ARTICLE pubs.acs.org/Organometallics
Iridium NHC Based Catalysts for Transfer Hydrogenation Processes Using Glycerol as Solvent and Hydrogen Donor Arturo Azua, Jose A. Mata,* and Eduardo Peris* Departamento de Química Inorganica y Organica, Universitat Jaume I, 12071 Castellon, Spain ABSTRACT: A series of iridium and ruthenium N-heterocyclic carbene based catalysts of general formula [IrI2(AcO)(bis-NHC)] or [Ru(η6-arene)(NHC)CO3] have been tested in the reduction of several organic carbonyl compounds using glycerol as solvent and hydrogen donor, by the transfer hydrogenation methodology. The Ir(III) complexes with a chelating bis-NHC ligand and sulfonate groups were the most efficient, due to their solubility in the reaction media and to the strong electron-donor properties of the bis-carbene ligands. The same two catalysts were moderately active in the reduction of olefins and alkynes and, more remarkably, show excellent chemoselectivity in the reduction of the alkenic double bond of α,β-unsaturated ketones, a valuable process for which glycerol had never been used before.
’ INTRODUCTION The rise of green chemistry has drawn attention to synthetic procedures that promote atom economy and the use of nontoxic reagents.1 Well-known cases of green catalysis include hydrogen transfer methodologies for the reduction of ketones or imines and oxidation of alcohols and amines, for which the hydrogen donor (typically 2-propanol) or acceptor (e.g., acetone) are easyto-handle, environmentally friendly reagents.2 7 The choice of a green solvent is among the 12 principles of green chemistry.1 A green solvent must meet numerous criteria, such as low toxicity, nonflammability, nonmutagenicity, nonvolatility, and widespread availability. Although many solvents meet the aforementioned criteria, glycerol has recently caught the attention of many researchers, due to its unique physical and chemical properties, its extraordinarily low cost, and itsready availability.8 Glycerol is the main coproduct of the vegetable oil industry, and its use has been boosted by the rapid emergence of biodiesel in the market.9,10 As a solvent, glycerol has a number of advantages, such as its ability to dissolve inorganic salts, acids, bases, metal complexes, and organic compounds that are poorly miscible in water. Its high boiling point (290 °C) allows reactions to be carried out at high temperatures and makes distillation of the reaction products a feasible separation technique. Additionally, glycerol is a nontoxic biodegradable and nonflammable solvent for which no special handling or storage precautions are needed.8 Apart from its use as a solvent, new and innovative catalytic processes based on the use of glycerol have been recently developed.11 16 In this context, the development of novel, selective chemistry to provide new applications for glycerolderived products remains a key challenge. Hydrogen-borrowing activation of alcohols may be considered as an important contribution of organometallic catalysts to r 2011 American Chemical Society
the development of greener chemical processes.17 Glycerol can be envisaged as a suitable hydrogen source for transfer hydrogenation processes to ketones and imines if a suitable catalyst is used. The hydrogen transfer is expected to selectively occur from the secondary alcohol, yielding dihydroxyacetone (DHA) as oxidation product. To our knowledge, only two reports regarding transfer hydrogenation of glycerol have recently appeared.18,19 We have recently been interested in the design of N-heterocyclic carbene based catalysts for “hydrogen-borrowing” processes.20 In our research, we also focused our attention on the preparation of highly effective catalysts that may be capable of reducing inert molecules such as carbon dioxide, using 2-propanol as the hydrogen source.21 23 For these reactions, we found that the best catalysts were those combining high stability, strong electron-donor ligands, and high solubility in polar solvents. These three properties were achieved by using chelate abnormally bound NHC ligands with sulfonate functionalities.21 These properties of the catalyst, which were valid for the use of an inert hydrogen acceptor, should also be valid for the use of an inert hydrogen donor and thus may be applied to the utilization of glycerol as the hydrogen source in a transfer hydrogenation process. In this context, we now report the use of a series of iridium(III) catalysts for the transfer hydrogenation of double bonds using glycerol as hydrogen donor.
