Abstract
A classical Merrifield resin was modified with pendant terpyridine heterocycles in order to develop a new material for heterogeneous catalysis. The protocol relies on the reaction of a pyrrolyl anion with chloromethyl groups present on the resin. The modified polymer was then reacted with a Pd salt to afford a catalyst that was tested in the Suzuki cross-coupling reaction in environmentally friendly solvents.
1 Introduction
Owing to their impressive complexing properties, 2,2′:6′,2″-terpyridine ligands and their complexes have been widely studied [1]. Amongst this huge amount of research work dedicated to terpyridine chemistry, there are numerous examples of polymers that were functionalized with terpyridine moieties in order to obtain functional materials [2]. One can cite terpyridine appended polyacrylates [3], polystyrene [4], polyvinylchloride [5], polythiophene [6] or silica [7] just to name a few. The well-known Merrifield resin, which is a chloromethylated polystyrene crosslinked with divinylbenzene polymer, has also been functionalized with pendent terpyridine ligands [8]. The functional polymer was obtained by reacting 4′-hydroxy-2,2′:6′,2″-terpyridine with the resin using a Williamson reaction. Nevertheless, preparation of the former from commercially available reagents (acetone and ethyl picolinate) is not as straightforward as it seems [9, 10]. In this paper, we describe a new method for the functionalization of Merrifield resin with terpyridine ligands. It is based on the reaction of 4′-(pyrrol-2-yl)-2,2′:6′,2″-terpyridine, a compound that is easily prepared in one pot from commercially inexpensive reagents, with the resin through N-alkylation of the pyrrole ring. The obtained material was tested in the utilization of its Pd complex to catalyze the Suzuki reaction in environmentally friendly solvents such as ethanol or water.
2 Materials and methods
All reagents were purchased from Acros Organics (Geel, Belgium) and Sigma-Aldrich (Saint-Quentin Fallavier, France) and used as received unless otherwise stated. Merrifield resin (2.8–3.2 mmol Cl/g) was purchased from Acros Organics (Geel, Belgium). Terpyridine 1 was prepared according to literature [11]. All compounds synthesized via the Suzuki reaction are known compounds. Their physical as well as spectroscopic properties are consistent with those reported in the literature [12–22]. All of these compounds were purified by flash column chromatography with a Teledyne ISCO (CombiFlash Rf+ Lumen) apparatus over silica gel using hexane/ethyl acetate mixtures as eluents, except compound 11, which was purified by recrystallization from ethanol/aqueous HCl. C, H, N elemental analyses were recorded at the “Centre de micro-analyse élémentaire” Vandoeuvre-les-Nancy, France. Palladium elemental analyses were recorded at Institut des Sciences Analytiques (Villeurbanne, France) or at Qualio (Besançon, France) by ICP-AES.
2.1 Terpyridine modified Merrifield resin (2)
In a round bottomed flask are successively placed powdered 85% potassium hydroxide (1.88 g) and DMSO (45 ml). The reaction media is stirred at room temperature under argon for 30 min. Ligand 1 (4.30 g) is then added and the red solution is stirred at room temperature under argon for 30 min. Merrifield resin (4.50 g) is then added and the suspension is stirred at 100°C for 72 h under argon. After cooling to room temperature, the reaction mixture is poured onto distilled water (150 ml). The solid is filtered, thoroughly washed with water and ethanol, and air dried. Final purification is effected by Soxhlet extraction with dichloromethane until no terpyridine is detected in the filtrate (approximately 24 h). This yields modified resin 2 (4.57 g).
2.2 Preparation of catalyst (3)
In a round bottomed flask is placed 2 (2.000 g) and the system is flushed with argon. Dichloromethane is then added (70 ml) followed by PdCl2(CH3CN)2 (0.294 g). The reaction mixture is stirred at room temperature under argon for 24 h. The solid is filtered, washed with dichloromethane and dried under vacuum in a Schlenck tube. The material (2.280 g) is stored in the tube under argon.
