catalyst was proved to be highly efficient in Suzukimiyaura reactions of aryl halides and aryl boronic acids.Furthermore, the PdCl2/ligand L3 catalyst can be easily separated and recovered from the reaction mixture by filtration and reused for up to 5 runs without noticeable losing activities.The utility of the PdCl2/ligand L catalysts in other coupling reactions such as Heck and Sonogashira reactions is being explored in our laboratory.

Experimental Section
General.All products were characterized by comparison of their spectra and physical data with authentic samples.Melting points were measured on an Electrothemal X6 microscopy digital melting point apparatus.IR spectra were recorded on a Bruker Equinox 55 spectrometer using KBr pellets. 1 H NMR spectra were recorded on a Bruker AVANCE 300 (300 MHz) instrument with the TMS at d 0.00 ppm as an internal standard.Elemental analyses were carried out on a PE EA2400 CHN analyzer.All chemicals were reagent grade and used as purchased.
Synthesis of the ionic liquid supported Schiff bases. 27A mixture of the ionic liquid 1-(2aminoethyl)-3-methylimidazolium hexafluorophosphate (1.028 g, 4.0 mmol) and aromatic aldehydes (3.0 mmol) was stirred for 4 h at room temperature under solvent-free conditions.After completion of the reaction, ethanol (30 mL) was added to the reaction mixture, the solid product formed was filtered off and washed with cold ethanol.The crude product was purified by recrystallization from ethanol/ethyl acetate (3:1 v/v).The structure for L3 was characterized by X-ray single crystal diffraction (CCDC 712469).

General procedure for Suzuki-Miyaura reaction
A mixture of aryl halide (1.0 mmol), arylboronic acid (1.2 mmol), L3 (0.005 mmol), PdCl2 (0.005 mmol), K2CO3 (2.0 mmol), and EtOH (10.0 mL) was added to a flask and stirred under reflux.After the reaction was judged to be complete by TLC analysis, the reaction mixture was cooled to room temperature, and to the solution was added Et2O (20 mL), the PdCl2/L3 catalyst was remained in the flask bottom and was washed with Et2OH (3 × 10 mL).The organic phase was evaporated and the residue was purified by recrystallization.All of the products 3a-3k are known and the data are found to be identical with those that reported in literature elsewhere.

CH 3 OC 6 H 3 Scheme 1.
Synthesis of the ionic liquid supported Schiff bases.

Table 1 .
Influence of ligands L on the palladium-catalyzed Suzuki-Miyaura coupling of 4indoanisole with phenylboronic acid a

Table 3 .
PdCl2/Ligand L3 catalyzed coupling reaction of aryl halides with aryl boronic acids a

Table 4 .
Reuse of catalytic system on the Suzuki-Miyaura coupling reaction of 4-indoanisole and phenylboronic acid a b Isolated yields.