Stereoselective multicomponent synthesis of [3-(5-substituted 2-methoxyphenyl)-5-aryl-2-phenyltetrahydro-4-isoxazolyl](2-thienyl)methanones via 1,3-dipolar cycloaddition

Article abstract of DOI:10.1002/jhet.5570420407

Three-component stereoselective synthesis of a set of new tetra substituted isoxazolidines from 5-substituted 2-methoxybenzaldehydes, N-phenylhydroxylamine and 1-(2-thienyl)-3-arylprop-2-en-1-ones has been achieved. The effect of microwave irradiation on the reaction under solvent-free conditions has also been investigated. The stereochemistry of the final products has been confirmed by NMR and single crystal X-ray analysis.

Full text of DOI:10.1002/jhet.5570420407

May-Jun 2005
515
Stereoselective Multicomponent Synthesis of [3-(5-Substituted
2-Methoxyphenyl)-5-aryl-2-phenyltetrahydro-4-isoxazolyl](2-
thienyl)methanones via 1,3-Dipolar Cycloaddition
a
b
a,
V. Sridharan, S. Pon Saravanakumar and S. Muthusubramanian *
a
Department of Organic Chemistry, Madurai Kamaraj University, Madurai-625 021, India
b
Department of Chemistry, S. N. College, Madurai-625 022, Indi
* Corresponding author, E mail: muthumanian2001@yahoo.com
Received October 11, 2004
Three-component stereoselective synthesis of a set of new tetra substituted isoxazolidines from 5-substi-
tuted 2-methoxybenzaldehydes, N-phenylhydroxylamine and 1-(2-thienyl)-3-arylprop-2-en-1-ones has been
achieved. The effect of microwave irradiation on the reaction under solvent-free conditions has also been
investigated. The stereochemistry of the final products has been confirmed by NMR and single crystal X-ray
analysis.
J. Heterocyclic Chem., 42, 515 (2005).
Introduction.
continuation of this work, we report the synthesis of a few
isoxazolidines with a thienyl ring using the multicompo-
nent tandem process. The 5-substituted 2-methoxyben-
zaldehydes (1) employed in this synthesis have been pre-
pared from the corresponding 4-substituted phenols [4].
The activated olefins, 1-(2-thienyl)-3-arylprop-2-en-1-
ones (2a-c) used for this work have been prepared from 2-
acetylthiophene and arylaldehydes in an equimolar mix-
ture with 10% sodium hydroxide solution at room temper-
ature in good yields.
The synthesis of isoxazolidines has been carried out in
toluene under reflux by mixing equimolar quantities of 5-
substituted 2-methoxybenzaldehydes (1), 1-(2-thienyl)-3-
arylprop-2-en-1-ones (2) and N-phenylhydroxylamine.
The reaction time varies between 10 to 15 hours and the
corresponding isoxazolidines (4) have been obtained in
good yields (Scheme 1). It should be noted that the initial
Multicomponent reactions (MCRs) are a promising,
"hot" field of chemistry, since they allow complicated mol-
ecules to be created using one reaction in a fast, efficient
and time efficient manner and they have found numerous
applications in synthetic organic chemistry by accessing
highly functionalized molecules in straightforward one
step transformations [1]. MCRs leading to interesting hete-
rocycles are particularly useful for the creation of diverse
chemical libraries of drug-like molecules for biological
screening, since the combination of three or more small
molecular weight building blocks in a single operation
leads to high combinatorial efficacy [2].
In recent years solvent-free organic synthesis attracted
the attention of organic chemists for a number of reasons,
the main one being the ability to synthesize large collec-
tions of compounds in few synthetic steps via the split and
mix technique [3-6]. Parallel to the multicomponent syn-
theses, microwave assisted solvent free syntheses have
also attracted attention [7-10].