2.3 Representative procedure for the Suzuki cross-coupling reaction using 3 as a catalyst
In a stoppered Erlenmeyer flask are successively placed the halide (10 mmol; 1 Eq.), ethanol (200 ml), boronic acid (12 mmol; 1.2 Eq.), potassium carbonate (2.76 g; 20 mmol; 2 Eq.) and catalyst 3 (0.21 g; 0.1 mmol of Pd). The resulting mixture is stirred at room temperature (20°C) for 24 h. To the mixture is then added dichloromethane (100 ml) and the resulting suspension is stirred at room temperature for half an hour. The solid (catalyst and base) is then filtered (glass sintered funnel) and washed with 50 ml of dichloromethane. Organic layers are combined, washed with water (2×100 ml), brine (100 ml), dried over sodium sulfate and concentrated under vacuo.
2.4 Catalyst recovery
The almost dry mixture of catalyst and base is suspended and stirred in water (100 ml) for half an hour. The solid is then filtered, washed with water (50 ml), small portions of ethanol and dried on the filter under vacuo. The brown powder so obtained can be re-used directly for another experiment. If the catalyst is to be stored for an extended period of time, it is further washed with small portions of diethyl ether and stored in a glass vial without specific caution.
2.5 Sonogashira coupling of phenylacetylene with iodobenzene
To a suspension of 3 (0.106 g) in water (10 ml) is added iodobenzene (2.04 g; 10 mmol). The resulting mixture is stirred at room temperature for 5 min. Then phenylacetylene (1.24 g; 12 mmol) and triethylamine (2.2 ml) are added and the solution is stirred at 80°C for 2 h. After cooling to room temperature, the solid is filtered and washed with dichloromethane (30 ml). Layers are separated and the aqueous layer is extracted with dichloromethane (3×10 ml). Organic layers are combined, washed with brine (50 ml), dried over sodium sulfate and concentrated. The crude product is purified by flash chromatography over silica gel using hexane as eluent. Pure diphenylacetylene is obtained as a white solid (0.60 g; 34%). Spectroscopic and physical properties are in agreement with literature values.
3 Results and discussion
The methodology used to anchor the terpyridine moiety onto Merrifield resin relies on the N-alkylation of the pyrrole heterocycle of 4′-(pyrrol-2-yl)-2,2′:6′,2″-terpyridine 1 [11] (Scheme 1).
Synthetic procedure for the preparation of terpyridine-functionalized Merrifield resin.
To achieve this, 1 was reacted with potassium hydroxide in DMSO to generate N-pyrrolyl anion. The nucleophilic character of the pyrrolyl anion was then exploited to displace a Cl atom onto the resin, thus giving birth to a new C-N bond and insuring anchorage of the ligand onto the polymeric network. The reaction was carried out both at room temperature and at 100°C. Final purification was achieved by thoroughly extracting the resin with dichloromethane in a Soxhlet apparatus.
Characterization techniques for this new material are limited due to its insolubility. Nevertheless, elemental analysis clearly demonstrates the presence of the nitrogen heterocycles. Since nitrogen atoms are only brought by the terpyridine-pyrrole moieties, the degree of functionalization was easily determined by measuring nitrogen content of the modified resin. The results (Table 1) indicate that the functionalization was increased when performing the modification at 100°C.
Degree of terpyridine-functionalization in function of reaction temperature.
| Reaction temperature (°C) | % N | Degree of functionalization (mmol/g) |
|---|---|---|
| RT | 0.86 | 0.15 |
| 100 | 3.16 | 0.56 |
Then, resin 2 was reacted with (CH3CN)2PdCl2 in dichloromethane to afford an anchored Pd-complex (3) suitable for use as heterogeneous catalyst (Scheme 2). The amount of Pd adsorbed was determined to be 5 wt% by elemental analysis (ICP-AES). As a control experiment, unmodified Merrifield resin was reacted with the palladium salt under the same conditions as 2. In this case, the measured palladium content was only 1.3 wt%. This result demonstrates the important role of the terpyridine moieties for immobilizing palladium onto the resin, and is in accordance with previous reports about terpyridine-modified polystyrene-based polymers as metals adsorbents [8, 23–25].
Complexation of Pd onto resin 2 and proposed structure of material 3.
The metal-loaded material 3 was then assessed as an heterogeneous catalyst for the Suzuki-Miyaura cross coupling reaction [26] between bromo- (4) or iodobenzene (5) and phenylboronic acid (6) to afford biphenyl (7) (Scheme 3).
