Zwitterionic phosphine ligand with a lysine tag and its application for hydroformylation of 1-octene in ionic liquid/MeOH system

Article abstract of DOI:10.1007/s10562-013-0984-8

Here we report a highly active and selective hydroformylation of 1-octene in ionic liquid (IL)/MeOH system based on a zwitterionic phosphine ligand bearing a lysine moiety (L(NH₂)COOH). The Rh-catalyst grafted lysine in the form of ammonium salt ([Rh-L(NH₃ ⁺)COOH]Tf ₂N) was successfully immobilized in the IL [bmim]Tf₂N and recycled for seventeen times without significant loss of activity, selectivity and Rh catalysts. This study has provided a novel strategy for efficient separation and recycling of Rh catalysts.

Full text of DOI:10.1007/s10562-013-0984-8

Catal Lett (2013) 143:839–843
DOI 10.1007/s10562-013-0984-8
Zwitterionic Phosphine Ligand with a Lysine Tag and its
Application for Hydroformylation of 1-Octene in Ionic Liquid/
MeOH System
•
Xin Jin Kun Zhao Fangfang Kong
•
•
•
Feifei Cui Daoxing Yang
Received: 3 January 2013 / Accepted: 24 February 2013 / Published online: 8 March 2013
Ó Springer Science+Business Media New York 2013
Abstract Here we report a highly active and selective
hydroformylation of 1-octene in ionic liquid (IL)/MeOH
system based on a zwitterionic phosphine ligand bearing
a lysine moiety (L(NH2)COOH). The Rh-catalyst grafted
lysine in the form of ammonium salt ([Rh-L(NH3?)COOH]
Tf2N) was successfully immobilized in the IL [bmim]Tf2N
and recycled for seventeen times without significant loss
of activity, selectivity and Rh catalysts. This study has
provided a novel strategy for efficient separation and
recycling of Rh catalysts.
suitable for higher alkenes (C6–C14 olefins) due to the poor
solubility of C6–C14 olefins in water.
In recent years the ionic liquid (IL) biphasic catalytic
system has attracted intense attention in this field [3] due to
its unique physical properties that can be fine-tuned to
realize a two-phase catalytic system, i.d. an ILs phase
dissolving the catalyst and an organic phase containing the
reagents or products [4–6]. For example, some early
attempts were made to carry out hydroformylation in ILs
using water-soluble phosphine ligands (e.g. TPPTS: tri-
phenylphosphine-3, 30, 300-trisulfonic acid trisodium salt),
in which the low solubility of water-soluble phosphine
ligands in ILs resulted in the low reaction rate [7–12].
Alternatively, many novel functionalized phosphines
ligands have been developed using ionic tag concept
[8, 13–29]. Following this strategy, the phosphine ligands
were immobilized to ionic groups with high similarity to
the IL cations, e.g. imidazolium, pyridinium and guanidi-
nium, etc., so as to increase the solubility and affinity of the
catalysts to ILs. Nevertheless, only a few systems have
demonstrated high activity, high selectivity and good
retention of the catalyst in hydroformylation of higher
olefins [17, 19].
Keywords Amino acid ꢀ Catalyst recycling ꢀ
Hydroformylation ꢀ Ionic liquid
1 Introduction
Over the last two decades, to effectively recycle the
expensive rhodium catalysts from hydroformylation prod-
ucts has remained a continuing research focus [1]. In
industry, aqueous biphasic catalytic systems have been used
for effective catalyst separation and the hydroformylation
of light alkenes (C2–C5 olefins) [2], but this process is not
Recently, we have reported a series of amino acid-tagged
chiral pyrrolidinodiphosphine ligands and their use in
Rh-catalysed asymmetric hydrogenation of methyl (Z)-2-
acetamidocinnamate in [bmim]BF4/MeOH system. Intro-
ducing amino acid tags into ligand backbone have been
proven to effectively improve the immobilization and
reusability of the Rh-catalysts in imidazole-based ILs [30].
Therefore, based on the ionic tag concept, we here have
synthesized a novel lysine-tagged triphenylphosphine
ligand (Scheme 1, 1) and evaluated the catalytic recycling
and reuse of Rh-catalyst in hydroformylation of 1-octene
in [bmim]Tf2N/MeOH system.
