A convenient synthesis of triazine-based dendrons and dendrimers via a convergent approach and a study of their interactions with tetrafluoro- benzoquinone

Article abstract of DOI:10.1055/s-0030-1258220

A convenient, efficient and convergent approach to prepare triazine-based dendrons and dendrimers is developed. The steric hindrance resulting from the presence of dioctylamino moieties in the peripheral regions allows the synthesis of soluble dendrons without employing protection and deprotection steps. The triazine-based dendrimers are prepared via reaction of N,N′- dimethylethane-1,2-diamine with the dendrons in a ratio of 1:2. Interactions of the dendrimers with tetrafluorobenzoquinone led to the appearance of new broad bands, red-shifted by approximately 180 nm, in the absorbance spectra. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0030-1258220

3
576
PAPER
A Convenient Synthesis of Triazine-Based Dendrons and Dendrimers via a
Convergent Approach and a Study of Their Interactions with Tetrafluoro-
benzoquinone
a
a
a
b
S
L
ynthesis of
T
ri
o
azine-Based
n
D
endrons
a
n
g
d Dendrime
-
a
Department of Applied Chemistry, National Chi Nan University, Puli, Taiwan 545
Fax +886(49)291795; E-mail: lilai@ncnu.edu.tw
Applied Chemistry Division, Material and Chemical Research Laboratories, Industrial Research Institute, Hsinchu, Taiwan 300
b
Received 7 April 2010; revised 25 June 2010
bonding interactions, the dendrimers were much less sol-
uble in organic solvents. Simanek and co-workers ap-
plied divergent, convergent and orthogonal methods to
Abstract: A convenient, efficient and convergent approach to pre-
pare triazine-based dendrons and dendrimers is developed. The ster-
ic hindrance resulting from the presence of dioctylamino moieties
7
in the peripheral regions allows the synthesis of soluble dendrons prepare triazine-based dendrimers with various function-
without employing protection and deprotection steps. The triazine- alities present on the peripheral arms, but protection and
based dendrimers are prepared via reaction of N,N¢-dimethylethane- deprotection steps were often required in their approach-
1
,2-diamine with the dendrons in a ratio of 1:2. Interactions of the
8a
es. Subsequently, the same group synthesized triazine-
dendrimers with tetrafluorobenzoquinone led to the appearance of
new broad bands, red-shifted by approximately 180 nm, in the ab-
sorbance spectra.
based dendrimers containing paclitaxcel or N–H function-
alities in order to study their transfection efficiency.8
With the increased potential applications of triazine-based
dendrimers, the use of various linkers to simplify their
b,c
Key words: dendrons, dendrimers, convergent approach, triazine,
tetrafluorobenzoquinone
8d,e
synthesis or analysis has been reported. Using pipera-
9
zine as a transannular effect linker, we reported an effi-
cient method to prepare a new series of triazine-based
dendrimers via a convergent approach in which protection
and deprotection steps were not needed. However, we
Dendrimers are highly branched molecules containing
central cores, bridging units and peripheral functional-
ities, and have attracted significant attention in biochemi-
10
envisaged that the presence of long alkyl chains, in the pe-
ripheral regions of the triazine-based dendrimers, might
lead to efficient syntheses without employing protecting
group strategies. Thus, we modified our synthetic ap-
proach to prepare triazine-based dendrimers with a differ-
ent linker. In addition, the interactions of the dendrimers
with tetrafluorobenzoquinone (TFB) were studied. The
results of our studies are reported herein.
1
cal and optical research. In particular, dendrimers display
single molecular weights and thus show interesting and
predictable properties. Dendrimers bearing peripheral
functional groups such as amino, hydroxy or carboxylate
may potentially function as catalytic materials or drug-
2
,3
transporting agents. As a result of the void spaces in the
dendritic framework, dendrimers may function as porous
4
materials that incorporate guest molecules. However, the
According to the literature, the reactivity of heteroaromat-
ics is influenced significantly by the substituents,11 and
therefore, one, two or three equivalents of amines can be
reacted with cyanuric chloride, under controlled condi-
tions, as the amino moieties can enrich the electron densi-
ty of the heteroaromatics and subsequently disfavor
synthesis of dendrimers is generally tedious as protection
and deprotection strategies are sometimes needed, and ex-
tremely poor solubility may be encountered for rigid or
1
,5
conjugated systems. In divergent synthetic approaches
the protection and deprotection steps may be incomplete,
leading to unexpected side reactions affording by-prod-
10
5
nucleophilic substitution. In our previous study, we re-
acted cyanuric chloride with dioctylamine in the ratio 2:1,
ucts which co-exist with the dendrimers. This, certainly
to a degree, results in difficulties during their purification
and characterization.
leading to dendron G -Cl in 97% yield. Treatment of den-
1
dron G -Cl with piperazine in the ratio 1:3 gave com-
1
Although there are challenges during their synthesis and
subsequent characterization, the development of efficient
strategies to prepare novel dendrimers with new peripher-
pound 1 in 90% yield. It is interesting to note that no trace
of dimeric product 2 was isolated from the same reaction
(
Scheme 1); this might be due to the transannular effect of
6
al functionalities is attractive. For example, Takagi em-
9
piperazine. However, the steric influence of the two di-
octylamino groups in the peripheral region of dendron G1-
Cl may also disfavor the formation of dimeric product 2.
