Microwave-induced clay-catalyzed ring opening of N-tosylaziridines: A green approach to achiral and chiral diamines

Article abstract of DOI:10.1016/j.tetlet.2005.01.132

N-Tosylaziridines react efficiently with amines in the presence of Montmorillonite K-10 as catalyst under microwave irradiation in solvent-free conditions to yield the corresponding achiral and chiral diamines regio- and stereoselectively, in a few minutes and in high yields.

Full text of DOI:10.1016/j.tetlet.2005.01.132

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 2083–2086
Microwave-induced clay-catalyzed ring opening of
N-tosylaziridines: a green approach to achiral and chiral diamines
Upender K. Nadir* and Anamika Singh
Department of Chemistry, Indian Institute of Technology, Delhi, Hauz Khas, New Delhi 110016, India
Received 15 December 2004; revised 21 January 2005; accepted 25 January 2005
Abstract—N-Tosylaziridines react efficiently with amines in the presence of Montmorillonite K-10 as catalyst under microwave irra-
diation in solvent-free conditions to yield the corresponding achiral and chiral diamines regio- and stereoselectively, in a few minutes
and in high yields.
Ó 2005 Elsevier Ltd. All rights reserved.
Aziridines are useful intermediates in organic synthe-
sis.1–3 N-Arylsulfonylaziridines, in particular, have re-
cently attracted considerable attention due to their
susceptibility towards highly regio- and stereoselective
nucleophilic ring opening2a and ring expansion reac-
tions. The nucleophilic ring opening of aziridines has
been used to prepare biologically active compounds
such as amino acids,2b,4 heterocycles5 and alkaloids.6
With nitrogen nucleophiles such as amines, aziridines
yield vicinal diamines,7 which are components of many
biologically and medicinally important compounds.8,9
A recent review describes ring opening reactions of azir-
idines with various nucleophiles.10 Our interest in the
synthesis11 and useful transformations12–15 of N-tosylaz-
iridines led us to study their reactions with amines. We
report, here, a facile, regioselective and high yielding
ring opening of N-tosylaziridines with amines leading
to mono-N-tosyl 1,2-diamines (Scheme 1).
R2
N
R1
NHR3
NHTs
NHTs
NHR3
R3NH2
R2
R2
R1
+
Ts
K 10, MW
R1
3
1
2
1a: R1 = Ph; R2 = H
1b: R1 = CH3; R2 = H
1c: R1 = CH3; R2 = COOCH3
Scheme 1. Regiochemistry of ring-opening of N-tosylaziridines with
amines.
(b) liquid extraction for isolation of products is not
required; (c) reaction times are shortened; (d) yields
are increased; (e) reactions are cleaner. When these
solvent-free green conditions were used to carry out
reactions of N-tosylaziridines with various amines,
diamines were obtained in high yields (Table 1).
The demand for increasingly clean and efficient chemical
synthesis is important from both economic and environ-
mental points of view.16 One commonly used method is
the combination of microwave irradiation17,18 and a
solid support19 like Montmorillonite K-10. This offers
a number of advantages (a) solvents, which are often
expensive, toxic and difficult to remove in the case of
aprotic solvents with high boiling points, are avoided;
The reaction times were short (3–5 min) and the prod-
ucts were cleanly separated by extraction from the clay
with minimal use of solvents. The aziridine opening
reaction was also smooth with disubstituted substrates
(1c–e) (Schemes 1 and 2). By conventional methods,
the reaction of aziridines with amines takes several
hours. Moreover, the regio- and stereoselectivity is vari-
able, with or without a Lewis acid, particularly with ali-
phatic amines like benzyl and alkylamines.20 The
starting aziridines 1a and 1f were synthesized by a
known three-step procedure;21 1c was prepared using
Keywords: Microwave; Aziridines; Diamines; Clay.
*
Corresponding author. Tel.: +91 11 26591518; fax: +91 11
26582037; e-mail: ukn@netearth.iitd.ac.in
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.01.132