X. Jin (&) ꢀ K. Zhao ꢀ F. Kong ꢀ F. Cui ꢀ D. Yang
College of Chemical Engineering, Qingdao University of
Science and Technology, 53 Zhengzhou Road,
Qingdao 266042, China
e-mail: jinx1971@163.com
X. Jin
Key Laboratory of Oil & Gas Fine Chemicals of Ministry of
Education, Xinjiang University, Wulumuqi 830046, China
123

840
X. Jin et al.
O
CO2H
2.3 General Procedure for Acid-Catalyzed Two-Phase
Hydrolysis of Dimethylacetals
N
N
N
H
NH2
Tf2N-
Ph2P
3 mL n-heptane solution containing the preceding hydro-
formylation products was added to 3 mL aqueous solution
of dodecylbenzenesulfonic acid (62 mg). The reaction
system was stirred for 2 h at 80 °C under an argon atmo-
sphere. After cooling the reaction mixture was allowed to
stand for 1 h. Then the upper phase was removed for GC
analysis. The result showed that about 90 % of dimethy-
lacetals were hydrolyzed to aldehyde.
[bmim]Tf2N
1
Scheme 1 Structure of zwitterionic phosphine ligand with a lysine
tag and imidazole-based IL used in this study
2 Experimental
2.1 General Procedures
2.4 Synthesis and Characterization of Ligand 3
Starting material 2 was obtained as described previously
[31]. The reagents and IL [bmim]Tf2N (\0.2 wt %
water and \150 ppm halide) were purchased commer-
cially. The standard Schlenk techniques were used for
the synthesis of 1 and hydroformylation. The solvents
and reagents were used after rigorous deoxygenation.
The hydroformylation was carried out in a home-made
60 ml stainless steel autoclave. The conversions and
selectivity were analyzed by GC with an OV-101 cap-
illary column. GC/MS were determined on a HP5890-
HP5989A apparatus using a DB-5 capillary column.
NMR spectra were recorded on Bruker 500 MB instru-
ment. High-resolution mass spectra (HRMS) were
obtained by using a Q-Tof Ultima Global mass spec-
trometry. ICP-AES data were detected on an IRIS
Istrepid II XSP apparatus.
A Schlenk flask was charged with 2 (0.70 g, 2.28 mmol),
DIC (0.29 g, 2.29 mmol), HOBt (0.31 g, 2.29 mmol) and
30 mL degassed CH2Cl2 under an argon atmosphere. Next
the H-L-Lys(Boc)-OtBu (0.69 g, 2.28 mmol) in 20 mL
CH2Cl2 was added via a syringe and the reaction mixture
was stirred for 4 h at room temperature. The reaction was
monitored by TLC analysis to completion. Then, the sol-
vent was partially removed under reduced pressure, and the
resulting white precipitate was filtered off. The filtrate was
concentrated and the residue was purified by column
chromatography (degassed SiO2, petroleum ether/EtOAc)
under argon to afford the pure product 3 as white solid;
yield: 1.20 g (89 %). 1H NMR (500.0 MHz, CDCl3):
d = 7.29–7.77 (m, 14H, Ph-H), 6.77 (d, J = 7.5 Hz, 1H,
Ha), 4.67 (m, 1H, Hb), 4.58 (m, 1H, Hg), 3.11 (m, 2H, Hf),
1.95 (m, 1H, Hc), 1.77 (m, 1H, Hc’), 1.52 (m, 2H, He), 1.48
(s, 9H, OtBu or Boc), 1.37–1.45 (m, 11H, Hd, OtBu or
Boc); 13C NMR (125.7 MHz, CDCl3): d = 171.71, 166.69,
156.06, 142.30, 136.34, 134.10, 133.84, 133.53, 129.03,
128.77, 128.62, 126.95, 82.36, 79.03, 52.90, 40.13, 32.41,
29.63, 28.38, 28.03, 22.33; 31P NMR (202.4 MHz, CDCl3):
d = -4.70; HR-MS (Q-Tof MS, ES?): m/z = 591.3015,
calcd. for C34H44N2O5P [M ? H]?: 591.2988.
