9-(Guanidinomethyl)-10-vinylanthracene: A suitable fluorescent monomer for MIPs

Article abstract of DOI:10.1016/S0040-4039(01)00738-9

9-(Guanidinomethyl)anthracene derivatives with a bromo (6) or a vinyl group (10) at the 10-position have been prepared starting from 9-bromoanthracene (1). They show 1:1 complexation with carboxylic acids or carboxylates with K-values of 1.2-1.4×10⁵ M^-1 in deuteriomethanol. Copolymerization of 9-vinylanthracene, 9-(guanidinomethyl)-10-vinylanthracene hydrochloride (10), and the 1:1 complex of 10 and ammonium benzoate with ethyleneglycol dimethacrylate (EDMA) gave the polymers in 77-92% yield.

Full text of DOI:10.1016/S0040-4039(01)00738-9

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 4413–4416
9-(Guanidinomethyl)-10-vinylanthracene: a suitable fluorescent
monomer for MIPs
Huiqi Zhang, Willem Verboom* and David N. Reinhoudt
Laboratory of Supramolecular Chemistry and Technology, Mesa+ Research Institute, University of Twente, PO Box 217,
7500 AE Enschede, The Netherlands
Received 19 February 2001; accepted 2 May 2001
Abstract—9-(Guanidinomethyl)anthracene derivatives with a bromo (6) or a vinyl group (10) at the 10-position have been
prepared starting from 9-bromoanthracene (1). They show 1:1 complexation with carboxylic acids or carboxylates with K-values
of 1.2–1.4×105 M−1 in deuteriomethanol. Copolymerization of 9-vinylanthracene, 9-(guanidinomethyl)-10-vinylanthracene hydro-
chloride (10), and the 1:1 complex of 10 and ammonium benzoate with ethyleneglycol dimethacrylate (EDMA) gave the polymers
in 77–92% yield. © 2001 Elsevier Science Ltd. All rights reserved.
Molecular imprinting is an increasingly important
methodology for the introduction of recognition or
catalytic sites into highly cross-linked polymeric
matrices. A template-directed assembly of specifically
functionalized monomers enables the formation of dis-
crete cavities, complementary in both shape and func-
tionality to the original template. Meanwhile molecular
imprinting has been successfully applied in a wide
variety of disciplines ranging from separation science,
catalysis to biomimetic sensors.1–5
Our first approach is outlined in Scheme 1. 9-Bromoan-
thracene (1) was reacted with N-(hydroxy-
methyl)phthalimide (2) in a 9:1 mixture of acetic acid
and sulfuric acid at 80°C for 24 h to give 9-bromo-10-
(phthalimidomethyl)anthracene (3) in 52% yield. Subse-
quent deprotection with hydrazine monohydrate
afforded the aminomethyl derivative 4 in 75% yield.
Reaction
of
4
with
N,N%-(bis-tert-butoxycar-
bonyl)thiourea8 in the presence of Mukaiyama’s
reagent gave the BOC-protected guanidinomethyl-
anthracene 5 in 81% yield. Deprotection with tri-
fluoroacetic acid in dichloromethane (1:4 v/v) followed
by base treatment of the resulting trifluoroacetate salt
afforded 9-bromo-10-(guanidinomethyl)anthracene (6)9
in 87% yield. Unfortunately, in our hands the bromo
atom in either compounds 5 or 6 could not be con-
verted into a vinyl group using Stille cross-coupling
reaction conditions. However, compound 6 could be
used as a model compound to investigate the complexa-
Fluorescent molecularly imprinted polymers (MIPs) are
very interesting, since a binding-dependent change of
the fluorescence allows the detection of an analyte at
very low concentrations.6 Recently, Wang et al.7
reported the preparation of a MIP-based fluorescent
sensor for
D-fructose based on the covalent interaction
of a boronic acid-containing anthracene derivative with
a cis-diol.
1
tion properties. From a H NMR dilution experiment a
K-value of 1.2×105 M−1 was calculated for the 1:1
complex of compound 6 and toluic acid in deuteri-
omethanol, demonstrating the strong non-covalent
interaction between the two components in this polar
solvent. Comparison of the fluorescence spectra of eth-
anol solutions (5×10−5 M) of compound 6 and of its 1:1
In this communication we report our preliminary
results on the development of MIPs containing anthra-
cene as a fluorescent tag to which a guanidinium moiety
as a recognition element is attached. This allows the
detection of suitable carboxylic acids.
complex with toluic acid showed
a fluorescence
enhancement of about 1.5 for the complex. This large
increase is very promising for the potential use of this
fluorescent recognition element in MIPs.
Keywords: fluorescence; hydrogen bonding; molecular recognition;
polymers.
The desired 9-(guanidinomethyl)-10-vinylanthracene
hydrochloride salt (10) was obtained as summarized in
* Corresponding author. Tel.: +31 (0)53 4892977; fax: +31 (0)53
4894645; e-mail: w.verboom@ct.utwente.nl
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00738-9

