Organocatalysis by an aprotic imidazolium zwitterion: Regioselective ring-opening of aziridines and applicable to gram scale synthesis

Article abstract of DOI:10.1039/c5gc01323b

An imidazole-based zwitterionic-salt, 4-(3-methylimidazolium)butane sulfonate (MBS), has been found to be an efficient organocatalyst for aziridine ring-opening regioselectively by various nucleophiles like indoles, pyrroles, methanol, ethanol, acetic aci

Full text of DOI:10.1039/c5gc01323b

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Organocatalysis by an aprotic imidazolium zwitterion:
regioselective ring-opening of aziridines and applicable on gram
scale synthesis †
Received 00th January 20xx,
Accepted 00th January 20xx
a
b
a
a
DOI: 10.1039/x0xx00000x
Nirnita Chakraborty Ghosal, Sougata Santra, Sudarshan Das, Alakananda Hajra, Grigory V.
b,c
a
Zyryanov and Adinath Majee*
www.rsc.org/
An imidazole-based zwitterionic-salt, 4-(3-methylimidazolium)butane sulfonate (MBS) has been found to be an efficient
organocatalyst for aziridine ring-opening regioselectively by various nucleophiles like indoles, pyrrole, methanol, ethanol,
acetic acid and di-iso-propylamine. The reactions are highly regioselective and they always afford the products from
benzylic attack. The present methodology is applicable on gram scale synthesis.
These compounds are usually obtained by the ring-opening
of N-substituted aziridines with appropriate nucleophiles. In
recent times a number of methods have been developed for
Introduction
Aziridines are very important molecules as key components of
various biologically-active natural products. These scaffolds
3
ring-opening reactions of aziridines with various nucleophiles,
4
using different catalytic systems such as Lewis acids or Lewis
1
were incorporated in many biologically-active molecules.
5
bases, transition metals and tetrabutyl ammonium fluoride.
6
7
Aziridines are also highly versatile intermediates in organic
synthesis due to their easy access and their susceptibility to
ring-opening by facile C-N bond cleavage. These ring opening
products are 1,2-bifunctional compounds like diamines,
aminols, amino ether, melatonin and α-amino-acid like
tryptophan derivatives which are very important in medicinal
chemistry as well as synthetically valuable in fundamentally
Very recently, Xia’s group developed a regioselective ring-
opening via nucleophilic addition reactions of aziridines in the
presence of visible light and a photoredox catalyst like
8
Ru(bpy) ]Cl . Regardless of their efficiency and reliability,
[
3
2
most of these methods suffer from one or more disadvantages
such as use of expensive reagents and catalysts, long reaction
times, requirement of inert atmosphere and harsh reaction
conditions. Again, it is important to note that all of these
2
important transformations (Scheme 1).
3
-8
methods are not general for the regioselective ring-opening
of aziridines by various nucleophiles using the same reaction
conditions. Therefore, finding a general and efficient method
for the regioselective ring-opening of aziridines by various
nucleophiles in terms of using basic chemicals as starting
materials, increasing efficiency, operational simplicity, mild
reaction conditions, and economic practicability is highly
desirable.
2
CO Me
CO
N
2
R
2
RO C
N
Lewis acid
H
OMe
+
N
O
H
N
H
Tryptophan derivative
COOH
2
H N
H
MeO
N
C
O
Over the past few years, significant interest has been
focused on the development of new protocols for
environmentally benign processes that are both economically
and technologically feasible, and an important area of green
N
N
H
H
Melatonin
Tryptophan
2b
Scheme 1 Ring opening of aziridines towards biologically active compounds.
9
chemistry deals with solvent minimization. Particularly, the
use of nonhazardous, inexpensive catalysts have attracted
interest for organic synthesis. In continuation of our research
on green synthesis, we have explored imidazole-based
zwitterionic-type molten salts as a new class of organocatalyst
a.
Department of Chemistry, Visva-Bharati (A Central University), Santiniketan-
31235, India, Tel./Fax: +913463 261526; E-mail: adinath.majee@visva-
bharati.ac.in
7
b.
Department of Organic Chemistry, Chemical Technological Institute, Ural Federal
University, 19 Mira Str., 620002 Yekaterinburg, Russian Federation
I. Ya. Postovskiy Institute of Organic Synthesis, Ural Division of the Russian
Academy of Sciences, 22 S. Kovalevskoy Str., 620219 Yekaterinburg, Russian
Federation
10
in various chemical transformations. By the reactions of the
c.
various imidazoles with 1,4-butane sultone / 1,3-butane
sultone the requisite zwitterionic-type molten salts are
11
obtained. These catalysts are non-volatile and generally
† Electronic Supplementary Informaꢀon (ESI) available: See
DOI: 10.1039/x0xx00000x
1
2
nonhazardous.
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From experience in our previous study, we found that the higher temperature as well as lower temperature the yields
C2-H of zwitterionic-type molten salt plays a crucial role in the are not satisfactory. Finally, the catalyst loading was checked
course of the reaction by activating the aldehydic oxygen under this reaction conditions using
1
A
as catalyst for the same
0b,c
through hydrogen bond formation.
It is a well-established reaction. We have observed that 10 mol% of A as catalyst
phenomenon that the cations of the ionic liquid (prepared afforded better yield (84%) compare to that of 5 mol% (70%
from the molten salt) activate the electrophiles, as the yield). Similarly using 15 mol% of the catalyst no considerable
hydrogen bond donors, and the anions of the ionic liquids improvement was observed (85% yield). In absence of any
1
3
activate the nucleophiles, as the hydrogen bond acceptors.
catalyst no conversion has been detected (entry 10, Table 1).
Very recently, we also observed that both the cation and anion
cooperatively affect the cycloaddition reaction of aryl nitriles
a
Table 1 Optimization of the reaction conditions.
with NaN
the C2-H of the imidazolium moiety plays a crucial role as
electrophilic activation” of nitrile through hydrogen bond
3
for the synthesis of 5-substituted 1H-tetrazoles and
Ph
“
Ts
N
Zwitterionic salt (10 mol%)
NHTs
1
4
+
formation. In this regard, we considered that an aziridine
moiety would potentially be suitable for the activation through
hydrogen bond formation between the C2–H of the
imidazolium cation and the nitrogen atom of the aziridine
group.
85 C
o
N
N
Ph
H
H
1a
2a
3a
Zwitterionic salts:
N
N
N
N
HN
N
H
3
C
SO
SO
3
3
B
A
Herein, we are very pleased to report our findings as an
efficient and facile regioselective ring-opening of aziridines by
various nucleophiles under mild and solvent-free conditions
using zwitterionic-type salt (Scheme 2).
