The effects of microenvironment polarity and dendritic branching of aliphatic hydrocarbon dendrons on the self-assembly of 2-ureido-4-pyrimidinones

Article abstract of DOI:10.1002/asia.201000359

Two series of aliphatic hydrocarbon-based G1-G3 dendritic 2-ureido-4-pyrimidinones (UPy) (S-Gn)₂ and (L-Gn)₂, differing from one another by the distance between the branching juncture to the urea end, were prepared and characterized.

Full text of DOI:10.1002/asia.201000359

DOI: 10.1002/asia.201000359
The Effects of Microenvironment Polarity and Dendritic Branching of
Aliphatic Hydrocarbon Dendrons on the Self-Assembly of 2-Ureido-4-
pyrimidinones
Chun-Ho Wong,[a] Lai-Sheung Choi,[a] Sui-Lung Yim,[a] Kwun-Ngai Lau,[a]
Hak-Fun Chow,*[a, b] Sin-Kam Hui,[c] and Kong-Hung Sze[c]
Abstract: Two series of aliphatic hydro-
carbon-based G1–G3 dendritic 2-
ureido-4-pyrimidinones (UPy) (S-Gn)2
and (L-Gn)2, differing from one anoth-
er by the distance between the branch-
ing juncture to the urea end, were pre-
pared and characterized. These hydro-
carbon dendrons were also appended
to a p-aminonitrobenzene solvatochro-
mic chromophore in order to probe
their microenvironment polarity. While
positive solvatochromism was observed
which indicated the chromophore was
solvent accessible, there was no signifi-
cant difference between the microen-
vironment polarities on going from the
G1 to the G3 dendrons. The self-as-
sembling behavior and tautomeric pref-
erence of the dendritic UPy derviatives
were examined by 1H NMR spectrosco-
mined to be 106 and 105 mÀ1 in CDCl3,
respectively. It was found that a closer
proximity of the dendron branching
juncture to the UPy unit could lead to
a destabilization effect on the dimeric
states. Hence, the (L-Gn)2 dimers are
more stable than those of (S-Gn)2 in
the DDAA form, but the latter are
more stable than the former in the tau-
tomeric DADA state. This study
showed that both the highly nonpolar
microenvironment and the proximity of
the dendritic branching juncture to the
UPy motif could alter the strength and
profile of the hydrogen bond-mediated
self-assembling process.
py. The dimerization constants (Kdim*
)
of the DDAA tautomers were un-
changed at 107 mÀ1 in CDCl3 at both 25
and 508C, which were comparable to
those of UPy compounds bearing other
nonpolar substitutents. Furthermore,
the lower limits on the K’dim* of the
DADA tautomeric forms of the (S-
Gn)2 and (L-Gn)2 series were deter-
Keywords: dendrimers · dimeriza-
tion
·
self-assembly
·
solvato-
chromism · tautomerism
Introduction
Molecular self-assembly provides a means to prepare mate-
rials with properties that are unattainable through tradition-
al covalent chemical synthesis. In particular, self-assembly
mediated by hydrogen bonding often furnishes materials
with novel and tunable properties.[1] For example, Zimmer-
man reported the supramolecular heteromolecular hydrogen
bonding interaction of ureidoguanosine and 2,7-diamido-1,8-
naphthyridine[2] and its subsequent elaboration to supra-
molecular polymers.[3] The Meijer-Sijbesma 2-ureido-4-pyri-
midinone (UPy) unit[4] has also been used extensively to
prepare supramolecular polymers[5a] as well as self-assem-
bled cyclic oligomers with tunable properties.[5b] One of the
important issues in supramolecular chemistry is the ability
to retain the binding mode and binding affinity of the key
hydrogen bonding components with the introduction of new
structural units in the binding motifs. However, it has been
noted that minor structural variations on the various hetero-
[a] C.-H. Wong, L.-S. Choi, S.-L. Yim, Dr. K.-N. Lau,
Prof. Dr. H.-F. Chow
Department of Chemistry and The Center of Novel Functional
Molecules The Chinese University of Hong Kong
Shatin, NT (Hong Kong SAR)
Fax : (+852)2603-3057
E-mail: hfchow@cuhk.edu.hk
[b] Prof. Dr. H.-F. Chow
Institute of Molecular Functional Materials
Areas of Excellence Scheme
University Grants Committee
Hong Kong SAR
[c] S.-K. Hui, Prof. Dr. K.-H. Sze
Department of Chemistry
University of Hong Kong
Pokfulam Road (Hong Kong SAR)
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/asia.201000359.
Chem. Asian J. 2010, 5, 2249 – 2257
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FULL PAPERS
cyclic hydrogen bonding components can have substantial
effects on the binding mode and binding affinity. For exam-
ple, UPy 1 containing a methyl group at the C-6 position
has a dimerization constant (Kdim*) of 6ꢁ107 mÀ1 in CDCl3 at
258C.[4b] Replacing this methyl group with a trifluoromethyl
[4a]
[6]
22
or dibutylamino group 32 resulted in a shift of the
binding mode of the UPy dimer from DDAA to DADA tau-
tomeric form. In the case of the trifluoromethyl derivative,
this change was accompanied by a reduction of the lower
limit of K’dim* to 5ꢁ105 mÀ1 owing to less favorable secondary
interactions in the DADA binding mode. Recently, it was re-
ported that substitution of the alkyl group on the urea end
of the UPy with an oligo(ethylene oxide) (OEO) chain 4
could also modify the dimerization strength depending on
the length of the spacer between the OEO and the UPy
groups.[7] In particular, the Kdim* values of UPy 5 bearing an
ethylene or trimethylene spacer (m=2 or 3) were 102–103
less than those bearing a hexamethylene spacer (m=6) or
vironment is significantly different from that of the aqueous
surroundings. In biomimetic chemistry, a dendrimer is one
of the ideal candidates to provide a tailor-made, local micro-
environment around the hydrogen bonding module. For ex-
ample, Kaifer reported one of the earliest examples of a
series of G1–G3 dendritic UPys (e.g., 6) encapsulated inside
an AB3-type oligoamide-oligoester dendron.[8] It was ob-
served that the Kdim* values of the DDAA tautomers 6 re-
mained constant at 107 mÀ1 for the G1 and G2 analogues,
but diminished abruptly to 3mÀ1 for the G3 compound. This
was attributed to the steric bulkiness and the highly polar
microenvironment of the G3 dendron by the authors, but
could also arise from backbiting of the oligoamide-oligoester
dendron in light of Meijerꢂs recent findings.[7] We also dis-
closed a series of G1–G3 dendritic UPys (e.g., 7) appended
with Frꢃchetꢂs oligoether dendron,[9] and yet all Kdim* values
of the DDAA tautomers 7 remained unperturbed at 107 mÀ1.
