Novel efficient procedure for the conjugate addition of amines to electron deficient alkenes

Article abstract of DOI:10.1134/S0023158410050058

The novel efficient procedure has been developed for the conjugate addition of amines to electron deficient alkenes using the novel SO₃H functionalized ionic liquid as catalyst. The results showed that the novel catalyst owned high activities for the reactions with excellent yields within several minutes. Various amines and electron deficient alkenes were successfully transformed to the corresponding products in the catalytic system. Operational simplicity, without need of any solvent, low cost of the catalyst used, room temperature, high yields, reusability, excellent chemoselectivity and wide applicability are the key features of this methodology.

Full text of DOI:10.1134/S0023158410050058

ISSN 0023ꢀ1584, Kinetics and Catalysis, 2010, Vol. 51, No. 5, pp. 653–656. © Pleiades Publishing, Ltd., 2010.
Novel Efficient Procedure for the Conjugate Addition
1
of Amines to Electron Deficient Alkenes
Xudong Sun, Yijun Du, Chunqing Li, and Chenze Qi
Institute of Applied Chemistry, Shaoxing University, Shaoxing, China
eꢀmail: Qichenze@zscas.edu.cn
Received September 1, 2009
Abstract—The novel efficient procedure has been developed for the conjugate addition of amines to electron
deficient alkenes using the novel SO H functionalized ionic liquid as catalyst. The results showed that the
3
novel catalyst owned high activities for the reactions with excellent yields within several minutes. Various
amines and electron deficient alkenes were successfully transformed to the corresponding products in the catꢀ
alytic system. Operational simplicity, without need of any solvent, low cost of the catalyst used, room temꢀ
perature, high yields, reusability, excellent chemoselectivity and wide applicability are the key features of this
methodology.
DOI: 10.1134/S0023158410050058
1
lonitrile, butyl acrylate, methyl acrylate, mefhyꢀ
The addition of nitrogen compounds across multiꢀ
ple carbon–carbon bonds is an unsolved synthetically lamine, ethylamine, morpholine were purchased from
important problem for both basic research and chemꢀ Shanghai Chemicals Co.
ical industry [1]. An alternative method for preparing
these compounds is via Michael addition. It is a
straightforward approach for the synthesis of substiꢀ
tuted amines and their derivatives with 100% atom
efficiency and without any byproduct formation [2].
Although a number of alternative procedures have
been reported recently using a variety of reagents such
as Pd compounds [3], InCl [4], CeCl [5], Yb(OTf)
Synthesis of the Catalyst
Preparations of zwitterions. Cyclopenta[b]pyridine
and equimolar 1,4ꢀbutane sulfonate were mixed
together and stirred magnetically for 72 h at 25°C
Then, a white solid zwitterion was formed and washed
repeatedly with ether. After dried in vacuum (110°C,
.01 Torr), the white solid zwitterion was obtained in
high yield (>95%) and sufficient purity as assessed by
a Varian DRXꢀ400 NMR spectroscopy. Spectroscopic
.
3
3
3
4
[
6], Bi(NO ) [7], Bi(OTf) [8], Cu(OAc) [9], LiClO
3 3 3 2
[
10], clay [11], silica gel [12], SmI [13], FeCl [14],
2 3
0
CrCl [15], SnCl [16], et al. Many suffer from the
3
4
limitations such as the requirement for a large excess
of reagents, long reaction time, harsh reaction condiꢀ
tions and involvement of toxic solvents such as acetoꢀ
1
data of NMR H (400 MHz, D O, TMS) for the zwitꢀ
2
nitrile or 1,2ꢀdichloroethane. Hence, the developꢀ terions:
δ
= 1.693 (m, 2H), 1.962 (m, 2H), 2.178 (m,
ment of less expensive, simpler, “greener” procedures 2H), 2.820 (t,
J
J
= 7.8 Hz, 2H), 3.041 (t,
= 7.8 Hz, 2H), 4.381 (t,
J
J
= 7.6 Hz,
= 7.6 Hz,
for the reactions is still highly desirable. Aiming to
these advantages, we developed a novel solventꢀfree
protocol for the conjugate addition of amines to elecꢀ
tron deficient alkenes at room temperature (R.T.)
using the ionic liquid as catalyst (Scheme 1). The
results showed that the catalyst was very efficient for
the reactions with high yields.
2
H), 3.243 (t,
R.T.
+
O
SO3−
72 h
N+
S
N
O
O
EXPERIMENTAL
–
H SO
2
4
HSO4
All organic reagents were commercial products of
the highest purity available (>98%) and used for the
reaction without further purification. Cyclohexamine,
cyclopenta[b]pyridine, 1,4ꢀbutane sulfonate, acryꢀ
80°C
SO H
3
N+
Scheme 1. The synthetic route with using of the ionic
liquid.
1
The article is published in the original.
653

