Highly efficient transformation of levulinic acid into pyrrolidinones by iridium catalysed transfer hydrogenation

Article abstract of DOI:10.1039/c3cc41661e

Levulinic acid (LA) is transformed into pyrrolidinones via iridium-catalysed reductive amination using formic acid as the hydrogen source under aqueous conditions. The catalytic system is the most active and performs under the mildest conditions ever reported for the reductive amination of LA.

Full text of DOI:10.1039/c3cc41661e

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Highly efficient transformation of levulinic acid into
pyrrolidinones by iridium catalysed transfer
hydrogenation†
Cite this: Chem. Commun., 2013,
49, 5408
Received 5th March 2013,
Accepted 22nd April 2013
Yawen Wei,a Chao Wang,*a Xue Jiang,a Dong Xue,a Jia Lia and Jianliang Xiao*ab
DOI: 10.1039/c3cc41661e
www.rsc.org/chemcomm
Levulinic acid (LA) is transformed into pyrrolidinones via iridium-
catalysed reductive amination using formic acid as the hydrogen
source under aqueous conditions. The catalytic system is the most
active and performs under the mildest conditions ever reported for
the reductive amination of LA.
Over 90% of chemicals are derived from fossil resources, which are
limited and non-renewable. Renewable biomass could be an ideal
replacement for fossil resources to provide fuels and particularly,
chemicals.1 Indeed, selective transformation of biomass into value-
Scheme 1 Transformation of biomass-derived LA into fine chemicals.
added products has attracted much attention, but it is still a acid remains an unrealised challenge. Herein, we disclose the first
challenge for chemists. LA, which can be obtained by simple acidic transfer hydrogenation system for RA of LA to produce pyrrolidinones
dehydration of carbohydrates,2 has been identified as a platform using formic acid as the hydrogen source and structurally well-defined
chemical from biomass-derived products.1o For example, it has been homogeneous catalysts under mild conditions.
transformed into g-valerolactone (GVL)3 and pyrrolidinones,4 which
Recently, we discovered that cyclometalated iridium complexes are
can serve as platform molecules for various applications in fuel highly efficient catalysts for reductive amination of carbonyl groups
and fine chemical industries.1h,x,y,4a,b However, successful catalytic with formic acid as the hydrogen source.7 These iridicycle catalysts
systems for converting LA to pyrrolidinones by reductive amination are also effective for transfer hydrogenation and RA of carbonyls in
(RA) are few.4 The first examples were reported by Shilling,4f Crook4e water.8 As aliphatic ketones were suitable substrates and carboxylic
and their co-workers, and later by Manzer,4a,b,g,h Cao and co-workers, groups could be tolerated under the conditions, we reasoned that LA
in which heterogeneous hydrogenation was used.4c The first homo- might also be a viable substrate. Hence, we set out to investigate
geneous RA of LA was reported only recently by Fu and co-workers.4d whether or not the iridicycle complexes could be exploited for the RA
During the transformation of carbohydrates into LA, an equal molar of LA. Water was chosen as solvent not only because of its consider-
amount of formic acid is produced under aqueous conditions.1e Formic able environmental and economical benefits but also due to the fact
acid is a green reducing reagent and is frequently used in transfer that biomass-derived LA and formic acid are generated in water.9
hydrogenation reactions as the hydrogen source.5 Thus, it would be
The RA of LA with p-anisidine using pure formic acid as the
ideal to use formic acid as a hydrogen source in the reductive hydrogen source was initially carried out in neat water at 80 1C
transformation of LA in water (Scheme 1). Successful demonstration for 12 h with 1a as catalyst, which was shown to be the best RA
of this idea has been reported.1w,3a,b,d,h,j,4c,d,6 However, in these systems, catalyst in our previous work (Scheme 2).7 However, no reaction
either harsh conditions are required3j or the real reducing reagent is took place under these conditions.