In addition, we prepared dendron P-Cl in 97% yield by re-
action of cyanuric chloride with piperidine, further treat-
ment of which with piperazine gave dendron P-NH and
the dimeric product P-N~N-P in 83% and 8% yields, re-
spectively. These results indicate that the steric bulk of the
ployed divergent and convergent approaches to prepare
dendrimers with an aromatic linkage based on the triazine
unit, however, because of the aryl moiety and hydrogen
SYNTHESIS 2010, No. 20, pp 3576–3582
x
x.
x
x
.
2
0
1
0
Advanced online publication: 18.08.2010
DOI: 10.1055/s-0030-1258220; Art ID: F06410SS
Georg Thieme Verlag Stuttgart · New York
©

PAPER
Synthesis of Triazine-Based Dendrons and Dendrimers
3577
peripheral alkyl chains disfavors formation of the dimeric
product during the reaction of dendron G -Cl with piper-
1
azine. To prove our assumption, dendron G -Cl was treat-
1
ed with N,N¢-dimethylethane-1,2-diamine in the ratio 1:3
to afford dendron G -NH and dendrimer G -N~N-G in
1
1
1
7
9% and 5% yields, respectively (Scheme 2). Even with-
out using piperazine as the linker, we only isolated a small
amount of dendrimer G -N~N-G in the corresponding
1
1
non-transannular effect reaction.
Cl
R
N
N
N
Et3N, 25 °C
N
Cl + R2NH
N
Cl
CH2Cl2
N
Cl
R
G1-Cl (97%); R = (C8H17)2N
P-Cl (97%); R =
N
R
R
NH
N
N
N
NH
4
0 °C
N
N
Cl +
N
THF
N
HN
R
R
1
(90%); R = (C8H17)2N
P-NH (83%); R =
N
R
R
N
N
N
N
N
N
N
N
R
R
1
Figure 1 The H NMR spectrum of dendron G -Cl
1
2
(0%); R = (C8H17)2N
P-N~N-P (8%); R =
N
actually observed. This provided confirmation that steric
congestion, due to the peripheral alkyl chains of dendron
Scheme 1 Preparation of dendrons G -Cl, P-Cl and P-NH, and di-
mer P-N~N-P
1
G -Cl, played a significant role in solution. Accordingly,
1
dendron G -Cl was obtained in 99% yield from the reac-
2
tion of G -NH with cyanuric chloride (Scheme 3). In a
1
R
Me
N
similar manner, reaction of G -Cl with N,N¢-dimethyl-
2
4
0 °C
+
H
N
ethane-1,2-diamine gave dendron G -NH in 92% yield
N
Cl
H
2
N
THF
N
whilst no detectable amount of dimeric G -N~N-G was
2
2
R
Me
present. As before, this result is probably due to the steric
G1-Cl
congestion imparted by the peripheral alkyl chains in G2-
R
R
Cl.
Me
N
Me
N
R
N
N
N
N
N
N
1
N
H
+
N
The H NMR chemical shifts of the four N-methyl groups
N
N
in dendron G -Cl would be expected to appear as two sin-
N
2
Me
Me
R
R
R
glets if steric hindrance from the peripheral alkyl chains
G1-NH (79%)
G1-N~N-G1 (5%)
was not significant. However, a multiplet in the range d
3
.04–3.15 (12 H, 4 × CH ) was observed which is indica-
R = N(C8H17)2
3
tive of the non-equivalent spatial positions of the four
Scheme 2 Preparation of compounds G -NH and G -N~N-G
1
1
1
methyls (Figure 2). Dendron G -Cl was isolated from the
3
reaction of G -NH with cyanuric chloride in 88% yield.
