Electronic substituent effects on hydrogen-bonding motifs modulate supramolecular polymerisation

Article abstract of DOI:10.1039/c2ra22715k

Hydrogen-bond assembled supramolecular polymers receive enormous interest as stimuli responsive materials that can be obtained using small easy to purify organic molecules. A key feature that determines materials properties in dilute solution is the strength of interaction between supramolecular synthons. In this work we illustrate that electronic substituents which are conjugated to the hydrogen-bonding motif can have subtle but significant effects on the degree of supramolecular polymerisation. Using ureidopyrimidines which contain electron donating phenolate and benzoate ester linkages in direct electronic communication with the self-complementary hydrogen-bonding motif, diffusion ordered spectroscopy (DOSY) demonstrates predictable differences in the extent of supramolecular polymerisation.

Full text of DOI:10.1039/c2ra22715k

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Electronic substituent effects on hydrogen-bonding
motifs modulate supramolecular polymerisation3
Cite this: RSC Advances, 2013, 3,
3103
Maria L. Pellizzaro,a Julie Fishera and Andrew J. Wilson*ab
Hydrogen-bond assembled supramolecular polymers receive enormous interest as stimuli responsive
materials that can be obtained using small easy to purify organic molecules. A key feature that determines
materials properties in dilute solution is the strength of interaction between supramolecular synthons. In
this work we illustrate that electronic substituents which are conjugated to the hydrogen-bonding motif
can have subtle but significant effects on the degree of supramolecular polymerisation. Using
ureidopyrimidines which contain electron donating phenolate and benzoate ester linkages in direct
electronic communication with the self-complementary hydrogen-bonding motif, diffusion ordered
spectroscopy (DOSY) demonstrates predictable differences in the extent of supramolecular polymerisation.
Received 31st October 2012,
Accepted 20th December 2012
DOI: 10.1039/c2ra22715k
www.rsc.org/advances
changing remote (but conjugated) electronic substituents.13
We were keen to extend this observation further and probe the
extent to which supramolecular polymerisation is affected by
substituent effects on the non-covalent interactions between
supramolecular monomers. Herein we illustrate that supra-
molecular polymerisation is indeed effected in a subtle
manner by proximal electronic substituents.
Introduction
Supramolecular polymers1,2 have received enormous interest
as functional materials as a direct consequence of the
emergent properties they elicit, notably stimuli responsive
behaviour1 and self-healing characteristics.3 Applications
include scaffolds for biomedical purposes and conductive
materials.2 A wide array of architectures have been assembled
using the full gamut of non-covalent interactions;1,4 of these,
hydrogen-bonding,5 owing to its tuneability and directionality
has received considerable attention. A central concept in
supramolecular polymer science is that the affinity between
monomeric building blocks must be sufficiently high to confer
materials properties in dilute solution,6,7 although lateral
association also plays a defining role.8–10 Therefore, the design
and synthesis of heterocyclic hydrogen-bonding motifs with
well defined and high-affinity molecular recognition beha-
viour11 plays a key role in defining the extent of supramole-
cular association and polymerisation.
Results and discussion
Design and synthesis
To test our hypothesis that remote substituent control over
hydrogen-bond mediated dimerisation translates into measur-
able differences in supramolecular polymerisation it was
necessary to identify a suitable synthetic test system. We have
previously reported that remote substituents can affect the
Our group has previously reported on the design and
synthesis of a series of hydrogen-bonding motifs capable of
forming triply12–14 and quadruply15 hydrogen-bonded hetero-
dimers that can be used to assemble supramolecular
polyurethane elastomers.16 Using one of these heterodi-
N
mers—the ureidoimidazole/amiodisocytosine 12 motif
(Fig. 1)—we illustrated that dimerisation affinity could be
tuned over nearly two orders of magnitude, simply by
aSchool of Chemistry, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, United
Kingdom. E-mail: A.J.Wilson@leeds.ac.uk; Fax: +44 (0)113 3436565;
Tel: +44 (0)113 3431409
N
Fig. 1 Triply hydrogen-bonded heterodimer 12 illustrating how substituent
effects can modulate dimerisation affinity. The substituent has a major effect on
the hydrogen-bonding ability of 1 with electron-withdrawing substituents
leading to greater H-bond acidity of the anilide whereas in 2 only minor effects
are observed because the carbonyl group insulates against the effect of the
substituent.
