Strain-Promoted Double Azide Addition to Octadehydrodibenzo[12]annulene Derivatives

Article abstract of DOI:10.1002/hlca.201900016

Octadehydrodibenzo[12]annulenes (DBAs), readily available by the oxidative acetylenic coupling of 1,2-diethynylbenzene derivatives, were reacted with organic azides. As compared to the well-known strain-promoted azide-alkyne cycloaddition (SpAAC) of 5,6,11,12-tetradehydrodibenzo[a,e][8]annulene, the reactivity of the DBA alkynes was lower due to the lower strain energy. However, the regioselective double azide addition occurred without any side reactions under mild conditions, yielding bis-triazole products. The structures of the products were confirmed by an X-ray crystal structure analysis, and the reaction mechanism was studied by ¹H-NMR spectroscopy and computational studies. It was also found that the DBAs were hardly fluorescent, while the bis-triazole products showed a green fluorescence with quantum yields up to 5.1 %. Finally, the new strain-promoted double azide addition to the DBAs was used for step-growth polymerization, successfully producing a high molecular weight triazole polymer.

Full text of DOI:10.1002/hlca.201900016

HELVETICA
chimica acta
Accepted Article
Title: Strain-Promoted Double Azide Addition to
Octadehydrodibenzo[12]annulene Derivatives
Authors: Satomi Fukushima, Minoru Ashizawa, Susumu Kawauchi, and
Tsuyoshi Michinobu
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Helvetica Chimica Acta
10.1002/hlca.201900016
HELVETICA
Strain-Promoted Double Azide Addition to
Octadehydrodibenzo[12]annulene Derivatives
Satomi Fukushima, Minoru Ashizawa, Susumu Kawauchi, and Tsuyoshi Michinobu*
Department of Organic and Polymeric Materials, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro-ku, Tokyo 152-8552, Japan,
e-mail: michinobu.t.aa@m.titech.ac.jp
Dedicated to the retirement of Prof. François Diederich
Octadehydrodibenzo[12]annulenes (DBAs), readily available by the oxidative acetylenic coupling of 1,2-diethynylbenzene derivatives, were
reacted with organic azides. As compared to the well-known strain-promoted azide-alkyne cycloaddition (SpAAC) of dibenzo-1,5-cyclooctadiene-3,7-
diyne, the reactivity of the DBA alkynes was lower due to the lower strain energy. However, the regioselective double azide addition occurred without
any side reactions under mild conditions, yielding bis-triazole products. The structures of the products were confirmed by an X-ray crystal structure
1
analysis, and the reaction mechanism was studied by H NMR spectroscopy and computational studies. It was also found that the DBAs were hardly
fluorescent, while the bis-triazole products showed a green fluorescence with quantum yields up to 5.1%. Finally, the new strain-promoted double
azide addition to the DBAs was used for step-growth polymerization, successfully producing a high molecular weight triazole polymer.
Keywords: annulene • click chemistry • polymerization • regioselectivity • strain-promoted azide-alkyne cycloaddition
In order to lower the reactivity of the strained alkynes and control
Introduction
the
regiochemistry,
we
investigated
the
Metal-free click chemistry is a powerful tool for connecting two different
components under mild conditions without any metal catalysts.[1-6] The
strain-promoted azide-alkyne cycloaddition (SpAAC) is a representative
metal-free click reaction, efficiently and quantitatively producing triazole
products.[7-10] The strained alkynes of SpAAC are being changed from the
octadehydrodibenzo[12]annulene (DBA) derivatives, which have
additional alkyne spacers.[31-36] Symmetric DBA derivatives can be readily
synthesized, and it was postulated that the reactivity control of the
alkynes is possible due to the lower strain energy. We now report for the
first time the double click reactions of the DBA derivatives with various
organic azides. It was found that two of the four alkynes of DBAs are
reactive towards azides under mild ambient conditions with the
regiochemistry of the products being perfectly controlled. The reaction
mechanism and addition pattern were supported by theoretical
calculations and an X-ray crystal structure analysis. Moreover, the DBAs
were hardly fluorescent due to their anti-aromatic character, while the
azide-adducts showed a green fluorescence. Finally, the double click
reaction of the DBAs was successfully applied to the step-growth
polymerization, yielding a high molecular weight triazole polymer.
