Microwave-enhanced catalyst-free aminolysis of epoxides with anilines in aqueous phase: Efficient synthesis of β-amino secondary alcohols

Article abstract of DOI:10.3184/174751911X13237015498335

β-Amino secondary alcohols were formed by aminolysis of epichlorohydrin and styrene oxide with aromatic amines using aqueous ethanol (1:1) as the solvent in conjunction with microwave irradiation without a catalyst. The methodology is fast, efficient, hig

Full text of DOI:10.3184/174751911X13237015498335

7
26 RESEARCH PAPER
DECEMBER, 726–728
JOURNAL OF CHEMICAL RESEARCH 2011
Microwave-enhanced catalyst-free aminolysis of epoxides with anilines
in aqueous phase: efficient synthesis of β-amino secondary alcohols
Zhengyin Du,* Wenwen Zhang, Yuanmin Zhang and Xiaohong Wei
Key Laboratory of Eco-Environment Related Polymer Materials of Ministry of Education, Key Laboratory of Polymer Materials of Gansu
Province & College of Chemistry and Chemical Engineering, Northwest Normal University, Lanzhou 730070, P. R. China
β-Amino secondary alcohols were formed by aminolysis of epichlorohydrin and styrene oxide with aromatic
amines using aqueous ethanol (1:1) as the solvent in conjunction with microwave irradiation without a catalyst. The
methodology is fast, efficient, highly regioselective, chemoselective and environmentally benign.
Keywords: amination, epoxides, ring opening, aqueous phase reaction, microwave irradiation, green chemistry
Epoxides play an important role in organic synthesis because
their highly strained three-membered ring makes them sensi-
tive to various nucleophiles. Apart from alcohols and thiols,
amines are also effective nucleophiles. The ring-opening of
epoxides with amines is an atom-economical reaction and an
important route for the preparation of β-amino alcohols that
are key intermediates in the synthesis of biologically active
group as a highly efficient catalyst for aminolysis of epoxides
1
4
under solvent-free conditions. In addition, a few examples of
the ring opening of epoxides without the use of any catalyst
have been disclosed. Highly chemoselective addition of amines
to epoxides in water was introduced by Saidi and Azizi in
1
5
16
2005. Qu et al. found that hot water of 60–100 °C acted as
a mild acidic catalyst and solvent to promote the ring-opening
of epoxides by aniline without any additive. Although the
microwave-assisted ring opening of epoxides by amines in
absolute ethanol in the absence of activators proceeded rapidly
and efficiently, the nucleophilic reagents were limited to
1
natural products and pharmaceuticals. It is also used in the
2
synthesis of unnatural amino acids and chiral auxiliaries.
This reaction shows a regioselectivity based on the electronic
properties of the substituents on the substrates and the reaction
conditions (Scheme 1).
17
aliphatic amines and not aromatic amines. However, the
Recently, the reaction has been studied in order to improve
the selectivity of the products and reaction conditions. Lautens
above-mentioned procedures suffer from some disadvantages.
The aminolysis of asymmetric epoxides by aromatic amines
described previously gave the corresponding β-amino primary
3
and Fagnou reported that the rhodium-catalysed ring opening
of vinyl epoxides with alcohols and aromatic amines possessed
excellent diastereo- and regioselectivity. As a strong Lewis
acid, stoichiometric amounts of indium tribromide were
reported to promote the ring opening of epoxides with aro-
matic amines to form β-amino secondary alcohols exclusively
4
alcohols B as main products, except in one case in which the
products were β-amino secondary alcohols A. In order to over-
come these shortcomings and based on our investigation about
1
8–20
green organic synthesis,
we have developed a practical,
rapid and efficient method for the aminolysis of epoxides with
aromatic amines.
4
in CH Cl at room temperature. The synthesis of β-amino
2
2
alcohols by the regioselective ring opening of styrylepoxides
with anilines catalysed by cobalt chloride gave the correspond-
5
Results and discussion
ing primary alcohols as the main product. The enantioselec-
tive ring opening of meso-epoxides by aromatic amines
We report here a catalyst-free ring-opening reaction of
epoxides with anilines using microwave irradiation in aqueous
alcohol. We obtained the corresponding β-amino secondary
alcohols exclusively in high yields, unlike the previous reports
(Scheme 2).
6
catalysed by lanthanide iodobinaphtholates, Sc(OSO C H ) /
3
12 25 3
7
chiral bipyridine ligand and Zn(II)/Cu(II) surfactant-type
catalysts has also been studied and good to excellent enanti-
8
oselectivities have been achieved with enantiomeric excesses
up to 96%. Some environmental friendly reagents and reaction
procedures have been investigated in the context of green
The ring-opening of epichlorohydrin (C) with aniline (D)
was used as the model reaction to examine the selectivity and
yield with respect to the solvent, the microwave power, the
molar ratio of the two substrates, and the reaction time. The
results are listed in Table 1. First, we surveyed the effects
of different solvents on the reaction with the molar ratio of
C/D=2/1 (Table 1, entries 1–16) and irradiating at 264 W for
10 min. A yield of 78% of the corresponding product was
observed in aqueous ethanol (1:1 in volume) (Table 1, entry
13). Then we explored the optimal power of microwave
irradiation (Table 1, entries 13 and 17–19) and found that the
optimal is 264 W. The ratio of the two substrates were also
examinedshowing that a molar ratio of C/D = 3:1 gave a yield
of 84% (Table 1, entry 21). Finally, the irradiation time was
studied revealing that 8 minutes was the most effective
(Table 1, entry 25).
9
chemistry. Three-dimensional mesoporous aluminosilicate
1
0
and nanoporous aluminosilicate materials as structure- direct-
ing agents and solid acids were prepared and found to be highly
selective and recyclable heterogeneous catalysts for the syn-
thesis of β-amino alcohols in good yields with high selectivity
for the Markovnikov addition product. Silica chloride nanopar-
1
1
ticles have also been described as catalysts for this reaction.
Tertiary amines, such as DABCO and triethylamine are highly
efficient catalysts in the ring-opening reactions of epoxides
1
2
with amines in water under mild conditions. The zinc (II)
perchlorate hexahydrate catalysed opening of epoxide ring by
amines, introduced by Chakraborti et al. under solvent-free
13
conditions, showed excellent chemo-, regio-, and stereose-
lectivities. A thiourea derivative was also reported by Chimni’s
Scheme 1 Ring-opening of epoxides with amines.
*
Correspondent. E-mail: clinton_du@126.com
Scheme 2 Ring-opening of epoxides with anilines.