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H. Zhang et al. / Tetrahedron Letters 42 (2001) 4413–4416
Scheme 1.
respectively, in deuteriomethanol. Also in the case of
compound 10 (5×10−5 M) complexation with different
carboxylates, ammonium acetate and -benzoate and
tetrabutylammonium acetate, in ethanol induced signifi-
cant changes in the fluorescence.
Scheme 2. In compound 3 the vinyl group was intro-
duced via a Stille cross-coupling reaction under the
conditions developed by Farina and Krishnan.10 Reac-
tion of 9-bromo-10-(phthalimidomethyl)anthracene (3)
with 3 equiv. of tributylvinyltin in the presence of
tris(dibenzylideneacetone)dipalladium (Pd2dba3) as a
catalyst and AsPh3 as additional ligand (ratio 1:4) for 9
days at 55°C gave, after chromatography, an insepara-
ble mixture of starting compound 3 (25%) and the
corresponding vinylanthracene 7 (61%). Prolonged
reaction times did not give rise to higher product yields.
Deprotection of the mixture of 3 and 7 with hydrazine
monohydrate in refluxing ethanol gave a mixture of
compound 4 and 9-(aminomethyl)-10-vinylanthracene
(8) that crystallized from the reaction mixture upon
cooling. Column chromatography drastically lowered
the yield of compound 8 because of decomposition on
the column. Both of the reactions described above were
carried out in the presence of a trace of 2,6-di-tert-
butyl-4-methylphenol as a radical scavenger. Reaction
of the mixture of 4 and 8 with N,N%-(bis-tert-butoxycar-
bonyl)thiourea, as described for the formation of com-
pound 5, afforded, after chromatography, the
BOC-protected guanidinomethylanthracene 9 as a yel-
low–green solid in 66% yield. Subsequent deprotection
The homo- and copolymerization of 9-vinylanthracene
(9-VA) have been investigated by different groups
because of the potential use of the polymers as semi-
conductors, photoresist materials, fluorescent probes,
etc.12 The radical polymerization of 9-vinylanthracene
is rather slow which is attributed to steric hindrance
and the formation of stabilized unreactive dibenzylic
radicals inhibiting the addition of the next monomer.
Katz13 obtained the homopolymer of 9-VA in only
16.5% yield after a reaction time of eight days, while
even the copolymer with styrene was only isolated in
7–11% yield. Takeuchi et al.12 found that in the pres-
ence of ethylaluminium sesquichloride, 9-VA copoly-
merizes with methyl methacrylate (MMA) in yields up
to 28%, dependent on the conditions. Both Krakovyak
et al.14 and Tiera et al.15 reported the copolymerization
of 9-VA with MMA in yields up to 43% containing 0.5
and 0.12 mol percent anthracene. There is some confu-
sion about the way 9-VA is incorporated in the polymer
chain. In principle, there are two possibilities, viz. 1,2-
addition and 1,6-addition. For the radical copolymer-
ization of 9-VA and MMA, Tiera et al.15 concluded
that only 1,2-addition of 9-VA took place, while both
Takeuchi et al.12 and Krakovyak et al.14 found that
11
of compound 9 with SnCl4 in ethyl acetate gave the
target compound 10 in quantitative yield. 1H NMR
dilution experiments gave K-values of 1.2×105 and 1.4×
105 M−1 for the 1:1 complex of compound 10 with
ammonium acetate and tetrabutylammonium acetate,