N
N
SO
3
H
3
C
SO3
H
3
C
CH
3
C
D
b
Entry
Catalyst (mol%)
A (10)
B (10)
C (10)
D (10)
A (10)
A (10)
A (10)
A (5)
Temp (°C)
Time (h) Yields (%)
Ts
N
Zwitterionic salt (10 mol%)
60-85 o
Ar
1
2
85
85
85
85
100
50
rt
3
3
84
70
64
ND
76
45
+
NuH
Nu
NHTs
Ar
C
1
2
3
NuH = indole, pyrrole, methanol, ethanol, acetic acid, N,N-diisopropylamine
3
3
Zwitterionic salt:
N
N
H
3
C
SO
3
c
4
3
4
-(3-Methylimidazolium)butane sulfonate (MBS)
Scheme 2 Regioselective ring-opening of aziridines by various nucleophiles.
5
3
Results and discussion
6
5
During our initial study, readily available indole (2a) as
nucleophile and aryl N-tosylaziridine (1a) were taken as model
substrates using 10 mol% of 4-(3-methylimidazolium)butane
7
10
3
Trace
70
sulfonate (MBS,
A) as catalyst. The reaction proceeded
8
85
85
85
smoothly at 85 °C and the product N-(2-(1H-indol-3-yl)-2-
phenylethyl)-4-methylbenzenesulphonamide (3a) was isolated
in 84% yield within 3 h. We have examined few other molten
salts synthesized in our laboratory as shown in the Table 1. It
9
A (15)
--
3
85
has been observed that other molten salts (
effective like MBS ( ) for this nucleophilic ring opening
process. When 4-(1-imidazolium)butane sulfonate (IBS, ) has
B
,
C
and
D
) are not
10
3
ND
A
a
B
Carried out with 0.5 mmol of 1a and 0.5 mmol of 2a in the presence of 10 mol%
b
c
been used (entry 2, Table 1) the yields are considerably lower catalyst in neat conditions. Isolated yields. ND = Not detected in TLC.
(
70%) than
propane sulfonate (
observed the desired product with 64% yield. According to our
A
(84%) as the catalyst. Similarly 3-(1-imidazolium)
Motivated by this result we further explored the scope of
this reaction (Table 2). At first, our attention was focused on
the use of different aziridine systems with various substituted
indoles to prove the general applicability of the reaction
conditions and the results are summarized in Table 2. It was
observed that electron-rich and electron-deficient indoles
reacted efficiently with various aziridines to afford the desired
products with good yields under the present reaction
C
, entry 3, Table 1) also less effective and
1
4
previous
dimethylimidazolium)butane sulfonate (
formation of desired product was observed. Accordingly, we
chose the aprotic zwitterion for this nucleophilic ring
observation
when
we
used
4-(2,3-
D
, entry 4, Table 1) no
A
opening. Effect of temperature has been studied as shown in
the table (entry 5-7, Table 1) and it has been observed that at
2
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conditions. N-Substituted indole also acted as an excellent Table 2 Zwitterionic salt-catalyzed regioselective ring-opening of aziridines with various
a
nucleophile to this ring-opening course and gave satisfactory indoles
yield (3b). The indole containing an electron donating -
Entry
1
Aziridines (1)
Indoles (2)
Products (3)
Yields
methoxy group at the 5-position showed good efficiency (3c).
The bromo-substituted indole gave the corresponding 3d in
b
(
%)
84
81% yield without forming any dehalogenated products.
Ts
N
Ph
Simple aryl N-tosylaziridine (1a) reacted well to give the
desired product with high yield (3a). Similarly, aryl N-
tosylaziridine substituted with chloro- at the benzene ring was
found as effective to afford the desired product (3f) with good
yield. Aziridines, substituted by different functional groups
underwent smooth reactions which highlighted the general
applicability of this reaction. In this regard, the effect of a
hydroxy group as well as carbonyl functionalities in the
aziridine system was also investigated where both of these
functionalities were unaffected under the present reaction
conditions and reacted smoothly with indole as well as the
N
H
NHTs
Ph
N
H
1
a
2a
3
a
2
81
Ts
N
Ph
NHTs
N
Me
Ph
1
N
Me
a
2b
3b
substituted indoles (3g-3j). The other aziridine systems, in
3
4
80
81
spite of simple aryl N-tosylaziridine did not affect the efficiency
and the regioselectivity of the reactions. All of the known
synthesized compounds have been characterized by spectral
data and the new compounds by spectral data and analytical
data. The reaction conditions are mild and give no
decomposition of the products or polymerization of the
starting materials. We have not observed any by-products for
all reaction combinations which are supported with high yields
and regioselectivity of the protocol.
Ts
N
MeO
Ph
NHTs
MeO
N
H
Ph
1
N
H
2
c
a
a
3c
Ts
N
Br
Ph
NHTs
Br
N
H
Ph
N
H
2
d
1
3
d
5
80
Ts
N
Ph
Me
NHTs
Me
N
H
e
Ph
N
H
2
1
a
3
e
6
79
Ts
N
Cl
N
H
Cl
NHTs
2
a
1
b
N
H
3
f
7
82
Ts
N
OH
Ph
OH
N
H
Ph
NHTs
1
c
N
H
2
a
3
g
8
77
Ts
N
OH
Ph
N
Me
OH
NHTs
Ph
1
c
N
Me
2
b
3
h
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78
Table 3 Zwitterionic salt-catalyzed regioselective ring-opening of aziridines with other
Ts
N
O
a
Ph
nucleophiles
N
H
Ph
Ph
Ph
NHTs
Entry
1
Aziridines (1)
Nucleophiles
2)
Products (3)
Temp Yields
O
b
1
d
2a
(
(°C)
(%)
N
H
MeOH (2f)
60
82
Ts
N
Ph
NHTs
3
i
OMe
Ph
1
0
76
Ts
N
Br
O
3k
Ph
1
a
Ph
Ph
N
H
2
MeOH (2f)
60
79
Ph
NHTs
Br
Ts
N
Cl
O
2
d
1
d
N
H
NHTs
OMe
Cl
3
j
3
l
1
b
a
Reaction Conditions: Aziridines 1 (0.5 mmol), indoles 2 (0.5 mmol), MBS (10
3
4
EtOH (2g)
EtOH (2g)
75
75
81
78
b
Ts
N
Ph
mol%) at 85 ᵒC for 3 h. All are isolated yields.