2084
U. K. Nadir, A. Singh / Tetrahedron Letters 46 (2005) 2083–2086
Table 1. Microwave-induced clay-catalyzed aziridine opening with
amines under solvent-free conditions
dichloramine-T as nitrogen source and Cu(acac)2 as
catalyst;11 1d and 1e were accessed by the Sharpless
and co-workers method.22
Aziridines
Amines
Product(s)
(ratio of 2:3)a (time, min)
Yieldb (%)
With arylamines (R3 = aryl) the reaction was completely
regiospecific and only one regioisomer 2 with 1a and 3
with 1b was obtained (Scheme 1). Benzylamines
afforded a mixture of 2 and 3 (90:10) and n-butylamine
led to a 56:44 mixture of 2 and 3. Disubstituted aziri-
dine 1e gave 5b with n-butylamine and 5c with
benzylamine. All the reactions proceeded in excellent
overall yield. The regiochemical course of these reac-
tions is in accord with our previous observations13 that
the nucleophile attacks at the more electrophilic centre,
which, for aryl-substituted aziridines, is the substituted
carbon, whereas for alkyl-substituted aziridines this is
the unsubstituted carbon. In the case of aziridine 1c,
nucleophilic attack takes place at the substituted carbon
(Scheme 1).
N
1a
Ts
C6H5NH2
2a
98 (3)
95 (5)
94 (5)
92 (5)
91 (3)
Ph
Ph
N
Ts
Ts
Ts
Ts
4-MeC6H4NH2
2b
1a
N
4-MeOC6H4NH2 2c
Ph
Ph
Ph
1a
N
PhCH2NH2
2d:3d
(90:10)
1a
N
c
n-BuNH2
2e:3e
(56:44)
1a
The reaction is completely stereoselective and only the
trans product from 1d and the erythro diastereomer 5a
from 1e were produced (Scheme 2). All the products
were either known or had the expected spectroscopic
properties. The products from aziridine 1e (5a–c) were
presumed to be the erythro diastereomers, based on
the fact that 1d gave the trans isomer and from our gen-
eral observations23 on the reactions of nucleophiles with
N-tosylaziridines. The lack of reactivity of aziridine 1f, is
also in accord with our previous observations.23 To our
knowledge, there has been no report on microwave-in-
duced clay-catalyzed ring opening of N-tosylaziridines
with amines.
Ts
Ts
N
C6H5NH2
3f
97 (3)
93 (5)
Me
Me
1b
N
PhCH2NH2
2g:3g
(10:90)
1b
Me
MeO2C
N
Ts
C6H5NH2
C6H5NH2
2h
4a
85 (3)
94 (3)
1c
N
N
Ts
Ts
1d
Attempts to carry out these reactions in the absence of
Montmorillonite K-10 did not yield the products indicat-
ing that the clay is acting as a catalyst. When the reactions
were carried out at room temperature in the presence of a
solvent and clay, the products were formed very slowly,
showing that microwave irradiation has a major role to
play in these reactions. It was found that the clay em-
ployed was reusable. Thus in the reaction of 1a with ani-
line, in three successive runs, the yield of the product 2a
was 98%, 96% and 95%, respectively.
4-MeC6H4NH2
4MeOC6H4NH2
4b
4c
89 (5)
84 (5)
1d
N
N
Ts
Ts
1d
1d
PhCH2NH2
C6H5NH2
n-BuNH2
4d
5a
5b
82 (5)
87 (5)
82 (5)
Ph
The reaction could also be extended to synthesize chiral
diamines by treating racemic aziridines 1d and 1e with
optically active a-methylbenzylamine to give a diaste-
reomeric mixture (50:50) of the corresponding diamines
(Scheme 2). Diastereomers 6 and 7 were separated by
column chromatography whereas 8 and 9 could be sep-
arated by recrystallization.
N
Ts
Ph
Ph
1e
N
Ts
Ts
Ts
Ph
Ph
1e
In conclusion, this letter describes an efficient, easy, eco-
friendly method for highly regio- and stereoselective
preparation of vicinal mono-N-tosyl diamines from N-
tosylaziridines using a solid support under microwave
irradiation. The attractive features of this procedure
are that it is quite general, proceeds rapidly, uses no
toxic and/or expensive solvents, uses mild reaction con-
ditions and the catalyst can be reused several times with-
out significant loss of activity. All these factors combine
to make it a ÔGreenÕ synthesis.
N
PhCH2NH2
C6H5NH2
5c
84 (5)
Ph
Ph
1e
N
No reaction
—
Ph
1f
a Ratio of isomers were determined by 1H NMR of the crude products.
b Isolated, unoptimized yields.
c 3 equiv n-BuNH2 was used.

U. K. Nadir, A. Singh / Tetrahedron Letters 46 (2005) 2083–2086
2085
H
H
N
Ts
RNH2
K 10, MW
N
H
R
H
4a: R = Ph
4b: R = 4-MeC6H4
4
Ts
N
4c: R = 4-MeOC6H4
4d: R = CH2Ph
Ph
H2N
H
H
CH3
NHTs
NHTs
Ph
1d
H
+
Ph
N
H
CH3
N
H
CH3
K 10, MW
H
H
H
H
6
7
H
H
H
Ts
Ph
Ph
N
RNH2
K 10, MW
N
H
R
5a: R = Ph
Ph
Ph
5b: R = n-butyl
5c: R = CH2Ph
5
Ts
N
Ph
NHTs
H
H2N
CH3
Ph
NHTs
Ph
1e
Ph
Ph
H
H
+
CH3
Ph
N
H
H
K 10, MW
H
NH
H
H
8
H3C
Ph
9
Scheme 2. Synthesis of achiral and chiral diamines.
6. Hudlicky, T.; Luna, H.; Price, J. D.; Rulin, F. J. Org.
Chem. 1990, 55, 4683–4687.
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work and for a fellowship to A.S.
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