A green chemical approach for the N-alkylation of aldoximes to form nitrones in organized aqueous media and their in situ cycloaddition with olefins

Article abstract of DOI:10.1039/b812290c

Aldoximes react with α,β-unsaturated carbonyl and sulfonyl compounds in organized aqueous media (nanoreactor system) using dodecylbenzenesulfonic acid (DBSA) as surfactant to generate N-alkylated nitrones, which undergo intermolecular cycloaddition in the same pot with maleimides to give the desired cycloadduct in absence of any organic solvent and catalyst. Divinyl sulfone was successfully used for both N-alkylation and intramolecular cycloaddition, affording only one cycloadduct. This is a new example of green chemistry and provides a new aspect of reactions in water.

Full text of DOI:10.1039/b812290c

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PAPER
www.rsc.org/greenchem | Green Chemistry
A green chemical approach for the N-alkylation of aldoximes to
form nitrones in organized aqueous media and their in situ
cycloaddition with olefins†
Sandip K. Hota, Amrita Chatterjee, Pranab K. Bhattacharya‡ and Partha Chattopadhyay*
Received 13th August 2008, Accepted 9th October 2008
First published as an Advance Article on the web 11th November 2008
DOI: 10.1039/b812290c
Aldoximes react with a,b-unsaturated carbonyl and sulfonyl compounds in organized aqueous
media (nanoreactor system) using dodecylbenzenesulfonic acid (DBSA) as surfactant to generate
N-alkylated nitrones, which undergo intermolecular cycloaddition in the same pot with
maleimides to give the desired cycloadduct in absence of any organic solvent and catalyst. Divinyl
sulfone was successfully used for both N-alkylation and intramolecular cycloaddition, affording
only one cycloadduct. This is a new example of green chemistry and provides a new aspect of
reactions in water.
Introduction
the formation of nitrones through N-alkylation of oximes in
organized aqueous media.
1
2
The concept of green chemistry and its application in syn-
thetic chemistry, has emerged as a major solution for the
development of cleaner and more benign chemical processes.
Various methodologies and routes have been developed for
Nitrones are well-known 1,3-dipoles in thermal cycloaddition
reactions with multiple bond systems to provide different
8
heterocyclic five membered ring systems. Various uses and
9
reactions of nitrones are well established. There are many
3
this purpose. Use of water as a solvent is undoubtedly the
10
standard routes for the formation of nitrones. Most of them
best alternative as there will be no use of hazardous and toxic
organic solvents and no need for vigorous drying of the solvents.
The problem of insolubility and hydrolytic decomposition of
many organic compounds in water may be solved by the use
include anhydrous conditions or dehydrative agents. For exam-
ple, one of the most convenient methods of nitrone generation
is the reaction of oximes with various alkylating agents or
11
dipolarophiles. When oximes are N-alkylated in this process,
4
of a surfactant, which in water forms an organized medium.
the formed nitrones have different functionalities and can take
The border between the homogeneous (solution phase) and
heterogeneous phases consists of micellar, reverse micellar,
microheterogeneous, colloidal phases etc. During the course
of surfactant catalyzed reactions, the organized medium acts
as a nanoreactor, which solubilizes and conforms hydrophobic
organic compounds into its hydrophobic cores and thus protects
part in various types of reactions leading to the synthesis of
11a,12
biologically active natural products.
Cycloaddition reaction
with externally added dipolarophiles is the most common
reaction of the formed nitrones. However, most of the processes
use anhydrous conditions, toxic organic solvents and different
catalysts (non-green process), along with high temperature and
long reaction times.
5
6
water labile substances from decomposition. Although different
research groups have developed various types of reactions in
3
,4
aqueous media, the preparation of nitrones by N-alkylation
7
Results and discussion
of aldoximes in water appears to be the first example of this type
of useful reaction, attempted so far. In the course of developing
efficient organic reactions in water, our group earlier reported a
one-pot process for nitrone formation in water, followed by its
Intermolecular pathway
We hereby report for the first time the formation of ni-
trone through the N-alkylation of aldoximes in water and
its subsequent cycloaddition (Table 1). Aldoximes react with
a,b-unsaturated carbonyl and sulfonyl compounds to give
N-alkylated nitrones in moderate to good yields, which then
undergo intermolecular cycloaddition with maleimide to give
the desired cycloadduct. We used dodecylbenzenesulfonic acid
4b
intermolecular cycloaddition to form isoxazolidines. Recently,
we also reported stereoselective synthesis of chiral oxepanes
and pyrans through intramolecular nitrone cycloaddition in
4c
organized aqueous media. These studies led us to investigate
(
DBSA) as surfactant to form the desired organized media.
Chemistry Division, Indian Institute of Chemical Biology, 4,
Raja S. C. Mullick Road, Jadavpur, Kolkata, 700 032, India.
E-mail: partha@iicb.res.in
Dynamic light scattering (DLS), i.e. a particle size analyzer
5a
study, proved the formation of the nanoreactor system (Fig. 1).
We also obtained the optical micrograph of the aqueous media
containing DBSA as surfactant (Fig. 2).
The applicability of the resultant N-alkylated nitrone, such
as its reaction with some dipolarophiles through intermolecular
†
Electronic supplementary information (ESI) available: NMR spectra
of all the cycloaddition products and synthetic procedures of the reac-
tants. CCDC reference number 686184. For ESI and crystallographic
data in CIF or other electronic format see DOI: 10.1039/b812290c
‡
Deceased.
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Green Chem., 2009, 11, 169–176 | 169

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Table 1 Surfactant-catalyzed conjugate additions of oximes to a,b-unsaturated carbonyl and sulfonyl compounds and intermolecular nitrone
cycloaddition with various N-substituted maleimides in organised aqueous media
a
b
Entry
Oximes
R
1
Acceptors
Maleimide
Time/h
Product (Yield) (%)
Product (exo:endo)
1
2
3
4
5
6
7
8
9
0
1
2
3
1a
1a
1b
1b
1c
1c
1d
1e
1e
1f
Ph
Ph
3-BrC
3-BrC
4-NO
4-NO
(E)-PhCH=CH
n-C
n-C
2-NO
3-NO
Ph
2a
2b
2a
2b
2a
2b
2a
2a
2b
2b
2a
2c
2c
3a
3a
3b
3b
3a
3a
3a
3a
3a
3a
3c
3b
3a
20
20
26
26
28
28
22
22
20
30
26
25
32
4a (58)
4b (68)
4c (55)
4d (68)
4e (53)
4f (66)
4g (57)
4h (70)
4i (75)
4j (55)
4k (58)
4l (53)
4m (52)
100:0
60:40
100:0
59:41
100:0
77:23
100:0
100:0
100:0
59:41
68:32
100:0
100:0
6
6
H
H
4
4
2
C
6
H
H
4
4
2
C
6
3
H
H
7
3
7
1
1
1
1
2
C
C
6
6
H
H
4
4
1g
1a
1c
2
4-NO
2
C
6
H
4
a
b
1
13
after purification by column chromatography. exo:endo ratio is determined by H and C spectra.
Fig. 1 Dynamic light scattering (DLS) data of the organised media using DBSA as surfactant.
nitrone cycloaddition, has not been investigated much
1
1b,13
except for some reports in organic solvents.
Kanemasa
7
et al. have reported N-alkylation of aldoximes in organic
solvents such as benzene, dichloromethane and toluene in the
presence of Lewis acid catalysts like ZnI
2
and BF
3
.OEt and the
2
subsequent intermolecular cycloaddition with maleimides. In
many cases, they had to reflux the hazardous organic solvents
for many hours to get a good yield.
The present unique and safe approach for the preparation
of nitrones by N-alkylation of aldoximes and their in situ
intermolecular cycloaddition with various maleimides provides
important cycloaddition products. As a part of our process
we prepared seven aldoximes (1a–g; see ESI†). The aldoximes
Fig. 2 Optical micrograph of the aqueous media containing DBSA as
surfactant.
