Enhanced rate of intramolecular nitrile oxide cycloaddition and rapid synthesis of isoxazoles and isoxazolines

Article abstract of DOI:10.1007/s00706-010-0323-3

An enhanced rate of intramolecular nitrile oxide cycloaddition and hence a rapid synthesis of isoxazoles and isoxazolines is described. Formation of nitrile oxides from oximes using only 1 or 2 Eq (equivalents) of aqueous sodium hypochlorite solution is also described. Springer-Verlag 2010.

Full text of DOI:10.1007/s00706-010-0323-3

Monatsh Chem (2010) 141:763–771
DOI 10.1007/s00706-010-0323-3
ORIGINAL PAPER
Enhanced rate of intramolecular nitrile oxide cycloaddition
and rapid synthesis of isoxazoles and isoxazolines
•
Brindaban Roy Rajendra Narayan De
Received: 11 November 2009 / Accepted: 3 May 2010 / Published online: 27 May 2010
Ó Springer-Verlag 2010
Abstract An enhanced rate of intramolecular nitrile
oxide cycloaddition and hence a rapid synthesis of isox-
azoles and isoxazolines is described. Formation of nitrile
oxides from oximes using only 1 or 2 Eq (equivalents) of
aqueous sodium hypochlorite solution is also described.
versatile methods for the preparation of synthetically useful
isoxazolines/isoxazoles [11, 12]. There are several methods
for the preparation of nitrile oxides [10, 11, 13–19]. One of
those methods is the reaction of aldoximes with alkali
hypochlorite. Existing reports describe that an excess, up to
40 Eq (equivalents), of aqueous sodium hypochlorite
[20–22] is required to give nitrile oxides from oximes, and an
organic base [21, 22] is generally used for the concomitant
cycloaddition reaction with olefin/alkyne. It has been
shown that benzonitrile oxides can be formed in water from
benzohydroximoyl chloride [23] and these undergo cycli-
zation in aqueous or organic biphasic medium in the
presence of a catalytic amount of organic base, e.g.,
triethylamine [24]. A recent study showed the rate
enhancement of cyclization reaction of nitrile oxides and
electron-rich dipolarophiles in water and protic solvents
[25]. No additional base was required when the cycload-
dition was performed in biphasic medium. Water in
biphasic medium enhances the rate, whereas the reaction in
water is slow [26].
Keywords Carbonyl compounds ꢀ Heterocycles ꢀ
Amines ꢀ 1,3-dipolar cycloaddition ꢀ Nitrile oxide
Introduction
Isoxazoles and isoxazolines are important molecules as they
exhibit a wide range of biological activities. Recent reports
have described isoxazoles as lysophosphatidic acid (LPA)
antagonists [1], inhibitors of human rhinovirus 2 replication
[2], and they also exhibit antitubulin [3] and insect antifee-
dant [4] activities. Isoxazolines have been described as
antimicrobial [5, 6], protein tyrosine phosphatase 1B
(PTPIB) inhibitors [7], and anti-inflammatory agents [8].
Some isoxazolines and isoxazoles have applications as dyes,
electric insulating oils, and high temperature lubricants [9].
Synthetic manipulation of isoxazolines and isoxazoles pro-
vides easy access to b-hydroxy ketones, b-hydroxy acids,
esters, b-hydroxy nitriles, a,b-unsaturated ketones, c-amino
alcohols, and so on [10]. So easy and rapid syntheses of these
compounds are very much essential.
Results and discussion
Existing reports describe the isoxazoline- and isoxazole-
forming reactions (inter- or intramolecular nitrile oxide
cycloaddition) as slow [20, 27]. Herein, we describe the
nitrile oxide formation and its concomitant cycloaddition
as a fast reaction. A rapid synthesis of benzopyrano- and
naphthopyrano-fused isoxazolines 2 and isoxazoles 5 is
also reported in a one-pot reaction from oximes 1 and 4
(Scheme 1) in dichloromethane–water or chloroform–
water biphasic medium at room temperature (rt) in good to
excellent yields with 4% aqueous sodium hypochlorite
solution within 10 min.
1,3-Dipolar cycloaddition reaction (inter- or intramo-
lecular) of nitrile oxides and olefins/alkynes is one of the
B. Roy (&) ꢀ R. N. De
Department of Chemistry, University of Kalyani,
Kalyani 741235, West Bengal, India
e-mail: broybs@rediffmail.com
123

764
B. Roy, R. N. De
R4
Table 1 Reaction of oxime 1a with 1 Eq of 4% aq. NaOCl solution
R1
R2
O
R1
R2
O
O
R5
aq. NaOCl solution
R4
O
O
N
N
R5
OH
CH2Cl2 or CHCl3
stir, rt
N
R3
N
O
R3
OH
2a 2m
-
1a-1m
N
O
2a
1a
R1
R2
R1
R2
O
aq. NaOCl solution
OH
CH2Cl2 or CHCl3
stir, rt
Entry Medium
Base Temperature Time Yield
(%)
R3
4a-4d
R3
5a 5d
N
O
(°C)
(h)
-
1
H2O
H2O
H2O
–
–
–
rt
rt
rt
0
0.17 15
Scheme 1
2
3.0
14.0
30
45
3
For our study we prepared different o-allylated arylal-
dehyde oximes (1a–1m, Table 2). Firstly, an aqueous
suspension of oxime 1a was treated with 1 Eq of 4%
aqueous sodium hypochlorite at room temperature and the
desired isoxazoline 2a was obtained. The reaction was
monitored by TLC and the product was characterized from
its spectral data. The characteristic peak of –OH stretching
of oxime 1a at 3,250 cm-1 was missing in the IR spectrum
of 2a. In the 1H NMR spectrum, the peaks at d = 7.79 and
8.54 for –OH and –N=CH, respectively, disappeared and a
new peak at d = 4.57 appeared for –OCH2 of compound
2a. The HRMS mass peak changed from 192.0945 of
oxime 1a to 190.0867 for the product 2a.
4
CH2Cl2–H2O (84:16) Et3N
CH2Cl2–H2O (84:16) Et3N
0.17 50
5
0
1.0
2.0
60
65
6
CH2Cl2–H2O (84:16) Et3N rt
7
CH2Cl2–H2O (84:16)
CHCl3–H2O (84:16)
THF–H2O (65:35)
THF–H2O (84:16)
CH3CN–H2O (84:16)
EtOAc–H2O (84:16)
–
–
–
–
–
–
rt
rt
rt
rt
rt
rt
0.17 92
0.17 90
8
9
22.0
70
72
50
65
10
11
12
45.0
2.0
2.0
material (Table 2, entries 2, 5, 9, 10, 13). Then we per-
formed the reactions with 2 Eq of sodium hypochlorite
solution. This time all reactions were complete within
10 min with better yields (86–95%) and no starting mate-
rials were recovered.
