Low pressure ethenolysis of renewable methyl oleate in a microchemical system

Article abstract of DOI:10.1021/ol200634y

Chemical equations presented. A microchemical system for ethenolysis of renewable methyl oleate was developed, in which the dual-phase, microfluidic design enabled efficient diffusion of ethylene gas into liquid methyl oleate through an increased contact area. The increased mass transfer of ethylene favored the formation of desired commodity chemicals with significantly suppressed homometathesis when compared to the bulk system. In addition to higher selectivity and conversion, this system also provides the typical advantages of a microchemical system, including the possibility of convenient scale-up.

Full text of DOI:10.1021/ol200634y

ORGANIC
LETTERS
2011
Vol. 13, No. 9
2398–2401
Low Pressure Ethenolysis of Renewable
Methyl Oleate in a Microchemical System
Chan Pil Park,† Matthew M. Van Wingerden,‡ So-Yeop Han,§ Dong-Pyo Kim,*,† and
Robert H. Grubbs*,‡
National Creative Research Center of Applied Microfluidic Chemistry, Chungnam
National University, Daejeon, 305-764, Korea, The Arnold and Mabel Beckman
Laboratory of Chemical Synthesis, Division of Chemistry and Chemical Engineering,
California Institute of Technology, Pasadena, California 91125, United States, and
Center for Catalysis and Synthesis, Ewha Womans University, Seoul, 120-750, Korea
rhg@caltech.edu; dpkim@cnu.ac.kr
Received March 10, 2011
ABSTRACT
A microchemical system for ethenolysis of renewable methyl oleate was developed, in which the dual-phase, microfluidic design enabled efficient
diffusion of ethylene gas into liquid methyl oleate through an increased contact area. The increased mass transfer of ethylene favored the formation of
desired commodity chemicals with significantly suppressed homometathesis when compared to the bulk system. In addition to higher selectivity and
conversion, this system also provides the typical advantages of a microchemical system, including the possibility of convenient scale-up.
The generation of useful, low molecular weight chemicals
from renewable natural resources is an important research
topic throughout the fields of chemistry and chemical en-
gineering. Because of environmental challenges and potential
economic advantages, the search for new feedstock sources
and the development of chemical and biological processes to
utilize the new feedstocks are the focus of much research.1
Ruthenium catalysts, which have become useful for organic
synthesis and polymer chemistry, have been tested in the
olefin methathesis of internal olefins with ethylene, known as
ethenolysis, which can be used to produce the desired low
molecular weight products from renewable seed oils (eq 1).2
Early studies of the ethenolysis of natural seed oils
showed promise but was limited by the high sensitivity of
the traditional molybdenum, tungsten, and rhenium cata-
lysts. The advent of ruthenium catalysts with low sensitiv-
ity but high activity has spurred a renewed interest in
ethenolysis, but limited selectivity and conversion have
hampered progress to commercially viable processes.
Homometathesis continues to be a troubling competing
reaction which reduces the yield.
† Chungnam National University.
‡ California Institute of Technology.
§ Ewha Womans University.