2
The steric congestion resulting from the presence of two
Steric effects due to the peripheral alkyl chains of the den-
drons were also exhibited in the corresponding prepara-
tion of dendrimers. As shown in Scheme 3, dendrimer G3-
N~N-G was obtained in 51% yield via reaction of G -Cl
dioctylamino groups in the peripheral part of dendron G -
1
1
Cl in solution was also confirmed by H NMR spectrosco-
py (Figure 1). The four N–CH groups should exist in
2
3
3
identical chemical environments in solution, and would be
expected to occur at the same chemical shift. In fact, two
with N,N¢-dimethylethane-1,2-diamine, the yield being
lower than those of the corresponding dendrimers G -
1
chemical shifts at d = 3.42 (t, J = 5.7 Hz, 4 H, 2 × CH )
2
N~N-G (71%) and G -N~N-G (69%). There are more
1
2
2
and d = 3.47 (t, J = 5.7 Hz, 4 H, 2 × CH ), in CDCl , were
2
3
Synthesis 2010, No. 20, 3576–3582 © Thieme Stuttgart · New York

3
578
L.-L. Lai et al.
PAPER
Cl
Dendrimers G -N~N-G (n = 1–3) were characterized by
n
n
N
N
1
Et3N, 25 °C
CH2Cl2
H NMR spectroscopy and mass spectrometry, together
with elemental analysis or high resolution mass spectrom-
etry. The molecular structure of G -N~N-G is shown in
N
Cl + Gn-NH
Gn+1-Cl
n = 1 (99%)
n = 2 (88%)
Cl
3
3
Me
Figure 3, and its mass spectrum, obtained by matrix-
assisted laser desorption ionization–time-of-flight
4
0 °C
H
N
Gn-Cl
+
n
G -NH
H
(
MALDI–TOF) analysis showed two peaks at 6058.2 and
N
THF
n = 2 (92%)
+
+
6
081.0 due to the (M + H) and (M + Na) mass ions, re-
Me
spectively. Typically, a sodium cation originating from
the sample holder is present during characterization by
Me
7
0 °C
H
N
2
Gn-Cl +
Gn-N~N-Gn
12
H
this technique. Dendrimer G -N~N-G was further char-
THF
3
3
N
n = 1 (70%)
n = 2 (69%)
n = 3 (50%)
acterized by microanalysis and the differences between
the calculated and experimental values (C, H and N) were
within 0.3%.
Me
G2
Me
Me
The interactions between the dendrimers and tetrafluo-
robenzoquinone in dichloromethane were studied. As
shown in Figure 4, dichloromethane solutions of den-
drimers G -N~N-G (n = 1–3) did not show any absor-
N
N
Me
N
N
R
N
N
= G3
R
n
n
N
Me
N
N
bances above 350 nm, whilst tetrafluorobenzoquinone in
N
Me
dichloromethane exhibited an absorbance at l = ~337
N
G2
max
Me
N
Me
nm. However, when tetrafluorobenzoquinone was mixed
with a dendrimer the resulting red solution provided an
absorbance at ~517 nm. Previously, Koch et al. showed
that 4-(N,N-dimethylamino)pyridine reacted with tetra-
fluorobenzoquinone to give a pyridinium salt in aqueous
N
N
Gn
N
N
=
G2
G -NH; NH =
H
n
N
Me
N
N
Me
N
N
Me
Me
Gn-N~N-Gn; N~N =
N
R
13
media. On the other hand, Goldmann and co-workers
N
N
demonstrated that tri(phenylamino)triazine derivatives
Me
R
8 17 2
R = N(C H )
formed weak p–p interactions with electron acceptors in
14
the solid state. To establish whether the new absorbance
Scheme 3 Preparation of G -NH and G -N~N-G
n
n
n
at l = ~517 nm was due to formation of a product be-
max
tween the triaminotriazine moiety and tetrafluorobenzo-
quinone (TFB), or due to a p–p interaction, the red-
colored solution of TFB–G -N~N-G was examined care-
2
2
fully by thin-layer chromatography, but no new product
was detected. A solution of TFB–G -N~N-G in deuterat-
2
2
1
ed chloroform was investigated by H NMR spectroscopy.
The proton chemical shifts of the G -N~N-G dendrimer
2
2
did not show any significant variations before and after
mixing with tetrafluorobenzoquinone. Hence, these re-
sults indicate strongly that the new absorbance occurs due
to formation of a complex via a face-to-face p–p interac-
tion. The difference between our result and those of Koch
would appear to be due to the presence of a more hindered
triaminotriazine moiety in the dendrimers. As three strong
electron-donating groups are present in our dendrimers,
the basicity of the aromatic nitrogens of the triazine ring
may be comparable with that of pyridine. However, these
aromatic nitrogens are surrounded by alkyl groups, and
this prevents lateral access of tetrafluorobenzoquinone,
thereby preventing formation of a new product. Thus
face-to-face access between tetrafluorobenzoquinone and
the triaminotriazine moiety becomes more favorable.14
1
Figure 2 The H NMR spectrum of G -Cl
2
dioctylamino moieties present in the peripheral regions of As shown in Figure 4, the concentration of tetrafluoroben-
–
3
G -Cl, and steric hindrance due to these alkyl chains zoquinone and the dendrimers was maintained at 2.5 × 10
3
would be expected to be more significant than in dendrons M, and the absorbance at ~517 nm due to the TFB–G
-
3
G -Cl and G -Cl. Hence, the yield of G -N~N-G was N~N-G
significantly lower.