The reaction was slow (Table 1, entries 1–3) in aqueous
medium. Then the reaction was carried out with 1 Eq of
4% aqueous sodium hypochlorite solution in the presence
of a base (Et3N) in dichloromethane as solvent, which gave
better yield in shorter reaction time (Table 1, entries 4–6).
In all cases we isolated some starting oxime and corre-
sponding deoximation compound (amount depending on
the reaction time) along with the desired isoxazoline. When
the same reaction was performed in the absence of base at
room temperature, a dramatic rate enhancement occurred
with excellent yield (Table 1, entry 7). For this case a very
small amount of deoximation product (less than 5%) [19]
and no starting oxime was isolated. We screened several
other solvents for the reaction; it was observed that in
tetrahydrofuran (THF) the reaction was slow (Table 1,
entries 9, 10), and in acetonitrile and ethyl acetate rates
were somewhat faster (Table 1, entries 11, 12). When
chloroform was used as solvent the reaction rate and yield
were comparable with that in dichloromethane (entry 8).
TLC indicated the completion of the reaction within
10 min, when the reaction was performed in dichloro-
methane or chloroform.
The rate enhancements for some o-propargyloxy aryl-
aldehyde oximes (4a–4d, Table 3) were also similarly
tested. Oxime 4a was treated with only 1 Eq of 4% aque-
ous sodium hypochlorite at room temperature for 10 min
(Scheme 1). The product (5a, Table 3) was obtained in
good yield (79%) and characterized from its spectral data.
The characteristic peak at 3,291 cm-1 for –OH stretching
of oxime 4a disappeared in the IR spectrum of 5a. In the
1H NMR spectrum the characteristic peaks at d = 2.51 and
7.83 ppm for propargylic hydrogen and N–O–H disap-
peared and a new peak at d = 8.19 appeared for O–CH= in
the product 5a. Similarly oximes 4b–4d were treated and
corresponding isoxazoles were obtained in 65–77% yield
within 10 min. Even better yields (82–90%) were obtained
by using 2 Eq of sodium hypochlorite solution.
Encouraged by these results, we also performed inter-
molecular 1,3-dipolar cycloaddition reactions to test
whether the reaction might show a similar rate enhance-
ment. Benzaldoxime 6 in dichloromethane was reacted
with dienophiles 7a and 7b (Scheme 2) in the presence of
1 Eq aqueous sodium hypochlorite solution. With dieno-
phile 7a, the reaction was complete in 45 min while with
dienophile 7b, the reaction required more than 1 h for
completion. However for both cases the reaction was
With optimized reaction conditions in hand, we carried
out the reaction with other o-allylated arylaldehyde oximes
1b–1m in chloroform or dichloromethane with 1 Eq of 4%
aqueous sodium hypochlorite (Table 2) for 10 min to
provide isoxazolines 2b–2m in 77–95% yields and for
some cases we recovered small amounts of starting
123

Enhanced rate of intramolecular nitrile oxide cycloaddition
765
Table 2 Reaction of various
oximes with aqueous NaOCl
solution
Entry
Substrates
Products
Yieldsa,b(%)
92 (92)
O
O
1
N
OH
Cl
1a
2a
N
O
O
O
78 (86)
95 (95)
Cl
2
N
OH
OH
OH
1b
2b
N
O
O
O
3
N
Me
Me
1c
2c
2d
2e
N
O
O
O
O
4
94
(94)
N
MeO
MeO
1d
N
O
O
77 (88)
91 (93)
5
N
Cl
Cl
OH
OH
1e
N
O
O
O
O
O
6
N
Me
Me
1f
2f
N
O
O
(93)
90
7
N
2g
OH
1g
N
complete in 10 min, if 2 Eq of aqueous sodium hypo-
chlorite solution was used and the yields were 82 and 85%,
respectively (Table 4). More deoximation product was
obtained when 1 Eq of aqueous sodium hypochlorite
solution was used (Table 4).
the 1,3-dipolar cycloaddition reactions. This might be due
to a difference in hypochlorous acid concentration in the
reaction medium as shown schematically in Scheme 3. In
the presence of a base, the concentration of hypochlorous
acid decreases in the organic phase due to the formation
of triethylamine hydrochloride in aqueous medium. Thus,
the formation of hydroximoyl chloride and the corre-
sponding nitrile oxide becomes slow, hence a longer time
is necessary for the completion of the reaction and more
deoximation product is obtained.
We studied the rate enhancement in large-scale intra-
molecular nitrile oxide cycloaddition reactions also.
Compound 1g (5.0 g) in dichloromethane was treated with
2 Eq of 4% aqueous sodium hypochlorite solution and
1.5 Eq of triethylamine. The reaction was not complete
even after 24 h. We performed the same reaction with 1 Eq
of 4% aqueous sodium hypochlorite solution in the absence
of base and the reaction remained incomplete even after
2 h. But when the reaction was repeated with 2 Eq of 4%
aqueous sodium hypochlorite solution, it was complete
within 20 min with satisfactory yield (88%).
In conclusion, we have shown the rate enhancement of
nitrile oxide cyclization and hence a rapid synthesis of
isoxazolines and isoxazoles at room temperature in biphasic
medium. Only 1–2 Eq of sodium hypochlorite solution is
sufficient for the completion of the reaction and no addi-
tional base is required to facilitate the cycloaddition. Again
dichloromethane–water or chloroform–water is the better
solvent where the reaction is rapid.
From the above observations, it is apparent that in
biphasic reaction conditions the absence of base speeds up
123

766
B. Roy, R. N. De
Table 2 continued
Entry
8
Substrates
Products
Yieldsa,b(%)
93 (94)
O
O
N
N
N
MeO
Me
MeO
Me
OH
OH
OH
2h
1h
N
O
O
O
O
9
80 (89)
82 (87)
1i
Me
O
2i
N
O
Me
10
11
1j
Me
2j
N
Me
O
Me
O
Me
O
85
(91)
N
N
2k
OH
1k
N
O
N
O
OH
O
O
12
13
88 (88)
80 (86)
1l
2l
O
N
Cl
O
OH
O
N
a
Deoximation product (less
than 5%) was isolated in each
case
Cl
b
Improved yields by using
2 Eq of NaOCl are given in
parenthesis
1m
2m
Experimental
TLC. Petroleum (pet) ether refers to the fraction boiling at
60–80 °C.
