Catalyst-free regioselective ring opening of epoxides with aromatic amines in water and solvent-free conditions

Article abstract of DOI:10.1007/s13738-012-0122-3

Without using any catalysts, a variety of epoxides undergo ring-opening by aromatic amines to afford the corresponding 1,2-amino alcohols in high to excellent yields with good regioselectivity in the presence of water as solvent and under solvent-free con

Full text of DOI:10.1007/s13738-012-0122-3

J IRAN CHEM SOC (2013) 10:7–11
DOI 10.1007/s13738-012-0122-3
ORIGINAL PAPER
Catalyst-free regioselective ring opening of epoxides
with aromatic amines in water and solvent-free conditions
•
A. Ziyaei-Halimehjani H. Gholami
•
M. R. Saidi
Received: 16 November 2011 / Accepted: 6 June 2012 / Published online: 3 July 2012
Ó Iranian Chemical Society 2012
Abstract Without using any catalysts, a variety of
epoxides undergo ring-opening by aromatic amines to
afford the corresponding 1,2-amino alcohols in high to
excellent yields with good regioselectivity in the presence
of water as solvent and under solvent-free conditions.
attracted considerable attention due to a wide range of
obvious advantages, such as cost, availability, safety, its
environmental friendliness, and enhancement of selectivity
with respect to the use of organic solvents [4–12]. Water
also has practical advantages over organic solvents, since
in contrast to many other solvents, water provides not only
a medium for solution chemistry, but also often participates
in elementary chemical events on a molecular scale and
acts as a catalyst to accelerate reactions [1, 9–12].
Keywords Ring opening Á Epoxides Á Aromatic amines Á
Water Á Regioselective Á Solvent-free
On the other hand, solvent-free reactions have several
advantages, such as reducing pollution and energy con-
sumption, high efficiency, low cost, simplified procedures
and handling, environmentally friendly with easy work up
procedure [2, 13–16].
Introduction
Increasingly, chemists are looking for cleaner, more envi-
ronmentally benign procedures to devise new synthetic
routes [1]. In order to this, chemists have placed a strong
emphasis on the improvement of traditional ways for
chemical reactions especially in organic synthesis. In
recent years, design of green processes has become an
eminent issue [2]. Currently, there are five main ‘‘green’’
systems: supercritical fluids (SCFs), using fluorinated sol-
vents, ionic liquids (ILs) or water as solvent and solvent-
free reactions [3]. In this report, we have used water as
green medium or solvent-free systems for ring opening of
epoxides. These two green approaches have gained special
attention by synthetic organic chemists, because of their
unique properties compared to the other three ‘‘green’’
systems. Reactions performed in water as solvent have
Epoxides are valuable intermediates in organic synthe-
sis. The strain of the three-membered rings and the polar-
ization of the C–O bonds in epoxides enhance their
reactivity with a large number of nucleophiles. High
reactivity of epoxides with various nucleophiles leads to
highly regioselective and stereospecific ring opening
products. Due to these properties of the epoxides and the
ease of preparation, epoxides are used as useful interme-
diates in organic synthesis. Epoxides can undergo ring
opening with amines, alcohols and thiols as nucleophilic
compounds to form the C–C [17–20], C–N [21–26],
C–O [27–30], or C–S [31, 32] bonds.
Since b-amino alcohols are a useful and important class
of organic compounds, organic and medicinal chemists
devoted considerable attention to use these compounds as
versatile intermediates in the synthesis of variety of bio-
logically active natural and synthetic products [33–40].
Nucleophilic ring-opening of epoxides by amines is an
important reaction for synthesizing b-amino alcohols. In
addition, almost all procedures reported so far for the
preparation of b-amino alcohols by ring opening of
A. Ziyaei-Halimehjani
Faculty of Chemistry, Tarbiat Moallem University,
P.O. Box 11465-9516, 11365 Tehran, Iran
H. Gholami Á M. R. Saidi (&)
Department of Chemistry, Sharif University of Technology,
P.O. Box 11465-9516, Tehran, Iran
e-mail: saidi@sharif.edu
123

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J IRAN CHEM SOC (2013) 10:7–11
Selected spectroscopic data for the major isomer
epoxides are restricted to simple aromatic and aliphatic
amines in the presence of various catalysts [33, 41–48]. But
aromatic amines have received less attention, maybe due to
their high affinity to Lewis acids or low nucleophilicity
[22, 26]. Bonollo et al. [49] have reported aminolysis of
epoxides with aliphatic and aromatic amines under mild
basic and pH-controlled conditions. We have successfully
used water as a reaction medium for the ring opening of
epoxides with aliphatic amines [50]. Therefore, an efficient
catalyst-free system for the ring opening of epoxides with
aniline derivatives in water or under solvent-free condi-
tions is developed.