2.2 General Procedure for Rh-Catalyzed
Hydroformylation of 1-Octene in [bmim]Tf2N/
MeOH and for Catalyst Recycling
A 60-mL autoclave was charged with Rh(acac)(CO)2
(1.0 mg, 3.87 9 10-3 mmol), 10 equivalents of ligand 1
(3.87 9 10-2 mmol), 1 g [bmim]Tf2N and 3 mL MeOH
containing 10 equivalents of Tf2NH (3.87 9 10-2 mmol)
under an argon atmosphere. Subsequently, 1-octene
(0.6 mL, 3.82 mmol) and internal standard (cyclohexane,
0.1 mL) were added via a syringe. The reactor was
pressurized with syngas to 2.0 MPa, followed by heating
the reaction system to 80 °C while stirring. After 2 h the
stirring was stopped and the autoclave was rapidly cooled
on ice. Upon releasing the gases, the reaction mixture
was transferred to a Schlenk tube under an argon atmo-
sphere and analysed by GC. Then the MeOH was
removed under reduced pressure. The n-heptane (3 mL)
was added to extract the hydroformylation products and
remove produced water by azeotrope. The new 1-octene
and MeOH were added into [bmim]Tf2N for next catalyst
recycling.
O
O
d
f
O
O
H
H H
H
N
N
O
H
b
H
H
H
H
H
a
H
g
e
c, c'
P
2.5 Synthesis and Characterization of Ligand 1
A Schlenk flask was charged with 3 (1.04 g, 1.76 mmol),
Et3SiH (0.51 g, 4.38 mmol) and 10 mL trifluoroacetic acid
123

Zwitterionic Phosphine Ligand with a Lysine Tag
841
under an argon atmosphere, and the solution was stirred for
10 h at 0 °C. Then, trifluoroacetic acid was evaporated
under reduced pressure to give a trifluoroacetic acid salt of
1. The salt was added into 5 mL MeOH and the obtained
solution was neutralized to pH 6–7 with an aqueous solution
of saturated Na2CO3. The solution was submitted to column
chromatography under argon to give the pure product 1 as
7 % isomerized octenes as the main byproducts and a
normal n/i ratio around 2.7. Increasing the phosphine/Rh
ratio from 10:1 to 30:1, no significant increase in n/i ratio
was observed. In addition, ICP analysis exhibited that
almost 24 % of the total rhodium charged leached from the
IL into the product phase.
Owing to the weak charge, the ligand 1 cannot effi-
ciently immobilize Rh complex in IL, which dominantly
contributes to the rhodium leaching. Therefore, the strong
acid Tf2NH with the ligands 1 were concomitantly intro-
duced into [bmim]Tf2N to form the ammonium salt
(1ꢀTf2NH, Scheme 3) of 1 that has the same anion moiety
as that of used [bmim]Tf2N, which is designed to improve
the affinity of Rh-catalyst towards [bmim]Tf2N.
1
white solid; yield: 0.44 g (60 %). H NMR (500.0 MHz,
CD3OD and CF3COOD): d = 7.27–7.82 (m, 14H, Ph-H),
4.63 (dd, J = 9.6, 4.8 Hz, 1H, Ha), 2.93 (m, 2H, He), 2.04
(m, 1H, Hb), 1.88 (m, 1H, Hb’), 1.72 (m, 2H, Hd), 1.56 (m,
2H, Hc); 13C NMR (125.7 MHz, CD3OD and CF3COOD):
d = 175.35, 170.13, 144.08, 137.76, 135.27, 134.98,
134.43, 130.32, 129.83, 128.50, 53.96, 40.59, 31.99, 28.06,
24.14; 31P NMR (202.4 MHz, CD3OD and CF3COOD):
d = -4.88; HR-MS (Q-Tof MS, ES?): m/z = 435.1845,
calcd. for C25H28N2O3P [M ? H]?: 435.1838.
