Synthesis of 1,2,4-triazole dendrimers

Article abstract of DOI:10.1016/j.tet.2005.12.027

A convergent synthetic strategy towards novel 1,2,4-triazole dendrimers, in which 3,5-dichloro-4-(4-methoxyphenyl)-4H-1,2,4-triazole was used as the heterocyclic building block, was successfully explored. Nucleophilic aromatic substitution at this novel A

Full text of DOI:10.1016/j.tet.2005.12.027

Tetrahedron 62 (2006) 2677–2683
Synthesis of 1,2,4-triazole dendrimers
*
Wouter Maes, Bert Verstappen and Wim Dehaen
Molecular Design and Synthesis, Department of Chemistry, Katholieke Universiteit Leuven,
Celestijnenlaan 200F, B-3001 Leuven, Belgium
Received 5 October 2005; revised 8 December 2005; accepted 14 December 2005
Available online 10 January 2006
Abstract—A convergent synthetic strategy towards novel 1,2,4-triazole dendrimers, in which 3,5-dichloro-4-(4-methoxyphenyl)-4H-1,2,4-
triazole was used as the heterocyclic building block, was successfully explored. Nucleophilic aromatic substitution at this novel AB2-
monomer was used as the key step in the propagation of the heterocyclic dendrons and these dendrons were attached to both a 1,3,5-triazine
and a methylene core. The peripheral 1,2,4-triazole could be varied not only by nucleophilic aromatic substitution but also by Suzuki cross-
coupling. The presented dendrimers are promising candidates to be used in applications where the large number of heteroatoms can be
exploited or a better resistance to the applied conditions is required.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
(Fig. 1). The synthesis of the oxadiazole dendrimers was
hampered by the poor reactivity of the system towards
NAS,6 while the triazine dendrimers were characterized
by a lack of stability.7 The pyrimidine system was of an
intermediate reactivity combining an easy synthesis and an
increased stability.8 We now envisaged to enlarge the scope
of our NAS strategy to 1,2,4-triazole dendrimers.
Dendrimers are monodisperse, well-defined macromole-
cules that are prepared through divergent or convergent
iterative procedures to different sizes or ‘generations’. The
unique properties associated with the perfectly branched
dendritic architecture are highly appreciated and have hence
been validated in a substantial amount of different
application fields in recent years.1–3
Some poly(1,2,3-triazole) dendrimers have already been
prepared. Earlier work in our group focused on the synthesis
of dendritic and hyperbranched polytriazoles through 1,3-
dipolar cycloadditions,9,10 while Fokin et al. recently
described a highly efficient ‘click-chemistry’ route to
1,2,3-triazole dendrimers by a copper(I)-catalyzed ligation
of azides and alkynes.11 The only 1,2,4-triazole dendrimers
described so far have been prepared by Diez-Barra et al., but
their synthesis was limited to the first generation.12,13
In the synthesis of dendrimers, it is crucial to employ
reactions with a high efficiency to reduce the probability of
defects in the large structure and to simplify purification.
Recently, we have started to use the nucleophilic aromatic
substitution (NAS) of halides with phenolates as a new
convergent strategy towards dendrimers.4–8 In order to
facilitate this substitution it is necessary to have an electron
poor (e.g., heterocyclic) group in the ortho- or para-position
of the aryl halide, but it is even more efficient to place
the halide directly on a heterocyclic structure. Dendrimers
consisting of 1,3,4-oxadiazoles, 1,3,5-triazines or pyrimi-
dines were successfully synthesized using this approach
Dendrimers are currently being studied as soluble supports
in homogeneous catalysis since their large size enables
recycling by membrane separation techniques.14,15 The
majority of applications of metallodendritic catalysts
N
N
N
N
Cl
N
Cl
F
F
N
N
N
N
O
O
H3CO
H3CO
Cl
Cl
OCH3
1
2
3
Figure 1. Heterocyclic monomers used for the synthesis of dendrimers through a NAS approach.
Keywords: Dendrimer synthesis; 1,2,4-Triazole; Convergent approach; Nucleophilic aromatic substitution; Suzuki cross-coupling.
*
Corresponding author. Tel.: C32 16327390; fax: C32 16327990; e-mail: wim.dehaen@chem.kuleuven.be
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.12.027

2678
W. Maes et al. / Tetrahedron 62 (2006) 2677–2683
concerns hydroformylation, hydrogenation, C–C coupling
reactions, polymerizations and related reactions in non-
oxidizing atmospheres. With a few exceptions,16 oxidation
processes are absent from this spectrum, mainly because of
the susceptibility of several of the previously used
dendrimers to oxidative degradation. Clearly, there is a
need for new, oxidatively stable dendritic macromolecules.
Because of their increased stability, our pyrimidine
dendrons could be used as (recyclable) dendritic catalysts
for oxidation reactions by embedding catalytically active
surface functionalities (benzimidazoles or porphyrins) at the
dendrons periphery.17,18 Incorporation of a benzimidazole
metal complexing moiety resulted in a heterogeneous
catalyst.17 In our search for a completely homogeneous
oxidation-resistant dendritic catalyst the presented 1,2,4-
triazole dendrimers show great potential. Due to the large
number of heteroatoms, polytriazole dendrimers are
excellent candidates for complex formation and coordi-
nation of catalytically active metal atoms. The complexing
azole moieties will now be suspended throughout the
dendritic structure while the periphery can be functionalized
independently to control solubility properties.
poor (hetero)aryl chloride functions in monomer 4,
nucleophilic aromatic substitution at this heterocyclic
building block was made possible and the NAS reaction
was used as the key reaction for the synthesis of the 1,2,4-
triazole dendrimers.