bAstbury Centre for Structural Molecular Biology, University of Leeds, Woodhouse
Lane, Leeds, LS2 9JT, United Kingdom
Electronic supplementary information (ESI) available: NMR spectra. See DOI:
3
10.1039/c2ra22715k
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Scheme 1 Synthesis of ditopic UPy bases supramolecular monomers 3 and 4.
binding affinity of triply hydrogen bonded systems.13
However, we chose not to use the triple hydrogen bond dimer
in this study because it was considered (a) too complex a
system for the purpose of this investigation in that it would be
difficult to ascribe any changes in supramolecular polymerisa-
tion to a change in the recognition properties of either
component of the heterodimer and (b) too low affinity a
system to get significant polymerisation in dilute solutions.
This challenge was compounded further by the fact that
different substituents could potentially exert other effects on
the supramolecular polymerisation of a ditopic monomer.
Thus a simpler ditopic building block capable of homodimer-
isation was desired: the ditopic ureidopyrimidines (UPys) 3
and 4 presented themselves as suitable building blocks. UPys 3
and 4 have the advantage of both being esters hence
minimising any differences in supramolecular polymerisation
arising as a consequence of interactions made by the remote
substituent group, however they should experience different
effects on hydrogen-bonding propensity. In 3, the ester group
is linked to the UPy motif via the electron withdrawing carboxy
functional group and in 4 through the electron donating
oxygen group. Intermediate acid 8 and phenol 9 were
synthesised following known standard methods based on
literature procedures as illustrated in Scheme 1. We attempted
to link these intermediates by ester formation with long chain
diols and diacids respectively, however these reactions failed
to yield isolable target material. We thus sought a different
strategy whereby ester formation was performed with a long
chain acid or alcohol possessing an alkene to yield a
metathesis substrate. Upon reaction with Grubbs’ first
generation catalyst, the desired targets 3 and 4 were isolated
as a mixture of E/Z isomers (1 : 1).
Supramolecular polymerisation
The 1H NMR spectra of both 3 and 4 exhibit the characteristic
low field resonances associated with hydrogen-bonded NH’s in
UPy derivatives.17 Notably, as the concentration was decreased
we observed that the 1H NMR peaks sharpened for both
compounds (see ESI ), indicative of smaller assemblies being
3
present and hence depolymerisation, as should be observed
for reversibly assembled polymers. To characterise the
molecular size of the supramolecular polymers in dilute
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Table 1 Diffusion coefficient (D) and degree of polymerisation (DP) for 3 and 4
3
4
Concentration (mM)
D (610210 m2 s21
2.315 ¡ 0.005
3.652 ¡ 0.016
5.817 ¡ 0.007
5.903 ¡ 0.070
)
DP
D (10210 m2 s21
2.089 ¡ 0.010
4.470 ¡ 0.120
5.040 ¡ 0.025
4.858 ¡ 0.060
)
DP
30
20
10
1
16.58 ¡ 0.48
4.22 ¡ 0.09
1.05 ¡ 0.03
1.00
12.57 ¡ 0.29
1.28 ¡ 0.06
0.90 ¡ 0.02
1.00
solution we identified DOSY as an ideal technique to monitor
aggregate size. DOSY can be used to measure the size of the
assemblies that are present in solution, and has been used to
study supramolecular polymerisation previously.18–20 Smaller
assemblies exhibit larger diffusion coefficients (D) consistent
with more rapid tumbling in solution. The diffusion coeffi-
cient was therefore measured for both UPy 3 and 4 at different
concentrations (Table 1).
supramolecular polymer formed by UPy 3 is larger than that
formed by UPy 4. This is consistent with a higher dimerisation
affinity that would be predicted on the basis of substituent
effects – the carbonyl group in 3 is electron withdrawing and
should enhance the acidity of the anilide proton whereas the
phenol ether group in 4 is electron donating and should
decrease the acidity of the anilide proton.
As might be expected upon increasing the concentration,
the diffusion coefficient decreases consistent with an increase
in molecular size. Because D was very similar for 10 and 1 mM
in both polymers we reasoned that this was the smallest
assembly that could be formed in solution; probably repre-
senting a single molecule. On this basis, the degree of
polymerisation (DP) could be calculated (Table 1); firstly the
molecular weights (MW) of the assemblies at each concentra-
tion were calculated (eqn (1)) where D[low] was the D for 1 mM
solutions and MW[low] was assumed to be the monomer. The
DP was then calculated using eqn (2).