initial
dibenzoazacyclooctynes,[13]
difluorocyclooctynes[11]
to
dibenzocyclooctynes,[12]
biarylazacyclooctynones,[14]
and
bicyclo[6.1.0]nonynes[15] mainly achieved by the optimization of the
reactivity and chemical stability. Recently, the SpAAC concept was
applied to double click chemistry, which was useful not only for
biological chemistry, but also for polymer chemistry.[16-19] For example,
dibenzo-1,5-cyclooctadiene-3,7-diyne (1) contains two strained alkynes,
and it was reported that the reaction rate of the second azide addition is
much faster due to the increased strain energy resulting from the first
addition (Scheme 1).[20-28] This feature was successfully applied to the
synthesis of cyclic polymers and step-growth polymerization.[29,30]
However, due to the very fast reaction, the regiochemistry of the bis-
triazole products (2a and 2b) was not totally controlled.
Results and Discussion
The DBA derivatives (4a-4c) were synthesized by the Cu-catalyzed
acetylenic oxidative coupling reaction of the 1,2-diethynylbenzene
derivatives (3a-3c), which were in-situ prepared from the corresponding
trimethylsilyl-substituted derivatives, under dilute conditions (Scheme 2).
The reaction yields of the 2-step reactions were reasonable (28-40%), and
the chemical structures were characterized by NMR spectroscopy (Figures
S1-S3). However, 4b had a lower solubility than 4a. In addition, there was
a stability problem for 4c. This may have been caused by the water
addition to the alkynes.[37] Therefore, the following azide addition studies
were mainly performed using 4a.
Scheme 1. Strain-promoted azide-alkyne cycloaddition of dibenzo-1,5-
cyclooctadiene-3,7-diyne 1.
1
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(
a
E ) of the reaction was determined by the Arrhenius plots (Figure 2). The
E
a
of the reaction between 4a and benzylazide in DMSO-d was 93.3 kJ
6
-1
mol . This value is higher than those of the cyclooctyne derivatives,
suggesting the lower strain energy of the alkynes.
Scheme 2. Synthesis of octadehydrodibenzo[12]annulene (DBA) derivatives. (i) O
CuCl, N,N,N’,N’-tetramethylethylenediamine, 1,2-dichlorobenzene.
2
,
The reaction of 4a and the commercially-available benzylazide was
initially studied. After 4a was dissolved into benzylazide and the solution
was stirred at room temperature overnight, the excess benzylazide was
removed in vacuo. This simple operation quantitatively produced a single
product, suggesting the click chemistry characteristic. The reaction
kinetics were then evaluated by 1H NMR spectroscopy. Due to the
alleviated strain energy with respect to 1, the reactivity of the DBA
alkynes was lowered. Thus, the reaction of 4a and benzylazide was
Figure 2. Arrhenius plots of the rate constants for the reaction between 4a and
benzylazide in DMSO–d .
6
o
1
heated to either 70, 80, 90, or 100 C in DMSO-d , and the H NMR spectral
6
Similar to these experiments, the reaction kinetics of 4a and
benzylazide were also determined in C . In order to avoid the self-
changes were monitored (Figure 1). Note that despite the limited
6
D
6
o
solubility of 4a in DMSO-d
6
at <60 C, this solvent was selected in order to
polymerization of 4a, the concentration was reduced to 1.0 mM and the
prevent the self-polymerization of 4a. Therefore, the spectra measured
within 30 min mainly depicted the benzylazide peaks. After 30 min, a set
of new peaks appeared and, at the same time, the peak intensities
ascribed to both 4a and benzylazide started to decrease. This set of new
peaks suggested the double addition of benzylazide to 4a, since no peaks
o
temperature was set at 40-65 C after the optimization of the reaction
conditions. We experimentally observed that the reaction in apolar
solvents, such as benzene, was quite slow even when the concentration
was increased (Figures S10 and S11). However, the estimated E
a
value in
-1
C
6
D
6
was 86.8 kJ mol , which is lower than that in DMSO-d
6
(Figure S12).
o
ascribed to the mono-adduct could be detected. After 150 min at 90 C,
This result is consistent with the common solvent effect of Diels-Alder
the reaction was completed without any byproducts.
reactions.[38] The DBA derivative 4b with the methoxy substituents was
also studied in the polar solvent of DMSO-d
6
in the temperature range
from 40 to 70 oC. The kinetic studies again suggested a second-order
-1
reaction (Figure S13). In addition, the E value (73.6 kJ mol ) was
a
unexpectedly lower than that of 4a (Figure S14). This result indicated that
the electron-donating substituents affect the reactivity of DBA alkynes.
