505
Solid lithium perchlorate as a powerful catalyst
for the synthesis of -aminoalcohols under
solvent-free conditions
Najmodin Azizi and Mohammad R. Saidi
Abstract: Lithium perchlorate catalyzed the ring opening of epoxides with amines to provide the corresponding β-
aminoalcohols in excellent yields with high regioselectivity. The reaction proceeds rapidly under mild and neutral con-
ditions and worked well with primary, secondary, aliphatic, aromatic, and hindered amines in short times at room tem-
perature, in the absence of solvent.
Key words: epoxide, lithium perchlorate, β-aminoalcohols, solvent-free.
Résumé : Le perchlorate de lithium catalyse l’ouverture de cycle des époxydes avec des amines qui conduit aux β-
aminoalcools correspondants avec d’excellents rendements et une régiosélectivité élevée. La réaction se produit rapide-
ment dans des conditions douces et neutres et elle se produit rapidement avec les amines primaires, secondaires, alipha-
tiques, aromatiques et empêchées, à la température ambiante et en l’absence de solvant.
Mots clés : époxyde, perchlorate de lithium, β-aminoalcools, sans solvant.
[Traduit par la Rédaction] Azizi and Saidi 507
Introduction
In recent years, to minimize the harmful organic solvents
used in chemical processes, much attention has been devoted
to the use of alternative media. Besides the use of supercriti-
cal fluid water and ionic liquids, the possibility of perform-
ing chemical reactions in the absence of solvent has been
receiving more attention (8).
β-Aminoalcohols are versatile intermediates in the synthe-
sis of a vast variety of biologically active natural and syn-
thetic products (1), unnatural amino acids (2), and chiral
auxiliaries for asymmetric synthesis (3). The classical syn-
thesis of β-aminoalcohols consists of heating an epoxide
with an excess of amine at elevated temperatures (4). High
temperatures may not be appropriate for certain functional
groups. Also, a variety of air-sensitive or expensive catalysts
had been reported in the literature to perform epoxide open-
ing at room temperature. Many of these catalysts are either
corrosive, or in some cases, they are being applied to aro-
matic amines with poor regioselectivity and with undesirable
side reactions such as rearrangement and polymerization (5–
7). However, there are still some limitations with the re-
ported methods in the literature. For example, deactivated
amines failed to open up the epoxides or require high
temperatures. Furthermore, they require a high catalyst-to-
substrate ratio, have a long reaction time, and they need
volatile organic solvents that eventually results in the gener-
ation of a large amount of toxic waste. To overcome these
limitations, the development of a better catalyst for the
activation of epoxides, rendering them more susceptible to
nucleophilic attack under a mild, efficient, and general
method, is of great interest.
Results and discussion
Because of our interest for developing solvent-free and
environmentally benign synthetic methods (9), herein, we re-
port a more simple, general, and new catalytic route for the
synthesis of β-aminoalcohols via opening of epoxides with
amines under solvent-free conditions in the presence of a
catalytic amount of LiClO4. At first, we examined the reac-
tion of cyclohexene oxide with aniline and 0.2 equiv. of
solid LiClO4 at room temperature. Complete conversion took
place within 120 min, leading to quantitative yield of trans-
2-phenyl amino cyclohexanol. This success encouraged us to
exploit the generality and scope of this reaction for the open-
ing of other epoxides with various aromatic and aliphatic
amines under catalytic amounts of LiClO4. The reaction pro-
ceeded well with aromatic, aliphatic, hindered, and unhin-
dered amines. The role of LiClO4 in catalyzing the opening
of epoxide rings with amines maybe realized through the co-
ordination of Li+ with the epoxide oxygen and renders the
epoxide more susceptible to nucleophilic attack by the
amine, which after protonation forms the aminoalcohol (Ta-
ble 1).
Received 26 July 2004. Published on the NRC Research
In the next step, we have examined various amines using
styrene oxide as the unsymmetrical epoxide to investigate
the regioselectivity outcome of the reaction. In all cases, the
ring openings take place in highly regioselective fashion, af-
fording the β-aminoalcohols in high yields. It should also be
N. Azizi and M.R. Saidi.1 Department of Chemistry, Sharif
University of Technology, P.O. Box 11365-9516, Tehran,
Iran.
1Corresponding author (e-mail: saidi@sharif.edu).
Can. J. Chem. 83: 505–507 (2005)
doi: 10.1139/V05-062
© 2005 NRC Canada