Communication pubs.acs.org/Organometallics
Acceptorless Dehydrogenative Coupling of Ethanol and Hydrogenation of Esters and Imines Denis Spasyuk and Dmitry G. Gusev* Department of Chemistry, Wilfrid Laurier University, 75 University Avenue West, Waterloo, Ontario N2L 3C5, Canada S Supporting Information *
ABSTRACT: This paper presents an outstanding air-stable ruthenium catalyst that has unprecedented efficiency (TON up to 17 000) for acceptorless dehydrogenative coupling of ethanol, yielding ethyl acetate and hydrogen gas, and for hydrogenation of esters and imines at 40 °C while using as low as 50 ppm [Ru].
A
II−V.4 These catalysts operate at high temperature; under normal pressure, they can dehydrogenate butanol (bp 118 °C) and the higher boiling alcohols. Two very recently reported compounds of Chart 1, the Takasago catalyst known as Ru-MACHO5a and the osmium dimer VI from our group, are the first ADC catalysts active for preparative conversion of ethanol to ethyl acetate under reflux.5 These complexes also proved to be very useful ester hydrogenation catalysts (the reverse reaction of Scheme 1).5a,b The Milstein complexes I and II similarly demonstrate dual functionality in ADC and ester hydrogenation, as expected on the basis of the principle of microscopic reversibility.3,4b We hypothesized that alcohol dehydrogenation, especially ADC of ethanol as a very challenging substrate, could be an excellent testing ground for the development of efficient catalysts for hydrogenation of compounds with polar CX bonds. The objective of this work was to screen a group of ruthenium and osmium complexes with the ligands of Chart 2 in ethanol dehydrogenationto further test the most efficient catalyst in ester and imine hydrogenation. The desired PNHP, NNHP, and NNHN complexes were prepared by conventional PPh3 or AsPh3 ligand exchange reactions of the readily available ruthenium and osmium precursors of Chart 2 (see the Supporting Information for details). The product complexes are shown in Chart 3; among these, compounds 2, 8, 9, and 11 are from our recently published research,5b,6 whereas 1, 3−7, 10, and 12 are new compounds. The structures of complexes 2, 4, 7−9, and 11 have been established by X-ray crystallography, and there appears to be a general preference for the mer configuration of the pincer-type XNHY ligands. The structure of complex 4 is presented in Figure 1.
cceptorless dehydrogenative coupling (ADC) of primary alcohols (Scheme 1) is an elegant catalytic approach to
Scheme 1. Alcohol Dehydrogenation and Reduction of Esters
symmetrical esters, usefully accompanied by formation of hydrogen gas.1 Some of the first homogeneous ADC catalysts were reported in 1985−1989 by Shvo and Cole-Hamilton (top three structures of Chart 1);2 however, major progress in this area is connected with the Milstein catalyst I, disclosed in 2005,3 and the related ligand-assisted pincer-type complexes Chart 1. Representative ADC Catalysts
Received: July 18, 2012 Published: July 24, 2012 © 2012 American Chemical Society
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Chart 2. Ligands and Precursors of This Work
Table 1. ADC of EtOH Catalyzed by Complexes 1−12
Chart 3. Complexes 1−12
a
cat.
[M],a mol %
amt of EtOH, mol
time, h
conversn, %
1 2 2 3 4 4 4 4 5 5 6 7 8 8 9 10 10 10 10 11 11 12 VI VI Ru-MACHO Ru-MACHO
0.05 0.05 0.01 0.05 0.05 0.01 0.01 0.005 0.05 0.01 0.05 0.05 0.05 0.01 0.05 0.05 0.05 0.01 0.01 0.05 0.01 0.05 0.05 0.01 0.01 0.005
0.1 0.1 0.2 0.1 0.1 0.2 0.2 0.2 0.1 0.2 0.1 0.1 0.1 0.2 0.1 0.1 0.1 0.2 0.2 0.1 0.2 0.1 0.1 0.2 0.2 0.2
16 16 24 16 16 24 24 40 16 24 16 16 16 24 16 16 16 24 24 16 24 16 16 24 24 40
17 57 47 0 95 89 91 85 41 42 12 30 23 35 2 39 40 11 13 27 35 20 45 66 47 42
Metal (Ru, Os) catalyst concentration.