Table 1 (entry 2) shows that the addition of Tf2NH into
[bmim]Tf2N has no obvious effect on catalytic activity and
selectivity, but the Rh loss has dropped from 24 to 2 %,
which indicates that the formation of ammonium salt
1ꢀTf2NH can effectively enhance the immobilization the
Rh-catalysts in [bmim]Tf2N.
c
COOH
e
H H
O
H
H
N
H
NH2
In the following two experiments, we investigated the
homogeneous hydroformylation of 1-octene in [bmim]Tf2N/
MeOH system (Table 1, entries 3, 4). For ligand 1 (Table 1,
entry 3), an obvious increase in aldehyde selectivity was
observed due to better mass transfer and diffusion in a
homogeneous system made of [bmim]Tf2N and MeOH, but
the Rh loss still remained at a high level (21 %). It is note-
worthy that about 2 % dimethylacetals were formed under
hydroformylation condition. Nevertheless, a significant
improvement (Table 1, entry 4), substituting 1 with
1ꢀTf2NH, efficiently reduced Rh leaching to a lower level
(only 0.4 %). In particular, the GC/MS analysis indicates
that under this system the acetals selectivity increased to
88 %. Although Rh-catalyzed acetalization has been repor-
ted [32], we think that the ammonium salt 1ꢀTf2NH as a
Brønsted acid is the catalyst for the formation of the acetals
(compare entries 3 and 4 in Table 1).
H
H
H
H
H
d
a
b, b'
P
3 Results and Discussion
The lysine-tagged triphenylphosphine ligand 1 can be
easily synthesized via a two-step synthetic route from
starting material 2 as described previously [31]. The pro-
tected lysine moiety was grafted to the carboxyl group of 2
by a DIC-promoted amidation with H-L-Lys(Boc)-OtBu,
which gives the monophosphines 3. Next, both Boc and
tBu were removed in the presence of trifluoroacetic acid
and triethylsilane to obtain 1 (Scheme 2).
Finally, we evaluated the recycling of the Rh-catalyst
in hydroformylation of 1-octene (Table 2). The hydro-
formylation was performed in homogeneous 1ꢀTf2NH-
[bmim]Tf2N/MeOH system, in which the best conver-
sion, selectivity (aldehydes plus acetals) and the lowest
Rh leaching were obtained. Upon completion of reaction,
the methanol was removed by reduced pressure and the
n-heptane was added to extract the hydroformylation
products and remove produced water by azeotrope.
We first evaluated the two-phase hydroformylation of
1-octene with Rh(acac)(CO)2 precursor and ligands 1 in
[bmim]Tf2N that is one of the most widely used imidazole-
based IL (Table 1, entry 1). The hydroformylation was
carried out at 80 °C under CO/H2 (1:1) pressure of
2.0 MPa. The ligand 1 offered a high conversion of ~98 %.
The selectivity for the aldehyde (normal aldehyde and
2-methyl aldehyde) achieved 92 %, accompanied by about
CO2tBu
CO2H
O
O
CO2H
DIC, HOBt/CH2Cl2
CF3COOH, Et3SiH
NHBoc
NH2
N
H
N
H
H-L-Lys(Boc)-OtBu
Ph2P
Ph2P
Ph2P
2
3
1
Scheme 2 Synthesis of lysine functionalized phosphine ligand 1
123

842
X. Jin et al.
Table 1 Rh-catalyzed hydroformylation of 1-octene in [bmim]Tf2N or [bmim]Tf2N/MeOH with ligand 1 or 1ꢀTf2NH
Entry
Medium
Ligand
Conver.a (%)
Sbald (%)
Scace (%)
Sdiso (%)
n/ie
Rh leachingf (%)
1
2
3
4
[bmim]Tf2N
1
98
97
98
98
92
90
97
10
–
7
8
1
1
2.7
2.9
2.8
2.8
24
2
–
1ꢀTf2NH
1
–
[bmim]Tf2N/MeOH
–
2
21
0.4
1ꢀTf2NH
88
Reaction conditions: p (H2/CO = 1:1) = 2.0 MPa, T = 80 °C, t = 2 h, 1.0 mg Rh(acac)(CO)2, 1/Rh = 10, 1-octene/Rh = 1000, 1 g
[bmim]Tf2N (entries 1, 2) or 1 g [bmim]Tf2N and 3 mL MeOH (entries 3, 4); the ammonium salt 1ꢀTf2NH was prepared in situ in methanol with
1 and Tf2NH (1/Tf2NH = 1/1)
a
Percent of converted 1-octene
b
Selectivity of produced aldehyde
c
Selectivity of produced acetal that was easily hydrolyzed to aldehyde in the presence of acids
d
Selectivity of isomerized octenes that are mainly 2-octene and 3-octene
e
n/i = mol (normal aldehyde ? normal acetal)/mol (iso-aldehyde ? iso-acetal)
f
Percentage of leached Rh in the total Rh charged, determined by ICP-AES analysis
acetals). In addition, the formation of ammonium salt
1ꢀTf2NH enhances the affinity of the Rh catalyst to
[bmim]Tf2N to effectively inhibit the Rh leaching [27].