’ RESULTS AND DISCUSSION Compounds 1 4 of general formula [IrI2(AcO)(bis-NHC)] or [Ru(η 6 -arene)(NHC)CO 3 ] (Scheme 1) were prepared Received: August 25, 2011 Published: September 30, 2011 5532
dx.doi.org/10.1021/om200796c | Organometallics 2011, 30, 5532–5536
Organometallics
ARTICLE
Scheme 1
as previously described by Crabtree 24 (complex 3) and us (complexes 1, 2, and 4).21 23,25 Similar complexes are known to be very efficient in transfer hydrogenation processes. Complexes 1, 2, and 4 incorporate sulfonate functionalities that make them insoluble in most organic solvents and very soluble in polar solvents such as MeOH and water. The solubility is reversed in the complex [IrI2(AcO)(bis-nBu-NHC)] (3) due to the absence of the sulfonate group, being very soluble in nonpolar solvents such us chloroform and dichloromethane. We recently described that the ruthenium complex 4 [Ru(η6-arene)(NHC)CO3] is highly active in the isomerization of allylic alcohols in water (TON 900) and could be recycled up to eight times without loss of activity.25 Complexes 1 and 2 are active in the reduction of carbon dioxide to potassium formate under transfer hydrogenation conditions with a maximum TON of 2700 in water as solvent.21 Complex 3 has been used for comparative reasons. It is a well-known transfer hydrogenation catalyst highly active in the reduction of ketones and is very stable toward air and moisture.24 In the catalytic transfer hydrogenation, unsaturated substrates are reduced using a hydrogen source that consists of an easily oxidizable molecule such us isopropyl alcohol. We have developed very active catalysts for this reaction based on rhodium,26 iridium, and ruthenium.20 Our initial approach using glycerol as hydrogen donor was carried out using acetophenone as substrate. A first set of experiments was done to optimize the reaction conditions. In a typical experiment acetophenone, base, catalyst, glycerol, and a cosolvent were heated to 80 120 °C for the appropriate time (Table 1). Under these reaction conditions acetophenone is partially reduced to 1-phenylethanol, thus validating our initial objective. Under the same reaction conditions, the catalysts [IrI2(AcO)(bis-NHC)] (1) and [IrI2(AcO)(bis-a-NHC)] (2; bis-a-NHC = bis abnormal NHC) redundantly afforded the best catalytic performances (entries 1 4). Catalyst 3 [Ru(η6-arene)(NHC)CO3] showed low activity, most probably due to its lower solubility, and the Ru-based catalyst 4 shows negligible activity (entries 5 8). The better performances of catalysts 1 and 2 compared to that of 3 may be attributed to their higher solubility in polar solvents, such as glycerol. Catalyst 2 is the most efficient due to the presence of the abnormally bound bis-NHC ligand, which has a strong electrondonor capacity and may favor the catalytic process. The same tendency was previously observed in the reduction of CO2 under transfer hydrogenation conditions.21 Longer reaction times of
Table 1. Optimization of Reaction Conditions in the Reduction of Acetophenonea
entry
cat.
solventb
T (°C)
t (h)
yield (%)b,c,d
1
1
2
1
glycerol
80
15
40
glycerol
120
24
3
45
2
glycerol
80
15
68
4
2
glycerol
120
24
69
5 6
3 3
glycerol glycerol
80 120
15 20
18 22
7
4
glycerol
80
15
2
8
4
glycerol
120
24
10
9
1
H2O
100
20
45
10
1
H2O
120
24
50
11
2
H2O
100
20
53
12
2
H2O
120
24
71
13 14
2 1
H2O CH3CN
120 120
48 20
89 12
15
2
CH3CN
120
20
16
16
3
toluene
80
20
3
17
1
DMSO
120
20
50
18
2
DMSO
120
20
85
a
Reactions were carried out with 0.5 mmol of acetophenone, and 0.5 mmol of KOH. b 0.8 mL of glycerol/0.8 mL of solvent. c 0.5 mmol of anisole was used as standard. d Yields determined by GC based on 1-phenylethanol produced.
