ORGANIC
LETTERS
2003
Vol. 5, No. 20
3713-3715
Direct and Practical Synthesis of
2-Arylbenzoxazoles Promoted by
Activated Carbon
Yuka Kawashita, Natsuki Nakamichi, Hirotoshi Kawabata, and Masahiko Hayashi*
Department of Chemistry, Faculty of Science, Kobe UniVersity,
Nada, Kobe, 657-8501, Japan
Received July 25, 2003
ABSTRACT
2-Arylbenzoxazoles were directly synthesized from substituted 2-aminophenols and aldehydes in the presence of activated carbon (Darco KB)
in xylene under an oxygen atmosphere.
Benzoxazole ring moieties are often found in compounds
that exhibit biological activities, including antitumor, anti-
microbial, and antiviral properties.1
(OAc)410 have been used. However, all of these oxidants are
required in stoichiometric or excess amounts relative to their
respective substrates. Therefore, a more effective process is
needed.
In this paper, we report a practical synthesis of 2-aryl-
benzoxazoles starting from 2-aminophenols and aldehydes
under an oxygen atmosphere in the presence of activated
carbon (Darco KB, Aldrich, Inc.).
We recently reported the Pd/C-catalyzed oxidative aro-
matization of 1,3,5-trisubstituted pyrazolines and Hantzsch
1,4-dihydropyridines, which led to the formation of pyrazoles
and pyridines.11
There are two general methods for synthesizing 2-substi-
tuted benzoxazoles. One is the coupling of 2-aminophenols
with carboxylic acid derivatives, which is either catalyzed
by strong acids2 or requires microwave conditions.3 The other
is the oxidative cyclization of phenolic Schiff bases derived
from the condensation of 2-aminophenols and aldehydes. In
the latter reactions, various oxidants such as DDQ,4 Mn-
- 7
(OAc)3,5 PhI(OAc)2,6 Th+‚ClO4 , BaMnO4,8 NiO2,9 and Pb-
In seeking to extend this system to the synthesis of
2-arylbenzoxazoles by the oxidative cyclization of phenolic
Schiff bases, we first attempted to react 2-(4′-methoxyben-
zylideneamino)phenol (1) with 20 wt % of 10% Pd/C at 80
°C in acetic acid, which are suitable conditions for the
reaction of pyrazolines and Hantzsch dihydropyridines.
However, the desired 2-(4′-methoxyphenyl)benzoxazole (2)
was obtained in quite low yield (9%), and the main product
was a hydrolysis product of the starting Schiff base 1.
After screening various catalysts and solvents, we found
that the above oxidative cyclization proceeded even in the
absence of palladium catalyst in m-xylene. As shown in Table
(1) (a) Deluca, M. R.; Kerwin, S. M. Tetrahedron Lett. 1997, 38, 199-
202. (b) Sato, Y.; Yamada, M.; Yoshida, S.; Soneda, T.; Ishikawa, M.;
Nizato, T.; Suzuki, K.; Konno, F. J. Med. Chem. 1998, 41, 3015-3021.
(c) Temiz, O.; Oren, I.; Sener, E.; Yalcin, I.; Ucarturk, N. Farmaco 1998,
53, 337-341. (d) Sato, S.; Kajiura, T.; Noguchi, M.; Takehana, K.;
Kobayashi, T.; Tsuji, T. J. Antibiot. 2001, 54, 102-104.
(2) Terashima, M.; Ishii, M.; Kanaoka, Y. Synthesis 1982, 484-485.
(3) (a) Bourgrin, K.; Loupy, A.; Soufiaoui, M. Tetrahedron 1998, 54,
8055-8064. (b) Pottorf, R. S.; Chadha, N. K.; Katkevics, M.; Ozola, V.;
Suna, E.; Ghane, H.; Regberg, T.; Player, M. R. Tetrahedron Lett. 2003,
44, 175-178.
(4) Chang, J.; Zhao, K.; Pan, S. Tetrahedron Lett. 2002, 43, 951-954.
(5) Varma, R. S.; Kumar, D. J. Heterocycl. Chem. 1998, 35, 1539- 1540.
(6) Varma, R. S.; Saini, R. K.; Prakash, O. Tetrahedron Lett. 1997, 38,
2621-2622.
(7) Park, K. H.; Jun, K.; Shin, S. R.; Oh, S. W. Tetrahedron Lett. 1996,
37, 8869-8870.
(8) Srivastava, R. G.; Venkataramani, P. S. Synth. Commun. 1988, 18,
1537-1544.
(10) Stephens, F. F.; Bower, J. D. J. Chem. Soc. 1949, 2971-2972.
(11) Nakamichi, N.; Kawashita, Y.; Hayashi, M. Org. Lett. 2002, 4,
3955-3957.
(9) Nakagawa, K.; Onoue, H.; Sugita, J. Chem. Pharm. Bull. 1964, 12,
1135-1138.
10.1021/ol035393w CCC: $25.00
© 2003 American Chemical Society
Published on Web 09/04/2003