Synthesis of a poly(ethylene glycol)-supported tetrakis ammonium salt: A recyclable phase-transfer catalyst of improved catalytic efficiency

Article abstract of DOI:10.1016/S0040-4039(02)00475-6

The immobilization of four quaternary ammonium groups on a poly(ethylene glycol) support provided an efficient and recyclable phase-transfer catalyst.

Full text of DOI:10.1016/S0040-4039(02)00475-6

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 3391–3393
Synthesis of a poly(ethylene glycol)-supported tetrakis
ammonium salt: a recyclable phase-transfer catalyst of
improved catalytic efficiency
Maurizio Benaglia,a,* Mauro Cinquini,a Franco Cozzia and Graziella Toccob
aCNR-ISTM and Dipartimento di Chimica Organica e Industriale, Universita’ degli Studi di Milano, via Golgi 19,
I-20133 Milano, Italy
bDipartimento Farmaco Chimico Tecnologico, Universita’ degli Studi di Cagliari, via Ospedale 72, I-09124 Cagliari, Italy
Received 19 February 2002; accepted 8 March 2002
Abstract—The immobilization of four quaternary ammonium groups on a poly(ethylene glycol) support provided an efficient and
recyclable phase-transfer catalyst. © 2002 Elsevier Science Ltd. All rights reserved.
We recently reported1 that immobilization of a benzyl
tributylammonium salt on the monomethylether of
mercially available, unfunctionalized polymer was 71%
over five steps.6,7 Catalyst 2 (loading=0.679 mmol/g)
was employed in some standard reactions carried
out under PTC conditions. These included the O-
and N-benzylation of phenol and pyrrole, respectively,
the bis-benzylation of diethyl malonate, and the
poly(ethylene glycol) of Mw 5000 Da (MeOPEG5000
)
by means of an inert spacer afforded compound 1
(Fig. 1), which proved to be an efficient and recyclable
catalyst for some standard reactions carried out under
phase-transfer catalysis (PTC) conditions.2 Due to the
high Mw of the polymeric support, catalyst 1 suffers
from a low loading, i.e. a low number of catalytic sites
per gram of polymer.†
MeO
O
CH2N+Bu3Br-
-(CH2CH2-O)n-CH2CH2-O
(CH2)3-
=
1,
We reasoned that an increase in the number and a
proper spatial arrangement of the catalytic sites would
likely provide a more efficient catalyst. Here, we
report that loading expansion of PEG carried out
exploiting the principles of dendrimer chemistry3 led to
the PEG-supported tetrakis ammonium salt 2. This
catalyst displayed a higher catalytic efficiency than 1,
while retaining the solubility properties peculiar of the
PEG support,4 that allowed simple catalyst recovery
and recycling by precipitation and filtration.
-BrBu3+N
-BrBu3+N
N+Bu3Br-
N+Bu3Br-
PEG4600
O
O
2,
PEG4600
= -CH2CH2-(O-CH2CH2)n- n = 104
Figure 1.
Catalyst 2 was readily prepared (Scheme 1) from tetra-
kis benzylalcohol 3, easily obtained from PEG4600,5 via
tetrakis bromide 4. The overall yield from the com-
R
R
PEG4600
O
O
a
R
R
Keywords: catalysis; phase transfer; polymers; supported catalysts.
* Corresponding author. Tel.: +39 02 5031 4171; fax:+39 02 5031
4159; e-mail: maurizio.benaglia@unimi.it
3, R = OH
4, R = Br
b
2
†
By assuming an average Mw of 5000 Da for the PEG fragment the
calculated loading for compound 1 is 0.183 mmol/g.
Scheme 1. Legend: (a) PBr3, DCM; (b) Bu3N, toluene.
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)00475-6

