Synthesis and Identification of Some New Isoxazolidine Compounds by 1,3 - Dipolar Cycloaddition Reaction of Nitrones and Olefin by Faeza A. Almashal

Journal of Basrah Researches ((Sciences))
Volume 37.Number 2
15 April ((2011))
Synthesis and Identification of Some New Isoxazolidine compounds by 1,3Dipolar Cycloaddition Reaction of Nitrones and Olefin
Faeza A. Almashal
Department of Chemistry. College of Education
University of Basrah. Basrah-Iraq
ISSN 1817 2695
(Received 16 February 2011; Accepted 30 March 2011)
Abstract:
The 1,3-dipolar cycloaddition reaction of different nitrones(a,b and c) with N-(p-acetyl phenyl)
maleimide under reflux condition proceed isoxazolidines (d,e and f) in good yields . The reaction
mixture was followed by TLC.The yields of products following recrystallization from hexane were be
in the order of 42%-65%.mp., IR,mass-spectra were used for identification of these compounds.
Key Words: Isoxazolidine, Nitrones, 1,3-Dipolar, Cycloaddition.
Introduction:
The nitrone-olefin 1,3-dipolar cycloaddition
is a powerful reaction in that it can create as
many as three new contiguous stereogenic
centers in a single step. Based on an evaluation
of the nitrone cycloaddition[1]. Nitrones are
important synthetic intermediates that have been
used extensively in organic chemistry[28].Some nitrones have been used for the
trapping and identifcation of free radicals[8],
particularly in biological studies [5]. Various
synthetic approaches for the synthesis of
nitrones have been reported by several groups
[919].The most general approach for the
.
preparation of nitrones is the condensation

reaction between aldehydes or ketones with Nmonosubstituted hydroxylamines [7]. Nitrones
can react as 1,3-dipolar species with a large
variety of dipolarophiles to give deferent
products. One of the most synthetic applications
of nitrones is their use as 1,3-dipoles in
cycloaddition reactions to olefins for preparation
isoxazolidines[20]. Isoxazolidines are known to
possess antibacterial activity[21-23]. The
purpose of the present work is synthesis some
new isoxazolidines by 1,3-dipolar cycloaddition
reaction
of
nitrones
and
olefins
Experimental
Melting points were determined with an
electronthermal digital point apparatus type
GallenKamp. IR spectra were obtained using
Shimdzu FT-IR84005 spectrophotometer at
science college . All the spectra were recoreded
as KBr discs.The mass spectra were obtained by
using a Helwett Packard University of Cairo,
Faculty of science, Micro Analytical center TLC
is performed on silica gel 60 F254 sheet layer
(Merck).The materials from Merk , Ridel and
Fluka ) companies.
General Procedure
Nitrones[8]
For
Preparation
Nitrones were synthesized using the

condensation reaction between corresponding
aldehydes and N-benzyl hydroxylamine in
ethanol solution to give (a,b and c) .
Synthesis of maleamic acid[24]:
To a solution of
2.8gm (0.3mole) paminoacetophenone in 5ml ether, a solution of
2.94gm (0.3mole) of malicanhydride in 5ml
ether was added drop wise with stirring at room
temperature for 30 min., the solid precipitate
was filtered off, yielding 85% with melting
point (198-200)o C.
of
128
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Synthesis and Identification of Some New Isoxazolidine compounds by 1,3-Dipolar Cycloaddition
2-phenyl -5-(p-acetyl phenyl)-3-(4-methoxy

phenyl) -4,6dioxo-2,3,3a,4,6,6a
hexahydropyrrolo[3,4-d] isoxazoles(e).
Synthesis
of
N-(p-acetyl
phenyl)
maleimide[25]:
Maleamic acid 4g(0.02mole) was heated on
steam bath in 8.5ml(0.0898mole) of acetic
anhydride
in
the
presence
of
0.82gm(0.0099mole) sodium acetate. Acetic
anhydride was hydrolyzed with iced water and
the reaction mixture was left for 1 hr. at room
temperature. The crystalline product was
filtered, washed 3 times with 25ml cooled
distilled water then with petrolium ether,
recrystallized from cyclohexane to get N-(pacetyl phenyl) maleimides 45% with melting
point (151-153)oC.
2-phenyl -5-(p-acetyl phenyl)-3-(4-nitro

hexahydropyrrolo[3,4-d] isoxazoles(f).
General procedure for the 1,3- dipolar
cycloaddition of nitrones to N-(p-acetyl
phenyl) maleimide
The nitrones (a,b and c) 0.1 mmol were
refluxed with 0.1 mmol of N-(p-acetyl phenyl)
maleimides in 10 ml benzene for 3 hrs ,the
reaction mixture was followed by TLC.The
solution then was evaporated ,the crystalline
product was crystallized to give isoxazolidine
compounds(d ,e and f) ,as shown in Table1
Synthesis of:
2-phenyl -5-(p-acetyl phenyl)-3-(4-chloro
hexahydropyrrolo[3,4-d] isoxazoles(d).
Table 1: Physical Properties of Nitrones and Isoxazolidines.