NHTs
O
Ph
Next, we explored our present methodology to probe the
general applicability using other nucleophiles to react with
aziridines regioselectively. To our delight, the corresponding
3
m
1a
Ts
N
Cl
ring-opening products (3) were obtained regioselectively in
good yields; the results are summarized in Table 3. We have
successfully used methanol and ethanol to synthesize the
NHTs
O
Cl
3
n
corresponding compounds (3k-3n) with good yields which
1
b
increases the scope of this transformation. Both aryl N-
tosylaziridine (1a) and chloro-substituted aryl N-tosylaziridine
5
6
CH
3
COOH
75
75
80
82
Ts
N
Ph
(
2h)
NHTs
(
1b) reacted smoothly with good yields. Acetic acid also
O
Ph
behaved as a very good nucleophile to open the aziridine
moiety; yielding the corresponding products 3o and 3p in 80%
and 82% yields, respectively.
O
1
a
3o
Moreover, the secondary amine such as diisopropylamine
also afforded the desired products (3q and 3r) with good yields
which is another important advantage of the adopted
methodology as amines are not a suitable nucleophile in mild
acidic conditions also. Aryl N-tosylaziridine (1a) underwent
cleavage by pyrrole (2j) with preferential attack at the benzylic
position resulting in the formation of 3-alkylated pyrrole
derivatives (3s) with 81% yield. In general, all of the reactions
were clean and the corresponding products were found to be
furnished regioselectively. No formation of the product by
terminal attack was observed during our study. The phenyl
groups substituted with electron-donating or electron-
withdrawing groups did not affect the efficiency or the
regioselectivity of the reactions. The reactions with other
nucleophiles (Table 3) required longer time (14 h) compared to
that for indoles and pyrrole (3 h).
CH
3
COOH
Ts
N
Cl
(
2h)
NHTs
O
Cl
O
1b
3
p
7
8
75
75
82
80
Ts
N
Ph
NHTs
N
H
N
Ph
(2i)
1
a
3q
Ts
N
Cl
N
H
NHTs
N
Cl
(2i)
3
r
1
b
c
9
85
81
Ts
N
Ph
N
H
NHTs
Ph
N
H
1
a
(2j)
3
s
a
Reaction Conditions: Aziridines 1 (0.5 mmol), 2 (1 mL), MBS (10 mol%) at specific
b
c
temperature for 14 h. Isolated yields. Aziridine 1a (0.5 mmol), pyrrole 2a (0.5
mmol), MBS (10 mol%) at 85 °C for 3 h.
4
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The applicability of this methodology is demonstrated for
the synthesis on gram scale. The key starting material 1d was
prepared in 52% yield by the reaction of chalcone with 1 equiv.
of anhydrous chloramine-T in the presence of 20 mol% of NBS
Ph
Zwitterionic salt
(20 mol%)
NHTs
+
Ts
N
Ts
N
1g
+
2a
+
+
OH
85 o
N
C
N
Ph
Me
H
H
1
5
1a
1g
2a
1 mmol
Scheme 5 Regioselectivity test with different aziridine moieties.
3a
Recovered
starting materials
(N-bromosuccinimide) in acetonitrile at room temperature.
0
.5 mmol 0.5 mmol
76% yield
The treatment of aziridine 1d with 5-methoxy indole 2c (1
equiv) at 85 °C for 3 h in the presence of MBS under neat
conditions afforded the corresponding ring opening product 3t
in 80% yield in one-pot. The preparation of this compound 3t
on the gram-scale afforded 74% of isolated product (Scheme
Though the mechanistic details have not been studied but
1
3a-f,16
based on literature
1
we can predict the possible pathway according to Scheme
as well as our previous observations
0,14
3).
6
where the aziridine 1a is activated through hydrogen bond
formation between C2–H of imidazolium cation (A) and
O
Ts
N
Ph
Ph
nitrogen atom of aziridine group. Similar to our previous
-
observation the role of the SO is not clear; it may stabilize the
MeO
+
10 mol% MBS
5 oC, 3 h
Ph
NHTs
Ph
MeO
N
3
8
O
H
N
transition state of the reaction through electrostatic
interaction which undergoes nucleophilic attack by different
H
1
d
2c
3
t
8
0% (0.42 g, 1 mmol scale)
4% (3.88 g, gram scale)
N
nucleophiles in an S 2 fashion to provide the ring-opening final
7
product (3).
Scheme 3 Gram-scale synthesis.
Me
H
We have observed that the product is very much
regioselective for benzylic attack. To explore and more
conclusive results we have examined it by using different
N
Ts
N
N
SO3
Me
H
N
[A]
Ph
Ph
Ph
1a
N
SO3
H
N
aliphatic aziridines (1f
-
1i) as shown in the Scheme 4 and found
NHTs
Ts
no ring opening products. It is worthy to mention that for
aziridine of stilbene (1e) where there are two symmetric
benzylic positions; we have got a mixture of product with 1:1
syn/anti product (3u). However, we could not prepare the
unsymmetrical aziridine bearing two different phenyl moieties
at both of the aziridine ring carbons and have not been tested.
N
H
N
H
N
H
2a
I
3
a
Scheme 6 Probable mechanistic pathway.
Conclusion
H
NHTs
Ph
In summary, the catalytic potential of zwitterionic molten salt
for aziridine ring-opening regioselectively by various
Ph
Ts
N
Zwitterionic salt (10 mol%)
85
H
(
a)
+
N
o
C
nucleophiles
has
been
assessed,
and
4-(3-
Ph
Ph
+
H
N
1
e
2a
H
methylimidazolium)butane sulfonate (MBS) has been found to
be a new and highly efficient catalyst. The advantages include
good yields, broad range of nucleophiles, low catalyst loading,
solvent-free synthesis and excellent regioselectivity. Not only
indoles but also pyrrole, methanol, ethanol, acetic acid and
diisopropylamine act as good nucleophiles for this
transformation. A complementarity in the regioselectivity has
been observed for the reaction of unsymmetrical aziridine
bearing a phenyl moiety at one of the aziridine ring carbon. In
all cases the ring-opening of the N-tosylaziridines gave the
desired products resulting from benzylic attack of the
nucleophiles preferentially. The extension of this methodology
for the synthesis of a melatonin derivative on a gram-scale
demonstrated the potentiality of industrial applications.
3
u, 78% yield
Zwitterionic salt (10 mol%)
5oC
Ts
N
(
b)
c)
No reaction
No reaction
No reaction
Br
N
8
H
1f
2a
Ts
N
Zwitterionic salt (10 mol%)
+
+
(
85 o
N
C
OH
H
1g
2a
Zwitterionic salt (10 mol%)
Ts
N
(
d)
e)
85 o
C
OH
N
Me
H
1h
2a
Ts
N
Zwitterionic salt (10 mol%)
85 o
+
No reaction
(
N
H
C
1i
2a
Scheme 4 Test of regioselectivity with various aziridines.