14 24 h or a temperature increase from 80 to 120 °C does not produce a considerable improvement in the yield of 1-phenylethanol. We observed that the addition of a cosolvent highly influenced the catalytic outcomes (Table 1, entries 9 18). For instance, the addition of water slightly improve the catalytic outcomes (entries 9 13), while the addition of a moderately coordinating solvent such as MeCN practically stops the catalytic activity (entries 14 and 15). Using toluene as cosolvent. a two-phase system was produced. In this case only traces of 1-phenylethanol were observed. The best catalytic results were obtained when 5533
dx.doi.org/10.1021/om200796c |Organometallics 2011, 30, 5532–5536
Organometallics
ARTICLE
Table 2. Reduction of Acetophenone with 1,2-Propanediola
entry
cat.
solventb
t (h)
yield (%)c,d
1
1
1,2-propanediol
14
64
2
1
DMSO
14
52
3 4
2 2
1,2-propanediol DMSO
14 14
70 60
5
2
DMSO
20
80
Table 3. Reduction of Aromatic and Aliphatic Carbonyl Derivatives with Glycerola
a
Reactions carried out with 0.5 mmol of acetophenone and 0.5 mmol of KOH at 120 °C. b 0.8 mL of 1,2-propanediol/0.8 mL of solvent. c 0.5 mmol of anisole was used as standard. d Yields determined by GC based on 1-phenylethanol produced.
DMSO was used as a cosolvent, especially when the catalyst [IrI2 (AcO)(bis-a-NHC)] (2) was used. It is important to point out that our optimized results (Table 1, entries 3, 4, and 12) are significantly better than those previously reported by Crotti and co-workers, in which a series of [Ir(diene)(N N)X] (diene =1,5-hexadiene, N N = bipyridine, X = Cl, I) catalysts were used, and maximum conversions of acetophenone of 26% were achieved under similar reaction conditions.18 Because the selective deoxygenation of 1,2-propanediol to give n-propanol has been recently described,27 we thought that this might be a good candidate as the hydrogen source in transfer hydrogenation reactions. As observed in Table 2, 1,2-propanediol is an effective hydrogen donor in the reduction of acetophenone. The addition of a cosolvent did not significantly improve the yield to the final product. As was observed in the case of glycerol, the best catalytic outcomes were observed for the catalyst [IrI2(AcO)(bis-a-NHC)] (2). In order to check the versatility of our catalysts, we decided to study the substrate scope of 1 and 2 with other carbonyl derivatives. Table 3 shows the results of the reduction of several aromatic and aliphatic ketones and aldehydes (benzaldehyde), using a 2.5 mol % loading of catalyst in a 1:1 mixture of glycerol and DMSO at 120 °C. While complexes [IrI2(AcO)(bis-NHC)] (1) and 2 show similar activity in the reduction of 2-naphthyl methyl ketone (entries 1 4), the complex [IrI2(AcO)(bis-aNHC)] (2) was a significantly better catalyst for the reduction of benzophenone, for which a maximum yield of 91% (entry 7) was obtained in the production of the final alcohol. Aliphatic ketones were reduced to a much lesser extent (entries 8 13). Remarkably, the reduction of benzaldehyde to benzyl alcohol is quantitatively produced by catalyst 2 in only 1.5 h (entry 15), thus exemplifying the high activity of this catalyst toward the reduction of aromatic aldehydes. The activity of 2 toward this substrate is substantially higher than that shown by 1 (compare entries 14 and 15). The activity of 2 in the reduction of benzaldehyde in glycerol is a clear improvement over previous results reported by Wolfson and co-workers, where full conversion to benzyl alcohol was obtained under similar reaction conditions after 24 h, using [RuCl2(p-cymene)]2 as catalyst.19 As seen from the results shown in Table 4, both 1 and 2 were poorly efficient catalysts in the reduction of olefins and acetylenes. The reduction of phenylacetylene yields styrene, 30%
a
Reactions were carried out with 0.5 mmol of substrate and 0.5 mmol of KOH at 120 °C.