The DBA derivatives 4a-4c were reacted with several organic azides,
producing the corresponding azide bisadducts (Scheme 3 and Figures S4-
S7). Benzylazide was used as both the reactant and solvent. For example,
4
a and 4b with alkyloxy substitutents were converted to the
corrresponding bis-triazole derivatives, 5a and 5b, at room temperature
in 96-99% yields (Table 1). In contrast, 4c with tris(ethylene glycol) chains
was gradually decomposed when it was stirred in benzylazide. Thus, the
optimized reaction conditions (at room temperature for 2 h) produced
the corresponding bis-triazole 5c in 32%. 5c was stable under dry
conditions. Other organic azides were added to 4a. For example, since
the melting point of 1-azidohexadecane was lower than room
temperature, it was used in place of benzylazide. The reaction between
4a and 1-azidohexadecane produced the corresponding bis-triazole 6a in
o
Figure 1. Reaction of 4a (7.70 mM) and benzylazide (15.4 mM) in DMSO-d
6
at 90 C
1
and its time-dependent H-NMR spectra (300 MHz, 293 K, DMSO-d
6
).
The reaction rate constants were estimated from the 1H NMR
9
4% yield. In contrast, ethyl 4-azidobenzoate was a solid at room
temperature. Thus, it was dissolved in DMSO, and the solution containing
a and ethyl 4-azidobenzoate was heated to 85 oC. This mild heating
spectra (Figure S9). The reaction kinetics were determined as a second-
order reaction. Based on the fact that the mono-adduct was not formed,
the first azide addition is the rate-determining step. The activation energy
4
2
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initiated the addition reaction, but at the same time, caused the partial
decomposition of 4a. Accordingly, the yield of 7a was dramatically
reduced to 48%.
reaction between benzylazide and 4b is shown in Figure 4 and supported
by the ωB97X-D/6-31G(d,p) calculations with the CH
2
2
Cl polarizable
continuum model (PCM) solvent. First, the reaction started with the
addition of a benzylazide to one of the alkynes of 4b. When the benzyl
group is located on the outer side of DBA, a higher-energy intermediate
N
R'
N
N
RO
RO
-
1
RO
RO
OR
OR
R' N3
(ΔG = 5.23 kJ mol ) was formed due to the steric reason. Thus, directing
OR
OR
the benzyl group toward the inner side produced a more energetically-
N
N
-1
R'
N
favored (by 8.37 kJ mol ) mono-triazole product (“in“ product in Figure 4).
4
4
4
a (R = C6H13)
b (R = CH3)
c (R = (C2H4O)3CH3)
5
6
7
5
5
a (R = C6H13, R' = CH2Ph)
a (R = C6H13, R' = C16H33)
a (R = C6H13, R' = (p-phenylene)CO2Et)
b (R = CH3, R' = CH2Ph)
This was followed by the second azide addition. The alkyne at the
diagonal position with respect to the triazole moiety was the most
reactive due to the highly-distorted structure. This was consistent with
the experimental result that no mono-triazoles were isolated. The
benzylazide orientation was again controlled. The benzyl group on the
inner side gave a more thermodynamically-stable intermediate and
product as compared to those on the outer side. It should be noted that a
similar preference of the benzylazide orientation was observed even for
the “out“ mono-triazole. Overall, the most stable structure of the “in-
in“ product, as revealed by X-ray crystallography, was exclusively formed
under mild conditions.
c (R = (C2H4O)3CH3, R' = CH2Ph)
Scheme 3. Double azide addition to the DBA derivatives.
Table 1. Click reactions of DBA derivatives with organic azides
o
DBA
Azide
Solvent
Temp. ( C)
Time (h)
Yield (%)
4
4
4
a
a
a
N
N
N
3
3
3
CH
2
Ph
-
r.t.
r.t.
85
24
24
24
96
94
48
C
16
H
33
-
(p-
DMSO
phenylene)CO Et
2
4
4
b
c
N
N
3
CH
2
Ph
Ph
-
-
r.t.
r.t.
