Quadruple hydrogen bonded cytosine modules: N-1 functionalised arrays

Article abstract of DOI:10.1039/c1nj20162j

A ureidocytosine (UCyt) module with a pendant amine linker at N-1 has been prepared for applications in supramolecular quadruple hydrogen bonded array synthesis. Subsequent conjugation to four amine terminated telechelic polymers led to the formation of oligomeric DDAA arrays, as determined by NMR diffusion measurements, establishing that N-1 as well as N-9 ureidocytosine polymeric arrays can readily be accessed. The Royal Society of Chemistry and the Centre National de la Recherche Scientifique.

Full text of DOI:10.1039/c1nj20162j

New Journal of Chemistry
A journal for new directions in chemistry
www.rsc.org/njc
Volume 35 | Number 7 | July 2011 | Pages 1337–1564
ISSN 1144-0546
1144-0546(2011)35:7;1-H

Dynamic Article Links
NJC
Cite this: New J. Chem., 2011, 35, 1522–1527
www.rsc.org/njc
PAPER
Quadruple hydrogen bonded cytosine modules: N-1 functionalised
arraysw
Valerie G. H. Lafitte,a Abil E. Aliev,a Elisabetta Greco,a Kason Bala,b
Peter Goldingb and Helen C. Hailes*a
Received (in Montpellier, France) 25th February 2011, Accepted 8th April 2011
DOI: 10.1039/c1nj20162j
A ureidocytosine (UCyt) module with a pendant amine linker at N-1 has been prepared for
applications in supramolecular quadruple hydrogen bonded array synthesis. Subsequent
conjugation to four amine terminated telechelic polymers led to the formation of oligomeric
DDAA arrays, as determined by NMR diffusion measurements, establishing that N-1 as well
as N-9 ureidocytosine polymeric arrays can readily be accessed.
Introduction
Linear hydrogen bonded supramolecular polymers have
emerged in the last decade as a new class of materials whose
unique properties can respond to external stimuli such as
temperature or solvent.1 In order to generate high molecular
weight polymers, a strong association between the repeating
units is a prerequisite. In this regard, multiple hydrogen
bonding units have been intensively studied and continue to
be of significant interest.1–3 Meijer’s quadruple hydrogen
bonded unit based on Ureidopyrimidinones (Upys) 1 containing
two donors (D) and two acceptors (A) have shown great
potential in this field.3 With a high dimerization constant
(Kdim 6 ꢀ 107 Mꢁ1 in CHCl3) the DDAA quadruple hydrogen
bonded unit has been extensively used in the synthesis of
supramolecular polymers. Despite several advantages, the
Upy module can exhibit up to three tautomeric forms depending
on the environment and substituents attached, which can
increase the number of species present.3 Several other modules
have been described that can generate complementary DDAA
arrays, including, ureidonaphthyridine (UN),2b ureidoimidazo-
[1,2-a]pyrimidines (Ulmp),2f and our ureidocytosine based
module (UCyt) 2 which forms DDAA dimers with a high
Kdim (49 ꢀ 106 Mꢁ1 in benzene and 42.5 ꢀ 105 Mꢁ1 in
CDCl3) (Fig. 1).4 However, compared to the Upy unit, the
UCyt module lacks an intramolecular N–Hꢂ ꢂ ꢂO hydrogen
bond resulting in some conformational flexibility in the ureido
fragment between unfolded 2 and 20 folded forms.4
Fig. 1 Upy 1.1 dimer and unfolded (2) and folded (20) monomer and
dimer forms of the UCyt module.
solvents such as DMSO the folded form 20 alone was
detected.4 In CDCl3 at room temperature it was observed that
the linear DDAA array was in fast exchange with approxi-
mately 5% of the folded form 20. More recently, the influence
of an alkyl chain at N-1 and N-9 was investigated and longer
alkyl chains were found to give rise to more of the unfolded
rotamer, with the chain length and degree of unsaturation at
N-1 having the major affect.5
Despite this methyl cytosine modules were prepared and
readily used in polymer synthesis with attachment of the
polymer at N-9.5 Studies investigating heterodimeric arrays
between 1 and 2 also suggested that the N-1 methyl and hexyl
UCyt DDAA units competed well with the Upy module.4,5
One advantage of modules such as the ureidocytosines is
that they can in principle readily be functionalised at N-1 and
N-9, enabling the introduction of alternative moieties such as
polymers or fluorescent groups at different positions in the
arrays. In previous work the capacity of the UCyt modules to
The folded conformer can dimerize via two hydrogen bonds
and in apolar solvents such as toluene or benzene, the
unfolded form 2 was found exclusively, while in very polar
a Department of Chemistry, University College London, 20 Gordon
Street, London, WC1H 0AJ, UK. E-mail: h.c.hailes@ucl.ac.uk;
Fax: +44 (0)20 7679 7463; Tel: +44 (0)20 7679 4654
b AWE plc., Aldermaston, Reading, Berkshire, RG7 4PR, UK
w Electronic supplementary information (ESI) available. See DOI:
10.1039/c1nj20162j
c
1522 New J. Chem., 2011, 35, 1522–1527
This journal is The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2011

Fig. 2 Head–head A and tail–tail B arrangement of quadruple H-bonding array and compounds 2a–c.