−10 °C with the help of a circulating bath (Figure S1, Supporting Information). Products of all reactions were analyzed by 1H NMR spectroscopy and showed formation of ethyl acetate without any observable intermediates such as acetaldehyde and 1-ethoxyethanol (see Figure S2 in the Supporting Information for a representative 1H NMR spectrum).8 The first round of screening of Table 1, using 0.05 mol % catalyst loading, allowed the selection of the best candidates for further, more stringent testing: ruthenium (2, 4, 5) and osmium complexes (VI, 8, 10, 11). The known dehydrogenation catalyst Ru-MACHO was also included in this work for comparison. Further experiments with 0.01 mol % catalyst loadings unambiguously established the superior efficiency of RuCl2(PPh3)[NNHP-Ph] (4)the catalyst that consistently afforded high yields of ethyl acetate. Subjecting 4 to the ultimate efficiency and longevity test using a 0.005 mol % loading produced 17 000 turnovers in 40 h. Since 4 is air-stable, we repeated the dehydrogenation experiment with 0.05 mol % loading while assembling the reaction in air and using commercial anhydrous ethanol bottled and stored in air. This reaction gave an impressive 83% conversion to ethyl acetate, clearly suggesting that 4 is both a remarkably efficient and a highly robust catalyst. Osmium dimer VI proved to be the second most efficient species of this study, affording 6600 turnovers in 24 h, while using 0.01 mol % [Os]. Evaluating the above results, it is worth noting that the 95% conversion observed with 0.05 mol % 4 corresponds to 4.2 system wt % H2 efficiency. For comparison, 3.6 system wt % H2
Figure 1. ORTEP diagram of complex 4 with thermal ellipsoids at the 50% probability level. All hydrogen atoms except for NH are omitted for clarity.
We first address the results of ethanol dehydrogenation experiments summarized in Table 1. All reactions were prepared under argon and run under reflux, wherein for the most time the temperature was presumably 71.8 °Cthe boiling point of ethanol/ethyl acetate mixtures.7 Particular care was taken to prevent vapor losses (containing 70 wt % of ethyl acetate) with the stream of evolving H2 gas. A satisfactory approach proved to be conducting the catalytic dehydrogenation in Schlenk tubes fitted with 10 cm long fingers cooled to 5240
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the mechanism proposed by Milstein, the amido complexes are protonated by ROH, affording alkoxide intermediates which subsequently undergo β-hydrogen elimination and H2 loss to regenerate the catalyst.3 There is strong literature evidence to believe that catalytic ethanol dehydrogenation might be quite facile. For example, a rhodium catalyst of Grützmacher gave turnover frequencies as large as 750 000 h−1 for transfer dehydrogenation of ethanol with ketones, at room temperature.10 Therefore, we believe that the likely rate-limiting step of the acceptorless process is H2 extrusion from the hydrogenated form of the catalyst: i.e. the step of catalyst regeneration. This implies that a successful ADC catalyst should not form stable hydride intermediates. In practical terms, creating a moderately crowded ligand environment around a metal center that is less electron-rich, such as in 4, is a possible direction to explore in further ADC catalyst development. Complex 4 was further tested in hydrogenation of compounds with polar CX bonds of Scheme 3. There has
