Microwave-assisted synthesis of N-hydroxyphthalimide derivatives

Article abstract of DOI:10.1081/SCC-200046498

N-Hydroxyphthalimide derivatives are readily obtained in good yields by the reaction of phthalic anhydrides with hydroxylamine hydrochloride in the presence of pyridine under microwave irradiation.

Full text of DOI:10.1081/SCC-200046498

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Microwave‐assisted Synthesis
of N‐Hydroxyphthalimide
Derivatives
a
a
Kazuhiro Sugamoto , Yoh‐ichi Matsushita , Yu‐hei
a
a
a
Kameda , Masahiko Suzuki & Takanao Matsui
a
Faculty of Engineering, University of Miyazaki,
Gakuen‐Kibanadai‐Nishi, Miyazaki, 889‐2192, Japan
Available online: 22 Jun 2006
To cite this article: Kazuhiro Sugamoto, Yoh‐ichi Matsushita, Yu‐hei Kameda,
Masahiko Suzuki & Takanao Matsui (2005): Microwave‐assisted Synthesis of
N‐Hydroxyphthalimide Derivatives, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 35:1, 67-70
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Synthetic Communications , 35: 67–70, 2005
Copyright # Taylor & Francis, Inc.
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1081/SCC-200046498
Microwave-assisted Synthesis of
N-Hydroxyphthalimide Derivatives
Kazuhiro Sugamoto, Yoh-ichi Matsushita, Yu-hei Kameda,
Masahiko Suzuki, and Takanao Matsui
Faculty of Engineering, University of Miyazaki, Miyazaki, Japan
Abstract: N-Hydroxyphthalimide derivatives are readily obtained in good yields by
the reaction of phthalic anhydrides with hydroxylamine hydrochloride in the
presence of pyridine under microwave irradiation.
Keywords: N-hydroxyphthalimide, microwave, phthalic anhydride
N-Hydroxyphthalimide and its derivatives are associated with various appli-
cabilities. In synthetic chemistry, N-hydroxyphthalimide acts as catalyst for
[
1–4]
radical oxidation of various organic compounds such as alkylbenzenes,
[3]
[1,3,4]
[3]
alkanes, or mediator for electrochemical
[6]
oxidation of olefins, amides, lactames, and alcohols. In biochemistry,
alkynes,
[
and sulfide,
[6]
5]
[7]
N-hydroxyphthalimide serves as mediator for laccase-assisted oxidation of
[
8]
[8]
[9]
[10]
methylbenzene, allyl alcohols, , benzyl alcohols, aryl alkanes,
and
In general, N-hydroxyphthalimide derivatives are prepared
by condensation between phthalic anhydride derivatives and hydroxylamine
[
11]
lignin model.
[12]
hydrochloride in the presence of excess amount of pyridine.
et al. reported a preparation of N-hydroxyphthalimide derivatives from
Wentzel
phthalic anhydrides and hydroxylamine hydrochloride in the presence of
[
13]
triethylamine in ethanol under reflux overnight.
However, the yield of
Received in Japan August 31, 2004
Address correspondence to Kazuhiro Sugamoto, Faculty of Engineering, University
of Miyazaki, Gakuen-Kibanadai-Nishi, Miyazaki 889-2192, Japan. Fax: þ81-985-58-
7
323; E-mail: sugamoto@cc.miyazaki-u.ac.jp

68
K. Sugamoto et al.
N-hydroxy-3-nitorophthalimide was only in 9% yield. Microwave irradiation
as an efficient thermal source has been applied to accelerate a variety of
[
organic reactions. Recently, microwave-assisted syntheses of N-substituted
14]
[
15–20]
phthalimides were reported.
To our knowledge, there are no reports for
synthesis of N-hydroxyphthalimides by the microwave irradiation method. In
this paper, we report the first example of the microwave-assisted synthesis of
N-hydroxyphthalimide derivatives.
When nitrophthalic anhydrides 1a and 1b were allowed to react with
.2 equiv. of hydroxylamine hydrochloride under the conventional heating
1
conditions, the yields of N-hydroxyphthalimides 2a and 2b were low
[
12]
(Table 1, entries 1 and 2).
On the other hand, under the microwave
irradiation method, the reaction of 1a with 1.2 equiv. of hydroxylamine
hydrochloride in the presence of 10 equiv. of pyridine took place smoothly
to give 2a in 50% yield (entry 3). On the reaction, the yield of 2a was
increased in increasing amount of hydroxylamine hydrochloride (entry 4).
The microwave irradiation brought about not only a considerable increase
in yield but also a remarkable reduction in time. Under similar conditions,
the reaction of 1b gave 2b in fairly good yield (entry 5). The reactions of
phthalic anhydrides bearing both electron-donating groups and electron-
withdrawing groups with hydroxylamine hydrochloride gave the corres-
ponding N-hydroxyphthalimide derivatives 2c–2h in high yields (Table 2,
Table 1. The reaction of nitrophthalic anhydrides with hydroxylamine hydrochloride
in pyridine under reflux or microwave irradiation
Conditions
NH
2
OH/
Pyridine/
equiv.
Yield
of 2/%
Entry Substrate
Method
equiv.
Time
72 h
72 h
1
2
3
4
5
1a
1b
1a
1a
1b
D(reflux)
D(reflux)
1.2
1.2
1.2
2.0
2.0
40
40
10
10
10
18
20
50
70
58
a
MW
MW
1 min ꢀ 7
1 min ꢀ 7
0.5 min ꢀ 4
a
a
MW
a
Microwave was irradiated by domestic microwave oven (2450 MHz, 500 W).