Experimental Section
A mixture (1:1) of aziridines with benzylic moiety (1a) and
aziridine containing no benzylic moiety (1g) when subjected to
General experimental methods
ring opening under the same reaction conditions only the Melting points were determined on a glass disk with an electric
1
former (1a) undergoes smooth reaction to afford the desired hot plate and are uncorrected. H NMR spectra were
product (3a) whereas the later one (1g) was recovered as determined on a Bruker 400 (400 MHz) spectrometer as
starting material (Scheme 5).
3
solutions in CDCl . Chemical shifts are expressed in parts per
million (δ) and are referenced to tetramethylsilane (TMS) as
internal standard and the signals were reported as s (singlet), d
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doublet), t (triplet), m (multiplet) and coupling constants J 2.33 (s, 3H); C NMR (CDCl
Journal Name
1
3
(
3
, 100 MHz): δ 143.5, 141.3, 137.3,
1
3
were given in Hz. C NMR spectra were recorded at 100 MHz 136.9, 129.8, 128.8, 128.0, 127.2, 127.0, 126.97, 126.8, 122.0,
in CDCl . TLC was done on silica gel coated glass slide (Merck, 119.3, 119.2, 114.0, 109.5, 47.6, 42.7, 32.8, 21.6; Anal. calcd
Silica gel G for TLC). Silica gel (60-120 mesh, SRL, India) was for C24 S: C, 71.26; H, 5.98; N, 6.93%; Found: C, 71.29;
3
24 2 2
H N O
used for column chromatography. Petroleum ether refers to H, 5.95; N, 6.96%.
the fraction boiling in the range of 60-80 °C unless it is
mentioned otherwise. All solvents were dried and distilled N-(2-(5-Methoxy-1H-indol-3-yl)-2-phenylethyl)-4-
before use. Commercially available substrates were freshly methylbenzenesulphonamide (3c)
distilled before the reaction. Solvents, reagents and other The typical procedure was applied to 2-phenyl-1-tosylaziridine
chemicals were purchased from Aldrich, Fluka, Merck, SRL,
(1a, 137 mg, 0.50 mmol), 5-methoxy indole (2c, 74 mg, 0.50
Spectrochem and Process Chemicals. All reactions involving mmol). Silica gel chromatography (eluent: petroleum
moisture-sensitive reactants were executed using oven-dried ether/ethyl acetate= 5/1) of the crude mixture afforded 3c as a
1
glassware. The aziridines were prepared by the reported brown solid (168 mg, 80% yield). Melting point 78 °C; H NMR
15
method. The zwitterionic molten salts were prepared (CDCl , 400 MHz): δ 7.99 (s, 1H), 7.55 (d, J = 8 Hz, 2H), 7.17-
according to previously reported methods.
3
1
1
7.09 (m, 8H), 6.82 (s, 1H), 6.74-6.61 (m, 1H), 6.60 (s, 1H), 4.47
s, 1H), 4.20 (t, J = 7.6 Hz, 1H), 3.63 (s, 3H), 3.59-3.52 (m, 1H),
(
1
3.46-3.39 (m, 1H), 2.33 (s, 3H); C NMR (CDCl , 100 MHz): δ
3
Typical procedure for the MBS-catalyzed regioselective ring-
opening of aziridines (1) with various nucleophiles (2)
3
154.0, 143.6, 141.1, 136.8, 131.7, 129.8, 128.8, 128.1, 127.2,
1
4
6
27.1, 127.0, 122.9, 115.3, 112.6, 112.1, 101.1, 55.8, 47.5,
2.8, 21.6; Anal. calcd for C24 S: C, 68.55; H, 5.75; N,
.66%; Found: C, 68.52; H, 5.78; N, 6.66%.
A mixture of aziridine (1, 0.50 mmol), 2 (0.50 mmol for indoles
24 2 3
H N O
and pyrrole, 1 mL for methanol, ethanol, acetic acid and
diisopropyl amine) and MBS (10 mg, 10 mol%) was taken in a
sealed tube and the reaction mixture was stirred for a certain
period of time at specific temperature as mentioned in tables.
The reaction was monitored by TLC. After completion (TLC),
N-(2-(5-Bromo-1H-indol-3-yl)-2-phenylethyl)-4-
methylbenzenesulphonamide (3d)
the reaction mixture was diluted with a 1:1 mixture of The typical procedure was applied to 2-phenyl-1-tosylaziridine
water/ethyl acetate (10 mL) and washed with brine solution
1a, 137 mg, 0.50 mmol), 5-bromo indole (2d, 98 mg, 0.50
1x10 mL). Then the combined organic layer was dried over mmol). Silica gel chromatography (eluent: petroleum
anhydrous Na SO
. Evaporation of solvent furnished the crude ether/ethyl acetate = 5/1) of the crude mixture afforded 3d as
product which was subjected to column chromatography using a brown solid (190 mg, 81% yield). Melting point 57 °C; H
petroleum ether-ethyl acetate as eluent to obtain the NMR (CDCl , 400 MHz): δ 8.17 (s, 1H), 7.57 (d, J = 8.4 Hz, 2H),
analytically pure product ( ).
7.21-7.12 (m, 1H), 7.06 (d, J = 6.8 Hz, 2H), 6.94 (s, 1H), 4.44 (s,
(
(
2
4
1
3
3
1
3
1
H), 4.12 (t, J = 7.6 Hz, 1H), 3.53-3.41 (m, 2H), 2.37 (s, 3H); C
N-(2-(1H-Indol-3-yl)-2-phenylethyl)-4-
3
NMR (CDCl , 100 MHz): δ 143.8, 140.7, 136.7, 135.2, 130.0,
4
j
methylbenzenesulphonamide (3a)
The typical procedure was applied to 2-phenyl-1-tosylaziridine
1a, 137 mg, 0.50 mmol), indole (2a, 59 mg, 0.50 mmol). Silica
gel chromatography (eluent: petroleum ether/ethyl acetate =
0/1) of the crude mixture afforded 3a as a pale brown solid
129.0, 128.3, 128.0, 127.3, 127.2, 125.4, 123.4, 121.7, 115.3,
1
5
13.0, 112.9, 47.5, 42.4, 21.7; Anal. calcd for C23
2 2
H21BrN O S: C,
8.85; H, 4.51; N, 5.97%; Found: C, 58.86; H, 4.50; N, 5.99%.
