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Chemistry Letters Vol.37, No.8 (2008)
Heteropoly Acid as Efficient, Cost-effective, and Recyclable Solid Acid
for the Rapid Synthesis of Substituted Imidazolines
J. S. Yadav,ꢀ B. V. Subba Reddy, T. Pandurangam, and U. V. Subba Reddy
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad-500 007, India
(Received May 19, 2008; CL-080505; E-mail: yadavpub@iict.res.in)
Aziridines undergo smooth ring opening with a range of
Ts
N
nitriles in the presence of 10 mol % of phosphomolybdic acid
supported on silica gel (PMA–SiO2) under mild reaction condi-
tions to afford the corresponding imidazolines in good yields and
with high regioselectivity. The use of silica gel as solid support
facilitates an easy recovery and reuse of the catalyst thereby
making the process quite simple, more convenient, and cost-
effective.
10 mol % PMA−SiO2
23 °C
PhCH2CN
+
N
Ts
Ph
N
3a
Ph
Ph
1
2
Scheme 1.
groscopic, and highly active catalytic system than unsupported
PMA.13
In continuation of our efforts to explore the synthetic utility
of phosphomolybdic acid supported on silica gel (PMA–SiO2),14
we herein report a simple and convenient method for the synthe-
sis of imidazolines from aziridines and nitriles. Initially, we at-
tempted 1,3-dipolar cycloaddition of styrene N-tosylaziridine
(1) with benzyl cyanide (2) in the presence of 10 mol % phospho-
molybdic acid supported on silica gel. The reaction went to
completion in 2.0 h at room temperature and the product was
obtained 3a in 80% yield (Scheme 1).
Similarly, benzonitrile and acetonitrile reacted effectively
with styrene aziridine to produce the corresponding imidazolines
in high yields (Entries b and c, Table 1). Aryl-N-tosylaziridines
underwent smooth cycloaddition with nitriles by preferential at-
tack at the benzylic position resulting in the formation of product
3a (Entries a–j, Table 1). Because of the stability of the benzylic
carbocation, the cycloaddition is highly regioselective.9 Further-
more; cyclohexene-N-tosylaziridine also reacted efficiently
with various nitriles such as benzyl cyanide, benzonitrile and
acetonitrile to afford the corresponding imidazoline 4 in good
yields (Entries k–m, Table 1, Scheme 2).
However, alkyl aziridines such as n-hexene- and n-octene-
N-tosylaziridines also participated well in this reaction (Entries
n and o, Table 1) under identical conditions. In case of alkyl azir-
idines, the nucleophile attacks at less hindered terminal position
to provide imidazolines 5 in moderate yields. In case of N-tosyl-
alkyl aziridines (Entries n and o), the corresponding cycload-
ducts 5n and 5o were isolated as the sole products (Scheme 3).9
Thus, this method is highly regioselective affording imida-
zolines relatively in good yields. The reaction conditions are
Aziridines are well-known carbon electrophiles capable of
reacting with various nucleophiles and their ability to undergo
regioselective ring-opening reactions contributes largely to their
synthetic value.1 They are useful intermediates for the synthesis
of many biologically interesting molecules such as amino acids,2
heterocycles,3 and alkaloids.4 Aziridines can also undergo a
formal [3 + 2] cycloaddition with a range of dipolarophiles
leading to five-membered nitrogen-containing heterocycles.5,6
In particular, the cycloaddition of aziridines with nitriles has
special interest because the resultant imidazolines are known
to exhibit a wide range of pharmacological activities.7 Conse-
quently, there have been some reports on the regioselective ring
opening of aziridines with nitriles using acid catalysis such as
boron trifluoride, zinc(II) bromide, scandium(III) triflate, and
copper(II) triflate.8,9 However, many of these procedures involve
the use of stoichiometric amount of catalysts and require anhy-
drous conditions and also involve the formation of side products
resulting in low conversion. Since, imidazolines are very useful
targets in medicinal chemistry, the development of simple,
convenient, cost-effective, and efficient approaches are highly
desirable. Moreover, no attempt has been made to recycle
the catalyst, thereby making the process more economic and
environmentally friendly.
The use of heteropoly acids, HPAs, as environmentally
friendly and economically viable solid acids, is increasing
continuously owing to their ease of handling, high catalytic
activities, and reactivities. They possess unique properties such
as well-defined structure, Brønsted acidity, possibility to modify
their acid–base and redox properties by changing their chemical
composition (substituted HPAs), ability to accept and release
electrons and high proton mobility, etc.10 HPAs are very strong
acids, approaching the super acid region, with a Brønsted acidity
greatly exceeding that of ordinary mineral acids and solid acids.
This makes it possible to carry out a catalytic process at low
concentrations and at lower temperatures. In view of green
chemistry, the substitution of harmful liquid acids by reusable
solid HPAs as catalysts in organic synthesis is the most promis-
ing application of this acids.11 Among them, phosphomolybdic
acid (PMA, H3PMo12O40) is one of the less expensive and
commercially available catalysts.12 Supported HPAs are more
active than unsupported HPAs. PMA–SiO2 is a stable, non-hy-
Ts
N
N
10 mol % PMA−SiO2
23 °C
N-Ts
R'CN
R'
+
4
Scheme 2.
Ts
Ts
+
10 mol % PMA−SiO2
23 °C
N
N
PhCN
Ph
N
5n
Scheme 3.
Copyright Ó 2008 The Chemical Society of Japan