1
70 | Green Chem., 2009, 11, 169–176
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Table 2 Effect of surfactants in the nitrone formation and intermolec-
ular cycloaddition reaction in water
Table 3 Reaction of oximes with divinyl sulfones
a
Entry
Oxime
Time/h
Product
Yield (%)
1
2
3
4
5
1a
1b
1c
1d
1e
16
17
20
17
15
6a
6b
6c
6d
6e
57
55
52
53
53
Entry
A
Time/h
Yield (%)
1
2
3
4
5
6
7
Surfactant DBSA
—
Surfactant CTAB
Surfactant SDS
Surfactant Tween 80
Toluene-4-sulfonic acid
Toluene-4-sulfonic
acid + Surfactant CTAB
26
> 50
> 50
> 50
> 50
> 50
> 50
55
nil
10–15
5–10
not detected
-do-
a
after purification by column chromatography.
25
nitrogen atom and thus promoting the Michael addition (or ene-
like step). It was also found that the majority of the aldoximes
afforded a single product (exo) with ethyl acrylate (2a) but a
mixture of diastereomers with trans-chalcone (2b). Only the
aliphatic aldoxime, butyraldehyde oxime (1e) produced solely
the exo product with both the nucleophiles. The structures
of the products were deduced on the basis of analytical and
spectroscopic data. For example, the relative configurations
among the three methine protons (3-H, 3a-H, and 6a-H) of
were successfully reacted with a,b-unsaturated carbonyl com-
pounds in presence of the surfactant in aqueous media to give
N-alkylated nitrones in moderate to good yield (Table 1). We
used ethyl acrylate and trans-chalcone as a,b-unsaturated car-
bonyl compounds and phenyl vinyl sulfone as a,b-unsaturated
sulfonyl compound for this purpose. The progress of the reaction
was monitored by TLC. Between ethyl acrylate and trans-
chalcone, formation of the N-alkylated nitrone was better with
the former, possibly due to the absence of any substituent at the
b-position.
As the conjugate addition step of aldoximes to a,b-
unsaturated carbonyl compounds towards formation of
N-alkylated nitrones was found to be a slow process, N-
substituted maleimide was added directly to the reaction mixture
after formation of nitrone (~70%) to drive the equilibrium
towards the end product.
We selected the reaction of 3-bromobenzaldoxime (1b) with
ethyl acrylate (2a) and subsequent intermolecular cycloaddition
with N-methylmaleimide (3b) as a model reaction (Table 2). We
performed this reaction in various conditions including the use
of different types of surfactants i.e. cationic, anionic, nonionic
and acidic surfactants. Excellent results were obtained by using
acidic surfactant DBSA. Yields were not good with cationic
4
c were deduced by COSY and NOESY. From NOESY, it
was evident that the 3a-H and 6a-H methine protons are in
cis orientation, whereas 3-H is trans to 6a-H i.e. trans to 3a-
H also. These results confirmed the exo structure. Exclusive or
predominant formation of exo product in most of the reactions
(Table 1) can be rationalised, as endo approach is sterically
hindered. The minor endo adducts were not separated and the
diastereomeric ratio was determined by NMR spectroscopy.
Intramolecular pathway
Aldoximes reacted with divinyl sulfone (5), a 1,4-diene, via a
tandem process involving an N-(4-alkenyl) nitrone intermediate
and gave rise to a bridged-ring product (6). Although the
intermediate N-(4-alkenyl) nitrones can undergo cycloaddition
in two different ways to yield the cycloadduct (6) or (7), we got
only 6a–e. The reaction of various aldoximes with divinyl sulfone
afforded only one product each, i.e. 8-aryl/alkyl-7-oxa-4-thia-1-
aza-bicyclo[3.2.1]octane 4,4-dioxide exclusively. Though Grigg
et al. had reported the formation of two types of bridged-ring
products in boiling xylene, we found only one in good yield
(Table 3). Here also, the nucleophilicity of the oxime nitrogen
atom controls the rate of the reaction by regulating the Michael
addition step. We observed that the greater the electron-density
on the oxime nitrogen atom, greater is the yield of the product.
The structure of the product was deduced from spectroscopic
(
CTAB), anionic (SDS) or nonionic (Tween 80) surfactants.
There were no reactions in neat conditions or in water without
surfactant. So it was evident that acidic surfactants had a
prominent role in the N-alkylation of aldoximes towards the
formation of the cycloadducts.
To confirm whether any non-surfactant type acid can promote
nitrone formation under this condition, we carried out the
reaction using a non-surfactant acid (toluene-4-sulfonic acid).
As no product could be detected, the role of surfactant was
established. The reaction also occurred in much lower yield
when toluene-4-sulfonic acid was used in conjunction with a
non-acidic surfactant (CTAB). Thus, the dual role of DBSA in
ensuring the success of the reaction is established.
Moderate to excellent yields (52–75%) were obtained (Table 1)
in this reaction. We observed that the nature of the alkyl or
aryl components present in the aldoxime moiety influenced the
course of the reaction. Generally electron donating substituents
gave better results by enhancing the nucleophilicity of the oxime
14
15
and analytical data and confirmed from X-ray crystal structure
determination (Fig. 3).
Conclusions
In conclusion, we have demonstrated a useful and ‘green’ ap-
proach to the preparation of nitrones through the N-alkylation
of aldoximes in organized aqueous media and subsequent
intermolecular or intramolecular cycloaddition reactions in the
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added successively to a solution of the surfactant (DBSA,
0
.05 mmol) in H O (2 mL) at room temperature in a 25 mL
2
round-bottom flask. The reaction was sonicated§ for 10 minutes,
◦
then stirred at 55 C and monitored by TLC. After satisfactory
formation of the N-alkylated nitrone, N-alkyl or aryl maleimide
(
0.6 mmol) was added and the stirring of the reaction mixture
was continued at that temperature. After stirring at that tem-
perature for the period of time listed in Table 1, the product
was extracted with ethyl acetate. Then it was washed with
brine, dried over Na
2
SO , and concentrated in rotavapor. The
4
crude product was then purified by silica gel column chromato-
graphy.
Fig. 3 X-Ray structure of the compound 6a.
3
-(4,6-Dioxo-3,5-diphenyl-hexahydro-pyrrolo[3,4-d]isoxazol-2-
same pot. This process leads to the formation of only one
product in most of the cases. This concept of a nanoreactor,
formed in the organized aqueous media, could be applicable to
various other types of reactions.
yl)-propionic acid ethyl ester (4a)
◦
Grayish solid; yield 58% (eluent PS-EA, 4:1); mp. 145 C; only
exo product is formed; H NMR (CDCl , 300 MHz): d 1.20 (t,
1
3
J = 7.1 Hz, 3H), 2.51–2.62 (m, 2H), 2.85–3.03 (m, 2H), 3.84
(
1
dd, J = 3.3, 7.3 Hz, 1H), 4.08 (q, J = 7.1 Hz, 2H), 4.37 (bs,
Experimental
13
H), 5.07 (d, J = 7.3 Hz, 1H), 7.31–7.50 (m, 10H); C NMR
(
(
(
(
CDCl
3
, 150 MHz): d 14.1 (CH
3
), 33.1 (CH
2
), 53.7 (CH
2
), 60.4
General
CH ), 68.4 (CH), 75.8 (CH), 79.1 (CH), 126.3 (Ar-CH), 128.2
Ar-CH), 128.8 (Ar-CH), 128.9 (Ar-CH), 129.0 (Ar-CH), 129.0
Ar-CH), 129.2 (Ar-CH), 129.3 (Ar-CH), 131.3 (C), 171.8 (C),
2
Some reagents were obtained from commercial sources and used
without purification. The solvents used were of technical grade,
1
and freshly distilled prior to use. H (300 MHz, 600 MHz) and
1
1
72.3 (C), 174.3 (C); IR (KBr) nmax: 3449, 2915, 1713, 1497,
1
3
C (75 MHz, 150 MHz) NMR spectra were recorded using
CDCl as solvent and tetramethyl silane (TMS) as internal
-1
+
389, 1324, 1193, 1070 cm ; ESIMS (m/z): 395 (M + 1), 417
+
3
(
M + 23). Elemental analysis for C22
H
N
5
O : Calcd. C, 66.99;
22
2
standard on Bruker DPX 300 MHz and Bruker DRX 600 MHz
NMR instruments at ambient temperature. Chemical shifts are
stated in parts per million in d scales. COSY and NOESY exper-
H, 5.62; N, 7.10. Found: C, 67.13; H, 5.73; N, 6.97.