Conclusions
In conclusion, we have described the design and synthesis of
two structurally similar UPy derivatives 3 and 4 that allowed us
to probe proximal substituent effects on dimerisation affinity
in the context of their impact on supramolecular polymerisa-
tion. Our results illustrate that the degree of polymerisation
can be affected in a predictable manner; electron withdrawing
substituents enhance polymerisation and electron-donating
substituents diminish polymerisation. The effect is small but
significant enough to warrant careful consideration of the
linking group chemistry that is used to conjugate supramole-
cular synthons to macromolecular building blocks. The effect
could also be used to exert fine control over materials
properties.
pffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi
3 MWLOW
D
½LOWꢀ
pffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi
MWHIGH
~
(1)
(2)
3 MWHIGH
D
½HIGHꢀ
DP~
MWLOW
A plot of DP against concentration for both polymers 3 and 4
(Fig. 2) reveals two features (a) that supramolecular polymer-
isation proceeds at lower concentrations for the UPy with the
electron withdrawing group (i.e. 3) and (b) that the size of the
Experimental section
General points
All reagents were purchased from Aldrich or Alfa–Aesar and
used without further purification unless otherwise stated.
Where anhydrous solvents were required, tetrahydrofuran was
freshly distilled from sodium benzophenone ketyl radical and
dichloromethane was freshly distilled from calcium hydride,
or they were obtained using a solvent purification system from
Innovative Technology Inc. PureSolv. Chloroform was freshly
distilled from calcium chloride under a nitrogen atmosphere.
Anhydrous DMF was obtained ‘‘sure-sealed’’ from Sigma–
Aldrich. Triethylamine was distilled from calcium hydride and
stored, under nitrogen, over potassium hydroxide pellets. All
non-aqueous reactions were carried out under a nitrogen
atmosphere. Analytical thin layer chromatography (TLC) was
conducted using Merck Kieslegel 0.25 mm silica gel pre-coated
aluminium plates with fluorescent indicator active at UV245
.
Purification by column chromatography was carried out using
Merck Kieselgel 60 silica gel. NMR spectra were obtained using
Bruker DMX500 or Bruker AMD300 spectrometers operating at
Fig. 2 Graph showing the correlation between the concentration and DP for
both 3 (dark blue) and 4 (light blue).
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500 MHz or 300 MHz for H spectra and 100 MHz or 75 MHz
for 13C spectra as stated. Proton spectra are referenced to TMS
at 0.00 ppm, and carbon spectra to CDCl3 at 77.4 ppm, unless
otherwise stated. Melting points were determined using a
Griffin D5 variable temperature apparatus and are uncor-
rected. IR spectra were obtained using Perkin–Elmer FTIR
spectrometer. Microanalysis was carried out on a Carlo Erba
Elemental Analyser MOD 1106 instrument. High Resolution
Mass Spectra (HRMS) were recorded on a Micromass GCT
Premier using electron impact ionisation (EI) or a Bruker
Daltonics microTOF using electrospray ionisation (ESI).
added. The suspension was filtered and sonicated in ethyla-
cetate (50 mL) before being filtered and washed (diethyl ether)
to give ethyl 4-(3-(4-oxo-6-tridecyl-1,4-dihydropyrimidin-2-yl)ur-
eido)benzoate (1.22 g, 74%) as a colourless powder; m.p. 218–
220 uC; Rf 0.38 (1 : 99 methanol : dichloromethane); dH (300
MHz, CDCl3); 12.95 (1H, s, NH), 12.52 (1H, s, NH), 12.32 (1H, s,
NH), 8.07 (2H, d, J = 8.7 Hz, ArCH), 7.86 (2H, d, J = 8.7 Hz,
ArCH), 5.94 (1H, s, ArCH), 4.41 (2H, q, J = 7.2 Hz, CH2), 2.47
(2H, t, J = 7.7 Hz, CH2), 1.65 (4H, m, 2 6 CH2), 1.44 (3H, t, J =
7.2 Hz, CH3), 1.32 (18H, m, 9 6 CH2), 0.92 (3H, t, J = 6.6 Hz,
CH3); dC (75 MHz, CDCl3); 172.8, 166.2, 154.4, 154.3, 152.9,
142.8, 130.5, 125.3, 119.3, 105.9, 60.8, 32.4, 31.9, 29.6–29.2 (6
7), 28.9, 26.3, 22.7, 14.4, 14.1; nmax/cm21 (neat); 3466–2850,
1698, 1650; ESI-HRMS found m/z 485.3139 [M+H]+,
C27H41N4O4 requires 485.3122.