complex was higher than those of the other
-N~N-G complexes (n = 1, 2). When the inten-
sity of the absorbance at ~517 nm increases, the tetrafluo-
2
1
3
3
3
TFB–G
n
n
Synthesis 2010, No. 20, 3576–3582 © Thieme Stuttgart · New York

PAPER
Synthesis of Triazine-Based Dendrons and Dendrimers
3579
R
R
N
N
R
N
R
N
R
N
N
R
N
N
N
N
R
N
N
R
N
N
N
N
R
R
N
N
N
R
N
N
R
N
N
N
N
N
N
N
N
N
N
N
N
R
N
N
N
R
N
N
N
R
N
N
R
N
N
N
N
N
N
R
R
N
N
R
N
R
N
R
N
N
R
N
N
N
N
N
N
N
N
R
N
N
N
N
N
N
N
N
N
N
N
R
R
N
N
G3-N~N-G3
R
N
N
R = C8H17
N
N
R
N
R
N
R
N
N
R
N
N
R
R
Figure 3 The molecular structure of dendrimer G -N~N-G
3
3
robenzoquinone absorbance at l = ~317 nm decreases Dendrimer G -N~N-G , as a representative example, was
max
2
2
accordingly. Varying the TFB–G -N~N-G concentra- mixed with tetrafluorobenzoquinone in various solvents.
n
n
tion, in dichloromethane, resulted in different absorption The respective N,N-dimethylformamide, chloroform and
intensities, and thus the molar absorptivity coefficients (e) cyclohexane solutions displayed broad absorbances at
of TFB–G -N~N-G (n = 1–3) at ~517 nm were 11.86, ~518, ~520 and ~513 nm. Although the dielectric con-
n
n
2
3
9.2 and 64.44 cm /mol, respectively. The molar absorp- stants for N,N-dimethylformamide, dichloromethane,
tivity coefficient of TFB–G -N~N-G was larger than chloroform and cyclohexane, at room temperature, are
3
3
those of TFB–G -N~N-G (n = 1, 2), which might be as a 37.4, 9.1, 4.8 and 2.0, the absorbances did not vary appre-
n
n
result of the greater number of triaminotriazine moieties ciably. Furthermore, solvatochromism was not significant
present at the same concentration of tetrafluorobenzo- in our system.15
quinone and dendrimers. It is noteworthy that the new ab-
In summary, using dioctylamine as the peripheral func-
sorbance band is quite broad and the difference in l
max
tionality, we have developed a method to prepare conve-
between this band and that of tetrafluorobenzoquinone is
niently triazine-based dendrons and dendrimers via a
~180 nm. This would not be expected to arise from a sim-
convergent approach in which the steric effects of the pe-
ripheral alkyl chains disfavor formation of dimeric prod-
ucts. Other linkers such as N,N¢-dimethylethane-1,2-
diamine can be used to construct higher generation den-
drons in excellent yields without employing protection
and deprotection steps. Dendrimers G -N~N-G (n = 1–
ple complex consisting of one dendrimer and one tetra-
fluorobenzoquinone unit, but instead, from a complicated
complex consisting of numerous dendrimers and tetra-
fluorobenzoquinone units which should resemble a stack
of large coins (dendrimers) and small coins (tetrafluoro-
benzoquinone). Although the molar absorptivity coeffi-
cients of TFB–G -N~N-G (n = 1–3) in solution are
n
n
3
) were prepared by reaction of the corresponding den-
n
n
drons with a linker. Additionally, interaction of dendrim-
rather low, their absorption coefficients in the solid state
might be large as a result of the face-to-face distances
between the dendrimers and tetrafluorobenzoquinone
being much shorter. This approach should provide an
efficient means to prepare a wide range of UV/Vis absorp-
tion mixtures, and related studies are being pursued.
ers G -N~N-G (n = 1–3) with tetrafluorobenzoquinone
n
n
led to the appearance of new, broad absorbance bands in
the UV/Vis spectra. The red shifts in absorbance of the
new of tetrafluorobenzoquinone–dendrimer complexes
were large (~180 nm), indicating that face-to-face p–p in-
Synthesis 2010, No. 20, 3576–3582 © Thieme Stuttgart · New York

3
580
L.-L. Lai et al.
PAPER
MS (EI): m/z = 282.2 [M + H]+.
Anal. Calcd for C H ClN : C, 55.41; H, 7.15, N, 24.85. Found: C,
1
3
20
5
5
5.30; H, 7.12; N, 24.80.