24
2
99
32
3
CH
2
The chemical structure of the bis-triazoles was confirmed by an X-
ray crystal structure analysis. Single crystals of 7a suitable for the X-ray
crystallographic analysis were prepared by slow diffusion of alcohols
(
methanol, ethanol, or isopropanol) into a solution of CH
2
2
Cl . No other
bis-triazoles, unfortunately, furnished the single crystals probably due to
the weak intermolecular interactions. The crystal structure of 7a is shown
in Figure 3. Due to the large disorder, the hexyloxy chains were depicted
1
as ethoxy groups. As anticipated from the H NMR spectrum, the double
azide addition occurred in a regiospecific way, yielding the symmetric
product. Since the central macrocyclic ring was nonplanar, the unreacted
alkynes of 7a were almost straight and did not have any strains.
Accordingly, the bis-triazoles were chemically stable and inert to
additional azide additions.
Figure 3. X-ray crystal structure of 7a: (left) top view and (right) side view. The
hexyloxy groups were simplified as ethoxy due to the high disorder.
The underlying reaction mechanism was also considered by
detailed computational investigations. The proposed mechanism of the
3
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fluorescence appeared in the visible range. Although the emission
maximum (em) of 7a with the ethyl benzoate group was slightly different
(
567 nm) probably due to the intramolecular electronic effect, the other
bis-triazoles exhibited the em of 533-539 nm. Note that the calculated
-1
Stokes shifts (21,900-22,200 cm ) were relatively high. The fluorescence
quantum yields ( ) of 7a and 5c were slightly lower (2.3-2.8%) than the
F
others (4.2-5.1%). This may also be caused by the electronic or solvation
effects of the polar substituents.
1
.5
1
1.5
1
Abs 5a
Abs 6a
Abs7a
Abs 5b
Abs 5c
FL 5a
FL 6a
FL 7a
FL 5b
FL 5c
0
.5
0
0.5
0
300 400 500 600 700 800
Wavelength (nm)
Figure 5. UV-vis absorption spectra and fluorescence spectra of bis-triazole
-5
derivatives at the concetration of 1.510 M in CH
2
Cl .
2
Finally, taking advantage of the bifunctionality of the DBAs, we
applied this SpAAC reaction to the step-growth polymerization. Heating
o
the solution of 4a and 2,7-diazidofluorene in DMF to 85 C for 2 days
successfully furnished the corresponding polymer 8a in the high yield of
7
9% (Scheme 4 and Figure S8). The polymer was sufficiently soluble in
common organic solvents, such as CH Cl and THF. The weight-average
molecular weight (M ) and polydispersity (M
2
2
w
w
/M ), determined by gel
n
o
4
-1
permeation chromatography (GPC) in THF at 40 C, were 1.3810 g mol
and 1.11, respectively.
Figure 4. Proposed reaction mechanism for the formation of 5b. Free energy
-
1
profiles (ΔG298 in kJ mol ) calculated at the ωB97X-D/6-31G(d,p)/PCM (in CH
2
Cl ).
2
The UV-vis absorption and fluorescence spectra of the DBAs and
bis-triazoles were measured in CH Cl . In order to avoid any effects of
aggregation, the concentration was 1.510-5 M. The DBAs 4a and 4b
Scheme 4. Polymerization of DBA and diazido monomers.
2
2
showed strong UV absoprtions with the peak maxima (max) of 312-316 Conclusions
nm (Figure S15 and Table S1). However, both DBAs were hardly
In summary, we have reported the metal-free double azide addition to
DBAs, which can be classified as a new SpAAC. Although the reactivity of
the DBAs was significantly lower as compared to the reported dibenzo-
fluorescent (Figure S15 and Table S1). These optical properties were
dramatically changed by the azide addition. All the bis-triazoles, 5a-5c, 6a,
and 7a, exhibited almost the same absorption and fluorescence
properties. The absorption of the bis-triazoles featured broad single
peaks with the max hypsochromically shifted to 245-252 nm as compared
to those of the DBAs (Figure 5 and Table S1). Interestingly, a well-defined
1
,5-cyclooctadiene-3,7-diyne, the regioselective double azide addition
was demonstrated. Both the experimental kinetic study and theoretical
calculations revealed the strain-accelerated addition of the second azide.
In other words, the mono-triazole products have a highly-strained alkyne,
4
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which very quickly reacted with the azides to form the bis-triazoles. The
regiosymmetric “in-in“ product was confirmed by an X-ray crystal
structure analysis of the derivative with ethyl benzoate substituents. In
addition, the bis-triazole products were highly fluorescent upon
structures had only one imaginary frequency corresponding to the
reaction coordinate.