The dendron propagation was started with the substitution
of the two chlorine functions by a phenolate with the desired
peripheral groups. These peripheral groups have a major
influence on the final properties of the dendron or
dendrimer. In order to ensure an easy synthesis, purification
and characterization of the dendritic structures we initially
used 3,5-bis(t-butyl)phenol (9), which is commercially
available at low cost, as a peripheral moiety (to enhance
solubility). This phenol was reacted with monomer 4 to
obtain a first generation dendron 10 (Scheme 2), but
theoretically all compounds bearing a phenol moiety are
insertable as peripheral groups.
The ideal circumstances for the NAS were investigated
(different base-solvent systems). On using the reaction
conditions optimized for the analogous triazine monomer 2
(triethylamine base in dichloromethane at room temperature)
no reaction was observed. The use of potassium t-butoxide
base in refluxing THF resulted in a mixture of mono- and
disubstituted products, even after 5 days of reaction. Both
G1-dendrons could be separated by column chromatography
and were obtained in poor yields (20% each). Another
attempt using the conditions optimized for pyrimidine
monomer 3 (potassium carbonate in refluxing acetonitrile)
did not result in any improvement. Disubstitution of the
1,2,4-triazole monomer 4 finally succeeded when quite harsh
conditions, potassium carbonate in a refluxing mixture of
DMF and toluene (2/1) while azeotropically removing
water, were used. After 3 days of reaction, the disubstituted
G1-dendron 10 could be obtained in an acceptable 80% yield.
To ensure complete substitution 2.2 equiv of the peripheral
phenol 9 were used and G1-dendron 10 was purified by
column chromatography to ensure the absence of 3,5-
bis(t-butyl)phenol or monosubstituted product and hence
avoiding defects in the higher generations.
Conjugated triazole moieties (e.g., 3-(4-biphenylyl)-4-
phenyl-5-(4-tert-butylphenyl)-1,2,4-triazole (TAZ)19,20
)
are known for their excellent electron transporting and
hole blocking ability and have therefore been used (by
itself or incorporated into a polymer (side) chain) in the
construction of organic light-emitting diodes (OLEDs).19–21
Suspension of triazole moieties throughout a dendritic
backbone hence also shows potential in this field. The
major advantage of dendrimers over analogous heterocyclic
polymers is that their electronic and physical properties can
be optimized independently.22
2. Results and discussion
2.1. Monomer synthesis
A 1,2,4-triazole system with the appropriate AB2-symmetry
(analogous to the previous heterocyclic monomers, Fig. 1)
that is well-suited for the convergent dendrimer synthesis is
3,5-dichloro-4-(4-methoxyphenyl)-4H-1,2,4-triazole (4)
(Scheme 1). The synthesis of this novel monomer was
started by the cyclocondensation of 4-methoxyphenyliso-
cyanate (5) with ethyl carbazate (6). The obtained
semicarbazide 7 was then cyclized using potassium
hydroxide after which the triazolidine-3,5-dione (or ‘ura-
zole’) 823–25 could be transformed into the desired monomer
4 using phosphorus oxychloride (in 74% yield).
The obtained first generation dendron 10 could be activated
again for a second substitution by a (high-yielding)
deprotection step using boron tribromide.6–8 Reiteration of
the NAS with the deprotected first generation dendron 11
and monomer 4 gave the second generation dendron 12.
This sequence was repeated up to the third generation
triazole dendron 14 (Scheme 2).
2.3. Peripheral functionalization by Suzuki cross-
coupling
2.2. Propagation of the dendrons
1,2,4-Triazole monomer 4 was also subjected to a Suzuki
cross-coupling reaction. To our knowledge, Suzuki
reactions have never been employed before on halogenated
The 1,2,4-triazole dendrimers were constructed using a
convergent approach. Due to the presence of the electron
Cl
N
O
NH2NHCOOEt
POCl3
74%
KOH
N
N
NH
NH
6
H3CO
N
H3CO
NCO
H3CO
7
94%
90%
5
8
4
Cl
O
Scheme 1. Synthesis of 1,2,4-triazole monomer 4.

W. Maes et al. / Tetrahedron 62 (2006) 2677–2683
2679
K2CO3
O
Cl
N
DMF/toluene
N
N
N
N
RO
N
+
H3CO
HO
80%
O
Cl
4
9
10 R = CH3
11 R = H
BBr3
91%
N
O
N
O
N
O
K2CO3
K2CO3
DMF/toluene
N
N
DMF/toluene
RO
N
G3
4
70%
4
75%
14 R = CH3
O
12 R = CH3
13 R = H
O
N
BBr3
89%
N
O
N
Scheme 2. Convergent propagation strategy towards 1,2,4-triazole dendrons.
triazole moieties. By applying this reaction the scope by
which the periphery of the dendrons can be functionalized
could be extended. While using a standard set of Suzuki
conditions (3 equiv of phenylboronic acid, Pd(PPh3)4
catalyst, Na2CO3 (2 M) base in refluxing DME) we obtained
(after 48 h reaction), besides the desired disubstituted
product 15 (37%), still a substantial amount of the
monosubstituted triazole 16 (47%) (Scheme 3). Optimiza-
tion of the Suzuki procedure (Pd source, ligand, solvent,
base, .) will likely provide a higher yield for the
disubstituted triazole.