Compound 4 was then used to alkylate cytosine 5 at N-1 and
the reaction was examined using different bases, including
potassium carbonate, caesium carbonate and sodium carbonate.
In all cases, the coupled product 6 was obtained in low yields
of typically 15%. Reaction of 6 with hexylisocyanate in
pyridine then gave 7 in a 50% yield. Problems have been
reported when alkylating cytosine at N-1 due to competing
O-2 alkylation and this is normally alleviated to some degree
by using N-4 acetylcytosine rather than cytosine.5,8 To
improve the yield for the alkylation step, rather than N-4
acetylation and deprotection, instead cytosine 5 was reacted
with hexylisocyanate in pyridine to form the urea 8 in 93%
yield. Alkylation was then performed at N-1 as before using
mesylate 4, which gave 7 in 49% yield after purification.
Removal of the Cbz group under standard conditions readily
gave the N-1 terminal amine 3 in high yield, and no reduction
of the heterocyclic ring was observed.
Scheme 1 Synthesis of amine terminated analogue 3. Reagents and
conditions: (i) K2CO3, DMF, 80 1C, 15%; (ii) C6H13NCO, pyridine,
110 1C, 50%; (iii) C6H13NCO, pyridine, 110 1C, 93%; (iv) 4, K2CO3,
DMF, 80 1C, 49%; (v) H2, Pd/C, MeOH, 84%.
form linear supramolecular polymers was assessed following
substitution at N-9 to give rise to a head–head arrangement A
(Fig. 2), directly incorporating a telechelic PEG (3400 g molꢁ1
Compound 3 was then activated using excess carbonyldi-
imidazole to give the intermediate 9 which was directly reacted
with a series of commercially available linear and branched
NH2-terminated telechelic polymers 10–13 to give materials
14–17 in 45 to 60% yield (Scheme 2, Table 1).
)
(2a) and via a hydrophobic spacer and carbamate poly-
(2-methyl-1,3-propylene adipate) (2000 g molꢁ1) (2b and 2c).4,5
Diffusion experiments showed slow diffusion coefficients (D)
indicative of the formation of high molecular weight supra-
molecular polymers. Cytosine has been widely substituted at
N-1, but bis-cytosines incorporating a linker at N-1 have
received little attention. With a view to expanding the diversity
of UCyt polymer architectures, in current work we have
investigated incorporating a polymer via a linker at N-1, to
generate a tail–tail arrangement B (Fig. 2) to establish whether
they readily assemble into DDAA arrays.
Purification of these polymers was performed using silica gel
chromatography and a gradient column with ethyl acetate/
methanol (3 : 1) and then chloroform/methanol (7 : 1).
Removal of the remaining traces of the carbonyldiimidazole
was not straightforward. However, it was carefully removed as
even small quantities can decrease the degree of polymerisation
in the final polymer.
Analysis of the 1H NMR spectra of polymers 14 to 17
indicated that the materials had formed quadruple hydrogen-
bonded arrays, with proton signals at d 10.9 ppm and 8.9 ppm
corresponding to the unfolded urea protons at 7-H and 9-H
(Fig. 2B and Fig. 3). Previous studies on model cytosine
DDAA array systems have established that 7-H is observed
at approximately d 10.9 ppm while the urea 9-H is at d 9.0 ppm.
Results and discussion
To prepare polymers at N-1 the amine terminated cytosine 3
was prepared (Scheme 1). 6-Aminohexanol was Cbz protected
then activated as the mesylate 4 as previously described.6,7
c
This journal is The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2011
New J. Chem., 2011, 35, 1522–1527 1523

Scheme 2 Synthesis of polymers 14–17 (X = polymers 10–13).
Reagents and conditions: (i) carbonyldiimidazole, Et3N; (ii) polymers
10–13, Et3N, 45–60% over 2 steps.
Fig. 3 1H NMR spectrum of polymer 15.