is the best result achieved in dehydrogenation of methylammonia−borane,9a whereas the best catalyst for ammonia− borane dehydrogenation afforded a total of 4.6 system wt % H2 (5700 turnovers) over three runs.9b While no attempt is made here to review the merits of different methods for H2 production and storage, the fact that bioethanol is widely available and ethyl acetate is a valuable solvent that can be readily hydrogenated back to ethanol (vide infra) makes ADC of ethanol an overall highly useful process. It is appropriate to look more closely at the data of Table 1. In the course of this work we made a surprising observation of ethanol dehydrogenation accelerating with lower catalyst loadings for some catalysts of Chart 3. For example, the turnover frequencies (TOF, h−1) changed as follows for 4 in four independent experiments: 135 (0.05 mol %, 4 h), 117 (0.05 mol %, 16 h), 375 (0.01 mol %, 24 h), 567 (0.005 mol %, 24 h). One notices, for instance, that reducing the concentration of 4 five times, from 0.05 to 0.01 mol %, resulted in a 3.2-fold increase of the TOF (from 117 to 375 h−1). Therefore, only a marginally longer reaction time (24 vs 16 h) was necessary in the latter experiment to reach a nearly quantitative conversion, despite the significantly lower catalyst loading. Another striking example of this behavior is the 5-fold increase in TOF (275 vs 56) for the osmium dimer VI upon reducing the catalyst loading from 0.05 to 0.01 mol %. Consequently, the less concentrated catalyst solution gave a greater conversion after 24 h (66%) in comparison with the conversion (45%) achieved in the 5 times more concentrated, 16 h long reaction. Relevant observations are also found in the literature, although they have not been noted before. One concerns the catalyst prepared in situ from PNHP-iPr and RuH2(CO)(PPh3)3 by Beller and co-workers, who observed a 4.4 increase in TOF for dehydrogenation of 2-propanol when using 4 vs 32 ppm [Ru].4f This catalyst system gave a large TOF = 690 h−1 for dehydrogenation of ethanol with 3.1 ppm [Ru], although it achieved only a 1.3% conversion after 6 h. Similarly, a relatively large TOF = 103 h−1 (2.9% conversion in 19 h) was observed by Cole-Hamilton in ethanol dehydrogenation at 150 °C, using a dilute (0.0015 mol %) solution of RuH2(N2)(PPh3)3.2b,c Reasons for higher catalyst activity with low catalyst loadings are not clear, although some associative/ dissociative processes seem to be implicated. Particularly, low concentrations of VI might give increased catalytic efficiency by favoring dissociation of the dimer to give the mononuclear 16electron amido species OsH(CO)[N(C2H4PiPr2)2]. Reversible formation of dimers analogous to VI is possible under basic conditions in solutions of other complexes of Chart 3. Scheme 2 compares the NNP ligand of 4 and related catalysts of this work with the classical Milstein ligand of catalysts I−III. Both systems possess M(II), a phosphorus donor, a hemilabile group (Py vs NEt2), and a central nitrogen donor group. Under catalytic conditions, both systems should produce the M(II) amido species of Scheme 2.3 According to
Scheme 3. Hydrogenation with 4a
a
Conditions: p(H2) = 50 bar, T = 40 °C.