2-Amino-6-tridecylpyrimidin-4-ol 5
Was synthesised following minor modifications to a literature
procedures.21 Triethylamine (50.0 mL, 360 mmol) was added
to a suspension of potassium ethyl malonate (40.8 g, 240
mmol) in acetonitrile (250 mL) stirred at 0 uC. The reaction
mixture was stirred for 15 min before magnesium chloride
(28.5 g, 300 mmol) in acetonitrile (80 mL) was added and
allowed to warm to 10 uC. After stirring for 2 h the reaction
mixture was cooled to 0 uC before myristoyl chloride (32.6 mL,
120 mmol) was added dropwise. The reaction mixture was
warmed to room temperature and stirred for 16 h before the
solvents were evaporated in vacuo. The resultant solid was
dissolved in ether (350 mL) and washed with 30% aqueous
hydrochloric acid (250 mL) and saturated aqueous sodium
bicarbonate (100 mL) before the organics were dried over
magnesium sulphate, filtered and evaporated in vacuo. The
resultant solid was purified by column chromatography
(chloroform) to give ethyl 3-oxohexadecanoate (26.9 g, 75%)
as a colourless powder, which was used in the next step
without further purification. Guanidinium carbonate (12.8 g,
142.6 mmol) was added to a solution of 3-oxohexadecanoate
(25.0 g, 83.9 mmol) and potassium tert-butoxide (9.4 g, 83.9
mmol) in EtOH (300 mL) and the reaction mixture was heated
to reflux for 3 days. After cooling the reaction mixture was
filtered and the filtrate was evaporated in vacuo. The resultant
solid was dissolved in water (500 mL) and the solution was
acidified to pH 6 (acetic acid). The resultant suspension was
filtered and the solid washed with acetone and ether before
being crystallised (propan-2-ol) to give the 2-amino-6-tridecyl-
pyrimidin-4-ol as a cream coloured powder; m.p. 162–165 C; Rf
0.19 (1 : 9 methanol : dichloromethane); dH (300 MHz, DMSO-
d6); 6.58 (2H, s, NH2), 5.33 (1H, s, ArCH), 2.20 (2H, t, J = 6.0 Hz,
CH2), 1.51 (2H, m, CH2), 1.23 (20H, m, 10 6 CH2), 0.85 (3H, t, J
= 6.0 Hz, CH3); the molecule was insufficiently soluble to
obtain a meaningful 13C spectrum; nmax/cm21 (neat); 3360,
3144, 2919, 2850, 2679 (br), 1637, 1468, 1401; ESI-HRMS found
m/z 294.2529 [M+H]+, C17H32N3O requires 294.2540.
1-(4-Methoxyphenyl)-3-(4-oxo-6-tridecyl-1,4-dihydropyrimidin-
2-yl)urea 7
4-Methoxyphenylisocyanate (0.24 mL, 1.90 mmol) was added
to a refluxing mixture of the 2-amino-6-tridecylpyrimidin-4-ol
(0.50 g, 1.71 mmol) and triethylamine (0.24 mL, 1.71 mmol) in
tetrahydrofuran (20 mL). The reaction mixture was then stirred
at reflux for 18 h before being allowed to cool and the volatiles
evaporated in vacuo. The resultant solid was triturated in hot
chloroform (50 mL), filtered and the filtrate evaporated to give
the crude product which was crystallised (chloroform/metha-
nol) to give 1-(4-methoxyphenyl)-3-(4-oxo-6-tridecyl-1,4-dihy-
dropyrimidin-2-yl)urea (0.55 g, 73%) as colourless needles;
m.p. 121–123 uC (Found: C, 67.7; H, 8.65; N, 12.7; C25H38N4O3
requires C, 67.8; H, 8.65; N, 12.7%); Rf 0.57 (1 : 1 ethyl
acetate : hexane); dH (300 MHz, CDCl3); 13.12 (1H, s, NH),
12.27 (1H, s,NH), 12.10 (1H, s, NH), 7.61 (2H, d, J = 9.1 Hz,
ArCH), 6.93 (2H, d, J = 9.1 Hz, ArCH), 5.94 (1H, s, ArCH), 3.84
(3H, s, OCH3), 2.50 (2H, t, J = 7.5 Hz, CH2), 1.68 (2H, m, CH2),
1.60 (4H, m, 2 6 CH2), 1.32 (16H, m, 8 6 CH2), 0.92 (3H, t, J =
6.8 Hz, CH3); dC (75 MHz, CDCl3); 173.1, 156.2, 154.7, 154.6,
152.7, 131.2, 122.4, 114.1, 105.9, 55.5, 32.6, 31.9, 29.7–29.2 (6
7), 28.9, 26.7, 22.7, 14.2; nmax/cm21 (neat); 2916 (br), 1707,
1651, 1574, 1509; ESI-HRMS found m/z 443.3017 [M+H]+,
C
25H39N4O3 requires 443.3017.