For the folded conformer these are both normally observed at
about 9.6 ppm. Furthermore, the N–H chemical shifts for
the new polymer urea bond were observed at approximately
d 5.2 ppm. Proton integrations were also in accordance with
formation of the desired bifunctional polymers.
polymers 16 and 17, although the decrease was less
pronounced, perhaps due to methyl side-groups in the
telechelic materials resulting in slightly weaker hydrogen-
bonding and polymerisation levels. Dilution of the materials
14–17 from 22 mM down to a concentration of 6 mM
in CDCl3, resulted in an increase in the diffusion as expected,
but it was still consistent with the formation of oligomeric
species.
The telechelic polymers 10 to 13 and supramolecular poly-
mers 14 to 17 were then studied using NMR diffusion
measurements in order to evaluate the diffusion coefficients
(D) and to estimate the average molecular weight (M). Two
concentrations were chosen for the diffusion experiments,
6 mM and 22 mM. From the data, the diffusion coefficients
for 22 mM solutions of the telechelic polymers in CDCl3
varied from 14.8 ꢀ 10ꢁ11 m2 sꢁ1 for the largest polymer
(11, PEG 3400 g molꢁ1) to 30.8 ꢀ 10ꢁ11 m2 sꢁ1 for the smallest
one (10, PEG 1500 g molꢁ1). The polymers 13 (PPG-PEG-PPG
The degree of polymerisation (DP) for 14 to 17 in 22 mM
CDCl3 solutions was approximately 5–19 monomeric units for
the supramolecular polymers generated (Table 1) (DPs of
approximately 2–4 were estimated at concentrations of 6 mM).
Differential scanning calorimetry (DSC) of the polymers
indicated glass transition temperatures Tg of just above
ꢁ50 1C for 15 and 17 although for 16 the Tg was not detectable
in the range ꢁ50 to 200 1C (not determined for 14). Overall the
data indicated that quadruple hydrogen-bonding arrays could
be prepared via the incorporation of polymers at N-1.
2000
g ) and polysiloxanes 12 (2500 g )
molꢁ1 molꢁ1
had intermediate diffusion coefficients of approximately
22 ꢀ 10ꢁ11 m2
s
ꢁ1. For the supramolecular polymers 14 to
17 there was a clear decrease in the diffusion coefficient at a
concentration of 22 mM in CDCl3, compared to the telechelic
polymers before functionalisation. For example polymer 15
showed a decrease from 14.8 ꢀ 10ꢁ11 m2 sꢁ1 to 3.8 ꢀ 10ꢁ11 m2 sꢁ1
consistent with the presence of high molecular weight species
in solution in CDCl3, as a consequence of the self-assembly.
This diffusion coefficient was comparable to that observed for
polymer 2a, previously prepared using polymer 11 conjugated
via a head–head quadruple array (A, Fig. 2) where D was
measured as 1.9 ꢀ 10ꢁ11 m2 sꢁ1 at a concentration of 37 mM
in CDCl3. A decrease in D was also observed for 14, when
incorporating the lower molecular weight telechelic polymer
10. Decreased diffusion coefficients were similarly observed for
Conclusions
In summary, supramolecular polymers have been generated
via the addition of a linker at N-1 in ureidocytosines, and
conjugation of this to telechelic polymers led to the formation
of oligomeric species, as determined by NMR diffusion
measurements. Since it has now been established that
DDAA-based UCyt polymers can be prepared via the attach-
ment of polymeric species at N-1 and N-9, bis-functionalised
polymeric assemblies can now be constructed.
Table 1 Polymers prepared (14–17), diffusion coefficients (D) and estimated degrees of polymerisation (DP)
Polymer X incorporated
MW X g molꢁ1
Diffusiona (D) m2 sꢁ1
Polymer
Diffusionb (D) m2 sꢁ1
Diffusiona (D) m2 sꢁ1
DPa
10
11
12
13
1500
3400
2500
2000
30.8 ꢀ 10ꢁ11
14.8 ꢀ 10ꢁ11
22.6 ꢀ 10ꢁ11
21.5 ꢀ 10ꢁ11
14
15
16
17
24.0 ꢀ 10ꢁ11
10.7 ꢀ 10ꢁ11
14.7 ꢀ 10ꢁ11
18.6 ꢀ 10ꢁ11
12.8 ꢀ 1ꢁ0ꢁ1111
3.8 ꢀ 10
5
19
7
8.5 ꢀ 10ꢁ11
10.6 ꢀ 10ꢁ11
6
a
b
Concentration 22 mM. Concentration 6 mM.
