Palladium acetate in polyurea microcapsules: A recoverable and reusable catalyst for hydrogenations

Article abstract of DOI:10.1055/s-2002-34862

Polyurea microcapsules containing palladium acetate have been used in a range of catalytic hydrogenation reactions.

Full text of DOI:10.1055/s-2002-34862

LETTER
1843
Palladium Acetate in Polyurea Microcapsules: A Recoverable and Reusable
Catalyst for Hydrogenations
a
a
a
b
b
P
N
alladium Acetate
a
in Polyurea
d
Microcapsu
i
les ne Bremeyer, Steven V. Ley,* Chandrashekar Ramarao, Ian. M. Shirley, Stephen C. Smith
a
Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK
Fax +44(1223)336442; E-mail: svl1000@cam.ac.uk
b
Syngenta, Jealott’s Hill International Research Centre, Bracknell, Berkshire RG42 6EY, UK
Received 13 September 2002
storage conditions and special precautions are not re-
quired. Differential scanning calorimetry (DSC) tests in-
dicate there is no self-heating on warming samples to 400
Abstract: Polyurea microcapsules containing palladium acetate
have been used in a range of catalytic hydrogenation reactions.
Key words: palladium, catalysis, hydrogenations, polyurea, micro-
capsules
°
C in an atmosphere of air. Preliminary DSC tests per-
formed on Pd(OAc) polyurea microcapsules reduced un-
2
der hydrogen have not detected any thermal activity or
large exothermic decomposition. These findings are sig-
nificant and imply that polyurea may function as an alter-
native support to activated carbon. This prompted an
investigation to ascertain if these microcapsules can func-
tion as catalysts in hydrogenation reactions. Pd EnCat
has been used in a series of hydrogenation experiments
and the observations are described herein.
Reductions of unsaturated functionalities using hydrogen
are frequently employed transformations in both labora-
tory synthesis and manufacturing processes. Many catal-
ytic hydrogenation reactions involve the use of metallic
palladium, a fact attributed to its unique ability to absorb
up to 900 times its own volume of hydrogen at room tem-
TM
1
perature. Supporting this precious metal on inert materi-
Pd EnCatTM was pre-reduced under H (50 bar) for two
als with high specific surface areas that are chemically
stable can permit easy and economical recovery and the
most commonly used insoluble support for palladium is
2
days and hydrogenations were then carried out with this
reduced catalyst.10 The reactions were performed on a 1
2
mmol scale (with respect to substrate) using 5 mol% of
activated carbon. An ongoing research programme dedi-
TM
pre-reduced Pd EnCat under an atmosphere of H main-
cated to the development of new supports for expensive
and sometimes toxic transition-metal catalysts led us to
2
tained by an inflated balloon, or under higher pressure us-
ing an autoclave. The studies carried out revealed that
these Pd microcapsules are effective in the hydrogena-
tions of alkenes, alkynes, imine and nitro functionalities
(Table 1). Ethyl alcohol (EtOH) and acetonitrile were
found to be the most suitable solvents. Simple alkenes,
alkynes and aryl nitro groups were reduced at room tem-
3
explore microencapsulation techniques. Microencapsu-
lation is a particle coating process widely used for entrap-
ping materials in capsules, generally in a size range of
4
1
–1000 microns. This technique has broad utility in the
5
development of drug delivery systems and in the manu-
facture of systems for the controlled release of pesticides.4
perature under an atmosphere of H (inflated balloon).
The use of an interfacial polymerisation procedure en-
2
The catalyst was recovered by a straightforward filtration
using a 20-micron polyethylene frit, leaving pure products
in solution. Using cyclohexene (entry 1) as a test sub-
abled the efficient entrapment of Pd(OAc) in spherical
2
polyurea microcapsules in a size range of 50–250 mi-
6
crons. The Pd(OAc) containing microcapsules were ef-
2
TM
strate, it was demonstrated that Pd EnCat could be re-
fective in catalysing carbon-carbon bond-forming
processes such as carbonylations, Suzuki, Heck and Stille
type reactions in both conventional and supercritical CO2
covered and recycled 20 times without any significant loss
in activity. Reductions of electron-deficient alkenes (en-
tries 7–10) were sluggish at room temperature and re-
quired slightly elevated temperatures (60 °C) to yield the
reduced products. Reduction of an imine (entry 11) could
not be carried out under these conditions and required the
use of higher pressure (50 bar). Interestingly, alkyl ep-
oxides, aryl halogens and benzyloxy groups (entries 12,
7
solvent systems in the absence of phosphine ligands. The
study also established that polyurea itself was capable of
chelating with the metal species, eliminating the need to
synthesize special chelating groups and incorporate them
8
within the polymer matrix in separate steps.
TM 9
The Pd(OAc) polyurea microcapsules (Pd EnCat
)
2
1
3 and 14, respectively) remained unaffected even after
proved to be robust, withstanding high temperatures, vig-
orous stirring and were insoluble in most aqueous and or-
ganic solvents. Studies on the stability of these
microcapsules reveal that they are air-stable under typical
being subjected to higher pressures (up to 50 bar) and ex-
tended reaction times (18 h). However, the N-benzyloxy-
carbonyl group in entry 15 was removed under high
pressure (50 bar) whilst performing the reaction under an
atmosphere of H (maintained by an inflated balloon)
2
Synlett 2002, No. 11, Print: 29 10 2002.
Art Id.1437-2096,E;2002,0,11,1843,1844,ftx,en;D14302ST.pdf.
gave the alkene reduced product in 93% isolated yield.
The crude products obtained after these reactions were
analysed for metal contamination to determine the extent
©
Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214