Melting points were determined in open capillaries. IR
spectra were recorded by using samples as neat liquid or
solid samples on KBr disks on a PerkinElmer L 120-000A
spectrophotometer. 1H NMR spectra (300, 400, and
500 MHz) were recorded on Bruker DPX-300, Bruker
DPX-400, Bruker DPX-500 spectrometer in CDCl3
(chemical shifts in ppm) with TMS as internal standard.
Elemental analyses were recorded on PerkinElmer 2400
series II CHN analyzer from the University of Kalyani,
India, and results agreed with calculated values. Mass
spectra were recorded on a Jeol JMS600 instrument from
IICS, Kolkata. HRMS spectra were recorded on a Qtof
Micro YA263 instrument. Silica gel (60–120, 230–400
mesh, Spectrochem, India) was used for chromatographic
separation. Silica gel G (Spectrochem, India) was used for
Representative procedure for preparation
of aldoxime 1a
A mixture of 0.424 g (E)-2-(but-2-enyloxy)benzaldehyde
(2.40 mmol), 0.284 g pyridine (3.6 mmol), 0.2 g hydrox-
ylamine hydrochloride (2.88 mmol), and 5 cm3 ethanol
was refluxed for 3 h. The solvent was evaporated and the
residue was acidified with 6 N HCl. It was extracted with
CHCl3 (3 9 20 cm3), washed with brine, and dried over
anhydrous sodium sulfate. After removal of solvent, the
crude product was recrystallized from ethyl acetate–
petroleum ether (3:1, unless stated otherwise) to give
0.418 g (91%) of the pure oxime 1a. Other oximes 1b–1m
were prepared by following this procedure. For known
123

Enhanced rate of intramolecular nitrile oxide cycloaddition
767
Table 3 Synthesis of various isoxazoles
Table 4 Intermolecular nitrile oxide cycloaddition reaction
Entry Substrate
Dipolarophiles
Products
Yieldsa(%)
Entry
Substrates
Products
Yieldsa,b(%)
79 (88)
O
O
N
OH
OH
O
O
N
N
1
O
1
82
85
7a
N
8a
Me
Me
OH
OH
6
5a
4a
N
O
N
O
O
O
Me
2
O
O
O
Me
O
8b
7b
O
6
2
3
4
76 (90)
77 (90)
N
N
a
7–8% Deoximation product was also isolated
5b
4b
N
O
O
Et3NHCl
Et3N
Water layer
MeO
OH
MeO
5c
4c
OH
N
O
HOCl + Na+ + OH-
O
H2O + Cl-
NaOCl + H2O
N
N
O
O
65 (82)
HOCl
Nitrile oxide
4d
Oxime
(presence of base will reduce active HOCl conc.)
Dichloromethane layer
Hydroximoyl chloride
5d
a
Deoximation product (less than 5%) was isolated
b
Improved yields by using 2 Eq of NaOCl are given in parenthesis
Scheme 3
O
7a
(E)-2-(2-Chloro-2-propenyloxy)benzaldehyde oxime
(1b, C10H10ClNO2)
OH
N
O
8a
O
N
White solid, yield 89%; m.p.: 57–58 °C; 1H NMR
(400 MHz, CDCl3): d = 4.63 (s, 2H, OCH2), 5.45 (s, 1H,
=CH2), 5.54 (s, 1H, =CH2), 6.87 (d, 1H, J = 8.4 Hz, ArH),
7.00 (t, 1H, J = 7.4 Hz, ArH), 7.33 (t, 1H, J = 7.5 Hz,
ArH), 7.73 (d, 1H, J = 7.4 Hz, ArH), 8.41(bs, 1H, OH),
8.55 (s, 1H, N=CH) ppm; 13C NMR (75 MHz, CDCl3):
d = 70.41, 112.73, 114.10, 121.08, 121.86, 127.11, 131.30,
CH2Cl2
aq. NaOCl solution,
stir, rt
O
O
Me
6
O
N
O
8b
Me
O
7b
Scheme 2
ꢀ
135.89, 146.27, 155.83 ppm; IR (KBr): m = 3,256, 2,926,
1,640, 1,600 cm-1; MS: m/z = 211 (M?).
compounds 1f [19], 1g [28], 1h [28], 4b [21], 4d [22], 2f
[19], 2g [28], 2h [28], 5b [21], 5d [22] data were in
agreement with reported values given in references.
(E)-2-((E)-2-Butenyloxy)-5-methylbenzaldehyde oxime
(1c, C12H15NO2)
Yellow solid, yield 92%; m.p.: 68 °C; 1H NMR (400 MHz,
CDCl3): d = 1.74 (d, 3H, J = 6.4 Hz, CHCH3), 2.27 (s,
3H, CH3), 4.46 (d, 2H, J = 5.7 Hz, OCH2), 5.66–5.72 (m,
1H, CH=CH), 5.78–5.85 (m, 1H, CH=CH), 6.79 (d, 1H,
J = 8.4 Hz, ArH), 7.10 (d, 1H, J = 8.6 Hz, ArH), 7.51 (s,
(E)-2-((E)-2-Butenyloxy)benzaldehyde oxime
(1a, C11H13NO2)
1
Light yellow solid, yield 91%; m.p.: 88–89 °C; H NMR
(400 MHz, CDCl3): d = 1.75 (d, 3H, J = 6.1 Hz, CH3),
4.49 (d, 2H, J = 5.5 Hz, OCH2), 5.67–5.74 (m, 1H,
CH=CH), 5.80–5.87 (m, 1H, CH=CH), 6.89 (d, 1H,
J = 8.3 Hz, ArH), 6.93 (t, 1H, J = 7.5 Hz, ArH), 7.32 (t,
1H, J = 7.5 Hz, ArH), 7.71 (d, 1H, J = 7.2 Hz, ArH),
7.79 (bs, 1H, OH), 8.54 (s, 1H, N=CH) ppm; 13C NMR
(75 MHz, CDCl3): d = 17.72, 69.02, 112.35, 120.71,
120.83, 125.68, 126.47, 130.27, 131.06, 146.54,
1H, ArH), 8.12 (bs, 1H, OH), 8.51 (s, 1H, N=CH) ppm; 13
C
NMR (75 MHz, CDCl3): d = 17.85, 20.46, 69.37, 112.70,
120.56, 125.97, 127.01, 130.12, 130.27, 131.73, 146.74,
ꢀ
154.90 ppm; IR (KBr): m = 3,400, 2,917, 1,638,
1,610 cm-1; MS: m/z = 205 (M?).