Scheme 1
Isoxazolidines are biologically interesting molecules
[11,12], which have been generally synthesized from the
1,3-dipolar cycloaddition of nitrones with activated olefins
[13-16]. The organosulfur compounds assume importance
because of their pharmaceutical and industrial applications
[17-18]. The presence of both isoxazolidine and sulfur het-
erocycles in a molecule may lead to additional interesting
biological activities. In the present investigation, it has
been planned to synthesize several substituted isoxazo-
lidines with a 2-thienylmethanone group at the 4-position
by a multicomponent synthesis.
1
2
R
R
Results and Discussion.
4a
4b
4c
4d
4e
4f
C(CH ) Ph
H
Cl
OCH
H
Cl
3 2
We have recently reported the synthesis of a set of tetra
substituted isoxazolidines from C-(5-substituted 2-
methoxyphenyl)-N-phenyl nitrones with different acti-
vated olefins and their structural features have been ana-
lyzed by employing NMR and X-ray techniques [16]. In
C(CH ) Ph
3 2
C(CH ) Ph
3 2
3
C(CH ) CH CH
3 2
2
3
C(CH )
3 3
C(CH )
OCH
Cl
3 3
3
4g
CH(CH )
3 2

516
V. Sridharan, S. P. Saravanakumar and S. Muthusubramanian
Vol. 42
formation of nitrone followed by the reaction with chal-
cone should have occurred, in spite of the fact that the
chalcones are very good Michael acceptors towards nucle-
ophiles like N-phenylhydroxylamine. It is interesting that
when the nitrones were treated with chalcones in toluene,
the reaction is completed in the same time duration and
with the same yield (70-80%) as in the case of the multi-
component reaction.
The use of microwave irradiation has also been explored
with respect to the above synthesis. An equimolar mixture
of aldehyde, N-phenylhydroxylamine and chalcones has
been irradiated in a domestic microwave oven of power
1200 W in the absence of solvent resulting in reaction
times within 10 minutes with no enhancement in yield. It is
interesting to note that when the nitrones obtained from 5-
substituted 2-methoxybenzaldehydes (1) and N-phenylhy-
droxylamine have been irradiated in a microwave oven
with chalcone 2, the formation of the products are rela-
tively poor (~50%) compared to the multicomponent irra-
diation process. When the aldehyde, N-phenylhydroxy-
lamine and the chalcone are mixed together under solvent-
free condition, it becomes a viscous liquid, but when the
nitrone and the chalcone are mixed together, the mixture
remains as a solid. This may be the reason for higher yield
of the multicomponent reaction during microwave irradia-
tion. A mixture of the aldehyde, hydroxylamine and the
chalcone left at room temperature in the absence of
microwave irradiation does not form the isoxazolidine but
leads to the nitrone.
Figure 2. ORTEP diagram of [3-[2-methoxy-5-(1-methyl-1-phenylethyl)-
phenyl]-2,5-diphenyltetrahydro-4-isoxazolyl](2-thienyl)methanone (4a).
the geminal dimethyl group of the cumyl group. Due to the
diastereotopic nature of these two methyl groups, they
appear at slightly different positions. The methoxy group
of the 3-aryl ring appears at 3.36 ppm as a sharp singlet.
The three one hydrogen signals at 5.63 (d, J = 5.2 Hz), 4.12
(dd, J = 9.2, 5.2 Hz) and 5.28 (d, J = 9.2 Hz) could be
assigned to H-3, H-4 and H-5 of isoxazolidines moiety by
analogy [16]. The coupling constants between H-4 and H-
5 (J = 9.2 Hz) and that between H-3 and H-4 (J = 5.2
4,5
3,4
Hz) suggest that this pair of hydrogen atoms are trans to
each other. This has been confirmed from the single crystal
X-ray analysis (vide infra). The other aromatic hydrogen
resonances appeared between 6.6 to 8.0 ppm. The one
hydrogen doublet at 6.67 ppm (J = 8.4 Hz) is due to H-3"
since it is ortho to the methoxy group. The hydrogen H-6"
appears in the comparatively downfield region as a singlet
at 7.90 ppm due to van der Waals deshielding effect of the
adjacent cumyl and isoxazolidine moieties. The hydrogen
atom ortho to sulphur atom, H-5"' appears as a doublet
with coupling constant 4.8 Hz at 7.53 ppm. The other two
hydrogen atoms, H-3"' and H-4"' of the thienyl ring, appear
as a doublet at 6.89 ppm (J = 3.2 Hz) and doublet of dou-
blets at 6.85 ppm (J = 4.8, 3.2 Hz) respectively. The
upfield one hydrogen triplet at 6.96 ppm is due to H-4'
since it is para to the nitrogen atom. The remaining 15
hydrogen atoms appear as a multiplet between 7.07 to 7.30
In total, seven new isoxazolidines have been synthesized
and were characterized by their NMR spectra. The yields,
physical constants and reaction times are given in the
experimental section. Compounds 4b, e and g are formed
at a relatively faster rate, while 4c and f are formed slowly.