2
-(3-Oxo-1,3-diphenyl-propyl)-3,5-diphenyl-tetrahydro-
1
iments have been carried out in order to assign the H spectra
pyrrolo[3,4-d]isoxazole-4,6-dione (4b)
completely. Infrared spectra were recorded on a JASCO-FT-
IR Model-410. Spectra were calibrated against the polystyrene
Yellowish sticky liquid; yield 68%; (eluent PS-EA, 4:1); mix-
1
-
1
ture of diastereomers; exo:endo = 60:40; H NMR (CDCl ,
absorption at 1601 cm . IR spectra were measured using a KBr
pellet or inneat condition. Mass spectrawere measuredmostlyin
ESIMS (+) and some in EIMS mode. DI-EIMS were recorded
on a GCMS-Shimadzu-QP5050A and ESIMS were done on
3
3
00 MHz): d 3.23 (dd, J = 4.9, 17.5 Hz, 1H), 3.53 (dd,
J = 6.6, 16.9 Hz, 1H), 3.58 (t, J = 8.1 Hz, 2H), 3.85 (d,
J = 8.7 Hz, 1H), 4.04–4.14 (m, 2H), 4.27 (t, J = 8.5 Hz,
1H), 4.59–4.68 (m, 2H), 4.84 (t, J = 5.6 Hz, 1H), 4.94 (d,
J = 7.3 Hz, 1H), 5.26 (d, J = 8.2 Hz, 1H), 6.65–6.68 (m,
1H), 7.08 (d-like, J = 6.8 Hz, 2H), 7.18–7.54 (m, 32H), 7.97
ꢀ
R
ꢀR
TM
a Waters Micromass Q-TOF micro Mass Spectrometer.
X-Ray crystallographic data of single crystals were collected on
˚
Bruker Kappa Apex II with Mo-Ka radiation (l = 0.71073 A).
1
3
(
t-like, J = 8.0 Hz, 4H); C NMR (CDCl
3
, 75 MHz): d
Dynamic light scattering (DLS) was performed by Malvern
Instruments (Model: Nano ZS 80). Optical micrograph was
taken at 10x magnification in a Nikon ECLIPSE (Model: E200)
microscope. The surfactants used were dodecyl benzene sulfonic
acid (DBSA), cetyl trimethyl ammonium bromide (CTAB),
sodium dodecyl sulfate (SDS) and polyoxyethylene(20) sorbitan
monooleate (Tween 80). TLC was performed on pre-coated
plates (0.25 nm, silica gel 60 F254). Organic extracts were
dried over anhydrous sodium sulfate. Column chromatography
and flash chromatography were carried out using commercial-
grade silica gel (100–200 mesh or 230–400 mesh). PS and
4
6
1
2.4 (CH
2
), 43.7 (CH
2
), 53.5 (CH), 54.1 (CH), 61.0 (CH),
4.0 (CH), 68.5 (CH), 69.0 (CH), 75.5 (CH), 78.0 (CH),
25.9 (Ar-CH), 127.6 (Ar-CH), 127.8 (Ar-CH), 128.0 (Ar-
CH), 128.1 (Ar-CH), 128.2 (Ar-CH), 128.4 (Ar- CH), 128.5
(
(
(
Ar-CH), 128.6 (Ar-CH), 128.7 (Ar-CH), 128.9 (Ar-CH), 129.0
Ar-CH), 130.1 (Ar-CH), 130.8 (Ar-CH), 131.2 (Ar-CH), 132.8
Ar-CH), 133.0 (Ar-CH), 133.2 (Ar-CH), 134.6 (C), 135.3 (C),
1
1
1
36.8 (C), 137.0 (C), 171.6 (C), 171.9 (C), 172.7 (C), 174.2 (C),
97.8 (C); IR (neat) nmax: 3492, 3062, 3028, 2923, 2342, 1958,
-
1
785, 1722, 1684, 1597, 1496, 1451, 1381, 1288, 1205 cm ;
+
◦
EIMS (m/z): 502(M ). Elemental analysis for C H N O :
EA stand for petroleum spirit (60–80 C) and ethyl acetate,
32
26
2
4
Calcd. C, 76.48; H, 5.21; N, 5.57. Found: C, 76.39; H, 5.33;
N, 5.66.
respectively.
Experimental procedure for N-alkylation of aldoximes and
subsequent cycloaddition reaction in organized aqueous media
§
It is well-known that sonication favors the formation of organized
An aromatic or aliphatic aldoxime (0.5 mmol) and an a,b-
unsaturated carbonyl compound (0.5 mmol, 1.0 equiv.) were
media and so we did it to obtain a shorter reaction time and better
result.
1
72 | Green Chem., 2009, 11, 169–176
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-
1
+
+
3
-[3-(3-Bromo-phenyl)-5-methyl-4,6-dioxo-hexahydro-
693 cm ; ESIMS (m/z): 462 (M + 23), 494 (M + 23 + MeOH).
Elemental analysis for C22 : Calcd. C, 60.13; H, 4.82; N,
.56. Found: C, 60.25; H, 4.72; N, 9.69.
pyrrolo[3,4-d]isoxazol-2-yl]-propionic acid ethyl ester (4c)
H
21
N
3
O
7
9
◦
Yellow solid; yield 55% (eluent PS-EA, 4:1); mpt. 140 C; only
exo product is formed; confirmed by COSY and NOESY; H
1
3
-(4-Nitro-phenyl)-2-(3-oxo-1,3-diphenyl-propyl)-5-phenyl-
tetrahydro-pyrrolo[3,4-d]isoxazole-4,6-dione (4f)
NMR (CDCl
J = 6.9 Hz, 2H), 2.80–2.89 (m, 1H), 2.97 (s, 3H), 3.06–3.16 (m,
H), 3.70 (t, J = 7.9 Hz, 1H), 3.93 (d, J = 8.7 Hz, 1H), 4.12 (q,
3
, 300 MHz): d 1.25 (t, J = 7.1 Hz, 3H), 2.68 (t,
1
Yellowish orange solid; yield 66%; (eluent PS-EA, 4:1); mp.