(E)-2-((E)-2-Butenyloxy)-5-methoxybenzaldehyde oxime
(1d, C12H15NO3)
ꢀ
156.74 ppm; IR (KBr): m = 3,250, 2,919, 1,618,
1,599 cm-1; HRMS: calcd. for C11H13NO2: 192.0946
Yellow solid, yield 87%; m.p.: 62–63 °C; Rf = 0.50 (15%
[M? ? H], found: 192.0945 [M? ? H].
1
EtOAc/pet ether); H NMR (400 MHz, CDCl3): d = 1.74
123

768
B. Roy, R. N. De
(d, 3H, J = 6.0 Hz, CHCH3), 3.77 (s, 3H, OCH3), 4.43 (d,
2H, J = 5.8 Hz, OCH2), 5.66–5.70 (m, 1H, CH=CH),
5.75–5.88 (m, 1H, CH=CH), 6.82–6.89 (m, 2H, ArH), 7.26
(d, 1H, J = 8.9 Hz, ArH), 8.11 (bs, 1H, OH), 8.51 (s, 1H,
N=CH) ppm; 13C NMR (75 MHz, CDCl3): d = 17.84,
55.74, 70.20, 110.17, 114.61, 117.68, 121.62, 126.02,
130.37, 146.58, 151.38, 153.67 ppm; IR (KBr): ꢀm = 3,396,
2,917, 1,630, 1,582 cm-1; MS: m/z = 221 (M?).
(m, 1H, OCH2CH), 6.70 (s, 1H, ArH), 6.76 (d, 1H,
J = 7.8 Hz, ArH), 7.59 (d, 1H, J = 7.8 Hz, ArH), 8.33 (bs,
1H, OH), 8.51 (s, 1H, N=CH) ppm; 13C NMR (75 MHz,
CDCl3): d = 21.48, 69.44, 112.20, 115.91, 117.08, 122.06,
129.92, 133.10, 143.82, 147.54, 156.57 ppm; IR (KBr):
m = 3,279, 2,920, 2,850, 1,608 cm-1; MS: m/z = 191 (M?).
ꢀ
(E)-2-(2-Propenyloxy)-1-naphthalenecarbaldehyde oxime
(1l, C14H13NO2)
(E)-2-((E)-2-Butenyloxy)-5-chlorobenzaldehyde oxime
(1e, C11H12ClNO2)
Recrystallized from ethyl acetate. White solid, yield 89%;
m.p.: 98–99 °C; Rf = 0.50 (15% EtOAc/pet ether); 1H
NMR (400 MHz, CDCl3): d = 4.71 (d, 2H, J = 5.3 Hz,
OCH2), 5.30 (d, 1H, J = 10.6 Hz, =CH2), 5.43 (d, 1H,
J = 17.8 Hz, =CH2), 6.03–6.13 (m, 1H, OCH2CH), 7.23
(d, 1H, J = 9.2 Hz, ArH), 7.37 (t, 1H, J = 7.4 Hz, ArH),
7.52 (t, 1H, J = 7.4 Hz, ArH), 7.75 (d, 1H, J = 5.6 Hz,
ArH), 7.83 (d, 1H, J = 9.1 Hz, ArH), 8.32 (bs, 1H, OH),
8.82 (d, 1H, J = 8.7 Hz, ArH), 8.91 (s, 1H, N=CH) ppm;
13C NMR (75 MHz, CDCl3): d = 70.28, 114.06, 114.19,
117.97, 124.22, 125.42, 127.89, 128.38, 129.24, 131.72,
Yellow solid, yield 88%; m.p.: 83–84 °C; Rf = 0.40 (15%
1
EtOAc/pet ether); H NMR (400 MHz, CDCl3): d = 1.75
(d, 3H, J = 5.8 Hz, CH3), 4.46 (d, 2H, J = 5.8 Hz,
OCH2), 5.63–5.70 (m, 1H, CH=CH), 5.79–5.87 (m, 1H,
CH=CH), 6.81 (d, 1H, J = 8.9 Hz, ArH), 7.23–7.26 (m,
1H, ArH), 7.62 (bs, 1H, OH), 7.70 (s, 1H, ArH), 8.45 (s,
1H, N=CH) ppm; 13C NMR (75 MHz, CDCl3): d = 17.85,
69.56, 113.90, 122.33, 125.36, 126.00, 126.28, 130.67,
ꢀ
130.91, 145.63, 155.32 ppm; IR (KBr): m = 3,277, 2,916,
1,680, 1,594 cm-1; MS: m/z = 225 (M?).
131.94, 133.03, 147.63, 155.97 ppm; IR (KBr): m = 3,243,
ꢀ
2,921, 1,644, 1,618 cm-1; MS: m/z = 227 (M?).
(E)-4,6-Dimethyl-2-(2-propenyloxy)benzaldehyde oxime
(1i, C12H15NO2)
(E)-2-(2-Chloro-2-propenyloxy)-1-naphthalenecarbalde-
hyde oxime (1m, C14H12ClNO2)
Yellow solid, yield 84%; m.p.: 77–78 °C; Rf = 0.50 (15%
1
EtOAc/pet ether); H NMR (400 MHz, CDCl3): d = 2.29
White solid, yield 88%; m.p.: 57–58 °C; Rf = 0.60 (20%
1
(s, 3H, CH3), 2.43 (s, 3H, CH3), 4.54 (d, 2H, J = 4.9 Hz,
OCH2), 5.26 (d, 1H, J = 10.2 Hz, =CH2), 5.38 (d, 1H,
J = 16.7 Hz, =CH2), 5.99–6.08 (m, 1H, OCH2CH), 6.56
(s, 1H, ArH), 6.65 (s, 1H, ArH), 8.21 (bs, 1H, OH), 8.56
(s, 1H, N=CH) ppm; 13C NMR (75 MHz, CDCl3): d = 21.71,
21.93, 69.33, 110.78, 116.79, 117.50, 124.60, 133.20,
EtOAc/pet ether); H NMR (400 MHz, CDCl3): d = 4.75
(s, 2H, OCH2), 5.46 (s, 1H, =CH2), 5.57 (s, 1H, =CH2), 7.19
(d, 1H, J = 9.2 Hz, ArH), 7.40 (t, 1H, J = 7.6 Hz, ArH),
7.54 (d, 1H, J = 7.7 Hz, ArH), 7.79 (d, 1H, J = 8.1 Hz,
ArH), 7.84 (d, 1H, J = 9.1 Hz, ArH), 8.11 (bs, 1H, OH),
8.77 (d, 1H, J = 8.6 Hz, ArH), 8.91 (s, 1H, N=CH) ppm;
13C NMR (75 MHz, CDCl3): d = 71.49, 114.05, 114.37,
114.64, 124.60, 125.71, 128.03, 128.38, 129.62, 131.62,
ꢀ
138.75, 140.32, 147.41, 157.55 ppm; IR (KBr): m = 3,300,
2,919, 1,649, 1,609, cm-1; MS: m/z = 205 (M?).
