Preparation of tetrazole-fused π-conjugated molecules and their fluorescence behavior

Article abstract of DOI:10.1246/cl.190150

New tetrazole-fused π-conjugated molecules were prepared from dibromobenzonitriles by repeated regioselective Sonogashira-Hagihara cross-coupling with acetylenes and intramolecular nucleophilic cyclizations. The conjugated tetracyclic compounds exhibited fluorescence with lifetimes of nanosecond order. From TD-DFT calculations, excited state wavefunctions of compounds indicated that the HOMO-1→LUMO and HOMO→LUMO+1 mainly became the first excited state (S₀→S₁) to contribute significantly to light emission.

Full text of DOI:10.1246/cl.190150

CL-190150
Received: February 25, 2019 | Accepted: March 26, 2019 | Web Released: June 22, 2019
Preparation of Tetrazole-fused π-Conjugated Molecules and Their Fluorescence Behavior
Takeshi Hata,*1 Yoshiki Hayashi,1 Yuki Hasegawa,2 Masaaki Iwai,2 Ayumi Ishii,2
Miki Hasegawa,*2 Masayuki Shigeta,1 and Hirokazu Urabe*1
1Department of Life Science and Technology, School of Life Science and Technology, Tokyo Institute of Technology,
4259-B-59 Nagatsuta-cho, Midori-ku, Yokohama, Kanagawa 226-8501, Japan
2College of Science and Engineering, Aoyama Gakuin University,
5-10-1 Fuchinobe, Chuo-ku, Sagamihara, Kanagawa 252-5258, Japan
E-mail: thata@bio.titech.ac.jp (T. Hata), hasemiki@chem.aoyama.ac.jp (M. Hasegawa), hurabe@bio.titech.ac.jp (H. Urabe)
New tetrazole-fused π-conjugated molecules were prepared
from dibromobenzonitriles by repeated regioselective
Sonogashira-Hagihara cross-coupling with acetylenes and intra-
molecular nucleophilic cyclizations. The conjugated tetracyclic
compounds exhibited fluorescence with lifetimes of nanosecond
order. From TD-DFT calculations, excited state wavefunctions
of compounds indicated that the HOMO¹1 ¼ LUMO and
HOMO ¼ LUMO+1 mainly became the first excited state
(S0 ¼ S1) to contribute significantly to light emission.
far and its physical properties should be interesting (Scheme 1).8
Thus, we herein report the synthesis of tetrazole-fused π-
conjugated compounds by using regioselective Sonogashira-
Hagihara cross-coupling followed by intramolecular nucleophil-
ic cyclization and their optical properties including photo-
luminescence spectra.
We aimed at preparing D-π-A-type molecules9 and planned
to make a tetrazole-fused π-conjugated compound where the
isoquinoline ring became the central π skeleton and π-electron
deficient tetrazole ring10 and also π-electron rich furan ring11,12
were fused to isoquinoline ring. The target molecules 8
were prepared from dibromoaryltetrazole 4 via regioselective
Sonogashira-Hagihara cross-coupling to acetylenes 5 and intra-
molecular nucleophilic cyclizations to 7, as shown in Scheme 2.
In greater detail, dibromoaryltetrazole 4 was derived from
dibromobenzonitrile 913 and Bu3SnN3 in good yield even in the
presence of the other functional groups (Scheme 3). Subsequent-
ly, the copper-catalyzed regioselective Sonogashira-Hagihara
cross-coupling with 1-octyne, followed by spontaneous intra-
molecular cyclization, proceeded to afford the corresponding
tetrazole-fused tricyclic product 10 as a single isomer.10f Finally,
the second Sonogashira-Hagihara cross-coupling reaction took
place at the remaining bromo group of 10, followed by
demethylation and cyclization in the presence of BBr3, to give
desired tetracyclic product 11 in a good yield. Tetrazole 13,
Keywords: Tetrazole
| π-Conjugated molecule | Fluorescence
Tetrazole is composed of four consecutive nitrogens and one
carbon1 and frequently used as one of the useful heterocycles in
the field of medicine (Figure 1, A), because the acidity of
tetrazole is similar to carboxylic acid but its lipophilicity is more
pronounced, so that the introduction of tetrazole could improve
the characteristics of potential pharmaceutical agents.2,3 Tetra-
zoles display the chemical property of decomposition with
release of nitrogen gas by heat, impact, or UV irradiation. For
example, while 5-aminotetrazole is utilized as an explosive for
airbags of cars (Figure 1, B),4 tetrazole derivatives have been
extensively studied in the field of molecular probes by UV
irradiation, the so-called photoclick reaction (Figure 1, C).5
Conjugated molecules containing tetrazole and linked with
unsaturated bonds such as acetylenes have been also reported as
organic electronics molecules as shown in Figure 1, D.6
On the other hand, hetero π-conjugated molecules 2, which
are the modification of π-conjugated molecules 1 by incorporat-
ing several heteroatoms, are widely used in the field of organic
electronics due to physical properties such as fluorescence
and specific redox responses.7 However, as far as we know,
compounds 3, where electron-deficient tetrazole is incorporated
directly into a π-conjugated skeleton, has rarely been reported so
many
reports
X
?
N
N
N
π
π
π
N
X
X
1
2
3
(X = heteroatom)
Scheme 1. Incorporation of Tetrazole in π-Conjugated Com-
pounds.
OMe
OMe
Cu-catalyzed
Sonogashira-Hagihara type
cross-coupling
Br
OMe
Br
intramolecular
cyclization
OH
Br
N
N
N
N
N
O
N
N
N
N
N
HN
N
R
N
N
N
N
N
OH
Br HN
N
R1
N
R1
O
OH
NH2
N
N
N
O
H
4
5
6
H
N
R2
O
N
R2
OH
N
N
intramolecular
cyclization
Sonogashira-Hagihara
cross-coupling
A: antihypertensive drug
B: 5-aminotetrazole
S
C: photoclick probe
N
N
N
N
then deprotection
N
N
N
N
N
N
C12H25
C12H25
N
N
N
N
R1
R1
N
N
N
N
7
8
D: organic electronics molecule
Scheme 2. Synthetic Plan of Tetrazole- and Furan-fused π-
Conjugated Compounds.
Figure 1. Tetrazoles Contained in Useful Compounds.
662 | Chem. Lett. 2019, 48, 662–665 | doi:10.1246/cl.190150
© 2019 The Chemical Society of Japan