1H NMR (500 MHz, CDCl3) d (ppm) 1.22 (6H, d,
J = 6.1 Hz), 3.11 (1H, dd, J = 12.4 and 3.8 Hz),
3.44–3.65 (3H, m), 3.95 (1H, m), 6.44 (1H, dd, J = 8.7
and 2.6 Hz), 6.69 (1H, d, J = 2.2 Hz), 7.17, (1H, d,
J = 8.7 Hz); 13C NMR (125 MHz, CDCl3) d (ppm) 22.5,
47.2, 69.3, 70.5, 72.8, 114.5, 116.9, 120.7, 131.1, 133.3,
148.1; MS (EI): m/z = 279, 277, 190, 188, 176, 174, 161,
99, 43 (100), 41 (Table 2, entry 7).
1H NMR (500 MHz, CDCl3) d (ppm) 1.20 (6H, d,
J = 6.1 Hz), 3.11 (1H, dd, J = 12.9 and 7.1 Hz), 3.25 (1H,
dd, J = 12.4 and 3.8 Hz), 3.42–3.63 (6H, m), 3.75 (3H, s),
3.95 (1H, m), 6.16–6.25 (3H, m), 7.02 (1H, m); 13C NMR
(125 MHz, CDCl3) d (ppm) 22.5, 47.2, 55.2, 69.3, 70.8,
72.6, 99.6, 103.2, 106.6, 130.2, 150.1, 161.2; MS (EI): m/
z = 239, 150, 136, 121, 93, 77, 45, 43 (100), 41, 39, 29, 27,
15 (Table 2, entry 9).
Experimental
General
1H NMR (500 MHz, CDCl3) d (ppm) 3.68–3.89 (2H,
m), 4.12 (1H, dd, J = 14.1 and 7.0 Hz), 4.60 (1H, br), 6.44
(1H, d, J = 8.6 Hz), 6.70 (1H, d, J = 2.1 Hz), 7.15–7.39
(6H, m); 13C NMR (125 MHz, CDCl3) d (ppm) 60.3, 67.3,
113.3, 116.9, 120.5, 127.1, 128.3, 129.4, 131.1, 133.0,
139.8, 147.4; MS (EI): m/z = 283, 281, 252, 250, 176, 174,
172, 147, 145, 103, 91, 77, 31(100) (Table 2, entry 11).
1H NMR (500 MHz, CDCl3) d (ppm) 2.95 (1H, br,
–OH), 3.07–3.23 (2H, m), 3.43–3.51 (2H, m), 3.97–4.03
(3H, m), 4.20 (1H, br, –NH), 5.22–5.31 (2H, m), 5.88 (1H,
m), 6.42 (1H, d, J = 8.0 Hz), 6.67 (1H, d, J = 2.2 Hz),
7.16 (1H, d, J = 8.7 Hz); 13C NMR (125 MHz, CDCl3) d
(ppm) 46.9, 68.9, 72.2, 72.7, 117.2, 114.8, 117.9, 120.2,
130.9, 133.0, 134.6, 148.2; MS (EI): m/z = 277, 275, 176,
174, 161, 84, 47, 39, 35 (100) (Table 2, entry 13).
1H NMR (500 MHz, CDCl3) d (ppm) 1.93 (3H, s), 3.10
(1H, dd, J = 12.9 and 7.4 Hz), 3.23 (1H, dd, J = 12.9,
4.0 Hz), 3.75 (1H, br, –NH), 4.05–4.22 (3H, m), 5.62 (1H,
s), 6.15 (1H, s), 6.42 (1H, d, J = 8.0 Hz), 6.67 (1H, d,
J = 2.2 Hz), 7.14 (1H, d, J = 8.7 Hz); 13C NMR
(125 MHz, CDCl3) d (ppm) 18.7, 46.8, 66.9, 68.7, 114.5,
116.8, 120.7, 126.9, 131.0, 133.3, 136.2, 147.9, 167.8; MS
(EI): m/z = 306, 304, 303, 178, 176, 174, 69, 43, 41 (100),
39 (Table 2, entry 17).