Table 4. Reduction of Olefins and Acetylenes Using Glycerola entry
substrate
cat.
product
1
phenylacetylene
1
styrene
T (°C) t (h) yield (%)b,c,d 120
14
2
2
120
14
12
3
1
120
14
18e
4 5
2 1
120 70
14 14
3e 17 25
6
120
14
7
2
120
14
9
8
1
70
14
16 35
9
styrene
1,5-cycloctadiene
1
ethylbenzene
30
120
14
10
1
120
20
38
11
2
120
3
55
1
cyclooctene
a
Reactions were carried out with 0.5 mmol of substrate and 0.5 mmol of KOH at 120 °C. b 0.8 mL of glycerol + 0.8 mL of DMSO. c 0.5 mmol of anisole was used as standard. d Yields determined by GC based on product formation. e 0.5 mmol of sodium acetate used instead of KOH.
being the maximum yield achieved by catalyst 1 (entries 1 5). The reduction of styrene to ethylbenzene is achieved with a maximum yield of 25%, again provided by the catalyst [IrI2(AcO)(bis-NHC)] (1) (entries 6 8). Internal olefins such as 1,5-cyclooctadiene can be transformed into cyclooctene in 55% yield when catalyst 2 [IrI2(AcO)(bis-a-NHC)] is used (entries 9 11). 5534
dx.doi.org/10.1021/om200796c |Organometallics 2011, 30, 5532–5536
Organometallics
ARTICLE
Table 5. Reduction of Benzylidene Ketone and Dibenzylidene Ketone with Glycerola
Reactions carried out with a 2.5 mol % catalyst loading, 0.5 mmol of substrate, KOH (0.5 mmol) at 120 °C in 1.6 mL of glycerol. b 0.5 mmol of anisole was used as standard. c Yields determined by GC based on product formation. d Reactions carried out at 100 °C. a
Allyl ketones (or α,β-insaturated ketones), can be considered as activated olefins. The selective hydrogenation of this type of substrate has attracted great attention because of its wide application in the synthesis of pharmaceutical compounds.28 30 Only a few catalysts have recently shown good chemoselectivities in the reduction of the double bonds of this type of enone,31 34 although this reaction has never been carried out with glycerol as the hydrogen source. Due to the catalytic properties shown by 1 and 2 in the reduction of olefins and aliphatic ketones, we thought that we could have a good chance to study their selectivity in substrates containing both types of unsaturated functionalities. In a recent study Albrecht and co-workers demonstrated that, in the hydrogenation of enones, the reduction of the olefinic double bond is kinetically preferred over the reduction of the ketone,35 thus implying that the saturated ketone may be the final product of the overall process if a suitable catalyst is used. Under these terms, a suitable catalyst for the selective reduction of the olefin in these substrates would not able to reduce the final saturated ketone. Table 5 shows the results of the reduction of benzylidene ketone and dibenzylidene ketone with glycerol using 1 and 2 (catalyst loading 2.5 mol %) at 120 °C. As can be seen from the data shown in the table, the reduction of benzylidene ketone is very selective in the production of the saturated ketone, and only traces of the fully hydrogenated compound (saturated alcohol) are detected. For the reduction of dibenzylidene ketone, again the reduction of the olefinic bonds is more favorable than the
reduction of the ketone, which is never observed. The reduction of only one of the CdC double bonds is preferred over the reduction of both olefins; therefore, the major product is always the monoolefinic ketone. This result is in contrast with the reduction of cinnamaldehyde (entries 8 and 9), for which the reduction of the alkenic double bond is followed by the rapid reduction of the carbonyl group, so that the major final product is the saturated alcohol. This reaction also illustrates the higher tendency of the two catalysts 1 and 2 to reduce aldehydes over ketones.