(
4
-Methyl-N-(2-(2-methyl-1H-indol-3-yl)-2-
phenylethyl)benzenesulphonamide (3e)
MHz): δ 8.06 (s, 1H), 7.57 (d, J = 8.4 Hz, 2H), 7.24 (d, J = 8 Hz, The typical procedure was applied to 2-phenyl-1-tosylaziridine
1
1
3
(163 mg, 84% yield). Melting point 109 °C; H NMR (CDCl , 400
1
=
1
1
4
H), 7.18-7.03 (m, 9H), 6.92-6.86 (m, 2H), 4.43 (s, 1H), 4.22 (t, J
1
(
1a, 137 mg, 0.50 mmol), 2-methyl indole (2e, 65 mg, 0.50
3
3
7.6 Hz, 1H), 3.59-3.41 (m, 2H), 2.34 (s, 3H); C NMR (CDCl ,
mmol). Silica gel chromatography (eluent: petroleum
00 MHz): δ 143.6, 141.1, 136.8, 136.6, 129.9, 128.9, 128.1, ether/ethyl acetate = 5/1) of the crude mixture afforded 3e as
27.2, 127.1, 126.6, 122.5, 122.2, 119.7, 119.2, 115.6, 111.4, a red coloured gummy mass (162 mg, 80% yield). H NMR
1
7.6, 42.7, 21.7.
(CDCl
.06 (m, 8H), 7.01-6.97 (m, 2H), 6.78 (t, J = 7.6 Hz, 1H), 4.30-
4.26 (m, 2H), 3.74-3.68 (m, 1H), 3.52-3.47 (m, 1H), 2.33 (s, 3H),
3
, 400 MHz): δ 7.99 (s, 1H), 7.50 (d, J = 8 Hz, 2H), 7.17-
7
4-Methyl-N-(2-(1-methyl-1H-indol-3-yl)-2-
1
3
phenylethyl)benzenesulphonamide (3b)
2.16 (s, 3H); C NMR (CDCl
3
, 100 MHz): δ 143.5, 141.5, 136.5,
35.6, 133.7, 129.8, 128.6, 127.7, 127.2, 127.0, 126.7, 121.2,
19.7, 118.7, 110.8, 109.0, 46.4, 42.1, 21.6, 12.1. Anal. calcd
S: C, 71.26; H, 5.98; N, 6.93 %; Found: C, 71.28;
1
1
The typical procedure was applied to 2-phenyl-1-tosylaziridine
(
1a, 137 mg, 0.50 mmol), N-methyl indole (2b, 66 mg, 0.50
24 2 2
for C24H N O
mmol). Silica gel chromatography (eluent: petroleum
H, 5.96; N, 6.97%.
ether/ethyl acetate = 10/1) of the crude mixture afforded 3b
1
as a brown solid (163 mg, 81% yield). Melting point 97 °C; H
N-(2-(4-Chlorophenyl)-(1H-indol-3-yl)ethyl)-4-
NMR (CDCl
3
, 400 MHz): δ 7.55 (d, J = 8.4 Hz, 2H), 7.18-7.08 (m,
methylbenzenesulphonamide (3f)
1
7
0H), 6.91-6.88 (m, 1H), 6.68 (s, 1H), 4.47 (s, 1H), 4.21 (t, J =
.6 Hz, 1H), 3.60 (s, 3H), 3.56-3.51 (m, 1H), 3.46-3.42 (m, 1H),
6
| J. Name., 2012, 00, 1-3
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ARTICLE
The typical procedure was applied to 2-(4-chlorophenyl)-1- 195.9, 143.7, 137.2, 136.2, 134.3, 134.0, 129.8, 129.6, 129.58,
tosylaziridine (1b, 154 mg, 0.50 mmol), indole (2a, 59 mg, 0.50 129.0, 128.3, 127.6, 127.5, 126.9, 123.3, 122.2, 119.4, 118.9,
26 2 3
mmol). Silica gel chromatography (eluent: petroleum 115.3, 111.3, 60.6, 45.0, 21.5; Anal. calcd for C30H N O S: C,
ether/ethyl acetate= 10/1) of the crude mixture afforded 3f as 72.85; H, 5.30; N, 5.66%; Found: C, 72.81; H, 5.34; N, 5.63%.
1
a pale brown solid (168 mg, 79% yield). Melting point 83 °C; H
NMR (CDCl
, 400 MHz): δ 8.12 (s, 1H), 7.53 (d, J = 8.4 Hz, 2H), N-(3-(5-Bromo-1H-indol-3-yl)-1-oxo-1,3-diphenylpropan-2-yl)-4-
3
7
.24 - 6.86 (m, 11H), 4.58 (t, J = 6 Hz, 1H), 4.19 (t, J = 7.6 Hz, methylbenzenesulphonamide (3j)
1
3
1
H), 3.54-3.48 (m, 1H), 3.42-3.35 (m, 1H), 2.33 (s, 3H); C NMR The typical procedure was applied to phenyl(3-phenyl-1-
CDCl , 100 MHz): δ 143.7, 139.8, 136.7, 136.6, 132.7, 129.9, tosylaziridine-2-yl)methanone (1d, 152 mg, 0.50 mmol), 5-
29.4, 128.9, 127.1, 126.4, 122.6, 122.2, 119.8, 119.1, 115.1, bromo indole
2d 98 mg, 0.50 mmol). Silica gel
(
3
1
1
(
,
11.5, 47.4, 42.2, 21.6; Anal. calcd for C23
H21ClN
2
O
2
S: C, 65.01; chromatography (eluent: petroleum ether/ethyl acetate = 5/1)
H, 4.98; N, 6.59%; Found: C, 65.04; H, 4.97; N, 6.55%.
of the crude mixture afforded 3j as an orange gummy mass
1
217 mg, 76% yield). H NMR (CDCl
(
3
, 400 MHz): δ 8.37 (s, 1H),
N-(3-Hydroxy-1-(1H-indol-3-yl)-1-phenylpropan-2-yl)-4-
methylbenzenesulphonamide (3g)
8
.06 (d, J = 2.4 Hz, 1H), 7.63-6.86 (m, 17H), 5.66-5.63 (m, 1H),
.20 (d, J = 10.4 Hz, 1H), 4.51 (d, J = 2.4 Hz, 1H), 2.13 (s, 3H);
5
1
3
The typical procedure was applied to (3-phenyl-1-
3
C NMR (CDCl , 100 MHz): δ 195.7, 143.9, 136.7, 136.1, 134.7,
tosylaziridine-2-yl)methanol (1c, 152 mg, 0.50 mmol), indole 136.2, 129.8, 129.6, 129.5, 129.1, 128.5, 128.2, 127.8, 127.5,
2a, 59 mg, 0.50 mmol). Silica gel chromatography (eluent: 126.6, 125.1, 124.6, 121.4, 115.1, 112.8, 60.7, 44.7, 21.5; Anal.
petroleum ether/ethyl acetate = 4/1) of the crude mixture calcd for C30 SBr: C, 62.83; H, 4.39; N, 4.88%; Found: C,
afforded 3g as a red gummy mass (172 mg, 82% yield). H NMR 62.81; H, 4.37; N, 4.89%.
