Orthogonal, convergent syntheses of dendrimers based on melamine with one or two unique surface sites for manipulation

Article abstract of DOI:10.1021/ja0041369

An orthogonal, convergent route for the introduction of substoichiometric numbers of latent surface sites into dendrimers based on melamine is used to prepare targets that display one or two Boc-protected amines on the periphery. Asymmetry is the result of the stepwise incorporation of functionalized and unfunctionalized dendrons onto the triazine cores, a highly selective process due to the different reactivities of the substituted triazines. The routes to the dendrons rely on iterative reactions of the growing dendrons with triazine cores and diamine linkers. p-Aminobenzylamine is used as a linking group to avoid functional group interconversions or protecting group manipulations. Addition of the benzylamine group to the monochlorotriazine of the dendron proceeds cleanly leaving a less reactive aniline for subsequent reaction with trichlorotriazine. The routes to these targets proceed in 5 or 6 linear steps (11 or 12 total steps) in 40% overall yield. The unique surface sites can be deprotected and subjected to additional chemistries. Reaction of the monofunctionalized dendrimer with trichlorotriazine yields the desired dimer, a molecule whose increased size is evident from light scattering and tapping mode atomic force microscopy, and corroborated with computation.

Full text of DOI:10.1021/ja0041369

8914
J. Am. Chem. Soc. 2001, 123, 8914-8922
Orthogonal, Convergent Syntheses of Dendrimers Based on Melamine
with One or Two Unique Surface Sites for Manipulation
Wen Zhang, Daniel T. Nowlan, III, Lisa M. Thomson,† William M. Lackowski,‡ and
Eric E. Simanek*
Contribution from the Department of Chemistry, Texas A&M UniVersity, College Station, Texas 77843
ReceiVed December 1, 2000. ReVised Manuscript ReceiVed July 9, 2001
Abstract: An orthogonal, convergent route for the introduction of substoichiometric numbers of latent surface
sites into dendrimers based on melamine is used to prepare targets that display one or two Boc-protected
amines on the periphery. Asymmetry is the result of the stepwise incorporation of functionalized and
unfunctionalized dendrons onto the triazine cores, a highly selective process due to the different reactivities of
the substituted triazines. The routes to the dendrons rely on iterative reactions of the growing dendrons with
triazine cores and diamine linkers. p-Aminobenzylamine is used as a linking group to avoid functional group
interconversions or protecting group manipulations. Addition of the benzylamine group to the monochlorotriazine
of the dendron proceeds cleanly leaving a less reactive aniline for subsequent reaction with trichlorotriazine.
The routes to these targets proceed in 5 or 6 linear steps (11 or 12 total steps) in 40% overall yield. The
unique surface sites can be deprotected and subjected to additional chemistries. Reaction of the monofunc-
tionalized dendrimer with trichlorotriazine yields the desired dimer, a molecule whose increased size is evident
from light scattering and tapping mode atomic force microscopy, and corroborated with computation.
Introduction
approaches to prepare a dendrimer incorporating a single nitrile
that could be reduced to afford an amine. While neither
orthogonal nor trivial in execution, it remained the solitary
example of a monofunctionalized dendrimer for almost 10 years.
Recently, Schluter and co-workers reported dendrimers synthe-
sized using Hawkers’s original strategy that display a single
aromatic bromide at three different positions including one near
the surface. Schluter has shown that the arylbromide can be
cross-coupled with 4-tert-butylphenylboronic acids under Suzuki
conditions to incorporate groups at specific positions within the
dendrimer.10 Here, we describe the synthesis and characterization
of a new class of dendrimers based on melamine with one or
two protected amine sites on the surface. The syntheses of targets
1 and 2 are orthogonal and convergent, can be executed
expeditiously, and proceed in excellent overall yields.
Our long-term goal is to develop routes that afford specific
control over the placement of diversity both on the interior and
periphery of dendrimers. Dendrimers based on melamine offer
an opportunity to generate diversity in a synthetically tractable
manner.11 While the syntheses of Hawker, Wooley, and Schluter
using Fre´chet-type dendrimers have successfully exploited
statistical reactions biased by sterics to obtain asymmetry, we
use the differential reactivity of the triazines. By controlling
the temperature, N,N′,N′′-trisubstituted triazines can be obtained
by sequential addition of amines (Scheme 1). Yields exceeding
90% are routine for these one-pot reactions. Employing diamines
offers an opportunity to interconnect triazines to afford den-
drimers.
The belief that structural diversity will lead ultimately to
functional utility inspires the synthetic dendrimer community.1-3
Thus, the synthesis of dendrimers that display specific patterns
of groups that are amenable to postsynthetic manipulation is
an area of great interest. The complexity of these targets varies
significantly in both the number and arrangement of groups.
Typically the result of divergent syntheses, dendrimers termi-
nated with latent or reactive surface groups are common, but
these molecules cannot be manipulated to generate single or
well-defined patterns of multiple functional groups.4-7 Of the
many examples of amine- and hydroxy-terminated dendrimers,
three are commercially available: poly(amidoamine) from
Dendritech (Midland, MI), poly(propyleneimine) from DSM
(Netherlands), and hyperbranched polyester polyols from Per-
storp (Sweden). Engineering fewer sites for manipulation greatly
increases the synthetic challenge.
The first example of a dendrimer displaying a single latent
group for postsynthetic manipulation was reported from Fre´-
chet’s laboratory. Hawker8 and Wooley9 employed convergent
† Laboratory for Molecular Simulation, Texas A&M University.
‡ Center for Integrated Microchemical Systems, Texas A&M University.
(1) Fre´chet, J. M. J. Science 1994, 263, 1710.
(2) Zeng, F.; Zimmerman, S. C. Chem. ReV. 1997, 97, 1681.
(3) Bosman, A. W.; Janssen, H. M.; Meijer, E. W. Chem. ReV. 1999,
99, 1665.
(4) Newkome, G. R.; Weis, C. D.; Moorefield, C. N.; Baker, G. R.;
Childs, B. J.; Epperson, J. Angew. Chem., Int. Ed. Engl. 1998, 37, 307.
(5) Leon, J. W.; Kawa, M.; Fre´chet, J. M. J. J. Am. Chem. Soc. 1996,
118, 8847.
(6) For a recent example with leading references, see: Grayson, S.;
Fre´chet, J. M. J. J. Am. Chem. Soc. 2000, 122, 10335.
(7) Strategies to generate diversity on the interior are also receiving great
attention. For a leading reference, see: Freeman, A. W.; Chrisstoffels, L.
A. J.; Fre´chet, J. M. J. J. Org. Chem. 2000, 65, 7612.
(8) Hawker, C. J.; Fre´chet, J. M. J. Macromolecules 1990, 23, 4726.
(9) Wooley, K. L.; Hawker, C. J.; Fre´chet, J. M. J. J. Chem. Soc., Perkins
Trans. 1 1991, 1059.