ꢀ
132.10, 136.10, 147.54, 155.09 ppm; IR (KBr): m = 3,214,
(E)-6-Methyl-2-(2-propenyloxy)benzaldehyde oxime
(1j, C11H13NO2)
Yellow gummy liquid, yield 93%; Rf = 0.40 (15% EtOAc/
2,943, 1,638, 1,617 cm-1; MS: m/z = 261 (M?).
1
Representative procedure for preparation of aldoximes
4a–4d
pet ether); H NMR (400 MHz, CDCl3): d = 2.46 (s, 3H,
CH3), 4.56 (d, 2H, J = 8.8 Hz, OCH2), 5.27 (d, 1H,
J = 10.8 Hz, =CH2), 5.39 (d, 1H, J = 17.6 Hz, =CH2),
5.99–6.07 (m, 1H, OCH2CH), 6.74 (d, 1H, J = 8.2 Hz,
ArH), 6.82 (d, 1H, J = 7.6 Hz, ArH), 7.18 (t, 1H,
J = 7.9 Hz, ArH), 8.11 (bs, 1H, OH), 8.59 (s, 1H,
N=CH) ppm; 13C NMR (75 MHz, CDCl3): d = 21.52,
69.38, 114.54, 115.09, 117.29, 124.01, 132.90, 133.23,
Aldoximes 4a–4d were prepared following the procedure
for preparation of 1a. The crude compound was purified by
column chromatography using 15% ethyl acetate–petro-
leum ether as eluent and recrystallized from chloroform–
petroleum ether 4:1 to give the pure oximes 4a–4d.
ꢀ
138.64, 147.41, 155.70 ppm; IR (KBr): m = 3,315, 2,924,
(E)-5-Methyl-2-(2-propynyloxy)benzaldehyde oxime
(4a, C11H11NO2)
1,596, 1,577 cm-1; MS: m/z = 191 (M?).
White solid, yield 86%; m.p.: 107–108 °C; Rf = 0.50 (15%
EtOAc/pet ether); H NMR (300 MHz, CDCl3): d = 2.3
(E)-4-Methyl-2-(2-propenyloxy)benzaldehyde oxime
(1k, C11H13NO2)
1
(s, 3H, –CH3), 2.51 (s, 1H, alkyne proton), 4.71 (s, 2H,
–OCH2), 6.94 (d, 1H, J = 8.4 Hz, ArH), 7.16 (d, 1H,
J = 8.4 Hz, ArH), 7.54 (s, 1H, ArH), 7.83 (bs, 1H, OH),
8.49 (s, 1H, N=CH) ppm; 13C NMR (75 MHz, CDCl3):
Yellow solid, yield 85%; m.p.: 68–70 °C; Rf = 0.40 (15%
EtOAc/pet ether); 1H NMR (400 MHz, CDCl3): d = 2.32 (s,
3H, CH3), 4.56 (d, 2H, J = 4.8 Hz, OCH2), 5.28 (d, 1H,
J = 10.4 Hz, =CH2), 5.40 (d, 1H, J = 17.0 Hz, =CH2), 6.04
123

Enhanced rate of intramolecular nitrile oxide cycloaddition
769
d = 20.48, 56.53, 75.83, 78.35, 113.05, 121.10, 127.28,
J = 11.0 Hz, OCH2), 7.03–7.05 (m, 1H, ArH), 7.08 (dd,
1H, J = 1.0, 7.8 Hz, ArH), 7.38–7.42 (m, 1H, ArH), 7.84
(dd, 1H, J = 1.5, 7.8 Hz, ArH) ppm; 13C NMR (75 MHz,
CDCl3): d = 71.26, 72.93, 78.77, 110.77, 117.69, 122.67,
ꢀ
131.25, 131.63, 146.56, 153.62 ppm, IR (KBr): m = 3,291,
2,853, 2,122, 1,495 cm-1; MS: m/z = 189 (M?).
(E)-5-Methoxy-2-(2-propynyloxy)benzaldehyde oxime
(4c, C11H11NO3)
ꢀ
126.24, 133.17, 152.05, 154.19 ppm; IR (KBr): m = 2,936,
2,916, 1,610, 1,593 cm-1; MS: m/z = 209 (M?).
Yellow solid, yield 90%; m.p.: 110–111 °C; Rf = 0.50
(15% EtOAc/pet ether); 1H NMR (300 MHz, CDCl3):
d = 2.51 (s, 1H, alkyne proton), 3.78 (s, 3H, –OCH3), 4.68
(s, 2H, OCH2), 6.89–6.93 (m, 2H, ArH), 6.99 (d, 1H,
J = 9 Hz, ArH), 7.89 (bs, 1H, OH), 8.49 (s, 1H, N=CH)
ppm; 13C NMR (75 MHz, CDCl3): d = 55.74, 57.41,
75.90, 78.44, 110.55, 115.20, 117.48, 122.36, 146.36,
3a,4-Dihydro-3,8-dimethyl-3H-[1]benzopyrano[4,3-c]is-
oxazole (2c, C12H13NO2)
Recrystallized from petroleum ether. Yellow solid, yield
1
95%; m.p.: 44 °C; Rf = 0.60 (15% EtOAc/pet ether); H
NMR (400 MHz, CDCl3): d = 1.58 (d, 3H, J = 5.5 Hz,
CHCH3), 2.28 (s, 3H, CH3), 3.45 (dt, 1H, J = 5.0, 12.4 Hz,
ring juncture H), 4.03 (dd & t, J = 11.3 Hz, OCH2), 4.37
(qd, 1H, J = 6.1, 12.1 Hz, CHCH3), 4.50–4.56 (m, 1H,
OCH2), 6.82 (d, 1H, J = 8.4 Hz, ArH), 7.11 (d, 1H,
J = 7.8 Hz, ArH), 7.57 (s, 1H, ArH) ppm; 13C NMR
(75 MHz, CDCl3): d = 18.27, 20.47, 51.69, 68.93, 80.14,
112.97, 117.10, 125.17, 131.23, 133.34, 153.49,
ꢀ
150.08, 154.41 ppm; IR (KBr): m = 3,288, 2,837, 2,121,
1,496 cm-1; MS: m/z = 205 (M?).