4-(3-(4-Oxo-6-tridecyl-1,4-dihydropyrimidin-2-
yl)ureido)benzoic acid 8
Synthesised following a literature procedure.22 1 M Aqueous
sodium hydroxide (4.12 mL, 4.12 mmol) was added to a
suspension of ethyl 4-(3-(4-oxo-6-tridecyl-1,4-dihydropyrimi-
din-2-yl)ureido)benzoate (500 mg, 1.03 mmol) in ethanol (50
mL) and the reaction mixture was heated to 70 uC for 18 h. The
solvent was then evaporated in vacuo and the resultant solid
was dissolved in water (25 mL) and acidified with 10%
aqueous hydrochloric acid. The reaction mixture was then
filtered to give 4-(3-(4-oxo-6-tridecyl-1,4-dihydropyrimidin-2-
yl)ureido)benzoic acid (457 mg, 97%) as a colourless solid;
m.p. 256–257 uC; Rf 0.39 (1 : 9 methanol : dichloromethane);
dH (300 MHz, DMSO-d6); 7.91 (2H, d, J = 9.0 Hz, 2 6 ArCH),
7.64 (2H, d, J = 9.0 Hz, 2 6 ArCH), 5.84 (1H, s, ArCH), 2.44 (2H,
t, J = 7.5 Hz, CH2), 1.59 (2H, m, CH2), 1.21 (20H, m, 10 6 CH2),
0.83 (3H, t, J = 6.0 Hz, CH3); the molecule was insufficiently
soluble to obtain a meaningful 13C spectrum; nmax/cm21
Ethyl 4-(3-(4-oxo-6-tridecyl-1,4-dihydropyrimidin-2-
yl)ureido)benzoate 6
Ethyl-4-isocyanatobenzoate (0.71 g, 3.75 mmol) was added to a
refluxing solution of 2-amino-6-tridecylpyrimidin-4-ol (1.00 g,
3.41 mmol) and triethylamine (0.48 mL, 3.75 mmol) in
tetrahydrofuran (50 mL). The reaction mixture was then
stirred at reflux for 18 h before being allowed to cool and
the volatiles evaporated in vacuo. The resultant solid was
suspended in ethyl acetate (50 mL) and water (50 mL) was
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(neat); 3200–2343, 1689, 1656; ESI-HRMS found m/z 438.2747
[M–H2O]2, C25H34N4O3 requires 438.2631.
allowed to cool to room temperature. The volatiles were then
removed in vacuo and the resultant solid was purified by
column chromatography (gradient elution: 0 : 1–1: 9 metha-
nol : dichloromethane) and crystallisation (chloroform :
methanol) to give the 4-(3-(4-oxo-6-tridecyl-1,4-dihydropyrimi-
din-2-yl)ureido)phenyl undec-10-enoate (758 mg, 54%) as a
colourless powder; m.p. 128–130 uC (Found: C, 70.5; H, 9.15;
N, 9.5; C35H54N4O4 requires C, 70.7; H, 9.15; N, 9.4%); Rf 0.28
(1 : 4 ethyl acetate : hexane); dH (300 MHz, CDCl3); 12.87 (1H,
s, NH), 12.22 (1H, s, NH), 12.11 (1H, s, NH), 7.66 (2H, d, J = 9.0
Hz, 2 6 ArCH), 6.97 (2H, d, J = 9.0 Hz, 2 6 ArCH), 5.75 (1H, m,
CH), 5.73 (1H, s, ArCH), 4.91 (2H, dd, J = 15.3, 22.2 Hz, CH2),
2.47 (2H, t, J = 7.4 Hz, CH2), 2.24 (2H, t, J = 7.5 Hz, CH2), 1.98
(2H, q, J = 6.9 Hz, CH2), 1.68 (2H, m, CH2), 1.48 (2H, m, CH2),
1.32–1.19 (30H, m, 15 6 CH2), 0.81 (3H, t, J = 6.6 Hz, CH3); dC
(75 MHz, CDCl3); 173.0, 172.2, 154.5 (6 2), 152.9, 146.7, 139.2,
135.9, 121.8, 121.2, 114.2, 106.0, 34.4, 33.8, 32.5, 31.9, 29.7–
28.8 (6 13), 26.7, 24.9, 22.7, 14.1; dmax/cm21(neat); 3143, 2924,
281, 1749, 1697, 1580, 1505, 1201; ESI-HRMS found m/z
617.4018 [M+Na]+, C35H54N4NaO4 requires 617.4037.