(
25 2 3
H N O
1
3
(CDCl , 400 MHz): δ 8.18 (s, 1H), 7.38 (d, J = 8.4 Hz, 2H), 7.27
(
d, J = 8 Hz, 1H), 7.20-6.89 (m, 11H), 4.81 (d, J = 6.8 Hz, 1H), N-(2-Methoxy-2-phenylethyl)-4-methylbenzenesulphonamide
4
g
4
.33 (d, J = 9.2 Hz, 1H), 3.94 (s, 1H), 3.70-3.66 (m, 1H), 3.55- (3k)
1
3
3
.51 (m, 1H), 2.32 (s, 3H), 1.99 (s, 1H); C NMR (CDCl
3
, 100 The typical procedure was applied to 2-phenyl-1-tosylaziridine
1a, 137 mg, 0.50 mmol), methanol (2f, 1 mL). Silica gel
26.9, 126.8, 122.3, 122.2, 119.7, 119.0, 115.4, 111.4, 63.6, chromatography (eluent: petroleum ether/ethyl acetate =
MHz): δ 143.5, 140.5, 136.7, 136.3, 129.7, 128.8, 128.5, 127.2,
(
1
5
8.9, 43.9, 21.6; Anal. calcd for C24
H
24
N
2
O
3
S: C, 68.55; H, 5.75; 10/1) of the crude mixture afforded 3k as a pale yellow solid
1
(125 mg, 82% yield). Melting point 46 °C; H NMR (CDCl , 400
N, 6.66%; Found: C, 68.57; H, 5.76; N, 6.67%.
3
MHz): δ 7.64 (d, J = 8 Hz, 2H), 7.30-7.11 (m, 7H), 5.07 (s, 1H),
N-(3-Hydroxy-1-(-1-methyl-1H-indol-3-yl)-1-phenylpropan-2-yl)-4-
4
.13-4.09 (m, 1H), 3.15-3.08 (m, 4H), 2.90-2.87 (m, 1H), 2.33 (s,
1
3
methylbenzenesulphonamide (3h)
3
3
H); C NMR (CDCl , 100 MHz): δ 143.6, 138.4, 137.0, 129.8,
The typical procedure was applied to (3-phenyl-1- 128.8, 128.5, 127.2, 126.7, 82.1, 56.9, 49.4, 21.6.
tosylaziridine-2-yl)methanol (1c, 152 mg, 0.50 mmol), N-
methyl indole
(
2b,
66 mg, 0.50 mmol). Silica gel N-(2-(4-Chlorophenyl)-2-methoxyethyl)-4-
chromatography (eluent: petroleum ether/ethyl acetate = 4/1) methylbenzenesulphonamide (3l)
of the crude mixture afforded 3h as a red gummy mass (167 The typical procedure was applied to 2-(4-chlorophenyl)-1-
1
mg, 77% yield). H NMR (CDCl
3
, 400 MHz): δ 7.39 (d, J = 8.4 Hz, tosylaziridine (1b, 154 mg, 0.50 mmol), methanol (2f, 1 mL).
2
6
3
1
1
1
H), 7.29 (d, J = 8 Hz, 1H), 7.16-7.03 (m, 9H), 6.94-6.90 (m, 1H), Silica gel chromatography (eluent: petroleum ether/ethyl
.82 (s, 1H), 4.81 (s, 1H), 4.32 (d, J = 9.2 Hz, 1H), 3.92 (s, 1H), acetate = 10/1) of the crude mixture afforded 3l as a colourless
1
.71-3.67 (m, 1H), 3.59 (s, 3H), 3.57-3.54 (m, 1H), 2.34 (s, 3H), gummy mass (134 mg, 79% yield). H NMR (CDCl , 400 MHz): δ
3
1
3
.99 (s, 1H); C NMR (CDCl
3
, 100 MHz): δ 143.4, 140.7, 137.0, 7.72 (d, J = 8.4 Hz, 2H), 7.32-7.28 (m, 4H), 7.17-7.15 (m, 2H),
36.7, 129.7, 128.8, 128.4, 127.2, 127.1, 126.84, 126.81, 122.0, 5.01-4.99 (m, 1H), 4.22-4.19 (m, 1H), 3.23-3.18 (m, 4H), 2.97-
1
3
19.3, 119.2, 114.0, 109.4, 63.6, 59.0, 43.9, 32.8, 21.7; Anal. 2.91 (m, 1H), 2.44 (s, 3H); C NMR (CDCl , 100 MHz): δ 143.7,
3
calcd for C25
H
26
N
2
O
3
S: C, 69.10; H, 6.03; N, 6.45%; Found: C, 137.02, 136.96, 134.3, 129.9, 129.0, 128.1, 127.2, 81.5, 57.0,
49.3, 21.7; Anal. calcd for C H ClNO S: C, 56.55; H, 5.34; N,
69.11; H, 6.02; N, 6.41%.
1
6
18
3
4.12%; Found: C, 56.58; H, 5.38; N, 4.15%.
N-(3-(1H-indol-3-yl)-1-oxo-1,3-diphenylpropan-2-yl)-4-
4
g
methylbenzenesulphonamide (3i)
N-(2-Ethoxy-2-phenylethyl)-4-methylbenzenesulphonamide (3m)
The typical procedure was applied to phenyl(3-phenyl-1- The typical procedure was applied to 2-phenyl-1-tosylaziridine
tosylaziridine-2-yl)methanone (1d, 189 mg, 0.50 mmol), indole
1a, 137 mg, 0.50 mmol), ethanol (2g, 1 mL). Silica gel
2a, 59 mg, 0.50 mmol). Silica gel chromatography (eluent: chromatography (eluent: petroleum ether/ethyl acetate =
petroleum ether/ethyl acetate = 4/1) of the crude mixture 10/1) of the crude mixture afforded 3m as a pale yellow solid
(
(
1
1
afforded 3i as a red gummy mass (186 mg, 75% yield). H NMR (129 mg, 81% yield). Melting point 49 °C; H NMR (CDCl , 400
3
3
(CDCl , 400 MHz): δ 8.24 (s, 1H), 8.02 (d, J = 1.6 Hz,1H), 7.63- MHz): δ 7.64 (d, J = 8 Hz, 2H), 7.30-7.11 (m, 7H), 5.03-5.01 (m,
6
.78 (m, 18H), 5.72-5.69 (m, 1H), 5.19 (d, J = 11.2 Hz,1H), 4.59 1H), 4.23-4.20 (m, 1H), 3.29-3.08 (m, 3H), 2.90-2.84 (m, 1H),
13
, 100 MHz): δ 2.33 (s, 3H), 1.05 (t, J = 7.2 Hz, 3H); C NMR (CDCl , 100 MHz):
1
d, J = 2.4 Hz, 1H), 2.13 (s, 3H); C NMR (CDCl
3
(
3
3
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ARTICLE
Journal Name
δ 143.5, 139.1, 137.1, 129.8, 128.7, 128.3, 127.1, 126.6, 80.2, 51.4, 47.4, 22.7, 21.5, 18.9; Anal. calcd for C21
30 2 2
H N O S: C,
64.5, 49.4, 21.6, 15.2. 67.34; H, 8.07; N, 7.48%; Found: C, 67.33; H, 8.02; N, 7.49%.