2.4. Dendrimer synthesis
The convergent approach to dendrimer synthesis implies
that the synthesized dendritic wedges are attached to a
central core in the final step. In our case, any core molecule
that can be coupled with a phenol functionality, either by
NAS or by some other methodology, can be applied.
2.4.1. Dendrimers with a 1,3,5-triazine core. The
trifunctional, reactive heterocycle 2,4,6-trichloro-1,3,5-
triazine has already been used before as a dendritic core
(by NAS).7 On applying this core, two dendritic
generations (17 and 18, respectively) were synthesized
easily and in high yields using mild NAS conditions
(triethylamine base in dichloromethane at room tempera-
ture) (Fig. 2).
1,2,4-Triazole derivative 15 could now be regarded as an
alternative G1-dendron and could be subjected to the same
NAS propagation strategy as employed for G1-dendron 10,
resulting in an enlarged scope of peripheral functionaliza-
tion possibilities.
Cl
PhB(OH)2
Pd(PPh3)4
N
N
N
N
N
N
H3CO
N
N
H3CO
H3CO
+
N
2 M Na2CO3
DME
4
15
16
Cl
Cl
Scheme 3. Suzuki cross-coupling on 1,2,4-triazole monomer 4.

2680
W. Maes et al. / Tetrahedron 62 (2006) 2677–2683
N
N
O
O
O
N
N
N
O
N
N
O
N
N
N
N
N
O
O
O
N
N
O
O
O
O
N
N
N
N
O
O
N
N
N
N
O
N
N
O
N
O
N
N
O
O
O
N
N
N
N
O
O
N
O
O
O
O
O
N N
O
O
N
N N
N
N
O
O
N
N
N
N
N
O
O
N
N
O
O
N
N
18
20
Figure 2. G2-dendrimers 18 and 20.
2.4.2. Dendron solvolysis in dichloromethane. While
performing NAS reactions in the dendron propagation
sequence it was observed that the presence of trace amounts
of dichloromethane in the reaction mixture (due to work-up
or sample transfer) resulted in the formation of novel
dendrimers by a substitution of the chlorine groups of
dichloromethane. While this reaction is obviously undesired
during the dendron propagation, it shows the potential of
dichloromethane to be used as a difunctional dendritic core.
When adding dichloromethane to a solution of the
deprotonated dendron (NaH) 11 (G1) or 13 (G2) in DMF,
substitution occurs rapidly, resulting in the difunctional
dendrimers 19 and 20, respectively (Fig. 2). Despite the
huge excess of dichloromethane used, no sign of mono-
substituted species could be observed.
by 1H NMR spectroscopy, this had to be done by 13C NMR
spectroscopy and mass spectrometry (ESI). On the other
hand, dendrimers 19 and 20 are easily identifiable by their
characteristic methylene core giving rise to a singlet at
5.8 ppm in the H NMR spectrum corresponding with a
methylene 13C NMR signal at 91 ppm.
1
Analytical scale gel permeation chromatography (GPC)
indicated that all dendrimers were obtained pure and
monodisperse (PDI!1.06).
The glass transition temperatures (Tg) of the dendrimers
were determined by differential scanning calorimetry
(DSC). First generation dendrimer 17 showed a glass
transition at 85 8C at first heating, immediately followed by
an exotherm at 107 8C (probably due to crystallization),
while the analogous G1-dendrimer 19 showed only a clear
Tg at 145 8C. The second generation dendrimers (18 and 20)
showed very broad glass transitions (TgZ133 and 135 8C,
respectively). Moreover, degradation of the dendrimers was
observed at temperatures of approximately 165–180 8C.
2.5. Characterization
Compounds 4, 10–13 and 15–20 were fully characterized
using NMR spectroscopy (1H and 13C) and mass spec-
trometry (CI or ESI).
1
The H NMR spectra of the different generation dendrons
clearly show the signals corresponding with the different
monomer layers and the integration indicates which
generation is involved.
The UV–vis absorption spectrum of the triazole monomer 4
showed a broad absorption peak centered at 234 nm. Phenyl
substitution on the monomer resulted in a red-shift of the
absorption maximum.
Although the formation of G3-dendron 14 could be
demonstrated by both mass spectrometry and NMR
spectroscopy, successful purification of this third generation
triazole dendron (from the excess of G2-dendron, necessary
to drive the reaction to completion, and possibly the
monosubstituted analogue) could not be achieved by
column chromatography.
3. Conclusions
By implementing a convergent nucleophilic aromatic
substitution approach, the synthesis of novel heterocyclic
1,2,4-triazole dendrimers was accomplished. 3,5-Dichloro-
4-(4-methoxyphenyl)-4H-1,2,4-triazole 4 was used as an
AB2-monomer and different cores, including a methylene
core resulting from substitution on dichloromethane, have
been employed to prepare the dendrimers. The reactivity of
Since no core protons are available to prove full core
functionalization of the triazine core dendrimers (17 and 18)

W. Maes et al. / Tetrahedron 62 (2006) 2677–2683
2681
the 1,2,4-triazole monomer towards NAS was proven to be
moderate since quite harsh conditions had to be employed to
promote complete substitution. As a result the propagation
sequence could only be carried out up to the third generation
triazole dendron. The peripheral 1,2,4-triazole could be
varied further by applying standard Suzuki conditions.