P-NH and P-N~N-P
Piperazine (2.07 g, 24.0 mmol, 3 equiv) in THF (100 mL) was add-
ed to P-Cl (2.25 g, 8.0 mmol) in THF (50 mL), and the resulting
soln stirred at 40 °C for 20 h. KOH (6.72 g, 120 mmol) in H O (150
2
mL) was added and the soln extracted with CH Cl (2 × 100 mL).
2
2
The combined organic extract was washed with aq buffer soln (100
mL, pH 10) and H O (2 × 100 mL), and then dried over MgSO . The
2
4
solvent was removed under reduced pressure and the residue chro-
matographed on silica gel (eluent: CH Cl ) to give P-NH (2.23 g,
2
2
8
3%) and dimer P-N~N-P (0.37 g, 8%).
P-NH
1
H NMR (300 MHz, CDCl ): d = 1.49–1.78 (m, 12 H, 6 × CH ),
3
2
1
.86 (br s, 1 H, NH), 2.88 (t, J = 4.2 Hz, 4 H, 2 × CH ), 3.65–3.77
2
Figure 4 The UV/Vis absorbance spectra of tetrafluorobenzoqui-
none, G -N~N-G (n = 1–3) and TFB–G -N~N-G (n = 1–3); the
(m, 12 H, 6 × CH ).
2
MS (EI): m/z = 332.2 [M + H]+.
n
n
n
n
concentrations of tetrafluorobenzoquinone and the dendrimers were
–
3
Anal. Calcd for C H N : C, 61.60; H, 8.82; N, 29.58. Found: C,
2.5 × 10
M
17 29
7
6
1.40; H, 8.88; N, 29.43.
teractions between the dendrimers and tetrafluorobenzo-
quinone were significant. To our knowledge, this is the
first occasion in which a red shift of such magnitude, orig-
inating from triazine-based dendrimers and an electron-
deficient compound, has been observed in solution.
P-N~N-P
1
H NMR (300 MHz, CDCl ): d = 1.43–1.79 (m, 24 H, 12 × CH ),
3
2
3
.70 (t, J = 4.2 Hz,16 H, 8 × CH ), 3.78 (s, 8 H, 4 × CH ).
2
2
MS (EI): m/z = 577.4 [M + H]+.
Anal. Calcd for C H N : C, 62.47; H, 8.39; N, 29.14. Found: C,
3
0
48 12
6
2.30; H, 8.46; N, 28.88.
All chemicals were commercially available and were used without
1
further purification. H NMR spectra (CDCl ) were recorded on a
Dendrons G -NH (n = 1, 2) and G -Cl (n = 2, 3); Typical Proce-
3
n
n
Bruker 300 MHz NMR spectrometer. Mass spectra (MS) and high-
resolution mass spectra (HRMS) were obtained using a VG-250
spectrometer (EI, 70 eV). MALDI–TOF mass spectra were ob-
tained using a Voyager-DE PRO (Applied Biosystems) time-of-
flight mass spectrometer. The UV spectra of dendrimers and den-
dritic complexes were recorded on a Cary Bio50 spectrometer. Ele-
mental analyses were obtained using an Elementar Vario EL III. Silica
gel (Merck, 230–400 mesh) was used for column chromatography.
dure
G -NH
1
N,N¢-Dimethylethane-1,2-diamine (6.55 g, 74.3 mmol, 3 equiv) in
THF (100 mL) was added to dendron G -Cl (14.69 g, 24.8 mmol)
in THF (100 mL), and the resulting soln stirred at 40 °C for 24 h.
KOH (14.1 g, 250.0 mmol) in H O (150 mL) was added and the
mixture extracted with CH Cl (2 × 150 mL). The combined organic
extract was washed with aq buffer soln (100 mL, pH 10) and H O
1
2
2
2
2
(
2 × 100 mL), and then dried over MgSO . The solvent was re-
4
G -Cl; Typical Procedure
Dioctylamine (24.15 g, 100 mmol, 2 equiv) in CH Cl (100 mL) and
moved under reduced pressure and the residue chromatographed on
silica gel (eluent: CH Cl ) to give G -NH (12.66 g, 79%) and dimer
G -N~N-G (1.24 g, 5%).
1
2
2
2
2
1
Et N (13.84 mL, 100 mmol, 2 equiv) were added to cyanuric chlo-
3
1 1
ride (9.22 g, 50 mmol) in CH Cl (100 mL). The resulting soln was
2
2
1
H NMR (300 MHz, CDCl ): d = 0.87 (t, J = 5.7 Hz, 12 H, 4 × CH ),
3
3
stirred in an ice-bath for 1 h and then at r.t. for 24 h. KOH (28.1 g,
00 mmol) in H O (300 mL) was added and the resulting mixture
1
.27 (br s, 40 H, 20 × CH ), 1.57 (br s, 8 H, 4 × CH ), 1.70 (br s, 1
2
2
5
2
H, NH), 2.45 (s, 3H, CH ), 2.81 (t, J = 6.3 Hz, 2 H, CH ), 3.09 (s, 3
H, CH ), 3.44 (br s, 8 H, 4 × CH ), 3.66 (t, J = 6.3 Hz, 2 H, CH ).
