An efficient method for the ring opening of epoxides with aromatic amines catalysed by indium trichloride

Article abstract of DOI:10.1039/b007729l

Indium trichloride catalyses for the first time the formation of β-amino alcohols from epoxides and aromatic amines in dichloromethane at room temperature.

Full text of DOI:10.1039/b007729l

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An efficient method for the ring opening of epoxides with aromatic
amines catalysed by indium trichloride¤
L. Rajender Reddy, M. Arjun Reddy, N. Bhanumathi and K. Rama Rao*
Organic Chemistry Division-1, Indian Institute of Chemical T echnology, Hyderabad-500 007,
India. E-mail: ramaraok=iict.ap.nic.in
L e t t e r
Received (in Montpellier, France) 20th September 2000, Accepted 20th November 2000
First published as an Advance Article on the web 11th January 2001
Indium trichloride catalyses for the Ðrst time the formation of
b-amino alcohols from epoxides and aromatic amines in
dichloromethane at room temperature.
With the present methodology, even sterically hindered
amines such as o-methyl (3b, 3m, 3q), o-methoxyaniline (3d, 3n,
3r) and a-naphthylamine (3j, 3o) react smoothly at room tem-
perature. The noteworthy feature of the present methodology
is that highly deactivated amines such as p-nitroaniline (3i, 3p)
also opened the epoxides in a reasonable yield at room tem-
perature. The unusual feature of this reaction is that only aro-
matic amines opened the epoxides, whereas aliphatic amines
such as diethylamine, benzylamine and pyrrolidine failed to
react with these epoxides at room temperature after 48 h
under the reaction conditions. The reaction of these epoxides
with diethylamine also did not take place even under
dichloromethane reÑux conditions. The lack of reactivity of
aliphatic amines may be due to stronger complexation with
the catalyst as a consequence of their higher basicity.
b-Amino alcohols are an important class of organic com-
pounds, which have found much use in medicinal chemistry
and organic synthesis.1 The classical synthesis of b-amino
alcohols consists heating an epoxide with an excess of amine
at elevated temperatures.2 Since some functional groups may
be susceptible to high temperatures, a variety of activators
have been introduced for the cleavage of epoxides at room
temperature.3 However, there are still some limitations with
the literature methods; for example, deactivated aromatic
amines and some sterically hindered aromatic amines fail to
open up these epoxides or still require high temperatures. To
overcome these limitations, we report herein an efficient,
simple and practical method for the ring opening of epoxides
with aromatic amines catalysed by indium trichloride (InCl )
in dichloromethane at room temperature.
Table 1 Indium trichloride catalysed epoxide opening with aromatic
amines
3
The use of indium trichloride as a catalyst in various
organic transformations,4 such as transmetallation with
organotin compounds,4ahc Mukaiyama aldol reactions,4d
imino DielsÈAlder reactions,4e Barbier reactions,4f etc., is well
documented. The opening of epoxides with indium trichloride
is known to give either the corresponding carbonyl com-
pounds or chlorohydrins.4g But this reaction has not so far
been attempted in the presence of amines, which can give rise
to versatile b-amino alcohols of great utility in medicinal and
organic chemistry. Herein, we have attempted for the Ðrst time
the cleavage of epoxides with aromatic amines using indium
trichloride as a catalyst since this is one of the most useful
synthetic transformations with varied applications.
The reaction was carried out by adding indium trichloride
to a mixture of epoxide (1) and amine (2) in dichloromethane
at room temperature (Scheme 1). The optimum ratio of
indium trichloride was found to be 0.20 mol.%. The reaction
mixture was stirred at room temperature for 12 h to give the
corresponding amino alcohols (3) in almost quantitative yields
(Table 1). All the compounds were fully characterised by IR,
1H NMR, 13C NMR and mass spectral data by comparison
with the known compounds.3a,b The trans stereochemistry of
the amino alcohols, for compound 3c as an example, was
determined from the coupling constants of the peaks at 3.31
ppm (CHÈOH) (ddd, J \ 9.8, 9.2, 4.5 Hz) and 3.07 ppm (CHÈ
NHPh) (ddd, J \ 9.8, 9.2, 3.9 Hz) in the 1H NMR spectra.3h
Amino alcohola
Yieldb (%)
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
Ar \ Phc
90
88
94
90
96
92
94
95
80
84
92
Ar \ C H -o-CH c
6
4
3
Ar \ C H -p-CH c
6
4
3
Ar \ C H -o-OCH c
6
4
3
Ar \ C H -p-OCH c
6
4
3
Ar \ C H -m-Brd
6
4
Ar \ C H -p-Brd
6
4
Ar \ C H -p-Fc
6
4
Ar \ C H -p-NO d
6
4
2
Ar \ a-naphthylc
Ar \ b-naphthylc
3l
Ar \ Phc
78
81
80
76
75
3m
3n
3o
3p
Ar \ C H -o-CH e
6
4
3
Ar \ C H -o-OCH e
6
4
3
Ar \ a-naphthyle
Ar \ C H -p-NO d
6
4
2
3q
3r
Ar \ C H -o-CH e
86
84
6
4
3
Ar \ C H -o-OCH e
6
4
3
a Substrates 1 and 2 were mixed in a 1 : 1 ratio with 0.2 mol.% of
Scheme 1
InCl . Substrates and catalyst were stirred in CH Cl at r.t. for 12 h.
3
2 2
b Isolated yields. c Ref. 3h. d Ref. 3b. e New compound.
¤ IICT Communication no. 4580.
DOI: 10.1039/b007729l
New J. Chem., 2001, 25, 221È222
221
This journal is ( The Royal Society of Chemistry and the Centre National de la Recherche ScientiÐque 2001