Compounds
M.p C 0
Rf
Solvent
Recry.
156-157
0.4
Ethanol
115-116
0.63
Ethanol
190-191
0.61
Ethanol
225-226
0.54
Hexane
184-185
0.45
Hexane
250-251
0.65
Hexane
Eluents
Methanol:Toluene
3:7
Methanol:Toluene
3:7
Methanol:Toluene
3:7
Methanol:Toluene
3:7
Methanol:Toluene
3:7
Methanol:Toluene
3:7
Yield
55.6%
42%
46%
65%
51%
54%
129
Almashal
Results and Discussion

Nitrones were prepared according to the
published method as far as possible[8].The
condensation reaction between the appropriate
aldehyde and phenylhydroxylamine offered the
desired nitrones in good yields.
1,3-Dipolar cycloaddition reaction of nitones to

olefin Scheme 1, which was carried out under
reflux condition and diferent times, aforded
isoxazolines d-f in average yield and high
selectivity Table 1.
X = - Cl ,- OCH3 , -NO2
Scheme 1:1,3-Dipolar cycloaddition reaction of nitones to olefin
The anti-isoxazolidines ( d-f ) arise from the

cycloaddition of trans nitrone through the endo
transition state or the cis-nitrone through the

exo-mode
Infrared Spectra
The IR Spectra of the studied prepared
compounds as KBr discs and most of their
representative spectra are shown in Table 2 .
The IR-spectra of the nitrones (a,b and c)
showed the strong absorption bands at 1050,
1072 and 1085 cm-1 that are characteristic of the
(NO) stretching, the spectrum showed weak
bands due to the (C=N) stretching vibration at
1600, 1610 and 1605 cm-1, while the IR spectra
of isoxazolidine compounds (d, e and f) showed
the absorption bands related to (N-O), (C-N) and

(C-O) stretching.Also the spectra showed strong
absorption bands between the range (1720-1725)
cm-1 for the (CO) stretching.
In general , it is clear that the frequency of the
(C=N) band which related to nitrones is
disappear in isoxazolidine compounds. The
suggest structures indicat that the reaction was
take place the cycloaddition.
Mass spectra
All
the
spectra
of
isoxazolidines
compounds(d,e
and
f)
show
similar
fragmentations pattern. . All the compounds
exhibit parent peaks, and the base peaks of the
compounds are dependent on the derivatives of

benzaldehyde.
The mass spectra of all compounds show the
presence of the N-(p-acetyl phenyl) maleimide
cation 215 and the ions M+ could be taken as
130
evidence that the bond between O-1 atom and

C-6a atom has an -cleavage of the molecular
ions followed by the heterolysis fission between
the C-3 atom and C-3a atom, as shown in

scheme 2.
Table 3 shows the import fragments in the mass
spectra of the isoxazolidines compounds. As
shown in Figures 1-3 .
Table 2 : IR Spectral Data of Nitrones and Isoxazolidines cm-1 .
Com.
C=CAr.Str
C=NStr.
C-N Str.
C-OStr.
N-O Str.
C=O Str.
1440-1490
1600(w)
1140(w)
1065(s)
1430-1540
1610(w)
1288(s)
1165(s)
1450-1530
1605(w)
1170(w)
1080(m)
1455-1480
1325(m)
1232(w)
1062(s)
1720(s)
1440-1485
1329(m)
1225(w)
1069(m)
1721(s)
1392-1490
1295(m)
1135(m)
1030(m)
1725(s)
Table 3 : Import fragments in the mass spectra of the prepared compounds
symb.
m/z
Parent ion
M+
231
RC
O+
phN+
ph+
phN+CR
139
91
77
215
446
442
227
135
91
77
215
457
242
150
91
77
215
214
210
225
131
Almashal
scheme 2: The major fragmentation paths of isoxazolidine compounds
132
Figure 1 : The mass spectrum of compound ( d )
133
Almashal
Figure 2 : The mass spectrum of compound ( e )
134
Figure3 : The mass spectrum of compound ( f )
135
Almashal
Conclusion:
1)This study is concerned with synthesis of
isoxazolidine compounds and consists of three
stages:
a.Synthesis of nitrones
b.Synthesis of N-(p-acetyl phenyl) maleimide.
c.Dipolar cycloaddition reactions
2) By comparing the IR- spectra of nitrones (a-c)
with that of isoxazolidine compounds (d-f), we
observed that the bands attributed to the

(CH=N+O-) group disappeared in the spectra of
isoxazolidine compounds Also the spectra of
isoxazolidine showed strong absorption bands
between the range (1720-1725) cm-1 for the (C=O)
stretching , which means that the cycloaddition of
nitrones with olefins occurred.
3) All the compounds exhibit parent peaks.
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136
-31

/
/ -
-31 ) (a,b,c )-- (

. 42%-65%
.
137

Synthesis and Identification of Some New Isoxazolidine Compounds by 1,3 - Dipolar Cycloaddition Reaction of Nitrones and Olefin by Faeza A. Almashal

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Journal of Basrah Researches ((Sciences))

preparation of nitrones is the condensation

Nitrones were synthesized using the

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