◦
1
J = 7.1 Hz, 2H), 4.89 (d, J = 7.2 Hz, 1H), 7.11 (d, J = 7.7 Hz,
192 C; mixture of diastereomers; exo:endo = 77:23; H NMR
1
1
H), 7.23 (t, J = 7.8 Hz, 1H), 7.33 (s, 1H), 7.46 (d, J = 7.9 Hz,
H); C NMR (CDCl , 75 MHz): 14.1 (CH ), 24.8 (CH ), 32.8
), 51.0 (CH ), 54.1 (CH), 60.5 (CH ), 72.5 (CH), 76.2 (CH),
22.9 (q), 126.3 (Ar-CH), 130.3 (Ar-CH), 130.7 (Ar-CH), 132.0
(CDCl , 600 MHz): d 3.35 (dd, J = 5.4, 16.8 Hz, 2H), 3.66 (t, J =
3
1
3
3
3
3
8.1 Hz, 2H), 3.94 (d, J = 8.4 Hz, 2H), 4.25 (dd, J = 8.4, 16.8 Hz,
(
CH
2
2
2
1H), 4.28 (t, J = 8.4 Hz, 1H), 4.58 (dd, J = 5.4, 8.4 Hz, 2H), 4.98
(d, J = 7.5 Hz, 2H), 6.79 (d, J = 8.1 Hz, 1H), 7.00–7.02 (m, 3H),
7.22–7.24 (m, 4H), 7.31–7.58 (m, 22H), 8.03 (d, J = 8.4 Hz, 4H),
1
(
Ar-CH), 135.8 (C), 171.7 (C), 172.6 (C), 174.8 (C); IR (KBr)
1
3
n
max: 2986, 1786, 1731, 1707, 1564, 1437, 1385, 1322, 1290, 1180,
8.27 (d, J = 8.4 Hz, 4H); C NMR (CDCl , 150 MHz): d 42.0
3
-
1
1131, 1070, 1045, 983, 856, 781 cm ; ESIMS (m/z): 433, 435
(CH ), 43.8 (CH ), 53.7 (CH), 54.2 (CH), 61.3 (CH), 64.5 (CH),
2
2
+
+
79
81
(
M + Na for Br, Br). Elemental analysis for C17
H
19BrN
2
O
5
:
67.6 (CH), 69.1 (CH), 75.4 (CH), 77.8 (CH), 123.4 (Ar-CH),
124.2 (Ar-CH), 125.6 (Ar-CH), 125.8 (Ar-CH), 127.8 (Ar-CH),
128.2 (Ar-CH), 128.3 (Ar-CH), 128.3 (Ar-CH), 128.6 (Ar-CH),
Calcd. C, 49.65; H, 4.66; N, 6.81. Found: C, 49.56; H, 4.78; N,
6.77.
128.7 (Ar-CH), 128.7 (Ar-CH), 128.9 (Ar-CH), 129.0 (Ar-CH),
3
-(3-Bromo-phenyl)-5-methyl-2-(3-oxo-1,3-diphenyl-propyl)-
129.2 (Ar-CH), 130.1 (Ar-CH), 130.9 (C), 133.3 (Ar-CH), 133.4
(Ar-CH), 134.0 (C), 136.6 (C), 137.0 (C), 139.8 (C), 140.6 (C),
tetrahydro-pyrrolo[3,4-d]isoxazole-4,6-dione (4d)
1
1
1
5
7
42.6 (C), 147.5 (C), 148.1 (C), 171.1 (C), 171.6 (C), 172.3 (C),
Yellowish white solid; yield 68% (eluent PS-EA, 4:1); mpt.
73.6 (C), 197.8 (2C, C); IR (KBr) nmax: 3449, 3065, 1723, 1685,
◦
1
34 C; mixture of diastereomers; exo:endo = 59:41; further
-1
598, 1521, 1496, 1449, 1385, 1348, 1205 cm ; ESIMS (m/z):
1
separation by column chromatography failed; H NMR (CDCl
3
,
+
70 (M + 23). Elemental analysis for C32
H
25
N
3
6
O : Calcd. C,
3
1
3
1
00 MHz): d 2.75 (s, 3H), 2.89 (s, 3H), 3.26 (dd, J = 5.7, 17.6 Hz,
0.19; H, 4.60; N, 7.67. Found: C, 70.28; H, 4.52; N, 7.80.
H), 3.41 (t, J = 8.0 Hz, 1H), 3.58 (dd, J = 7.0, 16.9 Hz, 1H),
.68 (d, J = 8.6 Hz, 1H), 3.92–4.05 (m, 3H), 4.36 (d, J = 9.0 Hz,
H), 4.49 (t, J = 6.7 Hz, 1H), 4.74 (q, J = 5.9 Hz, 2H), 5.02
3
-(4,6-Dioxo-5-phenyl-3-styryl-hexahydro-pyrrolo[3,4-
d]isoxazol-2-yl)-propionic acid ethyl ester (4g)
(
7
d, J = 7.7 Hz, 1H), 6.99–7.03 (m, 3H), 7.17–7.33 (m, 15H),
1
3
.44–7.48 (m, 7H), 7.94 (t, J = 7.0 Hz, 3H); C NMR (CDCl
3
,
Brown liquid; yield 57%; (eluent PS-EA, 4:1); only exo product
1
75 MHz): 24.4 (CH ), 24.6 (CH ), 42.5 (CH ), 43.0 (CH ), 53.5
3
3
2
2
is formed; H NMR (CDCl , 300 MHz): d 1.22 (t, J = 7.1 Hz,
3
(
CH), 54.3 (CH), 60.9 (CH), 64.3 (CH), 67.2 (CH), 69.1 (CH),
3H), 2.60–2.73 (m, 2H), 2.84–2.92 (m, 1H), 3.29–3.39 (m, 1H),
3.62 (t, J = 8.3 Hz, 1H), 3.76 (t, J = 7.5 Hz, 1H), 4.07–4.16
(m, 2H), 4.98 (d, J = 7.3 Hz, 1H), 5.99 (dd, J = 8.9, 15.8 Hz,
7
1
1
1
1
1
1
1
6
5.4 (CH), 77.2 (CH), 122.1 (q), 122.8 (q), 126.2 (Ar-CH),
27.8 (Ar-CH), 128.0 (Ar-CH), 128.2 (Ar-CH), 128.4 (Ar-CH),
28.4 (Ar-CH), 129.6 (Ar-CH), 130.0 (Ar-CH), 130.3 (Ar-CH),
30.6 (Ar-CH), 130.8 (Ar-CH), 131.0 (Ar-CH), 131.9 (Ar-CH),
33.0 (Ar-CH), 133.1 (Ar-CH), 134.4 (C), 135.4 (C), 136.6 (C),
36.9 (C), 137.3 (C), 139.5 (C), 172.3 (C), 172.7 (C), 173.9 (C),
74.9 (C), 197.5 (C), 197.6 (C); IR (KBr) nmax: 3482, 3065, 1786,
714, 1596, 1431, 1380, 1286, 1219, 1145, 1051, 996, 791, 749,
1
3
1H), 6.77 (d, J = 15.8 Hz, 2H), 7.29–7.50 (m, 5H); C NMR
(CDCl , 150 MHz): d 14.2 (CH ), 33.0 (CH ), 50.7 (CH ), 52.8
3
3
2
2
(CH), 60.5 (CH ), 72.3 (CH), 75.7 (CH), 121.2 (Ar-CH), 126.3
(Ar-CH), 127.0 (Ar-CH), 128.5 (Ar-CH), 128.6 (Ar-CH), 128.9
(Ar-CH), 129.2 (Ar-CH), 129.3 (Ar-CH), 131.4 (C), 135.8 (C),
137.0 (Ar-CH), 172.0 (C), 172.4 (C), 173.9 (C); IR (neat) nmax
2982, 1720, 1597, 1497, 1450, 1383, 1193, 1094, 1028, 969, 860,
754, 693 cm ; ESIMS (m/z): 443 (M + 23). Elemental analysis
for C H N O : Calcd. C, 68.56; H, 5.75; N, 6.66. Found: C,
2
:
-
1
+
79
81
93 cm ; ESIMS (m/z): 541, 543 (M + 23 for Br, Br).
: Calcd. C, 62.44; H, 4.46;
N, 5.39. Found: C, 62.36; H, 4.38; N, 5.50.
-
1
+
Elemental analysis for C27
H
23BrN
2
O
4
2
4
24
2
5
68.69; H, 5.86; N, 6.79.