The presented polytriazole system provides a promising
alternative for applications in the preparation of novel
rigid homogeneous dendritic (oxidation) catalysts or the
construction of organic light-emitting diodes.
(CH3); IR nmax (cmK1) 3065, 2930, 2848, 1732, 1610, 1513,
1442, 1290, 1257, 1172, 1027, 986, 839; UV–vis (CH2Cl2)
lmax (log 3) 234.0 (3.986). Anal. Calcd for C9H7Cl2N3O: C,
44.29; H, 2.89; N, 17.22. Found: C, 44.35; H, 3.04; N, 17.20.
4.2. General procedure for the synthesis of the protected
dendrons (RZCH3)
The Gx-dendron (3,5-bis(t-butyl)phenol (9), 11 or 13)
(2.2 equiv) in a DMF–toluene (2/1) solution was stirred at
room temperature for 0.5 h with an excess of K2CO3
(3 equiv). After another 0.5 h of reflux, 1,2,4-triazole
monomer 4 (1 equiv) was added and the mixture was
heated at reflux for 3–5 days while azeotropically removing
water. After evaporation of the solvents, CH2Cl2 was added
and the mixture was washed with water. The organic
fraction was dried with MgSO4, filtered and evaporated to
dryness. The 1,2,4-triazole dendrons were purified by
column chromatography (silica) and obtained as white
solids.
4. Experimental
4.1. General
NMR spectra were acquired on commercial instruments
(Bruker Avance 300 MHz or Bruker AMX 400 MHz) and
chemical shifts (d) are reported in parts per million
referenced to tetramethylsilane (TMS) (1H) or the carbon
signal of deuterated solvents (13C). Mass spectra were run
using a HP MS-Engine 5989A apparatus (chemical
ionization (CI), CH4) or a Micromass Quattro II apparatus
(electrospray ionization (ESI), usual solvent mixture:
CH2Cl2/MeOHCNH4OAc). Analytical scale GPC was
performed on a Shimadzu GPC with a Plgel mixed-D
column (Polymer Laboratories); RI and UV detector, mobile
phase THF or CHCl3, flow rate 1 mL minK1, 30 8C,
calibrated with linear polystyrene standards. UV–vis spectra
were taken on a Perkin-Elmer Lambda 20 spectrometer. IR
spectra were obtained on a Perkin-Elmer 1600 instrument as
KBr pellets. Melting points (not corrected) were determined
using a Reichert Thermovar apparatus. Differential scanning
calorimetry was run on a DSC 7 (Perkin Elmer) at a heating
rate of 2 K minK1. Elemental analysis (C, H and N) of
powdered samples was performed on a CE Instrument
EA-1110 elemental analyzer. For column chromatography
70–230 mesh silica 60 (E.M. Merck) was used as the
stationary phase. Chemicals received from commercial
sources were used without further purification. DMF was
4.2.1. G1-dendron (10). Eluent CH2Cl2–ethyl acetate (15/
1); Rf 0.80; yield 80%; MS (CI) m/z 584.5 (MHC); 1H NMR
(CDCl3, 400 MHz) d 7.35 (d, JZ8.7 Hz, 2H), 7.20 (t, JZ
1.8 Hz, 2H), 7.20 (d, JZ1.8 Hz, 4H), 6.99 (d, JZ8.7 Hz,
2H), 3.85 (s, 3H), 1.28 (s, 36H); 13C NMR (CDCl3,
100 MHz) d 160.2 (Ci–OCH3), 154.3, 154.0, 152.7 (Ci–t-
Bu), 127.9 (CHm–OCH3), 124.6 (Ci-triaz.), 119.6 (CH),
115.0 (CHo–OCH3), 113.7 (CH), 55.9 (CH3–O), 35.4, 31.7
(CH3). Anal. Calcd for C37H49N3O3: C, 76.12; H, 8.46; N,
7.20. Found: C, 75.96; H, 8.61; N, 7.03.
On using non-optimized NAS conditions or shorter reaction
times the monosubstituted G1-dendron could be isolated as a
side product. Rf 0.60; MS (CI) m/z 414.2 (100%) and 416.2
(40%) (MHC); 1H NMR (CDCl3, 400 MHz) d 7.35 (d, JZ
8.7 Hz, 2H), 7.23 (t, JZ1.8 Hz, 1H), 7.04 (d, JZ1.8 Hz,
2H), 7.02 (d, JZ8.7 Hz, 2H), 3.86 (s, 3H), 1.28 (s, 18H);
13C NMR (CDCl3, 100 MHz) d 171.5, 161.0 (Ci–OCH3),
153.6, 153.1 (Ci–t-Bu), 128.6 (CHm–OCH3), 124.3 (Ci-
triaz.), 120.1 (CH), 115.3 (CHo–OCH3), 113.9 (CH), 56.0
(CH3–O), 35.4, 31.7 (CH3). Anal. Calcd for C23H28ClN3O2:
C, 66.74; H, 6.82; N, 10.15. Found: C, 67.12; H, 7.10;
N, 9.60.
˚
dried on molecular sieves 4 A.
4.1.1. Synthesis of the 1,2,4-triazole monomer (4) [3,5-
dichloro-4-(4-methoxyphenyl)-4H-1,2,4-triazole]. POCl3
(25 mL) was added to triazolidine-3,5-dione 8 (3.14 g,
15.1 mmol) and the mixture was heated at reflux for 18 h.