’ CONCLUSIONS A new approach for the use of glycerol as solvent and hydrogen donor has been developed. The introduction of sulfonate groups attached to the ligand promotes a higher solubility of the catalysts in glycerol, which combined with the high electrondonating character of the bis-NHC ligands makes 1 and 2 excellent catalysts for the reduction of several substrates using glycerol as hydrogen source. Both catalysts proved to be very active in the reduction of aromatic ketones and aldehydes and moderately active in the reduction of a selected set of olefins, acetylenes. Probably the most remarkable result is the selective reduction of the olefinic double bonds of α,β-unsaturated ketones. Our results indicate that glycerol may be considered as a viable hydrogen source for the reduction of a wide variety of 5535
dx.doi.org/10.1021/om200796c |Organometallics 2011, 30, 5532–5536
Organometallics organic substrates, if suitable active catalysts are found. Further research into the preparation of highly active hydrogen transfer catalysts that may validate the use of glycerol as a suitable hydrogen source are currently underway in our laboratory.
’ EXPERIMENTAL SECTION General Procedures. Compounds 1 4 of general formula [IrI2(AcO)(bis-NHC)] or [Ru(η6-arene)(NHC)CO3] were prepared according to literature procedures.21,24,25 All other reagents and solvents were used as received from commercial suppliers. Catalytic experiments were carried out under aerobic conditions and without solvent pretreatment. NMR spectra were recorded on Varian Innova 300 and 500 MHz spectrometers. Elemental analyses were carried out with an EA 1108 CHNS-O Carlo Erba analyzer. Electrospray mass spectra (ESI-MS) were recorded on a Micromass Quatro LC instrument, and nitrogen was employed as drying and nebulizing gas. Qualitative analyses of the catalytic reaction products were performed on a GCMS-QP2010 (Shimadzu) gas chromatograph/mass spectrometer equipped with a Teknokroma (TRB-5MS, 30 m 0.25 mm 0.25 μm) column. Chemical yields were determined with a GC-2010 gas chromatograph (Shimadzu) equipped with a FID and a Teknokroma (TRB-5MS, 30 m 0.25 mm 0.25 μm) column, using anisole as an internal standard and analytically pure samples or commercial products for the instrument calibration. Catalytic Studies. In a typical experiment of transfer hydrogenation using glycerol as hydrogen donor, a capped vessel containing a stirrer bar was charged with the substrate (0.5 mmol), potassium hydroxide (0.5 mmol), anisole as internal reference (0.5 mmol), and catalyst (2.5%) in 0.8 mL of glycerol. The solution was heated to 80 120 °C for the appropriate time. During the reaction monitoring, yields and conversions were determined by GC chromatography. Products and intermediates were characterized by GC/MS. Isolated products were characterized by 1H NMR and 13C NMR after column chromatography purification using n-hexanes/ethyl acetate mixtures.
’ AUTHOR INFORMATION Corresponding Author
*E-mail:
[email protected] (E.P.),
[email protected] (J.A.M.). Fax: (+34) 964728214.
ARTICLE