1-(4-Hydroxyphenyl)-3-(4-oxo-6-tridecyl-1,4-dihydropyrimidin-
2-yl)urea 9
Synthesised following literature procedures.23 Boron tribro-
mide (3.4 mL, 1 M in dichloromethane, 3.39 mmol) was added
dropwise to a suspension of 1-(4-methoxyphenyl)-3-(4-oxo-6-
tridecyl-1,4-dihydropyrimidin-2-yl)urea (500 mg, 1.13 mmol) in
dichloromethane (10 mL) cooled to 278 uC. The reaction
mixture was then allowed to warm to room temperature and
was stirred for 20 h. Water (10 mL) was then added dropwise
before the reaction mixture was filtered and the resultant solid
was triturated with chloroform to give 1-(4-hydroxyphenyl)-3-
(4-oxo-6-tridecyl-1,4-dihydropyrimidin-2-yl)urea (448 mg, 93%)
as a colourless solid; m.p. 175–176 uC; Rf 0.39 methanol :
dichloromethane); dH (300 MHz, DMSO-d6); 9.80 (1H, s, OH),
7.25 (2H, d, J = 8.7 Hz, 2 6 ArCH), 6.73 (2H, d, J = 8.7 Hz, 2 6
ArCH), 5.84 (1H, s, ArCH), 2.43 (2H, t, J = 7.4 Hz, CH2), 1.59
(2H, m, CH2), 1.22 (20H, m, 10 6 CH2), 0.85 (3H, t, J = 6.6 Hz,
CH3); dC (75 MHz, DMSO-d6); 163.6, 163.4, 154.1, 153.5, 152.1,
129.5, 121.7, 115.7, 104.2, 36.1, 31.6, 29.4–29.1 (6 7), 28.7,
27.6, 22.4, 14.3; nmax/cm21 (neat); 3234–2853 (br), 1695, 1646,
1627, 1562, 1505, 1447, 1222, 834; ESI-HRMS found m/z
429.2870 [M+H]+, C24H37N4O3 requires 429.2860.
(E,Z)-Icos-10-ene-1,20-diyl-bis(4-(3-4-oxo-6-tridecyl-1,4-
dihydropyrimidin-2-yl)ureido)benzoate) 3
Grubbs’ (I) catalyst (10 mg, 0.01 mmol) in degassed dichlor-
omethane (2 mL) was added dropwise to a solution of undec-
10-enyl 4-(3-(4-oxo-6-tridecyl-1,4-dihydropyrimidin-2-yl)ureido)
benzoate (150 mg, 0.25 mmol) in degassed chloroform (10 mL)
and the reaction mixture was stirred at room temperature for 2
days. It was then filtered through celite before the solvent was
evaporated and the resultant solid was crystallised (CHCl3–
MeOH) to give (E,Z)-icos-10-ene-1,20-diyl-bis(4-(3-(4-oxo-6-tri-
decyl-1,4-dihydropyrimidin-2-yl)ureido)benzoate) (125 mg,
84%) as an off white powder; dH (300 MHz, CDCl3); 12.59
(2H, br, NH) 12.40 (2H, br, NH), 11.90 (2H, br, NH), 7.91 (4H,
br, ArCH), 7.75 (4H, br, ArCH) 5.60 (0.5H, br, CH), 5.45 (0.5H,
br, CH), 5.35 (1H, br, CH), 4.18 (4H, br, CH2), 1.92 (4H, br,
CH2), 1.68 (4H, br, CH2), 1.20 (72H, br, CH2), 0.85 (6H, br,
CH3); the molecule was insufficiently soluble to obtain a
meaningful 13C spectrum; ESI-HRMS found m/z 1211.8188
[M+Na]+, C70H108N8NaO8 requires 1211.8182.