Suzuki coupling using material 3 as a catalyst.
A first set of experiments was carried out in three different solvents, namely water, ethanol and 2-methyltetrahydrofuran (2-MeTHF). These solvents were selected because they are harmless (water) or can be obtained from biomass (EtOH [27, 28] or 2-MeTHF [29]) in order to have a synthetic process as sustainable as possible. Results are depicted in Table 2.
Isolated yield (after chromatography) for compound 7 using the Suzuki reaction with 3 as catalyst in different solvents.
| Solvent | Conditions | Isolated yield (%) |
|---|---|---|
| H2O | 4 (1 mmol), 6 (1.2 mmol) | 14.3 |
| EtOH | K2CO3 (2 mmol), Cat. 3 (1 mol%) | 3.9 |
| 2-MeTHF | RT, 24 h | 0 |
| H2O | 5 (1 mmol), 6 (1.2 mmol) | 87.3 |
| EtOH | K2CO3 (2 mmol), Cat. 3 (1 mol%) | 89.5 |
| 2-MeTHF | RT, 24 h | 0 |
2-MeTHF, 2-methyltetrahydrofuran.
From these experiments, it is clear that ethanol is more suitable for carrying out this coupling reaction. Then, different bases (Table 3) were assessed and compared in the coupling of iodobenzene with phenylboronic acid (Scheme 4).
Results for different bases.
| Base | Isolated yield (%) |
|---|---|
| K2CO3 | 89.5 |
| Na2CO3 | 63.5 |
| CaCO3 | 0 |
| K2HPO4 | 10.4 |
| CH3COONa | 7.1 |
| Et3N | 16.2 |
Coupling of iodobenzene with phenylboronic acid using different bases.
As can be seen in Table 3, the best base to achieve the reaction is potassium carbonate. All other bases, except sodium carbonate, gave poor results. This result is in accordance with a previous report [30] highlighting the importance of carbonate bases in Suzuki coupling in environmentally friendly solvents such as water.
Then, the effect of catalyst loading was estimated (Table 4) using the combination of ethanol as solvent and potassium carbonate as a base with a reaction time of 24 h as above. The best yield was obtained with a catalyst loading of 1% (based on metal content).
Effect of catalyst loading onto yield.
| Catalyst loading (% mol) | Yield (%) |
|---|---|
| 1 | 89.5 |
| 0.5 | 68 |
| 0.1 | 72.6 |
The recovery and reuse of a catalyst is a very important point in order to have a process as sustainable as possible. Thus, the recyclability of this new supported catalyst was tested on the model reaction. Material 3 can be recycled six times without significant loss of efficiency (Figure 1). The loss of reactivity can be explained by Pd-leaching. In fact, after five cycles, Pd content dropped to 2.7 wt%. It is interesting to note that the recovered catalyst can be stored for an extended period of time without specific caution while retaining its efficiency. This point is demonstrated by Run 6 which was carried out at least 1 month after Run 5. Furthermore, the stability of 3 was confirmed by running two experiments with a sample stored in air for more than a year (Table 5).
Recycling experiments for material 3.
Yields obtained in the coupling of 5 with 6 using a sample of 3 stored in air between two experiments at an interval >1 year.
| Date of experiment | Yield (%) |
|---|---|
| 16/12/2013 | 89.5 |
| 19/02/2015 | 90 |
Then, catalyst 3 was used to prepare a broad range of different compounds (Table 6) by coupling different (het)aryl halides and boronic acids (Scheme 5).
Results for coupling of different aryl halides and aryl boronic acids with 3 as catalyst.
| Entry | R= | X= | R′= | Product | Yield (%) |
|---|---|---|---|---|---|
| 1 |  | I |  |  | 72 |
| 2 |  | I |  |  | 73 |
| 3 |  | Br |  |  | 80 |
| 4 |  | I |  |  | 68 |
| 5 |  | I |  |  | 93 |
| 6 |  | I |  |  | 12 |
| 7 |  | I |  |  | 13 |
| 8 |  | I |  |  | 55 |
| 9 |  | I |  |  | 16 |
| 10 |  | Br |  |  | 10 |
| 11 |  | I |  |  | 0 |
| 12 |  | I |  |  | 0 |
| 13 |  | I |  |  | 56 |
Preparation of various di-(het)aryl compounds using 3 as catalyst.