been much recent interest in the catalytic hydrogenation of esters.5,11−14 Among the most successful in the field is the Firmenich catalyst, RuCl2(H2NC2H4PPh2)2, which is particularly efficient for reduction of benzoates and alkanoates, using 0.05 mol % catalyst under p(H2) = 50 bar, at 100 °C.12a Another useful catalyst, Ru-MACHO, has been recently disclosed by Takasago chemists.5a,13c This ruthenium complex is less efficient than the Firmenich catalyst toward unfunctionalized benzoates and alkanoates by requiring greater catalyst loadings (0.1−1 mol %) and a longer reaction time (16 h). However, Ru-MACHO is an excellent catalyst at 0.05 mol % loading for hydrogenation of methyl lactate and methyl menthoxyacetate, giving high yields of (R)-1,2-propanediol and 2-(l-menthoxy)ethanol, respectively.5a Although the performance of the “state of the art” industrial catalysts is impressive, further improvements are highly desirable to (a)
Scheme 2. NNP Ligand Systems
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Paneque-Sosa, M.; Lopez-Poveda, M. J. Chem. Soc., Dalton Trans. 1989, 489−495. (3) Zhang, J.; Leitus, G.; Ben-David, Y.; Milstein, D. J. Am. Chem. Soc. 2005, 127, 10840−10841. (4) (a) Zhang, J.; Gandelman, M.; Shimon, L. J. W.; Milstein, D. Dalton Trans. 2007, 107−113. (b) Zhang, J.; Balaraman, E.; Leitus, G.; Milstein, D. Organometallics 2011, 30, 5716−5724. (c) Gunanathan, C.; Shimon, L. J. W.; Milstein, D. J. Am. Chem. Soc. 2009, 131, 3146− 3147. (d) del Pozo, C.; Iglesias, M.; Sánchez, F. Organometallics 2011, 30, 2180−2188. (e) Musa, S.; Shaposhnikov, I.; Cohen, S.; Gelman, D. Angew. Chem., Int. Ed. 2011, 50, 3533−3537. (f) Nielsen, M.; Kammer, A.; Cozzula, D.; Junge, H.; Gladiali, S.; Beller, M. Angew. Chem., Int. Ed. 2011, 50, 9593−9597. (5) (a) Kuriyama, W.; Matsumoto, T.; Ogata, O.; Ino, Y.; Aoki, K.; Tanaka, S.; Ishida, K.; Kobayashi, T.; Sayo, N.; Saito, T. Org. Process Res. Dev. 2012, 16, 166 −171. (b) Spasyuk, D.; Smith, S.; Gusev, D. G. Angew. Chem., Int. Ed. 2012, 51, 2772−2775. (c) Nielsen, M.; Junge, H.; Kammer, A.; Beller, M. Angew. Chem., Int. Ed. 2012, 51, 5711− 5713. (6) (a) Bertoli, M.; Choualeb, A.; Gusev, D. G.; Lough, A. J.; Major, Q.; Moore, B. Dalton Trans. 2011, 40, 8941 −8949. (b) Bertoli, M.; Choualeb, A.; Lough, A. J.; Moore, B.; Spasyuk, D.; Gusev, D. G. Organometallics 2011, 30, 3479 −3482. (7) Zhang, D. L.; Deng, Y. F.; Li, C. B.; Chen, J. Ind. Eng. Chem. Res. 2008, 47, 1995−2001. (8) An equilibrium between ethanol, acetaldehyde, and 1ethoxyethanol is slow on the NMR time scale. We estimated K = 0.6 ± 0.05 (ΔG = −0.3 kcal/mol) at room temperature, using a sample of 63 mg of acetaldehyde in 727 mg of ethanol. (9) (a) Blaquiere, N.; Diallo-Garcia, S.; Gorelsky, S. I.; Black, D. A.; Fagnou, K. J. Am. Chem. Soc. 2008, 130, 14034−14035. (b) Conley, B. L.; Guess, D.; Williams, T. J. J. Am. Chem. Soc. 2011, 133, 14212− 14215. (10) Zweifel, T.; Naubron, J.-V.; Büttner, T.; Ott, T.; Grützmacher, H. Angew. Chem., Int. Ed. 2008, 47, 3245−3249. (11) (a) Zhang, J.; Leitus, G.; Ben-David, Y.; Milstein, D. Angew. Chem., Int. Ed. 2006, 45, 1113−1115. (b) Balaraman, E.; Gunanathan, C.; Zhang, J.; Shimon, L. J. W.; Milstein, D. Nature Chem. 2011, 3, 609 −614. (c) Fogler, E.; Balaraman, E.; Ben-David, Y.; Leitus, G.; Shimon, L. J. W.; Milstein, D. Organometallics 2011, 30, 3826−3833. (d) Gunanathan, C.; Milstein, D. Acc. Chem. Res. 2011, 44, 588−602. (12) (a) Saudan, L. A.; Saudan, C. M.; Debieux, C.; Wyss, P. Angew. Chem., Int. Ed. 2007, 46, 7473−7476. (b) Saudan, L.; Dupau, P.; Riedhauser, J.-J.; Wyss, P. (Firmenich SA) WO 2006106483, 2006. (c) Saudan, L.; Dupau, P.; Riedhauser, J.-J.; Wyss, P. (Firmenich SA) US 2010280273, 2010. (13) (a) Kuriyama, W.; Ino, Y.; Ogata, O.; Sayo, N.; Saitoa, T. Adv. Synth. Catal. 2010, 352, 92−96. (b) Ino, Y.; Kuriyama, W.; Ogata, O.; Matsumoto, T. Top. Catal. 