actually hydrogen gas, which comes from in situ decomposition of
As solution pH is crucial for RA and aqueous transfer hydrogena-
formic acid.3d,h,4c,d Thus, true transfer hydrogenation of LA with formic tion reactions,10 we turned our attention to the effect of solution pH
on the RA by addition of HCOONa to adjust the solution pH. As is
a Key Laboratory of Applied Surface and Colloid Chemistry, Ministry of Education,
Department of Chemistry & Chemical Engineering, Shaanxi Normal University,
Xi’an, 710062, China. E-mail: c.wang@snnu.edu.cn
shown in Scheme S1 (ESI†), the pH indeed affects the reaction
dramatically. The reaction only took place at a narrow acidic pH
window (around 2–5). The best activity was observed at ca. pH 3.5,
with a 75% conversion in 1 h at 80 1C at an impressive substrate to
catalyst ratio (S/C) of 3000. To the best of our knowledge, this is the
highest S/C ever reported for homogeneous reduction of LA.
b Department of Chemistry, University of Liverpool, Liverpool, L69 7ZD, UK.
E-mail: j.xiao@liv.ac.uk; Fax: +44 (0)151-7943588
† Electronic supplementary information (ESI) available: Experimental details. See
DOI: 10.1039/c3cc41661e
c
5408 Chem. Commun., 2013, 49, 5408--5410
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Table 2 RA of LA with aliphatic aminesa
Entry
R
Product
Time (h)
Yieldb (%)
1
2
Benzyl
2j
2k
2l
2m
2n
2o
2p
2q
4
4
86
94
94
96
94
91
88
73
Scheme 2 Attempted RA of LA with p-anisidine catalysed by 1a. Reaction
conditions: LA (0.5 mmol), p-anisidine (0.6 mmol), 1a (0.0025 mmol), HCOOH
(2.5 mmol), water 3 mL, 80 1C, 12 h. PMP = para-methoxylphenyl.
4-OMe-benzyl
3-OMe-benzyl
2-OMe-benzyl
3,4-OMe-benzyl
4-F-benzyl
n-Octyl
n-Undecyl
3
12
24
24
12
12
12
4c
5
6
7d
8e
Aiming to find a more active catalyst, we next examined the
effect of different substituents para to the imino group on the
coordinating phenyl ring of the iridicycle catalysts at pH 3.5, as well
as the activities of some other metal catalysts. The results are
summarised in Table S1 (ESI†). For iridicycle catalysts, the
electron-donating methoxyl group benefits the reaction, while
a
b
The reaction conditions were the same as in Table 1. Isolated yield.
S/C of 200 was used. pH = 4.5, S/C of 500 was used. MeOH as
c
d
e
solvent, HCOOH–Et3N azeotrope as a hydrogen source, and S/C = 500.
The catalytic system also worked well for aliphatic amines
methyl or hydrogen atoms afforded a relatively low conversion (Table 2). Thus, 86% yield was achieved for benzylamine in 4 h at
(Table S1, entries 1–3, ESI†). All the electron-withdrawing an S/C of 2000. Varying the position of the methoxyl substituent on
groups gave similarly lower conversions compared with catalyst the phenyl ring of the benzyl group affects the reaction rate, with
1a (Table S1, entries 4–7, ESI†). The other catalysts showed increasing steric hindrance requiring longer reaction time or a lower
low or almost no activities even at higher catalyst loadings S/C ratio (Table 2, entries 2–4). For instance, whilst (4-methoxy-
(Table S1, entries 8–12, ESI†).
phenyl)methanamine afforded 94% yield in 4 h under the standard
Further optimisation of the reaction conditions for 1a, including conditions, the 2-methoxy-substituted analogue gave a similar yield
increasing the amount of amine, catalyst loading and concentration, but at a much reduced S/C ratio and a much longer time (Table 2,
led to a satisfactory isolated yield of 94% at a 3.2 mmol scale of LA entry 2 vs. 4). Long chain aliphatic amines are more difficult
(Table 1, entry 1). The substrate scope of reacting LA with different substrates. Thus, 1-octylamine needed an S/C of 500 and pH 4.5 to
amines was then examined with catalyst 1a at S/C = 2000 and reach a good yield in 12 h (Table 2, entry 7), presumably due to the
pH 3.5. As can be seen from Table 1, the RA afforded good yields for poor miscibility of the amine with water and catalyst. Not surprisingly,
a range of aromatic amines. In particular, those with relatively for 1-undecylamine, it was necessary not only to increase the catalyst
electron-donating substituents gave higher yields than ones with loading but also to use a more powerful solvent MeOH and the
electron-withdrawing substituents. Thus, over 90% of isolated yields HCOOH–Et3N azeotrope as the hydrogen source (Table 2, entry 8),
were obtained in 2 h for 4-OMe, 4-Me and 4-H substituted substrates presumably due to the insolubility of 1-undecylamine in water.