Microwave-assisted Synthesis of N-Hydroxyphthalimide Derivatives
Table 2. Microwave-assisted synthesis of N-hydroxyphthalimide derivatives
69
.
OR HCl
NH
2
Entry
Substract
Time/min
R
Yield of 2/%
1
2
3
4
5
6
7
1c
1d
1e
1f
0.5
0.5
H
H
93
81
81
90
70
99
90
0.5
0.5
H
H
1g
1h
1g
1.0 ꢀ 5
0.5
H
H
Bn
0.5 ꢀ 14
entries 1–6). Furthermore, the reaction of 1g using O-benzylhydroxylamine
hydrochloride instead of hydroxylamine hydrochloride afforded the corre-
sponding O-benzyl derivative in 90% yield (entry 7).
The present microwave irradiation reaction proceeds in short time and
gives the N-hydroxyphthalimides in high yields compared with the conven-
[
12,13]
tional heating methods.
The use of microwave oven to accelerate the
reaction rate is becoming an important and useful technique in organic
synthesis. We have developed microwave-assisted synthesis of N-hydro-
xyphthalimide derivatives.
TYPICAL PROCEDURE
Typical procedure for the preparation of N-hydroxy-4-nitrophthalimide
(
Table 1, entry 4):
A mixture of 4-nitorophthalic anhydride (386 mg, 2 mmol), hydroxyla-
mine hydrochloride (278 mg, 4 mmol), and pyridine (1.58 g, 20 mmol) in

70
K. Sugamoto et al.
3
00 cm round-bottom flask was irradiated in a domestic microwave oven
2
(2450 MHz, 500 W) for 1.0 min. The microwave irradiation was repeated
seven times until the N-hydroxy-4-nitrophthalimide was completely
consumed by monitoring TLC. The pyridine was removed under reduced
3
3
pressure. The residue was cooled to 08C, and then 1 mol/dm HCl (10 cm )
was added. The yellow precipitate was filtered, washed with water (10 cm ),
and dried in vacuo to give N-hydroxy-4-nitrophthalimide (290 mg, 70%).
3
ACKNOWLEDGMENT
This work was supported by Grants-in-Aid for Young Scientists (No.
1
5750037) from Japan Society for the Promotion of Science.
REFERENCES
1
2
. Einhorn, C.; Einhorn, J.; Marcadal, C.; Pierre, J. Chem. Commun. 1997, 447.
. Arends, I. W.C.E.; Sasidharan, M.; K u¨ hnle, A.; Duda, M.; Jost, C.; Sheldon, R. A.
Tetrahedron 2002, 58, 9055.
3
4
. Ishii, Y.; Sakaguchi, S. J. Synth. Org. Chem. Jpn. 2003, 61, 16A review.
. Minisci, F.; Recupero, F.; Gambarotti, C.; Punta, C.; Paganelli, R. Tetrahedron
Lett. 2003, 44, 6919.
5. Masui, M.; Hosomi, K.; Tsuchida, K.; Ozaki, S. Chem. Pharm. Bull. 1985, 33,
4798.
6
7
. Masui, M.; Hara, S.; Ozaki, S. Chem. Pharm. Bull. 1986, 34, 975.
. Gorgy, K.; Lepretre, J.; Saint-Aman, E.; Einhorn, C.; Einhorn, J.; Marcadal, C.;
Pierre, J. Electrochemica Acta 1998, 44, 385.
8
9
. Fritz-Lenghals, E.; Kunath, B. Tetrahedron Lett. 1998, 39, 5995.
. Fabbrini, M.; Galli, C.; Gentili, P. J. Mol. Catal. B: Enzym. 2002, 16, 231.
1
1
0. Cantarella, G.; Galli, C.; Gentili, P. J. Mol. Catal. B: Enzym. 2003, 22, 135.
1. Barreca, A. M.; Fabbrini, M.; Galli, C.; Gentili, P.; Ljunggren, S. J. Mol. Catal. B:
Enzym. 2003, 26, 105.
12. Fieser, L. F.; Fieser, M. Reagents for Organic Synthesis; Wiley: New York, 1967;
Vol. 1, pp. 485–486.
13. Wentzel, B. B.; Donners, M. P.J.; Alsters, P. L.; Feiters, M. C.; Nolte, R. J. M. Tet-
rahedron 2000, 56, 7797.
1
1
4. Loupy, A. Microwaves in Organic Synthesis; WILLEY-VCH, 2003.
5. Bose, A. K.; Manhas, M. S.; Ghosh, M.; Raju, V. S.; Tabei, K.; Urbanczyk-
Lipkowska, Z. Heterocycles 1990, 30, 741.
16. Khajavi, M. S.; Nikpour, F.; Hajihadi, M. J. Chem. Research (S) 1996, 96.
17. Chandrasekhar, S.; Takhi, M.; Uma, G. Tetrahedron Lett. 1997, 38, 10116.
18. Lima, L. M.; Barreiro, E. J.; Fraga, C. A.M. Syn. Commun. 2000, 30, 3291.
19. Vidal, T.; Petit, A.; Loupy, A.; Gedye, R. N. Tetrahedron 2000, 56, 5473.
20. Hajipour, A. R.; Mallakpour, S. E.; Imanzadeh, G. Indian J. Chem. 2001, 40B, 250.