In contrast to the oxygen atoms of the OEO chains, the rela-
tively higher structural rigidity of Frꢃchetꢂs dendrons and
the relatively poor coordinating ability of the arylether
oxygen atoms should disfavor the backbiting process. How-
ever, it had been shown that the interior polarity of Frꢃ-
chetꢂs dendrons increased gradually with increasing dendron
generation according to a solvatochromic study.[10] Hence
the invariance of the Kdim* values across the three genera-
tions of Frꢃchet type UPys 7 might alternatively suggest that
the polarity of the microenvironment created by the den-
dron around the UPy unit may not have any significant
effect on binding strength. This, together with other intrigu-
ing findings that oligopropyleneimine dendrimers 8[11] and
oligoamide-oligo(carboxylic acid) dendrons 9,[12] despite
having many polar amino and amido functionalities, showing
decreasing polarity with increasing dendrimer generation,
prompt us to further investigate the effect of the polarity of
microenvironment on the strength of supramolecular bind-
ing
1
those without the OEO appendage. Based on H NMR evi-
dence, a backbiting model 5 in which the oxygen atoms of
the OEO chain serve as intramolecular hydrogen bond ac-
ceptors was formulated.
In addition to structural modifications described above,
the strength of supramolecular binding can be modified by a
change in solvent polarity. The binding constant can be re-
duced in the presence of a polar solvent, particularly a
protic solvent owing to the presence of competitive hydro-
gen bonding. On the other hand, non-polar solvents, such as
chloroform and toluene, are good solvents for promoting hy-
drogen bond mediated self-assembling owing to their non-
polar and non-competing nature.[1a]
It is often desirable to maintain the strong assembling
force in a polar solvent environment in order to enhance the
utilities of the hydrogen bonding molecules. In fact, the
strong binding of substrate molecules to enzyme active sites
or bio-receptors in aqueous medium is a key factor in con-
trolling the substrate selectivity in many biological recogni-
tion processes. In nature, biomolecules will wrap around
themselves to form a binding pocket in which the microen-
We decided to prepare two series of UPy dendrons (S-G1,
S-G2, and S-G3) and (L-G1, L-G2, and L-G3) equipped
with an aliphatic hydrocarbon dendron[13] and examine their
binding properties under various conditions. Since the den-
drons contain only sp3 hybridized carbon atoms, and no lone
pair or p electrons are available for backbiting and other
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Self-Assembly of 2-Ureido-4-pyrimidinones
complicating interferences, the variation of the binding
strength across the different generation of UPys should
arise solely from dendritic microenvironment and steric ef-
fects. These two series of compounds differ from one anoth-
er in the proximity of the dendron to the central UPy unit.
The first set of compounds S-Gn contains a methylene
spacer between the UPy and the first branching point of the
dendron, while the second L-Gn has a longer trimethylene
spacer. Hence, the steric effect of the dendron should be
less felt by the UPy unit in the latter series. We also exam-
ined the microenvironment of these hydrocarbon dendrons
by carrying out solvatochromic studies on dendritic p-nitro-
dritic amines (10–15), which in turn were synthesized from
the corresponding known alcohols (16–21)[14] using Mitsuno-
bu-type Gabriel amine synthesis. Reactions of these amines
with the known imidazolide 22[9,15] then afforded the desired
dendritic dimers (S-Gn)2 and (L-Gn)2 in 35–90% overall
yields from alcohols (16–21) (Scheme 1).
ACHTUNGTRENNUNGaniline derivatives (S-Gn-probe) of the shorter chain S-Gn
series. Based on these studies, we report that a) the polarity
of the microenvironment of the three generation of hydro-
carbon dendrons are nearly the same, b) all dendrons can
preserve the dimerization strength (Kdim* =107 mÀ1) of the
DDAA UPy tautomers at 258C, and for the dendrons L-Gn
with a longer spacer, even at 508C, c) the % amount of
DADA tautomer is different for these two series of com-
pounds, and is also temperature dependent, d) the lower
limits on K’dim* of the weaker DADA tautomers are found
to be 105–106 mÀ1, and e) the proximity of the dendritic
branching show that the UPy unit also exerts some effect on
the binding strength. Hence the Kdim* values of the (L-Gn)2
are two times higher than those of the (S-Gn)2 series in
10% [D6]DMSO/CDCl3 solution. Our experimental findings
show that the microenvironment polarity and the dendritic
branching can have significant influence on the binding
strength and profile in supramolecular hydrogen bonding.
Scheme 1. Reagents and conditions: a) DIAD, Ph3P, phthalimide, THF,
258C, 1 h, 77–99% yield; b) H2NNH2, THF, H2O, reflux, 12 h, 74–100%
yield; c) CHCl3, 608C, 6 h, 47–95% yield.
Synthesis of dendritic solvatochromic probes: The widely
studied p-(N,N-dialkylamino)nitrobenzene chromophore[16]
was chosen to probe the polarity around the hydrocarbon
dendrons. Our plan was to replace one of the alkyl groups
with the shorter aliphatic hydrocarbon dendrons G1–G3
(n=1) to produce the dendritic S-Gn-probe. However,
owing to strong steric shielding of the hydrocarbon den-
drons, direct N-alkylation of p-(N-methylamino)nitroben-
zene using the corresponding dendritic bromide proved to
be sluggish. In the end, a palladium catalyzed N-arylation of
dendritic amines 10–12 with p-bromonitrobenzene 23 was
employed (Scheme 2).[17] The reaction turned out to be very
Results and Discussion
Synthesis
Synthesis of dendritic UPy dimers: Preparations of dendritic
dimers (S-Gn)2 and (L-Gn)2 required the availability of den-
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H.-F. Chow et al.
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Scheme 2. Reagents and conditions: a) PdACHTUNRGTNEUNG(OAc)2, (oxydi-2,1-phenylene)-
bis(diphenyl-phosphine), Cs2CO3, toluene, 1108C, 2 d, 31–83% yield;
b) MeI, NaH, THF, 258C, 24 h, 74–94% yield.
facile for G1 10 and G2 11 amino dendrons, producing the
N-arylation products 24 and 25 in 67% and 83% yield, re-
spectively. For the G3 12 amino dendron, the yield of the
product 26 dropped to 31%. Subsequent N-methylation of
the N-arylation products 24–26 furnished the target solvato-
chromic probes S-Gn-probe (n=1–3) in 74–94% yield.