3
-[3-(4-Nitro-phenyl)-4,6-dioxo-5-phenyl-hexahydro-pyrrolo[3,4-
d]isoxazol-2-yl]-propionic acid ethyl ester (4e)
3-(4,6-Dioxo-5-phenyl-3-propyl-hexahydro-pyrrolo[3,4-
d]isoxazol-2-yl)-propionic acid ethyl ester (4h)
Brownish sticky liquid; yield 53%; (eluent PS-EA, 4:1); only exo
1
product is formed; H NMR (CDCl
7
3
(
3
, 300 MHz): d 1.22 (t, J =
Brownish orange sticky liquid; yield 70%; (eluent PS-EA, 4:1);
1
.1 Hz, 3H), 2.65 (t, J = 6.7 Hz, 2H), 2.97 (t, J = 6.7 Hz, 2H),
.80 (dd, J = 4, 7.4 Hz, 1H), 4.11 (q, J = 7.1 Hz, 2H), 4.45
only exo product is formed; H NMR (CDCl
3
, 300 MHz): d 1.0
(t, J = 6.8 Hz, 3H), 1.24 (t, J = 7.1 Hz, 3H), 1.52–1.73 (m,
bs, 1H), 5.09 (d, J = 7.4 Hz, 1H), 7.31–7.34 (m, 2H), 7.42–
4H), 2.66 (t, J = 6.9 Hz, 2H), 3.00–3.09 (m, 1H), 3.14–3.24 (m,
7
2
6
.54 (m, 3H), 7.62 (d, J = 8.6 Hz, 2H), 8.28 (d, J = 8.7 Hz,
H). C NMR (CDCl , 150 MHz): d 14.1 (CH ), 32.9 (CH ),
0.7 (CH ), 75.9 (CH), 124.2 (Ar-CH), 126.2 (Ar-CH), 129.0
1H), 3.41 (bs, 1H), 3.54 (dd, J = 3.5, 7.5 Hz, 1H), 4.13 (q, J =
1
3
13
3
3
2
7.1 Hz, 2H), 4.90 (d, J = 7.5 Hz, 1H), 7.29–7.50 (m, 9H);
C
),
2
NMR (CDCl
3
, 75 MHz): d 13.9 (CH
3
), 14.1 (CH
3
), 19.3 (CH
2
(
Ar-CH), 129.2 (Ar-CH), 129.4 (Ar-CH), 131.0 (C), 148.1 (C),
29.8 (CH ), 33.2 (CH
2
2
), 51.0 (CH ), 54.3 (CH), 60.5 (CH
2
2
), 69.7
1
71.5 (C), 173.7 (C). IR (neat) nmax: 3381, 3078, 2926, 2855, 2453,
(CH), 76.3 (CH), 126.1 (Ar-CH), 126.3 (Ar-CH), 128.8 (Ar-CH),
129.1 (Ar-CH), 129.2 (Ar-CH), 131.4 (C), 171.8 (C), 174.8 (C);
1788, 1722, 1599, 1521, 1383, 1348, 1195, 1108, 1015, 853, 754,
This journal is © The Royal Society of Chemistry 2009
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IR (neat) nmax: 3489, 2961, 2935, 2873, 1784, 1724, 1597, 1498,
300 MHz): d 0.80–0.94 (m, 9H), 1.25 (t, J = 7.1 Hz, 3H), 1.49–
1.63 (m, 4H), 2.66–2.75 (m, 3H), 2.80–2.99 (m, 3H), 3.09–3.16
(m, 2H), 3.37–3.51 (m, 4H), 3.56 (dd, J = 2.9, 8.2 Hz, 1H), 3.75
(t, J = 7.9 Hz, 1H), 4.09–4.13 (m, 4H), 4.32 (dd, J = 5.6, 7.9 Hz,
1H), 4.78 (d, J = 8.2 Hz, 1H), 4.83 (s, 1H), 4.92 (d, J = 7.3 Hz,
-
1
1
456, 1382, 1189, 1061, 1028, 858, 736, 692 cm ; ESIMS (m/z):
+
+
3
83 (M + 23), 415 (M + 23 + MeOH). Elemental analysis for
: Calcd. C, 63.32; H, 6.71; N, 7.77. Found: C, 63.22;
H, 6.63; N, 7.62.
C
19
H
24
N
2
O
5
1
H), 5.27 (d-like, 1H), 6.77 (d, J = 9.6 Hz, 1H), 7.57–7.65 (m,
2
-(3-Oxo-1,3-diphenyl-propyl)-5-phenyl-3-propyl-tetrahydro-
2H), 7.74 (d, J = 7.6 Hz, 1H), 8.08 (s, 1H), 8.19 (d, J = 7.7 Hz,
1
3
pyrrolo[3,4-d]isoxazole-4,6-dione (4i)
1H), 8.31 (s, 1H); C NMR (CDCl
3
, 150 MHz): d 11.0 (CH
), 21.9 (CH ), 32.6 (CH
), 48.9 (CH), 51.0 (CH
), 62.4 (CH), 67.8 (CH), 72.2 (CH), 76.0 (CH),
7.1 (CH), 122.1 (Ar-CH), 122.8 (Ar-CH), 123.3 (Ar-CH), 123.9
3
),
),
1
3
1.2 (CH
9.3 (CH
3
), 14.1 (CH
), 40.7 (CH
3
), 21.1 (CH
2
2
2
Yellowish orange sticky liquid; yield 75%; (eluent PS-EA, 4:1);
2
2
2
), 53.8 (CH), 55.7
1
only exo product is formed; H NMR (CDCl
3
, 300 MHz): d
(CH), 60.7 (CH
2
0
3
3
3
7
.68 (t, J = 6.7 Hz, 3H), 0.87–0.97 (m, 2H), 1.32–1.42 (m, 2H),
8
.54 (d, J = 8.1 Hz, 1H), 3.64 (dd, J = 9.5, 17.3 Hz, 1H), 3.74–
.78 (m, 1H), 3.97 (dd, J = 3.0, 17.3 Hz, 1H), 4.51 (dd, J =
.0, 9.0 Hz, 1H), 5.04 (d, J = 8.1 Hz, 1H), 7.20–7.27 (m, 5H),
.33–7.41 (m, 3H), 7.45–7.60 (m, 6H), 7.83 (d, J = 7.5 Hz, 1H);
(
(
Ar-CH), 129.8 (Ar-CH), 129.9 (Ar-CH), 133.1 (Ar-CH), 133.9
Ar-CH), 135.7 (C), 139.7 (C), 147.6 (C), 148.3 (C), 167.2 (C),
1
71.7 (C), 172.1 (C), 172.6 (C), 174.6 (C), 177.0 (C); ESIMS
+
(
m/z): 428 (M + Na+). Elemental analysis for C19
H
23
N
3
7
O :
1
3
C NMR (CDCl
CH ), 44.4 (CH
26.3 (Ar-CH), 126.5 (Ar-CH), 127.9 (Ar-CH), 128.1 (Ar-CH),
3
, 75 MHz): d 13.3 (CH
3
), 19.3 (CH
2
), 37.7
Calcd. C, 56.29; H, 5.72; N, 10.37. Found: C, 56.41; H, 5.85; N,
(
2
2
), 54.9 (CH), 65.2 (CH), 67.5 (CH), 78.7 (CH),
10.45.
1
1
1
1
28.2 (Ar-CH), 128.3 (Ar-CH), 128.4 (Ar-CH), 128.5 (Ar-CH),
28.7 (Ar-CH), 128.7 (Ar-CH), 129.1 (Ar-CH), 129.1 (Ar-CH),
29.2 (Ar-CH), 129.5 (Ar-CH), 131.4 (C), 133.0 (Ar-CH), 136.9
2
-(2-Benzenesulfonyl-ethyl)-5-methyl-3-phenyl-tetrahydro-
pyrrolo[3,4-d]isoxazole-4,6-dione (4l)
(
3
1
(
C), 139.3 (C), 173.8 (C), 175.4 (C), 197.5 (C); IR (neat) nmax
:
Yellowish orange amorphous solid; yield 53%; (eluent PS-EA,
1
064, 3029, 2960, 2874, 1785, 1720, 1683, 1596, 1496, 1453, 1380,
3:1); only exo product is formed; H NMR (CDCl
3
, 300 MHz):
-
1
+
189, 1078, 858, 750, 690 cm ; ESIMS (m/z): 491 (M + 23), 523
d 2.92 (s, 3H), 3.37–3.39 (m, 2H), 3.65 (dd, J = 3.2, 7.2 Hz,
1H), 3.71–3.84 (m, 2H), 4.79 (t-like, 1H), 5.04 (d, J = 7.2 Hz,
1H), 7.24–7.26 (m, 3H), 7.35–7.38 (m, 5H), 7.51–7.67 (m, 1H),
+
M + 23 + MeOH). Elemental analysis for C29
H
28
N
2
O : Calcd.