The reaction is highly regio- and stereoselective yielding
only one product in all the cases as observed in a related
system [16].
For a representative case (4a), the salient features of the
NMR and X-ray details are presented here. The 400 MHz
1
H NMR spectrum of 4a (Figure 1) has two singlets at 1.72
and 1.73 ppm each accounting for three hydrogens due to
13
ppm. The C NMR data are in accordance with the pro-
posed structure.
To confirm the assigned regio- and stereochemistry, sin-
gle crystal x-ray analysis has been carried out for 4a [19]
(Figure 2). The X-ray structure shows that the five mem-
bered isoxazolidine ring exists in an envelope form and the
torsional angles between N-C and C -C (2.50°) and C -
3
4
5
3
C and C -O (24.76°) clearly show that the oxygen atom,
4
5
rather than the nitrogen atom, is out of plane. The dihedral
Figure 1

May-Jun 2005
angles between the H -C and H -C and H -C and H -C
5
are in well agreement with the observed coupling con-
stants between these pairs suggesting that the molecule has
a similar stereochemistry in solution.
In conclusion, the multicomponent synthesis of isoxazo-
lidines has been found to be effective in the sense that it
decreases the overall reaction time and the number of steps
involved. Microwave irradiation has been found to be
more efficient. Regardless of the reaction conditions, the
regiochemistry and stereochemistry of the products are
unaltered.
Stereoselective Multicomponent Synthesis
517
6.67 (d, 1H, J = 8.4 Hz), 6.85 (dd, 1H, J = 4.8, 3.2 Hz), 6.89 (d,
1H, J = 3.2 Hz), 6.96 (t, 1H, J = 7.2 Hz), 7.07 – 7.29 (m, 15H),
3
3
4
4
4
4
5
13
7.53 (d, 1H, J = 4.8 Hz), 7.90 (s, 1H); C nmr*: δ 30.84, 30.94,
42.54. 54.43, 70.61, 70.89, 85.04, 109.34, 173.96, 121.34,
125.03, 125.51, 126.70, 126.88, 126.95, 127.95, 128.63, 128.69,
128.99, 129.62, 132.45, 134.39, 136.70, 143.22, 144.44, 150.93,
151.57, 153.74, 189.81.
* One aromatic carbon has merged with others
Anal. Calcd. for C H NO S: C, 77.25; H, 5.94; N, 2.50.
36 33
3
Found: C, 77.18; H, 5.99; N, 2.45.
5-(4-Chlorophenyl)-3-[2-methoxy-5-(1-methyl-1-
phenylethyl)phenyl]-2-phenyltetrahydro-4-isoxazolyl(2-
thienyl)methanone (4b).
EXPERIMENTAL
This compound was obtained as colorless crystals (petroleum
ether-ethyl acetate mixture), reaction time 11 h, yield 2.25 g
(76%), mp 153-154º; ir (potassium bromide): 3089, 2960, 1650,
1
13
Melting points are uncorrected. H and C NMR spectra were
-1
1596, 1490, 1411, 1355, 1241, 1081, 1022, 821, 767, 698 cm ;
recorded on a Bruker 400 MHz instrument in CDCl using TMS
3
1
H nmr: δ 1.71 (s, 3H), 1.72 (s, 3H), 3.35 (s, 3H), 4.05 (dd, 1H, J
as internal standard. Chemical shifts are given in parts per million
(δ-scale) and coupling constants are given in Hertz. The single
crystal X-ray data set was collected on a Nonius MACH3 Kappa
diffractometer with Mo Kalpha radiation (λ = 0.71073 A). The
structure was solved by direct methods using SHELXS-86 and
refined by full matrix least squares on F^2 by SHELXL-93. The
molecular views were realized by ZORTEP. IR Spectra were
recorded on a Jasco FT-IR instrument as KBr pellets. Column
chromatography was carried out in silica gel (60-120 mesh) using
pet ether-ethyl acetate as eluent.