Figure 1. Partial 1H NMR spectra (400 MHz, 50 mm in CDCl3, 258C) of
dimers (S-Gn)2 (top, G3; middle, G2; bottom, G1). Signals with an aster-
isk were as a result of the corresponding DADA tautomer.
Structural Characterizations
NMR spectroscopy: The structural identities and purities of
all intermediates and target compounds were fully character-
ized by 1H, 13C NMR spectroscopy, high-resolution mass
spectrometry (HRMS), and/or elemental analysis (see Sup-
electronic property of the shortened and the lengthened hy-
drocarbon dendrons. In fact, our observations are also in
agreement with literature precedents; an n-butyl substituent
at the urea position was found to give the DDAA dimer ex-
clusively while a tert-butyl substituent at the same position
was found to give rise to 3–3.5% DADA dimer when the
substituent on the pyrimidinone end was an alkyl group.[4a]
Careful examination of the structures of the two tauto-
meric UPy dimers revealed that the substituent on the urea
end in the DDAA form was located much closer to the pyri-
mindinone unit of its quadruple hydrogen bonding partner
than in the DADA form (Figure 2a). As a result, the prox-
imity of the dendritic branching indicates that the urea N
should exert a stronger effect on the stability of the DDAA
1
porting Information for details). The H NMR signal assign-
ments of the dendritic UPy dimers (S-Gn)2 and (L-Gn)2
were relatively straightforward. They all show three NH sin-
glets (d~13.1, 11.9, and 10.1), one vinylic singlet (d~5.8),
and one methyl singlet (d~2.2), indicating that the DDAA
dimeric form is the dominant tautomer in CDCl3. All other
1H signals arising from the dendritic hydrocarbon moiety
are located at the upfield region (d=1.8–0.8) except for the
CH2N signal (d~3.2). For the dendritic solvatochromic
probes S-Gn-probe, their 1H NMR spectra revealed the
characteristic AB system signals (d~8.1 and 6.6) originating
from the para-substituted aromatic moiety.
1
Tautomeric behavior: H NMR spectroscopy revealed one
notable difference between the tautomeric properties of (S-
Gn)2 and (L-Gn)2. For the (S-Gn)2 series, another set of NH
signals arising from the DADA tautomeric dimer was found
at d=13.4, 11.2, and 9.8 (Figure 1). Based on the relative in-
tegration of the vinylic singlets at d=6.1 versus 5.8, the
amount of DADA UPy dimer was found to be 4–6% (G1:
4%; G2: 4%; G3: 6%). However, the amount of DADA
dimers was much less (~0.5%) for the (L-Gn)2 series. It was
also noted that the percentage of DADA tautomer was
found to be, and theoretically should be (see Supporting In-
formation for details), concentration independent in CDCl3
solutions in the range of 2–50 mm. It is of interest to note
that our previously reported oligoether-based dendritic UPy
dimers 72 were shown to exist exclusively as DDAA tauto-
mers in CDCl3. The relative amount of DDAA was previ-
ously shown to be affected by the electronic property of the
substituents on both the urea and pyrimidinone units.[4a] In
our case, this must be as a result of steric or microenviron-
ment factors as there is hardly any difference between the
Figure 2. Proximity of the dendritic branching juncture at the urea end
on the tautomeric behavior of DDAA and DADA UPy dimers.
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Self-Assembly of 2-Ureido-4-pyrimidinones
Table 1. lmax values (nm) for dendritic hydrocarbon-based solvatochro-
mic probes S-Gn-probe (G1-G3) in various solvents.[a]
than on the DADA dimers. For (S-Gn)2, the branching junc-
ture is just one carbon atom away from the urea N and this
produces a stronger steric destabilization on the DDAA
binding mode which then gives rise to a higher percentage
of DADA tautomer as compared to the (L-Gn)2 series (Fig-
ure 2b). This model can also be used to explain the presence
of a substantial amount of DADA tautomeric dimer when
the substituent at the urea end was a tert-butyl moiety as
well as the finding that the amount of DADA tautomer in-
creases with increasing size of the hydrocarbon dendrons.
Furthermore, theoretical calculations indicated that the
DADA tautomer had a smaller dipole moment than the
DDAA monomer.[8] For the (S-Gn)2 series, the DADA tau-
tomers are relatively more stable than those of the (L-Gn)2
compounds because the nonpolar hydrocarbon dendron is
closer to the UPy unit. This effect was similar to the higher
DADA ratio observed in nonpolar solvents such as tolu-
ene.[8]
Mass spectrometry: The formation of dendritic dimers
was also supported by the observation of [2M+H]+ or
[2M+Na]+ peaks in ESI-MS (Figure 3). The relative abun-
dances of [2M+H]+ to [M+H]+ were not used to estimate
the Kdim* values. In mass spectrometry, the solvation effect
changes dramatically upon transition from solution phase to
gas phase. Quantitative correlation of the relative abundan-
ces with the concentrations could lead to substantial errors
in dimerization constants unless factors such as solvation for
each ion are properly addressed.[18]
Solvent
p*[b]
S-G1-probe
S-G2-probe
S-G3-probe
Diethyl ether
Toluene
Ethanol
Benzene
Acetone
CH2Cl2
0.28
0.54
0.54
0.59
0.71
0.82
0.88
1.00
374
386
395
388
394
399
406
412
374
385
394
388
396
399
405
413
374
384
393
387
395
398
404
DMF
DMSO
[c]
-
[a] 0.1–0.01 mm at 258C. [b] Solvent polarizability parameter. [c] Insolu-
ble.
of hydrocarbon dendrons, revealing that the dendrons pos-
sessed a microenvironment of nearly the same polarity irre-
spective of the dendron size. This finding was in sharp con-
trast to the decreasing polarity with increasing generation
observed for the oligopropyleneimine[11] and oligoamide-oli-
go(carboxylic acid) dendritic species,[12] and also different
from the increasing polarity with increasing size for the Frꢃ-
chet type oligoether dendrons.[10] Hence, in contrast to con-
ventional polymers where they are always more polar than
their small molecule analogues irrespective of polymer
structure,[20] the polarity change of the microenvironment
with increasing dendrimer size is structure dependent.
