Synthesis, characterization, and biological studies of novel isoxazolidines: 1,3-Dipolar cycloaddition reactions

Article abstract of DOI:10.1081/SCC-120004084

1,3-Dipolar cycloaddition reaction of nitrones to olefins is of synthetic interest. In the present work, isoxazolidines have been synthesized in high yield via intermolecular cycloaddition of N-arylnitrone with monosubstituted olefins and are employed for

Full text of DOI:10.1081/SCC-120004084

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SYNTHESIS, CHARACTERIZATION, AND BIOLOGICAL
STUDIES OF NOVEL ISOXAZOLIDINES: 1,3-DIPOLAR
CYCLOADDITION REACTIONS
a
a
b
B. K. Vishu Kumar , K. Dhananjaya & K. S. Rangappa
a
Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore, 570
06, India
0
b
Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore, 570
06, India
0
Version of record first published: 17 Oct 2011.
To cite this article: B. K. Vishu Kumar , K. Dhananjaya & K. S. Rangappa (2002): SYNTHESIS, CHARACTERIZATION, AND
BIOLOGICAL STUDIES OF NOVEL ISOXAZOLIDINES: 1,3-DIPOLAR CYCLOADDITION REACTIONS, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 32:12, 1887-1890
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SYNTHETIC COMMUNICATIONS, 32(12), 1887–1890 (2002)
SYNTHESIS, CHARACTERIZATION,
AND BIOLOGICAL STUDIES OF NOVEL
ISOXAZOLIDINES: 1,3-DIPOLAR
CYCLOADDITION REACTIONS
B. K. VishuK um ar, K. Dhananjaya,
and K. S. Rangappa*
Department of Studies in Chemistry, University of
Mysore, Manasagangotri, Mysore-570 006, India
ABSTRACT
1,3-Dipolar cycloaddition reaction of nitrones to olefins is
of synthetic interest. In the present work, isoxazolidines
have been synthesized in high yield via intermolecular cyclo-
addition of N-arylnitrone with monosubstituted olefins and
are employed for biological evaluation.
Key Words: Synthesis; Isoaxazolidines; 1-3Dipolar cyclo-
addition; Biological studies
The chemistry of nitrones and their cycloadducts in particular has
[
1,2]
attracted considerable attention both from synthetic
and biological
stand point of view. Cycloaddition reactions of nitrones to unsaturated
substrates constitute the best procedure for the construction of isoxazolidine
*
Corresponding author. Fax: 0821-518835; E-mail: rangappaks@yahoo.com
887
1
Copyright & 2002 by Marcel Dekker, Inc.
www.dekker.com

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2002 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
1
888
VISHU KUMAR, DHANANJAYA, AND RANGAPPA
[3–5]
ring system
with regio and stereo chemical control. The present paper
reports a new 1,3-dipolar cycloaddition reaction between C-anthranyl-
N-phenyl nitrone with olefins (i–viii), which provides a novel method for
[
6]
the synthesis of isoxazolidines. This method is very simple, rapid and
convenient.
RESULTS AND DISCUSSION
The generation of N-arylhydroxylamine 2a from N-arylnitro com-
pound 1a is highly dependent on the reaction conditions. Best results
were achieved by using a mild reducing agent Zn dust/NH Cl mixture in
4
a heterogeneous aqueous medium at pH 7.0 and it was adjusted, maintained
by adding small amount of NH OH. Since the reaction is exothermic, care
4
was taken while adding Zn dust in such a way that the reaction temperature
ꢀ
lies in the range of 50–60 C throughout the process. The product is obtained
in good yield at this temperature and pH with mild reducing agent.
[7]
[8]
Since nitrones are synthetic intermediates and traping agents, this
N-arylhydroxylamine is utilized for the synthesis of nitrone 3a by condensa-
tion with 9-anthraldehyde in dichloromethane at room temperature in dark.
TLC monitoring of reaction mixture confirmed that a period of 24 h was
required for the completion of the reaction and to obtain the product in
good yield (92%). On removal of solvent nitrone was obtained, which was
stored under dark in order to avoid decomposition and hydrolysis. Thus, in
the present context because of biological interest isoxazolidines have been
synthesized via 1,3-dipolar cycloaddition reaction of N-arylnitrone 3a with
olefins.
These reactions were carried out with equimolar amount of reactants
in toluene. It has been shown that a period of 20–30 h was necessary for the
completion of the reaction and to obtain the products in good yield. The
reaction mixture was chromatographed over silica gel column and obtained

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2002 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
1
,3-DIPOLAR CYCLOADDITION REACTIONS
1889
pure product. The structure of the synthesized compounds was assigned
1
on the basis of C, H and N analysis, IR and H NMR spectral data.
The compounds were evaluated for antimicrobial screening against
Gram positive, Gram negative bacteria and fungal strain, showed significant
inhibition.
EXPERIMENTAL SECTION
General Procedure for the Synthesis of
C-Anthranyl-N-phenyl Nitrone: 3a
Equimolar solution of N-arylhydroxylamine 2a and 9-anthraldehyde
in minimum volume of dichloromethane were kept at room temperature in
dark. The reaction was monitored by TLC and found that the time required
for the completion of reaction is 24 h. Chromatographed over silica gel,
evaporated off the solvent and thus obtained needle like crystals were recrys-
tallised from n-hexane. This nitrone was successfully used to synthesize new
N-aryl isoxazolidines.
General Procedure for the Synthesis of Novel
Isoxazolidines: 4a (i–viii)
Equimolar mixture of nitrone 3a and different alkene were dissolved
in 10 ml of toluene. The reaction mixture was refluxed till the reaction

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2002 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
1
890
VISHU KUMAR, DHANANJAYA, AND RANGAPPA
completes, which was monitored by TLC. The pure product was separated
by using silica gel column.
SUPPLEMENTARY MATERIAL AVAILABLE
1
Tabulations of IR, H NMR and C, H and N analysis of 3a and 4a
i–viii) (4 pages). Ordering information is given in any current masthead
(
page.
ACKNOWLEDGMENTS
We are grateful to Council of Scientific and Industrial Research
CSIR), Govt. of India, for financial support under the project vide
(
No. 01 (1458)/97/EMR-II.
REFERENCES
. Padwa, A. Angew. Chem. Int. Ed. Engl. 1976, 15, 123and references
cited therein.
1
2
. 1,3-Dipolar Cycloaddition Chemistry, Vol. 1 & 2, Padwa, A., Ed.;
John Wiley & Sons: New York, 1984 and references cited therein.
. Black, D.St.C.; Crozier, R.F.; Davis, C. Synthesis 1975, 4, 205.
. Banerji, A.; Sahu, A. J. Scient. Indus. Res. 1986, 45, 355.
. Torsell, K.B.G. Nitrile Oxide, Nitrones and Nitronates in Organic
Synthesis; VCH: New York, Weinheim, 1988.
3
4
5
6. Ph.D. Thesis Submitted to the University of Mysore by Vishukumar,
B.K., 2001.
7. Torsell, K.B.G. Nitrile Oxides, Nitrones and Nitronates in Organic
Synthesis; VCH Publishers: New York, 1988; Tufariello, J.J. In
1,3-Dipolar Cycloaddition Chemistry, Vol. 2, Padwa, A., Ed.; Wiley:
New York, 1984; p.83.
. Barton, D.H.R.; Beaton, J.M. J. Am. Chem. Soc. 1960, 82, 2641; ibid,
8
1961, 83, 4083.
Received in the Netherlands June 27, 2001