3392
M. Benaglia et al. / Tetrahedron Letters 43 (2002) 3391–3393
dichlorocyclopropanation of styrene. The activity of
compound 2 was compared to that displayed by com-
pound 1 in the same reactions (Table 1).
tion of styrene (entries 17–20). In the alkylation of
malonate, some decrease in chemical yield was observed
when the catalyst was re-used for the third time (entry
11); however, when the twice-recycled catalyst was
employed for a longer reaction time (15 min instead of
5 min), a yield as high as 91% was achieved (entry 12).
In the cyclopropanation reaction catalyst 2 did not
show virtually any erosion of activity up to the fifth
cycle (entry 20), in which a yield as high as 95% was
still observed.
The reported data showed that, in all of the benzylation
reactions examined, catalyst 2 afforded the products in
yields similar to those obtained with catalyst 1 but with
shorter reaction times (for O-alkylation see entries 2
and 3 versus 1, for N-alkylation see entry 6 versus 5
and for C-alkylation see entry 9 versus 8). The presence
of a higher number of catalytic sites in 2 than in 1
allowed a ten-fold decrease of the catalyst loading
(entry 7).
The catalytic activity of the PEG-supported tetrakis
ammonium salt 2 favorably compares to that of other
ammonium salts supported on insoluble polymers such
as cross linked polystyrenes.8,9 The use of these cata-
lysts generally required higher temperatures and cata-
lyst concentrations, and longer reaction times than
those employed here. In addition, optimum reaction
conditions were observed for these insoluble polymer-
supported catalysts only after long conditioning times,
necessary to ensure the bead swelling that facilitates
accessibility of substrate and reagents to the catalytic
sites. It is also worth mentioning that catalysts such as
1 and 2 do not suffer from the extensive mechanical
degradation experienced by polystyrene-supported cata-
lysts after operating at the high stirring rates required
by PTC conditions.8 A useful comparison for catalyst 2
is also provided by the dendrimeric, poly(penta-
erythrol)-based polyammonium salts synthesized by
Ford,7 featuring a surface containing up to 36 trimethyl
At this low catalyst concentration, however, a longer
reaction time was required in order to obtain the
product in a reasonably high yield. Catalyst 2 com-
pared nicely to 1 also in the dichlorocyclopropanation
of styrene performed under liquid/liquid PTC condi-
tions (entry 16 versus 15), a process in which the latter
was not particularly efficient.
One of the most important reasons for catalyst immobi-
lization resides in the possibility of catalyst recovery
and recycling. Recovery of catalyst 2 was conveniently
performed by precipitation with diethyl ether directly
from the reaction mixture, followed by filtration. Aver-
age recovery yields ranged from 80 to 95%. Catalyst
recycling was studied for the bis-benzylation of diethyl
malonate (entries 10–12) and the dichlorocyclopropana-
Table 1. Phase-transfer reactions catalyzed by ammonium salts 1 and 2
Entry
Substrate
Reagent
Catalyst (mol%)
Conditions
Product
Time (min)
Yield (%)a
1
2
3
4
5
6
7
8
PhOH
PhOH
PhOH
PhOH
Pyrrole
Pyrrole
Pyrrole
CH2(COOEt)2
CH2(COOEt)2
CH2(COOEt)2
CH2(COOEt)2
CH2(COOEt)2
Styrene
Styrene
Styrene
Styrene
Styrene
BnBr
BnBr
BnBr
BnBr
BnBr
BnBr
BnBr
BnBr
BnBr
BnBr
BnBr
BnBr
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
1 (1)
2 (1)
2 (1)
2 (1)
1 (1)
2 (1)
2 (0.1)
1 (3)
2 (3)
2 (3)b
2 (3)c
2 (3)c
1 (1)
2 (1)
1 (1)
2 (1)
2 (1)f
2 (1)g
2 (1)h
2 (1)i
NaOH solid
NaOH solid
NaOH solid
NaOH solid
NaOH solid
NaOH solid
NaOH solid
NaOH solid
NaOH solid
NaOH solid
NaOH solid
NaOH solid
NaOH solid
NaOH solid
NaOH aqueouse
NaOH aqueouse
NaOH solid
NaOH solid
NaOH solid
NaOH solid
PhOBn
PhOBn
PhOBn
PhOBn
N-Bn pyrrole
N-Bn pyrrole
N-Bn pyrrole
CBn2(COOEt)2
CBn2(COOEt)2
CBn2(COOEt)2
CBn2(COOEt)2
CBn2(COOEt)2
60
15
60
180
30
5
400
30
5
54
72
89
95
99
98
85
99
99
90
75
91
93
98
40
84
97
98
97
95
9
10
11
12
13
14
15
16
17
18
19
20
5
5
15
30
30
200
200
30
30
30
30
d
–
–
–
–
d
d
d
d
–
d
Styrene
Styrene
Styrene
–
d
–
–
d
a Isolated yields after flash chromatography. Reaction solvent was DCM and the temperature 25°C for entries 1–12; reaction solvent was CHCl3
and the temperature 30°C for entries 13–20.
b With a catalyst sample recovered after use in entry 9.
c With a catalyst sample recovered after use in entries 9 and 10.
d The product is 1,1-dichloro-2-phenylcyclopropane.
e NaOH was 9 M in water.
f With a catalyst sample recovered after use in entry 14.
g With a catalyst sample recovered after use in entries 14 and 17.
h With a catalyst sample recovered after use in entries 14, 17, and 18.
i With a catalyst sample recovered after use in entries 14, 17, 18, and 19.