2010, 53, 1019−1024. (c) Kuriyama, W.; Matsumoto, T.; Ino, Y.; Ogata, O.; Saeki N. (Takasago Int. Co.) WO 2011048727, 2011. (14) (a) Sun, Y.; Koehler, C.; Tan, R.; Annibale, V. T.; Song, D. Chem. Commun. 2011, 47, 8349−8351. (b) Stempfle, F.; Quinzler, D.; Heckler, I.; Mecking, S. Macromolecules 2011, 44, 4159−4166. (c) Hanton, M. J.; Tin, S.; Boardman, B. J.; Miller, P. J. Mol. Catal. A 2011, 346, 70−78. (d) O, W. W. N.; Lough, A. J.; Morris, R. H. Chem. Commun. 2010, 46, 8240−8242. (e) Touge, T.; Hakamata, T.; Nara, H.; Kobayashi, T; Sayo, N.; Saito, T.; Kayaki, Y.; Ikariya, T. J. Am. Chem. Soc. 2011, 133, 14960−14963. (f) Ito, M.; Ootsuka, T.; Watari, R.; Shiibashi, A.; Himizu, A.; Ikariya, T. J. Am. Chem. Soc. 2011, 133, 4240−4242. (g) Takebayashi, S.; Bergens, S. H. Organometallics 2009, 28, 2349−2351. (h) Teunissen, H.; Elsevier, C. J. Chem. Commun. 1988, 1367−1368.
reduce the reaction temperature, preferably to as low as 20−40 °C, and (b) reduce the catalyst loading, preferably to less than 0.05 mol %. Guided by these considerations, we tested complex 4 in the hydrogenation of several benchmark substrates of Scheme 3, all at 40 °C. To our satisfaction, the results of the hydrogenation experiments of Scheme 3 fully support the expectation behind this work that an outstanding ethanol dehydrogenation catalyst might also have superior efficiency in hydrogenation of substrates with polar CX bonds. Catalyst 4 is particularly successful for the reduction of alkanoates, giving an unprecedented 20 000 turnovers in 16 h for ethyl acetate and 18 800 turnovers in 18 h for methyl hexanoate, both at 40 °C. The best TON reported to date for this type of substrate was 7100 in 18 h at 100 °C for methyl hexanoate, using a ruthenium dimer analogous to VI, {RuH(CO)[N(C2H4PiPr2)2]}2.5b For another comparison, the best Firmenich catalyst, RuCl2(H2NC2H4PPh2)2, would theoretically need 27 h to produce 18 600 turnovers for methyl octanoate at 100 °C, on the basis of the reported TOF = 688 h−1 over a 2.5 h reaction time.12c Complex 4 is also a competent imine hydrogenation catalyst, giving a particularly high TON = 50 000 for Nbenzylaniline. In conclusion, this paper presents the air-stable catalyst RuCl2(PPh3)[PyCH2NHC2H4PPh2] (4), which can be prepared on a large scale from inexpensive and readily available starting materials, following the methods developed in this work. Complex 4 is an outstanding versatile catalyst for alcohol dehydrogenation and for reduction of compounds with polar CX bonds. Catalyst 4 has unprecedented efficiency for acceptorless dehydrogenative coupling of ethanol under reflux (TON up to 17 000) and for hydrogenation of esters and imines while using as low as 50 ppm [Ru] under mild conditions.
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ASSOCIATED CONTENT
S Supporting Information *
Text, figures, tables, and a CIF file giving experimental and characterization details and crystallographic data. This material is available free of charge via the Internet at http://pubs.acs.org.
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AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected],
[email protected]. Author Contributions
The manuscript was written through contributions of both authors. Both authors have given approval to the final version of the manuscript. Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS We are grateful to the NSERC of Canada, the Ontario Government, and Wilfrid Laurier University for financial support.
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REFERENCES
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