Experimental
-1
excitation by UV light with the high Stokes shifts of ca. 22,000 cm . This
feature is advantageous for many applications including bioorthogonal
click chemistry and labeling of the azidated proteins.[39,40] Moreover, step-
growth polymerization was possible by using the SpAAC of the DBAs,
indicating that this efficient reaction is also a useful tool in materials
science. Further studies using this reaction in polymerization and
polymer crosslinking are currently underway.
Synthesis of 4a. To
a
50 mL flask, 1,2-dihexyloxy-4,5-
CO (0.50 g, 3.40
bis(trimethylsilylethynyl)benzene (0.40 g, 0.85 mmol), K
2
3
mmol), and MeOH/THF (1:1, 10 mL) were placed and the mixture was
stirred at room temperature for 30 min. The organic layer was extracted
with ether, washed with aqueous NH
After filtration, the solvents were evaporated. Column chromatography
(SiO , CHCl ) afforded 1,2-diethynyl-4,5-dihexyloxybenzene (3a) as a
4
Cl solution, and dried over MgSO .
4
2
3
yellow solid. This solid was directly used for the next reaction. After 3a
was dissolved in 1,2-dichlorobenzene (170 mL), CuCl (100.0 mg, 1.01
mmol) and N,N,N’,N’-tetramethylethylenediamine (3.0 mL, 20.2 mmol)
Experimental Section
General
o
were added and the mixture was stirred at 50 C for 2 d. The solvent was
removed in vacuo, and CH
2
Cl
2
and water were added. The organic layer
. Column chromatography (SiO
3:2) afforded the desired compound as a yellow solid (211
, 300 MHz, 293 K):  = 6.39 (s, 4H), 3.85 (t, 8H),
, 75
MHz, 293 K):  = 149.70, 123.75, 113.48, 92.19, 83.29, 69.10, 31.47, 29.69,
All reagents and chemicals were purchased from Tokyo Chemical
Industry (TCI), Kanto Chemical Co., Inc., and Sigma Aldrich and used as
was extracted and dried over MgSO
4
2
,
3a[41]
3b[42]
3c[43]
1-azidohexadecane[44]
hexane/CHCl
3
received.
,
,
,
,
ethyl 4-
1
azidobenzoate[45], and 2,7-diazidofluorene[46] were prepared according to
mg, 40%). H NMR (CDCl
3
1
.80-1.21 (m, 32H), 0.89 (t, 12H), 0.27 ppm (s, 18H). 13C NMR (CDCl
3
a literature method.
NMR spectra were recorded using a JEOL model AL300 (300 MHz)
at room temperature. Deuterated chloroform was used as the solvent
unless otherwise noted. Chemical shifts of NMR were reported in ppm
2
5.53, 22.54, 13.97 ppm. IR (neat):  = 2184.0 (C ≡C symmetric vibration),
-1
1
590.0 (Ar-H stretching vibration), 1546.6 (C ≡C asymmetric vibration) cm .
MALDI-TOF MS (dithranol): m/z calcd for C44
H
56
O
+: 648.42; found: 648.38
4
1
relative to the residual solvent peak at 7.26 ppm for H NMR spectroscopy
+
and 77.6 ppm for 13C NMR spectroscopy. Coupling constants (J) were
[M ]. Elemental analysis calcd (%) for C H O (648.93): C 81.44, H 8.70;
44 56
4
found: C 81.29, H 8.70.
given in Hz. The resonance multiplicity was described as s (singlet), d
Synthesis of 4b. To
a
50 mL flask, 1,2-dimethoxy-4,5-
CO (5.0 g, 34
(
doublet), t (triplet), and m (multiplet). FT-IR spectra were recorded on a
-1
JASCO FT/IR-4100 spectrometer in the range from 4000 to 600 cm .
MALDI-TOF mass spectra were measured on Shimadzu/Kratos
bis(trimethylsilylethynyl)benzene (0.661 g, 2.00 mmol), K
2
3
a
mmol), and MeOH/THF (1:1, 10 mL) were placed and the mixture was
stirred at room temperature for 15 min. The organic layer was extracted
AXIMACFR mass spectrometer equipped with a nitrogen laser ( = 337
with ether, washed with aqueous NH
After filtration, the solvents were evaporated. Column chromatography
(SiO , CHCl ) afforded 1,2-diethynyl-4,5-dimethoxybenzene (3b) as a
4
Cl solution, and dried over MgSO .