The reaction was successful for coupling different aryl iodides with boronic acids. Interestingly, 1-bromo-4-nitrobenzene was sufficiently reactive (Table 6, entries 3 and 10) to be used, but electron-deficient boronic acids (Table 6, entries 6–10) are poor substrates with this catalyst. More surprising is the low reactivity of thiophene-2-boronic acid (Table 6, entries 11–13) which requires the halide to be activated by an electron-withdrawing group. This phenomenon is not elucidated yet. Finally, in order to extend the possible uses of this new catalyst, one preliminary experiment was carried out to test the feasibility of using 3 in a copper-free Sonogashira coupling between phenylacetylene and iodobenzene in water using conditions recently described [31] (Scheme 6). The reaction afforded the desired diphenylacetylene (20) in 34% yield, thus confirming the potential utilization of this new catalyst in Sonogashira reactions.
Sonogashira coupling in water catalysed by 3.
4 Conclusion
A new heterogeneous catalyst suitable for the Suzuki cross-coupling reaction between aryl iodides and boronic acids has been designed. It is based on a polymeric Merrifield resin that is functionalized with terpyridine ligands which were used to complex the active metal palladium. This new metal-containing polymer can be re-used up to six times.
Although being not efficient onto electron-deficient boronic acids, its main advantages are an easy preparation from commercially available reagents and an excellent stability in time, making it a new tool for the preparation of biaryls. Furthermore, a preliminary experiment indicates that this new material is suitable for the Sonogashira coupling. Thus, future work will focus on broadening the scope of reactions which can be catalyzed with it.
About the authors
Jérôme Husson is an Associate Professor at Institute UTINAM, Université de Franche-Comté, France. His main research interests are focused on the preparation of new molecules and materials (sensitizers for dye-sensitized solar cells, functionalized polymers for water treatment and catalysis) for sustainable development.
Laurent Guyard is a Professor at the Institute UTINAM, University of Franche-Comté. He works on several topics: green chemistry, terpyridines, sensors and conducting polymers.
References
[1] Schubert US, Newkome GR. Modern Terpyridine Chemistry. Wiley VCH: Weinheim, 2006.10.1002/3527608486Search in Google Scholar
[2] Schubert US, Winter A, Newkome GR. Terpyridine-Based Materials, Wiley VCH: Weinheim, 2011.10.1002/9783527639625Search in Google Scholar
[3] Calzia KJ, Tew GN. Macromolecules 2002, 35, 6090–6093.10.1021/ma025551jSearch in Google Scholar
[4] Koohmareh GA, Sharifi M. J. Appl. Polym. Sci. 2010, 116, 179–183.Search in Google Scholar
[5] Meier MAR, Schubert US. J. Polym. Sci., Part A: Polym. Chem. 2003, 41, 2964–2973.10.1002/pola.10881Search in Google Scholar
[6] Scanu R, Manca P, Zucca A, Sanna G, Spano N, Seeber R, Zanardi C, Pilo MI. Polyhedron 2013, 49, 24–28.10.1016/j.poly.2012.09.056Search in Google Scholar
[7] Sattari E, Moazzen E, Amini MM, Ebrahimzadeh H, Heravi MRP. Acta Chim. Slov. 2013, 60, 124–130.Search in Google Scholar
[8] Saadeh HA, Abu Shairah EA, Charef N, Mubarak MS. J. Appl. Polym. Sci. 2012, 124, 2717–2724.10.1002/app.34977Search in Google Scholar