Here, we use p-aminobenzylamine to interconnect triazines
to avoid functional group interconversions and protecting group
manipulations. The benzylic amine reacts exclusively with
monochlorotriazines leaving a less reactive arylamine for
(10) Bo, Z.; Schafer, A.; Franke, P.; Schluter, A. D. Org. Lett. 2000, 2,
1645.
(11) Zhang, W.; Simanek, E. E. Org. Lett. 2000, 2, 643.
10.1021/ja0041369 CCC: $20.00 © 2001 American Chemical Society
Published on Web 08/24/2001

Orthogonal, ConVergent Syntheses of Dendrimers
Scheme 1. Differential Reactivity of Triazines
J. Am. Chem. Soc., Vol. 123, No. 37, 2001 8915
atoms from triazines by TLC, and offering easy separation of
these materials after reaction. The difference in polarity between
two anilines is not significant at higher generations.
Synthesis of the Functionalized Dendrons. Scheme 4 shows
the synthesis of the functionalized dendrons. The Boc-protected
diamine selected offers a long, flexible handle that we subse-
quently show to be available for additional chemistries, and
a RNH2 at 0 °C in THF with diisoproylethylamine (DIPEA). b R′NH2
at 25 °C in THF with DIPEA. c R′′NH2 at 80 °C in THF with DIPEA.
Scheme 2. Chemoselective Reaction Affords an Orthogonal
Route to These Dendrimers
1
provides characteristic lines in an uncrowded region of the H
NMR spectrum. Synthesis of 9 proceeds in 86% overall yield
through the sequential addition of Boc-protected amine to
trichlorotriazine at low temperature (0 °C) followed by addition
of butylamine at room temperature. Elaboration with p-
aminobenzylamine at elevated temperature (70 °C) proceeds
selectively to yield aniline 10. To obtain 11, trichlorotriazine is
reacted first with 4 at -10 °C. TLC reveals only the formation
of the dichlorotriazine intermediate. Following the addition of
10, the reaction is warmed to room temperature and monitored
for disappearance of the dichlorotriazine and appearance of 11.
After purification by silica gel chromatography, NMR spec-
troscopy and mass spectrometry do not provide any evidence
of 5, a product that might result from reaction of 2 equiv of 4
with trichlorotriazine. Similarly, no evidence for the product
resulting from reaction of 2 equiv of 10 with trichlorotriazine
is observed. Reaction of 11 with p-aminobenzylamine provides
aniline 12 cleanly. Careful addition of 6 to trichlorotriazine
followed by addition of 12 provides 13. Again, the entire
reaction sequence to provide 13 can be monitored easily by TLC
to ensure complete reaction at each stage.
reaction with the subsequent trichlorotriazine core (Scheme 2).
This orthogonal strategy differs from routes described by
Zimmerman,12 Yu,13 Fre´chet,14 and Kakimoto15 in that chemo-
selectivity and not orthogonal reactivity is used.
Results and Discussion
The convergent route to the preparation of dendrimers with
a unique surface site(s) requires reaction of trichlorotriazine with
the functionalized and unfunctionalized dendrons at each
generation. The dendron syntheses are described individually
beginning with the unfunctionalized dendrons, molecules that
serve as reagents in our discussion of the synthesis of func-
tionalized dendrons.
Synthesis of Unfunctionalized Dendrons. Scheme 3 shows
the synthesis of the unfunctionalized dendrons used to construct
1 and 2. The route entails iterative reactions of cyanuric chloride
and p-aminobenzylamine. Butyl groups on the periphery are
large enough to convey solubility in organic solvents, while
being small enough to afford crystalline (as opposed to waxlike)
solids.
Synthesis of Dendrimers. Reaction of 8 with 13 affords the
monofunctionalized dendrimer 1 (Scheme 5). Reacting 2 equiv
of 13 with piperazine yields 2. Assessing the overall purity of
these molecules is difficult. The 1H NMR spectra of these
molecules do not reveal impurities, but the broad lines can
obscure any such observation. Mass spectrometry provides
evidence for contamination: a line corresponding to the reaction
product of 7 and 8 (yielding the unfunctionalized, all-butyl
terminated dendrimer) is evident in the spectra of 1. We estimate
the impurity exists at <3% based on doping samples of 1 with
a sample of the all-butyl dendrimer that we prepared as a control.
Trace amounts of dendron 7 that contaminate dendron 12 can
lead to the appearance of dendrimer 1 in preparations of
dendrimer 2. A line corresponding to 1 appears in the mass
spectrum of 2 at <3% relative intensity.
Manipulation of Unique Surface Sites. Treatment of den-
drimers 1 and 2 with a 1:1 solution of trifluoroacetic acid and
dichloromethane provides quantitative deprotection (Scheme 6).
Molecules 14 and 15 are purified using silica gel chromatog-
raphy. Encouragingly, neither the NMR nor mass spectra of
the resulting products show evidence of impurities. The amine
groups can be acylated with isocyanates or reacted with
trichlorotriazine. Indeed, reaction of 14 with 0.5 equiv of
trichlorotriazine provides dimer 16. Efforts to polymerize 15
with bisisocyanates to provide a popcorn-on-a-string motif have
yielded precipitates that are the object of further study.
Monochlorotriazine 3 is available in one step from butyl-
amine and trichlorotriazine. Reaction with p-aminobenzylamine
at elevated temperatures proceeds specifically to provide the
desired aniline, 4, in excellent yield. Reaction with 0.5 equiv
of trichlorotriazine in the presence of Hunig’s base at low
temperature provides 5, which is elaborated with p-amino-
benzylamine to 6. Reaction of 6 with trichlorotriazine yields 7.
Piperazine is more reactive than primary amines, and is suited
ideally for reaction with another hindered monochlorotriazine
dendron. The reaction of 7 to yield 8 proceeds cleanly using
excess piperazine. All molecules are soluble in a range of
organic solvents, allowing purification by conventional silica
1
gel chromatography to give satisfactory H and 13C NMR and
mass spectra.
Throughout our iterative approach to these dendrimers, we
choose to isolate the monochlorotriazine instead of elaborating
to the amine in a single, one-pot sequence. That is, starting with
4, we could proceed to 6 without isolating or purifying
intermediate 5 by addition of the p-aminobenzylamine linker
in one pot. Our primary motivation for using a multipot protocol
is purification and characterization. The differences in polarity
between the anilines and monochlorotriazines is significant,
allowing us to monitor the stepwise displacement of chlorine
Characterization. In addition to 1H and 13C NMR spectros-
copy, and mass spectrometry, the dendrimers were characterized
by light scattering and atomic force microscopy to evaluate
differences in size. Computational models corroborate experi-
mental results. Combustion analyses proved satisfactory for
dendrimer-solvent complexes. The targets did not provide
traces by size exclusion chromatography.
(12) Zeng, F.; Zimmerman, S. C. J. Am. Chem. Soc. 1996, 118, 5326.
(13) Deb, S. K.; Maddux, T. M.; Yu, L. J. Am. Chem. Soc. 1997, 119,
9079.
(14) Freeman, A. W.; Fre´chet, J. M. J. Org. Lett. 1999, 685.