4
nm) and pulsed ion extraction, which was operated in a linear-positive
ion mode at an accelerating potential of 20 kV. THF solutions containing 1
g L-1 of a sample, 10 g L-1 of dithranol, and 1 g L-1 of sodium
2
3
yellow solid. This solid was directly used for the next reaction. After 3b
was dissolved in 1,2-dichlorobenzene (500 mL), CuCl (274 mg, 2.40 mmol)
and N,N,N’,N’-tetramethylethylenediamine (7.15 mL, 228 mmol) were
added and the mixture was stirred at 50 oC for 2 d. The solvent was
trifluoroacetate were mixed to a ratio of 1:1:1, and then 1 L aliquot of
this mixture was deposited onto a sample target plate. Gel permeation
chromatography (GPC) was measured on a JASCO GULLIVER 1500
equipped with a pump (PU-2080 Plus), an absorbance detector (RI-2031
Plus), and two Shodex GPC KF-803 columns (8.0 mm I.D. x 300 mm L)
based on a conventional calibration curve using polystyrene standards.
removed in vacuo, and CH
2
Cl
2
and water were added. The organic layer
. Column chromatography (SiO
was extracted and dried over MgSO
4
2
,
o
-1
hexane/CHCl 3:2) afforded the desired compound as a yellow solid (202
THF (40 C) was used as a carrier solvent at the flow rate of 0.5 mL min .
UV-vis spectra were recorded on a JASCO V-670 spectrophotometer.
Fluorescence spectra were recorded on a JASCO FP-8500.
3
1
mg, 31%). H NMR (CDCl
12H). 13C NMR (CDCl
, 75 MHz, 293 K):  = 149.67, 124.05, 111.63, 92.12,
83.49, 55.95 ppm. IR (neat):  = 2180.1 (C ≡C symmetric vibration), 159.9
3
, 300 MHz, 293 K):  = 6.41 (s, 4H), 3.78 ppm (t,
3
All calculations were carried out using the Gaussian 16 program.[47]
The DFT calculations were carried out using the long-range and
dispersion-corrected ωB97X-D functional.[48] The 6-31G(d,p) basis set was
-1
(Ar-H stretching vibration), 1547.6 (C ≡C asymmetric vibration) cm ;
MALDI-TOF MS (dithranol): m/z calcd for C24
H
16
O
4
+: 368.10; found: 367.92
(368.39): C 78.25, H 4.38;
used for H, C, O, and S atoms.[49,50] The solvent effect of CH
Cl
2
was taken
[M ]. Elemental analysis calcd (%) for C24
found: C 77.95, H 4.29.
+
H
O
2
16
4
into account by the Polarizable Continuum Model using the integral
equation formalism (IEFPCM)[51] for DFT calculations. The optimized
molecular structures were verified by vibrational analysis; equilibrium
structures did not have imaginary frequencies and transition state
Synthesis of 4c. To
a
50 mL flask, ((4,5-bis(2-(2-(2-
methoxyethoxy)ethoxy)ethoxy)-1,2-phenylene)bis(ethyne-2,1-
5
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1
diyl))bis(trimethylsilane) (0.591 g, 1.00 mmol), K
2
CO
3
(1.0 g, 0.68 mmol),
solid (34.3 mg, 94%). H NMR (CDCl
3
, 300 MHz, 293 K):  = 7.53 (s, 2H), 6.99
and MeOH/THF (1:1, 10 mL) were placed and the mixture was stirred at
room temperature for 2 h. The organic layer was extracted with ether,
(s, 2H), 4.37 (t, J = 6.9 Hz, 4H), 4.13 (t, J = 6.9 Hz, 4H), 3.99 (t, J = 6.6 Hz, 4H),
1.89-1.21 (m, 88H), 0.89-0.88 ppm (m, 30H). IR (neat):  = 2225.5 (C≡C
-
1
washed with aqueous NH
4
Cl solution, and dried over MgSO
4
. After
symmetric vibration) cm . MALDI-TOF MS (dithranol): m/z calcd for
+: 1183.96; found: 1185.31 [M+H]+.