C6H13
(a) Compound 11
OMe
O
OMe
OMe
Br
Br
Br
a
c
b
Ψ1 = 0.57 HOMO–1→LUMO – 0.35
Ψ2 = 0.62 HOMO→LUMO + 0.29
HOMO→LUMO+1
N
N
N
N
N
N
N
CN
HOMO–1→LUMO+1
N
N
N
N
Br HN
Br
C6H13
10
C6H13
11
HOMO
LUMO
9
4
C6H13
OMe
OMe
O
OMe
Br
Br
Br
C6H13
N
a
b
d
C6H13
Br
Br
H
N
N
N
N
CN
N
N
N
N
N
N
N
12
13
14
15
HOMO–1
LUMO+1
Scheme 3. Syntheses of Tetrazole- and Furan-fused π-Con-
jugated Compounds 11 and 15. Reagents and conditions: (a)
Bu3SnN3 (3 equiv), xylene, 150 °C, 12 h; (b) 1-octyne (4 equiv),
CuI (20 mol %), K2CO3 (4 equiv), DMSO, 100 °C, 24 h; (c) 1-
octyne (4 equiv), Pd(PPh3)2Cl2 (1 mol %), PPh3 (2 mol %), CuI
(2 mol %), Et3N, 80 °C, 15 h, then BBr3 (3 equiv), CH2Cl2,
¹78 °C to rt, 12 h; (d) 1-octyne (4 equiv), Pd(PPh3)2Cl2
(1 mol %), PPh3 (2 mol %), CuI (2 mol %), Et3N, 80 °C, 15 h.
(b) Compound 15
Ψ1 = 0.47 HOMO–1→LUMO – 0.42
–0.20 HOMO→LUMO – 0.18
Ψ2 = 0.54 HOMO→LUMO + 0.34
+0.19 HOMO–1→LUMO – 0.18
HOMO→LUMO+1
HOMO–1→LUMO+1
HOMO–1→LUMO+1
HOMO→LUMO+1
7
6
5
4
3
2
1
0
5
4
3
2
1
0
ε
ε
HOMO
LUMO
250
300
350
400
450
500
250
300
350
400
450
500
Wavelength / nm
Wavelength / nm
Figure 2. UV-Vis Absorption (Dashed Line) and PL Spectra
(Solid Line) of Compound 11 (Left: 3.51 © 10¹5 M) and 15
(Right: 2.11 © 10¹5 M) in Dichloromethane (λex = 280 nm).
prepared from benzonitrile 1213 by an analogous treatment
with Bu3SnN3, regioselectively reacted with 1-octyne at the
sterically more hindered bromo group to afford tricyclic
compound 14. During Sonogashira-Hagihara cross-coupling
reaction with 14 and 1-octyne, the similar demethylation and
intramolecular cyclization simultaneously progressed to afford
the corresponding tetracyclic molecule 15. These compounds
HOMO–1
LUMO+1
1
were characterized by H and 13C NMR spectroscopy, IR, and
ESI mass spectroscopy.14
Figure 2 shows the photoluminescence (PL) spectra of
compounds 11 and 15 in dichloromethane. The fluorescence
bands at high energy of compounds 11 and 15 appeared at 340.0
and 354.2 nm, respectively. Fluorescence quantum yields (Φf)
were Φf = 0.26 and 0.18 for 11 and 15, respectively, with
an absolute PL quantum yield measurement system (see
Experimental Section for details). To study the origin of the
PL emissions, the fluorescence lifetimes for compounds 11 and
15 were also measured in dichloromethane. It was revealed that
these compounds have each PL component, which decays as a
single luminescent component with lifetimes of nanosecond
order (11: 5.1 ns, 15: 7.2 ns, and -ex = 280 nm).
Figure 3. Grand State Wavefunctions of Compound 11 (a) and
15 (b) and Their Contributed MOs.
molecular orbitals (HOMOs) and lowest unoccupied molecular
orbitals (LUMOs) of 11 and 15 are representatively shown
in Figure 3 with the excited wavefunctions (The calculated
HOMO-LUMO levels, 11: HOMO ¹6.07 eV, LUMO ¹1.47 eV,
15: HOMO ¹6.10 eV, LUMO ¹1.36 eV).
The HOMO and LUMO are localized mainly on the central
isoquinoline moiety of 11 and 15, while in the HOMOs, the lone
pairs on the oxygen or nitrogen atoms play a pivotal role in
π-system expansion; in the LUMOs, the antibonding orbitals of
the central isoquinoline ring serve to promote the expansion of
the π-system. Excited state wavefunctions of 11 and 15 indicated
that the HOMO¹1 ¼ LUMO and HOMO ¼ LUMO+1 mainly
contributed to the first excited state (S0 ¼ S1) that greatly
provides the light emission and the HOMO ¼ LUMO became
the second excited state (S0 ¼ S2). Since compound 15 exhibits
a similarity in the calculated results, it means that the lumi-
Intriguingly, each radiative rate constant (11: 5.10 © 107
s
¹1, 15: 2.50 © 107 s¹1) and oscillator strength (11: 1.45 ©
108 s¹1, 15: 1.14 © 108 s¹1) was calculated from the above
fluorescence quantum yields and fluorescence lifetimes, and the
number of compound 11 was larger than that of compound 15.
To elucidate the origin of the observed fluorescence, TD-
DFT calculations were performed for 11 and 15 at the CAM-
B3LYP/6-31G* level using Gaussian09.15 The highest occupied
Chem. Lett. 2019, 48, 662–665 | doi:10.1246/cl.190150
© 2019 The Chemical Society of Japan | 663