JOURNAL OF CHEMICAL RESEARCH 2011 727
Table 1 Ring-opening reaction of epichlorohydrin C with
Table 2 Ring-opening reaction of epoxides with various
a
aromatic aminesa
aniline D in different conditions
Entry Solvent
V/V)
Molar ratio Power
Time Yield
Entry R1
R2
Product
Yield
b
b
(
of C/D
/W
/min
/%
/%
1
2
3
4
5
6
7
8
9
THF
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
1:1
3:1
4:1
1:2
3:1
3:1
3:1
3:1
3:1
264
264
264
264
264
264
264
264
264
264
264
264
264
264
264
264
136
440
616
264
264
264
264
264
264
264
264
264
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
5
21
59
12
7
17
20
38
16
77
30
3
39
78
56
47
68
51
63
61
70
84
66
61
82
87
81
85
77
THF/H
THF/H
THF/H
2
2
2
O (1:1)
O (2:1)
O (4:1)
1
2
3
4
5
6
7
8
9
ClCH
ClCH
ClCH
ClCH
ClCH
ClCH
ClCH
ClCH
ClCH
2
2
2
2
2
2
2
2
2-Cl
48
57
a21,22
CH
CH
CH
CH
CH
2
3
3
3
3
Cl
CN
CN/H
OH
OH/H
2
3-Cl
b21
2
O (1:1)
2
O (1:1)
O (1:1)
1
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
PEG-400/H
Toluene
EtOH
2
4-Cl
68
c21,23
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
EtOH/H
EtOH/H
EtOH/H
2
2
2
O (1:1)
O (1:2)
O (2:1)
2-CH
3-CH
4-CH
3
3
3
82
d23
2
H O
EtOH/H
EtOH/H
EtOH/H
EtOH/H
EtOH/H
EtOH/H
EtOH/H
EtOH/H
EtOH/H
EtOH/H
EtOH/H
EtOH/H
2
2
2
2
2
2
2
2
2
2
2
2
O (1:1)
O (1:1)
O (1:1)
O (1:1)
O (1:1)
O (1:1)
O (1:1)
O (1:1)
O (1:1)
O (1:1)
O (1:1)
O (1:1)
89
e24
93
f21,23
8
3-NO
H
2
73
12
15
20
g23
a
The scale of aniline was 0.5 mmol and the total volume of
solvents was 4 mL.
Isolated yield after column chromatography.
87
h21,22
b
2
2
2,4-(CH
3
)
2
100
i
After optimisation of the reaction conditions, we investi-
gated the scope and limitation of the ring-opening reaction.
Epichlorohydrin and styrene oxide, as representatives of
aliphatic and aromatic epoxide respectively, were examined in
this reaction. The results shown in Table 2 reveal that epoxides
reacted with a number of aromatic amines with different sub-
stituents to form the corresponding β-amino alcohols in good
to excellent yields. The reaction was completely regioselective
and chemoselective since the only products isolated were
β-amino secondary alcohol isomers arising from attack of the
amine at the less substituted carbon of epoxides. No diols of
hydrolysis of epoxides were observed. This selectivity was
observed even for styrene oxide (Table 2, entries 11–17),
10
ClCH
Ph
2,5-(CH
3
O)
2
95
81
j21
11
12
2-CH3
k23
Ph
Ph
4-CH
3
89
70
91
85
l23
5
,9–11,13–16
unlike most previously reports.
In comparison with
13
14
15
16
3-NO
2
electron-withdrawing groups, electron-donating groups
attached to the aromatic ring of amines gave higher yields in
the ring-opening of epichlorohydrin to form β-amino alcohols
m23
3 2
Ph 2,5-(CH O)
(
Table 2, entries 1–10). Styrene oxide showed the same pattern
n
under these conditions (Table 2, entries 11–17). For the same
aniline, the reaction of styrene oxide resulted in a lower yield
than epichlorohydrin. This may be explained by greater steric
hindrance and conjugative effects of benzene ring of styrene
oxide.
In conclusion, we have developed a new methodology for
C–N bond-formation via aminolysis of epoxides with aromatic
amines without catalysts in aqueous alcohol under microwave
irradiation. It is a simple, high efficient, completely regioselec-
tive and chemoselective procedure for the synthesis of β-amino
secondary alcohols.
Ph
H
o22,23
Ph
Ph
4-Cl
4-Br
66
69
p23
17
q23
a
Reaction conditions: amines (0.5 mmol), epoxides (1.5 mmol),
EtOH (2 mL), water (2mL), MW 264 W, 8 minutes.
Isolated yields after column chromatography; all known
products were characterised by H and C NMR, which were
consistent with literature data.
Experimental
b
1
13
All reagents were used as obtained from commercial sources without
further purification. The H and C NMR spectra were recorded on a
1
13