Dimerization Strengths
Similar to previous studies,[4a] the lower limits on Kdim* of
the two series of dendritic UPy dimers were estimated by
1
1H NMR (600 MHz) studies in CDCl3 at 258C. The H sig-
nals of hydrogen bonded NHs owing to the DDAA tauto-
meric dimers were sharp and their chemical shift values re-
mained unchanged in the concentration range from 10 mm
to 10 mm (Figure 4). Furthermore, no signals attributable to
the monomeric UPy species could be identified. Assuming
DDAA dimer formation was above 95% at the lowest con-
centration (i.e., 10 mm) studied, the lower limit on Kdim* was
calculated to be greater than 2ꢁ107 mÀ1 (Table 2). These
values are comparable to those of Frꢃchet type oligoether
dendritic UPy compounds and other UPy compounds bear-
ing nonpolar substituents.[4,9]
The chemical shift values of the hydrogen bonded NHs
owing to the DADA tautomeric pyrimidin-4-ol dimers in
the (S-Gn)2 series were also found to be concentration inde-
pendent down to 100 mm. The lower limit on K’dim* of the
DADA tautomer could then be calculated using the rela-
Figure 3. ESI-Mass spectrum of UPy dimer (S-G3)2 showing monomeric
and dimeric peaks.
Solvatochromic Study
Despite several reports on the microenvironment polarity of
different types of dendrons, there is little information on the
aliphatic hydrogen dendrons used in this study. Hence, sol-
vatochromatic studies were carried out on the S-Gn-probe
in various solvents (Table 1). For all three dendritic probes,
the UV absorption maximum (lmax) underwent a bathochro-
mic shift with increasing solvent polarity, suggesting the cen-
tral chromophore was solvent accessible.[19] The lmax values
remained essentially unchanged for the different generation
tionship K’dim* =Kdim* ꢁ[DADAdim]/ACHTUNGRETNNU[G DDAAdim] (see Support-
ing Information for details). As the amount of DADA
dimers only accounted for 3–6% of the total UPy concen-
tration in the (S-Gn)2 series, hence the lower limits on K’dim*
were around 106 mÀ1. On the other hand, owing to the lower
abundance (0.2–0.6%) of the DADA tautomers in the (L-
Gn)2 series, the lower limits on the respective K’dim* values
were lower (105 mÀ1). These values are also comparable to
the K’dim* lower limits (4.5ꢁ105 mÀ1) observed for several
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H.-F. Chow et al.
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more stable as compared to the DDAA forms at higher
temperature. Furthermore, the positions of the DADA NH
signals of the (S-Gn)2 series also remained unchanged down
to 100 mm at 508C, while those of the (L-Gn)2 series were
difficult to assess owing to their lower abundance.
The difference between binding strengths of these two
series of dendritic UPy compounds could not be addressed
accurately as data obtained from the previous experiments
were all lower limit values of Kdim* and K’dim*. It was also dif-
ficult to extract information from competition experiments
with these two structurally similar dendritic series. We there-
fore deliberately weakened the dimeric state by switching
the measurements to a more polar solvent system. Previous-
ly it was shown that the 6[1H]-monomer was in equilibrium
with the 4[1H] DDAA dimer in 10% [D6]DMSO/CDCl3.[4a]
We therefore conducted 1H NMR experiments (20 mm,
258C) in this solvent system and also found two sets of sig-
nals for both the (S-Gn)2 and (L-Gn)2 series. The Kdim*
values of both series of compounds were then calculated
from the relative integration of the two methyl signals on
the UPy unit (see Supporting Information for details). It
was found that the L-Gn possessed a Kdim* value (3.0Æ0.6ꢁ
102 mÀ1) that was three times that of the S-Gn compounds
(1.0Æ0.2ꢁ102 mÀ1). Hence the proximity of the dendritic
branching indicates that the UPy unit does have some influ-
ence on the dimerization constant, although this effect is
less pronounced than expected.
Figure 4. Partial 1H NMR (600 MHz, CDCl3, 258C) spectra of (S-G3)2 at
different concentrations. Signals with an asterisk (*) and a square symbol
(&) arose from the corresponding DADA tautomer and electronic arti-
fact, respectively.
Table 2. Kdim* and K’dim* values of various dendritic DDAA and DADA
UPy compounds.
Compound Kdim* of DDAA tautomer [MÀ1
]
K’dim* of DADA
tautomer [MÀ1
]
CDCl3
CDCl3
10% [D6]DMSO in CDCl3 (258C)
(258C)[a] (508C)[a]
CDCl3 (258C)[c]
[b]
S-G1
S-G2
S-G3
L-G1
L-G2
L-G3
>2ꢁ107
>2ꢁ107
>2ꢁ107
–
–
–
110Æ20
120Æ20
120Æ20
290Æ50
320Æ60
320Æ60
>0.6ꢁ106
>0.8ꢁ106
>1.2ꢁ106
>0.4ꢁ105
>1ꢁ105
[b]
[b]
Conclusions
>2ꢁ107 >2ꢁ107
>2ꢁ107 >2ꢁ107
>2ꢁ107 >2ꢁ107
We show here that the strength of hydrogen bonding inter-
actions of dendritic UPy compounds can be affected by the
polarity and the steric size of the dendron. By attaching a
highly nonpolar hydrocarbon dendron to the quadruple hy-
drogen bonding UPy unit, the binding strength of the
DDAA UPy tautomer was found to be constant at 107 mÀ1 at
258C and even at 508C for the L-Gn series. The weaker
binding DADA UPy tautomers were found to possess a
K’dim* around 105–106 mÀ1, and the value was dependent on
the branching pattern of the appended dendron. It was
noted that S-Gn dendrons, having a branching point closer
to the UPy moieties, exerted a stronger destabilization
effect on the dimeric state as compared to the L-Gn series,
and on the DDAA rather than the DADA tautomeric
dimers. Solvatochromic studies of these nonpolar hydrocar-
bon dendrons revealed little differences in the polarity of
the microenvironment from the smallest G1 to the biggest
G3 dendron. Hence, rather surprisingly, increasing the size
of the hydrocarbon dendron does not lead to a significant
increase of the nonpolar microenvironment. Our study also
revealed that the microenvironment polarity of a dendritic
species can be higher, lower, or the same as its non-dendritic
analog, and the direction of change is dependent on the
chemical structure of the dendrimer itself. This finding is dif-
ferent from that of conventional polymers, where their po-
larity is generally higher than that of the monomeric unit.
>1.2ꢁ105
[a] Based on <5% dissociation. [b] Not determined as a result of poor S/
N ratio at 10 mm. [c] Based on 10% integration error.