After being cooled to room temperature, the mixture was
poured on ice (150 g). The aqueous solution was extracted
with CH2Cl2 (3!50 mL) and the combined organic layers
were dried with MgSO4, filtered and evaporated. The crude
product was further purified by precipitation from an ethyl
acetate solution and monomer 4 was obtained as a white
solid (which could be recrystallized from ethyl acetate)
(2.74 g, 74%). Rf (ethyl acetate) 0.70; mp 200.5–201.5 8C;
MS (CI) m/z 244.0 (100%), 246.0 (67%) and 248.0 (11%)
(MHC); 1H NMR (CDCl3, 300 MHz) d 7.25 (d, JZ8.7 Hz,†
2H), 7.07 (d, JZ8.7 Hz, 2H), 3.90 (s, 3H); 13C NMR
(CDCl3, 75 MHz) d 161.6 (Ci–OCH3), 143.6 (C–Cl), 128.8
(CHm–OCH3), 124.2 (Ci-triaz.), 115.6 (CHo–OCH3), 56.1
4.2.2. G2-dendron (12). Eluent ethyl acetate–petroleum
ether (1/5); Rf 0.15; yield 75%; MS (ESI) m/z 1312.1 [MC
1
H]C, 656.4 [MC2H]2C; H NMR (CDCl3, 400 MHz) d
7.54 (d, JZ9.0 Hz, 4H), 7.49 (d, JZ9.0 Hz, 4H), 7.35 (d,
JZ9.0 Hz, 2H), 7.23 (t, JZ1.5 Hz, 4H), 7.16 (d, JZ1.5 Hz,
8H), 7.03 (d, JZ9.0 Hz, 2H), 3.85 (s, 3H), 1.30 (s, 72H);
13C NMR (CDCl3, 100 MHz) d 160.4 (Ci–OCH3), 153.6,
153.5, 153.4, 153.3, 152.7 (Ci–t-Bu), 128.6, 127.5 (CH),
127.3 (CHm–OCH3), 123.4, 119.8 (CH), 119.3 (CH), 115.0
(CHo–OCH3), 113.3 (CH), 55.6 (CH3–O), 35.0, 31.3 (CH3).
4.2.3. G3-dendron (14). Yield 70%; MS (ESI) m/z 2764.1
[MCH]C, 1382.7 [MC2H]2C, 1296.1 [G2], 570.6 [G1]; 1H
NMR (CDCl3, 400 MHz) d 7.54 (mbr, 28H), 7.23 (sbr, 8H),
7.16 (sbr, 16H), 3.88 (s, 3H), 1.29 (s, 144H).
† For all p-substituted benzene parts (AA0XX0 higher-order spin system) of
the described compounds, the given coupling constant J is actually the
0
sum of the ortho (JAX) and para (JAX ) coupling.

2682
W. Maes et al. / Tetrahedron 62 (2006) 2677–2683
4.3. General procedure for the synthesis of the
deprotected dendrons (RZH)
Monosubstituted G1-dendron 16. Rf 0.60; mp 148.0–
149.0 8C; MS (CI) m/z 286.3 (100%) and 288.3 (34%)
(MHC); 1H NMR (CDCl3, 300 MHz) d 7.45–7.25 (m, 5H),
7.16 (d, JZ8.8 Hz, 2H), 7.01 (d, JZ8.8 Hz, 2H), 3.88 (s,
3H); 13C NMR (CDCl3, 75 MHz) d 160.6 (Ci–OCH3), 155.3
(Ctriaz.), 143.3 (C–Cl), 130.1 (CH), 128.6 (CH), 128.5 (CH),
128.0 (CH), 126.3, 125.9, 115.1 (CHo–OCH3), 55.6 (CH3);
UV–vis (CH2Cl2) lmax (log 3) 232.1 (4.243), 248.0 (4.132).
Anal. Calcd for C15H12ClN3O: C, 63.05; H, 4.23; N, 14.71.
Found: C, 62.97; H, 4.38; N, 14.65.
To a solution of the protected Gx-dendron 10 or 12 (1 equiv)
in CH2Cl2 an excess of BBr3 (1 M in CH2Cl2, 5 equiv/
generation) was added at K78 8C under dry conditions and
the mixture was placed in the freezer (K18 8C). After 4 days
of reaction at K18 8C, ice water was added. After separation
of the organic layer, the aqueous phase was extracted with
CH2Cl2. The organic layers were collected, dried with
MgSO4, filtered and evaporated in vacuum. The dendrons
were purified by column chromatography (silica) and
obtained as white solids.
4.5. General procedure for the synthesis of the triazine
dendrimers
4.3.1. G1-dendron (11). Eluent ethyl acetate–petroleum
ether (1/4); Rf 0.35; yield 91%; MS (CI) m/z 570.7
(MHC); 1H NMR (CDCl3, 400 MHz) d 7.39 (d, JZ
8.7 Hz, 2H), 7.24 (t, JZ1.8 Hz, 2H), 7.08 (d, JZ1.8 Hz,
4H), 6.88 (d, JZ8.7 Hz, 2H), 4.37 (s, 1H, OH), 1.26 (s,
36H); 13C NMR (DMSO-d6, 100 MHz) d 158.1 (Ci–OH),
153.5, 153.4, 152.2, 127.9 (CHm–OH), 121.9 (Ci-triaz.),
118.7 (CH), 115.8 (CHo–OH), 113.1 (CH), 34.6, 31.0
(CH3).
