220 RESEARCH PAPER
APRIL, 220–221
JOURNAL OF CHEMICAL RESEARCH 2008
An efficient method for the ring opening of epoxides with aromatic
amines by Sb(III) chloride under microwave irradiation
Dadkhoda Ghazanfaria, Mohammed M. Hashemib, Mohammad Mehdi Mottaghic and
Mohammad Mehdi Foroughia
aDepartment of Chemistry, Kerman Branch, Islamic Azad University, PO Box 194, Kerman, Iran
bDepartment of Chemistry, Sharif University of Technology, PO Box 11365-9516, Tehran, Iran
cDepartment of Food Science and Technology, Science and Research Branch, Islamic Azad University, PO Box 14515-775, Tehran,
Iran
SbCl3 supported on montmorillonite K-10 is an efficient catalyst for the ring opening of epoxides with aromatic
amines under solvent-free conditions and microwave irradiation to give the corresponding b-amino alcohols in high
yields with high regioselectivity
Keywords: epoxides, SbCl3, aromatic amines, b-amino alcohols
b-Amino alcohols are a very important class of organic
compounds and have considerable application in medicinal
chemistry.1,2 The classical synthesis of b-amino alcohols
consists of heating an epoxide with an excess of amine.2,3
These reactions are usually carried out in a solvent, requiring
many hours of reflux, which is environmentally unfriendly.
Recently, the use of catalysts to carry out these reactions under
mild conditions has been developed.4-11 However, there are
still some limitations with these methods including the failure
of deactivated aromatic amines and some sterically hindered
aromatic amines to open the epoxides, the need for an excess
of reagent, reactions at reflux temperatures and sluggish
reactions. Therefore, it is desirable to develop improved
catalysts for the activation of epoxides, which render them
to be more susceptible to nucleophilic attack under mild
conditions. Stringent environmental protection laws in recent
years prompted an increasing emphasis on the use and design
of eco-friendly reagents, solid state procedures, and solvent-
free reactions.12 Application of microwaves is currently under
extensive examination,13 and dry procedures have recently
attracted much attention.14 We report herein a simple fast and
efficient procedure for the nucleophilic opening of epoxides
with aromatic amines catalysed by Sb(III) chloride, supported
on montmorillonite K-10 under microwave irradiation.
The corresponding b-amino alcohols are obtained in high
yields with high regioselectivity. In the absence of Sb(III)
chloride, the epoxide ring opening reaction of n-hexyl oxirane
(1d) with aniline under similar reaction conditions does not
occur even after 20 minutes microwave irradiation, indicating
that the SbCl3 effectively promotes the opening of the
epoxides. An alternative reaction of n-hexyl oxirane (1d) with
aniline under similar reaction conditions without microwave
irradiation led to the formation of only 36% of 3a after
6 hours mixing in the presence of Sb(III) chloride impregnated
on montmorillonite K-10, at room temperature. Note that
when unsymmetrical epoxides were allowed to react in the
presence of Sb (III) chloride, the ring opening takes place
HPh
N
O
Montmorillonite K-10, SbCl3
Microwave irradiation
R
Ph-NH
+
2
R
OH
1
2
Scheme 1
in a completely regioselective fashion. The attack at the less
substituted oxirane carbon affording the desired compound
as the only product. However, when styrene oxide (1j) was
allowed to react with aniline under the mentioned conditions,
two regioisomers (2j, 3j) were formed in the ratio 20:80.
The major product (3j) was obtained by attack of aniline at
the benzylic carbon of the epoxide.
Furthermore, cycloalkyl epoxides such as cyclopentene and
cyclohexene oxide reacted with aromatic amines in excellent
yieldsinwhichatransstereospecificitywasobserved(Scheme2
and Table 2). In the case of cyclohexene oxide, the trans
stereochemistry of b-amino alcohols was determined from the
coupling constant of the ring methine protons at d 3.33 (ddd,
J = 10.2, 10.1 and 5.5 Hz, 1H, N–CH) and at d 3.54 (ddd,
10.1, 8.6 and 4.2 Hz, 1H, O–CH) in 1H NMR of 4k.
After using SbCl3 supported on montmorillonite K-10 for
the ring opening of n-hexyl oxirane (1d) with aniline under
microwave irradiation the catalyst can be recovered after
reaction with hydrochloric acid, and then it was used for the
ring opening of n-hexyl oxirane (1d) with aniline. The second
use of SbCl3 for the ring opening of n-hexyl oxirane (1d) with
aniline to 2d showed about 5% decrease in the reactivity.
However, the third use showed no further decrease in reaction
yields (cf. Table 3).
This simple procedure gives short reaction times, and
generally gives high yields under microwave irradiation after
several uses of SbCl3 supported on montmorillonite K-10.
R1
R1
OH
Montmorillonite K-10, SbCl3
Microwave irradiation
(CH2)n
+ H2N
O
(CH2)n
R 2
N
H
R2
3
2
4
(a-m)
Scheme 2
* Correspondent. E –mail: dadkhodaghbk@ yahoo. com
PAPER: 08/5033