4
C, 74.34; H, 6.02; N, 5.98. Found: C, 74.42; H, 5.96; N, 6.09.
1
3
7
.81 (d, J = 7.4 Hz, 1H). C NMR (CDCl
3
, 150 MHz): d
3
-(2-Nitro-phenyl)-2-(3-oxo-1,3-diphenyl-propyl)-5-phenyl-
25.2 (CH ), 34.4 (CH ), 54.2 (CH), 54.3 (CH ), 66.8 (CH), 79.8
3
2
2
tetrahydro-pyrrolo[3,4-d]isoxazole-4,6-dione (4j)
(CH), 127.3 (Ar-CH), 127.9 (Ar-CH), 128.2 (Ar-CH), 128.3 (Ar-
CH), 128.7 (Ar-CH), 128.8 (Ar-CH), 129.0 (Ar-CH), 129.1 (Ar-
CH), 129.2 (Ar-CH), 133.8 (Ar-CH), 135.0 (C), 139.3 (C), 174.8
Brownish red sticky liquid; yield 55%; (eluent PS-EA, 4:1);
mixture of diastereomers; exo:endo = 59:41; 1H NMR (CDCl
00 MHz): d 3.29–3.41 (m, 2H), 4.06–4.09 (m, 1H), 4.14–4.17
m, 1H), 4.24 (dd, J = 8.4, 16.8 Hz, 2H), 4.38 (t, J = 8.4 Hz,
H), 4.55 (t, J = 6.8 Hz, 1H), 4.81 (t, J = 5.4 Hz, 1H), 4.98 (d,
3
,
(
1
C). IR (KBr) nmax: 3454, 2938, 1709, 1439, 1382, 1289, 1141,
3
(
1
-1
+
047 cm . ESIMS (m/z): 423 (M + 23). Elemental analysis
S: Calcd. C, 59.99; H, 5.03; N, 7.00. Found: C,
0.08; H, 4.96; N, 6.88.
for C20
6
H
20
N
2
O
5
J = 7.2 Hz, 1H), 5.15 (d, J = 9.2 Hz, 1H), 5.22 (d, J = 7.7 Hz,
1
7
H), 7.00 (d, J = 6.4 Hz, 4H), 7.08–7.39 (m, 17H), 7.48 (t, J =
.1 Hz, 6H), 7.55–7.68 (m, 6H), 7.94 (d, J = 7.1 Hz, 1H), 8.03
2
-(2-Benzenesulfonyl-ethyl)-3-(4-nitro-phenyl)-5-phenyl-
tetrahydro-pyrrolo[3,4-d]isoxazole-4,6-dione (4m)
1
3
(
4
d, J = 7.9 Hz, 3H); C NMR (CDCl
3
, 150 MHz): 41.7 (CH ),
2
1.8 (CH
2
), 52.8 (CH), 53.2 (CH), 61.2 (CH), 63.4 (CH), 64.0
Yellow sticky liquid; yield 52%; (eluent PS-EA, 3:1); only exo
1
(
(
(
(
(
(
(
CH), 66.3 (CH), 75.2 (CH), 76.7 (CH), 125.2 (Ar-CH), 125.2
Ar-CH), 125.8 (Ar-CH), 126.0 (Ar-CH), 127.3 (Ar-CH), 127.6
Ar-CH), 127.8 (Ar-CH), 128.2 (Ar-CH), 128.3 (Ar-CH), 128.4
Ar-CH), 128.6 (Ar-CH), 128.7 (Ar-CH), 128.7 (Ar-CH), 128.8
Ar-CH), 128.8 (Ar-CH), 128.9 (Ar-CH), 128.9 (Ar-CH), 129.0
Ar-CH), 129.0 (Ar-CH), 129.1 (Ar-CH), 129.2 (Ar-CH), 129.5
Ar-CH), 129.7 (Ar-CH), 131.0 (Ar-CH), 131.1 (C), 131.4 (C),
product is formed; H NMR (CDCl
3
, 300 MHz): d 3.04–3.16
(m, 2H), 3.38–3.53 (m, 2H), 3.80 (dd, J = 3.5, 6.9 Hz, 1H),
4.43 (bs, 1H), 5.00 (d, J = 7.4 Hz, 1H), 7.32 (d, J = 7.7 Hz,
2H), 7.45–7.68 (m, 8H), 7.85 (d, J = 7.7 Hz, 2H), 8.28 (d, J =
1
3
8.0 Hz, 2H). C NMR (CDCl
3
, 150 MHz): d 49.1 (CH ), 54.2
2
(CH ), 56.8 (CH), 66.3 (CH), 75.9 (CH), 124.1 (Ar-CH), 124.3
2
(Ar-CH), 126.2 (Ar-CH), 127.8 (Ar-CH), 128.4 (Ar-CH), 128.9
(Ar-CH), 129.2 (Ar-CH), 129.4 (Ar-CH), 130.9 (Ar-CH), 134.0
(Ar-CH), 139.2 (C), 142.5 (C), 147.8 (C), 148.2 (C), 173.3 (C).
IR (neat) nmax: 3489, 3068, 1721, 1601, 1520, 1447, 1383, 1348,
1
1
1
n
33.3 (C), 133.4 (Ar-CH), 133.4 (C), 133.7 (C), 134.0 (Ar-CH),
36.5 (C), 137.1 (C), 140.1 (C), 148.5 (C), 149.2 (C), 171.6 (C),
72.0 (C), 173.3 (C), 173.9 (C), 197.9 (C), 198.1 (C); IR (neat)
-
1
-1
+
max: 1721, 1680, 1593, 1526, 1494, 1380, 1202, 750 cm ; ESIMS
1308, 1195, 1146, 1083 cm . ESIMS (m/z): 508 (M + 1), 530
+
+
(
m/z): 570 (M + 23). Elemental analysis for C32
H
25
N
3
O
6
: Calcd.
(M + 23). Elemental analysis for C25
H
21
N
3
O S: Calcd. C, 59.16;
7
C, 70.19; H, 4.60; N, 7.67. Found: C, 70.32; H, 4.53; N, 7.56.
H, 4.17; N, 8.28. Found: C, 59.30; H, 4.26; N, 8.37.