c
1524 New J. Chem., 2011, 35, 1522–1527
This journal is The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2011

dried under vacuum to give 8 (0.200 g, 93%) as a white solid,
which was used without further purification. Mp 178–180 1C
(hexane); nmax/cmꢁ1 (solid) 3414, 3362, 3232, 3136, 2927, 2858,
1728, 1701, 1633, 1598; 1H NMR (400 MHz; DMSO-d6)
d 11.26 (1H, broad s, 1-H), 9.83 (1H, broad s, 7-H), 9.13
(1H, broad, 9-H), 7.65 (1H, d, J 7.0 Hz, 6-H), 6.16 (1H, broad
d, 5-H), 3.15 (2H, app. q, J 6.6 Hz, NHCONHCH2), 1.45
(2H, m, CH2), 1.26 (6H, m, 3 ꢀ CH2), 0.85 (3H, t, J 6.6 Hz,
CH3); 13C NMR (125 MHz; DMSO-d6) d 163.5 (C-4), 155.1
(NHCONH), 153.3 (C-2), 145.3 (C-6), 93.8 (C-5), 39.0
(CH2N), 30.9, 29.3, 26.1, 22.1 (CH2CH3), 13.9 (CH3); HRMS
(+CI) calculated for C11H19N4O2 (MH+) 239.15079,
measured 239.15105.
Experimental
General methods
Unless otherwise noted, solvents and reagents were reagent
grade from commercial suppliers and used without further
purification. Anhydrous solvents were obtained using anhydrous
alumina columns.9 All moisture-sensitive reactions were per-
formed under
a nitrogen atmosphere using oven-dried
glassware. Reactions were monitored by TLC on Kieselgel
60 F254 plates with detection by UV, or permanganate, and
phosphomolybdic acid stains. Flash column chromatography
was carried out using silica gel (particle size 40–63 mm).
Melting points are uncorrected. 1H NMR and 13C NMR
spectra were recorded in CDCl3 at the field indicated. J values
are given in Hz. Cbz protected aminohexanol and compound 4
were prepared as previously described.5,6 Full details of
methods for NMR diffusion measurements (all at 298 K) were
previously described.10 Assuming that supramolecular
polymers 14–17 are monodisperse, a relationship between
Dw in water and molecular weight M of a polymer was used
to estimate M of 14–17.11 First, an estimate of diffusion
coefficients in water (Dw) was made by dividing the D values
measured in CDCl3 (Table 1) by the ratio of the solvent
viscosities (Z(H2O)/Z(CHCl3) = 1.75) based on the Einstein–
Smoluchowski relation. Then using the relationship between
{6-[4-(3-Hexyl-ureido)-2-oxo-2H-pyrimidin-1-yl]-hexyl}-
carbamic acid benzyl ester 7
Method 1. The reaction was carried out under anhydrous
conditions. To a solution of compound 6 (0.700 g, 2.03 mmol)
in dry pyridine (9 ml) was added hexylisocyanate (0.336 g,
2.64 mmol) and the mixture was stirred at 110 1C for 15 h. The
reaction was cooled to rt and hexane was added that led to the
formation of a white precipitate, which was collected by
filtration. The product was washed with hexane, dried under
vacuum and recrystallised from ethyl acetate to give 7 (0.478 g,
50%) as a white solid, and the characterisation data was
identical to that given for 7 below.
Dw and M (Dw = 10ꢁ7.62 Mꢁ0.62, with Dw in units of m2 sꢁ1 11
)
approximate values of degrees of polymerisation (DP) were
estimated as M/Mmono, where Mmono is the molecular weight
of the monomeric unit.
Method 2. The reaction was carried out under anhydrous
conditions. To a solution of compound 8 (1.00 g, 4.20 mmol)
in dry DMF (100 ml) was added potassium carbonate (0.640 g,
4.64 mmol) and mesylate 4 (1.73 g, 5.26 mmol). The mixture
was stirred under nitrogen at 80 1C for 20 h. The solution was
then filtered and the solvent was evaporated under vacuum.