(15) Ishida, Y.; Jikei, M.; Kakimoto, M.-a. Macromolecules 2000, 33,
3302.
1
(a) NMR Spectroscopy. Both the 13C and H NMR spec-
troscopy reveal clues of the iterative nature of the synthesis.
While some of this detail is obscured by the broadening of the

8916 J. Am. Chem. Soc., Vol. 123, No. 37, 2001
Zhang et al.
Scheme 3. Synthesis of the Unfunctionalized Dendrons
a p-Aminobenzylamine at 70 °C in THF with DIPEA. b C3N3Cl3 (0.5 equiv) at 0 °C in THF with DIPEA. c Excess piperazine.
Scheme 4. Synthesis of the Functionalized Dendrons
a p-Aminobenzylamine at 70 °C in THF with DIPEA. b Room temperature; after addition of 4 at -10 °C to C3N3Cl3 in THF with DIPEA.
c Room temperature to 40 °C; after addition of 6 at -10 °C to C3N3Cl3 in THF with DIPEA.
1
lines of the H NMR, the appearance of the aniline resonance
and positions of the benzylic and aromatic protons of the
p-aminobenzylamine are indicative of the extent of reaction.16
We attribute the broadness of the spectra to many factors
including rotational isomers about the triazine linkage (single
bond isomers arising from hindered rotation of the triazine ring-
NHR bond) and intra- and intermolecular hydrogen bonding.17-19
Indeed, the 1H NMR recorded in DMSO-d6 of larger dendrons
and the dendrimers reveal hydrogen bonding: exchangeable
melamine protons appear downfield at ∼9 ppm; multiple broad
peaks appear between 7 and 8 ppm.20
Similar trends in the appearance and disappearance of lines
in the 13C spectra corresponding to aromatic carbons of
(18) For 1H and 13C solution state analyses of triazine rotamers, see:
Birkett, H. E.; Harris, R. K.; Hodgkinson, P.; Carr, K.; Charlton, M. H.;
Cherryman, J. C.; Chippendale, A. M.; Glover, R. P. Magn. Reson. Chem.
2000, 38, 504.
(16) This trend has been verified by the synthesis of larger generation
dendrons based on p-aminobenzylamine: Zhang, W.; Simanek, E. E.
Tetrahedron Lett. 2001, in press.
(19) For 15N analyses of triazine rotamers, see: Amm, M.; Platzer, N.;
Guilhem, J.; Bouchet, J. P.; Volland, J. P. Magn. Reson. Chem. 1998, 36,
587.
(17) Such broadness is useful for studying self-assembling aggregates
based on polymelamines. See, for example: Whitesides, G. M.; Simanek,
E. E.; Mathias, J. P.; Seto, C. T.; Chin, D. N.; Mammen, M.; Gordon, D.
M. Acc. Chem. Res. 1995, 28, 37.
(20) Similar shifts in H-bonded melamine protons have been reported
in hydrogen-bonded aggregates; for a general discussion, see ref 16. For
Seto’s initial report, see: Seto, C. T.; Whitesides, G. M. J. Am. Chem. Soc.
1991, 112, 6409.

Orthogonal, ConVergent Syntheses of Dendrimers
Scheme 5. Synthesis of the Dendrimers
J. Am. Chem. Soc., Vol. 123, No. 37, 2001 8917
Scheme 6. Manipulation of the Dendrimers
and potassium adducts) is observed. For the dendrimers, the
mass spectra reveal the desired ion, gas-phase aggregates of
the desired ion, and lines corresponding to multiply charged
adducts of the desired ion. Smaller lines attributed to fragment
ions from the loss of the BOC group can be observed by altering
the ionization conditions. The results for molecules 1 and 2, as
well as the other dendrons, are all very good.
In general, dendrimers based on melamine show unexpected
behavior by mass spectrometry. While fast atom bombardment
strategies typically provide excellent agreement between cal-
culated and observed ions, MALDITOF gives broad lines that
typically overestimate the MW value by approximately 0.05-
0.1%. This disagreement increases with size and polarirty with
the deprotected amines providing the largest errors. Unfortu-
nately, as these molecules become larger, FAB no longer
produces ions, and we are left to rely on isotope distributions
that match the theortical distribution calculated for our mol-
ecules. As a result the mass spectra of molecules 14-16 display
p-aminobenzylamine are also useful. In larger dendrons and
dendrimers, lines corresponding to aromatic carbons without
protons (typically the triazine) are sometimes absent. We
continue to explore variable-temperature experiments and ad-
ditional solvent(s) in an effort to identify these lines.
(b) Mass Spectrometry. A majority of the mass spectra
reported were acquired using a MALDI-TOF instrument with
trihydroxyacetophenone as the matrix. For the dendrons, a single
line corresponding to the appropriate ion (and those for sodium

8918 J. Am. Chem. Soc., Vol. 123, No. 37, 2001
Table 1. Combustion Analysis of Targets
Zhang et al.
compd
solvent
found (C, H, N)
calcd (C, H, N)
calcd (C, H, N + n solvent)
1
1
2
14
15
16
THF
MeOH
THF
TFA
TFA
THF
61.22, 7.10, 29.20
60.45, 6.96, 29.42
60.28, 7.17, 27.57
54.03, 6.20, 25.63
52.52, 5.96, 23.99
60.58, 6.90, 29.74
61.08, 7.10, 29.82
61.08, 7.10, 29.82
60.46, 7.13, 28.60
61.10, 7.07, 30.59
60.49, 7.09, 30.03
60.70, 6.94, 30.69
61.17, 7.17, 29.29 (1 THF)
60.70, 7.18, 29.35 (1 MeOH)
60.66, 7.27, 27.66 (2 THF)
54.29, 6.02, 25.39 (7 TFA)
52.45, 5.82, 23.92 (9 TFA)
60.80, 7.02, 30.14 (2 THF)
an error (100-600 ppm) outside the range of what is normally
seen for small molecules. The isotope distribution pattern,
however, matches the predicted values.
(c) Combustion Analyses. Combustion analyses of 1, 2, 14,
15, and 16 appear in Table 1. While none of the molecules give
satisfactory analyses as pure analytes, differences can be
rationalized by including solvent molecules from which the
sample was derived.
(d) Size Exclusion Chromatography. We are surprised to
find that the substitution of butyl groups for one or two Boc-
amine groups dramatically affects our ability to obtain SEC
traces for these materials. While all intermediates, 3-13, elute
off the column to provide clean SEC traces, none of the larger
molecules incorporating this side chain (1, 2, 14-16) elute from
the column. We prepared the all-butyl dendrimer (corresponding
to reaction of 7 with 8) to confirm that these polyether side
chains influenced the behavior of these molecules on the column.
Indeed, this molecule provides a trace consistent with dendrimers
that present BOC-protected p-aminobenzylamine groups on the
surface.