Undec-10-enyl 4-(3-(4-oxo-6-tridecyl-1,4-dihydropyrimidin-2-
yl)ureido) benzoate 10
10-Undecen-1-ol (358 _L, 1.79 mmol) was added to a solution
of 4-(3-(4-oxo-6-tridecyl-1,4-dihydropyrimidin-2-yl)ureido)ben-
zoic acid (900 mg, 1.97 mmol), dimethylaminopyridine (328
mg, 2.69 mmol) and EDCI (412 mg, 2.15 mmol) in chloroform
(50 mL) and the reaction mixture was heated to reflux for 3
day. It was then allowed to cool to room temperature before
the solvent was evaporated in vacuo and the resultant solid was
purified by column chromatography (gradient elution: 0 : 1–
1: 19 methanol : dichloromethane) to give undec-10-enyl 4-(3-
(4-oxo-6-tridecyl-1,4-dihydropyrimidin-2-yl)ureido)
benzoate
(740 mg, 68%) as a colourless powder; m.p. 122–125 uC; Rf
0.51 (1 : 19 ether : chloroform); dH (500 MHz, CDCl3); 12.96
(1H, s, NH), 12.48 (1H, s, NH), 12.33 (1H, s, NH), 8.03 (2H, d, J
= 8.3 Hz, ArCH), 7.82 (2H, d, J = 8.3 Hz, ArCH), 5.96 (1H, s,
ArCH), 5.82 (1H, ddt, J = 11.0, 17.0, 6.6 Hz, CH), 4.97 (2H, ddd,
J = 11.0, 17.0, 32.3 Hz, CH2), 4.30 (2H, t, J = 6.6 Hz, CH2), 2.52
(2H, t, J = 7.2 Hz, CH2), 2.05 (2H, q, J = 7.2 Hz, CH2), 1.79–1.26
(36H, m, alkyl), 0.87 (3H, t, J = 6.9 Hz, CH3); dC (75 MHz,
CDCl3); 172.9, 166.3, 154.4, 154.3, 153.0, 142.8, 139.2, 130.6,
125.4, 119.4, 114.2, 106.0, 65.0, 33.9, 32.5, 32.0, 29.7–28.8 (6
14), 26.4, 26.1, 22.7, 14.2; nmax/cm21 (neat); 3454, 2922, 2850,
1714, 1696, 1660; ESI-MS found m/z 609.4 [M+H]+, C36H56H4O4
requires 609.4.
(E,Z)-Bis(4-(3-(4-oxo-6-tridecyl-1,4-dihydropyrimidin-2-
yl)ureido)phenyl)icos-10-enedioate 4
Grubbs’ (I) catalyst (10 mg, 0.01 mmol) in degassed dichlor-
omethane (1 mL) was added dropwise to a solution of 4-(3-(4-
oxo-6-tridecyl-1,4-dihydropyrimidin-2-yl)ureido)phenyl undec-
10-enoate (150 mg, 0.25 mmol) in degassed dichloromethane
(10 mL) and the reaction mixture was stirred at room
temperature for 2 days. It was then filtered through celite
before the solvent was evaporated and the resultant solid was
precipitated (chloroform : methanol) to give (E,Z)-bis(4-(3-(4-
oxo-6-tridecyl-1,4-dihydropyrimidin-2-yl)ureido)phenyl)icos-10-
enedioate (140 mg, 93%) as an off white powder; dH (300 MHz,
CDCl3); 12.80 (2H, br, NH), 12.30 (2H, br, NH), 11.95 (2H, br,
NH), 7.70 (4H, br, ArCH), 6.95 (4H, br, ArCH), 5.60 (2H, br,
CH), 5.42 (2H, br, CH), 2.60 (4H, br, CH2), 1.90 (4H, br, CH2),
1.70 (4H, br, CH2), 1.20 (68H, br, CH2), 0.75 (6H, br, CH3); the
4-(3-(4-Oxo-6-tridecyl-1,4-dihydropyrimidin-2-yl)ureido)phenyl
undec-10-enoate 11
10-Undecenoic acid (473 mg, 2.57 mmol) was added to a
solution of 1-(4-hydroxyphenyl)-3-(4-oxo-6-tridecyl-1,4-dihydro-
pyramidn-2-yl)urea (1.00 g, 2.34 mmol), DMAP (428 mg, 3.50
mmol) and EDCI (538 mg, 2.80 mmol) in CHCl3 (50 mL) and
the reaction mixture was heated to reflux for 15 h before being
molecule was insufficiently soluble to obtain a meaningful 13
C
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spectrum; ESI-HRMS found m/z 1183.7869 [M+Na]+,
C68H104N8NaO8 requires 1183.7869.
