4
ΦF value, although the degree of change was dependent on
the 2-substituents. It seems likely that, although most of the
2-substituents basically increase the ΦF value, when the 2-
substituent is a strong electron-withdrawing group with a
longer conjugation length, the ΦF value would decrease.
Having clarified the substituent effect of the methyl
group at the C6-position, we were curious about the other
functional groups, such as the electron-withdrawing group
and aromatic group. Thus, epoxide 9f containing methyl
ester was synthesized, and 9f was subjected to similar
sequential reactions, leading to 1f, which possessed a methyl
ester at the 6-position. The epoxide-opening reaction of 9f
proceeded at 40 °C to give 10f in 67% yield, and the
subsequent treatment of 10f with acetic anhydride in TEA
directly afforded 1f in 40% yield without KHMDS treatment.
Although the 6-methyl ester analog 1f was obtained, the
fluorescence of 1f was too small to measure the fluorescence
quantum yield. The inductive effect from the electron-
withdrawing group at the C6-position probably disturbs the
charge transfer from the triazapentalene skeleton to the 2-
substituent. On the other hand, epoxides containing phenyl
group instead of the methyl ester did not afford the bicyclic
ions 10 under various reaction conditions.
based on 1,3a,6a-triazapentalenes by taking advantage of the
substituent effects revealed herein
This work was supported by JSPS KAKENHI Grant
Numbers JP16H01156 in Middle Molecular Strategy and
JP16H03292, 15K18830. K.N. is grateful to the Naito
Foundation, Yamada Foundation, the Kurata Foundation,
and the Uehara Memorial Foundation for support through a
Research Fund. A. M. is grateful to the fellowship from
Suntory Bioorganic Research Institute.
Supporting
Information
is
available
on
http://dx.doi.org/10.1246/cl.******.
References and Notes
1
(a) J. Shinar, Ed. Organic Light-Emitting Devices, Springer, New
York, 2004. (b) B. Valeur, Molecular Fluorescence, WILEY-
VCH, Weinheim, 2002. (c) R. K. Willardson, E. Weber, G.
Mueller, Y. Sato, Electroluminescence 1, Semiconductors and
Semimetals Series, Academic Press, New York, 1999.
M. Ueda, Chem. Lett. 2012, 41, 658, and references are therein.
J. Chan, S. C. Dodani, C. J. Chang, Nat. Chem. 2012, 4, 973, and
references are therein.
2
3
4
5
K. Namba, A. Osawa, S. Ishizaka, K. Kitamura, K. Tanino, J. Am.
Chem. Soc. 2011, 133, 11466.
R. Cai, D. Wang, Y. Chen, W. Yan, N. R. Geise, S. Sharma, H. Li,
J. L. Petersen, M. Li, X. Shi, 2014, 50, 7303.
CO2Me
CO2Me
CO2Me
HO
O
6
6
7
B. Verbelen, W. Dehaen, Org. Lett., 2016, 18, 6412.
R. Kamada, F. Tano, F. Kudoh, N. Kimura, Y. Chuman, A.
Osawa, K. Namba, K. Tanino, K. Sakaguchi, PLoS ONE 2016, 11,
e0160625.
-OTf
+
1) TfOH
Ac2O, TEA
40%
+
N
N
N
N
N
N
2) tBuOH,
N
N
-
N
rt to 40 °C
67%
2
C6H4Ph
C6H4Ph
8
9
J. Sawada, A. Osawa, T. Takeuchi, M. Kaneda, S. Oishi, N. Fujii,
A. Asai, K. Tanino, K. Namba, Bioorg. Med. Chem. Lett. 2016,
26, 5765.
K. Namba, A. Osawa, A. Nakayama, A. Mera, F. Tano, Y.
Chuman, E. Sakuda, T. Taketsugu, K. Sakaguchi, N. Kitamura, K.
Tanino, Chem. Sci. 2015, 6, 1083.
C6H4Ph
9f
10f
1f (no fluorescence)
λmaxabs (nm) 334
λmaxem (nm)
433
Scheme 3. Synthetic effort for 6-methoxycarbonyl- and 6-phenyl-
1,3a,6a-triazapentalene 6a.
10
11
12
13
14
K. Namba, A. Mera, A. Osawa, E. Sakuda, N. Kitamura, K.
Tanino, Org. Lett. 2012, 14, 5554.
A. Nakayama, S. Nishio, A. Otani, A. Mera, A. Osawa, K. Tanino,
K. Namba, Chem. Pharm. Bull., 2016, 64. 830.
A. P. Demchenko, Advanced Fluorescence Reporters in
Chemistry and Biology I, Springer, Berlin, 2010.
H. Koga, M. Hirobe, T. Okamoto, Tetrahedron Lett. 1978, 19,
1291.
Treatment of 1-azidobutane-2,3-diol with 2.2 equiv of Tf2O and
5.0 equiv of 2,6-lutidine afforded small amount of 2b in less than
20% yield, whereas gram scales of 2a was obtained in 82% yield
under the similar condition. The methyl group of 2b readily
causes an elimination of resulting triflate to give low-molecular-
weight azide derivatives. Thus, as the preparation of 2b is
potentially hazardous, only small scale of 2b was synthesized.
A. Osawa, A. Mera, K. Namba, K. Tanino, Synlett, 2013,24, 207.
Introductions of other leaving groups such as mesyl, tosyl, and
triflate gave complex mixture, and the desired 6a was not detected.
For large Stokes Shift dyes, see (a) J. R. Lakowicz, Principles of
Fluorescence Spectroscopy, 3rd ed.; Springer: New York, 2006.
In conclusion, various 2,6-disubstituted-1,3a,6a-
triazapentalenes were synthesized and their fluorescence
properties were revealed. The conventional cascade reaction
using azidoditriflate was not applicable to 2,6-disubstituted-
1,3a,6a-triazapentalenes, and thus a new synthetic method
using an epoxide-opening reaction followed by elimination
of the resulting hydroxyl group was established. Although
the yields of 2,6-disubstituted-1,3a,6a-triazapentalenes were
not high, the substituent effect at the C6-position of 1,3a,6a-
triazapentalens was elucidated for the first time. The
electron-donating groups at the C6-position, such as the
15
16
methyl group, induced
a longer-wavelength shift of
fluorescence maximum and changed the quantum yield in a
manner dependent on the 2-substituent, i.e., the 6-methyl
group changed both the fluorescence wavelength and
fluoresce quantum yield differ from those observed with the
4- and the 5-methyl groups. On the other hand, electron-
withdrawing groups such as methyl ester quenched the
fluorescence of 1,3a,6a-triazapentalenes. Based on our
elucidation of the substituent effect at the remaining 6-
position in this study, the substituent effects at all positions
17
of
1,3a,6a-triazapentalenes
were
defined.
Further
investigations are currently underway in our laboratory to
develop novel functional fluorescent organic molecules