Representative procedure for the preparation
of 2a from 1a
To a solution of 0.191 g 1a (1.0 mmol) in 5 cm3 dichlo-
romethane at room temperature was added dropwise
3.6 cm3 4% aqueous sodium hypochlorite solution (2 Eq)
within 2 min. After completion of the addition the reaction
mixture was stirred for 7 min. Water (10 cm3) was added
to the reaction mixture and it was extracted with dichlo-
romethane (3 9 15 cm3). The organic layer was dried over
anhydrous sodium sulfate, filtered, and concentrated, and
the residue was subjected to flash column chromatography
using an eluent of petroleum ether–ethyl acetate (4:1) to
afford 0.174 g (92%) 2a. The product was recrystallized
from ethanol (unless stated otherwise). Compounds 2b–2m
were prepared similarly.
154.06 ppm; IR (KBr): m = 2,973, 2,929, 1,621,
ꢀ
1,603 cm-1; MS: m/z = 203 (M?).
3a,4-Dihydro-8-methoxy-3-methyl-3H-[1]benzopyr-
ano[4,3-c]isoxazole (2d, C12H13NO3)
Recrystallized from petroleum ether. Yellow solid, yield
94%; m.p.: 59–60 °C; Rf = 0.50 (15% EtOAc/pet ether);
1H NMR (400 MHz, CDCl3): d = 1.59 (d, 3H,
J = 5.9 Hz, CHCH3), 3.46 (dt, 1H, J = 5.8, 12.4 Hz, ring
juncture H), 3.77 (s, 3H, OCH3), 4.02 (dd & t, 1H,
J = 11.4 Hz, OCH2), 4.39 (qd, 1H, J = 6.1, 12.3 Hz,
CHCH3), 4.51–4.55 (m, 1H, OCH2), 6.85 (d, 1H,
J = 9.0 Hz, ArH), 6.9 (d, 1H, J = 8.4 Hz, ArH), 7.23 (s,
1H, ArH) ppm; 13C NMR (75 MHz, CDCl3): d = 18.25,
51.71, 55.79, 68.98, 80.39, 106.96, 107.13, 118.59, 120.92,
3a,4-Dihydro-3-methyl-3H-[1]benzopyrano[4,3-c]isoxazole
(2a, C11H11NO2)
ꢀ
146.47, 149.95, 154.32 ppm; IR (KBr): m = 2,976, 2,905,
White solid, yield 92%; m.p.: 99 °C; Rf = 0.50 (15% EtOAc/
1,600, 1,581 cm-1; MS: m/z = 219 (M?).
1
pet ether); H NMR (400 MHz, CDCl3): d = 1.59 (d, 3H,
8-Chloro-3a,4-dihydro-3-methyl-3H-[1]benzopyrano-
[4,3-c]isoxazole (2e, C11H10ClNO2)
J = 6.0 Hz, CH3), 3.48 (dt, 1H, J = 5.8, 12.0 Hz, ring
juncture H), 4.07 (dd, 1H, J = 10.7, 12.0 Hz, OCH2), 4.39
(qd, 1H, J = 6.0, 12.2 Hz, CHCH3), 4.57 (dd, 1H, J = 5.8,
10.4 Hz, OCH2), 6.92 (d, 1H, J = 8.3 Hz, ArH), 6.98 (t, 1H,
J = 7.4 Hz, ArH), 7.31(t, 1H, J = 7.2 Hz, ArH), 7.76(d, 1H,
J = 7.1 Hz, ArH) ppm; 13C NMR (75 MHz, CDCl3):
d = 18.22, 51.50, 68.83, 80.10, 113.30, 117.29, 121.73,
Light yellow solid, yield 88%; m.p.: 91–92 °C; Rf = 0.40
(15% EtOAc/pet ether); 1H NMR (400 MHz, CDCl3):
d = 1.59 (d, 3H, J = 5.7 Hz, CHCH3), 3.45 (dt, 1H,
J = 5.7, 12.4 Hz, ring juncture H), 4.04 (dd & t, 1H,
J = 11.3 Hz, OCH2), 4.41 (qd, 1H, J = 6.1, 12.2 Hz,
CHCH3), 4.59 (dd, 1H, J = 6.0, 10.1 Hz, OCH2), 6.85–
6.91 (m, 1H, ArH), 7.21–7.26 (m, 1H, ArH), 7.74 (s, 1H,
ArH) ppm; 13C NMR (75 MHz, CDCl3): d = 18.31, 51.14,
69.04, 80.59, 114.58, 118.91, 124.71, 126.94, 132.23,
ꢀ
125.30, 132.28, 153.75, 155.39 ppm; IR (KBr): m = 2,895,
2,883, 1,600, 1,611 cm-1; HRMS: calcd. for C11H11NO2:
190.0868 [M? ? H]; found: 190.0867 [M? ? H].
ꢀ
152.95, 153.94 ppm; IR (KBr): m = 2,928, 1,605,
3a-Chloro-3a,4-dihydro-3H-[1]benzopyrano[4,3-c]isoxaz-
ole (2b, C10H8ClNO2)
1,480 cm-1; MS: m/z = 223 (M?).
White solid, yield 86%; m.p.: 122 °C; Rf = 0.60 (15%
EtOAc/pet ether); H NMR (500 MHz, CDCl3): d = 4.32
3a,4-Dihydro-7,9-dimethyl-3H-[1]benzopyrano[4,3-c]is-
oxazole (2i, C12H13NO2)
1
(d, 1H, J = 11.0 Hz, OCH2), 4.39 (d, 1H, J = 12.0 Hz,
OCH2), 4.78 (d, 1H, J = 12.0 Hz, OCH2), 4.85 (d, 1H,
Yellow solid, yield 89%; m.p.: 119–120 °C; Rf = 0.50
(15% EtOAc/pet ether); 1H NMR (400 MHz, CDCl3):
123

770
B. Roy, R. N. De
d = 2.28 (s, 3H, CH3), 2.53 (s, 3H, CH3), 3.82 (dd, 1H,
J = 7.6, 13.0 Hz, OCH2), 3.87–3.95 (m, 1H, ring juncture
H), 4.03 (dd & t, 1H, J = 11.0 Hz, OCH2), 4.59–4.63 (m,
OCH2), 4.87 (d, 1H, J = 10.8 Hz, OCH2), 4.88 (d, 1H,
J = 11.8 Hz, OCH2), 7.17 (d, 1H, J = 8.9 Hz, ArH), 7.46
(t, 1H, J = 7.6 Hz, ArH), 7.61–7.65 (m, 1H, ArH), 7.79 (d,
1H, J = 8.1 Hz, ArH), 7.86 (d, 1H, J = 9.0 Hz, ArH),
8.98 (d, 1H, J = 8.5 Hz, ArH) ppm; 13C NMR (75 MHz,
CDCl3): d = 72.38, 72.92, 77.85, 104.12, 118.10, 125.14,
126.57, 128.60, 128.80, 129.64, 130.64, 134.21, 152.72,
2H, OCH2), 6.61 (s, 1H, ArH), 6.68 (s, 1H, ArH) ppm; 13
C
NMR (75 MHz, CDCl3): d = 21.46, 22.96, 47.09, 68.63,
69.41, 109.73, 115.07, 125.10, 139.25, 142.18, 153.57,
156.19 ppm; IR (KBr): ꢀm = 2,921, 2,861, 1,613,
1,586 cm-1; MS: m/z = 203 (M?).