= 9.2, 4.8 Hz), 5.27 (d, 1H, J = 9.2 Hz), 5.59 (d, 1H, J = 4.8 Hz),
6.67 (d, 1H, J = 8.8 Hz), 6.89 (dd, 1H, J = 4.0, 4.8 Hz), 6.94 –
6.98 (m, 2H), 7.05 (d, 2H, J = 8.0 Hz), 7.11 (dd, 1H, J = 8.8, 2.0
Hz), 7.16 – 7.31 (m, 11H), 7.55 (d, 1H, J = 4.8 Hz), 7.83, d, 1H, J
13
= 2.0 Hz); C nmr: δ 30.83, 30.89, 42.53, 54.45, 70.46, 70.88,
84.15, 109.39, 114.02, 121.53, 125.12, 125.64, 126.69, 126.86,
127.96, 128.05, 128.22, 128.85, 129.01, 129.35, 132.44, 134.42,
134.61, 135.40, 143.28, 144.29, 150.89, 151.39, 153.73, 189.54.
Anal. Calcd. for C H ClNO S: C, 72.77; H, 5.43; N, 2.36.
36 32
3
Found: C, 72.85; H, 5.49; N, 2.25.
Preparation of (E)-1-(2-Thienyl)-3-arylprop-2-en-1-ones (2).
[3-[2-Methoxy-5-(1-methyl-1-phenylethyl)phenyl]-5-(4-
methoxyphenyl)-2-phenyltetrahydro-4-isoxazolyl](2-
thienyl)methanone (4c).
General Procedure.
A mixture of 3 g of sodium hydroxide in 30 mL of water and
0.05 mole of 2-acetylthiophene in 15 mL of ethanol was cooled
in an ice bath. To this mixture, 0.05 mole of arylaldehyde was
added with constant stirring and the temperature was maintained
below 15 °C during the addition. This stirring was continued at
25 °C for 3 hours and the mixture was poured into crushed ice.
The separated solid was collected by filtration, dried and recrys-
tallised from ethanol.
This compound was obtained as colorless crystals (petroleum
ether-ethyl acetate mixture), reaction time 14 h, yield 2.30 g
(78%), mp 158-159º; ir (potassium bromide): 3087, 2962, 1654,
-1
1604, 1492, 1413, 1357, 1247, 1080, 1027, 825, 767, 700 cm ;
1
H nmr: δ 1.71 (s, 3H), 1.72 (s, 3H), 3.35 (s, 3H), 3.72 (s, 3H),
4.10 (dd, 1H, J = 9.2, 5.2 Hz), 5.20 (d, 1H, J = 9.2 Hz), 5.55 (d,
1H, J = 5.2 Hz), 6.65 (d, 1H, J = 8.4 Hz), 6.86 (dd, 1H, J = 4.8,
4.0 Hz), 6.90-7.11 (m, 5H), 7.18-7.32 (m, 11H), 7.56 (d, 1H, J =
4.8 Hz), 7.82 (d, 1H, J = 2.0 Hz).
Multicomponent Synthesis of Isoxazolidines (4).
General Procedure.
Anal. Calcd. for C H NO S: C, 75.35; H, 5.98; N, 2.38.
37 35
4
Found: C, 75.45; H, 6.10; N, 2.27.