Finally, the product aldehydes may cause the Rh leaching
from the IL into the product phase by coordination of
carbonyl group to Rh [33], but the coordination-induced Rh
loss can be efficiently suppressed due to the formation of
acetal.
CO2H
O
Tf2N-
NH3
N
H
Ph2P
1 Tf2NH
Scheme 3 Ammonium salt (1ꢀTf2NH) form of ligands 1
We emphasize that the formation of dimethylacetals is
a vital step for inhibiting the Rh-catalyst loss in the
hydroformylation. Though the accessorial hydrolysis step
(Scheme 4) of acetals may be disadvantageous, this prob-
lem can be easily solved by using a sulfonic acid-catalyzed
aqueous two-phase hydrolysis system that consists of a
reusable aqueous phase dissolving the sulfonic acid and
n-heptane phase containing the extracted hydroformylation
products.
Table 2 Recycling of the Rh-catalyst for hydroformylation of
1-octene in [bmim]Tf2N/MeOH with ligand 1ꢀTf2NH
Entry Cycle Conver. Sald
(%)
Sace
(%)
Siso
(%)
n/i Rh
leaching
(%)
(%)
1
2
3
4
5
6
7
8
1
98
98
98
98
98
98
97
92
10
10
10
11
19
24
25
30
88
87
87
87
77
72
66
51
1
2.8 0.4
2.7 0.4
3
1
5
2
2.7
2.7
2.7
–
–
–
7
2
9
2
11
15
17
3
2.8 0.3
4 Conclusions
8
2.9
2.7
–
–
18
In summary, we have synthesized a zwitterionic phosphine
ligand bearing a lysine tag and applied it for the Rh-cata-
lyzed hydroformylation of 1-octene in IL systems. In
[bmim]Tf2N two-phase system the ligand 1 showed a high
activity associated with significant Rh leaching. Upon the
addition of acid Tf2NH into [bmim]Tf2N, the ammonium
salt (1ꢀTf2NH) was formed, which efficiently improved the
affinity of Rh-catalyst to [bmim]Tf2N and kept the Rh loss
at 2 % level. We further established a homogeneous system
made of Rh-1ꢀTf2NH, [bmim]Tf2N and MeOH, in which
the formation of dimethylacetals was a critical step that
reduced the Rh loss to 0.3~0.4 %, such that long-term good
activity and selectivity were achieved during seventeen
runs.
Reaction conditions:
t = 2 h, 1.0 mg Rh(acac)(CO)2, 1/Rh = 10, 1-octene/Rh = 1000,
1/Tf2NH = 1/1, 1 g [bmim]Tf2N and 3 mL MeOH
p
(H2/CO = 1:1) = 2.0 MPa, T = 80 °C,
The new 1-octene and MeOH were replenished into
[bmim]Tf2N for next catalyst recycling.
Table 2 shows long-term excellent activity and selec-
tivity, and no significant Rh loss (only 0.3~0.4 %) was
observed during 17 continuous runs. We consider that the
long-term stability in catalytic performance mainly benefits
from the following several aspects. Firstly, the [bmim]
Tf2N/MeOH provided a homogeneous catalytic system that
ensures high conversion and selectivity (aldehydes plus
123

Zwitterionic Phosphine Ligand with a Lysine Tag
843
OMe
OMe
CO/H2
CHO
CHO
H+/MeOH
H+
Rh-1 Tf2NH
H2O
+
+
+
[bmim]Tf2N/MeOH
OMe
OMe
Scheme 4 Hydroformylation of 1-octene in [bmim]Tf2N/MeOH system with 1ꢀTf2NH as ligand
Acknowledgments We gratefully thank the financial support from
National Natural Science Foundation of China (No. 20606019,
20976086), Foundation of Key Laboratory of Oil & Gas Fine
Chemicals, Ministry of Education, China (No. XJDX0908-2010 -01)
and Qingdao Science and Technology Basic Research Foundation of
China (No. 12-1-4-3-(6)-jch).