(Table 1, entries 1–3). However, for the halide and 4-OCF3 substi-
The generality of this catalytic system was further tested in the
tuents, a longer time of 4 h was required to reach reasonably good reaction of 5-oxohexanoic acid with various amines to produce six
yields (Table 1, entries 4–7). Installing a substituent at the 3-position membered heterocycles, which are another class of important
of aniline decreases the reaction rate, possibly due to steric hin- heterocycle compounds (Table 3). Interestingly, the highest yield
drance (Table 1, entries 8 and 9). This is further evidenced by the was obtained with the slightly electron-withdrawing 4-F substituted
poor reactivity of 2,5-dimethoxyl aniline (o10% conversion).
aniline (Table 3, entries 1–4), in contrast to the RA of LA (Table 1).
Again, 1-octylamine requires an S/C of 500 (Table 3, entry 5).
A proposed mechanism for the transformation of LA into
pyrrolidinones is presented in Scheme 3. The formation of iridium
hydride from iridicycle catalysts is now well established.11 Based on
Table 1 RA of LA with aromatic aminesa
Table 3 RA of 5-oxohexanoic acida
Entry
R
Product
Time (h)
Yieldb (%)
1
2
3
4
5
6
7
8c
9
4-OMe
4-CH3
4-H
4-F
4-Cl
2a
2b
2c
2d
2e
2f
2g
2h
2i
2
2
2
4
4
4
4
12
12
94
93
91
88
73
86
72
76
82
Entry
R
Product
Time (h)
Yieldb (%)
4-Br
1
2
3
4-OMe-phenyl
4-F-phenyl
4-OMe-benzyl
4-F-benzyl
n-Octyl
2r
2s
2t
2u
2v
12
12
24
12
12
84
97
82
81
86
4-OCF3
3-OMe
3,4-Me
4
5c
a
Reaction conditions: LA (3.2 mmol), p-anisidine (8.6 mmol), catalyst
a
b
(0.0016 mmol), aqueous HCOOH–HCOONa solution (14.5 M, 3 mL),
80 1C, 1 h. Isolated yield. S/C of 1000 was used.
The reaction conditions were the same as in Table 1. Isolated yield.
S/C = 500.
b
c
c
c
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Angew. Chem., Int. Ed., 2012, 51, 5802–5808; (o) P. Gallezot, Chem.
Soc. Rev., 2012, 41, 1538–1558; (p) J. C. Serrano-Ruiz, A. Pineda,
A. M. Balu, R. Luque, J. M. Campelo, A. A. Romero and J. M. Ramos-
´
Fernandez, Catal. Today, 2012, 195, 162–168; (q) F. W. Lichtenthaler
and S. Mondel, Pure Appl. Chem., 1997, 69, 1853–1866;
(r) G. W. Huber, J. N. Chheda, C. J. Barrett and J. A. Dumesic,
Science, 2005, 308, 1446–1450; (s) P. Gallezot, Catal. Today, 2007,
121, 76–91; (t) H. Zhao, J. E. Holladay, H. Brown and Z. C. Zhang,
Science, 2007, 316, 1597–1600; (u) G. Yong, Y. Zhang and J. Y. Ying,
Angew. Chem., Int. Ed., 2008, 47, 9345–9348; (v) J. B. Binder and
R. T. Raines, J. Am. Chem. Soc., 2009, 131, 1979–1985;
(w) T. Thananatthanachon and T. B. Rauchfuss, Angew. Chem., Int.
Ed., 2010, 49, 6616–6618; (x) J. Q. Bond, D. M. Alonso, D. Wang,
R. M. West and J. A. Dumesic, Science, 2010, 327, 1110–1114;
(y) J. P. Lange, R. Price, P. M. Ayoub, J. Louis, L. Petrus, L. Clarke
and H. Gosselink, Angew. Chem., Int. Ed., 2010, 49, 4479–4483.