(e) Light Scattering. Light scattering confirms the expected
difference in size between 1, 2, and 16. The hydrodynamic
diameters of 1 and 2 are measured to be 3.3 and 3.2 nm,
respectively, corresponding to molecular weights of 4.4 and 4.1
kDa. The hydrodynamic radius calculated for the dimer, 16, is
5.4 nm, corresponding to a molecular weight of 10.9 kDa.
Computation corroborates these measurements.
(f) Atomic Force Microscopy. Dendrimers have been shown
to spontaneously absorb to clean, atomically flat Au(111)
surfaces allowing direct visualization with tapping mode(TM)-
AFM.21-23 The micrographs shown in Figure 1 include (a) the
clean Au(III) surface before adsorbtion, (b) incubation of the
surface with a solution of 1, and (c) incubation with dimer 16.
The monoatomic steps present on the clean Au(111) surface
are identifiable in the first panel. Treatment of the surface with
THF provides an identical micrograph. The monolayers of
dendrimers (lighter contrast) that appear in subsequent panels
result from immersion of the Au for 30 s in a THF solution of
the materials. Consistent with observations from other labora-
tories, monolayers formed over a 106-dilution range.24 The
apparent dispersion in the sizes of the dendrimers is due to either
dendrimer aggregation, stacking, or differences in tip-dendrimer
interactions which result in an apparent broadening of features
on the surface.25-27 This broadening becomes worse as the
features approach the size of the end of the tip. All three panels
Figure 1. TM-AFM micrographs of (a) the clean Au(111) surface,
(b) Au(111) surface modified with 1, and (c) Au(111) surface modified
with 16. The lateral dimensions and height scale in all three micrographs
are 500 × 500 and 2.5 nm, respectively.
were recorded with the same AFM tip to keep the tip broadening
interaction similar in all three images.
(21) Hierlemann, A.; Campbell, J. K.; Baker, L. A.; Crooks, R. M. J.
Am. Chem. Soc. 1998, 120, 5323.
The tip-dendrimer interaction does not affect the measured
height of the features on the surface. Dendrimers typically
appear flattened on the surface. Using Digital Instruments
software, we determined that 1 has an average height of 1.4
nm, while 16 is larger with an average height of 1.9 nm. The
widths of these molecules are exaggerated by the nature of the
experiment, but are consistent with the differences in size: 1
has an average width of 11 nm, 16 has an average width of 21
nm.
(22) Lackowski, W. M.; Campbell, J. K.; Edwards, G.; Chechik, V.;
Crooks, R. M. Langmuir 1999, 15, 7632.
(23) Friggeri, A.; Schonherr, H.; van Manen, H.-J.; Huisman, B.-H.;
Vancso, G. J.; Huskens, J.; van Veggel, F. C. J. M.; Reinhoudt, D. N.
Langmuir 2000, 16, 7757.
(24) Rahman, K. M. A.; Durning, C. J.; Turro, N. J.; Tomalia, D. A.
Langmuir 2000, 16, 10154.
(25) Markiewicz, P.; Goh, M. C. Langmuir 1994, 10, 5.
(26) Keller, D. J.; Franke, F. S. Surf. Sci. 1993, 294, 409.
(27) Vesenka, J.; Miller, R.; Henderson, E. ReV. Sci. Instrum. 1994, 65,
2249.

Orthogonal, ConVergent Syntheses of Dendrimers
J. Am. Chem. Soc., Vol. 123, No. 37, 2001 8919
Figure 2. Computational models of the gas-phase structures of 1 and 16. Piperazine cores are shown in maroon. The Boc-protected amine of 1 is
shown in green. The triazine core of 16 is shown in green. The scale bar represents 5 nm.
(g) Computation. The gas-phase minimized structures of 1
and 16 are shown in Figure 2. These models serve to both
ground our intuition and challenge our preconceptions of the
structure of these molecules. Stacking of aromatic rings is
responsible for the low-energy structures that were obtained
starting from the fully extended, planar, butterfly-shaped
structures (similar to that shown for 1 in Scheme 5).
Both molecules are small enough that the “core” piperazines
(shown in maroon) of 1 and 16 and the Boc-protected amine of
1 (shown in green) are accessible to solvent in these models.
However, the linker triazine of the dimer 16 (shown in green)
is much less accessible to solvent. Calculations show that 1 has
edge dimensions of 3 nm, and a radius of gyration of 1.05 nm.
Dimer 16 is egg-shaped with dimensions of 3 nm and 5 nm.
The calculated radius of gyration of 16 is 1.3 nm. As expected,
these values are smaller than the dimensions observed by light
scattering, and more consistent with the height of the dendrimers
determined by TM-AFM.
first described by Tomalia, offer opportunities to explore the
synthesis and properties of molecules of a new length scale.28,29
Tomalia’s strategy, one that employs a cationic PAMAM
dendrimer to recognize anionic PAMAM dendrimers before
covalently cross-linking the assembly with a carbodiimide
reagent, takes advantage of commercially available building
blocks, and as such, is executed rapidly for the assemblies he
has described. Our strategy differs somewhat from Tomalia’s,
however, in that we can manipulate the number and nature of
the bonds between the dendrimer units. Ultimately, with
synthesis, this strategy could afford greater control over structure
and greater structural complexity.
Experimental Section
Computation. Computational results were obtained using the
software package Cerius2 4.2 by Accelrys Minimization and dynamics
calculations in the gas phase were performed with the Open Force Field
(OFF) program, using the pcff second generation force field.30 Charges
for the dendrimer were calculated using the QEq charge equilibration
method. The dendrimer was initially minimized in the fully extended
conformation. Constant volume and temperature (NVT) molecular
dynamics (MD) calculations were then performed on the minimized
structure via simulated annealing. The simulated annealing was carried
out for 140.0 ps, over a temperature range of 300-1000 K, with ∆T )
50 K, using the Nose´ temperature thermostat, a relaxation time of 0.1
ps, and a time step of 0.001 ps. Charges for the dendrimer were
reequilibrated using QEq every 2.8 ps. The dendrimer was minimized
after each anneal cycle of the 50 cycles performed. The minimized
structures shown31 in Figure 2 are the lowest energy structures found
during the simulated annealing.
Conclusions
The differential reactivity of triazines can be used to generate
dendrimers with substoichiometric numbers of surface sites as
demonstrated with the synthesis of 1 and 2. The orthogonal,
convergent route to these molecules proceeds in excellent yields
with only traces of impurities that disappear upon purification
of the deprotected targets. The surface sites can be manipulated
as evident from the synthesis of the dimer, 16, a molecule that
represents the simplest “megamer” of a series of molecules that
we are currently exploring.28 These poly(dendrimer) assemblies,
(29) Uppuluri, S.; Swanson, D. R.; Piehler, L.; Li, J.; Hagnauer, G. L.;
Tomalia, D. A. AdV. Mater. 2000, 12, 796.
(28) Tomalia has proposed the term “megamer” to refer to any poly-
(dendrimer) assembly: Tomalia, D. A.; Uppuluri, S.; Swanson, D. R.; Li,
J. Pure Appl. Chem. 2000, 72, 2343.
(30) Cerius2 Forcefield-Based Simulations, September 1998, San Diego;
Accelrys Inc., 2000.