DADA pyrimidin-4-ol dimers in CDCl3.[4a] It was also noted
that slight structural variations of the dendritic appendage
could significantly alter the relative stabilities of the two
tautomeric forms.
We also examined the dimerization behavior of the den-
1
drons in CDCl3 at 508C. However, the H NMR signal to
noise ratios at 10 mm for the (S-Gn)2 compounds were very
poor to allow a reliable determination of the Kdim* values.
For the (L-Gn)2 series, no change in NH chemical shift
values was observed down to 10 mm and no other NH signals
arising from the 6[1H] monomer could be identified in the
region of d=9.2–6.0. In general, raising the temperature of
the system should lead to a reduction of the dimerization
constant, but in this case it was proven that the lower limits
on Kdim* of the (L-Gn)2 compounds at 508C were still in the
order of 107 mÀ1. The percentage of DADA tautomeric
dimers in both series of compounds also increased (S-G1:
7%; S-G2: 7%; S-G3: 11%; L-G1: 1%; L-G2: 2%; L-G3:
2%), indicating that the DADA forms became relatively
2254
www.chemasianj.org
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Asian J. 2010, 5, 2249 – 2257

Self-Assembly of 2-Ureido-4-pyrimidinones
m/z (%): 751 (35) [2M+Na]+, 387 (100) [M+Na]+; HRMS
ACTHUNRTGNE(GNU ESI) calcd
Experimental Section
for [2M+Na]+: 751.5569; found: 751.5568; elemental analysis: calcd (%)
for C20H36N4O2 (364.53): C 65.90, H 9.95, N 15.36; found: C 66.28,
H 10.22, N 15.18.
ACHTUNGTRENNUNG(S-G1)2: A solution of 10 (379 mg, 2.05 mmol) and imidazolide 22
(539 mg, 2.46 mmol) in CHCl3 (10 mL) was heated to 608C for 6 h. The
solution was cooled to 258C and filtered, washed with 1m HCl (2ꢁ
30 mL) and brine, dried (MgSO4), filtered and concentrated in vacuo to
afford the desired compound (651 mg, 95%) as a white solid. M.p.: 174–
1758C; 1H NMR (300 MHz, CDCl3, 258C): d=13.10 (s, 1H, UPyNH),
11.89 (s, 1H, CH2NHCONH), 10.08 (brs, 1H, CH2NH), 5.78 (s, 1H,
AHCTUNGTREG(NUNN L-G2)2: A solution of 14 (555 mg, 1.19 mmol) and imidazolide 22
(340 mg, 1.55 mmol) in CHCl3 (10 mL) was heated to 608C for 12 h then
cooled to 258C and filtered. The solution was washed with 1m HCl (2ꢁ
30 mL) and brine, dried (MgSO4), filtered, and concentrated in vacuo.
The residue was purified by flash chromatography (hexane/EtOAc=5:1)
to afford the desired compound (670 mg, 91%) as a white solid. Rf =0.40
C=CH), 3.15 (t, 2H, 3J
1.65–1.05 (m, 11H), 0.85 ppm (d, 12H, 3J
AHCTUNGTRENNUNG
ACHTUNGTRENNUNG
1
(hexane/EtOAc=3:1); m.p. 41–428C; H NMR (300 MHz, CDCl3, 258C):
(75.5 MHz, CDCl3, 258C): d=173.0, 156.8, 154.9, 148.2, 106.8, 43.9, 38.4,
35.7, 29.3, 28.5, 22.82, 22.76, 19.1 ppm; IR (KBr): n˜ =3217, 2956, 2866,
2604, 1699, 1662, 1591, 1522, 1467, 1444, 1408, 1383, 1365, 1338, 1303,
d=13.15 (s, 1H), 11.83 (s, 1H), 10.19 (s, 1H, NHCH2), 5.77 (s, 1H,
C=CH), 3.19 (q, 2H, 3J
ACHTUNGTRENNUNG
1.65–1.35 (m, 6H), 1.35–1.00 (m, 33H), 0.84 ppm (d, 24H, 3J
ACHTUNGTRENNUNG
1294, 1259, 1248, 1170, 1156, 1139, 1117 cmÀ1; MS
ACHTUNGTRENNUNG
6.6 Hz, CH3); 13C NMR: d=173.1, 156.7, 154.8, 148.2, 106.7, 40.6, 37.9,
37.3, 36.01, 35.99, 34.2, 34.1, 31.3, 31.2, 28.5, 27.0, 23.8, 22.8, 19.0 ppm; IR
(KBr): n˜ =3215, 2954, 2926, 2868, 2718, 2606, 1701, 1668, 1589, 1526,
(70) [2M+Na]+, 337 (100) [M+H]+; HRMS
ACHTUNGTRENNUNG
695.4943; found: 695.4955; elemental analysis: calcd (%) for C18H32N4O2
(336.5): C 64.25, H 9.59, N 16.64; found: C 64.17, H 9.66, N 16.68.
1467, 1413, 1383, 1366, 1304, 1255, 1170, 1139, 1041, 1016 cmÀ1; MS
ACHTUNGTRENNUNG
m/z (%) 1234 (39) [2M+H]+, 617 (100) [M+H]+; HRMS
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG(S-G2)2: A solution of 11 (530 mg, 1.14 mmol) and imidazolide 22
[2M+H]+: 1234.1383; found: 1234.1377; elemental analysis: calcd (%)
for C38H72N4O2 (617.0): C 73.97, H 11.76, N 9.08; found: C 73.62, H 11.95,
N 8.90.
(310 mg, 1.41 mmol) in CHCl3 (10 mL) was heated to 608C for 6 h. The
solution was cooled to 258C, filtered, then washed with 1m HCl (2ꢁ
30 mL) and brine, dried (MgSO4), filtered, and concentrated in vacuo.
The residue was purified by flash chromatography (hexane/EtOAc=4:1)
to afford the desired compound (529 mg, 79%) as a pale yellow solid.
Rf =0.75 (hexane/EtOAc=4:1); m.p.: 60–618C; 1H NMR (300 MHz,
AHCTUNGTERG(NUNN L-G3)2: A solution of 15 (137 mg, 0.141 mmol) and imidazolide 22
(40 mg, 0.183 mmol) in CHCl3 (5 mL) was heated to 608C for 12 h. The
solution was cooled to 258C and filtered, then washed with 1m HCl (2ꢁ
15 mL) and brine, dried (MgSO4), filtered, and concentrated in vacuo.