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Microchemical systems have provided new strategies
and new challenges as new process techniques.3 The ben-
efits of precise control of reaction variables and high
surface area-to-volume ratios are manifest in reduced
r
10.1021/ol200634y
Published on Web 04/01/2011
2011 American Chemical Society

waste, higher yield, and reduced reaction times. Further-
more, the difficulties of scale-up can largely be avoided by
simple parallelization of small-scale microfluidic test reac-
tors. In addition to traditional, one-step microchemical
reactions, several consecutive reactions, including separa-
tion, purification, and detection, have been successfully
integrated as complete microchemical processes.4
and the slow diffusion of ethylene into the solution favor
homometathesis instead of the desirable ethenolysis. Over-
coming the bias for homometathesis suggests two straight-
foward strategies: developing catalysts with a high kinetic
selectivity for ethenolysis, or engineering processes to drive
ethylene into the reaction. The engineering approach was
the main strategy of this work and was accomplished by
increasing the contact area between methyl oleate and
ethylene, thereby maximizing the transfer of the ethylene
intothe methyl oleate phase withhigh diffusion efficiency.6
A particularly challenging type of microchemical system
is the heterogeneous reaction involving any combination
of the gas, liquid, and solid phases.5 The heterogeneous
reactions between gas and liquid are mainly conducted
with two main modes of contact:6 one with the two phases
flowing in contact in parallel, the other with alternative
bands of gas bubbles and liquid slugs. In a recent report we
described a microchemical system with the former mode of
contact mediated by a PDMS (polydimethylsiloxane)
membane.7 As an alternative to this strategy, however,
we feel the segmented mode of contact has its own unique
advantages due mainly to the simple, convenient setup and
a broader choice of available capillary materials, allowing
better chemical stability and mechanical strength even at
high pressure. Herein, we report a facile and efficient
microchemical ethenolysis under various reaction condi-
tions, through the continuous segmented flow of ethylene
and methyl oleate in a capillary tube with a 0.5 mm inner
diameter. Moreover, the reaction was performed nearly
solvent-free, except for a minimun amount of toluene to
dissolve the catalyst (1.0 mg of catalyst in 2.0 mL of
toluene), which avoids the use of excess organic solvent
to facilitate the dissolution of ethylene gas as has been
reported.8 The poor solubilty of ethylene in methyl oleate
(mole fraction of ethylene/methyl oleate = 0.108, 60 psi)2a
Figure 1. (A) Microchemical ethenolysis of methyl oleate (MO)
with Ru catalyst (1.0 mg/2 mL toluene). (B) Segmented flow of
ethylene and methyl oleate in a capillary microreactor.
In the initial design a mode of merging phases which is a
general approach for reactions of this type was adopted
(see Supporting Information for the system, Figure 1SA).
Ethylene gas and methyl oleate were mixed in the first
T-junction where slugs of liquid formed in the gas flow. In
the second T-junction the flow was merged with the
catalyst solution to form larger liquid slugs in the gas flow.
However, this system resulted in an irregular distribution
of catalyst in the methyl oleate due to slight variations
in the flow rate between the two T-junctions. Because of
the unsatisfactory results, the mixing order was changed so
that the catalyst (at 1.0 μL/min) and substrate (at 5.7 μL/min)
were mixed first and the ethylene gas was added second
(Figure 1). This created the potential for a deleterious
side reaction when the catalyst and substrate were mixed
with no ethylene, but this was mitigated by lowering
the temperature in the section between the T-junctions.
The lower temperature also was expected to facilitate the
diffusion of ethylene into solution. The cooled mixture of
catalyst and methyl oleate was quickly saturated with
ethylene injected in the second T-juction and then heated
to start the reaction, taking advantage of the rapid heat
transfer of microchemical systems.3 The flow rate of the
solution, and consequently the retention time, was finely
controlled by a peristaltic pump instead of the more
general approach of regulating the back pressurre.
(3) (a) Fukuyama, T.; Rahman, M. T.; Sato, M.; Ryu, I. Synlett 2008,
151–163. (b) Mason, B. P.; Price, K. E.; Steinbacher, J. L.; Bogdan,
A. R.; McQuade, D. T. Chem. Rev. 2007, 107, 2300–2318. (c) Micro-
reactors in Organic Synthesis; Wirth, T., Ed.; Wiley-VCH: Weinheim, 2008.
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Wang, Y., Yoshida, J. I., Eds.; Wiley-VCH: Weinheim, 2009. (e) Ahmed-
Omer, B.; Brandtand, J. C.; Wirth, T. Org. Biomol. Chem. 2007, 5, 733–740.
(f) Watts, P.; Wiles, C. Chem. Commun. 2007, 443–467. (g) Yoshida, J.;
Nagaki, A.; Yamada, T. Chem.;Eur. J. 2008, 14, 7450–7459. (h) Lin,
W.; Wang, Y.; Wang, S.; Tseng, H. Nano Today 2009, 4, 470–481. (i)
McMullen, J. P.; Jensen, K. F. Annu. Rev. Anal. Chem. 2010, 3, 19–42. (j)
Webb, D.; Jamison, T. F. Chem. Sci. 2010, 675–680. (k) Yoshida, J.