A mixture of 0.005 mole of 5-substituted 2-methoxybenzalde-
hydes (1), 0.005 mole of (E)-1-(2-thienyl)-3-arylprop-2-en-1-
ones (2) and 0.005 mole of N-phenylhydroxylamine was refluxed
in 50 mL of dry toluene for the time period specified below. The
progress of the reaction was monitored by tlc. After completion
of the reaction, the solvent was evaporated under reduced pres-
sure and the product was separated by silica column using petro-
leum ether-ethyl acetate as eluent and recrystallised from petro-
leum ether-ethyl acetate mixture.
3-[2-Methoxy-5-(t-pentyl)phenyl]-2,5-diphenyltetrahydro-4-
isoxazolyl(2-thienyl)methanone (4d).
This compound was obtained as colorless crystals (petroleum
ether-ethyl acetate mixture), reaction time 10 h, yield 1.92 g
(75%), mp 128-129º; ir (potassium bromide): 3065, 2960, 1652,
-1
1594, 1492, 1411, 1355, 1240, 1075, 1022, 813, 763, 696 cm ;
1
H nmr: δ 0.75 (t, 3H, J = 7.5 Hz), 1.33 (s, 6H), 1.72 (q, 2H, J =
7.5 Hz), 3.38 (s, 3H), 4.12 (dd, 1H, J = 9.2, 5.2 Hz), 5.25 (d, 1H,
J = 9.2 Hz), 5.58 (d, 1H, J = 5.2 Hz), 6.65 (d, 1H, J = 8.4 Hz),
3-[2-Methoxy-5-(1-methyl-1-phenylethyl)phenyl]-2,5-diphenyl-
tetrahydro-4-isoxazolyl(2-thienyl)methanone (4a).
6.85 (dd, 1H, J = 4.8, 4.0 Hz), 6.88 (d, 1H, J = 4.0 Hz), 7.05-7.28
13
This compound was obtained as colorless crystals (petroleum
ether-ethyl acetate mixture), reaction time 12 h, yield 2.10 g
(75%), mp 112-113º; ir (potassium bromide): 3064, 2960, 1654,
(m, 11H), 7.56 (d, 1H, J = 4.8 Hz), 7.85 (d, 1H, J = 2.0 Hz);
C
nmr*: δ 9.20, 28.69, 36.96, 37.61, 54.40, 70.64, 71.08, 85.12,
109.35, 114.02, 121.34, 124.51, 125.66, 127.01, 127.94, 128.66,
129.03, 129.58, 132.37, 134.26, 136.87, 141.11, 144.62, 151.76,
153.65, 189.82.
-1
1596, 1492, 1413, 1355, 1241, 1064, 1024, 815, 763, 698 cm ;
1
H nmr: δ 1.72 (s, 3H), 1.73 (s, 3H), 3.36 (s, 3H), 4.12 (dd, 1H, J
= 9.2, 5.2 Hz), 5.28 (d, 1H, J = 9.2 Hz), 5.63 (d, 1H, J = 5.2 Hz),
* One aromatic carbon has merged with other

518
V. Sridharan, S. P. Saravanakumar and S. Muthusubramanian
Vol. 42
Anal. Calcd. for C H NO S: C, 75.11; H, 6.50; N, 2.74.
Found: C, 75.22; H, 6.58; N, 2.67.
(2) and 0.005 mole of N-phenylhydroxylamine was ground well
and the pasty reaction mixture was placed in a domestic
microwave oven of power 1200 W for 10 minutes. After comple-
tion of the reaction the mixture was recrystallised from petroleum
ether-ethyl acetate mixture to give compounds 4 in the following
yields: 4a, 1.96 g (70%); 4b, 2.22 g (75%); 4c, 2.33 g (79%); 4d,
2.00 g (78%); 4e, 2.13 g (80%); 4f, 1.98 g (75%); 4g, 2.08 g (80%).
32 33
3
[3-[5-(t-Butyl)-2-methoxyphenyl]-5-(4-chlorophenyl)-2-phenyl-
tetrahydro-4-isoxazolyl](2-thienyl)methanone (4e).
This compound was obtained as colorless crystals (petroleum
ether-ethyl acetate mixture), reaction time 9 h, yield 2.21 g
(83%), mp 173-174º; ir (potassium bromide): 3070, 2960, 1658,
-1
Acknowledgements.