3
-[3-(3-Nitro-phenyl)-4,6-dioxo-5-propyl-hexahydro-pyrrolo[3,4-
Experimental procedure for intramolecular nitrone cycloaddition
reaction in aqueous media
d]isoxazol-2-yl]-propionic acid ethyl ester (4k)
Brownish red sticky liquid; yield 58%; (eluent PS-EA, 4:1);
An aromatic or aliphatic aldoxime (0.5 mmol) and divinyl
sulfone (0.5 mmol, 1.0 equiv) were added successively to a
mixture of diastereomers; exo:endo = 68:32; 1H NMR (CDCl
3
,
1
74 | Green Chem., 2009, 11, 169–176
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solution of surfactant (DBSA, 0.05 mmol) in H
room temperature in a 25 mL round-bottom flask. The reaction
was sonicated for 10 minutes and then stirred at 55 C. After
stirring at that temperature for the period of time listed in
Table 3, the product was extracted with ethyl acetate. Then it
2
O (2 mL) at
16.0 Hz, 1H), 6.78 (dd, J = 1.0, 16.0 Hz, 1H), 7.27–7.41 (m, 5H).
C NMR (CDCl , 75 MHz): d 46.1, 53.4, 67.7, 68.8, 69.6, 123.3,
126.7, 128.5, 128.8, 129.0, 133.3, 135.7. IR (neat) nmax: 2980,
1
3
3
◦
-
1
1493, 1447, 1326, 1284, 1211, 1119, 965 cm . ESIMS (m/z): 288
+
(M + 23). Elemental analysis for C13
H
15NO S: Calcd. C, 58.85;
3
was washed with brine, dried over Na
2
SO , and concentrated
4
H, 5.70; N, 5.28. Found: C, 59.01; H, 5.83; N, 5.40.
in rotavapor. The crude product was then purified by silica gel
column chromatography.
8-Propyl-7-oxa-4-thia-1-aza-bicyclo[3.2.1]octane 4,4-
dioxide (6e)
8
-Phenyl-7-oxa-4-thia-1-aza-bicyclo[3.2.1]octane 4,4-
◦
dioxide (6a)
Off white solid; m.p. 115 C; yield 53%; (eluent PS-EA, 3:1);
1
H NMR (CDCl
3
, 300 MHz): d 0.96 (t, J = 7.0 Hz, 3H), 1.29–
◦
Colorless needles; m.p. 170 C; yield 57%; (eluent PS-EA, 3:1);
1
.56 (m, 4H), 2.99–3.05 (m, 1H), 3.24–3.34 (m, 2H), 3.61–3.65
1
H NMR (CDCl , 300 MHz): d 3.04–3.16 (m, 1H), 3.36–3.48
3
(
1
1
m, 2H), 3.90 (t, J = 6.7 Hz, 1H), 4.14 (dd, J = 6.0, 9.8 Hz,
(
m, 2H), 3.74–3.90 (m, 3H), 4.50 (d, J = 9.0 Hz, 1H), 5.15 (s,
13
H), 4.48 (d, J = 9.8 Hz, 1H). C NMR (CDCl
3
, 75 MHz): d
1
3
1
H), 7.29–7.46 (m, 5H). C NMR (CDCl
), 53.4 (CH ), 68.1 (CH ), 69.1 (CH), 70.5 (CH), 125.5 (Ar-
CH), 128.1 (Ar-CH), 128.8 (Ar-CH), 136.3 (C). IR (KBr) nmax
3
, 150 MHz): d 45.9
3.5 (CH
3
), 19.2 (CH
2
), 33.7 (CH
2
), 45.8 (CH
2
), 53.5 (CH
2
), 66.8
(
CH
2
2
2
(
CH), 68.7 (CH & CH
2
). IR (neat) nmax: 3434, 2949, 2871, 1455,
325, 1282, 1195, 1121, 963 cm . ESIMS (m/z): 206 (M + 1),
28 (M + 23). Elemental analysis for C
6.81; H, 7.37; N, 6.82. Found: C, 46.69; H, 7.49; N, 6.99.
:
-1
+
1
2
4
-
1
3433, 2998, 2945, 1607, 1453, 1304, 1224, 1169, 1121, 1083 cm .
+
8
H
15NO S: Calcd. C,
3
+
+
ESIMS (m/z): 240 (M + 1), 262 (M + 23). Elemental analysis
S: Calcd. C, 55.21; H, 5.48; N, 5.85. Found:
for C11
H
13NO
3
1
C, 55.33; H, 5.52; N, 5.92. Melting point and H spectra are
literature consistent.
1
4c
Acknowledgements
Financial support from the Department of Science and Tech-
nology (DST), New Delhi, Government of India is gratefully
acknowledged. We thank CSIR (India) for financial assistance,
as well as for research fellowship to S.H. and A.C. Thanks are
also due to Dr B. Achari, Emeritus Scientist, IICB for valuable
suggestions and Mr S. Samanta, IICB for X-ray analysis.
8
4
-(3-Bromo-phenyl)-7-oxa-4-thia-1-aza-bicyclo[3.2.1]octane
,4-dioxide (6b)
1
Yellowish white solid; yield 55%; (eluent PS-EA, 3:1); H NMR
(
CDCl
3
, 300 MHz): d 3.06–3.17 (m, 1H), 3.42 (d-like, J = 9.0 Hz,
H), 3.76–3.92 (m, 3H), 4.51 (d, J = 9.0 Hz, 1H), 5.12 (s, 1H),
.23–7.28 (m, 1H), 7.37 (d, J = 7.7 Hz, 1H), 7.46 (d, J = 7.7 Hz,
H), 7.65 (s, 1H). C NMR (CDCl , 150 MHz): d 45.9 (CH ),
3.4 (CH ), 68.1 (CH ), 69.0 (CH), 70.0 (CH), 123.1 (C), 124.2
2
7
1
5
1
3
3
2
Notes and references
2
2
(
(
Ar-CH), 128.9 (Ar-CH), 130.4 (Ar-CH), 131.4 (Ar-CH), 138.5
1
(a) P. Anastas, L. G. Heine, T. C. Williamson, in Green Chemical
Syntheses and Processes, Oxford University Press, New York, 2000;
(b) M. Lancaster, in Green Chemistry: An Introductory Text, Royal
Society of Chemistry, Cambridge, UK, 2002; (c) I. T. Horvath, Acc.
Chem. Res., 2002, 35, 685–685; (d) J. Andraos, Org. Process Res. Dev.,
2005, 9, 149–163; (e) A. S. Matlack, Introduction to Green Chemistry,
Marcel Dekker, New York, NY, 2001.
C). IR (KBr) nmax: 3418, 2962, 2896, 1567, 1471, 1419, 1316,
-
1
+
1
223, 1161, 1120 cm . ESIMS (m/z): 341 (M + 23). Elemental
S: Calcd. C, 41.52; H, 3.80; N, 4.40.
Found: C, 41.69; H, 3.88; N, 4.28.
analysis for C11
H
12BrNO
3
2
(a) M. Lancaster, in Handbook of Green Chemistry and Tech-
nology, ed. J. H. Clark, D. J. Macquarrie, Blackwell Publishing,
Abingdon, 2002; (b) P. T. Anastas and M. M. Kirchhoff, Acc.
Chem. Res., 2002, 35, 686–694; (c) Green Chemistry: Theory and
Practice, ed. P. T. Anastas, J. C. Warner, Oxford University Press,
Oxford, UK, 1998; (d) U. S. Environmental Protection Agency,
http://www.epa.gov/greenchemistry/principles.html.
8
4
-(4-Nitro-phenyl)-7-oxa-4-thia-1-aza-bicyclo[3.2.1]octane
,4-dioxide (6c)
◦
1
Off white solid; m.p. 240 C; yield 52%; (eluent PS-EA, 3:1); H
NMR (CDCl
3
, 300 MHz): d 3.13–3.17 (m, 1H), 3.40–3.55 (m,
H), 3.78–3.94 (m, 3H), 4.55 (d, J = 9.8 Hz, 1H), 5.24 (s, 1H),
.67 (d, J = 8.4 Hz, 2H), 8.26 (d, J = 8.4 Hz, 2H). C NMR
, 150 MHz): d 45.9 (CH ), 53.3 (CH ), 68.2 (CH ), 68.9
CH), 70.2 (CH), 124.1 (Ar-CH), 126.9 (Ar-CH), 143.2 (C),
2
7
1
3
3 (a) U. M. Lindstrom, Organic Recations in Water: Principles,
Strategies and Application, Blackwell Publishing, Abingdon, 2007
and references cited therein; (b) J. B. F. N. Engberts and M. J.
