Synthesis and characterization of higher generation dendrons based on melamine using p-aminobenzylamine. Evidence for molecular recognition of Cu(II)

Article abstract of DOI:10.1016/S0040-4039(01)01007-3

The difference in nucleophilicity between the amines of p-aminobenzylamine can be used to synthesize dendrimers based on melamine using a convergent, orthogonal approach. The resulting molecules comprise groups that donate and accept hydrogen-bonds, limiting synthetic accessibility due to intermolecular aggregation. Dendrons with molecular weights exceeding 10 kDa can be prepared by this strategy, but yields drop off significantly at the highest generation (D5) due to difficulties in purification. The addition of Cu(II) reduces the extent of aggregation as evident in SEC traces. UV-vis spectroscopy confirms recognition.

Full text of DOI:10.1016/S0040-4039(01)01007-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 5355–5357
Synthesis and characterization of higher generation dendrons
based on melamine using p-aminobenzylamine. Evidence for
molecular recognition of Cu(II)
Wen Zhang and Eric E. Simanek*
Department of Chemistry, Texas A&M University, College Station, TX 77843, USA
Received 30 March 2001; accepted 6 June 2001
Abstract—The difference in nucleophilicity between the amines of p-aminobenzylamine can be used to synthesize dendrimers
based on melamine using a convergent, orthogonal approach. The resulting molecules comprise groups that donate and accept
hydrogen-bonds, limiting synthetic accessibility due to intermolecular aggregation. Dendrons with molecular weights exceeding 10
kDa can be prepared by this strategy, but yields drop off significantly at the highest generation (D5) due to difficulties in
purification. The addition of Cu(II) reduces the extent of aggregation as evident in SEC traces. UV–vis spectroscopy confirms
recognition. © 2001 Elsevier Science Ltd. All rights reserved.
Our interest in dendrimers based on melamine stems
from the potential structural diversity that can be intro-
duced into these scaffolds by interconnecting the tria-
zine cores with a variety of diamine linkers.1 Initially,
p-aminobenzylamine was chosen as a linking group
because it offers an orthogonal, convergent route to
these dendrimers.2–5 We recognized, however, that p-
aminobenzylamine could also limit the synthetic
tractability of these architectures by facilitating aggre-
gation. Newkome and co-workers reported similar
difficulties with dendrimers containing diaminopyridine
groups.6 Evidence for aggregation was already sug-
gested in dendrimers with molecular weights of ꢀ3
kDa.1 Here, we report the limitations of p-aminobenzyl-
amine as a linking group. Evidence for the recognition
of Cu(II) by these molecules, and the use of these
complexes during analysis is also described.
protons of p-aminobenzylamine groups (A–C) reveal
the extent of reaction. That is, lines from Boc-protected
groups (A) are different from those of a free aniline (B),
and from those of a p-aminobenzylamine group on the
interior (C). Similar trends in the appearance of the
aniline NH2 groups (D) and the aromatic protons of the
free aniline (E, F) are also evident.
Dendrons comprising p-aminobenzylamine can be pre-
pared cleanly up to the fifth generation dendron, 10,
when repeated purification fails to remove traces (<5%)
of 9 from the desired product. The starting material is
apparent by NMR, mass spectrometry,14 and size exclu-
sion chromatography (Fig. 2). We attribute difficulties
in purification to intermolecular aggregation. Indeed,
the generation-dependent broadening that we attribute
to aggregation can be significantly reduced by the addi-
tion of excess Cu(II).13 The sharper peaks in the SEC
traces suggest that Cu(II) coordinates to the dendrimer
and interferes with intermolecular hydrogen-bonding
between melamine groups. The coordination of Cu(II)
is confirmed by the appearance of three absorption
bands between 400 and 480 nm for these complexes
with dendrons 2, 4, 6, 8, and 10 (stacked respectively in
Fig. 2b). MALDI/TOF spectra show the ions corre-
sponding to Cu(II) complexes for 2 and 4.
The synthetic route to these dendrons relies on iterative
reactions between cyanuric chloride and p-aminobenzyl-
amine (Scheme 1).7–11 The difference in nucleophilic-
ities between the aryl- and alkylamine groups of
p-aminobenzylamine allows the reaction of p-
aminobenzylamine with a monochlorotriazine to pro-
1
ceed with excellent selectivity and in high yield. The H
NMR spectra of dendrimers in DMSO-d6 reveal the
iterative nature of the synthesis (Fig. 1). For example,
the positions and relative intensities of the benzylic
While we have determined that the use of p-aminoben-
zylamine as an orthogonal linker is limited to medium-
sized dendrons due to aggregation, we have uncovered
a valuable technique for probing aggregation: the addi-
* Corresponding author.
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)01007-3

5356
W. Zhang, E. E. Simanek / Tetrahedron Letters 42 (2001) 5355–5357
Scheme 1. Synthesis of dendrons. Large dendrons are shown schematically. Reagents and conditions: a. C3N3Cl3, THF, 0–25°C,
DIPEA. b. p-aminobenzylamine, THF, 80°C, DIPEA.12
Figure 1. 1H NMR spectra of 2–10 in the region of 3.5–8 ppm in DMSO-d6.
tion of Cu(II) leads to sharpening of SEC traces. Den-
dritic structures based on triazines have recently been
shown to be useful scavengers of protons and amines.15
The ability of the reported molecules to sequester cop-
per ions is not unique to these dendrons, but offers
potential application of melamine-based architec-
tures.16–22
Acknowledgements
This work was supported by grants from Texas A&M
University and the Robert A. Welch Foundation. We
thank Dr. David Bergbreiter for the use of his appara-
tus for SEC.