7 W. H. Binder, S. Bernstorff, C. Kluger, L. Petraru and M.
J. Kunz, Adv. Mater., 2005, 17, 2824–2428.
8 S. Sivakova, D. A. Bohnsack, M. E. Mackay, P. Suwanmala
and S. J. Rowan, J. Am. Chem. Soc., 2005, 127, 18202–18211.
9 W. C. Yount, D. M. Loveless and S. L. Craig, Angew. Chem.,
Int. Ed., 2005, 44, 2746–2748.
DOSY experiments
10 H. Kautz, D. J. M. van Beek, R. P. Sijbesma and E.
W. Meijer, Macromolecules, 2006, 39, 4265–4267.
11 S. C. Zimmerman and P. S. Corbin, Struct. Bonding, 2000,
96, 63–94.
12 A. Gooch, A. M. McGhee, L. C. Renton, J. P. Plante, C.
I. Lindsay and A. J. Wilson, Supramol. Chem., 2009, 21,
12–17.
13 A. Gooch, A. M. McGhee, M. L. Pellizzaro, C. I. Lindsay and
A. J. Wilson, Org. Lett., 2011, 13, 240–243.
14 M. L. Pellizzaro, A. M. McGhee, L. C. Renton, M. G. Nix,
J. Fisher, W. B. Turnbull and A. J. Wilson, Chem.–Eur. J.,
2011, 17, 14508–14517.
15 M. L. Pellizzaro, S. A. Barrett, J. Fisher and A. J. Wilson, Org.
Biomol. Chem., 2012, 10, 4899–4906.
16 A. Gooch, C. Nedolisa, K. A. Houton, C. I. Lindsay, A. Saiani
and A. J. Wilson, Macromolecules, 2012, 45, 4723–4729.
17 F. H. Beijer, R. P. Sijbesma, H. Kooijman, A. L. Spek and E.
W. Meijer, J. Am. Chem. Soc., 1998, 120, 6761–6769.
DOSY NMR measurements were made on a Varian Inova 500
MHz spectrometer. All experiments were conducted at 20 uC
on CDCl3 solutions, and used a 5 mm ID probe. The bipolar
pulse pair simulated echo (BPPSTE) sequence24 was employed
operating in ONESHOT mode.25 Additional parameters:
number of different gradient strengths, 20; gradient stabilisa-
tion delay 0.002 s; gradient length 0.002 s; diffusion delay 0.03
s; relaxation delay 2.5 s (following measurement of T1);
acquisition time 2 s; kappa (unbalancing factor, 0.2). Data
were processed using a 3 Hz line broadening and exponential
multiplication. Data were zero-filled once. Spectra were phased
and baseline corrected prior to production of the pseudo 2D
DOSY plots. For measurement of diffusion coefficients, a
calibration curve was plotted (using the Stokes–Einstein
relationship) for diffusion coefficient (6106 cm2 21) versus
s
the reciprocal cube root of the molecular mass (1/(molecular
mass)1/3) as described previously.14
¨
18 S. H. M. Sontjens, R. P. Sijbesma, M. H. P. van Genderen
and E. W. Meijer, Macromolecules, 2001, 34, 3815–3818.
19 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, 2634–2642.
20 V. G. H. Lafitte, A. E. Aliev, E. Greco, K. Bala, P. Golding
and H. C. Hailes, New J. Chem., 2011, 35, 1522–1527.
21 T. F. A. de Greef, M. M. L. Nieuwenhuizen, P. J. M. Stals, C.
F. C. Fitie, A. R. A. Palmans, R. P. Sijbesma and E.
W. Meijer, Chem. Commun., 2008, 4306–4308.
Acknowledgements
This work was supported by the Leverhulme Trust [F/00122/
AN].
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3108 | RSC Adv., 2013, 3, 3103–3108
This journal is ß The Royal Society of Chemistry 2013