filtration, the solvents were evaporated. The crude product (3c) was
directly used for the next reaction. After 3c was dissolved in 1,2-
dichlorobenzene (500 mL), CuCl (119 mg, 1.20 mmol) and N,N,N’,N’-
tetramethylethylenediamine (3.58 mL, 24.0 mmol) were added and the
C
76
H
123
N
6
O
4
Synthesis of 7a. To a 20 mL flask, 4a (20.0 mg, 0.0308 mmol), ethyl 4-
azidobenzoate (12 mg, 0.0628 mmol), and DMSO (0.5 mL) were placed,
and the mixture was stirred at 85 oC for 24 h. After the solvent was
o
mixture was stirred at 50 C for 2 d. The solvent was removed in vacuo,
removed in vacuo, column chromatography (SiO
2
, hexane/CH
2
2
Cl 2:3)
1
and CH
2
Cl
2
and water were added. The organic layer was extracted and
afforded the desired compound as a white solid (15.2 mg, 48%). H NMR
dried over MgSO
4
. Column chromatography (SiO
2
, CH
2
Cl
2
/MeOH 50:1)
(CDCl , 300 MHz, 293 K):  = 8.17 (d, J = 8.7 Hz, 2H), 7.96 (d, J = 8.4 Hz, 2H),
3
1
afforded the desired compound as a red solid (165 mg, 28%). H NMR
7.57 (s, 2H), 6.98 (s, 2H), 4.38 (q, J = 7.2 Hz, 2H), 4.13 (t, J = 6.6 Hz, 4H), 3.98
(t, J = 6.6 Hz, 4H), 1.89-1.21 (m, 32H), 0.93-0.86 ppm (m, 18H). 13C NMR
(
CDCl
3
, 300 MHz, 293 K):  = 6.45 (s, 4H), 4.05 (t, J = 4.8 Hz, 8H), 3.80 (t, J =
.8 Hz, 8H), 3.71-3.69 (m, 8H), 3.64 (t, J = 4.5 Hz, 16H), 3.57-3.53 (m, 8H),
.38 ppm (s, 12H).
4
3
(CDCl , 75 MHz, 293 K):  = 165.42, 150.92, 149.46, 139.70, 130.81, 129.70,
3
129.02, 128.59, 128.21, 122.79, 118.44, 111.62, 104.97, 78.81, 77.21, 69.20,
Synthesis of 5a. To a 20 mL flask, 4a (50.0 mg, 0.0770 mmol) and
benzylazide (0.5 mL, 4.00 mmol) were placed, and the mixture was stirred
at 20 oC for 24 h. After evaporation of excess benzylazide, column
61.38, 31.58, 28.98, 25.61, 22.59, 14.25, 14.00 ppm. IR (neat):  = 2220.6
-1
(C ≡C symmetric vibration), 1717.3 (C=O vibration) cm . MALDI-TOF MS
+
+
(dithranol): m/z calcd for C H N O : 1030.56; found: 1030.72 [M ].
6
2
74
6
8
chromatography (SiO
2
, hexane/ethylacetate 10:1) afforded the desired
Elemental analysis calcd (%) for C H N O (1031.31): C 72.21, H 7.23, N
6
2
74
6
8
1
compound as a white solid (67.7 mg, 96%). H NMR (CDCl
3
, 300 MHz, 293
8.15; found: C 72.21, H 7.23, N 8.15.
K):  = 7.50 (s, 2H), 7.26-7.15 (m, 10H), 6.86 (s, 2H), 5.49 (s, 4H), 4.13 (t, J =
.6 Hz, 4H), 1.89-1.25 (m, 32H), 0.91-0.89 ppm (m, 12H). 13C NMR (CDCl
, 75
MHz, 293 K):  = 150.72, 149.19, 149.02, 134.46, 128.53, 128.42, 128.34,
Synthesis of 8a. To a 20 mL flask, 4a (50.0 mg, 0.0771 mmol), 2,7-
diazidofluorene (19.1 mg, 0.0771 mmol), and DMF (10 mL) were placed,
and the mixture was stirred at 85 oC for 48 h. After the solvent was
removed in vacuo, the crude product was washed by methanol, hexane,
6
3
1
6
2
27.35, 119.36, 116.16, 113.71, 111.55, 104.37, 102.63, 78.66, 77.21, 69.22,
9.07, 59.63, 53.05, 31.49, 28.95, 25.59, 22.58, 14.01 ppm. IR (neat):  =
and acetone using a Soxhlet extractor. After that, the CHCl soluble
3
-1
220.2 (C ≡C symmetric vibration) cm . MALDI-TOF MS (dithranol): m/z
+: 914.55; found: 914.35 [M+].
