Urea host monomers for stoichiometric molecular imprinting of oxyanions

Article abstract of DOI:10.1021/jo048470p

(Chemical Equation Presented) A series of urea-based vinyl monomers was synthesized and investigated for their ability to function as polymerizable hosts for the molecular imprinting of N-Z-D- or L-glutamic acid in polar media (DMSO or DMF). The monomers were synthesized in one step from a polymerizable isocyanate and a nonpolymerizable amine or vice versa, with yields typically over 70%. Prior to polymerization their solution binding properties vis-a-vis tetrabutylammonium benzoate in DMSO were investigated by ¹H NMR, UV-vis and fluorescence monitored titrations. The affinities of the urea monomers for benzoate depended upon the substitution pattern of the urea, with all diaryl ureas exhibiting high affinity. EDMA-based imprinted polymers prepared in DMF or DMSO against Z-D-(or L)-glutamic acid using 2 equiv of the urea monomer and 2 equiv of base were able to recognize the imprinted dianion as well as larger molecules containing the glutamic acid substructure. The affinity, reflected in liquid chromatography retention data, correlated with the solution binding properties of the corresponding monomers.

Full text of DOI:10.1021/jo048470p

Urea Host Monomers for Stoichiometric Molecular Imprinting of
Oxyanions§
Andrew J. Hall,*,† Panagiotis Manesiotis,† Marco Emgenbroich,† Milena Quaglia,‡
Ersilia De Lorenzi,‡ and Bo¨rje Sellergren*,†
INFU, Universita¨t Dortmund, Otto Hahn Str. 6, 44221 Dortmund, Germany, and Department of
Pharmaceutical Chemistry, University of Pavia, Via Taramelli 12, 27100 Pavia, Italy
andy@infu.uni-dortmund.de; borje@infu.uni-dortmund.de
Received August 31, 2004
A series of urea-based vinyl monomers was synthesized and investigated for their ability to function
as polymerizable hosts for the molecular imprinting of N-Z-D- or L-glutamic acid in polar media
(DMSO or DMF). The monomers were synthesized in one step from a polymerizable isocyanate
and a nonpolymerizable amine or vice versa, with yields typically over 70%. Prior to polymerization
their solution binding properties vis-a`-vis tetrabutylammonium benzoate in DMSO were investigated
1
by H NMR, UV-vis and fluorescence monitored titrations. The affinities of the urea monomers
for benzoate depended upon the substitution pattern of the urea, with all diaryl ureas exhibiting
high affinity. EDMA-based imprinted polymers prepared in DMF or DMSO against Z-D-(or L)-
glutamic acid using 2 equiv of the urea monomer and 2 equiv of base were able to recognize the
imprinted dianion as well as larger molecules containing the glutamic acid substructure. The affinity,
reflected in liquid chromatography retention data, correlated with the solution binding properties
of the corresponding monomers.
Introduction
template complexes in a cross-linked polymer matrix and
removal of the template, binding sites remain which are
capable of rebinding the template with high affinity and
selectivity. The advantage of this “top down” approach
in receptor design lies in its use of the self-assembly
principle to guide the binding groups to their positions
in the receptor site; thus, the structure of the final
binding site is a priori unknown.
With few exceptions, imprinted polymers for anion
recognition have been prepared from commercially avail-
able functional monomers (e.g., vinylpyridine, N,N-di-
ethyl-2-aminoethyl methacrylate, methacrylamide), which
are able to provide only weak interactions with the
template molecule in solvents of low polarity.8 Generally,
Recent progress in the area of host-guest chemistry
directed toward anion recognition has resulted in low
molecular weight hosts capable of selective complexation
of anions in water-rich media.1-3 However, it is difficult
to engineer them in useful formats for the recognition of
guests of higher complexity or of larger size. Thus,
general recognition strategies directed toward biomol-
ecules based on artifical receptors remain an important
challenge.4 In this context the concept of molecular
imprinting appears very appealing.5-7 Here, monomers
are chosen in order to complement functional groups of
a template molecule. After incorporation of the monomer-
§ Dedicated to Professor Gu¨nther Wulff on the occasion of his 70th
birthday.