N-(2-(4-Chlorophenyl)-2-ethoxyethyl)-4-
N-(2-(4-Chlorophenyl)-2-(diisopropylamino)ethyl)-4-
methylbenzenesulphonamide (3n)
methylbenzenesulfonamide (3r)
The typical procedure was applied to 2-(4-chlorophenyl)-1- The typical procedure was applied to 2-(4-chlorophenyl)-1-
tosylaziridine (1b, 154 mg, 0.50 mmol), ethanol (2g, 1 mL). tosylaziridine (1b, 154 mg, 0.50 mmol), diisopropylamine (2i, 1
Silica gel chromatography (eluent: petroleum ether/ethyl mL). Silica gel chromatography (eluent: petroleum ether/ethyl
acetate = 10/1) of the crude mixture afforded 3n as a white acetate = 10/1) of the crude mixture afforded 3r as a pale
1
1
solid (138 mg, 78% yield). Melting point 56 °C; H NMR (CDCl
00 MHz): δ 7.63 (d, J = 8.4 Hz, 2H), 7.25-7.19 (m, 4H), 7.07 (d, MHz): δ 7.44 (d, J = 8.4 Hz, 2H), 7.12-7.04 (m, 6H), 3.96 (s, 1H),
J = 8.4 Hz, 2H), 4.98-4.96 (m, 1H), 4.23-4.20 (m, 1H), 3.28-3.07 2.80 (brs, 2H), 2.54-2.47 (m, 1H), 2.31 (s, 3H), 2.25-2.15 (m,
3
,
3
yellow gummy mass (164 mg, 80% yield). H NMR (CDCl , 400
4
1
3
(
1
m, 3H), 2.88-2.81 (m, 1H), 2.34 (s, 3H), 1.05 (t, J = 7.2 Hz, 3H); 1H), 0.96 (d, J = 6.4 Hz, 6H), 0.83 (d, J = 4.8 Hz, 6H); C NMR
3
C NMR (CDCl
28.9, 128.0, 127.1, 79.7, 64.7, 49.3, 21.6, 15.2; Anal. calcd for 127.5, 127.3, 54.9, 51.3, 47.4, 22.7, 21.6, 19.0; Anal. calcd for
S: C, 57.70; H, 5.70; N, 3.96%; Found: C, 57.67; H, S: C, 61.67; H, 7.15; N, 6.85%; Found: C, 61.69; H,
.73; N, 3.92%.
3 3
, 100 MHz): δ 143.6, 137.7, 137.0, 134.1, 129.8, (CDCl , 100 MHz): δ 143.4, 136.8, 129.8, 129.3, 128.7, 128.5,
1
C
17
H
20ClNO
3
21 2 2
C H29ClN O
5
7.12; N, 6.81%.
2-(4-Methylphenylsulfonamido)-1-phenylethyl acetate (3o)
4-Methyl-N-(2-phenyl-2-(1H-pyrrol-2-yl)ethyl)benzenesulfonamide
4
j
The typical procedure was applied to 2-phenyl-1-tosylaziridine (3s)
1a, 137 mg, 0.50 mmol), acetic acid (2h, 1 mL). Silica gel The typical procedure was applied to 2-phenyl-1-tosylaziridine
chromatography (eluent: petroleum ether/ethyl acetate=
1a, 137 mg, 0.50 mmol), pyrrole (2j, 35 µL, 0.50 mmol). Silica
0/1) of the crude mixture afforded 3o as a yellow gummy gel chromatography (eluent: petroleum ether/ethyl acetate =
(
(
1
1
mass (133 mg, 80% yield). H NMR (CDCl
3
, 400 MHz): δ 7.64 (d, 5/1) of the crude mixture afforded 3s as a deep brown gummy
1
J = 8 Hz, 2H), 7.23-7.13 (m, 7H), 5.63 (t, J = 6.4 Hz, 1H), 5.18 (s, mass (137 mg, 81% yield). H NMR (CDCl , 400 MHz): δ 7.85 (s,
3
1
H), 3.23 (t, J = 6.4 Hz, 2H), 2.34 (s, 3H), 1.94 (s, 3H); C NMR 1H), 7.61 (d, J = 8.4 Hz, 2H), 7.24-7.17 (m, 5H), 7.02-7.00 (m,
3
1
(
CDCl
3
, 100 MHz): δ 170.2, 143.7, 137.2, 137.0, 129.9, 128.8, 2H), 6.59-6.57 (m, 1H), 6.07-6.05 (m, 1H), 5.87 (s, 1H), 4.43 (s,
1
28.7, 127.1, 126.5, 74.3, 47.8, 21.6, 21.1; Anal. calcd for 1H), 4.03 (t, J = 7.6 Hz, 1H), 3.46-3.32 (m, 2H), 2.36 (s, 3H);
C
3
1
C
17
H19NO
4
S: C, 61.24; H, 5.74; N, 4.20%; Found: C, 61.27; H, NMR (CDCl , 100 MHz): δ 143.8, 140.0, 136.8, 130.8, 129.9,
3
5.73; N, 4.21%.
129.1, 128.1, 127.7, 127.3, 117.8, 108.6, 105.8, 47.6, 44.7,
2
1.7.
