Synthesis and characterisation of polyamide dendrimers with systematically varying surface functionality

Article abstract of DOI:10.1039/b903190a

Remarkable changes of properties result from systematically varying the surface functionality of polyamide dendrimers within a single generation. The Royal Society of Chemistry 2009.

Full text of DOI:10.1039/b903190a

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Synthesis and characterisation of polyamide dendrimers with
systematically varying surface functionalityw
Helen Willcock, Andrew I. Cooper, Dave J. Adams and Steve P. Rannard*
Received (in Cambridge, UK) 16th February 2009, Accepted 25th March 2009
First published as an Advance Article on the web 15th April 2009
DOI: 10.1039/b903190a
Remarkable changes of properties result from systematically
varying the surface functionality of polyamide dendrimers within
a single generation.
functional groups. We also describe early observations of the
impact of surface group number and placement on dendrimer
physical properties.
Our convergent strategy relies upon selective chemistries,
previously developed within our group,12 that utilise carbonyl
imidazole derivatives. Three key dendrons (7, 9, 10) were
required to generate the systematically varying polyamide
dendrimer series, Scheme 1. Firstly, tert-butanol, 1, was
reacted in excess with 1,10-carbonyl diimidazole (CDI), 3, to
form the monosubstituted imidazole carboxylic ester, 4, as
previously described.12 In order to reduce the number of
purification steps, dipropylenetriamine (DPTA, 6) was added
directly to the reaction mixture and the selectively substituted
product, 7, was recovered in 86% yield, Scheme 1A.
Confirmation of selective reaction was provided by electro-
spray mass spectrometry (ESMS) (MH+ = 332 Da) and
nuclear magnetic resonance spectroscopy (NMR) (selected
resonances: 1H NMR (CDCl3) d = 2.65 ppm (t, 4H,
NH(CH2)2); 13C NMR (CDCl3) d = 39.3 ppm (NH(CH2)2),
The combined control of polymer functionality and archi-
tecture is often difficult to achieve. Linear copolymers may be
synthesised using addition polymerisation with exquisite
control of chain length, composition and functional group
segregation using a range of controlled synthesis techniques.1
The introduction of branching leads only to a statistical
control of average architecture and functionality on the
individual molecule level.2 Hyperbranched polymers synthe-
sised by ABn step-growth methods also suffer from an
averaged architecture,3 whereas the number of functional
groups present in each molecule is dependent on the archi-
tecture generated i.e. the number of linear, terminal and
dendritic monomer residues.4 Divergent growth of ideal
dendrimers allows the control of branching architecture but
ideal growth is only allowed if the surface is entirely func-
tional, and usually of the same functional group.5 Modifica-
tion of reactive divergent dendrimers by post-synthesis
reaction reverts to a statistical process and the placement
of controlled numbers or actual spatial arrangement of
functional groups is not readily possible.6 Recently, Matmour
and Gnanou have shown the control of branched architectures
using anionic polymerisation and generated narrow poly-
dispersity materials of predetermined size and branching.7
To date, the most flexible synthesis approach to the control
of architecture combined with control of number and place-
ment of functional groups is convergent dendrimer synthesis.8
The majority of structure–property studies of dendrimers
involve the formation of a series of materials that vary
specifically by generation9 and there are extremely few studies
that utilise single generation materials with subtle variations in
structure, chemistry or functionality. Some years ago, the
formation of dendrimers with single functional groups or
site-isolated functionality was demonstrated;10 however, since
those early papers, few studies of surface functionality
control,11 other than complete or statistical modification, have
been reported. We describe here the first reported synthesis of
a systematically varying, single generation series of polyamide
dendrimers with controlled numbers and placement of surface
t
156.6 (NHCO2 Bu)).
A second symmetric dendron, 9, was synthesised using
2-ethylhexanoic acid, 2, Scheme 1B. 2 was reacted at ambient
temperature with CDI to form the acid imidazolide 5 which
Department of Chemistry and Centre for Materials Discovery,
University of Liverpool, Crown Street, Liverpool, UK L69 7ZD.
E-mail: srannard@liv.ac.uk; Fax: +44 (0)151 794 3501;
Tel: +44 (0)151 794 3501
w Electronic supplementary information (ESI) available: Experimental
procedures, 1H and 13C NMR spectra, mass spectrometry and table of
organogelation. See DOI: 10.1039/b903190a
Scheme 1 Selective synthesis of symmetric and asymmetric poly-
amide dendrons.
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was not purified or isolated prior to addition of DPTA and
warming to 60 1C. Polyamide dendron 9 was generated
selectively (96% yield), confirmed by chemical ion mass
spectrometry (CIMS) (MH+ = 384 Da) and NMR (selected
resonances (CDCl3): 1H NMR d = 2.59 ppm (t, 4H,
NH(CH2)2); 13C NMR d = 38.4 ppm (NH(CH2)2), 179.2
(NHCOR)).
The asymmetric dendron 10 was synthesised using an initial
3-fold molar excess of DPTA. The monosubstituted triamine,
8, was isolated in 95% yield (CIMS MH+ = 258 Da) and
further reaction was achieved in a one-pot, multi-step
synthesis, initially forming 4 using an excess of 1 to ensure
full consumption of CDI. The synthesis of 4 was calculated to
ensure a slight excess of 8, which was directly added to the
reaction mixture. Dendron 10 was isolated in an 84% yield