MS (EI): m/z = 646.8 [M + H]+.
3
2
extracted with CH Cl (2 × 150 mL). The combined organic extract
2
2
3
2
2
was washed with aq buffer soln (100 mL, pH 10) and H O (2 × 100
2
mL), and then dried over MgSO . The solvent was removed under
4
reduced pressure and the residue chromatographed on silica gel
+
HRMS (EI): m/z [M + H] calcd for C H N : 646.6431; found:
646.6476.
3
9
80
7
(
eluent: CH Cl ) to give G -Cl (29.30 g, 99%) as a liquid.
2 2 1
1
H NMR (300 MHz, CDCl ): d = 0.88 (t, J = 5.1 Hz, 12 H, 4 × CH ),
3
3
Dimer G -N~N-G was identified as the product of the reaction of
dendron G -Cl and N,N¢-dimethylethane-1,2-diamine in the ratio
1
1
1
(
.27–1.29 (m, 40 H, 20 × CH ), 1.53–1.58 (m, 8 H, 4 × CH ), 3.42
2
2
1
t, J = 5.7 Hz, 4 H, 2 × CH ), 3.47 (t, J = 5.7 Hz, 4 H, 2 × CH ).
2
2
2:1.
MS (EI): m/z = 594.5 [M + H]+.
G -Cl
+
2
HRMS (EI): m/z [M + H] calcd for C H ClN : 594.5241; found:
3
5
69
5
Dendron G -NH (2.2 equiv) in CH Cl (100 mL) and Et N (2.2
equiv) were added to cyanuric chloride in CH Cl (50 mL). After
1
2
2
3
5
94.5240.
2
2
typical work-up, dendron G -Cl (12.93 g, 99%) was obtained.
2
P-Cl
1H NMR (300 MHz, CDCl
1.28 (br s, 80 H, 40 × CH
): d = 0.88 (t, J = 6.0 Hz, 24 H, 8 × CH
),
), 3.04–
2
Dendron P-Cl (5.46 g, 97%) was prepared by reaction of piperidine
with cyanuric chloride.
3
2
3
), 1.56–1.59 (m, 16 H, 8 × CH
3
4
.15 (m, 12 H, 4 × CH ), 3.44 (br s, 16 H, 8 × CH ), 3.74 (br s, 8 H,
1
3
2
H NMR (300 MHz, CDCl ): d = 1.49–1.75 (m, 12 H, 6 × CH ),
3
2
× CH ).
2
3
.73 (t, J = 4.8 Hz, 8 H, 4 × CH ).
2
MS (EI): m/z = 1403.3 [M + H]+.
Synthesis 2010, No. 20, 3576–3582 © Thieme Stuttgart · New York

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Synthesis of Triazine-Based Dendrons and Dendrimers
3581
1
Anal. Calcd for C H ClN : C, 69.31; H, 11.20; N, 16.96. Found:
C, 69.17; H, 11.30; N, 16.73.
H NMR (300 MHz, CDCl ): d = 0.85 (br s, 96 H, 32 × CH ), 1.25
8
1
156
17
3
3
(br s, 320 H, 160 × CH ), 1.54 (br s, 64 H, 32 × CH ), 3.06 and 3.10
(
H, 26 × CH ).
2
2
2 × s, 78 H, 26 × CH ), 3.42 (br s, 64 H, 32 × CH ), 3.70 (br s, 52
3
2
G -NH
2
2
Dendron G -NH (11.15 g, 92%) was prepared in a similar manner
+
+
2
MS (MALDI-TOF): m/z = 6058.2 [M + H] , 6081.0 [M + Na] .
to that described for G -NH by reaction of G -Cl with N,N¢-di-
1
2
Anal. Calcd for C350H674N : C, 69.37; H, 11.21; N, 19.42. Found:
C, 69.37; H, 11.12; N, 19.20.
methylethane-1,2-diamine in the ratio 1:3.
84
1
H NMR (300 MHz, CDCl ): d = 0.87 (t, J = 5.7 Hz, 24 H, 8 × CH ),
3
3
1
3
.28 (br s, 80 H, 40 × CH ), 1.57 (br s, 17 H, NH, 8 × CH ), 2.45 (s,
2
2
H, CH ), 2.83 (br s, 2 H, CH ), 3.08 and 3.12 (2 × s, 15 H, 5 ×
3
2
Acknowledgment
CH ), 3.45 (br s, 16 H, 8 × CH ), 3.71 (br s, 10 H, 5 × CH ).
