A poly(ethylene glycol)-supported quaternary ammonium salt: An efficient, recoverable, and recyclable phase-transfer catalyst

Article abstract of DOI:10.1021/ol005901r

(matrix presented) A quaternary ammonium salt readily immobilized on a soluble poly(ethylene glycol) polymer support efficiently catalyzes different reactions carried out under phase-transfer catalysis conditions; the catalyst, easily recovered by precipitation and filtration, shows no appreciable loss of activity when recycled three times.

Full text of DOI:10.1021/ol005901r

ORGANIC
LETTERS
2000
Vol. 2, No. 12
1737-1739
A Poly(ethylene glycol)-Supported
Quaternary Ammonium Salt: An
Efficient, Recoverable, and Recyclable
Phase-Transfer Catalyst
,†
Rita Annunziata,† Maurizio Benaglia,* Mauro Cinquini,† Franco Cozzi,† and
Graziella Tocco‡
Centro CNR and Dipartimento di Chimica Organica e Industriale, UniVersita’ degli
Studi di Milano, Via Golgi 19, I-20133 - Milano, Italy, and Dipartimento Farmaco
Chimico Tecnologico, UniVersita' degli Studi di Cagliari, Via Ospedale 72,
I-09124 - Cagliari, Italy
franco.cozzi@unimi.it
Received April 6, 2000
ABSTRACT
A quaternary ammonium salt readily immobilized on a soluble poly(ethylene glycol) polymer support efficiently catalyzes different reactions
carried out under phase-transfer catalysis conditions; the catalyst, easily recovered by precipitation and filtration, shows no appreciable loss
of activity when recycled three times.
One of the major problems associated with the use of soluble
catalysts lies in the recovery of the catalyst from the reaction
medium. Immobilization of the catalyst on a polymeric
matrix can provide a simple solution to this problem.1 In
this context, the ideal polymer support should be soluble in
some solvents, for the catalyzed reaction to be carried out
under optimum conditions, and insoluble in other solvents,
so that the supported catalyst can easily be isolated and
recovered by precipitation and filtration.2
been used for the immobilization of cinchona alkaloid-
derived ligands for the asymmetric dihydroxylation reaction.4
To the best of our knowledge, however, a whole catalytic
system has never been attached to PEG.
Here we report that a quaternary ammonium salt can be
easily synthesized on a modified MeOPEG, and this sup-
ported catalyst is an efficient and recoverable promoter of
several reactions carried out under phase-transfer catalysis
(PTC) conditions.5
Poly(ethylene glycol)s (PEGs) of Mw greater than 2000
Da are readily functionalized, inexpensive polymers that
feature these convenient solubility properties.3 Recently, the
mono methyl ether of PEG5000 (MeOPEG) has successfully
(4) (a) Han, H.; Janda, K. D. Tetrahedron Lett. 1997, 38, 1527-1530;
and references therein. (b) Bolm, C.; Gerlach, A. Eur. J. Org. Chem. 1998,
21-27.
(5) Starks, C. M.; Liotta, C. L.; Halpern, M. Phase-Transfer Catalysis;
Chapman & Hall: New York, 1994.
† Universita’ di Milano.
(6) (a) Benaglia, M.; Annunziata, R.; Cinquini, M.; Cozzi, F.; Ressel, S.
J. Org. Chem. 1998, 63, 8628-8629. (b) Annunziata, R.; Benaglia, M.;
Cinquini, M.; Cozzi, F. Chem. Eur. J. 2000, 6, 133-138.
(7) For a detailed description of the isolation, purification, and yield and
purity determination of PEG-supported compounds, see the Experimental
Section of ref 6b or the Supplementary Information.
(8) (a) Hodge, P.; Khosdel, E.; Waterhouse, J. J. Chem. Soc., Perkin
Trans. 1 1984, 2451-2455. (b) Bram, G.; Loupy, A.; Pedoussant, M. Bull.
Soc. Chim. Fr. 1986, 124-128. (c) McKillop, A.; Fiaud, J.-C.; Hug, R. P.
Tetrahedron 1974, 30, 1379-1382. (d) Wang, N.-C.; Teo, K.-E.; Anderson,
H. J. Can. J. Chem. 1977, 55, 4112-4116. (e) Crossland, I. Org. Synth.
1981, 60, 6-10.
‡ Universita’ di Cagliari.
(1) (a) Fruchtel, J. S.; Jung, G. Angew. Chem., Int. Ed. Engl. 1996, 35,
17-42. (b) Thomson, L. A.; Ellmann, J. A. Chem. ReV. 1996, 96, 555-
600. (c) Hermkens, P. H. H.; Ottenhejim, H. C. J.; Rees, D. Tetrahedron
1996, 52, 4527-4554. (d) Shuttleworth, S. J.; Allin, S. M.; Sharma, P. K.
Synthesis 1997, 1217-1239.
(2) (a) Bergbreiter, D. E.; Zhang, L.; Mariagnanam, V. M. J. Am. Chem.
Soc. 1993, 115, 9295-9296. (b) Neumann, R.; Cohen, M. Angew. Chem.,
Int. Ed. Engl. 1997, 36, 1738-1740. (c) Felder, M.; Giffels, G.; Wandrey,
C. Tetrahedron: Asymmetry 1997, 8, 1975-1977.
(3) Gravert, D. J.; Janda, K. D. Chem. ReV. 1997, 97, 489-509.
10.1021/ol005901r CCC: $19.00 © 2000 American Chemical Society
Published on Web 05/19/2000