All reactions were carried out in an atmosphere of air. All
chemicals and solvents except water (tap water) were
purchased from Merck or Fluka and used as received. All
reactions were monitored by TLC on silica gel 60 F254
(0.25 mm), visualization being effected with UV and/or
by developing in iodine. 1H NMR and 13C NMR were
recorded on a Brucker 500 MHz spectrometer. Chemical
shifts are reported in (ppm) relative to TMS or CDCl3 as
internal.
General procedure for the ring opening of epoxides
with aromatic amines in water
To a stirred solution of an epoxide (2.5 mmol) and an
amine (3 mmol), water (4 mL) was added, and the mixture
was stirred at 60 °C for 18 h. The mixture was extracted by
ethyl acetate (3 9 10 mL), and the crude product was
purified by flash column chromatography to provide the
corresponding product. For solvent-free conditions, the
mixture of an epoxide (2 mmol) and an amine (2 mmol)
was stirred at 60 °C for 18 h. All compounds were char-
acterized on the basis of their spectroscopic data (NMR)
and by comparison with those reported in the literature.
General procedure for large scale synthesis
Results and discussion
In a 100-mL round bottom flask equipped with magnetic
stir bar, aniline (10 g, 107 mmol), H2O (50 ml) and
1,2-epoxybutane (7.7 g, 107 mmol) were added and the
mixture stirred at 60 °C for 20 h. After completion, the
mixture was separated and the organic phase was washed
with water (100 mL), and evaporated in rotary evaporator
to remove unreacted epoxide. The product was obtained in
95 % isolated yield with 84:16 ratios.
As part of our ongoing efforts to explore environmentally
friendly synthesis [51–56], herein we describe a simple,
catalyst-free, efficient, and regioselective method for the
synthesis of b-hydroxyl amines in high to excellent yields
in water or solvent-free conditions (Scheme 1).
In the first step, we have examined the reaction of
2,3-epoxypropyl isopropyl ether with aniline as a model
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J IRAN CHEM SOC (2013) 10:7–11
9
Scheme 1 Epoxide ring
opening with aromatic amines
OH
NHAr
H2O, 60 °C
O
O
O
ArNH2
O
or
NHAr
major
OH
Solvent-free, 60 o
C
minor
Table 1 Study of the solvent effect in the model reaction of aminolysis of epoxide
HO
O
NH2
HN
HN
O
O
OH
Solvent (4ml)
(60 °C)
O
+
+
A
B
Entry
Solvent
Yield (%)
Ratio (A:B)a
1
MeOH
C2H5OH
Pentane
CH3CN
CHC13
THF
100
100
27
(81:19)
2
(80:20)
3
–
4
100
100
23
(82:18)
5
–
6
–
7
CH2CI2
DMF
100
100
100
28
(80:20)
8
–
9
Toluene
C2H4CI2
H2Ob
–
10
11
12c
a
–
95
(83:17)
(73:27)
S.F.
100
Ratio was determined by NMR spectroscopy
b
c
Double distilled water
Solvent-free condition
reaction in water at room temperature (20 °C) to obtain the
corresponding amino alcohol (Table 2, entry 5). The
reaction was not complete at this temperature. By
increasing the temperature, the epoxide was converted to
the products completely. The optimum temperature was
found to be 60 °C (Table 2, entry 5). It is clear that the
temperature plays an important role in this reaction.
These results encouraged us to continue this procedure
for exploiting the generality of this reaction by ring-opening
of other epoxides with various activated and deactivated
aromatic amines. Aniline, 4-chloroaniline, 3,4-dichloroan-
iline, and p-anisidine were reacted well with epoxides such
as 2,3-epoxypropyl phenyl ether, 2,3-epoxypropyl methac-
rylate, 1,2-epoxybutane, 1,2-epoxypropane, allyl 2,3-ep-
oxypropyl ether, epoxystyrene, and epoxycyclohexane to
give the corresponding amino alcohols with good to
excellent yields (Table 2). The reaction did not proceed
with highly deactivated aromatic amines such as p-nitro-
aniline. Large scale synthesis of b-amino alcohol was also
carried out by the reaction of aniline with 1,2-epoxybutane
in water with 95 % yield (Table 2, entry 2).