W. Zhang, E. E. Simanek / Tetrahedron Letters 42 (2001) 5355–5357
5357
Figure 2. The SEC traces of dendrons 10, 8, 6, 4, and 2 (left) and the respective Cu(II) complexes (middle) with the associated
UV–vis spectra. Times for the SEC are reported in minutes.
MHz, DMSO) l 166.10, 164.56, 156.48, 139.44, 134.15,
127.78, 120.53, 78.39, 43.74, 28.96. MS: Calcd, 13140.16
(M+); Found (MALDITOF): 13142.81.
References
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7. Molecules 1–6 have been described in Ref. 1. The use of
13C NMR is also described.
12. DIPEA is N,N-diisopropylethylamine.
13. The complexes were prepared by the reactions of den-
drons with CuCl2·2H2O in refluxing CH2Cl2–CH3OH.
Titrations with this salt or with Cu(OAc)2 were unsuc-
cessful suggesting a weaker association between copper
ions and the dendrons than the counterions.
14. The line corresponding to molecular ions for some of
these dendrons is broad, and has a position that is highly
dependent 0.1% on the conditions of ionization.
Accordingly, some of the mass spectra of these dendrons,
especially 9, deviate from the predicted mass. Subsequent
molecules prove satisfactory, however, and isotope distri-
bution patterns match the predicted pattern. The origins
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col for obtaining accurate masses of these polymers is
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15. Marsh, A.; Carlisle, S. J.; Smith, S. C. Tetrahedron Lett.
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cyclononanes to recognize copper ions has been reported:
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B. D. Chem. Commun. 1997, 25, 515–516.
19. Self-assembly of a dendrimer around a Cu(II) core has
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8. Data for compound 7: 1H NMR (300 MHz, DMSO) l
9.07 (br, 7H), 9.00 (br, 7H), 7.73 (m, 28H), 7.55 (br, 6H),
7.32 (m, 8H), 7.21 (m, 12H), 7.12 (br, 16H), 6.98 (d,
J=11.5 Hz, 2H), 6.46 (d, J=12 Hz, 2H), 4.86 (s, 2H),
4.48 (br, 12H), 4.34 (br, 2H), 4.05 (br, 16H), 1.39 (s,
72H). 13C NMR (75 MHz, DMSO) l 166.47, 164.77,
156.47, 148.02, 139.58, 133.98, 128.69, 127.73, 120.43,
114.38, 78.35, 43.73, 28.93. MS: Calcd, 3158.55 (M+);
Found (MALDITOF), 3156.23.
9. Data for compound 8: 1H NMR (300 MHz, DMSO) l
9.07 (s, 15H), 9.00 (s, 15H), 7.70 (m, 60H), 7.58 (br,
14H), 7.30 (br, 16H), 7.20 (d, J=11.5 Hz, 28H), 7.10 (br,
32H), 4.46 (br, 28H), 4.05 (br. 32H), 1.38 (s, 144H). 13C
NMR (75 MHz, DMSO) l 166.48, 164.77, 156.49,
139.60, 133.99, 127.76, 120.44, 78.38, 43.74, 28.97. MS:
Calcd, 6428.57 (M+); Found (MALDITOF): 6429.92.
10. Data for compound 9: 1H NMR (300 MHz, DMSO) l
9.06 (br, 15H), 8.98 (br, 15H), 7.71 (m, 60H), 7.56 (br,
14H), 7.30 (m, 16H), 7.20 (m, 28H), 7.09 (br, 32H), 6.98
(d, J=11.5 Hz, 2H), 6.48 (d, J=12 Hz, 2H), 4.83 (br,
2H), 4.46 (br, 28H), 4.36 (br, 2H), 4.05 (br, 32H), 1.38 (s,
144H). 13C NMR (75 MHz, DMSO) l 166.48, 164.78,
156.49, 148.00, 139.61, 133.99, 128.73, 127.76, 120.43,
114.39, 78.39, 43.74, 28.97. MS: Calcd, 6514.28 (M+);
Found (MALDITOF): 6520.96.
20. A recent report of the interaction of Cu(OAc)2 and
melamine derivatized polystyrene resins, and their use as
oxidation catalysts has appeared: Wang, Y.-P.; Luo, Y.;
Wang, W.-M. React. Funct. Polym. 1997, 33, 81–85.
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Goddard, III, W. A.; Tomalia, D. Environ. Sci. Technol.
1999, 33, 820–824.
1
11. Data for compound 10: H NMR (300 MHz, DMSO) l
22. Gebbink, R. J. M. K.; Bosman, A. W.; Feiters, M. C.;
Meijer, E. W.; Nolte, R. J. M. Chem. Eur. J. 1999, 5,
65–69.
9.08 (s, 32H), 9.03 (s, 32H), 7.69 (m, 124H), 7.61 (br,
30H), 7.28 (br, 32H), 7.18 (m, 60H), 7.08 (br, 64H), 4.45
(br, 60H), 4.03 (br, 64H), 1.36 (s, 288H). 13C N
MR (75
.