The residue was purified by flash chromatography (hexane/EtOAc=
10:1) to afford the desired compound (140 mg, 88%) as a pale yellow
liquid. Rf =0.42 (hexane/EtOAc=5:1); 1H NMR (300 MHz, CDCl3,
258C): d=13.18 (s, 1H), 11.87 (s, 1H), 10.20 (s, 1H, NHCH2), 5.81 (s,
CDCl3, 258C): d=13.14 (s, 1H, UPyNH), 11.90 (s, 1H, CH2NHCONH),
10.10 (br s, 1H, CH2NH), 5.79 (s, 1H, C=CH), 3.16 (q, 2H, J
3
(H,H)=6.0,
CH2N), 2.20 (s, 3H, UPy-CH3), 1.80–1.60 (m, 1H), 1.55–1.05 (m, 34H),
0.85 ppm (d, 24H, 3J(H,H)=6.6, CH3); 13C NMR (75.5 MHz, CDCl3,
ACHTUNGTRENNUNG
258C): d=172.9, 156.8, 154.9, 148.0, 106.8, 44.1, 37.9, 37.8., 36.0, 34.2,
32.2, 31.35, 31.29, 28.5, 23.6, 22.9, 19.0 ppm; IR (KBr): n˜ =3227, 3014,
2953, 2927, 2865, 2716, 2601, 1702, 1659, 1587, 1528, 1467, 1416, 1382,
1H, C=CH), 3.21 (q, 2H, 3J
C=CCH3), 1.67–1.37 (m, 11H), 1.37–1.02 (m, 76H), 0.87 ppm (d, 48H, J-
(H,H)=6.6 Hz, CH3); 13C NMR (75.5 MHz, CDCl3, 258C): d=173.1,
ACHTUNGRTEN(NUNG H,H)=5.1 Hz, CH2NH), 2.21 (s, 3H,
3
1365, 1302, 1260, 1245, 1170, 1141 cmÀ1; MS
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
[2M+H]+, 589 (100) [M+H]+; HRMS
AHCTUNGTRENNUNG
156.7, 154.9, 148.2, 106.9, 40.8, 37.9, 37.7, 37.5, 36.1, 34.5, 34.3, 31.4, 31.3,
28.6, 27.2, 24.0, 23.8, 22.91, 22.90, 19.0 ppm; IR (KBr): n˜ =3214, 2950,
2925, 2864, 2717, 2596, 1699, 1664, 1613, 1592, 1526, 1463, 1416, 1385,
1178.0757; found: 1178.0762; elemental analysis: calcd (%) for
C36H68N4O2 (589.0): C 73.42, H 11.64, N 9.51; found: C 73.90, H 12.00,
N 9.28.
1367, 1324, 1303, 1252, 1189, 1172, 1138, 1036 cmÀ1; MS
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG(S-G3)2: A solution of 12 (86 mg, 0.091 mmol) and imidazolide 22
2244 (35) [2M+H]+, 1122 (100) [M+H]+; HRMS
[2M+H]+ 2243.2651; found: 2243.2662.
ACHTUNGTRENNUNG
(40 mg, 0.18 mmol) in CHCl3 (2 mL) was heated to 608C for 6 h. The so-
lution was cooled to 258C and filtered. The resulting solution was con-
centrated in vacuo. The residue was purified by flash chromatography
(hexane/EtOAc=20:1 gradient to 5:1) to afford the desired compound
(70 mg, 70%) as a pale yellow liquid. Rf =0.56 (hexane/EtOAc=10:1);
1H NMR (300 MHz, CDCl3, 258C): d=13.17 (s, 1H, UPyNH), 11.91 (s,
1H, CH2NHCONH), 10.11 (brs, 1H, CH2NH), 5.80 (s, 1H, C=CH), 3.17
Compound 24: A mixture of p-bromonitrobenzene (0.65 g, 3.22 mmol),
Pd(OAc)2 (0.072 g, 0.32 mmol), (oxydi-2,1-phenylene)bis(diphenylphos-
AHCTUNGTRENNUNG
phine) (0.35 g, 0.65 mmol), and Cs2CO3 (0.68 g, 3.52 mmol) in toluene
(10 mL) was degassed in a sealed tube using three freeze-pump-thaw
cycles. After warming the mixture to room temperature, 10 (0.65 g,
3.51 mmol) was first dissolved in toluene (5 mL) and then added using a
syringe. The mixture was then heated to 1108C for 2 d with stirring. Et2O
was added to the reaction mixture after cooling to room temperature.
The mixture was filtered through a pad of Celite and the filtrate was
evaporated in vacuo to give a yellow oil which was purified by flash chro-
matography on silica gel (hexane/EtOAc=15:1) to give the desired com-
pound (0.66 g, 67%) as a yellow oil. Rf =0.17 (hexane/EtOAc=15:1);
1H NMR (300 MHz, CDCl3, 258C): d=8.13–8.02 (2H, m, ArH), 6.57–
(q, 2H, 3J
83H), 0.86 ppm (d, 48H, 3J
AHCTUNGTRENNUNG
ACHTUNGTRENNUNG
CDCl3, 258C): d=173.0, 156.9, 154.9, 148.0, 106.9, 44.1, 38.2, 37.9, 37.6,
36.1, 34.6, 34.3, 34.2, 32.3, 31.4, 28.6, 28.3, 23.8, 22.9, 19.1 ppm; IR (KBr):
n˜ =3440, 3220, 2950, 2924, 2863, 2720, 2610, 1698, 1664, 1651, 1613, 1591,
1537, 1466, 1385, 1367, 1326, 1250, 1187, 1170, 1039, 1021 cmÀ1; MS
ACHTUNGTRENNUNG
m/z (%) 2188 (10) [2M+H]+, 1094 (85) [M+H]+; HRMS
ACHTUNGTRENNUNG
[2M+H]+: 2187.2025; found: 2187.2036; elemental analysis: calcd (%)
for C72H140N4O2 (1093.9): C 79.05, H 12.90, N 5.12; found: C 79.39,
H 13.13, N 4.76.
6.45 (2H, m, ArH), 4.46 (1H, br s, NH), 3.11 (2H, t, 3J
NCH2), 1.66–1.57 (1H, m, CH), 1.51 (2H, septet, 3J
AHCTUNGTRENNUNG
ACHTUNGTRENNUNG
CHMe2), 1.41–1.28 (4H, m, CH2), 1.27–1.12 (4H, m, CH2), 0.89 ppm
(12H, d, 3J(H,H)=6.6 Hz, CH3); 13C NMR (75.5 MHz, CDCl3, 258C):
d=154.1, 136.9, 126.4, 110.8, 46.8, 37.8, 35.7, 29.4, 28.3, 22.5 ppm; MS-
(ESI): m/z (%): 307 (100) [M+H]+; HRMS(ESI) calcd for [M+H]+
307.2385; found: 307.2395; elemental analysis: calcd (%) for C18H30N2O2
(306.4): C 70.55, H 9.87, N 9.14; found: C 70.32, H 9.89, N 9.12.