† Universita¨t Dortmund.
(5) Molecularly imprinted polymers. Man made mimics of antibodies
and their applications in analytical chemistry. In Techniques and
Instrumentation in Analytical Chemistry; Sellergren, B., Ed.; Elsevier
Science B.V.: Amsterdam, 2001; Vol. 23.
‡ University of Pavia.
(1) Best, M. D.; Tobey, S. L.; Anslyn, E. V. Coord. Chem. Rev. 2003,
240, 3-15.
(2) Gale, P. A. Coord. Chem. Rev. 2003, 240, 191-221.
(3) Suksai, C.; Tuntulani, T. Chem. Soc. Rev. 2003, 32, 192-202.
(4) Peczuh, M. W.; Hamilton, A. D. Chem. Rev. 2000, 100, 2479-
2494.
(6) Wulff, G.; Knorr, K. Bioseparation 2002, 10, 257.
(7) Molecularly Imprinted Materials-Sensors and other Devices;
Shea, K. J., Roberts, M. J., Yan, M., Ed.; Materials Research Society
Symposium Proceedings: San Francisco, 2002; Vol. 723, M1.3.
10.1021/jo048470p CCC: $30.25 © 2005 American Chemical Society
Published on Web 01/29/2005
1732
J. Org. Chem. 2005, 70, 1732-1736

Urea Host Monomers for Imprinting
SCHEME 1
functional monomers for preparing polymeric receptors
and catalytic sites.9 However, the examples reported so
far involve an elaborate multistep synthesis to prepare
the host monomer. With synthetic accessibility as one
design criterion, we were interested in extending the
palette of functional monomers available for oxyanion
imprinting. A further concern was to be able to achieve
improved imprinting in more polar environments than
those generally reported. There are numerous examples
from the field of supramolecular chemistry showing that
the 1,3-disubstituted urea moiety is a very capable
binding element for this purpose.2,11-14
FIGURE 1. Urea monomers used to prepare imprinted
polymers for oxyanion recognition. The monomers were pre-
pared in one step from 1-isopropenyl-4-isopropyl-2-isocyanate
and the corresponding amine (monomers 1, 2 and 8) or
4-vinylaniline and the corresponding isocyanate (3-7) as
described in the experimental section.
To exploit this binding element in molecular imprint-
ing, we have prepared the monourea monomers 1-7 (Fi-
gure 1) and assessed their usefulness as binding and re-
porter monomers in the imprinting of N-Z-D-(or L)-glu-
tamate (Z-Glu) (see Figure 2). For preliminary accounts
on the behavior of monomers 8 and 5 in the imprinting
of these templates, see refs 15 and 16, respectively.
Compounds 1-7 were prepared in a single step, from
commercially available reagents, in moderate to good
yields. We used benzoate (as its TBA-salt) as the model
oxyanion for our 1H NMR studies in the competitive
solvent DMSO-d6. Self-association of monomer and/or
guest does not occur in these systems. A Job plot
confirmed a 1:1 monomer-guest stoichiometry (Scheme
1) and fitting the raw titration data to a 1:1 binding
isotherm afforded the respective association constants
listed in Table 1.
this means that a large excess of functional monomer is
used in order to ensure a high degree of complexation of
the template. Such conditions are not compatible with
the vast majority of biomolecules, which instead require
polar or aqueous environments for imprinting.
One approach to improve this situation involves the
preparation of functional monomers which provide strong
and stoichiometric interactions with a given template.6,9,10
If the monomer-template interactions are sufficiently
strong, stoichiometric use of the monomer should lead
to a high percentage of complex in the pre-polymerization
solution, which would then be transformed into a high
yield of imprinted sites in the polymer and lead to a
drastic reduction in the degree of nonspecific binding in
the obtained imprinted polymer. This has been demon-
strated by Wulff et al. with the use of amidine-based
FIGURE 2. Imprinting of Z-D-Glu using urea host monomer (5), ethyleneglycol dimethacrylate (EDMA) as cross-linking monomer
and DMF as solvent.