after the reaction had stirred for 18 hours at 60 1C (ESMS,
MH+ = 358 Da; 1H NMR d = 3.21 ppm (q, 2H,
t
CH2NHCO2 Bu), 3.36 (q, 2H, CH2NHCOR); 13C NMR
t
d = 156.5 ppm (NHCO2 Bu), 176.4 (NHCOR)).
To synthesise a series of dendrimers with systematically
varying numbers of amide groups and urethane groups,
derived from 2 and 1, respectively, the dendrons 7, 9 and 10
were coupled to a tetraamine core molecule (tris(aminoethyl)-
amine, 11) in various combinations (Fig. 1).
Scheme 2 Monosubstitution of tris(amino ethyl) amine by generation
zero dendrons with varying surface functionality.
Dendrons 7, 9 and 10 were individually reacted with succinic
anhydride to generate amic acid derivatives. Without purifica-
tion, the acid functional dendrons were treated with CDI to
produce the imidazolide functional dendrons, followed by
direct addition of 11 to form the uniformly coupled first
generation dendrimers shown in Fig. 1A (top: six tBOC
dendrimer series with systematically varying surface tBOC
and EH groups was synthesised using similar approaches.
Dendrimers 19, 20 and 21 (see ESIw) are therefore analogous
to 18, 15 and 17 with respect to surface group composition and
internal chemistry. The formation of an analogous structure to
t
groups, 14; middle: three BOC and three ethyl hexyl (EH)
t
groups, 16; bottom: six EH groups, 18). Dendrons 7 and 9
were also reacted to form the imidazolide functional materials,
and reacted to monofunctionalise 11, Scheme 2 (recovered
yields after purification: 12 (63%); 13 (65%)). Further reaction
of 12 with imidazolide functional 9, and further reaction of 13
with the imidazolide functional 7, led to the formation of the
non-uniformly substituted first generation dendrimers shown
16 (3 BOC and 3 EH groups) is, however, not possible using
BEHA. Two lower generation dendrimers 22 and 23 were
synthesised to complete the series. During the synthesis of
these materials, the effect of the number, type and placement
of the surface functional groups on solubility and organo-
gelation behaviour became apparent. The dendrons 7 and 10
were synthesised without complication; however, dendron 9,
containing two EH groups and two secondary amides, gelled
the toluene reaction solvent (also used to prepare 7 and 10)
during synthesis. The toluene gel persisted even at 60 1C.
Reactions conducted in tetrahydrofuran (THF) also gelled at
temperatures up to 60 1C. As shown in Fig. 1 and Scheme 2,
dendron 9 was reacted with succinic anhydride and CDI to
form the amic acid and subsequent imidazolide derivatives.
Both of these intermediates were able to gel THF and toluene
at temperatures up to 60 1C.
t
in Fig. 1B (top: four BOC and two EH groups, 15; bottom:
t
two BOC and four EH groups, 17). The successful control
of substitution was confirmed by ESMS and NMR analysis
(see ESIw).
The introduction of the EH surface group into convergent
dendrimers can also be achieved through the utilisation of
bis(2-ethyl hexyl) amine (BEHA).12b A second analogous
The series of dendrimers (Fig. 2) showed variable organo-
gelation (Table S1; Fig. S18, ESIw), directly related to the
number and placement of EH groups and the type of amide
present. 14, 15 and 16 formed homogeneous solutions in THF,
CH2Cl2, methanol (MeOH) and toluene; however, 17 gelled
CH2Cl2. 18 gelled all solvents studied (CH2Cl2, THF (up to
60 1C), toluene (up to 60 1C) and MeOH). Although a
full evaluation of the organogels has not been conducted,
gelation was observed over
a range of concentrations
from 0.1 to 21 w/v%. The dendrimers 19, 20, 21, 22 and 23
exhibited no organogelation behaviour under the conditions
studied.
Fig. 1 Schematic representation of systematic coupling of dendrons
to control surface functionality.
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capability of the dendrimers whilst the introduction of a
t
further BOC group, and the mixing of the functionalities on
each component dendron (16), inhibits organogelation under
these conditions. In conclusion, we report the first synthesis of
two analogous single generation series of polyamide
dendrimers with systematically varying surface functionality.
Remarkably, the number, type and position of the surface
groups control the ability of these achiral dendrimers to gel a
range of common organic solvents. Further work will
characterise the gel structures and gelation mechanisms.
We thank the Royal Society for an Industry Fellowship
(SR), Unilever for financial support and Allan Mills for help
with mass spectrometry.
Notes and references
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Fig. 2 Polyamide dendrimers with controlled and systematically
´
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and achiral dendrimers.13 All structures within this study are
achiral and the self-assembly is related directly to surface
functionality. The inability of 19 and 21 to form organogels
is interesting as these materials are analogous with 18 and 17,
respectively. 19 and 18 (highlighted) have six EH groups,
identical polyamide core structures and similar molecular
weights (18 = 1543 Da; 19 = 1116 Da). The structures of
17 and 21 (highlighted) have greater similarity: four EH and
two tBOC surface groups, identical polyamide cores and
similar molecular weights (17 = 1491 Da; 21 = 1206 Da).
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tertiary amides and are therefore less able to hydrogen bond
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t
through the periphery. The introduction of just two BOC
groups into 18, to form 17, significantly disrupts the gelling
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Chem. Commun., 2009, 3095–3097 | 3097