fraction was collected and further purified by reprecipitation into
methanol, yielding the desired polymer as a brown solid (54.4 mg, 79%).
calcd for C58
H
70
N
6
O
4
o
4
-1
1
Synthesis of 5b. To a 20 mL flask, 4b (20.0 mg, 0.0543 mmol) and
GPC (THF, 40 C): M
w
= 1.3810 g mol , M
w
/M
n
= 1.11. H NMR (CDCl , 300
3
benzylazide (0.5 mL, 4.00 mmol) were placed, and the mixture was stirred
MHz, 293 K):  = 7.98 (d, J = 13.8 Hz, 2nH), 7.85-7.80 (m, 2nH), 7.58-7.57 (m,
2nH), 7.20 (s, 2nH), 7.09-6.94 (m, 2nH), 4.15 (br s, 2nH), 3.95 (br s, 8nH),
1.87 (br s, 8nH), 1.34 (br s, 24nH), 0.91 ppm (br s, 12nH). IR (neat):  =
2107.8 (C ≡C symmetric vibration).
o
at 20 C for 24 h. Evaporation of excess benzylazide afforded the desired
1
compound as a white solid (34.5 mg, 99%). H NMR (CDCl
3
, 300 MHz, 293
K):  = 7.53 (s, 2H), 7.26-7.23 (m, 10H), 6.86 (s, 2H), 5.50 (s, 4H), 4.00 (s, 4H),
3
1
1
.86 ppm (s, 4H). 13C NMR CDCl
3
, 75 MHz, 293 K):  = 150.55, 149.15,
Crystallographic data for 7a have been deposited with the Cambridge
Crystallographic Data Centre as CCDC-1889612. These data can be
obtained free of charge via http://www.ccdc.cam.ac.uk/data_request/cif,
by emailing data_request@ccdc.cam.ac.uk or by contacting the
Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2
1EZ, UK.
49.11, 134.38, 128.56, 128.40, 127.57, 119.36, 114.19, 112.35, 111.83,
04.22, 78.67, 77.20, 56.20, 56.00, 53.11 ppm. IR (neat):  = 2226.4 (C≡C
-1
symmetric vibration) cm . MALDI-TOF MS (dithranol): m/z calcd for
+: 634.23; found: 633.43 [M+].
C
38
H
30
N
6
O
4
Synthesis of 5c. To a 20 mL flask, 4c (13.4 mg, 0.0149 mmol) and
benzylazide (1.5 mL, 12 mmol) were placed, and the mixture was stirred
at 20 oC for 2 h. After evaporation of excess benzylazide, column
Supplementary Material
chromatography (SiO
2
,
CH
2
Cl
2
/MeOH 20:1) afforded the desired
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/MS-number.
1
compound as a white solid (5.6 mg, 32%). H NMR (CDCl
3
, 300 MHz, 293 K):

= 7.54 (s, 2H), 7.26-7.13 (m, 10H), 6.91 (s, 2H), 5.48 (s, 4H), 4.36-4.29 (m,
H), 4.17-4.01 (m, 8H), 3.98-3.81 (m, 8H), 3.75-3.50 (m, 24H) 3.37-3.34 ppm
Acknowledgements
8
(
m, 12H).
This work was partially supported by the JSPS KAKENHI Grant 15H03863
and the Support for Tokyotech Advanced Researchers. The numerical
calculations were carried out on the TSUBAME2.5 supercomputer at the
Tokyo Institute of Technology, Tokyo, Japan, and on the supercomputer
at the Research Center for Computational Science, Okazaki, Japan.
Synthesis of 6a. To a 20 mL flask, 4a (20.0 mg, 0.0308 mmol) and 1-
azidohexadecane (500 mg, 1.87 mmol) were placed, and the mixture was
stirred at 20 oC for 24 h. Column chromatography (SiO
2
,
hexane/ethylacetate 10:1) afforded the desired compound as a white
6
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Helvetica Chimica Acta
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HELVETICA
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Entry for the Table of Contents
(
(Insert TOC Graphic here; max. width: 17.5 cm; max. height: 7.0 cm))
SpAAC
DBA
9
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