7
28 JOURNAL OF CHEMICAL RESEARCH 2011
Bruker MERCURY-PLUS 400 MHz NMR spectrometer. Chemical
shifts were reported in parts per million (ppm, δ). IR spectra were
measured on an Alpha Centauri FT-IR spectrometer. Melting points
were determined on an XT-4 electrothermal micromelting-point appa-
ratus. Microwave irradiation was carried out with a modified Midea
MM823ESJ-PA domestic microwave oven. In order to avoid the un-
reliable and un-reproducible results by using this microwave oven, all
experiments were conducted at least twice under parallel conditions to
obtain coincident yield.
Electron Supplementary Information
Electron Supplementary Information includes spectroscopic
1
13
data and H NMR, C NMR spectra of all products and is
available online via http://www.ingentaconnect.com/content/
stl/jcr.
Financial support by Natural Science Foundation of China
(20702042), Key Laboratory of Polymer Materials of Gansu
Province (zd-06-18), and NWNU Young Teachers Reseach
Improving Program (NWNU-LKQN-10-11) is acknowl-
edged.
Caution: the use of a domestic microwave oven for chemical
purposes has been found to be potentially hazardous.
Synthesis of β-amino alcohols
A mixture of the amine (0.5 mmol), epoxide (1.5 mmol), EtOH
Received 12 November 2011; accepted 1 December 2011
Paper 1100980 doi: 10.3184/174751911X13237015498335
Published online: 27 December 2011
(
2.0 mL) and H O (2.0 mL) were added to a 50 mL round-bottomed
2
flask. The flask was placed into the domestic microwave oven at
64 W for 8 minutes. After cooling the reaction mixture to room tem-
perature, the contents were extracted with ethyl acetate (4 × 5 mL).
2
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−
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11
16
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2
1
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3
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