Microencapsulated linear polymers: "Soluble" heterogeneous catalysts

Article abstract of DOI:10.1021/ja063688+

A new strategy for supporting catalysts based on the microencapsulation of linear polymers is presented. In this paper, we present a DMAP capsule that is capable of catalyzing acylation reactions. The catalyst is compared to DMAP on cross-linked and linear polystyrene, as well as small molecule DMAP. Rapid optimization through modification of encapsulation conditions is demonstrated. The optimization provides a dynamic range of catalysis from 90 to 300% of the rate of DMAP on polystyrene. Copyright

Full text of DOI:10.1021/ja063688+

Published on Web 07/21/2006
Microencapsulated Linear Polymers: “Soluble” Heterogeneous Catalysts
Kristin E. Price, Brian P. Mason, Andrew R. Bogdan, Steven J. Broadwater,
Jeremy L. Steinbacher, and D. Tyler McQuade*
Baker Laboratory, Department of Chemistry and Chemical Biology, Cornell UniVersity, Ithaca, New York 14853
Received May 26, 2006; E-mail: dtm25@cornell.edu
Catalysts are often the most expensive component of a reaction
and are frequently difficult to separate from the product. A wide
variety of solid supports are used to facilitate catalyst removal and
recycling.1 Cross-linked polymers are especially flexible supports
-8
for organo-catalysts and ligands because myriad methods are
available for covalent attachment.7
,9-14
The high surface area and
porous structure allow small molecules to rapidly diffuse in and
out of the polymeric supports.1
5,16
The catalysts on the support,
conversely, diffuse very little and experience a different solvation
environment than homogeneous catalysts, often rendering them less
selective and less active, unless painstakingly optimized.9
It would be desirable to have a system that combines the ease
of cross-linked polymers with the catalytic activity of homogeneous
,10
7
17,18
catalysts. Inspired by recent work of Ley and others,
we propose
that catalysts attached to soluble polymers entrapped within
microcapsules will yield higher activities and be more readily
tunable than catalysts attached to cross-linked resins.19 In this paper,
we provide the first example of catalysis using encapsulated linear
polymer-catalyst conjugates. This new approach not only provides
a more active catalyst than that supported on cross-linked-
polystyrene but also allows for simpler tuning.
Figure 1. SEM images of microcapsules containing LPSDMAP. A-D are
made with 5, 7, 13, and 17% PMPPI, respectively. SEM images and size
distribution data are available in Supporting Information.
Scheme 1. Synthesis of DMAP Polymer and Microcapsules
The model reaction we investigated is a 4-(N,N-dimethylamino)-
pyridine (DMAP)-catalyzed acylation. DMAP is an ideal model
20,21
because it has been studied as a small molecule,
on linear
and insoluble polymeric
DMAP is also extremely sensitive to its electronic
22-24
25-27
polymers,
supports.9
inorganic supports,
,28-33
environment, as demonstrated by the extensive linker and backbone
changes required to optimize its activity on polymeric support.9
In contrast, we show that catalytic microencapsulated polymers can
be optimized with minimal synthetic modification.
,28,34
Table 1. Relative Rates of Acylation of sec-Phenethyl Alcohol in
the Presence of 0.5 mol % of Catalyst
The microencapsulated polymer is synthesized in two steps.19
The DMAP-modified linear polystyrene (LPSDMAP, 2) is formed
by a copolymerization of a DMAP-modified monomer (1) and
styrene (Scheme 1). LPSDMAP is then dissolved in chloroform
along with poly(methylene[polyphenyl]isocyanate) (PMPPI). This
organic phase is then dispersed in an aqueous phase containing
poly(vinyl alcohol) as a stabilizer. The interfacial polymerization
is initiated with tetraethylenepentamine (TEPA). Once washed and
dried, the capsules are isolated as a free-flowing solid (Figure 1).
Acylation of sec-phenethyl alcohol with acetic anhydride in
tetrahydrofuran (THF) was used as the test reaction. The capsules
were compared to a commercially available (dimethylamino)-
pyridine on polystyrene-co-divinylbenzene (PSDMAP), as well as
LPSDMAP (2), and the small molecule model, 4-(N-benzyl-N-
methyl)aminopyridine (BMAP) (Table 1). As shown in Table 1,
the rate of acylation is cut in half between DMAP and its benzyl
derivatives (BMAP and LPSDMAP). BMAP’s rate is then de-
creased by another factor of 4 when attached to an insoluble support
d
catalyst
k
rel
conversion
DMAP
BMAP
9.2
4.2
5.1
1.0
0.9
3.2
2.8
99%
98%
98%
89%
LPSDMAP (2)
PSDMAP
a
unoptimized LPSDMAP capsule
b
LPSDMAP capsule
91%
84%
LPSDMAP capsulec
e
a
PMPPI (7%), THF wash. b PMPPI (5%), no THF wash. c PMPPI (5%),
THF wash. d Background krel ) 0.007. The reaction rates were measured
e
using the method of initial rates. The THF washing may expose amines
in the shell that partially hydrolyze the acetic anhydride.
rounds of recycling, we see little change in rate or reaction yield
(99, 97, and 94%).
(
PSDMAP). The initial microcapsule samples gave rates similar
The exciting feature of microcapsules is that a number of factors
can be changed to create capsules with a desired strength,
permeability, or size, without changing the interior polymer. In
to those for PSDMAP (Table 1). The encapsulated catalyst is simply
filtered off after the reaction is complete and is reusable. In three
3
5
10376
9
J. AM. CHEM. SOC. 2006, 128, 10376-10377
10.1021/ja063688+ CCC: $33.50 © 2006 American Chemical Society