J. Org. Chem, Vol. 70, No. 5, 2005 1733

Hall et al.
TABLE 1. Association Constants (Ka) and Complexation
Induced Shifts (CIS) for the Interaction of
1,3-Disubstituted Monoureas with TBA-Benzoate in
DMSO-d6
(TEA) in the polar solvents DMSO or DMF. Analysis of
the extracts after polymer washing indicated that greater
than 95% of the template was removed from the im-
printed polymers and that the functional monomers were
stoichiometrically incorporated in the polymer matrices.
The molecular recognition properties of the materials
were then investigated via chromatography comparing
the retention of the template, Z-Glu, with that of more
complex biologically active molecules such as metho-
trexate (MTX), containing the glutamic acid substructure,
and structurally related analogues N-Z-Asp and N-Z-Gly.
In our previous reports we concluded that addition of an
organic base to a mobile phase consisting of pure MeCN
led to enhanced imprinting factors and retentions, mainly
for the template,15 in agreement with the previously
proposed mechanism of binding. Thus, our initial evalu-
ations used a mobile phase consisting of MeCN contain-
ing 1% TEA. The column efficiency was in general very
poor indicating slow mass transfer processes related to
the strong carboxylate-urea interaction. As seen in Figure
3, the retention order seems to agree with the affinity
toward TBA-benzoate displayed by the monomers in
solution. Thus, the retention of the acid containing
solutes increased in the order P119 < P8 < P2 < P5.
Unfortunately, this is also the case for the nonimprinted
reference polymer, leading to a total retention of all
solutes on P5 and PN5 in this mobile phase system.
To weaken the affinity displayed by this recognition
element we added water to the above mobile phase
system, keeping the base content fixed (Figure 4). Above
6% water, a dramatic drop in retention was observed.
This was most pronounced for the nonimprinted polymer
leading to high imprinting factors within a small interval
of mobile phase water content. Thus, when passing from
6% to 7% (v/v) water in the mobile phase, the retention
time dropped from more than 70 to 2.3 min on PN5,
whereas no elution was observed on P5 within the run
time of the measurement (120 min).
A further increase in the water content eluted the
analyte from the imprinted polymer as well. A water
content of 7% was thus chosen for further investigations
of the selectivity of the materials. First we observed that
P5 exhibited no or very low enantioselectivity in the
chromatographic mode in contrast to other imprinted
polymers prepared using less strongly associating mono-
mers where separation factors over 2 are common. This
conflicts with the results under equilibrium conditions
where high enantioselective uptake was observed,16 with
the amount of adsorbed Z-D-Glu exceeding that of Z-L-
Glu by ca. 13 µmol/g.
We explain this dichotomy in the following manner.
Three points of contact are required for enantioselective
discrimination.20 In our stoichiometrically imprinted
polymers, two strong interactions to the analytes are
provided by the polymeric urea units, while any further
interaction must be provided by the polymer matrix. Such
interactions, most probably van der Waals in nature, are
necessarily weak and, under dynamic conditions, prob-
ably not strong enough to impart enantioselectivity to
a
monomer
Ka (M-1
)
CISa
1
2
3
4
5
6
7
8
30 ( 4
1.21
2.34
3.28
3.48
3.54
3.39
2.31
1.80d
121 ( 6
1322 ( 48
6520 ( 1099
6498 ( 170 (4600)b
8820 ( 1600
613 ( 61 (699)c
1500 ( 200d
a CIS of both urea protons were monitored. Ka refers to the
average of the individual values except for 6 where due to excessive
broadening the ortho protons of the 3,5-bis(trifluoromethyl)phenyl
group were monitored. b Value from Benesi-Hildebrand plot (see
Supporting Information) of the UV-vis titration data. c Value from
Stern-Vollmer plot (see Supporting Information) of fluorescence
titration data. d Value calculated for the association of 8 with bis-
TBA-glutarate.15
In agreement with previous reports,17 dramatic in-
creases in the binding strengths of the monomers are
observed on varying the substitution of these simple
monourea systems. These are attributed to the nature
of the urea substituents, which leads to increases in the
acidity of the urea protons18 and, hence, increased
magnitudes of association with the carboxylate guest.