In the next step, we have performed the reaction in various
commonorganicsolvents. We have foundthatthe reactioncan
also proceed in low-polar solvents such as toluene, CHCl3,
DMF, acetonitrile, and CH2Cl2. The yields were lower in
1,2-dichloroethane, THF, and pentane. Among these solvents,
waterwasfoundtobethebestsolventforthisreaction. Wealso
performed the model reaction in double distilled water to
diagnose the effects of mineral ions in regular water. We
observed that minerals in tap water had no effect on the
reaction.Also,wehavedonethemodelreactionundersolvent-
free conditions and in the presence of two drops of water as
catalyst. Theresult wasthesameaswaterwasusedassolvent.1
The solvent optimization results are listed in Table 1.
In continuation of our attempt to approach green prin-
ciples, we also investigated ring opening of epoxides with
aromatic amines under solvent-free conditions. Since
almost all of the epoxides that we used were liquid, it was
possible to implement solvent-free condition. By mixing
aromatic amines with all the epoxides (1 to 1 ratio) and
stirring of the mixture at 60 °C for 18 h, the products were
obtained as well as using water, except in the case of
1
It is difficult to distinguish in/on water in this reaction.
123

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J IRAN CHEM SOC (2013) 10:7–11
Table 2 Aminolysis of epoxides in water or solvent-free condition
Water (60 °C, 18 h)
OH
H
N
H
N
O
+
ArNH2
Ar
OH
+
Ar
R'
or
R
R'
Solvent-free (60 °C, 18 h)
(A)
(B)
Entry
1
Epoxide
Aromatic amine
Aniline
Water [yield % (A:B)a,b
100 (75:25) [42]
]
Solvent-free [yield % (A:B)]
–
O
2
Aniline
100 (86:14) [57]
O
Aniline
95 (84:16)c [57]
100 (96:4) [57]
100 (67:33) [57]
100 (85:15) [57]
–
3
4
5
p-Chloroaniline
p-Anisidine
Aniline
–
85 (68:32)
95 (80:20)
O
O
Aniline
80 (89:11)d
92 (85:15)e
100 (79:21)f
96 (84:16)g
100 (94:6) [57]
84
–
Aniline
–
Aniline
–
Aniline
–
6
p-Chloroaniline
3,4-Dichloroaniline
p-Anisidine
m-Anisidine
Aniline
98 (80:20)
78 (80:20)
100 (92:8)
94 (86:14)
90 (29:71)
7
8
100 (96:4) [57]
–
9
10
100 (19:81) [57]
O
11
12
3,4-Dichloroaniline
Aniline
89 (22:78)
–
100 (85:15) [57]
100 (72:28)
O
O
O
13
14
15
3,4-Dichloroaniline
p-Chloroaniline
Aniline
63 (93:7)
43 (100:0)
89 (82:18)
95 (81:19)
100 (90:10) [57]
100 (95:5) [57]
O
O
16
17
18
p-Chloroaniline
3,4-Dichloroaniline
Aniline
100 [57]
80 (80:20)
100 [42]
100 (100:0)
72 (100:0)
N.R.
O
19
20
a
p-Anisidine
p-Toluidine
100 [22]
100 [22]
–
–
The ratio was determined by NMR spectroscopy
References are given for known compound
Large scale
b
c
d
e
f
The reaction was carried out at 20 °C
The reaction was carried out at 35 °C
The reaction was carried out in the presence of two drops of H2O
g
The reaction was carried out with double distilled water
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J IRAN CHEM SOC (2013) 10:7–11
11
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In conclusion, we have investigated an economical and
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epoxides using aniline derivatives. Distinctive points of
this work are using water as medium, catalyst-free, and
also implementing solvent-free conditions, which are an
important feature for the developing of green chemistry.
Probably in these reactions water acts as a catalyst and
implements the reaction with high efficiency and regiose-
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