154.51 ppm; IR (KBr): m = 2,926, 1,618, 1,599 cm-1; MS:
ꢀ
m/z = 259 (M?).
3a,4-Dihydro-9-methyl-3H-[1]benzopyrano[4,3-c]isoxaz-
ole (2j, C11H11NO2)
Representative procedure for the preparation
of 5a–5d from 4a–4d
White solid, yield 87%; m.p.: 122 °C; Rf = 0.40 (15%
1
EtOAc/pet ether); H NMR (500 MHz, CDCl3): d = 2.58
(s, 3H, CH3), 3.86 (dd, 1H, J = 7.7, 12.8 Hz, OCH2),
3.90–3.98 (m, 1H, ring juncture H), 4.07 (dd, 1H, J = 10.2,
12.0 Hz, OCH2), 4.63–4.66 (m, 2H, OCH2), 6.80 (d, 1H,
J = 8.3 Hz, ArH), 6.86 (d, 1H, J = 7.5 Hz, ArH), 7.20 (t,
1H, J = 7.9 Hz, ArH) ppm; 13C NMR (75 MHz, CDCl3):
d = 23.08, 46.89, 68.64, 69.54, 112.47, 114.76, 123.86,
Compounds 5a–5d were prepared following the procedure
for the preparation of 2a described above. The products
were purified by column chromatography using 10% ethyl
acetate–petroleum ether as eluent and were recrystallized
from petroleum ether.
ꢀ
131.40, 139.54, 153.51, 156.21 ppm; IR (KBr): m = 2,921,
8-Methyl-4H-[1]benzopyrano[4,3-c]isoxazole
(5a, C11H9NO2)
2,850, 1,600 cm-1; MS: m/z = 189 (M?).
White solid, yield 88%; m.p.: 103–104 °C; Rf = 0.60 (10%
EtOAc/pet ether); H NMR (300 MHz, CDCl3): d = 2.34
3a,4-Dihydro-7-methyl-3H-[1]benzopyrano[4,3-c]isoxaz-
ole (2k, C11H11NO2)
1
(s, 3H, –CH3), 5.20 (s, 2H, –OCH2), 6.92 (d, 1H,
J = 8.4 Hz, ArH), 7.16 (d, 1H, J = 8.4 Hz, ArH), 7.68 (s,
1H, ArH), 8.19 (s, 1H, O–CH=) ppm; 13C NMR (75 MHz,
CDCl3): d = 20.60, 61.28, 111.39, 113.65, 117.59, 124.67,
131.92, 132.90, 150.54, 152.76, 153.89 ppm; IR (KBr):
ꢀm = 2,852, 1,621, 1,489 cm-1; MS: m/z = 187 (M?).
White solid, yield 91%; m.p.: 144 °C; Rf = 0.40 (15%
EtOAc/pet ether); H NMR (500 MHz, CDCl3): d = 2.33
1
(s, 3H, CH3), 3.87–3.95 (m, 2H, OCH2), 4.06–4.08 (m, 1H,
ring juncture H), 4.65–4.69 (m, 2H, OCH2), 6.76 (s, 1H,
ArH), 6.82 (d, 1H, J = 8.0 Hz, ArH), 7.67 (d, 1H,
J = 8.0 Hz, ArH) ppm; 13C NMR (75 MHz, CDCl3):
d = 21.74, 46.07, 69.23, 70.43, 110.22, 117.58, 123.10,
8-Methoxy-4H-[1]benzopyrano[4,3-c]isoxazole
(5c, C11H9NO3)
ꢀ
125.46, 143.42, 152.85, 155.56 ppm; IR (KBr): m = 2,924,
2,870, 1,619, 1,605 cm-1; MS: m/z = 189 (M?).
Light yellow solid, yield 90%; m.p.: 57–58 °C; Rf = 0.60
(10% EtOAc/pet ether); 1H NMR (300 MHz, CDCl3):
d = 3.82 (s, 3H, –OCH3), 5.18 (s, 2H, –OCH2), 6.93–6.98
(m, 2H, ArH), 7.36 (s, 1H, ArH), 8.20 (s, 1H, O–CH=) ppm;
13C NMR (75 MHz, CDCl3): d = 55.85, 61.27, 107.41,
111.56, 114.24, 118.96, 119.61, 148.98, 150.62, 154.12,
3a,4-Dihydro-3H-naphtho[10,20:5,6]pyrano[4,3-c]isoxaz-
ole (2l, C14H11NO2)
Recrystallized from petroleum ether. White solid, yield
1
88%; m.p.: 64 °C; Rf = 0.50 (15% EtOAc/pet ether); H
NMR (400 MHz, CDCl3): d = 3.93 (dd, 1H, J = 8.0,
12.7 Hz, OCH2), 4.04–4.14 (m, 1H, ring juncture H), 4.23
(dd, 1H, J = 10.4, 12.1 Hz, OCH2), 4.70 (dd, 1H, J = 8.0,
9.6 Hz, OCH2), 4.76 (dd, 1H, J = 5.4, 10.1 Hz, OCH2),
7.10 (d, 1H, J = 8.9 Hz, ArH), 7.42 (t, 1H, J = 7.5 Hz,
ArH), 7.59 (t, 1H, J = 7.7 Hz, ArH), 7.75–7.80 (m, 2H,
ArH), 9.02 (d, 1H, J = 8.6 Hz, ArH) ppm; 13C NMR
(75 MHz, CDCl3): d = 46.89, 69.19, 69.48, 106.09,
118.22, 124.72, 126.54, 128.37, 128.49, 129.26, 130.48,
154.77 ppm; IR (KBr): m = 2,917, 1,620, 1,490 cm-1; MS:
ꢀ
m/z = 203(M?).