1596, 1492, 1411, 1361, 1245, 1085, 1024, 825, 728, 694 cm ;
1
H nmr: δ 1.32 (s, 9H), 3.30 (s, 3H), 4.11 (dd, 1H, J = 9.2, 5.2
One of the authors (V.S) thanks CSIR, New Delhi for a Senior
Research Fellowship.
Hz), 5.22 (d, 1H, J = 9.2 Hz), 5.56 (d, 1H, J = 5.2 Hz), 6.66 (d,
1H, J = 8.4 Hz), 6.84 (dd, 1H, J = 4.8, 4.0 Hz), 6.89 (d, 1H, J =
4.0 Hz), 7.00-7.31 (m, 10H), 7.55 (d, 1H, J = 4.8 Hz), 7.83 (d,
1H, J = 2.0 Hz).
REFERENCES AND NOTES
Anal. Calcd. for C H ClNO S: C, 69.97; H, 5.68; N, 2.63.
Found: C, 70.05; H, 6.57; N, 2.70.
31 30
3
[1a] I. Ugi, A. Domling and W. Horl, Endeavour, 18, 115
(1994); [b] I. Ugi, A. Domling and B. Werner, J. Heterocyclic Chem.,
37, 647 (2000); [c] A. Jacobi von Wangelin, H. Neumann, D. Gordes,
S. Klaus, A. Strubing, and M. Beller, Chem. Eur. J., 9, 4283 (2003);
[d] G. Balme and M. N. Bossharth, Eur. J. Org. Chem., 4101 (2003);
[e] L. Weber, Curr. Med. Chem., 9, 1241 (2002); [f] S. L. Schreiber,
Science, 287, 1964 (2000); [g] A. Domling, and I. Ugi, Angew. Chem.
Int. Ed., 39, 3168 (2000); [h] A. Domling, Curr. Opin. Chem. Biol., 6,
306 (2002).
[2a] J. -M. Lehn, Nat. Rev. Drug Discovery, 1, 26 (2002); [b] S.
Otto, R. L. E. Furlan and J. K. M. Sanders, Drug Discov. Today, 7, 117
(2002); [c] L. Weber, Drug Discov. Today, 7, 143 (2002); [d] F. Modi,
Med. Res. Rev., 20, 304 (2000).
[3-[5-(t-Butyl)-2-methoxyphenyl]-5-(4-methoxyphenyl)-2-
phenyltetrahydro-4-isoxazolyl](2-thienyl)methanone (4f).
This compound was obtained as colorless crystals (petroleum
ether-ethyl acetate mixture), reaction time 15 h, yield 2.03 g
(77%), mp 137-138º; ir (potassium bromide): 3064, 2958, 1656,
-1
1602, 1490, 1413, 1359, 1247, 1074, 1027, 823, 765, 690 cm ;
1
H nmr: δ 1.33 (s, 9H), 3.28 (s, 3H), 3.72 (s, 3H), 4.12 (dd, 1H, J
= 9.2, 5.2 Hz), 5.22 (d, 1H, J = 9.2 Hz), 5.53 (d, 1H, J = 5.2 Hz),
6.64 (d, 1H, J = 8.4 Hz), 6.86 (dd, 1H, J = 4.8, 4.0 Hz), 6.91-7.15
(m, 4H), 7.20-7.35 (m, 7H), 7.55 (d, 1H, J = 4.8 Hz), 7.81 (d, 1H,
J = 2.0 Hz).
[3] K. Tanaka and F. Toda, Chem. Rev., 100, 1025 (2000).
[4] V. Sridharan, S. Muthusubramanian and S. Sivasubramanian,
Indian J. Chem., 43B, 857 (2004).
[5] V. Sridharan, S. Muthusubramanian and S. Sivasubramanian,
Synth. Commun., 34, 1087 (2004).
Anal. Calcd. for C H NO S: C, 72.84; H, 6.30; N, 2.65.
32 33
4
Found: C, 72.90; H, 6.45; N, 2.72.