The residue was recrystallised using ethyl acetate to give 7 as a
white solid (0.966 g, 49%). Mp 270 1C decomp. (hexane);
6-[(4-Amino-2-oxo-2H-pyrimidin-1-yl)-hexyl]-carbamic acid
benzyl ester 6
To a solution of cytosine 5 (0.258 g, 2.33 mmol) in DMF
(30 ml) was added mesylate 4 (1.00 g, 3.03 mmol) and
anhydrous potassium carbonate (0.385 g, 2.79 mmol). The
solution was heated at 80 1C for 18 h, then cooled, filtered and
the solvent evaporated under vacuum. The residue was recrys-
tallised from ethyl acetate affording 6 (0.120 g, 15%) as a white
solid. Mp 160–162 1C (ethyl acetate); 1H NMR (500 MHz;
CDCl3) d 7.30 (5H, m, Ph), 7.19 (1H, d, J 7.1 Hz, 6-H), 5.63
(1H, d, J 7.1 Hz, 5-H), 5.1 (2H, s, CH2Ph), 4.92 (1H, broad s,
NHCOO), 3.72 (2H, t, J 7.2 Hz, CH2N), 3.15 (2H, q, J 6.7 Hz,
CH2NHCOO), 1.76 (2H, broad s, NH2), 1.68 (2H, m,
CH2CH2N), 1.48 (2H, m, OCONHCH2CH2), 1.25 (4H, m,
2 ꢀ CH2); 13C NMR (100 MHz; CDCl3) d 165.3 (C-2), 156.5
(C-4), 145.8 (C-6), 136.6 (C-Ph), 128.4 (signals superimposed),
93.7 (C-5), 66.9 (CH2OCONH), 50.3 (CH2N), 41.1
(CH2NHCOO), 30.0, 29.1, 26.5 (signals superimposed);
HRMS (+CI) calculated for C18H25N4O3 (MH+) 345.19267,
measured 345.19272.
n
max/cmꢁ1 3327, 3217, 3059, 2860, 1700, 1660, 1620, 1554,
1
1514; H NMR (500 MHz; CDCl3) d 10.88 (1H, s, 7-H), 8.94
(1H, s, 9-H), 7.53 (1H, broad, 5-H), 7.37 (1H, d, J 7.1 Hz,
6-H), 7.30 (5H, m, Ph), 5.06 (2H, s, CH2Ph), 4.73 (1H, s,
NHCOO), 3.77 (2H, t, J 7.2 Hz, CH2N), 3.21 (2H, broad q,
NHCONHCH2), 3.18 (2H, q, J 6.7 Hz, CH2NHCOO), 1.71
(2H, quint, J 6.9 Hz, CH2CH2N), 1.56 (2H, broad quint,
NHCONHCH2CH2), 1.50 (2H, m, CH2CH2NHCOO), 1.33
(6H, m, 3 ꢀ CH2), 1.29 (4H, m, 2 ꢀ CH2), 0.84 (3H, t, J 7.3
Hz, CH3); 13C NMR (125 MHz; CDCl3) d 164.9 (C-4), 157.2
(C-2), 156.4 (NHCOOCH2), 154.3 (NHCONH), 146.6 (C-6),
136.6 (C-Ph), 128.5 (C-Ph), 128.1 (C-Ph), 97.4 (C-5), 66.6
(CH2OCONH), 50.6 (CH2N), 40.8 (CH2NHCOO), 40.1
(CH2NHCONH), 31.5, 29.8, 29.4, 28.8, 26.6, 26.2, 26.1, 22.6
(CH2CH3), 14.1 (CH3); HRMS (+CI) calculated for
C25H38N5O4 (MH+) 472.29183, found 472.29041.
1-Hexyl-3-(2-oxo-1,2-dihydro-pyrimidin-4-yl)-urea 8
1-[1-(6-Amino-hexyl)-2-oxo-1,2-dihydro-pyrimidin-4-yl]-3-
hexyl-urea 3
The reaction was carried out under anhydrous conditions. To
a solution of cytosine (0.100 g, 0.900 mmol) in pyridine (5 ml)
was added hexylisocyanate (0.140 ml, 0.960 mmol). The
reaction was heated at 110 1C for 16 h, then cooled to rt
and hexane was added, which led to the formation of a white
precipitate, which was collected by filtration. The product was
To compound 7 (0.700 g, 1.48 mmol) in methanol (25 ml),
Pd/C (10% Degussa wet; 0.070 g) was added. The reaction was
stirred for 18 h under a hydrogen atmosphere. The reaction
was then filtered through Celite, and the residual solvent
evaporated under vacuum giving compound 3 (0.420, 84%)
c
This journal is The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2011
New J. Chem., 2011, 35, 1522–1527 1525