H. Zhang et al. / Tetrahedron Letters 42 (2001) 4413–4416
4415
Scheme 2.
mainly 1,6-addition and only a small amount of 1,2-
addition occurred.
3. Whitcombe, M. J.; Alexander, C.; Vulfson, E. N. Synlett
2000, 911–923.
4. Asanuma, H.; Hishiya, T.; Komiyama, M. Adv. Mater.
For the ultimate application in MIPs crosslinking of
our monomer was performed with ethyleneglycol
dimethacrylate (EDMA). As a model reaction first 9-
VA was copolymerized with 15 equiv. of EDMA in the
presence of AIBN as initiator in THF at 60°C for 60 h
to give the polymer in a surprisingly high yield of 92%.
Elemental analysis showed the presence of 5.33 mol
percent of 9-VA (theoretical value 6.25%). Thermo-
gravimetric analysis revealed that the polymer had
good thermal stability (decomposition >250°C). IR
spectroscopy pointed to 1,6-addition since the signal at
733 cm−1, assigned to the anthracene, disappeared and
a new signal at 780 cm−1 appeared, which is characteris-
tic for the formed exocyclic double bond.12 In the same
way 9-(guanidinomethyl)-10-vinylanthracene (10) was
copolymerized in refluxing methanol for 48 h to give
the polymer in 83% yield. Copolymerization in the
presence of ammonium benzoate using identical reac-
tion conditions gave the pure MIP in 77% yield.
2000, 12, 1019–1030.
5. Haupt, K.; Mosbach, K. Chem. Rev. 2000, 100, 2495–
2504.
6. For a recent example, see: Rathbone, D. L.; Su, D.;
Wang, Y.; Billington, D. C. Tetrahedron Lett. 2000, 41,
123–126.
7. Wang, W.; Gao, S.; Wang, B. Org. Lett. 1999, 1, 1209–
1212.
8. Iwanowicz, E. J.; Poss, M. A.; Lin, J. Synth. Commun.
1993, 23, 1443–1445.
9. All new compounds show satisfactory spectral data.
Compound 6: mp 168–170°C; 1H NMR (CD3OD): l
8.68–8.64 (m, 2 H, ArH), 8.36–8.32 (m, 2 H, ArH),
7.72–7.68 (m, 4 H, ArH), 5.35 (s, 2 H, CH2); MS–FAB
(3-nitrobenzyl alcohol) m/z 328.1 ([M+H]+; calcd for
C16H15BrN3: 328.2). Compound 10: mp 232–234°C; 1H
NMR (CD3OD): l 8.45–8.42 (m, 2 H, ArH), 8.29–8.26
(m, 2 H, ArH), 7.68–7.50 (m, 5 H, ArH+1 vinyl H), 6.09
(dd, 1 H, J=2.0 and 11.4 Hz, vinyl H), 5.55 (dd, 1 H,
J=2.0 and 17.7 Hz, vinyl H), 5.37 (s, 2 H, CH2); 13C
NMR (CD3OD): l 156.6, 135.45, 132.95, 129.50, 128.4,
126.1, 126.0, 125.75, 124.4, 122.65, 122.15, 37.4; MS–
FAB (3-nitrobenzyl alcohol) m/z 276.1 ([M−Cl]+, calcd
for C18H18N3: 276.1).
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