Chem. Rec. 2010, 10, 332–341.
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Chem. 2002, 74, 2623–2636. (b) Auroux, P. A.; Iossifidis, D.; Reyes,
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Nature 2006, 442, 368–373.
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2005, 347, 1889–1892. (b) Wang, N.; Matsumoto, T.; Ueno, M.;
Miyamura, H.; Kobayashi, S. Angew. Chem., Int. Ed. 2009, 48, 4744–
4746. (c) Shore, G.; Morin, S.; Organ, M. G. Angew. Chem., Int. Ed.
2006, 45, 2761–2766. (d) Park, C. P.; Kim, D.-P. Angew. Chem., Int. Ed.
2010, 49, 6825–6829.
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H.; Bender, D.; Passchier, J.; Gee, A. Angew. Chem., Int. Ed. 2007, 46,
2875–2878. (b) Rahman, M. T.; Fukuyama, T.; Kamata, N.; Sato, M.;
Ryu, I. Chem. Commun. 2006, 21, 2236–2238. (c) Rebrov, E. V.; Klinger,
E. A.; Berenguer-Murcia, A.; Sulman, E. M.; Schouten, J. C. Org.
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Org. Lett., Vol. 13, No. 9, 2011
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A noticeable shortening of the length of ethylene bubbles
was observed through the length of the microreactor, a not
unexpected observation asethylene isconsumed during the
reaction.9 The pressure drop across the length of the
microreactor caused by the increased friction of the seg-
mented liquid flow was worrisome because of the ponten-
tially variable solubility of ethylene, but the pressure at the
exit was measured to be 56 psi when the inlet pressure was
set to 60 psi. The pressure differential and corresponding
solubility difference were thus concluded to be negligible.
Figure 3. Ruthenium catalysts for ethenolyis of methyl oleate.
cooled, an increase in homometathesis was observed as
expected (entry 3). Hoveyda-type catalyst 7 was slightly
more effective than catalyst 6 (entries 4 and 5), and the
typical second generation catalyst 8 gave the poorest
results in selectivity and yield, although the more active
catalyst required less time than catalysts 6 and 7 to achieve
a similar conversion (entries 6ꢀ8). The second generation
catalysts 9 and 10, which contain a sterically hindered
NHC ligand, also gave lower yields than PCy3-based
catalysts 6 and 7 (entries 9ꢀ12), even though it is known
that catalysts with NHC ligands have better stability and
activity toward olefin metathesis than catalysts with PCy3
ligands. In this case the homocoupling reaction, while not
significant for phosphine-based catalysts 6 and 7, ac-
counted for about half the activity of the NHC-based
Figure 2. Ethenolysis under different temperature and pressure
conditions. Catalyst 6 (300 ppm) was used. (a) Yield (%) = con-
version ꢁ selectivity = (1 ꢀ final moles of 1/initial moles of 1) ꢁ
{(2 þ 3)/(2 þ 3 þ 4 þ 5)} ꢁ 100. Conversion and selectivity were
determined by GC analysis. (b) Selectivity after 120 min reten-
tion time.
As the effects of pressure and temperature in the batch
system were well documented in previous reports,2 the
same variables were carefully studied in the microchemical
system. With 300 ppm of catalyst6, the pressure was varied
from 15 to 60 psi and the temperature was varied from 20
to 40 °C. The results illustrate that the pressure of ethylene
has a direct impact on the yield (Figure 2).10 Elevating the
temperature over 30°C resultedina 5%lossin the net yield
after 120 min, due tothe decreasedselectivity (30 psi and 30
°C: 48% conversion, 85% selectivity, 30 psi and 40 °C:
50% conversion, 72% selectivity). These good results at
low temperature and high pressure are well consistent with
the batch studies, where the same factors increase the
selectivity and yield of ethenolysis.2
For the ethenolyis of methyl oleate 1, six ruthenium
catalysts were selected: first generation catalysts 6 and 7;
second generation catalysts 8, 9, and 10; and cyclic alkyl-
amino carbene (CAAC)-based catalyst 1111 (Figure 3).