as a white solid. Mp 169–171 1C (methanol); nmax/cmꢁ1 3365,
3217, 3058, 2923, 2852, 1708, 1660, 1620, 1566, 1562; 1H NMR
(500 MHz; DMSO-d6) d 8.98 (1H, s, 7-H), 8.94 (1H, s, 9-H),
7.90 (1H, d, J 7.1 Hz, 6-H), 6.24 (1H, d, J 7.1 Hz, 5-H), 3.70
Polymer 16 incorporating 12 (MW 2500)
1H NMR (500 MHz; CDCl3) d 10.88 (2H, broad s, 7-H), 8.92
(2H, broad s, 9-H), 7.49 (2H, broad s, 5-H), 7.42 (2H, d, J 7.1
Hz, 6-H), 4.45 (4H, broad s, NHCONH), 3.78 (4H, m, 16-H),
3.22 (4H, m, 10-H), 3.10 (8H, m, CH2CH2NHCONH-
CH2CH2CH2Si+ NHCONHCH2CH2CH2Si), 1.55–1.24
(36H, m, 18 ꢀ CH2), 0.83 (6H, t, J 6.6 Hz, 2 ꢀ CH3), 0.50
(4H, m, 2 ꢀ CH2Si), 0.08 (250H, s, 125 ꢀ CH3Si); 13C NMR
(125 MHz; CDCl3) d 164.6 (C-4), 158.2 (CH2NHCONHCH2),
157.1 (C-2), 154.3 (C-8), 146.7 (C-6), 97.1 (C-5), 50.5 (CH2N),
43.3 (OSiCH2CH2CH2NH), 40.1 (C-10+CH2NHCONH(CH2)3
SiO), 33.0 (CH2NHCH2CH2Si), 31.5, 30.0, 29.4, 28.8, 26.6,
26.3, 26.0, 24.1, 22.6, 15.3 (CH2Si), 14.0 (CH3), 0.7 (CH3Si).
(2H, t,
J 7.2 Hz, CH2N), 3.15 (2H, q, J 6.4 Hz,
NHCONHCH2), 1.57 (2H, m, CH2), 1.43 (2H, m, CH2),
1.30 (12H, m, 6 ꢀ CH2), 0.84 (3H, t, J 7.3 Hz, CH3);
13C NMR (125 MHz; DMSO-d6) d 162.3 (C-4), 154.1 (C-2),
153.6 (NHCONH), 148.4 (C-6), 94.2 (C-5), 49.2 (CH2N), 41.4
(CH2NH2), 39.5 (CH2NHCONH), 33.5, 31.3, 29.7, 28.8, 26.4,
26.2, 22.4 (CH2CH3), 14.2 (CH3); HRMS (+CI) calculated for
C17H32N5O2 338.25505 (MH+), measured 338.25484.
General polymer synthesis
1,10-Carbonyldiimidazole (0.166 g, 1.02 mmol) and amine 3
(0.300 g, 0.890 mmol) were stirred in chloroform (10 ml) for
18 h at rt. Hexane (40 ml) was added and the precipitate 9
(0.366 g, 95%) collected by filtration, then used directly in the
next step. To a solution of the polymer (e.g. PEG 3400)
(0.350 g, 1.04 mmol) in dry THF (15 ml) was added the
imidazolide 9 (0.180 g, 4.17 mmol). The solution was heated
at reflux for 16 h, then evaporated to dryness and the residue
redissolved in chloroform. The organic phase was washed with
water (10 ml) and brine (20 ml), then dried (MgSO4). The
solvent was evaporated under vacuo and the product purified
using flash silica chromatography (methanol/ethyl acetate,
1 : 2 then chloroform/methanol, 7 : 1) to give polymers 14 to
17 in approximately 45–60% yield.
Polymer 17 incorporating 13 (MW 2000)
Mp 40 1C; 1H NMR (500 MHz; CDCl3) d 10.85 (2H, broad s,
7-H), 8.92 (2H, broad s, 9-H), 7.49 (2H, broad s, 5-H), 7.42
(2H, d, J 7.1 Hz, 6-H), 5.08 (4H, broad s, NHCONH), 3.76
(4H, m, 16-H), 3.50 (216H, m, CH2O+CHCH3), 3.20 (4H, m,
10-H), 3.10 (4H, m, 21-H), 1.69 (4H, m, 2 ꢀ CH2), 1.55–1.24
(28H, m, 14 ꢀ CH2), 1.08 (23H, m, CH3), 0.83 (6H, t, J 6.6 Hz,
2 ꢀ CH3); 13C NMR (100 MHz; CDCl3) d 164.7 (C-4), 158.4
(CH2NHCONHCH(CH3)), 157.1 (C-2), 154.2 (C-8), 146.8
(C-6), 97.1 (C-5), 75.1 (OCHCH3), 70.5 (CH2O, signals super-
imposed), 50.5 (CH2N), 46.2 (NHCONHCH(CH3)), 40.0
(CH2NHCONHCH2CH(CH3)O+C-10), 31.4, 30.2, 29.3
(CH2), 28.8 (CH2), 26.6, 26.4, 26.1, 22.5, 18.4 (OCH(CH3),
17.0 (NHCHCH3), 13.0 (CH2CH3).