2 (a) W. F. Stephen, US Pat., 5608105, 1997; (b) M. G. Viswas and
A. H. Milford, US Pat., 5859263, 1999; (c) A. F. William and
E. C. John, US Pat., 6054611, 2000.
3 (a) H. Heeres, R. Handana, D. Chunai, C. Borromeus Rasrendra,
B. Girisuta and H. Jan Heeres, Green Chem., 2009, 11, 1247–1255;
(b) L. Deng, Y. Zhao, J. Li, Y. Fu, B. Liao and Q. X. Guo,
ChemSusChem, 2010, 3, 1172–1175; (c) J. C. Serrano-Ruiz, D. Wang
and J. A. Dumesic, Green Chem., 2010, 12, 574–577; (d) X. L. Du,
Q. Y. Bi, Y. M. Liu, Y. Cao and K. N. Fan, ChemSusChem, 2011, 4,
1838–1843; (e) A. M. Hengne, N. S. Biradar and C. V. Rode, Catal.
Lett., 2012, 142, 779–787; ( f ) S. G. Wettstein, J. Q. Bond,
D. M. Alonso, H. N. Pham, A. K. Datye and J. A. Dumesic, Appl.
Scheme 3 Proposed mechanism for iridium-catalysed RA of LA.
our previous studies on RA,10e,11 we believe that an iminium
intermediate, generated in situ under the acidic conditions, is
reduced by an iridium hydride. To gain insight into the cyclisation
step, we isolated and characterised the RA product 3 (R = PMP). Full
conversion of 3 to 2a was observed under the standard conditions in
1 h, but without the iridium catalyst. In fact, when running the NMR
of 3 in CDCl3, spontaneous cyclisation happened (Scheme S2, ESI†),
indicating that the iridicycle catalyst is not required for this step.
In conclusion, the first and a highly efficient transfer hydro-
genation system for RA of LA has been developed, which uses
formic acid as the hydrogen source under aqueous conditions,
allowing transformation of LA into valuable pyrrolidinones
under mild conditions. The system is also applicable to
5-oxohexanoic acid to produce six membered heterocycles. This
mild and green system provides a practical means for converting
biomass-derived chemicals into value-added products.
´
Catal., B, 2012, 117–118, 321–329; (g) H. Mehdi, V. Fabos, R. Tuba,
´
A. Bodor, L. T. Mika and I. T. Horvath, Top. Catal., 2008, 48, 49–54;
(h) L. Deng, J. Li, D. M. Lai, Y. Fu and Q. X. Guo, Angew. Chem., Int.
Ed., 2009, 48, 6529–6532; (i) F. M. A. Geilen, B. Engendahl,
A. Harwardt, W. Marquardt, J. Klankermayer and W. Leitner, Angew.
Chem., Int. Ed., 2010, 49, 5510–5514; ( j) D. Kopetzki and
M. Antonietti, Green Chem., 2010, 12, 656–660; (k) F. M. A. Geilen,
¨
B. Engendahl, M. Holscher, J. Klankermayer and W. Leitner, J. Am.
Chem. Soc., 2011, 133, 14349–14358.
4 (a) L. E. Manzer, US Pat., 6743819, 2004; (b) L. E. Manzer, US Pat.,
6841520, 2005; (c) X. L. Du, L. He, S. Zhao, Y. M. Liu, Y. Cao, H. Y. He
and K. N. Fan, Angew. Chem., Int. Ed., 2011, 50, 7815–7819;
(d) Y. B. Huang, J. J. Dai, X. J. Deng, Y. C. Qu, Q. X. Guo and
Y. Fu, ChemSusChem, 2011, 4, 1578–1581; (e) L. R. Crook,
B. A. Jansen, K. E. Spencer and D. H. Watson, GB Pat., 1036694,
1996; ( f ) W. L. Shilling, US Pat., 3235562, 1996; (g) L. E. Manzer and
F. E. Herkes, US Pat., 2004192933, 2003; (h) L. E. Manzer, WO Pat.,
2004084633, 2004.
5 (a) M. Wills, M. Palmer, A. Smith, J. Kenny and T. Walsgrove,
Molecules, 2000, 5, 4–18; (b) S. Gladiali and E. Alberico, Chem. Soc.
Rev., 2006, 35, 226–236; (c) T. Ikariya and A. J. Blacker, Acc. Chem.