1
844
N. Bremeyer et al.
LETTER
of leaching. Inductively coupled plasma (ICP) analysis in- In conclusion, Pd EnCatTM is an effective catalyst for the
dicated the levels of palladium (in the reaction mixture af- selective reduction of unsaturated bonds. Recovery of the
ter filtration) to be under 10 ppm, corresponding to an catalyst is simple and efficient and the levels of metal con-
original metal loss of 0.025%. In comparison with Pd/C, tamination in crude products are extremely low.
this system is clearly less reactive leading to longer reac-
tion times, but providing the ability to selectively reduce
Acknowledgement
double bonds in the presence of other sensitive function-
1
1
TM
alities. Unlike Pd/C, Pd EnCat does not appear to be The authors thanks D. Mortimer (Avecia) for ICP analysis and D.
Pears (Avecia) for discussions. Financial support from Syngenta
(NB and CR), the BP Endowment and the Novartis Research Fel-
lowship (to SVL) is gratefully acknowledged.
pyrophoric in the presence of air and solvent making the
1
2
operational handling straightforward. These features
gain significance when compared with systems that re-
quire fine filters for recovery, especially if they are prone
to self-ignite under aerobic conditions in the presence of References
flammable solvent vapour. These advantages suggest that
the current procedure may have benefits in scale-up oper-
ations.
(
(
(
1) Hammond, C. R. CRC Handbook of Chemistry and Physics,
81st ed.; Lide, D. R., Ed.; CRC Press: Boca Raton Florida,
2002, 4–22.
2) King, D. O.; Shinkai, I. Encyclopaedia of Reagents for
Organic Synthesis, Vol. 6; Paquette, L. A., Ed.; John Wiley
and Sons: New York, , 3867.
Table 1 Hydrogenations using Pd EnCatTM
Entry Substrate
1
Product
Methoda Time (h)d
3) (a) Akiyama, R.; Kobayashi, S. Angew. Chem. Int. Ed. 2001,
40, 3469. (b) Kobayashi, S.; Ishida, T.; Akiyama, R. Org.
A
2
Lett. 2001, 3, 2649. (c) Kobayashi, S.; Endo, M.;
Nagayama, S. J. Am. Chem. Soc. 1999, 121, 11229.
(
d) Nagayama, S. M.; Endo, M.; Kobayashi, S. J. Org.
2
3
A
A
3
Chem. 1998, 63, 6094. (e) Kobayashi, S.; Nagayama, S. J.
Am. Chem. Soc. 1998, 120, 2985.
60
(
4) Mars, G. J.; Scher, H. B. Controlled Delivery of Crop
Protecting Agents; Wilkens, R. M., Ed.; Taylor and Francis:
London, 1990, 65.
4
A
18
(
5) Jain, R. A. Biomaterials 2000, 21, 2475.
Ab
(6) Ramarao, C.; Ley, S. V.; Smith, S. C.; Shirley, I. M.;
5
6
18
18
DeAlmeida, N. Chem. Commun. 2002, 1132.
(
7) Ley, S. V.; Ramarao, C.; Gordon, R. S.; Holmes, A. B.;
Morrison, A. G.; McConvey, I. F.; Shirley, I. M.; Smith, S.
C.; Smith, M. D. Chem. Commun. 2002, 1134.
A
B
7
3
(
(
8) Zhang, K.; Necker, D. C. J. Polym. Sci. 1983, 21, 3115.
9) Samples of Pd EnCat can be obtained on request from
TM
8
9
B
B
5
3
Avecia U. K.
(
10) All hydrogenation reactions were carried out using Pd
TM
EnCat that had been pre-reduced under H (50 bar) for two
2
days. This pre-reduction is required for high activity and
reduced reaction times.
(11) The reduction of 4-nitrotoluene (entry 6, method A) to p-
toluidine using Pd/C was complete in 1 h. Using Pd/C under
the same conditions used for entry 14 resulted in the
1
1
1
1
0
1
2
3
B
5
Cc
18
18
18
C
C
reduction and complete removal of the benzyloxy group.
(
12) The veracity of this statement has not been established on
reaction scales greater than those commonly employed in
research laboratories.
1
1
4
5
C
A
18
4e
a
10
TM
Conditions : Method A, 5 mol% Pd EnCat , EtOH, r.t., H (bal-
2
TM
loon); Method B, 5 mol% Pd EnCat , EtOH–MeCN (1:1), 60 °C, H
2
TM
(
balloon); Method C, 5 mol% Pd EnCat , EtOH, r.t., H (50 bar).
EtOH–MeCN (1:1) was used as solvent.
MeCN was used as solvent.
Complete conversion to products was observed by GC or LCMS.
2
b
c
d
e
9
3% Yield plus 7% cleavage product.
Synlett 2002, No. 11, 1843–1844 ISSN 0936-5214 © Thieme Stuttgart · New York