8920 J. Am. Chem. Soc., Vol. 123, No. 37, 2001
Zhang et al.
AFM. Tapping-mode atomic force microscopy (TM-AFM) was used
to characterize both the monomer and dimer dendrimer species. To
perform the TM-AFM analysis the dendrimers were first adsorbed to
Au(111) single-crystal surfaces. Au(111) single-crystal substrates were
created by flame annealing and zone-refining Au wire to form 1.5-
2.5 mm diameter beads containing single-crystal Au(111) facets.32,33
The atomically smooth Au(111) surface serves as a flat reference plane
onto which the dendrimer can be adsorbed. All Au(111) facets were
imaged in the AFM prior to adsorption of the dendrimer to determine
the structure of the Au. The Au was modified by immersion in dilute
THF solutions of the dendrimer and dendrimer dimer for 30 s followed
by rinsing in THF and drying under a stream of N2. The gold bead
was then mounted in the AFM with an Au(111) facet normal to the
AFM tip. TM-AFM images were obtained in air using a Digital
Instruments Nanoscope III (Santa Barbara, CA) fitted with a 200 mm
j scanner. Tapping-mode cantilevers (NanoSensors, Wetzlar-Blanken-
feld, Germany) had resonant frequencies between 260 and 280 kHz,
force constants of 20-100 N/m, and tip apex radii of ∼10 nm. Images
were acquired at 512 × 512 pixels at 1.0 Hz using a near-minimal
contacting force. The resulting images were flattened and plane-fit using
Digital Instruments software.
room temperature, the solid was filtered and solvent was removed. The
residue was purified by column chromatography with CH2Cl2/CH3OH
(100:1, 50:1) to afford the product as a white solid (6.40 g, 96%). H
NMR (300 MHz, DMSO) 6.94 (br, 2H), 6.50-6.70 (br, 2H), 6.46 (d,
J ) 12 Hz, 2H), 6.22 (br, 1H), 4.88 (s, 2H), 4.22 (d, J ) 7.5 Hz, 2H),
3.17 (br, 4H), 1.43 (br, 4H), 1.28 (m, 4H), 0.87 (t, 6H). 13C NMR (75
MHz, DMSO) 166.45, 166.37, 147.80, 128.83, 114.26, 43.62, 32.32,
20.32, 14.45. MS: calcd, 343.45 (M+); found (MALDITOF) 344.16
(M + H+). HR-MS: calcd 344.2563 (M + H+); found (+LSIMS)
344.2547 (M + H+).
1
Intermediate 5. Intermediate 4 (4.40 g, 12.81 mmol) was dissolved
in 100 mL of THF and cooled in an ice bath. Triazine trichloride (1.18
g, 6.40 mmol) and DIPEA were added in single portions. After 1 h the
mixture was warmed to room temperature and stirring continued for
24 h. Upon removal of the solvent, the residue was purified by
chromatography with CH2Cl2/CH3OH (100:1, 50:1, 25:1) to give 5 (4.86
g, 95%). 1H NMR (300 MHz, DMSO) 10.22-9.90 (br, 2H), 7.70 (br,
2H), 7.52 (d, J ) 12 Hz, 4H), 7.23 (br, 4H), 7.00 (br, 2H), 6.22-6.90
(br, 4H), 4.37 (d, J ) 7.50 Hz, 4H), 3.18 (br, 8H), 1.42 (br, 8H), 1.27
(m, 8H), 0.85 (t, 12H). 13C NMR (75 MHz, DMSO) 169.00, 166.46,
164.63, 137.27, 128.06, 121.55, 43.44, 32.32, 20.36, 14.47. MS: calcd
798.50 (M+); found (MALDITOF) 798.12 (M+). HR-MS: calcd
820.4491 (M + Na+); found (+LSIMS) 820.4456 (M + Na+).
Intermediate 6. Intermediate 5 (2.50 g, 3.13 mmol) was dissolved
in 100 mL of THF and p-aminobenzylamine (1.15 g, 9.40 mmol) was
added. The resulting solution was bubbled with nitrogen, sealed in a
Parr vessel, and stirred at 80 °C for 24 h. Upon cooling and removal
of the solvent, the residue was purified by column chromatography
with CH2Cl2-CH3OH (30:1, 20:1) to give a white solid (2.54 g, 92%).
1H NMR (300 MHz, DMSO) 9.00 (s, 1H), 8.90 (s, 1H), 7.67 (d, J )
11 Hz, 4H), 7.38 (br, 2H), 7.15 (br, 4H), 7.01 (d, J ) 12 Hz, 2H), 6.50
(d, J ) 11.5 Hz, 2H), 6.22-7.00 (br, 5H), 4.92 (br, 2H), 4.35 (d, J )
7.5 Hz, 4H), 3.18 (br, 8H), 1.43 (br, 8H), 1.27 (m, 8H), 0.87 (t, 12H).
13C NMR (75 MHz, DMSO) 166.40, 164.74, 147.90, 139.37, 134.73,
128.66, 127.97, 120.34, 114.43, 43.73, 32.25, 20.27, 14.37. MS: calcd
884.09 (M+); found (MALDITOF) 884.24 (M+).
Intermediate 7. Intermediate 6 (800 mg, 0.90 mmol) was dissolved
in 50 mL of THF. Triazine trichloride (83.4 mg, 0.45 mmol) and DIPEA
(0.4 mL) were added. The reaction mixture was stirred at room
temperature for 24 h and then at 50 °C for 4 h. The solvent was removed
and the residue was dissolved in CH2Cl2-CH3OH (30:1) and purified
by chromatography with CH2Cl2-CH3OH (30:1) to give a white solid
(756 mg, 89%). 1H NMR (300 MHz, DMSO) 8.97-9.03 (br, 6H), 7.61
(br, 12H), 7.27 (br, 4H), 7.14 (br, 8H), 6.22-7.10 (br, 14H), 4.48 (br,
4H), 4.34 (br, 8H), 3.17 (br, 16H), 1.42 (br, 16H), 1.26 (m, 16H), 0.85
(br, 24H). 13C NMR (75 MHz, DMSO) 168.10, 166.44, 164.78, 139.29,
137.60, 136.50, 134.88, 127.96, 121.57, 120.53, 43.64, 32.29, 20.31,
14.42. MS: calcd 1879.71 (M+); found (MALDITOF) 1878.96 (M+),
1900.97 (M + Na+), 1916.99 (M + K+).