3
2
2
This work was supported financially by the National Chi Nan Uni-
versity and the National Science Council (NSC 96-2113-M-260-
002).
MS (EI): m/z = 1456.8 [M + H]+.
Anal. Calcd for C H N : C, 70.15; H, 11.57; N, 18.29. Found: C,
85
167 19
7
0.00; H, 11.63; N, 18.17.
G -Cl
References
3
Dendron G -Cl (8.83 g, 88%) was obtained in a similar manner to
that described for G -Cl from the reaction of G -NH with cyanuric
chloride in the ratio 2:1.
3
(
1) (a) Medina, S. H.; El-Sayed, M. E. H. Chem. Rev. 2009, 109,
141. (b) Mastalerz, M.; Fischer, V.; Ma, C. Q.; Jassen, R.
1
2
3
A.; Bäuerle, P. Org. Lett. 2009, 11, 4500. (c) Li, J.; Liu, D.
J. Mater. Chem. 2009, 19, 7584. (d) Wang, J.-L.; Zhou, Y.;
Li, Y.; Pei, J. J. Org. Chem. 2009, 74, 7449.
1
H NMR (300 MHz, CDCl ): d = 0.87 (t, J = 5.7 Hz, 48 H, 16 ×
3
3
CH ), 1.28 (br s, 160 H, 80 × CH ), 1.56 (br s, 32 H, 16 × CH ), 3.08
2
2
and 3.12 (2 × s, 36 H, 12 × CH ), 3.45 (br s, 32 H, 16 × CH ), 3.73
(2) (a) Yu, J.; RajanBabu, T. V.; Parquette, J. R. J. Am. Chem.
Soc. 2008, 130, 7845. (b) Peng, X.; Pan, Q.; Rempel, G. L.
Chem. Soc. Rev. 2008, 37, 1619. (c) Javor, S.; Delort, E.;
Darbre, T.; Reymond, J.-L. J. Am. Chem. Soc. 2007, 129,
13238. (d) Reynhardt, J. P. K.; Yang, Y.; Sayari, A.; Apler,
H. Chem. Mater. 2004, 16, 4095.
3
2
(
br s, 24 H, 12 × CH ).
2
MS (MALDI-TOF): m/z = 3023.3 [M + H]+.
Anal. Calcd for C173H332N Cl: C, 68.75; H, 11.07; N, 19.00. Found:
C, 68.70; H, 11.14; N, 19.00.
41
(
3) (a) Azagarsamy, M. A.; Sokkalingam, P.; Thayumanavan, S.
J. Am. Chem. Soc. 2009, 131, 14184. (b) Chen, G.; Kumar,
J.; Gregory, A.; Stenzel, M. H. Chem. Commun. 2009, 6291.
Dendrimer G -N~N-G ; Typical Procedure
1
1
A mixture of dendron G -Cl (5.93 g, 10.0 mmol) and N,N¢-dimeth-
1
ylethane-1,2-diamine (0.44 g, 5 mmol) in THF (100 mL) was stirred
(c) Gao, Y.; Gao, G.; He, Y.; Liu, T.; Qi, R. Mini Rev. Med.
at 80 °C for 24 h. KOH (1.12 g, 20 mmol) in H O (50 mL) was add-
2
Chem. 2008, 8, 889. (d) Kim, Y.; Klutz, A. M.; Jacobson, K.
A. Bioconjugate Chem. 2008, 19, 1660.
ed and the resulting soln extracted with CH Cl (2 × 40 mL). The
2
2
combined organic extract was washed with aq buffer soln (50 mL,
(
4) (a) Bertrand, B.; Guillon, D. Adv. Polym. Sci. 2006, 201, 45.
(b) Kato, T.; Mizoshita, N.; Kishimoto, K. Angew. Chem.
Int. Ed. 2006, 45, 38. (c) Grafe, A.; Janietz, D.; Frese, T.;
Wendroff, J. H. Chem. Mater. 2005, 17, 4979.
pH 10) and H O (2 × 50 mL), and then dried over MgSO . The sol-
2
4
vent was removed under reduced pressure and the residue purified
by chromatography on silica gel (eluent: CH Cl ) to give G -N~N-
2
2
1
G (4.25 g, 71%).
1
(5) Newkome, G. R.; Moorefield, C. N.; Vögtle, F. Dendrimers
1
H NMR (300 MHz, CDCl ): d = 0.87 (t, J = 5.4 Hz, 24 H, 8 × CH ),
and Dendrons; Wiley-VCH: Weinheim, 2000.