C O M M U N I C A T I O N S
reagent diffusion and mixing. This approach represents a new
strategy for creating heterogeneous catalysts.
Acknowledgment. We thank ARO (MAP-MURI), the Dreyfus
and Beckman Foundations, 3M, Rohm and Haas, NIH (CBI), NSE
(SENSORS), NYSTAR, and the CCMR Microscopy facility.
Supporting Information Available: Experimental methods, DMAP
loading determinations, rate data, capsule size data, and SEM images.
This material is available free of charge via the Internet at http://
pubs.acs.org.
Figure 2. Comparison of rates of LPSDMAP (2) and PSDMAP (Fluka, 3
mmol/g) to THF-washed capsules made with varied PMPPI loading (5-
1
7%).
References
Scheme 2. Model of DMAP Capsule Catalysis
(
1) Wittcoff, H. A.; Reuben, B. G.; Plotkin, J. S. Industrial Organic Chemicals,
2
nd ed.; Wiley-Interscience: Hoboken, NJ, 2004; p 662.
(
(
(
2) Song, C. E.; Lee, S. G. Chem. ReV. 2002, 102, 3495-3524.
3) Duchateau, R. Chem. ReV. 2002, 102, 3525-3542.
4) De Vos, D. E.; Dams, M.; Sels, B. F.; Jacobs, P. A. Chem. ReV. 2002,
102, 3615-3640.
(
(
(
5) Dickerson, T. J.; Reed, N. N.; Janda, K. D. Chem. ReV. 2002, 102, 3325-
343.
6) McNamara, C. A.; Dixon, M. J.; Bradley, M. Chem. ReV. 2002, 102,
275-3299.
7) Ley, S. V.; Baxendale, I. R.; Bream, R. N.; Jackson, P. S.; Leach, A. G.;
Longbottom, D. A.; Nesi, M.; Scott, J. S.; Storer, R. I.; Taylor, S. J. J.
Chem. Soc., Perkin Trans. 1 2000, 3815-4195.
3
3
(
8) Barrett, A. G. M.; Hopkins, B. T.; Kobberling, J. Chem. ReV. 2002, 102,
3301-3323.
(
9) Deratani, A.; Darling, G. D.; Fr e´ chet, J. M. J. Polymer 1987, 28, 825-
this case, we achieved the optimized rate (Table 1) of the
encapsulated DMAP catalyst by varying the wall thickness of the
microcapsules. Wall composition was varied by changing PMPPI
concentration in the emulsion (Figure 1). As the amount of PMPPI
is increased, the walls grow thicker, which causes the walls to
collapse differently. Walls that are thin crumple like paper (Figure
830.
(
10) Selkala, S. A.; Tois, J.; Pihko, P. M.; Koskinen, A. M. P. AdV. Synth.
Catal. 2002, 344, 941-945.
(
(
(
(
(
11) Benaglia, M.; Puglisi, A.; Cozzi, F. Chem. ReV. 2003, 103, 3401-3429.
12) Reger, T. S.; Janda, K. D. J. Am. Chem. Soc. 2000, 122, 6929-6934.
13) Parrish, C. A.; Buchwald, S. L. J. Org. Chem. 2001, 66, 3820-3827.
14) Leadbeater, N. E.; Marco, M. Chem. ReV. 2002, 102, 3217-3273.
1
A,B), while thicker walls fold less when dried (Figure 1C,D). By
15) Gambs, C.; Dickerson, T. J.; Mahajan, S.; Pasternack, L. B.; Janda, K.
D. J. Org. Chem. 2003, 68, 3673-3678.
Varying only the encapsulation procedure, a more actiVe catalyst
is created. As seen in Figure 2, the catalytic activity of the capsules
increases with decreasing PMPPI concentration. The final catalyst
was approximately 3-fold faster than PSDMAP.
Recovered capsules were examined by both light and electron
microscopy after each reaction to establish that the capsule walls
did not rupture under reaction conditions. Since capsule rupture
was not evident, the possibility of polymer diffusion through the
wall had to be considered. To test whether the catalyst was leaching
from the capsules, we extracted them with THF using a Soxhlet
(
16) Yamane, Y.; Kobayashi, M.; Kuroki, S.; Ando, I. Macromolecules 2001,
34, 5961-5967.
(
17) Kobayashi, S.; Akiyama, R. Chem. Commun. 2003, 449-460.
(18) He, S. H.; Yan, J. J.; Shen, R.; Zhou, S.; Toy, P. H. Synlett 2006, 563-