To a solution of Gx-dendron 11 or 13 (3.3 equiv) in CH2Cl2,
Et3N (3.6 equiv) was added and the mixture was stirred for
0.5 h at room temperature. 2,4,6-Trichloro-1,3,5-triazine
(1 equiv) was added to this solution and the mixture was
stirred for another 6 h and then evaporated in vacuum. After
purification through column chromatography (silica) the
title compounds (white solids) were obtained.
4.5.1. G1-dendrimer (17). Eluent ethyl acetate–petroleum
ether (1/3); Rf 0.70; yield 92%; MS (ESI, CH3CN) m/z
1807.7 [MCNa]C, 1785.4 [MCH]C, 904.5 [MCNaC
4.3.2. G2-dendron (13). Eluent ethyl acetate–petroleum
ether (1/3); Rf 0.25; yield 89%; MS (ESI) m/z 1296.9 [MC
1
H]2C, 893.0 [MC2H]2C; H NMR (CDCl3, 300 MHz) d
1
H]C, 649.1 [MC2H]2C; H NMR (CDCl3, 400 MHz) d
7.61 (d, JZ8.7 Hz, 6H), 7.38 (d, JZ8.7 Hz, 6H), 7.24 (sbr,
6H), 7.18 (sbr, 12H), 1.29 (s, 108H); 13C NMR (CDCl3,
100 MHz) d 173.4 (Ctriazine), 153.5, 153.2, 152.7 (Ci–t-Bu),
151.1, 129.7, 127.2 (CH), 122.5 (CH), 119.5 (CH), 113.5
(CH), 35.0, 31.3 (CH3); GPC (THF) MwZ2087, PDIZ
1.034; IR nmax (cmK1) 3075, 2961, 2869, 1812, 1737, 1569,
1514, 1453, 1424, 1368, 1292, 1208, 1121, 1081, 1006, 935,
870, 705; Tg 85 8C.
8.77 (sbr, 1H, OH), 7.52 (m, 8H), 7.22 (t, JZ1.5 Hz, 4H),
7.14 (d, JZ1.5 Hz, 8H), 7.13 (d, JZ8.8 Hz, 2H), 6.84 (d,
JZ8.8 Hz, 2H), 1.27 (s, 72H); 13C NMR (CDCl3, 100 MHz)
d 158.5 (Ci–OH), 153.7, 153.6, 153.4, 153.2, 152.7 (Ci–t-
Bu), 128.2, 127.4 (CH), 127.1 (CHm–OH), 121.8, 119.9
(CH), 119.5 (CH), 116.6 (CHo–OH), 113.4 (CH), 35.0,
31.3 (CH3).
4.4. Suzuki reaction on 1,2,4-triazole monomer 4
4.5.2. G2-dendrimer (18). Eluent ethyl acetate–petroleum
ether (1/2); Rf 0.70; yield 81%; MS (ESI, CH3CNC
To a mixture of 1,2,4-triazole 4 (100 mg, 410 mmol,
1 equiv) and Pd(PPh3)4 (3 mol%) in DME (2.5 mL),
phenylboronic acid (150 mg, 1.23 mmol, 3 equiv) was
added, immediately followed by aqueous Na2CO3 (2 M,
1.25 mL). The mixture was flushed with N2 for 5 min and
the reaction mixture was then heated under reflux for 48 h.
After cooling, the reaction mixture was evaporated to
dryness under reduced pressure, CH2Cl2 (25 mL) was added
and the organic fraction was washed with water (3!
25 mL). The organic layer was dried with MgSO4, filtered
and evaporated in vacuum. Purification by column
chromatography (silica, CH2Cl2/ethyl acetate 1/1) furnished
disubstituted triazole 15 (50 mg, 37%) and monosubstituted
triazole 16 (55 mg, 47%) as white solids (which could be
crystallized from CH2Cl2/heptane).
NH4OAc) m/z 3966.0 [MCH]C, 1983.1 [MC2H]2C
,
1322.6 [MC3H]3C; H NMR (CDCl3, 400 MHz) d 7.58
(m, 30H), 7.45 (d, JZ9.0 Hz, 6H), 7.23 (t, JZ1.8 Hz, 12H),
7.16 (d, JZ1.8 Hz, 24H), 1.28 (s, 216H); 13C NMR (CDCl3,
100 MHz) d 173.4 (Ctriazine), 153.5, 153.2, 153.0, 153.0,
152.6 (Ci–t-Bu), 151.5, 129.1, 128.9, 127.5 (CH), 127.2
(CH), 122.8 (CH), 120.1 (CH), 119.4 (CH), 113.4 (CH),
35.0, 31.3 (CH3); GPC (CHCl3) MwZ3806, PDIZ1.032; IR
nmax (cmK1) 3076, 2961, 2870, 1733, 1570, 1510, 1454,
1424, 1366, 1292, 1206, 1120, 1080, 1007, 936, 869, 705;
Tg 133 8C.