3
3
1
2
.28 (br s, 80 H, 40 × CH ), 1.55 (br s, 16 H, 8 × CH ), 3.09 (s, 6 H,
(6) (a) Parrott, M. C.; Benhabbour, R.; Saab, C.; Lemon, J. A.;
Parker, S.; Valliant, J. F.; Adronov, A. J. Am. Chem. Soc.
2
2
× CH ), 3.45 (br s, 16 H, 8 × CH ), 3.69 (br s, 4 H, 2 × CH ).
3
2
2
2009, 131, 2906. (b) Washio, I.; Shibasaki, Y.; Ueda, M.
MS (EI): m/z = 1205.0 [M + H]+.
Org. Lett. 2007, 9, 1363. (c) Kohman, R. E.; Zimmerman, S.
C. Chem. Commun. 2009, 794. (d) Endo, K.; Ito, Y.;
Higashihara, T.; Ueda, M. Eur. Polym. J. 2009, 45, 1994.
+
HRMS (EI): m/z [M + H] calcd for C H N : 1204.1871; found:
7
4
147 12
1
204.1872.
(
e) Rolland, O.; Turrin, C.-O.; Bacquet, G.; Poupot, R.;
2
G -N~N-G2
Poupot, M.; Caminade, A.-M.; Majoral, J.-P. Tetrahedron
Lett. 2009, 50, 2078.
Dendrimer G -N~N-G (69%, 17.83 g) was prepared in a similar
manner by reaction of G -Cl with N,N¢-dimethylethane-1,2-di-
amine in the ratio 2:1.
2
2
2
(7) Takagi, K.; Hattori, T.; Kunisada, H.; Yuki, Y. J. Polym.
Sci., Part A: Polym. Chem. 2000, 38, 4385.
(8) (a) Steffensen, M. B.; Hollink, E.; Kuschel, F.; Bauer, M.;
Simanek, E. E. J. Polym. Sci., Part A: Polym. Chem. 2006,
1
H NMR (300 MHz, CDCl ): d = 0.89 (br s, 48 H, 16 × CH ), 1.29
3
3
(
(
br s, 160 H, 80 × CH ), 1.59 (br s, 32 H, 16 × CH ), 3.10 and 3.14
2
2
4
4, 3411. (b) Mintzer, M. A.; Merkel, O. M.; Kissel, T.;
2 × s, 30 H, 10 × CH ), 3.46 (br s, 32 H, 16 × CH ), 3.74 (br s, 20
3
2
Simanek, E. E. New J. Chem. 2009, 33, 1918. (c) Lim, J.;
Simanek, E. E. Org. Lett. 2008, 10, 201. (d)Mintzer, M. A.;
Perez, L. M.; Simanek, E. E. Tetrahedron Lett. 2010, 51,
1631. (e) Lim, J.; Mintzer, M. A.; Perez, L. M.; Simanek, E.
E. Org. Lett. 2010, 12, 1148.
H, 10 × CH ).
2
MS (MALDI-TOF): m/z = 2823.3 [M + H]+.
Anal. Calcd for C166H322N : C, 70.64; H, 11.50; N, 17.86. Found:
C, 70.28; H, 11.50; N, 18.00.
36
(
9) Lai, L. L.; Wang, E.; Luh, B. J. Synthesis 2000, 361.
G -N~N-G3
(10) (a) Lai, L. L.; Wang, L. Y.; Lee, C. H.; Lin, Y. C.; Cheng, K.
L. Org. Lett. 2006, 8, 1541. (b) Lai, L. L.; Lee, C. H.; Wang,
L. Y.; Cheng, K. L.; Hsu, H. F. J. Org. Chem. 2008, 73, 485.
(11) Schnabel, W. J.; Rätz, R.; Kober, E. J. Org. Chem. 1962, 27,
3
Dendrimer G -N~N-G (51%, 3.87 g) was prepared in a similar
manner by reaction of G -Cl with N,N¢-dimethylethane-1,2-di-
amine in the ratio 2:1.
3
3
3
2514.
Synthesis 2010, No. 20, 3576–3582 © Thieme Stuttgart · New York

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L.-L. Lai et al.
PAPER
(14) Goldmann, D.; Janietz, D.; Schmidt, C.; Wendroff, J. H.
Angew. Chem. Int. Ed. 2000, 39, 1851.
(15) Reichart, C. Chem. Rev. 1994, 94, 2319.
(
(
12) Minard-Basquin, C.; Weil, T.; Hohner, A.; Rädler, J. O.;
Müllen, K. J. Am. Chem. Soc. 2003, 125, 5832.
13) Koch, A. S.; Harbison, W. G.; Hubbard, J. M.; de Kort, M.;
Roe, B. A. J. Org. Chem. 1996, 61, 5959.
Synthesis 2010, No. 20, 3576–3582 © Thieme Stuttgart · New York