We further assessed the ability of monomer 5 to bind
benzoate in a water-containing environment. A 1H NMR
titration using DMSO-d6/D2O (9/1) as solvent led to Ka
) 250 ( 9 M-1. As reported for similar low molecular
weight host molecules,12,14 monomers 5 and 7, with their
extended π-systems, exhibited UV-vis and fluorescence
spectral changes, respectively, upon association allowing
corresponding association constants to be determined
(Table 1 and Supporting Information).
Imprinted (P1, P2, P5) and nonimprinted (PN1, PN2,
PN5) polymers were then prepared from the monourea
monomers 1, 2 and 5. We chose these monomers as
representative examples of the three classes of monomer
prepared. While monomer 6 exhibited a higher associa-
tion with benzoate compared to monomer 5, we were
interested to extend our studies on the latter monomer
because of its ability to signal, chromogenically, a specific
binding event.16 Polymerizations were performed in the
presence of Z-D-(or L)-Glu and 2 equiv of triethylamine
(8) Sellergren, B. Angew. Chem., Int. Ed. 2000, 39, 1031-1037.
(9) Wulff, G.; Gross, T.; Scho¨nfeld, R. Angew. Chem., Int. Ed. Engl.
1997, 36, 1962-9164.
(10) Lu¨bke, C.; Lu¨bke, M.; Whitcombe, M. J.; Vulfson, E. N.
Macromolecules 2000, 33, 5098-5105.
(11) Linton, B. R.; Goodman, M. S.; Fan, E.; van Arman, S. A.;
Hamilton, A. D. J. Org. Chem. 2001, 66, 7313-7319.
(12) Kato, R.; Nishizawa, S.; Hayashita, T.; Teramae, N. Tetrahedron
Lett. 2001, 42, 5053-5056.
(13) Lee, D. H.; Lee, H. Y.; Lee, K. H.; Hong, J.-I. Chem. Commun.
2001, 1188.
(14) Mei, M.; Wu, S. New J. Chem. 2001, 25, 471.
(15) Hall, A. J.; Achilli, L.; Manesiotis, P.; Quaglia, M.; De Lorenzi,
E.; Sellergren, B. J. Org. Chem. 2003, 68, 9132-9135.
(16) Manesiotis, P.; Hall, A. J.; Emgenbroich, M.; Quaglia, M.; De
Lorenzi, E.; Sellergren, B. Chem. Commun. 2004, 2278-2279.
(17) Wilcox, C. S.; Kim, E.; Romano, D.; Kuo, L. H.; Burt, L. B.;
Curran, D. P. Tetrahedron 1995, 51, 621.
(18) Meta substitution furthermore enhances the acidity of the ortho
aromatic ring proton, which in turn enhances its ability to act as a
hydrogen bond donor towards the carbonyl oxygen. This effect is
important in the crystalline state leading it to cocrystallize with Lewis
basic solvents but is likely to be of less importance in solution. See ref
17 and Etter, M. C.; Panunto, T. W. J. Am. Chem. Soc. 1988, 110,
5896-5897.
(19) Using the bis-TBA salt of Z-Glu as the oxyanion and acetonitrile
as the mobile phase, P1 exhibited a retention factor much lower (k ,
1) than that of P2 (k > 1) and P8 (k > 1). P1 was therefore not
investigated any further.
(20) Dalgleish, C. E. J. Chem. Soc. 1952, 3940.
1734 J. Org. Chem., Vol. 70, No. 5, 2005

Urea Host Monomers for Imprinting
FIGURE 3. Retention factors for Z-Glu and MTX on imprinted (grey bars) and nonimprinted (black bars) polymers prepared
using the depicted monomers. The mobile phase was MeCN/TEA: 99/1 (v/v), the injection volume was 20 µL, analyte concentration
was 10 mM, flow rate was 1 mL/min and detection was performed at 262 nm for the Z-Glu and 260 nm for the MTX.