[9] Potts KT, Konwar D. J. Org. Chem. 1991, 56, 4815–4816.10.1021/jo00015a050Search in Google Scholar
[10] Constable EC, Ward MD. J. Chem. Soc., Dalton Trans. 1990, 4, 1405–1409.10.1039/DT9900001405Search in Google Scholar
[11] Husson J, Guyard L. Heterocycl. Commun. 2015, 21, 199–202.10.1515/hc-2015-0058Search in Google Scholar
[12] Alizadeh A, Khodaei MM, Kordestani D, Beygzadeh M. Tetrahedron Lett. 2013, 54, 291–294.10.1016/j.tetlet.2012.11.031Search in Google Scholar
[13] Hamilton AE, Buxton AM, Peeples CJ, Chalker JM. J. Chem. Educ. 2013, 90, 1509–1513.10.1021/ed4002333Search in Google Scholar
[14] Camp JE, Dunsford JJ, Cannons EP, Restorick WJ, Gadzhieva A, Fay MW, Smith RJ. ACS Sustainable Chem. Eng. 2014, 2, 500–505.10.1021/sc400410vSearch in Google Scholar
[15] Mao S-L, Sun Y, Yu G-A, Zhao C, Han Z-J, Yuan J, Zhu X, Yang Q, Liu S-H. Org. Biomol. Chem. 2012, 12, 9410–9417.10.1039/c2ob26463cSearch in Google Scholar PubMed
[16] Gupta S, Basu B, Das S. Tetrahedron 2013, 69, 122–128.10.1016/j.tet.2012.10.055Search in Google Scholar
[17] Sithebe S, Robinson RS. Beilstein J. Org. Chem, 2014, 10, 1107–1113.10.3762/bjoc.10.109Search in Google Scholar PubMed PubMed Central
[18] Shaughnessy KH, Booth RS. Org. Lett. 2001, 3, 2757–2759.10.1021/ol0163629Search in Google Scholar PubMed
[19] Kondolff I, Doucet H, Santelli M. J. Heterocyclic Chem. 2008, 45, 109–118.10.1002/jhet.5570450109Search in Google Scholar
[20] Li J-H, Liang Y, Wang D-P, Liu W-J, Xie Y-X, Yin D-L. J. Org. Chem. 2005, 70, 2832–2834.10.1021/jo048066qSearch in Google Scholar PubMed
[21] Damkaci F, Altay E, Waldron M, Knopp MA, Snow D, Massaro N. Tetrahedron Lett. 2014, 55, 690–693.10.1016/j.tetlet.2013.11.111Search in Google Scholar
[22] Yang J, Liu S, Zheng J-F, Zhou J. Eur. J. Org. 2012, 31, 6248–6259.10.1002/ejoc.201200918Search in Google Scholar
[23] Suzuka T, Nagamine T, Ogihara K, Higa M. Catal. Lett. 2010, 139, 85–89.10.1007/s10562-010-0422-0Search in Google Scholar
[24] Schubert US, Alexeev A, Andres PR. Macromol. Mater. Eng. 2003, 288, 852–860.10.1002/mame.200300140Search in Google Scholar
[25] Suzuka T, Sueyoshi H, Maehara S, Ogasawara H. Molecules 2015, 20, 9906–9914.10.3390/molecules20069906Search in Google Scholar PubMed PubMed Central
[26] Suzuki A. Proc. Jpn. Acad., Ser. B 2004, 80, 359–371.10.2183/pjab.80.359Search in Google Scholar
[27] Vohra M, Manwar J, Manmode R, Padgilwar S, Patil S. J. Environ. Chem. Eng. 2014, 2, 573–584.10.1016/j.jece.2013.10.013Search in Google Scholar
[28] Kumar S, Singh SP, Mishra IM, Adhikari DK. Chem. Eng. Technol. 2009, 32, 517–526.10.1002/ceat.200800442Search in Google Scholar
[29] Pace V, Hoyos P, Castoldi L, Dominguez de Maria P, Alcantara AR. ChemSusChem 2012, 5, 1369–1379.10.1002/cssc.201100780Search in Google Scholar PubMed
[30] Edwards GA, Trafford MA, Hamilton AE, Buxton AM, Bardeaux MC, Chalker JM. J. Org. Chem. 2014, 79, 2094–2104.10.1021/jo402799tSearch in Google Scholar PubMed
[31] Yi W-B, Shi X-L, Cai C, Zhang W. Green Process. Synth. 2012, 1, 175–180.10.1515/gps-2012-0002Search in Google Scholar
Supplemental Material:
The online version of this article (DOI: 10.1515/gps-2015-0144) offers supplementary material, available to authorized users.
©2016 by De Gruyter
This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