M. Benaglia et al. / Tetrahedron Letters 43 (2002) 3391–3393
489–510.
3393
ethylammonium groups. In this case, a strong catalytic
activity was achieved only for dendrimers possessing a
large number of catalytic sites (at least 12). Remark-
ably, the corresponding tetrakis ammonium salt did not
show any rate enhancement with respect to non-cata-
lyzed reaction conditions. The recycling of these den-
drimeric catalysts was not reported.
5. Benaglia, M.; Annunziata, R.; Cinquini, M.; Cozzi, F.;
Ressel, S. J. Org. Chem. 1998, 63, 8628–8629.
6. For the isolation, yield and purity determination of PEG-
supported compounds, see: Annunziata, R.; Benaglia,
M.; Cinquini, M.; Cozzi, F. Chem. Eur. J. 2000, 6,
133–138.
7. Reports describing the synthesis of non-polymeric
molecules containing more than one quaternary ammo-
nium function: (a) Brunelle, D. J. In Phase-Transfer
Catalysis, ACS-Symposium Series 326, Starks, C. M.,
Ed.; Washington, DC, 1987; Chapter 5, pp. 38–53; (b)
Lee, J. J.; Ford, W. T.; Moore, J. A.; Li, Y. Macro-
molecules 1994, 27, 4632–4634; (c) Balakrishnan, T.; Jay-
achandran, J. P. J. Chem. Soc., Perkin Trans. 2 1995,
2081–2085.
8. For the immobilization of quaternary ammonium salts
on cross-linked polystyrenes, see: (a) Regen, S. L. J. Org.
Chem. 1977, 42, 875; (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. For the use of cationic
polymer colloids containing ammonium salts, see: (d)
Lee, J. J.; Ford, W. T. J. Am. Chem. Soc. 1994, 116,
3753–3759.
In conclusion, a simple and high yielding synthesis of a
new phase-transfer catalyst supported on poly(ethylene
glycol) has been reported. The catalyst, that featured
four quaternary ammonium groups located at the ter-
mini of the polymer backbone, displayed a remarkable
efficiency in promoting different reactions carried out
under PTC conditions at low catalyst concentrations
(1–3 mol%) for short reaction times and under mild
conditions. The polymer support allowed to easily
recover and recycle the catalyst.10
References
1. Annunziata, R.; Benaglia, M.; Cinquini, M.; Cozzi, F.;
Tocco, G. Org. Lett. 2000, 2, 1737–1739.
2. Starks, C. M.; Liotta, C. L.; Halpern, M. Phase-Transfer
9. At the border line between dendrimer- and polymer-sup-
ported phase-transfer catalysis (Refs. 7 and 8) lies a
report (Kenawy, E. R. J. Macromol. Sci., Pure Appl.
Chem. 1998, A35, 657–672) that describes the synthesis of
dendrimers supported on a polymer/montmorillonite sys-
tem and modified with ammonium salts.
10. Financial support by CNR (Agenzia 2000) and MIUR
(Progetto Nazionale Stereoselezione in Sintesi Organica.
Metodologie ed Applicazioni) is acknowledged.
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