Each catalyst was screened at a variety of catalyst loadings,
and the results were tabulated (Table 1). When catalyst 6
was used at 0 °C only a negligible amount of product was
formed, confirming that no olefin metathesis occurs in the
first cooled mixing zone as was expected in the redesigned
system (entry 1). When the first mixing section was not
Table 1. Ethenolyses of Methyl Oleate 1 in the Microchemical
Systema
cat.
t
time
conv
(%)c
select
(%)d
yield
(%)e
(ppm)
(°C)
(min)
TONf
1
2
3
4
5
6
7
8
6 (150)
6 (300)
6b(300)
7 (100)
7 (300)
8 (50)
8 (100)
8 (100)
9 (50)
9 (100)
10 (50)
10 (100)
11 (50)
11 (100)
11 (100)
0
30
30
30
30
40
30
40
40
40
40
40
40
40
40
180
120
120
120
120
60
120
60
60
60
40
40
60
3
65
66
39
69
58
59
61
54
57
61
63
80
81
72
99
96
91
94.8
93.7
45
43.5
41
52
50
58
55
87
84
88
3.0
62.4
60.1
37.0
64.7
26.1
25.7
25.0
28.1
28.5
35.4
34.7
69.6
68.0
63.4
600
5800
5600
7500
4400
11 000
5400
5300
13 500
6800
22 300
10 900
27 200
13 300
12 400
9
10
11
12
13
14
15
60
30
a General reaction conditions: 60 psi ethylene, the microchemical
(9) In additon to the higher surface area-to-volume ratio, the micro-
fluidic system is free from pressure drop, even though much of the gas is
consumed, which is a property not found in batch systems.
(10) Conversion and selectivity for each condition are in the Supporting
Information, Table 1S.
(11) Anderson, D. R.; Lavallo, V.; O’Leary, D. J.; Bertrand, G.;
Grubbs, R. H. Angew. Chem., Int. Ed. 2007, 46, 7262–7265.
system described in Figure 1A. Conversion and selectivity were deter-
mined by GC analysis. b No cooling of the mixing zone. c Conversion =
(1 ꢀ final moles of 1/initial moles of 1) ꢁ 100. d Selectivity (%) = (2 þ 3)/
(2þ 3þ 4þ 5) ꢁ 100. e Yield (%) = conversion ꢁ selectivity/100. f TON =
yield ꢁ [(initial moles of 1)/(moles of cat.)].
2400
Org. Lett., Vol. 13, No. 9, 2011

catalysts 8, 9, and 10. The resultfrom catalyst11isthemost
noteworthy as the catalyst is currently the most selective
catalyst known for ethenolysis among the NHC-based
catalysts. Catalyst 11 gives the highest yield in this study,
even when compared with phosphine-based catalysts 6 and
7. Catalyst 11 gave a 69.6% yield with only 50 ppm catalyst
and a 60 min retention time (entry 13). The selectivity is
comparable to the result of the batch reaction tested at
higher pressure (selectivities up to 83% were measured at
150 psi), but because of the higher conversion the yield was
higher in the microchemical system.2b Additionally, the
selectivities of catalysts 6, 7, 8, 9, and 10 are superior in the
microchemical system at 60 psi compared to the batch
reaction at 150 psi.
of ethylene were comparable to the results of batch
reactions at 150 psi of ethylene. This is expected to be
due to the high surface area-to-volume ratio suitable for
fast mass transfer of the gas into the solution phase. The
sterically hindered CAAC-based ruthenium catalyst 11
gave 80% conversion and 87% selectivity with only 50
ppm catalyst.
Acknowledgment. We gratefully acknowledge financial
support from the NRF (CRI project 2008-0061983), the
NRF (WCU project R33-2009-000-10169-0), and the
DOE (DE-FG02-05ER46218). We thank Materia, Inc.
for a generous donation of ruthenium complexes 6ꢀ10.
In conclusion, a microchemical system for gasꢀliquid
dual-phase reactions was developed which was applied
to the ethenolysis of methyl oleate. The results at 60 psi
Supporting Information Available. Experimental pro-
cedures. This material is available free of charge via the
Internet at http://pubs.acs.org.
Org. Lett., Vol. 13, No. 9, 2011
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