The preparation of the immobilized catalyst is described
in Scheme 1. On the basis of our previous experience in the
(obtained in quantitative yield from MeOPEG)6b was reacted
with the Cs salt of commercially available 4-hydroxybenzyl
alcohol (3 equiv, DMF, 50 °C, 15 h) to afford alcohol 2 in
nearly quantitative yield.7 Reaction of 2 with PBr3 (3 equiv,
CH2Cl2, 0 °C to room temperature, 15 h) gave bromide 3 in
95% yield. This was converted into ammonium salt 4 by
reaction with tributylamine (10 equiv) in toluene (65 °C, 72
h, 85% yield).
Scheme 1
Compound 4 was then used as catalyst in a series of
standard transformations carried out under PTC conditions.
The results are reported in Table 1. For sake of comparison,
the yields of the same reactions promoted by nonsupported
and structurally related catalysts were also included.8
The reported data indicate that 4 showed a catalytic activity
that was similar to, or even better than that of the nonsup-
ported catalysts. Remarkably, the benzylation of phenol and
pyrrole (entries 7-10) required only 0.01 equiv of catalyst
4 to occur in g95% yield. Dichloromethane, in which the
catalyst is readily soluble, was found to be the organic solvent
of choice, but the reaction could satisfactorily be carried out
also in the absence of organic solvent (entries 3 and 4).
Generally the use of solid/liquid conditions led to higher
yields than those observed under liquid/liquid conditions
(entries 2 vs 1, 7 vs 5, 10 vs 9). As shown by entries 11-13
and 15, catalyst 4 could be recovered by precipitation and
filtration, and recycled three times to run the same (entries
11 and 12) or a different reaction (entry 13) without any
appreciable loss of the catalytic activity.9
It is also worth mentioning that compound 4 favorably
compares as catalyst to other quaternary ammonium salts
immobilized on insoluble polystyrene supports.10 The use
of these catalysts generally required higher reaction temper-
synthesis of small organic molecules bound to modified
PEG,6 ethereal bonds were selected for connecting the
polymer core to the reactive functionality. Mesylate 1
Table 1. Phase-Transfer Reactions Catalyzed by Ammonium Salt 4
entry
substrate
reagent
conditionsa
product
time (h); °C
yield (%)b
lit. yield (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
n-C8H17Br
n-C8H17Br
n-C8H17Br
BnBr
phenol
phenol
KI
KI
H2O
n-C8H17
n-C8H17
n-C8H17CN
BnCN
PhOBn
PhOBn
I
I
5; 40
4; 40
8; 85
2; 25
56
75
85
97
18
90
95
95
99
99
95h
93i
92j
95
90n
93c
-
93c
97e
86f
-
-
-
67g
-
-
-
-
88m
-
solid/liquid
H2Od
H2Od
KCN
KCN
BnBr
BnBr
BnBr
BnBr
BnBr
BnBr
BnBr
BnBr
BnBr
CHCl3
CHCl3
NaOH aq
NaOH solid
NaOH solid
NaOH aq
NaOH aq
NaOH solid
NaOH solid
NaOH solid
NaOH solid
NaOH aqk
NaOH aqk
22; 25
3; 25
22; 25
3; 40
24; 40
0.25; 25
0.25; 25
0.25; 25
22; 25
2.5; 40-60
2.5; 40-60
phenol
PhOBn
pyrrole
pyrrole
pyrrole
pyrrole
pyrrole
phenol
N-Bn-pyrrole
N-Bn-pyrrole
N-Bn-pyrrole
N-Bn-pyrrole
N-Bn-pyrrole
PhOBn
l
styrene
styrene
-
-
l
a All the reactions were carried out in a two-phase system. Under liquid/liquid and solid/liquid conditions, the organic solvent was CH2Cl2 unless otherwise
stated. NaOH aq was a 0.1 M solution in H2O unless otherwise stated. The amount of catalyst was 0.04 equiv in entries 1-4, 11, and 15 assuming an average
MW of 6250 g/mol, and 0.01 equiv in entries 5-10 and 12-14. b Isolated yields, except for entries 1-3 (GC yields; the remainder was starting material).
e
c 0.05 mol equiv of (n-C8H17)4N+Br-; toluene/H2O; 5 h, 90 °C; GC yield (ref 8a). d No organic solvent was added. 0.05 mol equiv of Aliquat 336; H2O;
2h, rt (ref 8b). f 0.01-0.10 mol equiv of n-Bu3BnN+Br-; NaOH 0.3 M in H2O; 2-12 h, rt (ref 8c). g 0.10 mol equiv of Et3BnN+Br-; NaOH 19 M in H2O;
20 h, 40 °C (ref 8d). h Reaction carried out with a sample of 4 recovered after use in entry 10. i Reaction carried out with a sample of 4 recovered after use
in entries 10 and 11. j Reaction carried out with a sample of 4 recovered after use in entries 10-12. k The organic solvent was CHCl3.NaOH aq was 9 M
in H2O. l The product is 1,1-dichloro-2-phenylcyclopropane. m 0.05 mol equiv of catalyst; NaOH was 19 M in H2O; 2.5 h, 40-60 °C (ref 8e). n Reaction
carried out with a sample of 4 recovered after use in entry 14.
1738
Org. Lett., Vol. 2, No. 12, 2000