Differential Scanning Calorimetry (DSC) thermograms
were obtained using a TA instrument Q100 DSC. Samples
were analysed in a pierced lid pan. An initial melt run was
carried out from room temperature (18 1C) to 300 1C at
20 1C minꢁ1. The sample was then equilibrated at ꢁ90 1C,
heated to 300 1C at a rate of 10 1C minꢁ1 and stabilised again
at 300 1C then cooled to 90 1C at the same rate. Samples were
analysed in triplicate.
Polymer 14 incorporating 10 (MW 1500)
Mp 169 1C; 1H NMR (500 MHz; CDCl3) d 10.84 (2H, broad s,
7-H), 8.89 (2H, broad s, 9-H), 7.47 (2H, broad s, 5-H), 7.43
(2H, d, J 7.1 Hz, 6-H), 5.20 (2H, broad s, 23-H), 4.95
(2H, broad s, 22-H), 3.76 (4H, m, 16-H), 3.50 (130H, m,
65 ꢀ CH2O), 3.21 (8H, m, 24-H and 10-H), 3.10 (4H, m, 21-H),
1.69 (8H, m, 4 ꢀ CH2), 1.55–1.24 (28H, m, 14 ꢀ CH2), 0.83
(6H, t, J 6.6 Hz, 2 ꢀ CH3); 13C NMR (100 MHz; CDCl3)
d 164.7 (C-4), 158.8 (CH2NHCONHCH2), 157.1 (C-2), 154.3
(C-8), 146.8 (C-6), 97.1 (C-5), 70.5 (CH2O signals super-
imposed), 69.8 (NHCH2CH2O), 69.6 (NHCH2CH2O), 50.6
(CH2N), 40.0 (OCH2CH2NH), 40.0 (CH2NHCONHCH2CH2O),
38.5 (CH2NH), 31.5, 30.7, 29.3, 28.8, 26.6, 26.4, 26.1, 22.6,
14.1 (CH3).
Acknowledgements
We thank AWE plc. for studentships and funding (V.G.H.L.
and E.G.).
Notes and references
Polymer 15 incorporating 11 (MW 3400)
1 Examples of general reviews on hydrogen bonded supramolecular
polymers and assemblies (a) L. Brunsveld, B. J. B. Folmer,
E. W. Meijer and R. P. Sijbesma, Chem. Rev., 2001, 101, 4071;
(b) A. T. ten Cate and R. P. Sijbesma, Macromol. Rapid Commun.,
2002, 23, 1094; (c) A. W. Bosma, L. Brunsveld, B. J. B. Folmer,
R. P. Sijbesma and E. W. Meijer, Macromol. Symp., 2003, 201,
143; (d) A. J. Wilson, Soft Matter, 2007, 3, 409; (e) J. L. Sessler,
C. M. Lawrence and J. Jayawickramarajah, Chem. Soc. Rev., 2007,
36, 314; (f) P. Y. W. Dankers and E. W. Meijer, Bull. Chem. Soc.
Jpn., 2007, 80, 2047; (g) T. F. A. de Greef, M. M. J. Smulders,
M. Wolfs, A. P. H. J. Schenning, R. P. Sijbesma and E. W. Meijer,
Chem. Rev., 2009, 109, 5687.
Mp 40 1C; 1H NMR (400 MHz; CDCl3) d 10.89 (2H, broad s,
7-H), 8.88 (2H, broad s, 9-H), 7.51 (2H, broad s, 5-H), 7.44
(2H, d, J 7.3 Hz, 6-H), 5.28 (2H, broad s, 24-H), 5.10
(2H, broad s, 22-H), 3.80 (4H, m, 16-H), 3.50 (150H, m,
75 ꢀ CH2O), 3.33 (4H, q, J 5.1 Hz, 25-H), 3.23 (4H, br q,
J 6.0 Hz, 10-H), 3.12 (4H, m, 21-H), 1.72 (4H, m, 2 ꢀ CH2),
1.55–1.24 (28H, m, 14 ꢀ CH2), 0.86 (6H, t, J 6.6 Hz, 2 ꢀ CH3);
13C NMR (125 MHz; CDCl3)
d 164.7 (C-4), 158.7
(CH2NHCONHCH2), 156.2 (C-2), 154.2 (C-8), 146.7 (C-6),
97.0 (C-5), 70.4 (CH2O, signals superimposed), 70.2, 69.8
(NHCH2CH2O), 50.5 (CH2N), 40.1 (OCH2CH2NH), 40.0
(CH2NHCONHCH2CH2O), 39.9 (CH2NH), 31.4, 30.1, 29.6,
29.3, 28.7, 26.5, 26.3, 26.1, 22.6, 13.9 (CH3).