FIGURE 4. Retention factors for Z-Glu on imprinted (P5) and
nonimprinted (PN5) polymers prepared using urea monomer
(5). The mobile phase consisted of MeCN with increasing
contents of water and a fixed concentration of TEA (1% (v/v)).
Conditions were otherwise as described in Figure 3.
our systems. Under equilibrium conditions, there is
sufficient time for these low strength tertiary interactions
to exert their influence.
Nevertheless, pronounced substrate selectivities were
observed that were strongly dependent on the presence
of base in the mobile phase (Figure 5). Thus, in the
absence of TEA, the solutes exhibited similar retention
factors and were, moreover, similarly retained on both
P5 and PN5. This resulted in low and similar imprinting
factors and contrasts with the retention behavior in the
presence of TEA where high imprinting factors were
FIGURE 5. Retention factors (k) for Z-Glu and other car-
observed for Z-Glu and MTX. Interestingly, the other
boxylic acid solutes on imprinted (P5) and nonimprinted (PN5)
control substances, Z-Asp and Z-Gly, were still similarly
polymers and corresponding imprinting factors (IF ) kMIP/kNIP).
retained on P5 and PN5, indicating the presence of well-
The mobile phase was (A) MeCN/H2O/TEA 92/7/1 (v/v/v) and
defined binding sites.
(B) MeCN/H2O 93/7 (v/v).
In summary, dramatic increases in the binding of
oxyanions by simple, 1,3-disubstituted monourea mono-
mers occurs on variation of the substitution pattern.
Monomer (5) also shows moderate binding to benzoate
in an even more competitive water-containing environ-
J. Org. Chem, Vol. 70, No. 5, 2005 1735

Hall et al.
([M + H]+) 375.0. Calculated for C17H12F6N2O: C 54.55, H 3.23,
N 7.48. Found: C 54.10, H 3.15, N 7.40
ment. Given that a large range of biologically important
molecules containing oxyanion functionality are compat-
ible with imprinting in such solvent systems as those
described above, these monomers may lead to a new
range of MIP-based applications.
1-(4-Vinylphenyl)-3-(1-naphthyl)urea (7). Yield (ethanol/
toluene) 81%, mp 240.8 °C. 1H NMR (DMSO-d6) δ: 5.10 (d,
1H), 5.67 (d, 1H), 6.64 (dd, 1H), 7.37-7,62 (m, 8H), 7.89-8.10
(m, 3H), 8.75 (s, 1H), 9.10 (s, 1H). 13C NMR (DMSO-d6) 112.4,
117.8, 118.2, 121.7, 123.3, 126.1, 126.2, 126.3, 127.1, 128.8,
131.2, 134.1, 134.6, 136,6, 129.9, 153.1. MS (EI) m/z (M+) 288.
Calculated for C19H16N2O: C 79.14, H 5.59, N 9.72. Found: C
78.80, H 5.55, N 9.55
Experimental Section
Benzylamine, aniline, phenyl isocyanate, 3-nitrophenyl iso-
cyanate, 3-(trifluoromethyl)phenyl isocyanate and 1-naphthyl
isocyanate, 4-aminostyrene, 3-isopropenyl-R,R-dimethylbenzyl
isocyanate and 1,3-bis(trifluoromethyl)phenyl isocyanate were
used as received. Ethylene glycol dimethacrylate (EDMA) was
purified by the following procedure prior to use: the received
material was washed consecutively with 10% aqueous NaOH,
water, brine and finally water. After drying over MgSO4, pure,
dry EDMA was obtained by distillation under reduced pres-
sure. All other reagents were used as received. N,N′-Azo-bis-
(2,4-dimethyl)valeronitrile (ABDV) was purchased from Wako.
DMSO-d6 was purchased from Deuterio-GmbH (Kastellaun,
Germany). Anhydrous solvents, dichloromethane and tetrahy-
drofuran, were stored over appropriate molecular sieves. Other
solvents were of reagent grade or higher. 1H NMR spectra were
recorded at 400 MHz. UV-visible spectra were obtained using
a Perkin-Elmer Lambda 20 instrument. Elemental microanal-
yses were performed using a CHN-rapid HERAEUS analyzer.