atures and/or longer reaction times than those employed here.
For instance, the reactions of entries 2 and 4 required 15 h
heating at 110 °C to occur in 8110b and 8510a % yield,
respectively, in the presence of catalysts similar to compound
4 anchored on microporous polystyrene cross-linked with
2% divinylbenzene. In addition, solid supported phase-
transfer catalysts required a preliminary, long conditioning
time (up to 15 h) to ensure bead swelling and optimum
accessibility of substrate and reagent to the catalytic site.10c
Finally, the high stirrring rate necessary with these catalysts
resulted in extensive mechanical degradation of the polymer
beads, that were difficult to recover by filtration.11
Since PEG itself is known to be a phase-transfer cata-
lyst,5,12 the catalytic activity of alcohol 2 was tested in the
benzylation of pyrrole under the conditions of entries 8 and
10.
In these reactions the product was obtained in 27 and 32%
yield, respectively, thus showing that the ammonium moiety
of catalyst 4 decisively contributed to the catalytic activity.
Remarkably, the ammonium salt 5, featuring a shorter spacer
between the PEG core and the quaternary nitrogen atom is
a catalyst less efficient than 4 (60 vs 75% yield in the reaction
of entry 2).
In conclusion, the immobilization of an ammonium salt
on a modified PEG provided an efficient phase-transfer
catalyst that could easily be recovered and recycled. The
possibility of exploiting enantiopure ammonium salts at-
tached to modified PEG in asymmetric phase-transfer
catalyzed reactions is currently under active investigation in
our laboratories.
Acknowledgment. This work was supported by MURST
(Progetto Nazionale Stereoselezione in Sintesi Organica.
Metodologie e Applicazioni) and CNR.
(9) The catalyst employed in reaction 10 when recovered by precipitation
and filtration contained undetermined amounts of NaOH and was used as
such in reactions 12-14 (see Supplementary Information). These were
carried out on the same scale as reaction 10.
(10) (a) Regen, S. L. J. Org. Chem. 1977, 42, 875-879. (b) Chiles, M.
S.; Jackson, D. D.; Reeves, P. C. J. Org. Chem. 1980, 45, 2915-2918. (c)
Molinari, H.; Montanari, F.; Quici, S.; Tundo, P. J. Am. Chem. Soc. 1979,
101, 3920-3927.
(11) Ford, W. T.; Tomoi, M. AdV. Polym. Sci. 1984, 55, 49-104.
(12) Sauvagnat, B.; Lamaty, F.; Lazaro, R.; Martinez, J. Tetrahedron
Lett. 1998, 39, 821-824.
Supporting Information Available: Full experimental
details for the preparation of catalyst 4 and its use in phase-
transfer catalyzed reactions. This material is available free
of charge via the Internet at http://pubs.acs.org.
OL005901R
Org. Lett., Vol. 2, No. 12, 2000
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