1
4.6. General procedure for the synthesis of the
dendrimers with a methylene core
4.4.1. G1-dendron (15). Rf 0.30; mp 255.5–256.5 8C; MS
(CI) m/z 328.3 (MHC); 1H NMR (CDCl3, 300 MHz) d 7.50–
7.25 (m, 10H), 7.06 (d, JZ8.8 Hz, 2H), 6.90 (d, JZ8.8 Hz,
2H), 3.84 (s, 3H); 13C NMR (CDCl3, 75 MHz) d 160.0 (Ci–
OCH3), 154.9 (Ctriaz.), 129.5 (CH), 128.7 (CH), 128.4 (CH),
128.3 (CH), 127.7, 127.0, 115.0 (CHo–OCH3), 55.5 (CH3);
UV–vis (CH2Cl2) lmax (log 3) 228.7 (4.294), 261.2 (4.210).
Anal. Calcd for C21H17N3O: C, 77.04; H, 5.23; N, 12.84.
Found: C, 76.96; H, 5.30; N, 12.77.
To a solution of Gx-dendron 11 or 13 (88 mmol, 1 equiv) in
DMF (2 mL), NaH (3 equiv) and CH2Cl2 (0.5 mL) were
added. The mixture was stirred at 45 8C during 2 h and then
evaporated in vacuum. CH2Cl2 (10 mL) was added, the
organic phase was washed with water (3!10 mL), dried
with MgSO4, filtered and the solvent was removed under
reduced pressure. After purification through column
chromatography (silica) the title compounds (white solids)
were obtained.

W. Maes et al. / Tetrahedron 62 (2006) 2677–2683
2683
9. Van Wuytswinkel, G.; Verheyde, B.; Compernolle, F.;
Toppet, S.; Dehaen, W. J. Chem. Soc., Perkin Trans. 1 2000,
1337–1340.
4.6.1. G1-dendrimer (19). Eluent ethyl acetate–petroleum
ether (1/3); Rf 0.50; yield 88%; MS (ESI) m/z 1174.1 [MC
1
Na]C; H NMR (CDCl3, 300 MHz) d 7.42 (d, JZ8.8 Hz,
4H), 7.24 (d, JZ8.8 Hz, 4H), 7.21 (t, JZ1.5 Hz, 4H), 7.12
(d, JZ1.5 Hz, 8H), 5.80 (s, 2H, CH2), 1.28 (s, 72H); 13C
NMR (CDCl3, 100 MHz) d 156.8 (Ci–OCH2), 153.7, 153.4,
152.5 (Ci–t-Bu), 127.5 (CH), 126.0, 119.2 (CH), 116.9
(CH), 113.3 (CH), 90.7 (CH2), 34.9, 31.3 (CH3); GPC
(THF) MwZ1293, PDIZ1.059; IR nmax (cmK1) 3073,
2961, 2869, 1810, 1741, 1599, 1514, 1459, 1423, 1363,
1293, 1243, 1206, 1121, 1081, 1000, 937, 900, 871, 840,
705; Tg 145 8C.
10. Smet, M.; Metten, K.; Dehaen, W. Collect. Czech. Chem.
Commun. 2004, 69, 1097–1108.
11. Wu, P.; Feldman, A. K.; Nugent, A. K.; Hawker, C. J.;
´
Scheel, A.; Voit, B.; Pyun, J.; Frechet, J. M. J.; Sharpless, K. B.;
Fokin, V. V. Angew. Chem., Int. Ed. 2004, 43, 3928–3932.
12. Diez-Barra, E.; Garcia-Martinez, J. C.; Guerra, J.;
Hornillos, V.; Merino, S.; del Rey, R.; Rodriguez-Curiel,
R. I.; Rodriguez-Lopez, J.; Sanchez-Verdu, P.; Tejeda, J.;
Tolosa, J. ARKIVOC 2002, v, 17–25.
13. Diez-Barra, E.; Guerra, J.; Rodriguez-Curiel, R. I.; Merino, S.;
Tejeda, J. J. Organomet. Chem. 2002, 660, 50–54.
4.6.2. G2-dendrimer (20). Eluent ethyl acetate–petroleum
ether (1/3); Rf 0.50; yield 80%; MS (ESI) m/z 2606.0 [MC
14. Astruc, D.; Chardac, F. Chem. Rev. 2001, 101, 2991–3023.
15. van Heerbeek, R.; Kamer, P. C. J.; van Leeuwen, P. W. N. M.;
Reek, J. N. H. Chem. Rev. 2002, 102, 3717–3756.
1
H]C, 1303.3 [MC2H]2C; H NMR (CDCl3, 400 MHz) d
7.57 (dbr, JZ9.0 Hz, 8H), 7.52 (dbr, JZ9.0 Hz, 8H), 7.44
(dbr, JZ8.8 Hz, 4H), 7.31 (dbr, JZ8.8 Hz, 4H), 7.23 (sbr,
16. Some examples: (a) Drake, M. D.; Bright, F. V.; Detty, M. R.
J. Am. Chem. Soc. 2003, 125, 12558–12566. (b) Gamez, P.;
de Hoog, P.; Lutz, M.; Spek, A. L.; Reedijk, J. Inorg. Chim.
Acta 2003, 351, 319–325. (c) Plault, L.; Hauseler, A.; Nlate,
S.; Astruc, D.; Ruiz, J.; Gatard, S.; Neumann, R. Angew.
Chem., Int. Ed. 2004, 44, 2924–2928. (d) Yang, Z.-W.; Kang,
Q.-X.; Ma, H.-C.; Li, C.-L.; Lei, Z.-Q. J. Mol. Catal. A 2004,
213, 169–176. (e) Zweni, P. P.; Alper, H. Adv. Synth. Catal.
2004, 346, 849–854.