[5-(4-Chlorophenyl)-3-(5-isopropyl-2-methoxyphenyl)-2-
[6] F. Toda and K. Tanaka, Tetrahedron Lett., 29, 551 (1988).
[7] R. S. Varma, J. Heterocyclic Chem., 36, 1565 (1999).
[8] N. Elander, J. R. Jones, S. -Y. Lu and S. Stone-Elander, Chem.
Soc. Rev., 29, 239 (2000).
[9] A. de la Hoz, A. Diaz-Ortis, A. Moreno and F. Langa, Eur. J.
Org. Chem., 3659 (2000).
[10] M. Larhed, C. Morberg and A. Hallberg, Acc. Chem. Res., 35,
717 (2002).
[11] K. V. Gothelf and K. A. Jorgensen, Chem. Rev., 98, 863
(1998).
[12] M. Frederickson, Tetrahedron, 53, 403 (1997).
[13] J. J. Tufariello, in 1,3-Dipolar Cycloaddition Chemistry, Vol 2,
A. Padwa, ed, Wiley-Interscience, New York, 1984, New York, 1984,
Vols. 1-2.
[14] K. M. Werner, J. M. de los Santos, S. M. Weinreb and M. A.
Shang, J. Org. Chem., 64, 686 (1999).
phenyltetrahydro-4-isoxazolyl](2-thienyl)methanone (4g).
This compound was obtained as colorless crystals (petroleum
ether-ethyl acetate mixture), reaction time 11 h, yield 2.05 g
(79%), mp 125-126º; ir (potassium bromide): 3064, 2960, 1656,
-1
1
1596, 1490, 1411, 1361, 1243, 1083, 1024, 825, 728 cm ; H
nmr: δ 1.27 (d, 6H, J = 6.8 Hz), 2.94 (sep, 1H, J = 6.8 Hz), 3.31
(s, 3H), 4.11 (dd, 1H, J = 9.2, 5.2 Hz), 5.27 (d, 1H, J = 9.2 Hz),
5.59 (d, 1H, J = 5.2 Hz), 6.71 (d, 1H, J = 8.4 Hz), 6.89 (dd, 1H, J
= 4.4, 4.0 Hz), 6.95-6.99 (m, 2H), 7.08 (d, 2H, J = 8.0 Hz), 7.15
(dd, 1H, J = 8.4, 2.0 Hz), 7.24-7.32 (m, 6H), 7.56 (d, 1H, J = 4.8
13
Hz), 7.79 (d, 1H, J = 2.0 Hz); C nmr*: δ 24.25, 24.28, 54.26,
70.23, 71.29, 84.50, 109.66, 113.77, 121.47, 124.71, 125.86,
128.08, 128.25, 128.84, 129.08, 129.61, 132.28, 134.51, 135.01,
141.46, 144.39, 151.58, 153.84, 189.40.
* One aromatic carbon has merged with other
[15] U. Chiacchio, A. Rescifina, D. Iannazzo and G. Romeo, J.
Org. Chem., 64, 28 (1999).
Anal. Calcd. for C H ClNO S: C, 69.55; H, 5.45; N, 2.70.
30 28
3
[16] V. Sridharan, S. Muthusubramanian, S. Sivasubramanian and
K. Polborn, Tetrahedron, 60, 8881 (2004).
[17] R. J. Huxtable, in Biochemistry of Sulfur, Plenum Press, New
York, 1986.
Found: C, 70.05; H, 5.51; N, 2.78.
Microwave-assisted Multicomponent Synthesis of Isoxazolidines
(4).
[18] B. Vittal Rao and V. V. Somayajulu, Indian. J. Chem., 19B,
232 (1980).
General Procedure.
A mixture of 0.005 mole of 5-substituted 2-methoxybenzalde-
hyde (1), 0.005 mole of (E)-1-(2-thienyl)-3-arylprop-2-en-1-one
[19] V. Sridharan, S. Pon Saravanakumar, S. Muthusubramanian,
K. Anitha and B. Sridhar, Acta. Cryst., E60, 2503 (2004).