Synthesis of Monoureas 1-7. General Procedure. To
a stirred solution of the desired amine (20 mmol) in THF (50
mL) under an inert atmosphere was added the required
isocyanate (20 mmol) either neat (in the case of liquid
isocyanates) or as a solution in THF (10 mL) (in the case of
solid isocyanates). The solution was allowed to stir at room
temperature overnight and then the solvent was evaporated
under reduced pressure. The resulting solid residue was
recrystallized from ethanol if not otherwise mentioned.
1-(3-Isopropenyl-R,R-dimethylbenzyl)-3-(benzyl)urea (1).
1H NMR Titrations and Estimation of Association
Constants. All 1H NMR titrations were performed in DMSO-
d6. Association constants (KSL) for the interactions between
hosts and guests were determined by titrating an increasing
amount of guest (tetrabutylammonium benzoate, TBABz) into
a constant amount of functional monomer. The concentration
of functional monomer was 1 mM and the amounts of added
guest were 0, 0.5, 1, 2, 3, 4, 5, 7.5 and 10 equiv, respectively.
The complexation induced shifts (∆δ) of the host urea protons
were followed and titration curves were then constructed of
∆δ versus guest concentration. The raw titration data were
fitted to a 1:1 binding isotherm by nonlinear regression using
Microcal Origin 5.0 from which the association constants could
be calculated.
Polymer Preparation. An imprinted polymer was pre-
pared in the following manner. The template molecule, Z-D-
Glu-OH (1 mmol), if not otherwise stated, functional monomer
(2 mmol) and EDMA (20 mmol) were dissolved in DMF (P5)
or DMSO (P1, P2, P8) (5.6 mL). To the solution were added
TEA (2 mmol) and the initiator ABDV (1% w/w of total
monomers). The solution was transferred to a glass ampule,
cooled to 0°C and purged with a flow of dry nitrogen for 10
min. The tubes were then flame-sealed while still under cooling
and the polymerization initiated by placing the tubes in a
thermostated water bath preset at 40°C. After 24 h (P5) or 48
h (P1, P2, P8) the tubes were broken and the polymers lightly
crushed. Removal of the template molecule from the polymers
was achieved by extraction with methanol in a Soxhlet
apparatus for 24 h. Thereafter, the polymers were crushed and
sieved to obtain particles in the size range 25-50 µm. A
nonimprinted polymer (PN#) was prepared in the same way
as described above, but with the omission of the template
molecule and TEA from the pre-polymerization solution.
Elemental analyses of extracted polymers: P5/PN5, calculated
C 60.97; H 6.81; N 1.86; found P5 C 60.0; H 7.0; N 1.7. PN5:
C 59.9; H 7.1; N 1.6
1
Yield: 85%. H NMR (DMSO-d6) δ: 1.53 (s, 6H), 2.07 (s, 3H),
4.13 (d, 2H), 5.05 (s, 1H), 5.33 (s, 1H), 6.26 (t, 1H), 6.40 (s,
1H), 7.15-7.27 (m, 8H), 7.47 (s, 1H); 13C NMR (DMSO-d6) δ:
21.85, 30.44, 42.78, 54.45, 112.48, 122.02, 123.07, 124.51,
126.75, 127.08, 128.10, 128.43, 140.28, 141.28, 143.34, 149.36,
157.35. Calculated for C20H24N2O: C 77.89, H 7.84, N 9.08.
Found: C 77.47, H 8.07, N 8.95
1-(3-Isopropenyl-R,R-dimethylbenzyl)-3-(phenyl)urea
1
(2). Yield: 80%. H NMR (DMSO-d6) δ: 1.56 (s, 6H), 2.06 (s,
3H), 5.03 (s, 1H), 5.33 (s, 1H), 6.55 (s, 1H), 6.81 (t, 1H), 7.11-
HPLC Evaluation. The 25-36 µm particle size fraction
was repeatedly sedimented (80/20 methanol/water) to remove
fine particles and then slurry-packed into HPLC columns (100
mm × 4.6 mm, i.d.) using the same solvent mixture as pushing
solvent. Subsequent analyses of the polymers were performed
using an Agilent HP1100 system equipped with a diode array-
UV detector and a workstation. Analyte detection was per-
formed at 262 nm (Z-Glu), 260 nm (MTX), 282 nm (Z-Asp),
and 284 nm (Z-Gly).