2 Examples of quadruple hydrogen bonded modules (a) C. Schmuck
and W. Wienand, Angew. Chem., Int. Ed., 2001, 40, 4363;
(b) P. S. Corbin, S. C. Zimmerman, P. A. Theissen,
N. A. Hawryluk and T. J. Murray, J. Am. Chem. Soc., 2001,
123, 10475; (c) U. Luning, C. Kuhl and A. Uphoff, Eur. J. Org.
¨
Chem., 2002, 4063; (d) R. P. Sijbesma and E. W. Meijer,
¨
c
1526 New J. Chem., 2011, 35, 1522–1527
This journal is The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2011

Chem. Commun., 2003, 5; (e) T. Park, S. C. Zimmerman and
S. Nakashima, J. Am. Chem. Soc., 2005, 127, 6520;
(f) Y. Hisamatsu, N. Shirai, S. Ikeda and K. Odashima, Org.
Lett., 2009, 11, 4342.
and P. Woisel, Chem. Commun., 2007, 2246; (i) T. F. A. de Greef,
M. M. L. Nieuwenhuizen, R. P. Sijbesma and E. W. Meijer,
J. Org.Chem., 2010, 75, 598.
4 V. G. H. Lafitte, A. E. Aliev, P. N. Horton, M. B. Hursthouse,
K. Bala, P. Golding and H. C. Hailes, J. Am. Chem. Soc., 2006,
128, 6544.
5 E. Greco, A. E. Aliev, V. G. H. Lafitte, K. Bala, D. Duncan,
L. Pilon, P. Golding and H. C. Hailes, New J. Chem., 2010, 34,
2634.
6 E. Boseggia, M. Gatos, L. Lucatello, F. Mancin, S. Moro,
M. Palumbo, C. Sissi, P. Tecilla, U. Tonellato and G. Zagotto,
J. Am. Chem. Soc., 2004, 126, 4543.
7 K. C. Nicolaou, K. Koide and M. E. Bunnage, Chem.–Eur. J.,
1995, 1, 454.
8 W. E. Lindsell, C. Murray, P. N. Preston and T. A. J. Woodman,
Tetrahedron, 2000, 56, 1233.
9 A. B. Pangborn, M. A. Giardello, R. H. Grubbs, R. K. Rosen and
F. J. Timmers, Organometallics, 1996, 15, 1518.
10 C. E. Atkinson, A. E. Aliev and W. B. Motherwell, Chem.–Eur. J.,
2003, 9, 1714.
11 A. Chen, D. Wu and C. S. Johnson, Jr., J. Am. Chem. Soc., 1995,
117, 7965.
3 Examples of Upy quadruple hydrogen bonded systems
(a) R. P. Sijbesma, F. H. Beijer, L. Brunsveld, B. J. B. Folmer,
J. H. K. K. Hirschberg, R. F. M. Lange, J. K. L. Lowe and
E. W. Meijer, Science, 1997, 278, 1601; (b) F. H. Beijer,
R. P. Sijbesma, H. Kooijman, A. L. Spek and E. W. Meijer,
J. Am. Chem. Soc., 1998, 120, 6761; (c) S. H. M. Sontjens,
R. P. Sijbesma, M. H. P. van Genderen and E. W. Meijer,
J. Am. Chem. Soc., 2000, 122, 7487; (d) J. B. Folmer,
R. P. Sijbesma, R. M. Versteegen, J. A. J. van der Rijt and
E. W. Meijer, Adv. Mater., 2000, 12, 874; (e) S. H. M. Sontjens,
R. P. Sijbesma, M. H. P. van Genderen and E. W. Meijer,
Macromolecules, 2001, 34, 3815; (f) V. G. H. Lafitte, A. E. Aliev,
H. C. Hailes, K. Bala and P. Golding, J. Org. Chem., 2005, 70,
2701; (g) V. G. H. Lafitte, A. E. Aliev, P. N. Horton,
M. B. Hursthouse and H. C. Hailes, Chem. Commun., 2006,
2173; (h) A.-M. Alexander, M. Bria, G. Brunklaus, S. Caldwell,
G. Cooke, J. F. Garety, S. G. Hewage, Y. Hocquel, N. McDonald,
G. Rabani, G. Rosair, B. O. Smith, H. W. Speiss, V. M. Rotello
c
This journal is The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2011
New J. Chem., 2011, 35, 1522–1527 1527