Dendrimer 1. Intermediate 8 (137 mg, 0.071 mmol) was dissolved
in 3 mL of THF. To the solution 13 (149 mg, 0.071 mmol) and 0.1
mL of N,N-diisopropylethylamine (DIPEA) were added. The solution
was bubbled with nitrogen and sealed in a Parr vessel. The mixture
was heated to 80 °C and stirred for 36 h. Upon cooling and removal of
the solvent, the residue was purified by column chromatography with
CH2Cl2:CH3OH (30:1, 20:1, 15:1) to give the product as a white solid
1
(230 mg, 81%). H NMR (300 MHz, DMSO) 8.94-9.13 (m, 12H),
7.66 (br, 24H), 7.50 (br, 1H), 7.23 (d, J ) 12 Hz, 8H), 7.13 (br, 16H),
6.20-7.00 (br, 28H), 4.46 (br, 8H), 4.32 (br, 16H), 3.84 (br, 8H), 3.46
(br, 10H), 3.33 (br, 4H), 3.16 (br, 30H), 3.04 (m, 2H), 1.40 (br, 30H),
1.35 (s, 9H), 1.24 (br, 30H), 0.84 (br, 45H). 13C NMR (75 MHz,
DMSO) 166.41, 165.34, 164.77, 156.47, 139.31, 134.84, 134.32, 127.86,
120.47, 78.26, 70.41, 70.17, 69.86, 43,40, 32.27, 28.89, 20.29, 14.42.
MS:33 calcd 3991.94 (M+); found (MALDITOF) 3992.82 (M + H+).
Hi-Res: Confirmed Isotope Distribution (+LSIMS).
Dendrimer 2. Intermediate 7 (1276 mg, 0.61 mmol) was dissolved
in 10 mL of THF before DIPEA (0.15 mL) and piperazine (26.14 mg,
0.30 mmol) were added. The solution was bubbled with nitrogen, sealed
in a Parr vessel, and heated to 80 °C with stirring for 36 h. Upon cooling
and removal of the solvent, the residue was purified by column
chromatography on silica gel with CH2Cl2-CH3OH (20:1, 16:1) to
afford the product as a white solid (960 mg, 75%).1H NMR (300 MHz,
DMSO) 8.95-9.14 (m, 12H), 7.67 (br, 24H), 7.50 (br, 2H), 7.23 (d, J
) 11.5 Hz, 8H), 7.14 (br, 16H), 6.20-7.00 (br, 28H), 4.47 (br, 8H),
4.34 br, 16H), 3.84 (br, 8H), 3.46 (br, 20H), 3.33 (br, 8H), 3.17 (br,
28H), 3.04 (m, 4H), 1.40 (br, 28H), 1.35 (s, 18H), 1.24 (br, 28H), 0.84
(br, 42H). 13C NMR (75 MHz, DMSO) 166.40, 165.34, 164.77, 139.31,
134.86, 134.33, 127.87, 120.47, 78.24, 70.41, 70.20, 69.86, 43.45, 32.26,
28.88, 20.29, 14.42. MS: calcd 4211.01 (M+); found (MALDITOF)
4212.63 (M + H+), 4236.93 (M + Na+), 4253.56 (M + K+). Hi-Res:
Confirmed Isotope Distribution (+LSIMS).
Intermediate 8. Intermediate 7 (252 mg, 0.134 mmol) was dissolved
in 6 mL of THF before piperazine (69 mg, 0.80 mmol) and DIPEA
(0.1 mL of N,N-diisopropylethylamine) were added. The resulting
solution was bubbled with nitrogen, sealed in a Parr vessel, and stirred
at 80 °C for 24 h. Upon cooling and removal of the solvent, the residue
was purified by column chromatography with CH2Cl2-CH3OH (20:1,
Intermediate 3. n-Butylamine (5.0 g, 68.36 mmol) was dissolved
in 100 mL of THF. After cooling in an ice bath, triazine trichloride
(6.30 g, 34.18 mmol) and DIPEA (15 mL) in 100 mL of THF were
added dropwise. After 1 h the reaction mixture was warmed to room
temperature and stirred for 12 h. Upon cooling and removal of the
solvent, the solid was washed with CH3OH-H2O (2:1) to afford a white
1
10:1, 5:1) to give a white solid (238 mg, 92%). H NMR (300 MHz,
DMSO) 8.93-9.07 (m, 6H), 7.64 (br, 12H), 7.50 (br, 2H), 7.23 (d, J
) 11 Hz, 4H), 7.13 (br, 8H), 6.22-7.00 (br, 12H), 4.45 (br, 4H), 4.32
(br, 8H), 4.09 (br, 1H), 3.70 (br, 4H), 3.16 (br, 16H), 2.78 (br, 4H),
1.41 (br, 16H), 1.25 (br, 16H), 0.85 (br, 24H). 13C NMR (75 MHz,
DMSO) 166.46, 165.23, 164.67, 139.39, 134.82, 134.28, 127.81, 120.41,
49.27, 45.55, 43.68, 32.28, 20.30, 14.43. MS: calcd 1929.39 (M+);
found (MALDITOF) 1928.88 (M+), 1950.90 (M + Na+), 1966.88 (M
+ K+).
Monoboc-Protected Diamine for the Synthesis of 9. To a solution
of 5,8,11-trioxa-1,13-diamine (9.46 g, 49.27 mmol) in 30 mL of dioxane
was added a 30 mL dioxane solution of di-tert-butyl dicarbonate (1.79
g, 8.21 mmol) dropwise. After the solution was stirred for 12 h at room
temperature and solvent removed, 100 mL of water was added. The
aqueous phase was extracted five times with 50 mL portions of
dichloromethane. The organic phases were combined, extracted four
1
solid (8.28 g, 94%). H NMR (300 MHz, DMSO) 7.78 (br, 1H), 7.66
(br, 1H), 3.20 (m, 4H), 1.46 (m, 4H), 1.23 (m, 4H), 0.87 (t, 6H). 13C
NMR (75 MHz, DMSO) 166.68, 166.02, 31.48, 20.18, 14.32. MS:
calcd 257.76 (M+); found (MALDITOF) 258.07 (M + H+). HR-MS:
calcd 258.1486 (M+); found (+LSIMS) 258.1493 (M+).
Intermediate 4. Intermediate 3 (5 g, 19.4 mmol) was dissolved in
100 mL of THF and 4-aminobenzylamine (7.10 g, 58.2 mmol) was
added. Nitrogen was bubbled through the solution, the Parr vessel was
sealed, and the mixture was heated to 70 °C for 12 h. After cooling to
(31) Materials Studio 1.0; Accelrys Inc. 2000.
(32) Hsu, T.; Cowley, J. M. Ultramicroscopy 1983, 11, 239.
(33) Ross, C. B.; Sun, L.; Crooks, R. M. Langmuir 1993, 9, 632.

Orthogonal, ConVergent Syntheses of Dendrimers
J. Am. Chem. Soc., Vol. 123, No. 37, 2001 8921
times with 50 mL of saturated NaCl solution, and dried over MgSO4.
The solid was filtered and dichloromethane was removed to provide
the monoprotected diamine as a sticky oil (2.36 g, yield 98%). 1H NMR
(300 MHz, DMSO) 6.81 (t, 1H), 3.47 (m, 10H), 3.56 (m, 4H), 3.05
(m, 2H), 2.64 (br, 2H), 1.37 (s, 9H). 13C NMR (75 MHz, DMSO)
156.26, 78.24, 73.60, 70.44, 70.20, 69.86, 67.03, 41.96, 28.89.