16. Sirieix J, Ossberger M, Betzemeier B, Knochel P (2000) Synlett
11:1613–1615
17. Brasse CC, Englert U, Salzer A, Waffenschmidt H, Wasserscheid
P (2000) Organometallics 19:3818–3823
18. Favre F, Olivier-Bourbigou H, Commereuc D, Saussine L (2001)
Chem Commun 1360–1361
19. Bronger RPJ, Silva SM, Kamer PCJ, van Leeuwen PWNM
(2002) Chem Commun 3044–3045
20. Lee S, Zheng YJ, Piao JY, Yoon H, Song CE, Choi JH, Hong J
(2003) Chem Commun 2624–2625
References
21. Yao Q, Zhang Y (2003) Angew Chem Int Ed 42:3395–3398
22. Audic N, Clavier H, Mauduit M, Guillemin JC (2003) J Am
Chem Soc 125:9248–9249
23. Baleiza˜o C, Gigante B, Garcia H, Corma A (2003) Tetrahedron
Lett 44:6813–6816
24. Gadenne B, Hesemann P, Moreau JJE (2005) Tetrahedron
Asymmetry 16:2001–2006
25. Doherty S, Goodrich P, Hardacre C, Knight JG, Nguyen MT,
1. Frohning CD, Kohlpainter CW (1996) In: Cornils B, Herrmann
WA (eds) Applied homogeneous catalysis with organometallic
compounds, 1st edn. Wiley, Weinheim, p 29
2. Kuntz EG (1987) ChemTech 17:570–575
3. Haumann M, Riisager A (2008) Chem Rev 108:1474–1497
4. Welton T (1999) Chem Rev 99:2071–2084
5. Dupont J, de Souza RF, Suarez PAZ (2002) Chem Rev 102:
3667–3692
ˆ
Parvulescu VI (2007) Adv Synth Catal 349:951–963
ˆ
6. Parvulescu VI, Hardacre C (2007) Chem Rev 107:2615–2665
26. Gavrilov KN, Lyubimov SE, Bondarev OG, Maksimova MG,
Zheglov SV (2007) Adv Synth Catal 349:609–616
27. Feng X, Pugin B, K}usters E, Sedelmeier G, Blaser HU (2007)
Adv Synth Catal 349:1803–1807
ˆ
28. Doherty S, Goodrich P, Hardacre C, Parvulescu V, Paun C (2008)
Adv Synth Catal 350:295–302
7. Chauvin Y, Mussmann L, Olivier H (1995) Angew Chem Int Ed
34:2698–2700
8. Wasserscheid P, Waffenschmidt H, Machnitzki P, Kottsieper
KW, Stelzer O (2001) Chem Commun 451–452
9. Dupont J, Silva SM, de Souza RF (2001) Catal Lett 77:131–133
10. Webb PB, Sellin MF, Kunene TE, Williamson S (2003) Slawin
AMZ J Am Chem Soc 125(15577–1558):8
11. Silva SM, Bronger RPJ, Freixa Z, Dupont J, van Leeuwen
PWNM (2003) New J Chem 27:1294–1296
ˇ
29. Sebesta R, Bilc¯ık F (2009) Tetrahedron Asymmetry 20:1892–
ˇ
1896
30. Jin X, Xu X, Zhao K (2012) Tetrahedron Asymmetry 23:1058–
1067
12. Mehner CP, Cook RA, Dispenziere NC, Mozeleski EJ (2004)
Polyhedron 23:2679–2688
31. Kuang SM, Fanwick PE, Walton RA (2002) Inorg Chim Acta
338:219–227
13. Ni B, Headley AD (2010) Chem Eur J 16:4426–4436
14. Lombardo M, Trombini C (2010) ChemCatChem 2:135–145
32. Hoffman RV (1974) Tetrahedron Lett 28:2415–2416
33. Krompieca S, Penkalaa M, Szczubiałkab K, Kowalska E (2012)
Coord Chem Rev 256:2057–2095
ˇ
15. Sebesta R, Kmentova I, Toma S (2008) Green Chem 10:484–496
ˇ
123