(8) Gu, Y. L.; Jerome, F. Green Chem. 2010, 12, 1127. (9) Pagliaro, M.; Ciriminna, R.; Kimura, H.; Rossi, M.; Della Pina, C. Angew. Chem., Int. Ed. 2007, 46, 4434. (10) Wolfson, A.; Litvak, G.; Dlugy, C.; Shotland, Y.; Tavor, D. Ind. Crop. Prod. 2009, 30, 78. (11) Armaroli, N.; Balzani, V. Angew. Chem., Int. Ed. 2007, 46, 52. (12) Chheda, J. N.; Huber, G. W.; Dumesic, J. A. Angew. Chem., Int. Ed. 2007, 46, 7164. (13) Corma, A.; Iborra, S.; Velty, A. Chem. Rev. 2007, 107, 2411. (14) Gu, Y.; Azzouzi, A.; Pouilloux, Y.; Jerome, F.; Barrault, J. Green Chem. 2008, 10, 164. (15) Soares, R. R.; Simonetti, D. A.; Dumesic, J. A. Angew. Chem., Int. Ed. 2006, 45, 3982. (16) Painter, R. M.; Pearson, D. M.; Waymouth, R. M. Angew. Chem., Int. Ed. 2010, 49, 9456. (17) Crabtree, R. H. Organometallics 2011, 30, 17. (18) Farnetti, E.; Kaspar, J.; Crotti, C. Green Chem. 2009, 11, 704. (19) Wolfson, A.; Dlugy, C.; Shotland, Y.; Tavor, D. Tetrahedron Lett. 2009, 50, 5951. (20) Corberan, R.; Mas-Marza, E.; Peris, E. Eur. J. Inorg. Chem. 2009, 1700. (21) Azua, A.; Sanz, S.; Peris, E. Chem. Eur. J. 2011, 17, 3963. (22) Sanz, S.; Azua, A.; Peris, E. Dalton Trans. 2010, 39, 6339. (23) Sanz, S.; Benitez, M.; Peris, E. Organometallics 2010, 29, 275. (24) Albrecht, M.; Miecznikowski, J. R.; Samuel, A.; Faller, J. W.; Crabtree, R. H. Organometallics 2002, 21, 3596. (25) Azua, A.; Sanz, S.; Peris, E. Organometallics 2010, 29, 3661. (26) Albrecht, M.; Crabtree, R. H.; Mata, J.; Peris, E. Chem. Commun. 2002, 32. (27) Schlaf, M.; Ghosh, P.; Fagan, P. J.; Hauptman, E.; Bullock, R. M. Adv. Synth. Catal. 2009, 351, 789. (28) Keinan, E.; Greenspoon, N. J. Am. Chem. Soc. 1986, 108, 7314. (29) Lee, H. Y.; An, M. Y. Tetrahedron Lett. 2003, 44, 2775. (30) Neri, G.; Mercadante, L.; Donato, A.; Visco, A. M.; Galvagno, S. Catal. Lett. 1994, 29, 379. (31) Bagal, D. B.; Qureshi, Z. S.; Dhake, K. P.; Khan, S. R.; Bhanage, B. M. Green Chem. 2011, 13, 1490. (32) Li, X. F.; Li, L. C.; Tang, Y. F.; Zhong, L.; Cun, L. F.; Zhu, J.; Liao, J.; Deng, J. G. J. Org. Chem. 2010, 75, 2981. (33) Himeda, Y.; Onozawa-Komatsuzaki, N.; Miyazawa, S.; Sugihara, H.; Hirose, T.; Kasuga, K. Chem. Eur. J. 2008, 14, 11076. (34) Shibahara, F.; Bower, J. F.; Krische, M. J. J. Am. Chem. Soc. 2008, 130, 14120. (35) Horn, S.; Gandolfi, C.; Albrecht, M. Eur. J. Inorg. Chem. 2011, 2863.
’ ACKNOWLEDGMENT We thank the Ministerio de Ciencia e Innovacion of Spain (CTQ2008-04460) and Bancaixa (P1.1B2010-02 and P1.1B2008-16) for financial support. We also thank the “Generalitat Valenciana” for a fellowship (A.A.). We are grateful to the Serveis Centrals d’Instrumentacio Científica (SCIC) of the Universitat Jaume I for providing us with spectroscopic facilities. ’ REFERENCES (1) Anastas, P. T.; Warner, J. Green Chemistry: Theory and Practice; Oxford University Press: Oxford, U.K., 1998. (2) Brieger, G.; Nestrick, T. J. Chem. Rev. 1974, 74, 567. (3) Dobereiner, G. E.; Crabtree, R. H. Chem. Rev. 2010, 110, 681. (4) Hamid, M.; Slatford, P. A.; Williams, J. M. J. Adv. Synth. Catal. 2007, 349, 1555. (5) Samec, J. S. M.; Backvall, J. E.; Andersson, P. G.; Brandt, P. Chem. Soc. Rev. 2006, 35, 237. (6) Zassinovich, G.; Mestroni, G.; Gladiali, S. Chem. Rev. 1992, 92, 1051. (7) Bakhrou, N.; Lamaty, F.; Martinez, J.; Colacino, E. Tetrahedron Lett. 2010, 51, 3935. 5536
dx.doi.org/10.1021/om200796c |Organometallics 2011, 30, 5532–5536