Intermediate 9. Triazine trichloride (1.46 g, 7.92 mmol) and DIPEA
were dissolved in 10 mL of THF and cooled to -10 °C. Monoprotected
diamine (2.32 g, 7.92 mmol) was added dropwise, and then the reaction
mixture was stirred for 4 h at -10 °C. After warming to room
temperature, the reaction was stirred for an additional hour. To this
solution n-butylamine (0.79 mL, 7.92 mmol) was added. After the
solution was stirred for 12 h, the solid was removed by filtration, and
the solvent was evaporated. The residue was purified by column
chromatography (eluted with CH2Cl2-CH3OH, 50:1, 35:1, 25:1) to give
the product as a white solid (3.36 g, 89%). 1H NMR (300 MHz, DMSO)
7.82, 7.61 (t, 1H), 7.74 (br, 1H), 6.70 (br, 1H), 3.49 (m, 10H), 3.37
(m, 4H), 3.20 (m, 2H), 3.07 (m, 2H), 1.45 (m, 2H), 1.28 (m, 2H), 0.87
(t, 3H).13C NMR (75 MHz, DMSO) 169.90, 168.25, 166.13, 156.23,
78.21, 70.43, 69.87, 69.37, 69.12, 31.42, 28.85, 20.16, 14.28. MS: calcd
477.09 (M+); found (MALDITOF) 477.172 (M+), 499.13 (M + Na+),
515.10 (M + K+). HR-MS: calcd 477.2592 (M+); found (+LSIMS)
477.2612 (M+).
dissolved in 50 mL of THF and cooled to -10 °C before 12 (2.0 g,
1.81 mmol) and DIPEA (0.4 mL) in 50 mL of THF were of added
dropwise to the solution. The reaction mixture was stirred for 4 h at
low temperature before being warmed to room temperature and stirred
for another 2 h. Intermediate 6 (1.61 g, 1.81 mmol) was added to the
solution in one portion. Reaction continued at room temperature for
12 h and then at 40 °C for 2 h. The solvent was removed and the
residue was purified by flash chromatography (eluted with CH2Cl2-
CH3OH, 30:1, 25:1, 20:1) to give a white solid (3.17 g, 82%). 1H NMR
(300 MHz, DMSO) 8.99-9.04 (br, 6H), 7.67 (br, 12H), 7.29 (br, 4H),
7.16 (br, 8H), 6.20-7.05 (br,15H), 4.50 (br, 4H), 4.36 (br,8H), 3.48
(br, 10H), 3.40 (br, 4H), 3.18 (br, 14H), 3.07 (m, 2H), 1.42 (br, 14H),
1.27 (br, 14H), 0.86 (br, 21H). 13C NMR (75 MHz, DMSO) 166.42,
164.77, 156.27, 139.28, 137.54, 136.29, 134.97, 127.95, 121.59, 120.49,
78.26, 70.42, 70.19, 69.88, 43.72, 32.28, 28.87, 20.31, 14.42. MS: calcd
2099.01 (M+); found (MALDITOF) 2097.61 (M+), 2119.57 (M + Na+),
2135.53 (M + K+).
All-Butyl Dendrimer. Intermediate 7 (51 mg, 0.027 mmol) was
dissolved in 0.5 mL of THF and a drop of DIPEA and piperazine (1.2
mg, 0.0135 mmol) were added before the solution was bubbled with
nitrogen, sealed in a Parr vessel, and heated to 80 °C with stirring for
36 h. After cooling and removal of the solvent, the residue was purified
by column chromatography on silica gel with CH2Cl2-CH3OH (25:1,
1
Intermediate 10. Intermediate 9 (4.07 g, 8.53 mmol) was dissolved
in 20 mL of THF and 4-aminobenzylamine (3.12 g, 25.59 mmol) was
added. The solution was bubbled with nitrogen, sealed in a Parr vessel,
and stirred at 70 °C for 12 h. After cooling and removal of the solvent,
the residue was purified by column chromatography (eluted with CH2-
Cl2-CH3OH, 50:1, 35:1, 20:1) to give the product (4.56 g, 94%) as a
20:1) to afford the product as a white solid (37 mg, 73%). H NMR
(300 MHz, DMSO) 8.95-9.25 (m, 12H), 7.68 (br, 24H), 7.24 (d, J )
11.5 Hz, 8H), 7.16 (br, 16H), 6.20-7.00 (br, 28H), 4.46 (br, 8H), 4.34
(br, 16H), 3.70-3.90 (br, 8H), 3.17 (br, 32H), 1.38 (br, 32H), 1.25
(br, 32H), 0.85 (br, 48H). 13C NMR (75 MHz, DMSO) 166.44, 165.35,
164.73, 139.31, 134.84, 134.28, 127.82, 120.41, 45.55, 43.66, 32.28,
20.31, 14.43. MS: calcd 3772.72 (M+); found (MALDITOF) 3774.64
(M + H+).
Monoamine 14. Dendrimer 1 (60 mg, 0.015 mmol) was dissolved
in 2 mL of a 1:1 mixture of CH2Cl2 and TFA and the solution was
stirred for 12 h. After removal of the solvent, the residue was purified
by column chromatography with CH2Cl2-CH3OH-NH4OH (10:1:0.5)
to give the product as a white solid (55 mg, 94%). 1H NMR (300 MHz,
DMSO) 9.20 (br, 12H), 8.00-8.80 (br, 28H), 7.71 (br, 24H), 7.23 7.24
(br, 24H), 4.45 (br, 24H), 3.55 (br, 12H), 3.27 (br, 30H), 2.98 (m,
4H), 1.48 (br, 30H), 1.27 (br, 30H), 0.88 (br, 45H). 13C NMR (75 MHz,
DMSO) 166.45, 165.35, 164.73, 139.59, 134.29, 133.70, 127.89, 120.46,
70.33, 69.70, 67.33, 43.78, 43.48, 31.87, 20.20, 14.32. MS: calcd
3891.76 (M+); found (MALDITOF) 3894.93 (M + H+).
1
sticky oil. H NMR (300 MHz, DMSO) 6.94 (br, 2H), 6.76 (t, 1H),
6.66-6.10 (br, 3H), 6.46 (d, J ) 12 Hz, 2H), 4.87 (s, 2H), 4.22 (d, J
) 7.5 Hz, 2H), 3.49 (m, 10H), 3.35 (m, 4H), 3.18 (br, 2H), 3.06 (m,
2H), 1.43 (m, 2H), 1.37 (s, 9H), 1.26 (m, 2H), 0.87 (t, 3H). 13C NMR
(75 MHz, DMSO) 166.42, 156.27, 147.79, 128.85, 114.28, 78.28, 70.44,
70.20, 69.98, 69.87, 43.60, 32.27, 28.90, 20.31, 14.44. MS: calcd
562.68 (M+); found (MALDITOF) 563.22 (M+). HR-MS: calcd
585.3489 (M + Na+); found (+LSIMS) 585.3510 (M + Na+).