1-(4-Chlorophenyl)-2-(4-methylphenylsulfonamido)ethyl acetate
(3p)
Typical procedure for the synthesis of melatonin derivative N-(2-
The typical procedure was applied to 2-(4-chlorophenyl)-1- (5-methoxy-1H-indol-3-yl)-1-oxo-1,3-diphenylpropan-2-yl)-4-
tosylaziridine (1b, 154 mg, 0.50 mmol), acetic acid (2h, 1 mL). methylbenzenesulfonamide (3t)
Silica gel chromatography (eluent: petroleum ether/ethyl
A mixture of phenyl(3-phenyl-1-tosylaziridine-2-yl)methanone
acetate = 10/1) of the crude mixture afforded 3p as a yellowish
(
1d, 377 mg, 1 mmol), 5-methoxy indole (2c, 147 mg, 1 mmol)
1
3
green gummy mass (151 mg, 82% yield). H NMR (CDCl , 400
and MBS (20 mg, 10 mol%) was taken in a sealed tube and the
reaction mixture was stirred for 3 h at 85 °C. The reaction was
monitored by TLC. After completion (TLC), the reaction mixture
was diluted with a 1:1 mixture of water/ethyl acetate (20 mL)
and washed with brine solution (2 x 10 mL). Then the
MHz): δ 7.61 (d, J = 8 Hz, 2H), 7.22-7.17 (m, 4H), 7.08 (d, J = 8.4
Hz, 2H), 5.61 (t, J = 6 Hz, 1H), 5.17 (s, 1H), 3.21 (t, J = 5.2 Hz,
1
3
2
1
7
4
H), 2.35 (s, 3H), 1.95 (s, 3H); C NMR (CDCl
70.0, 143.8, 136.9, 135.7, 134.5, 129.9, 129.0, 128.0, 127.1,
3.6, 47.6, 21.6, 21.1; Anal. calcd for C17 S: C, 55.51; H,
.93; N, 3.81%; Found: C, 55.55; H, 4.90; N, 3.79%.
3
, 100 MHz): δ
H
18ClNO
4
2 4
combined organic layer was dried over anhydrous Na SO .
Evaporation of solvent furnished the crude product which was
subjected to column chromatography using petroleum ether-
ethyl acetate (5/1) as eluent to obtain the analytically pure
N-(2-(Diisopropylamino)-2-phenylethyl)-4-
methylbenzenesulfonamide (3q)
1
product as red gummy mass (420 mg, yield 80%). H NMR
The typical procedure was applied to 2-phenyl-1-tosylaziridine
3
(CDCl , 400 MHz): δ 8.31 (s, 1H), 8.05 (d, J = 2 Hz, 1H), 7.73 (d, J
(
1a, 137 mg, 0.50 mmol), diisopropylamine (2i, 1 mL). Silica gel
chromatography (eluent: petroleum ether/ethyl acetate =
0/1) of the crude mixture afforded 3q as a pale yellow
=
7.2 Hz, 2H), 7.72 - 7.57 (m, 3H), 7.41(t, J = 8 Hz, 2H), 7.25-
.19 (m, 4H), 7.05-7.00 (m, 4H), 5.33 (d, J = 8.2 Hz, 1H), 4.64 (d,
7
1
J = 2.8 Hz,1H), 3.46 (s, 3H), 2.24 (s, 3H); C NMR (CDCl
3
1
3
, 100
1
gummy mass (154 mg, 82% yield). H NMR (CDCl
3
, 400 MHz): δ
.44 (d, J = 8 Hz, 2H), 7.16-7.05 (m, 7H), 4.00 (s, 1H), 2.81 (brs,
H), 2.56-2.53 (m, 1H), 2.32-2.23 (m, 4H), 0.96 (d, J = 5.6 Hz,
MHz): δ 196.1, 153.8, 143.7, 137.3, 136.2, 134.4, 134.0, 131.3,
7
2
6
1
1
1
29.6, 129.5, 128.9, 128.3, 128.2, 127.6, 127.5, 127.4, 124.1,
14.9, 112.0, 111.9, 101.1, 60.5, 55.8, 45.1, 21.4; Anal. calcd
13
3
H), 0.82 (d, J = 5.2 Hz, 6H); C NMR (CDCl , 100 MHz): δ
for C31
H
28
N
2
O
4
S: C, 70.97; H, 5.38; N, 5.34%; Found: C, 70.94;
43.0, 136.9, 129.8, 129.2, 128.3, 127.6, 127.5, 127.3, 55.4,
H, 5.37; N, 5.30%.
8
| J. Name., 2012, 00, 1-3
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as a white solid (182 mg, 78% yield). Melting point 61 °C; H
Typical procedure for the synthesis of 3t on a gram scale.
NMR (CDCl
3
, 400 MHz): δ 7.65-6.62 (m, 40H), 5.25 (d, J = 14Hz,
A mixture of phenyl(3-phenyl-1-tosylaziridine-2-yl)methanone
1
H), 4.93 (d, J = 14 Hz, 1H), 4.78 (d, J = 6 Hz, 1H), 4.40 (d, J = 6
(
1d, 3.77 g, 10 mmol), 5-methoxy indole 2c (1.47 g, 10 mmol)
1
Hz, 1H), 2.24 (s, 3H), 2.19 (s, 3H); C NMR (CDCl
3
3
, 100 MHz): δ
and MBS (200 mg, 10 mol%) was taken in a sealed tube and
the reaction mixture was stirred for 3 h at 85 °C. The reaction
was monitored by TLC. After completion (TLC), the reaction
mixture was diluted with a 1:1 mixture of water/ethyl acetate
1
1
1
1
1
44.6, 142.9, 139.4, 138.7, 137.3, 136.2, 136.0, 129.6, 129.5
29.1, 129.0, 128.7, 128.5, 128.1, 127.9, 127.8, 127.7, 127.4,
27.3, 127.2, 127.1, 127.0 (2C), 125.8, 122.9, 122.8, 122.6,
22.1, 121.5, 119.8, 119.6, 119.5, 119.4, 119.1, 118.9, 118.4,
15.9, 111.4, 111.1, 110.9, 60.6, 56.3, 50.0, 39.0, 21.6, 21.5.
(250 mL) and washed with brine solution (2 x 50 mL). Then the
combined organic layer was dried over anhydrous Na SO
2
4
.
Evaporation of solvent furnished the crude product which was
subjected to column chromatography using petroleum ether-
ethyl acetate (5/1) as eluent to obtain the analytically pure
product as red gummy mass (3.88 g, yield 74%).
Acknowledgements
A. Majee and N. Chakraborty are pleased to acknowledge the
financial support from BRNS-DAE, Govt. of India (Grant No.
37(2)/14/35/2014-BRNS/563). We are thankful to DST-FIST and
UGC-SAP. S. Santra and G. V. Zyryanov acknowledge the
Russian Scientific Foundation (Ref. # 15-13-10033) for funding.
N-(2-(1H-indol-3-yl)-1,2-diphenylethyl)-4-
methylbenzenesulfonamide (3u)
The typical procedure was applied to 2,3-diphenyl-1-
tosylaziridine (1e, 175 mg, 0.50 mmol), indole (2a, 58 mg, 0.50
mmol). Silica gel chromatography (eluent: petroleum
ether/ethyl acetate = 10/1) of the crude mixture afforded 3u
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Organocatalysis by an aprotic imidazolium zwitterion: regioselective
ring-opening of aziridines and applicable on gram scale synthesis
Nirnita Chakraborty Ghosal, Sougata Santra, Sudarshan Das, Alakananda Hajra, Grigory V.
Zyryanov and Adinath Majee*