Res., 2007, 40, 1300–1308; (d) X. F. Wu and J. L. Xiao, Chem.
Commun., 2007, 2449–2466; (e) C. Wang, X. F. Wu and J. L. Xiao,
Chem.–Asian J., 2008, 3, 1750–1770.
We are grateful for the financial support of the National Science
Foundation of China (21103102), Program for Changjiang Scholars
and Innovative Research Team in University (IRT 1070), the Cheung
Kong Scholar Programme, the Fundamental Research Funds for the
Central Universities (GK200902009) and Distinguished Doctoral
Research Found from Shaanxi Normal University (S2011YB02).
6 T. Thananatthanachon and T. B. Rauchfuss, ChemSusChem, 2010, 3,
1139–1141.
7 C. Wang, A. Pettman, J. Bacsa and J. L. Xiao, Angew. Chem., Int. Ed.,
2010, 49, 7548–7552.
References
1 (a) J. R. Rostrup-Nielsen, Science, 2005, 308, 1421–1422; (b) G. W.
Huber, S. Iborra and A. Corma, Chem. Rev., 2006, 106, 4044–4098;
(c) M. Schlaf, Dalton Trans., 2006, 4645–4653; (d) J. N. Chheda,
G. W. Huber and J. A. Dumesic, Angew. Chem., Int. Ed., 2007, 46,
7164–7183; (e) A. Corma, S. Iborra and A. Velty, Chem. Rev., 2007,
107, 2411–2502; ( f ) L. D. Schmidt and P. J. Dauenhauer, Nature,
8 (a) Q. Lei, Y. W. Wei, D. Talwar, C. Wang, D. Xue and J. L. Xiao,
Chem.–Eur. J., 2013, 19, 4021–4029; (b) Y. W. Wei, D. Xue, Q. Lei,
C. Wang and J. L. Xiao, Green Chem., 2013, 15, 629–634.
9 (a) T. Dwars, E. Paetzold and G. Oehme, Angew. Chem., Int. Ed., 2005,
44, 7174–7199; (b) C. J. Li, Chem. Rev., 2005, 105, 3095–3166;
(c) A. Chanda and V. V. Fokin, Chem. Rev., 2009, 109, 725–748.
2007, 447, 914–915; (g) P. Gallezot, ChemSusChem, 2008, 1, 734–737; 10 (a) S. Ogo, T. Abura and Y. Watanabe, Organometallics, 2002, 21,
(h) J. J. Bozell, Science, 2010, 329, 522–523; (i) J. J. Bozell and
G. R. Petersen, Green Chem., 2010, 12, 539–554; ( j) U. Biermann,
2964–2969; (b) S. Ogo, K. Uehara, T. Abura and S. Fukuzumi, J. Am.
Chem. Soc., 2004, 126, 3020–3021; (c) X. F. Wu, X. G. Li, F. King and
J. L. Xiao, Angew. Chem., Int. Ed., 2005, 44, 3407–3411; (d) Y. Himeda,
N. Onozawa-Komatsuzaki, S. Miyazawa, H. Sugihara, T. Hirose and
K. Kasuga, Chem.–Eur. J., 2008, 14, 11076–11081; (e) C. Wang,
C. Q. Li, X. F. Wu, A. Pettman and J. L. Xiao, Angew. Chem., Int.
Ed., 2009, 48, 6524–6528.
¨
U. Bornscheuer, M. A. R. Meier, J. O. Metzger and H. J. Schafer,
Angew. Chem., Int. Ed., 2011, 50, 3854–3871; (k) D. J. Braden,
C. A. Henao, J. Heltzel, C. C. Maravelias and J. A. Dumesic, Green
Chem., 2011, 13, 1755–1765; (l) A. A. Rosatella, S. P. Simeonov,
R. F. M. Frade and C. A. M. Afonso, Green Chem., 2011, 13, 754–793;
(m) S. Van de Vyver, J. Geboers, P. A. Jacobs and B. F. Sels, 11 C. Wang, H. Y. T. Chen, J. Bacsa, C. R. A. Catlow and J. L. Xiao,
ChemCatChem, 2011, 3, 82–94; (n) S. Chikkali and S. Mecking,
Dalton Trans., 2013, 42, 935–940.
c
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