Surface-functionalised nano-beads as novel supports for organic synthesis

Article abstract of DOI:10.1016/S0040-4039(03)01679-4

A novel polymer support has been prepared in which functional link points are located on the surface of polymer nano-beads; the use of the support has been demonstrated in the syntheses of unsymmetrical porphyrins.

Full text of DOI:10.1016/S0040-4039(03)01679-4

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 6633–6634
Surface-functionalised nano-beads as novel supports for
organic synthesis
Andrew N. Cammidge,* Stuart Downing and Zainab Ngaini
Wolfson Materials and Catalysis Centre, School of Chemical Sciences and Pharmacy, University of East Anglia,
Norwich NR4 7TJ, UK
Received 14 May 2003; revised 23 June 2003; accepted 3 July 2003
Abstract—A novel polymer support has been prepared in which functional link points are located on the surface of polymer
nano-beads; the use of the support has been demonstrated in the syntheses of unsymmetrical porphyrins.
© 2003 Elsevier Ltd. All rights reserved.
The use of solid-phase supports in organic synthesis is
now widely employed.1 Although inorganic supports
such as silica gels and controlled pore glasses2 are
frequently used, organic polymers still comprise the
largest class of support materials. Lightly crosslinked,
swellable polymers are typically prepared by emulsion
polymerisation techniques to give beads in sizes ranging
from mm to mm. Such insoluble polymers are conve-
nient for application as supports for synthesis, reagents,
scavengers etc. Their efficiency is governed by their
ability to swell (allowing access through the polymer
matrix) and therefore requires the use of suitable sol-
vents. This limitation is usually accommodated but
complications can be envisaged when attempts are
made to build up large molecules within the pores of
such supports.
polymerisation, as functional link point for solid-phase
organic synthesis. We chose a polymerisable carboxylic
acid derivative as surfactant to ensure a useful link
group would be attached to the final polymer (reason-
ing that the carboxylic acid could be reduced to provide
additional scope). Initial experiments with simple ‘sur-
factants’ such as 4-vinylbenzoic acid were unsuccessful
and led to the choice of amphiphile 4.4 Compound 4
was most conveniently synthesised by the route
depicted in Scheme 1.
In a typical procedure polymerisable amphiphile 4 (1.2
g) and CTAB (6.8 g) were used as surfactants to
stabilise a styrene/divinylbenzene (10:1, 2.4 g) micro-
emulsion in water (189 mL). The microemulsion was
polymerised (AIBN initiation) at 60°C for 7 h to give a
transparent solution of the surface-functionalised
nanoparticles. Acidification and addition of methanol
precipitated the polymer from solution and it was
filtered off and washed repeatedly with water to remove
CTAB. The resulting polymer was dried under vacuum
and characterised by TEM (average bead diameter 317
nm5), IR spectroscopy (wCꢀO 1707 cm−1) and titration
(loading=0.89 mmol/g COOH) (Scheme 2).
In this letter we describe the preparation of a new type
of polymeric support based on surface-functionalised
nanoparticles. We envisaged that an ideal solid support
could comprise small solid particles (ca. 50–300 nm)
bearing link points exclusively at the surface. Such
supports would be soluble in reaction media but easily
isolated by precipitation or SEC. Locating the link
points at the surface obviates the problems associated
with ‘buried’ functionality within a porous polymer
(heterogeneity of sites, accessibility etc).
We reasoned that such a support could be realised via
polymerisation of a microemulsion3 in which a poly-
merisable sufactant serves as amphiphile and, following
* Corresponding author.
Scheme 1. Synthesis of 4.
0040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)01679-4

6634
A. N. Cammidge et al. / Tetrahedron Letters 44 (2003) 6633–6634
methanol to cleave the bound porphyrins which were
isolated (preparative TLC) in yields of 4% (5) and 8%
(6), respectively. It is significant to note that these yields
are higher than those reported for their synthesis on
conventional solid phase.7
In conclusion, surface-functionalised nanoparticles have
been prepared and their utility as solid supports has
been demonstrated. Their reaction sites are uniformly
located at the accessible surface of (selectively) soluble
nanoparticles and they could, therefore, offer advan-
tages over their conventional counterparts in challeng-
ing applications.
Scheme 2. Preparation of surface-functionalised nanoparticles
(see text for details).
References
The utility of the novel polymer supports was investi-
gated using the syntheses of unsymmetrical porphyrins
as model reactions. The synthesis of unsymmetrical
porphyrins is generally a difficult process with typical
yields ranging from 0.5 to 5%.6 The synthesis of unsym-
metrical tetraarylporphyrins on conventional polymer
supports was reported by Leznoff7 using polymer
bound 3- or 4-hydroxybenzaldehyde (Scheme 3) and
this reaction was chosen to permit evaluation of the
nanoparticulate solid support.
1. See for example: Guillere, F.; Orani, D.; Bradley, M.
Chem. Rev. 2000, 100, 2091.
2. Matteucci, C. D.; Caruthers, M. H. J. Am. Chem. Soc.
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molecules 1998, 31, 272; (b) Pyrasch, M.; Tieke, B. Colloid
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5. Polymerisation conditions have been refined to give parti-
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ca. 100 nm. These results will be reported elsewhere.
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The carboxylic acid functionalised support was treated
with oxalyl chloride in CH2Cl2 (DMF initiation)8 and
the resulting polymer-bound acid chloride treated with
either 3- or 4-hydroxybenzaldehyde and pyridine. Com-
plete conversion to the polymer bound aldehyde-ester
was confirmed by IR spectroscopy of the isolated poly-
mer (wCꢀO 1766 and 1705 cm−1). The polymer bound
aldehydes were treated with excess pyrrole and p-tolyl-
benzaldhyde in refluxing propionic acid for 1 h.9 After
washing with CH2Cl2 the resulting polymers (IR 1765
cm−1) were treated with potassium carbonate in
Scheme 3. Polymer supported synthesis of unsymmetrical porphyrins.