ACHTUNGTRENNUNG(L-G1)2: A solution of 13 (510 mg, 2.39 mmol) and imidazolide 22
AHCTUNGTRENNUNG
(630 mg, 2.87 mmol) in CHCl3 (20 mL) was heated to 608C for 12 h. The
solution was cooled to 258C and filtered, then washed with 1m HCl (2ꢁ
30 mL) and brine, dried (MgSO4), filtered, and concentrated in vacuo.
The solid was recrystallized in CH2Cl2/MeOH (1:1) solution and afforded
the desired compound (408 mg, 47%) as a white crystal. M.p.: 144–
1458C; 1H NMR (300 MHz, CDCl3, 258C): d=13.13 (s, 1H, UPyNH),
11.86 (s, 1H, CH2NHCONH), 10.17 (brs, 1H, CH2NH), 5.79 (s, 1H,
G
ACHTUNGTRENNUNG
S-G1-probe: NaH (60% in mineral oil) (0.15 g, 3.75 mmol) was added to
a THF solution (10 mL) of 24 (0.63 g, 2.06 mmol) at 08C for 30 min. MeI
(0.25 mL, 3.98 mmol) was added to the solution using a syringe. The mix-
ture was then stirred at 258C for 24 h. H2O was added to the reaction
mixture and the aqueous layer was extracted with CH2Cl2 (3ꢁ50 mL).
The combined organic extracts were washed with brine, dried (MgSO4),
filtered, and evaporated in vacuo to give a yellow oil which was purified
by flash chromatography (hexane/EtOAc=10:1) to give the target com-
C=CH), 3.21 (q, 2H, 3J
ACHTUNGTRENNUNG
1.75–1.40 (m, 3H), 1.35–1.05 (m, 12H), 0.84 ppm (d, 12H, 3J
ACHTUNGTRENNUNG
6.6 Hz, CH3); 13C NMR (75.5 MHz, CDCl3, 258C): d=173.1, 156.7, 154.9,
148.3, 106.8, 40.6, 37.8, 36.0, 31.3, 31.0, 28.5, 27.0, 22.8, 19.1 ppm; IR
(KBr): n˜ =3400, 3215, 2954, 2926, 2860, 1700, 1667, 1586, 1525, 1457,
1413, 1383, 1366, 1303, 1254, 1170, 1147, 1137, 1040, 1019 cmÀ1; MS
ACTHNUTRGNE(NUG ESI):
Chem. Asian J. 2010, 5, 2249 – 2257
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemasianj.org
2255

H.-F. Chow et al.
FULL PAPERS
pound (0.62 g, 94%) as a yellow oil. Rf =0.54 (hexane/EtOAc=10:1).
1H NMR (300 MHz, CDCl3, 258C): d=8.16–8.03 (2H, m, ArH), 6.63–
137.9, 126.6, 111.0, 47.1, 37.9, 37.4, 36.0, 34.3, 34.20, 34.16, 32.7, 31.4, 28.6,
24.0, 23.8, 22.92, 22.90, 22.8 ppm; MSACTHNUTRGNEUNG
(ESI): m/z (%): 1064 (13) [M+H]+;
HRMS (ESI) calcd for [M+H]+: 1064.0836; found: 1064.0851; elemental
analysis: calcd (%) for C72H138N2O2 (1063.9): C 81.29, H 13.07, N 2.63;
found: C 81.22, H 13.67, N 2.69.
6.52 (2H, m, ArH), 3.32 (2H, d, 3J
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
3
(12H, d, J
153.7, 136.3, 126.0, 110.1, 57.0, 39.8, 36.7, 35.4, 29.0, 28.3, 22.6, 22.4 ppm;
MS
(ESI): m/z (%): 321 (100) [M+H]+; HRMS(ESI) calcd for [M+H]+
ACHTUNGTRENNUNG
(H,H)=6.6 Hz, CH3). 13C NMR (75.5 MHz, CDCl3, 258C): d=
S-G3-probe: NaH (60% in mineral oil) (0.077 g, 1.92 mmol) was added
to a THF solution (10 mL) of 26 (0.15 g, 0.14 mmol) at 08C for 30 min.
MeI (0.2 mL, 3.18 mmol) was added to the solution using a syringe. The
mixture was then stirred at 258C for 24 h. H2O was added to the reaction
mixture and the aqueous layer was extracted with CH2Cl2 (3ꢁ50 mL).
The combined organic extracts were washed with brine, dried (MgSO4),
filtered, and evaporated in vacuo to give a yellow oil which was purified
by flash chromatography (hexane/CH2Cl2 =3:1) to give the target com-
pound (0.14 g, 93%) as a yellow oil. Rf =0.33 (hexane/CH2Cl2 =3:1).
N
ACHTUNGTRENNUNG
321.2542; found: 321.2535; elemental analysis: calcd (%) for C19H32N2O2
(320.1): C 71.21, H 10.06, N 8.74; found: C 71.66, H 10.24, N 8.79.
Compound 25: A mixture of p-bromonitrobenzene (0.14 g, 0.69 mmol),
PdACHTUNGTRENNUNG(OAc)2 (0.031 g, 0.14 mmol), (oxydi-2,1-phenylene)bis(diphenylphos-
phine) (0.15 g, 0.28 mmol), and Cs2CO3 (0.48 g, 2.49 mmol) in toluene
(10 mL) was degassed in a sealed tube using three freeze-pump-thaw
cycles. After warming the mixture to room temperature, 11 (0.34 g,
0.78 mmol) was first dissolved in toluene (10 mL) and was then added
using a syringe. The mixture was then heated to 1108C for 2 d with stir-
ring. Et2O was added to the reaction mixture after cooling to room tem-
perature. The mixture was filtered through a pad of Celite and the filtrate
was evaporated in vacuo to give a yellow oil which was purified by flash
chromatography on silica gel (hexane/CH2Cl2 =2:1) to give the desired
compound (0.32 g, 83%) as a yellow oil. Rf =0.4 (hexane/CH2Cl2 =2:1).