8H), 7.16 (sbr, 16H), 5.80 (sbr, 2H, CH2), 1.29 (s, 144H); 13
C
NMR (CDCl3, 100 MHz) d 157.5 (Ci–OCH2), 153.5, 153.3,
153.2, 153.1, 152.6 (Ci–t-Bu), 128.6, 127.5 (CH), 125.4,
119.9, 119.4 (CH), 117.4 (CH), 113.4 (CH), 91.3 (CH2),
35.0, 31.3 (CH3); GPC (CHCl3) MwZ2954, PDIZ1.031; IR
nmax (cmK1) 3075, 2960, 2868, 1733, 1594, 1511, 1458,
1424, 1364, 1297, 1208, 1120, 1081, 1003, 936, 869, 843,
705; Tg 135 8C.
17. Chavan, S.; Maes, W.; Wahlen, J.; Jacobs, P.; De Vos, D.;
Dehaen, W. Catal. Commun. 2005, 6, 241–246.
Acknowledgements
18. Chavan, S. A.; Maes, W.; Gevers, L. E. M.; Wahlen, J.;
Vankelecom, I. F. J.; Jacobs, P. A.; Dehaen, W.; De Vos, D. E.
Chem. Eur. J. 2005, 6754–6762.
Wouter Maes and Wim Dehaen wish to thank the FWO-
Vlaanderen, the Ministerie voor Wetenschapsbeleid (IUAP/
V/3) and the Katholieke Universiteit Leuven for their
financial support. They are also grateful to Prof. S. Toppet,
K. Duerinckx, B. Demarsin and R. De Boer for NMR and
mass spectroscopic measurements.
19. Kido, J.; Ohtaki, C.; Hongawa, K.; Okuyama, K.; Nagai, K.
Jpn. J. Appl. Phys. 1993, 32, 917–920.
20. Strukelj, M.; Papadimitrakopoulos, F.; Miller, T. M.;
Rothberg, L. J. Science 1995, 267, 1969–1972.
21. Some examples: (a) Bradley, D. C. C.; Grell, M.; Grice, A.;
Tajbakhsh, A. R.; O’Brien, D. F.; Bleyer, A. Opt. Mater. 1998,
9, 1–11. (b) Lu, J.; Miyatake, K.; Hill, A. R.; Hay, A. S.
Macromolecules 2001, 34, 5860–5867. (c) Chen, S.-H.; Chen,
Y. Macromolecules 2005, 38, 53–60.
References and notes
22. Some examples: (a) Shirota, Y.; Kuwabara, Y.; Inada, H.;
Wakimoto, T.; Nakada, H.; Yonemoto, Y.; Kawami, S.;
Inai, K. Appl. Phys. Lett. 1994, 65, 807–809. (b) Wang, P. W.;
Liu, Y. J.; Devadoss, C.; Bharathi, P.; Moore, J. S. Adv. Mater.
1996, 8, 237–241. (c) Halim, M.; Pillow, J. N. G.;
Samuel, I. D. W.; Burn, P. L. Adv. Mater. 1999, 11,
371–374. (d) Kwok, C. C.; Wong, M. S. Macromolecules
2001, 34, 6821–6830. (e) Furuta, P.; Brooks, J.; Thompson,
¨
1. Newkome, G. R.; Moorefield, C. N.; Vogtle, F. In Dendrimers
and Dendrons: Concepts, Syntheses, Applications; Wiley-
VCH: Weinheim, 2001.
2. Recent Developments in Dendrimer Chemistry; Tetrahedron
Symposium-in-Print 96, Smith, D. K., Ed.; Tetrahedron 2003,
59, 3787–4024.
3. Special Issue: Dendrimers and Dendritic Polymers,
´
Tomalia, D. A., Frechet, J. M. J., Eds.; Prog. Polym. Sci.
2005, 30, 217–505.
´
M. E.; Frechet, J. M. J. J. Am. Chem. Soc. 2003, 125,
13165–13172. (f) Kwon, T. W.; Alam, M. M.; Jenekhe, S. A.
4. Dzielendziak, A.; Tarasov, E.; Smet, M.; Dehaen, W. Mater.
Sci. Eng., C 2001, 18, 165–169.
Chem. Mater. 2004, 16, 4657–4666. (g) Markham, J. P. J.;
¨
Samuel, I. D. W.; Lo, S.-C.; Burn, P. L.; Weiter, M.; Bassler,
5. Abramov, M. A.; Shukla, R.; Amabilino, D. B.; Dehaen, W.
J. Org. Chem. 2002, 67, 1004–1007.
H. J. Appl. Phys. 2004, 95, 438–445.
23. Stickler, J. C.; Pirkle, W. H. J. Org. Chem. 1966, 31,
3444–3445.
6. Verheyde, B.; Dehaen, W. J. Org. Chem. 2001, 66,
4062–4064.
24. Cookson, C. R.; Gupte, S. S.; Stevens, I. D. R.; Watts, C. T.
Org. Synth. 1971, 121–127.
7. Verheyde, B.; Maes, W.; Dehaen, W. Mater. Sci. Eng., C 2001,
18, 243–245.
25. Burrage, M. E.; Cookson, R. C.; Gupte, S. S.; Stevens, I. D. R.
J. Chem. Soc., Perkin Trans. 2 1975, 2, 1325–1334.
8. Maes, W.; Amabilino, D. B.; Dehaen, W. Tetrahedron 2003,
59, 3937–3943.