Intermediate 11. Triazine trichloride (1.31 g, 7.11 mmol) was
dissolved in 50 mL of THF and the solution was cooled to -10 °C
before 10 (4.0 g, 7.11 mmol) and DIPEA (1.5 mL) were added dropwise
as a solution in THF. After the solution was stirred for 4 h at -10 to
0 °C and then at room temperature for 1 h, 4 (2.44 g, 7.11 mmol) was
added in one portion. Stirring was continued at room temperature for
12 h. The solvent was removed and the residue was purified by
chromatography with CH2Cl2-CH3OH (50:1, 35:1, 25:1) to afford the
Diamine 15. Dendrimer 2 (586 mg, 0.14 mmol) was dissolved in
10 mL of a 1:1 mixture of CH2Cl2 and TFA. The resulting solution
was stirred at room temperature for 36 h. After removal of the solvent,
the residue was purified by column chromatography with CH2Cl2-
CH3OH:NH4OH (10:1:1) to give the product as a white solid (521 mg,
1
product as a white solid (6.01 g, 83%). H NMR (300 MHz, DMSO)
10.18 (br, 2H), 7.64 (br, 1H), 7.51 (d, J ) 11.50, 4H), 7.21 (br, 4H),
6.20-7.10 (br, 6H), 4.36 (d, J ) 8 Hz, 4H), 3.48 (br, 10H), 3.33 (br,
4H), 3.18 (br, 6H), 3.04 (m, 2H), 1.42 (br, 6H), 1.36 (s, 9H), 1.25 (m,
6H), 0.86 (t, 9H). 13C NMR (75 MHz, CDCl3) 168.90, 166.36, 164.47,
156.25, 137.34, 136.95, 128.06, 121.48, 78.26, 70.42, 70.17, 69.88,
43.62, 32.27, 28.89, 20.30, 14.42. MS: calcd 1017.73 (M+); found
(MALDITOF) 1017.26 (M+), 1039.23 (M + Na+), 1055.22 (M +
K+).
1
93%). H NMR (300 MHz, DMSO) 8.97-9.13 (m, 12H), 7.92 (br,
2H), 7.66 (br, 24H), 7.51 (br, 2H), 7.32 (br, 12H), 7.22 (d, J ) 12 Hz,
8H), 7.14 (br, 14H), 7.03 (br, 14H), 4.45 (br, 8H), 4.35 (br, 16H), 4.10
(br, 4H), 3.82 (br, 8H), 3.42-3.50 (m. 12H), 3.16 (br, 28H), 2.94 (m,
4H), 1.41 (br, 28H), 1.24 (br, 28H), 0.83 (br, 42H). 13C NMR (75 MHz,
DMSO) 166.46, 165.34, 164.74, 139.60, 139.37, 134.30, 133.70, 127.88,
120.47, 70.34, 69.69, 67.33, 43.78, 43,47, 31.87, 20.20, 14.32. MS:
calcd 4010.79 (M+); found (MALDITOF) 4012.90 (M+), 4038.17 (M
+ Na+).
Dimer 16. Monoamine 14 (40 mg, 0.01 mmol) and triazine
trichloride (0.95 mg, 0.005 mmol) were dissolved in 0.5 mL of THF
and 1 drop of DIPEA was added to the solution. The mixture was stirred
at room temperature for 12 h and then warmed to 50° C for another 12
h. After removing the solvent the residue was purified by column
chromatography with CH2Cl2-CH3OH (25:1, 20:1) to yield a white
solid (24 mg, 58%) that was analyzed by mass spectrometry. 1H NMR
(300 MHz, DMSO) 8.92-9.20 (m, 24H), 7.67 (br, 48H), 7.52 (br, 4H),
7.24 (d, J ) 12 Hz, 16H), 7.16 (br, 32H), 6.50-7.00 (br, 54H), 4.47
(br, 16H), 4.35 (br, 32H), 3.84 (br, 16H), 3.47 (m, 32H), 3.17 (br,
60H), 1.40 (br, 60H), 1.24 (br, 60H), 0.84 (br, 90H). 13C NMR (75
MHz, DMSO) 166.48, 166.10, 164.77, 139.35, 134.50, 134.30, 127.87,
120.49, 70.43, 70.24, 69.92, 43.68, 39.00, 32.23, 20.29, 14.41. MS:
calcd 7895.00 (M+); found (MALDITOF) 7900.46 (M+).
Intermediate 12. p-Aminobenzylamine (0.91 g, 7.43 mmol) was
added to a solution of 11 (2.52 g, 2.48 mmol) in 50 mL of THF. After
nitrogen was bubbled through the solution, the reaction was sealed in
a Parr vessel and stirred at 80 °C for 24 h. After the solid was filtered
and the solvent was removed, the residue was purified by column
chromatography with CH2Cl2-CH3OH (30:1, 25:1, 20:1) to give the
1
product (2.43 g, 89%) as a white solid. H NMR (300 MHz, DMSO)
9.00 (br, 1H), 8.90 (br, 1H), 7.67 (br, 4H), 7.38 (br, 1H), 7.14 (br,
4H), 7.00 (d, J ) 11.5 Hz, 2H), 6.75 (br, 2H), 6.50 (d, J ) 12 Hz,
2H), 6.20-6.65 (br, 5H), 4.91 (s, 2H), 4.34 (d, J ) 8.0 Hz, 4H), 3.48
(br, 10H), 3.35 (br, 4H), 3.18 (m, 6H), 3.05 (m, 2H), 1.42 (br, 6H),
1.36 (s, 9H), 1.26 (m, 6H), 0.87 (m, 9H). 13C NMR (75 MHz, DMSO)
166.47, 164.75, 155.93, 148.02, 139.40, 128.73, 128.02, 127.70, 120.39,
114.38, 78.29, 70.44, 70.20, 69.86, 43.82, 32.31, 28.93, 20.37, 14.50.
MS: calcd 1103.32 (M+); found (MALDITOF) 1103.31 (M+), 1125.29
(M + Na+).
Intermediate 13. Triazine trichloride (334 mg, 1.81 mmol) was

8922 J. Am. Chem. Soc., Vol. 123, No. 37, 2001
Zhang et al.
Acknowledgment. This manuscript is dedicated to Professor
Kenneth L. Rinehart, Jr., in recognition of 47 years of chemistry
at the University of Illinois at Urbana-Champaign (1954-
2001). We thank Texas A&M University and the Welch
Foundation (A-1430) for support. Software and hardware for
computation are provided by the Laboratory for Molecular
Simulation of Texas A&M University.
Note Added in Proof: Kawaguchi and Moore reported the
synthesis of a monofunctionalized poly(arylacetylene) dendrimer
bearing an aldehyde group (Kawaguchi, T.; Moore, J. S. Polym.
Prepr. 1994, 35, 872). Takagi and coworkers have also reported
on the synthesis of triazine dendrimers (Takagi, K.; Hattori, T.;
Kunisada, H.; Yuki, Y. J. Polym. Sci., Part A 2000, 38, 4385).
JA0041369