1H NMR (300 MHz, CDCl3, 258C): d=8.11 (2H, d, 3J
ArH), 6.59 (2H, d, 3J(H,H)=9.3 Hz, ArH), 3.33 (2H, d, 3J
7.2 Hz, NCH2), 3.08 (3H, s, NCH3), 1.92–1.75 (1H, m, CH), 1.48 (8H,
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
3
septet, J
3J(H,H)=6.6 Hz, CH3); 13C NMR (75.5 MHz, CDCl3, 258C): d=153.9,
136.8, 126.3, 110.3, 57.5, 40.1, 37.9, 37.4, 36.7, 36.0, 34.4, 34.2, 32.3, 31.4,
28.6, 23.8, 23.7, 22.92, 22.90, 22.8 ppm; MS(ESI): m/z (%): 1078 (5)
[M+H]+; HRMS(ESI) calcd for [M+H]+: 1078.0993; found: 1078.1000;
ACHTUNGTREN(NUNG H,H)=6.6 Hz, CHMe2), 1.37–1.01 (74H, m), 0.87 ppm (48H, d,
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
1H NMR (300 MHz, CDCl3, 258C): d=8.08 (2H, d, 3J
6.52 (2H, d, 3J(H,H)=9.0 Hz, ArH), 4.46 (1H, brs, NH), 3.12 (2H, t, 3J-
(H,H)=5.4 Hz, NCH2), 1.73–1.60 (1H, m, CH), 1.47 (4H, septet, 3J-
(H,H)=6.6 Hz, CHMe2), 1.38–1.01 (30H, m), 0.86 ppm (24H, d, 3J-
(H,H)=6.6 Hz, CH3); 13C NMR (75.5 MHz, CDCl3, 258C): d=153.9,
137.5, 126.5, 110.9, 47.1, 37.8, 37.6, 35.9, 34.0, 32.4, 31.2, 28.5, 23.8,
ACHTUNGTREN(NGNU H,H)=9.0, ArH),
elemental analysis: calcd (%) for C73H140N2O2 (1077.9): C 81.34, H 13.09,
N 2.60; found: C 80.99, H 12.86, N 2.28.
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
Acknowledgements
22.8 ppm; MSACHTUNGTRENNUNG HCATUNGTREN(NNGU ESI) calcd for
(ESI): m/z (%): 560 (65) [M+H]+; HRMS
[M+H]+ 559.5202; found: 559.5213; elemental analysis: calcd (%) for
C36H66N2O2 (558.9): C 77.36, H 11.90, N 5.01; found: C 77.01, H 11.89,
N 5.06.
This work was supported by the Research Grants Council, HK (Account
No. CUHK 400506). K.-H. Sze would like to thank the support by the
Research Grants Council, HK (Account No. HKU 753306).
S-G2-probe: NaH (60% in mineral oil) (0.077 g, 1.92 mmol) was added
to a THF solution (10 mL) of 25 (0.30 g, 0.54 mmol) at 08C for 30 min.
MeI (0.2 mL, 3.18 mmol) was added to the solution using a syringe. The
mixture was then stirred at 258C for 24 h. H2O was added to the reaction
mixture and the aqueous layer was extracted with CH2Cl2 (3ꢁ50 mL).
The combined organic extracts were washed with brine, dried (MgSO4),
filtered, and evaporated in vacuo to give a yellow oil which was purified
by flash chromatography (hexane/CH2Cl2 =2:1) to give the target com-
pound (0.23 g, 74%) as a yellow oil. Rf =0.48 (hexane/CH2Cl2 =2:1).
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1H NMR (300 MHz, CDCl3, 258C): d=8.11 (2H, d, 3J
ArH), 6.59 (2H, d, 3J(H,H)=9.3 Hz, ArH), 3.24 (2H, d, 3J
7.5 Hz, NCH2), 3.08 (3H, s, NCH3), 1.91–1.77 (1H, m, CH), 1.46 (4H,
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
3
septet, J
3J(H,H)=6.6 Hz, CH3); 13C NMR (75.5 MHz, CDCl3, 258C): d=153.9,
136.6, 126.3, 110.2, 57.4, 40.0, 37.8, 36.5, 36.0, 34.1, 32.1, 31.3, 28.5, 23.6,
ACHTUNGTRENNUNG(H,H)=6.6 Hz, CHMe2), 1.37–1.03 (30H, m), 0.86 ppm (24H, d,
ACHTUNGTRENNUNG
22.8 ppm; MSACHTUNGTRENNUNG HCATUNGTREN(NNGU ESI) calcd for
(ESI): m/z (%): 574 (56) [M+H]+; HRMS
[M+H]+ 573.5359; found: 573.5355; elemental analysis: calcd (%) for
C37H68N2O2 (573.0): C 77.56, H 11.96, N 4.89; found: C 77.48, H 11.95,
N 4.64.
Compound 26: A mixture of p-bromonitrobenzene (0.084 g, 0.42 mmol),
PdACHTUNGTRENNUNG(OAc)2 (0.019 g, 0.085 mmol), (oxydi-2,1-phenylene)bis(diphenylphos-
phine) (0.089 g, 0.17 mmol), and Cs2CO3 (0.29 g, 1.50 mmol) in toluene
(10 mL) was degassed in a sealed tube using three freeze-pump-thaw
cycles. After warming the mixture to room temperature, 12 (0.46 g,
0.49 mmol) was first dissolved in toluene (10 mL) and was then added
using a syringe. The mixture was then heated to 1108C for 2 d with stir-
ring. Et2O was added to the reaction mixture after cooling to room tem-
perature. The mixture was filtered through a pad of Celite and the filtrate
was evaporated in vacuo to give a yellow oil which was purified by flash
chromatography on silica gel (hexane/CH2Cl2 =2:1) to give the desired
compound (0.16 g, 31%) as a yellow oil. Rf =0.5 (hexane/CH2Cl2 =2:1).
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1811–1814.
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1H NMR (300 MHz, CDCl3, 258C): d=8.08 (2H, d, 3J
ACHTUNGTRENNUNG
ArH), 6.51 (2H, d, 3J
ACHTUNGTRENNUNG
(2H, d, 3J
A
3
septet, J
G
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5743–5751.
ACHTUNGTRENNUNG
3J(H,H)=6.6 Hz, CH3); 13C NMR (75.5 MHz, CDCl3, 258C): d=153.7,
2256
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Chem. Asian J. 2010, 5, 2249 – 2257

Self-Assembly of 2-Ureido-4-pyrimidinones
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Received: May 16, 2010
Published online: August 2, 2010
Chem. Asian J. 2010, 5, 2249 – 2257
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemasianj.org
2257