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In summary, we have demonstrated a novel, mild and effi-
cient method for the ring opening of epoxides with aromatic
amines using indium trichloride as a catalyst. This method is
also compatible with deactivated and sterically hindered aro-
matic amines. We believe that this will be a useful addition to
modern synthetic methodology.
(m, 3H). EI-MS (70 ev): m/z 227 (M`). Anal. calc. for
C
H
NO: C 79.26, H 7.54, N 6.16; found: C 79.12, H 7.48,
15 17
N 5.98%.
Compound 3q. Pale yellow viscous liquid. IR (neat): 3100È
3550 cm~1. 1H NMR (CDCl , 200 MHz): d 2.21 (s, 3H), 3.75
3
(m, 1H), 3.92 (m, 1H), 4.05 (br s, 2H, NH and OH), 4.51 (m,
1H), 6.69 (m, 4H), 7.38 (m, 5H). EI-MS (70 ev): m/z 227 (M`).
Experimental
Anal. calc. for C
H
NO: C 79.26, H 7.54, N 6.16; found: C
15 17
79.48, H 7.66, N 6.28%.
General procedure
Compound 3r. Pale yellow viscous liquid. IR (neat): 3050È
To a mixture of epoxide 1 (1 mmol) and amine 2 (1 mmol) in
dichloromethane (5 ml) was added anhydrous InCl (0.2
mmol) at room temperature; the mixture was stirred at room
3500 cm~1. 1H NMR (CDCl , 200 MHz): d 3.80 (m, 1H), 3.95
3
(m, 4H, ÈOCH , H), 4.05 (br s, 2H, NH and OH), 4.55 (m,
3
3
1H), 6.40 (m, 1H), 6.75 (m, 3H), 7.38 (m, 5H). EI-MS (70 ev):
temperature for 12 h. It was then quenched by the addition of
aqueous sodium hydrogen carbonate (10%, 25 ml), extracted
with dichloromethane (3 ] 25 ml), dried over anhydrous
sodium sulfate, Ðltered and concentrated. The residue was
puriÐed by column chromatography on silica gel (100È200
mesh) using chloroform as eluent. The characterisation data
for 3b (for comparison with the literature) and for all new
compounds are given below.
m/z 243 (M`). Anal. calc. for C
5.76; found: C 74.26, H 6.95, N 5.88%.
H
NO : C 74.05, H 7.04, N
15 17
2
Acknowledgements
L. R. R. and M. A. R. thank CSIR, New Delhi, India for the
award of Research Fellowships.
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Compound 3b. Pale yellow viscous liquid. IR (neat): 3150È
3600 cm~1. 1H NMR (CDCl , 200 MHz): d 1.08 (m, 1H), 1.39
3
(m, 3H), 1.75 (m, 2H), 2.08 (m, 2H), 2.18 (s, 3H), 2.81 (br s, 2H,
NH and OH), 3.14 (ddd, J \ 10.9, 9.3, 3.9, 1H, CHÈNHPh),
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3
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13 19
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2
C
H
NO: C 75.35, H 8.96, N 7.32; found: C 75.45, H 8.88,
L. Rajender Reddy, M. Arjun Reddy, N. Bhanumathi and K.
12 17
N 7.36%.
Rama Rao, Synlett, 2000, 3, 339 (cyclodextrin); (i) J. Iqbal and A.
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2
Overman and L. A. Flippin, T etrahedron L ett., 1981, 22, 175 (Al
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3
(m, 3H), 2.05 (m, 1H), 2.30 (m, 1H), 3.60 (m, 1H), 3.85 (s, 3H),
4.00 (m, 1H ), 4.15 (br s, 2H, NH and OH), 6.76 (m, 4H).
EI-MS (70 ev): m/z 207 (M`). Anal. calc. for C
69.54, H 8.27, N 6.76; found: C 69.52, H 8.17, N 6.55%.
H
NO : C
4
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12 17
2
Compound 3o. White solid, mp 78È80 ¡C. IR (neat): 3120È
3550 cm~1. 1H NMR (CDCl , 200 MHz): d 1.41 (m, 1H), 1.78
3
(m, 3H), 2.01 (m, 1H), 2.25 (m, 1H), 3.65 (m, 1H), 4.05 (m, 1H),
4.20 (br s, 2H, NH and OH), 7.30 (m, 2H), 7.45 (m, 2H), 7.84
222
New J. Chem., 2001, 25, 221È222