7.15 (m, 2H), 7.21-7.29 (m, 5H), 7.46 (s, 1H), 8.35 (s, 1H); 13
C
NMR (DMSO-d6) δ: 21.84, 29.99, 54.60, 112.64, 117.65, 121.16,
121.99, 123.26, 124.48, 128.24, 128.87, 140.36, 140.75, 143.26,
148.73, 154.34. Calculated for C19H22N2O: C 77.52, H 7.53, N
9.52. Found: C 77.32, H 7.66, N 9.35
1-(4-Vinylphenyl)-3-(phenyl)urea (3). Yield: 50%. 1H
NMR (DMSO-d6) δ: 5.11 (d, 1H), 5.66 (d, 1H), 6.63 (dd, 1H),
6.94 (t, 1H), 7.25 (m, 2H), 7.33-7.45 (m, 5H), 8.63 (broad s,
1H), 8.71 (broad s, 1H). Calculated for C15H14N2O: C 75.60, H
5.92, N 11.76. Found: C 75.45, H 5.69, N 11.63
Acknowledgment. Work supported in part by the
European Community’s program for Training and Mo-
bility of Researchers (TMR) under contract FMRX-CT-
98-0173, [MICA] and the European Community’s Im-
proving Human Potential Program under contract
HPRN-CT-2002-00189, [AquaMIP]. Ms. Scilla Pelletti
and Ms. Ilaria Cei are gratefully acknowledged for their
technical support with the chromatographic experi-
ments.
1-(4-Vinylphenyl)-3-(3-trifluromethylphenyl)urea (4).
Yield: 65%. 1H NMR (DMSO-d6) δ: 5.12 (d, 1H), 5.68 (d, 1H),
6.64 (dd, 1H), 7.27-7.56 (m, 7H), 7.99 (s, 1H), 8.83 (broad s,
1H), 9.01 (broad s, 1H). Calculated for C16H13F3N2O (%): C
62.74, H 4.28, N 9.14. Found: C 62.41, H 4.40, N 9.01
1-(4-Vinylphenyl)-3-(3-nitrophenyl)urea (5). Yield: 70%.
1H NMR (DMSO-d6) δ: 5.06 (d, 1H), 5.68 (d, 1H), 6.64 (dd, 1H),
7.36-7.80 (m, 7H), 8.54 (s, 1H), 8.87 (broad s, 1H), 9.18 (broad
s, 1H). Calculated for C15H13N3O3: C 63.59, H 4.63, N 14.84.
Found: C 63.98, H 4.53, N 14.69
1-(4-Vinylphenyl)-3-(3,5-bis(trifluromethyl)phenyl)-
urea (6). Yield: 64%, mp 192.4 °C. 1H NMR (DMSO-d6) δ:
5.11 (d, 1H), 5.68 (d, 1H), 6.63 (dd, 1H), 7.37 (d, 2H), 7.43 (d,
2H), 7.59 (s, 1H), 9.02 (s, 1H), 9.35 (s, 1H). 13C NMR (DMSO-
d6) 112,7, 114.7, 122.3, 118.3, 119.1, 125.0, 127.0, 130.9, 131.2,
131.8, 136.5, 139.1, 142.2, 152.6. MS (FAB) m/z (M+) 374.0,
Supporting Information Available: Titration data con-
taining 1H NMR CIS curves of monomers 1-7, UV-vis spectra
and Benesi-Hildebrand plots of 5, fluorescence emission
spectra and Stern-Volmer plot of 7. This material is available
free of charge via the Internet at http://pubs.acs.org.
JO048470P
1736 J. Org. Chem., Vol. 70, No. 5, 2005