Blandamer, Chem. Commun., 2001, 1701–1708; (c) U. M. Lindstrom,
Chem. Rev., 2002, 102, 2751–2772; (d) M. C. Pirrung and K. Das
Sarma, J. Am. Chem. Soc., 2004, 126, 444–445; (e) D. Dallinger and
C. O. Kappe, Chem. Rev., 2007, 107, 2563–2591 and references cited
therein; (f) C.-J. Li, T.-H. Chan, Organic Reactions in Aqueous Media,
John Wiley & Sons, New York, 1997; (g) C.-J. Li, Chem. Rev., 2005,
105, 3095–3166; (h) Organic Synthesis in Water, ed. P. A. Grieco,
Blackie Academic and Professional, England, 1998; (i) Y. Kita, H.
Nambu, N. G. Ramesh, G. Anilkumar and M. Matsugi, Org. Lett.,
2001, 3, 1157–1160; (j) T. Okino and Y. Takemoto, Org. Lett., 2001,
3, 1515–1517.
(CDCl
3
2
2
2
(
1
1
47.8 (C). IR (KBr) nmax: 3423, 3111, 2948, 1601, 1514, 1347,
-
1
+
320, 1230, 1121, 1020 cm . ESIMS (m/z): 285 (M + 1), 307
+
(
M + 23). Elemental analysis for C11
H
12
N
2
5
O S: Calcd. C, 46.47;
H, 4.25; N, 9.85. Found: C, 46.32; H, 4.33; N, 9.94. Melting point
and H spectra are literature consistent.
1
14c
8
-Styryl-7-oxa-4-thia-1-aza-bicyclo[3.2.1]octane 4,4-
dioxide (6d)
4
(a) K. Manabe, S. Iimura, X.-M. Sun and S. Kobayashi, J. Am. Chem.
Soc., 2002, 124, 11971–11978; (b) A. Chatterjee, D. K. Maiti and P. K.
Bhattacharya, Org. Lett., 2003, 5, 3967–3969; (c) A. Chatterjee and
P. K. Bhattacharya, J. Org. Chem., 2006, 71, 345–348.
(a) We performed the dynamic light scattering (DLS) study and
observed that the surfactant in aqueous solution is self-assembled to
◦
1
Off white solid; m.p. 194 C; yield 53%; (eluent PS-EA, 3:1); H
NMR (CDCl , 300 MHz): d 3.03–3.07 (m, 1H), 3.36–3.44 (m,
2
J = 9.7 Hz, 1H), 4.72 (d, J = 5.0 Hz, 1H), 6.01 (dd, J = 5.3,
3
H), 3.70–3.79 (m, 2H), 4.15 (dd, J = 5.8, 9.7 Hz, 1H), 4.54 (d,
5
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form the nanoreactor, with hydrodynamic radii of 1.167 nm (27.65%)
and 97.75 nm (72.35%); (b) D. M. Vriezema, M. Comellas Aragones,
J. A. A. W. Elemans, J. J. L. M. Cornelissen, A. E. Rowan and R. J. M.
Nolte, Chem. Rev., 2005, 105, 1445–1490.
13 (a) D. Francois, A. Maden and W. V. Murray, Org. Lett., 2004, 6,
1931–1934; (b) R. Grigg, F. Heaney, J. Markandu, S. Surendrakumar,
T.-P. Mark and W. J. William, Tetrahedron, 1991, 47, 4007–4030;(c) A.
Hassner, R. Maurya, O. Friedman, H. E. Gottlieb, A. Padwa and D.
Austin, J. Org. Chem., 1993, 58, 4539–4546.
14 (a) P. Armstrong, R. Grigg and W. J. Warnock, J. Chem. Soc.,
Chem. Commun., 1987, 1325–1327; (b) R. Grigg, J. F. Malone,
M. J. Dorrity, F. Heaney, S. Rajviroongit, V. Sridharan and S.
Surendrakumar, Tetrahedron Lett., 1988, 29, 4323–4324; (c) R. Grigg,
M. J. Dorrity, F. Heaney, J. F. Malone, S. Rajviroongit, V. Sridharan
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6
7
M. Lee, C.-J. Jang and J.-H. Ryu, J. Am. Chem. Soc., 2004, 126,
8
082–8083.
For the generation of nitrones by N-alkylation of aldoximes in
non-aqueous media, see: K. Nakama, S. Seki and S. Kanemasa,
Tetrahedron Lett., 2001, 42, 6719–6722.
8
9
(a) A. Padwa, Angew. Chem., Int. Ed. Engl., 1976, 15, 123–136; (b) W.
Oppolzer, Angew. Chem., Int. Ed. Engl., 1977, 16, 10–23; (c) C. P.
Dell, J. Chem. Soc., Perkin Trans. 1, 1998, 3873–3905.
(a) M. Lombardo and C. Trombini, Synthesis, 2000, 6, 759; (b) K. V.
Gothelf and K. A. Jorgensen, Chem. Rev., 1998, 98, 863–910; (c) S.
Kanemasa, T. Tsuruoka and H. Yamamoto, Tetrahedron Lett., 1995,
15 Crystal data of compound 6a: C11
clinic, space group P21/c, a = 17.1392 (5) A˚ , b = 6.0512 (2) A˚ , c =
10.9857 (4) A˚ , b = 93.007 (2) , V = 1137.79 (7) A˚ , Z = 4, T = 296
H
13NO
3
S, FW = 239.28, mono-
◦
3
-3
3
6, 5019–5022.
0 (a) A. Padwa, in New Synthetic Methods, Verlag Chemie, New York,
979, vol. 5; (b) M. A. Voinov and I. A. Grigorev, Tetrahedron
(2) K, dcalcd = 1.397 g cm , F (000) = 504. Diffraction data were
1
1
measured with Mo K
a
(l = 0.71073 A˚ ) radiation at 296 K using a
1
Bruker Kappa Apex 2 CCD system. A total of 2660 unique reflections
◦
Lett., 2002, 43, 2445–2447; (c) R. Alibes, P. Blanco, P. March, M.
Figueredo, J. Font, A. Alvarez-Larena and J. F. Piniella, Tetrahedron
Lett., 2003, 44, 523–525.
were measured (qmax = 30.87 ). Data analyses were carried out
with the Difference Vectors program. The structures were solved by
16
direct methods using the SHELXS-97 program. Refinements were
carried out with a full matrix least squares method against F using
SHELXL-97. Non-hydrogen atoms were refined with anisotropic
thermal parameters. The final R value was R1 = 0.0456 and wR2 =
0.1500 with I > 2s(I). Crystallographic data have been deposited at
the Cambridge Crystallographic Data Centre with reference numbers
CCDC 686184.
2
1 (a) 1,3-Dipolar Cycloaddition Chemistry, ed. A. Padwa, Wiley, New
York, 1984, vol. 2, ch. 9, pp. 83–168; (b) M. Noguchi, H. Okada, S.
Nishimura, Y. Yamagata, S. Takamura, M. Tanaka, A. Kakehi and
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Miyabe, K. Yoshida, V. K. Reddy, A. Matsumura and Y. Takemoto,
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Fishwick, R. Grigg and M. Thornton-Pett, Tetrahedron, 2003, 59,
17
16 G. M. Sheldrick, SHELXS-97, Program for solution of crystal
structures, University of G o¨ ttingen, Germany, 1997; G. M. Sheldrick,
Acta Crystallogr. A, 1990, 46, 467–473.
17 G. M. Sheldrick, SHELXL-97, Program for refinement of crystal
structures, University of G o¨ ttingen, Germany, 1997.
9
997–10007 and references cited therein.
1
2 (a) S. E. Denmark and A. Thorarensen, Chem. Rev., 1996, 96, 137–
1
66; (b) R. Grigg, Chem. Soc. Rev., 1987, 16, 89–121 and references
cited therein.
1
76 | Green Chem., 2009, 11, 169–176
This journal is © The Royal Society of Chemistry 2009