nescence of the skeleton shown in Figure 3 will be enhanced by
the transition dipole moment along a long axis localized on π-
electronic systems (Figure 3). The simulated absorption spec-
trum, comprising a linear combination of oscillator strengths
obtained via TD-DFT calculations, shows good agreement with
the excitation profiles (see Supporting Information, Table S1).
Additionally, TD-DFT calculations also showed that the
transition moment of compound 11 differs from that of com-
pound 15 at the first excited state (see Supporting Information).
This means that positions of heteroarenes like tetrazole and furan
rings changed total transition moment of the molecules to effect
radiative rate constants and oscillator strengths.
In summary, we synthesized new structures, hetero-π-
conjugated compounds fused with tetrazole and furan rings, by
using repeated regioselective Sonogashira-Hagihara cross-cou-
pling of acetylenes and dibromoaryltetrazoles and intramolec-
ular nucleophilic cyclizations. Each tetracycle has PL compo-
nent, which decays through one relaxation pathway with
lifetimes of nanosecond order, respectively. TD-DFT calcula-
tions shows that the HOMOs and LUMOs are located mainly
in the central isoquinoline parts of each molecule. Thus, the
tetrazole-fused polycyclic compounds had delocalized and rigid
π-conjugated systems with fluorescence independent of the
positions of heterocycles. Further investigations on the optical
properties of the new structures and their application to organic
materials are underway.
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This work was supported in part by JSPS KAKENHI
Grant Numbers 26410112, 17H06347, and 17K05855, the
PRESTO Program on Molecular Technology and FRONTIER
(A.I.) from the Japan Science Technology Agency (JST) Grant
Numbers JPMJPR14KC and JPMJPR17P2, Tonen General
Sekiyu Research Foundation, The Asahi Glass Foundation,
Foundation for Interaction in Science & Technology, The
Iwatani Naoji Foundation, Tokuyama Science Foundation, and
Research Foundation for Electrotechnology of Chubu. We are
also grateful to Prof. Dr. Shohei Saito (Kyoto University) for
TD-DFT calculations and helpful discussions.
8
Supporting Information is available on https://doi.org/
10.1246/cl.190150.
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© 2019 The Chemical Society of Japan | 665