565.
(
19) Price, K. E.; Broadwater, S. J.; Bogdan, A. R.; Keresztes, I.; Steinbacher,
J. L.; McQuade, D. T. Macromolecules 2006, accepted.
(20) Ragnarsson, U.; Grehn, L. Acc. Chem. Res. 1998, 31, 494-501.
(21) Hofle, G.; Steglich, W.; Vorbruggen, H. Angew. Chem., Int. Ed. Engl.
1978, 17, 569-582.
(
22) Koning, C. E.; Eshuis, J. J. W.; Viersen, F. J.; Challa, G. React. Polym.
1986, 4, 293-309.
apparatus. No significant decrease in catalytic activity was ob-
served.36 Since THF is an excellent solvent for the entrapped
polymer, these data indicate that the linear polymers are too large
to diffuse through the capsule shell (Scheme 2).
(23) Bergbreiter, D. E.; Osburn, P. L.; Li, C. M. Org. Lett. 2002, 4, 737-740.
(24) Delaney, E. J.; Wood, L. E.; Klotz, I. M. J. Am. Chem. Soc. 1982, 104,
799-807.
(
25) Goldstein, S. L.; Hamer, A. D.; Katz, L. E.; McGeary, M. J.; Smith, C.
P. Dialkyl amino pyridine catalysts which are bound to inorganic matrixes
and processes for their preparation. U.S. Patent 5,315,004, 19940511, 1995.
Since the polymer remains within the capsule throughout the
reaction and the PMPPI concentration affects the rate of catalysis,
we conclude that reagents, substrates, and products must enter and
exit the shell faster than the acylation occurs (Scheme 2). Therefore,
the rate of the reaction will depend on the rate of the diffusion
preequilibria as well as the rate of the DMAP acylation step. This
preequilibria, we believe, is responsible for making the thin shelled
capsules slower than the LPSDMAP. As the shell becomes thicker,
the diffusion of molecules to the interior slows, causing the overall
reaction rate to decrease (Figure 2). These data show that the shell
can be used to tune the encapsulated catalyst.
In conclusion, we demonstrated that catalytic polymers can be
encapsulated within microcapsules and that the polymers are
retained within the capsules throughout a reaction. We also showed
that by varying shell thickness the reaction rate is tuned and that
with thin, strong walls the capsules’ reaction rate nears that of an
unencapsulated polymer. High reactivity is important because
increased catalyst loadings fill the reaction vessel with resin, limiting
(
26) Rubinsztajn, S.; Zeldin, M.; Fife, W. K. Macromolecules 1990, 23, 4026-
4027.
(27) Chen, H. T.; Huh, S.; Wiench, J. W.; Pruski, M.; Lin, V. S. Y. J. Am.
Chem. Soc. 2005, 127, 13305-13311.
(28) Guendouz, F.; Jacquier, R.; Verducci, J. Tetrahedron 1988, 44, 7095-
7108.
(29) Menger, F. M.; McCann, D. J. J. Org. Chem. 1985, 50, 3928-3930.
(30) Shinkai, S.; Tsuji, H.; Hara, Y.; Manabe, O. Bull. Chem. Soc. Jpn. 1981,
54, 631-632.
(31) Tomoi, M.; Goto, M.; Kakiuchi, H. J. Polym. Sci., Part A: Polym. Chem.
1987, 25, 77-86.
(32) Storck, W.; Manecke, G. J. Mol. Catal. 1985, 30, 145-169.
(33) McQuigg, D. W.; Webb, H. K.; Sowers, E. E. Polymer-supported 4-(N-
benzyl-N-methylamino)pyridine catalyst and process for same. U.S. Patent
5,229,479, 19890921, 1990.
(34) Guendouz, F.; Jacquier, R.; Verducci, J. Tetrahedron Lett. 1984, 25, 4521-
524.
4
(35) Koba sˇ lija, M.; McQuade, D. T. Macromolecules 2006, accepted.
(
36) Capsules were extracted aggressively for 24 h in refluxing THF under
air. Even these roughly handled capsules maintained 89% of their former
activity.
JA063688+
J. AM. CHEM. SOC.
9
VOL. 128, NO. 32, 2006 10377