Representative procedure for the preparation
of 8a and 8b
A 4% aqueous sodium hypochlorite solution (3.6 cm3,
2.0 mmol) was added dropwise to a solution of 0.134 g
allyloxybenzene 7a (1.0 mmol) and 0.121 g benzaldehyde
oxime 6 (1.0 mmol) in 10 cm3 dichloromethane at room
temperature within 2 min. After completion of the addi-
tion, the reaction mixture was stirred for 8 min. Water
(10 cm3) was added to the reaction mixture and it was
extracted with dichloromethane (3 9 15 cm3). The organic
layer was dried over anhydrous sodium sulfate, filtered, and
concentrated, and the residue was subjected to flash column
ꢀ
133.41, 153.20, 155.65 ppm; IR (KBr): m = 2,938, 2,887,
1,622, 1,597 cm-1; MS: m/z = 225 (M?).
3a-Chloro-3a,4-dihydro-3H-naphtho[10,20:5,6]pyrano[4,3-
c]isoxazole (2m, C14H10ClNO2)
White solid, yield 86%; m.p.: 151 °C; Rf = 0.60 (20%
1
EtOAc/pet ether); H NMR (400 MHz, CDCl3): d = 4.35
(d, 1H, J = 10.9 Hz, OCH2), 4.54 (d, 1H, J = 11.9 Hz,
123

Enhanced rate of intramolecular nitrile oxide cycloaddition
771
2. Kuz’min VE, Artemenko AG, Muratov EN, Volineckaya IL,
Makarov VA, Riabova OB, Wutzler P, Schmidtke M (2007)
J Med Chem 50:4205
3. Kaffy J, Pontikis R, Carrez D, Croisy A, Monnereta M, Florenta
J-C (2006) Bioorg Med Chem 14:4067
chromatography using an eluent of petroleum ether–ethyl
acetate (5:1) to afford 0.207 g (82%) 8a. The product was
recrystallized from petroleum ether. Compound 8b was
prepared similarly.
4. Soni AK, Krupadanam GLD, Srimannarayana G (2006) Arkivoc
xvi:35
5. Gaonkar SL, Lokanatha Rai KM, Prabhuswamy B (2007) Med
Chem Res 15:407
6. Solankee A, Thakor I (2006) Indian J Chem Sect B Org Chem
Incl Med Chem 45:517
5-(Phenoxymethyl)-3-phenyl-4,5-dihydroisoxazole
(8a, C16H15NO2)
White solid, yield 82%; m.p.: 79–80 °C; Rf = 0.50 (15%
1
EtOAc/pet ether); H NMR (400 MHz, CDCl3): d = 3.40
(dd, 1H, J = 6.8, 16.8 Hz), 3.53 (dd, 1H, J = 10.4,
16.8 Hz), 4.05 (dd, 1H, J = 6.0, 9.6 Hz), 4.18 (dd, 1H,
J = 4.8, 9.6 Hz), 5.09–5.16 (m, 1H), 6.91 (d, 2H,
J = 8.0 Hz, ArH), 6.97 (t, 1H, J = 7.6 Hz, ArH), 7.28 (t,
2H, J = 8.0 Hz, ArH), 7.42–7.45 (m, 3H, ArH), 7.69–7.72
(m, 2H, ArH) ppm; 13C NMR (75 MHz, CDCl3):
d = 37.69, 68.42, 78.75, 114.61, 121.34, 126.79, 128.76,
129.35, 129.55, 130.23, 156.47, 158.42 ppm; IR (KBr):
7. Ahmad G, Mishra PK, Gupta P, Yadav PP, Tiwari P, Tamrakar
AK, Srivastava AK, Maurya R (2006) Bioorg Med Chem Lett
16:2139
8. Park KK, Ko DH, You Z, Khan MOF, Lee HJ (2006) Steroids
71:103
9. Pinho e Melo TMVD (2005) Curr Org Chem 9:925
10. Gothelf KV, Jorgensen KA (1998) Chem Rev 98:863
11. Baraldi PG, Barco A, Benetti S, Pollini GP, Simoni D (1987)
Synthesis 857
12. Caramella P, Grunanger P (1984) In: Padwa A (ed) 1,3-Dipolar
cycloaddition chemistry, vol 1, chap 3. Wiley, New York, p 177
13. Just G, Dahl K (1968) Tetrahedron 24:5251
14. Shang YJ, Wang YG (2002) Synthesis 1663
15. Huisgen R (1984) In: Padwa A (ed) 1,3-Dipolar cycloaddition
chemistry, vol 1. Wiley, New York, p 291
16. Bhasle S, Kurhade S, Viplava Prasad U, Palle VP, Bhuniya D
(2009) Tetrahedron Lett 50:3948
17. Meldelshon BA, Lee S, Kim S, Teyssier F, Aulakh VS, Ciufolini
MA (2009) Org Lett 11:1539
18. Chatterjee N, Pandit P, Halder S, Patra A, Maiti DK (2008) J Org
Chem 73:7775
19. Das B, Mahender G, Holla H, Banerjee (2005) Arkvoc iii:27
20. Noguchi M, Tsukimoto A, Kadawaki A, Hikata J, Kakelib A
(2007) Tetrahedron Lett 48:3539
m = 2,918, 1,599, 1,497 cm-1; MS: m/z = 253(M?).
ꢀ
Methyl 3-phenyl-4,5-dihydroisoxazole-5-carboxylate
(8b, C11H11NO3)
White solid, yield 85%; m.p.: 61–62 °C; Rf = 0.40 (20%
EtOAc/pet ether); 1H NMR (400 MHz, CDCl3): d = 3.64–
3.72 (m, 2H), 3.82 (s, 3H, OCH3), 5.20 (dd, 1H, J = 7.6,
10.4 Hz), 7.39–7.45 (m, 3H, ArH), 7.67–7.69 (m, 2H, ArH)
ppm; 13C NMR (75 MHz, CDCl3): d = 38.92, 52.86, 77.95,
126.95, 128.48, 128.80, 130.56, 156.09, 170.74 ppm;
IR (KBr): m = 2,952, 1,752, 1,603, 1,441 cm-1; MS:
ꢀ
m/z = 205 (M?).
21. Vaidya VV, Wankhede KS, Salunkhe MM, Trivedi GK (2008)
Synth Commun 38:2392
22. Liaskopoulos T, Skoulika S, Tsoungas PG, Varvounis G (2008)
Synthesis 711
Acknowledgments We thank Prof. K. C. Majumdar for providing
some chemicals. R. N. De is grateful to U.G.C. (New Delhi) and
University of Kalyani for financial support.
23. Dignam KJ, Hegarly AF, Quain PL (1977) J Chem Soc Perkin
Trans II 1457
24. Lee GAA (1982) Synthesis 508
25. Van Mersbergen D, Wijnen JW, Engberts JBFN (1998) J Org
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