6
54
XUDONG SUN et al.
R1
EWG
EWG cat, R.T.
R1
The conjugate additions of various amines with alkenes
NH +
N
R2
R2
Entry
1
Amines
–NH2
Alkenes
COOCH3
COOCH3
COOCH3
Reaction time, min
5
Yield, %
99
2
3
NH2
NH2
10
10
98
97
4
5
15
25
96
94
O
NH
COOCH3
COOCH3
NH2
6
7
8
–NH2
NH2
7
15
20
99
96
96
COOC H9
4
COOC H9
4
NH2
NH
COOC H9
4
9
25
35
94
92
O
COOC H9
4
1
0
NH2
COOC H
4
9
1
1
2
–NH2
NH2
4
5
99
98
CN
CN
1
1
3
4
15
20
97
95
NH2
CN
CN
1
O
NH
15
25
95
NH2
CN
The reaction conditions: amine 20 mmol, alkenes 24 mmol, catalyst 50 mg, R.T. (25°C). The yield was estimated by GC analysis.
2
(
H), 7.598 (t,
d, 1H).
Preparation of the novel strong Br
J
= 7.0 Hz, 1H), 8.110 (d, 1H), 8.337
Conjugate Addition of Amines
to Electron Deficient Alkenes
ønsted acidic
Typical procedure for the conjugate addition of
ionic liquid. A stoichiometric amount of sulfuric acid
was added to the above obtained zwitterion and the amines was the next. A mixture of amine (20 mmol),
mixture was stirred at 80°C for 6 h to form the ionic alkene (24 mmol) and the catalyst (50 mg) was stirred
liquid. The ionic liquid phase was then washed repeatꢀ
edly with toluene and ether to remove nonꢀionic resiꢀ
dues, and dried in vacuum (110°C, 0.01 Torr). The
product was formed quantitatively and in high purity
at room temperature for the certain time as shown
below. The process of the reaction was monitored by
GC analysis. The reaction mixture was extracted with
ethyl acetate (
dried over anhydrous Na
2
×
20 ml) and the combined extract was
SO and evaporated to leave
1
as assessed by mass balance and NMR H specꢀ
1
2
4
troscopies. NMR H (400 MHz, D O, TMS):
δ
=
2
a crude product, which was separated by column chroꢀ
matography using neutral alumina as stationary phase
1
(
J
J
.781 (m, 2H), 2.043 (m, 2H), 2.258 (m, 2H), 2.896
t, = 7.6 Hz, 2H), 3.121 (t, = 7.6 Hz, 2H), 3.325 (t,
= 7.6 Hz, 2H), 4.463 (t,
= 7.0 Hz, 1H), 8.189 (d, 1H), 8.420 (d, 1H).
J
J
J
= 7.6 Hz, 2H), 7.678 (t, and petroleum ether/ethyl acetate mixture (95 : 5) as
eluent to give the corresponding product.
KINETICS AND CATALYSIS Vol. 51
No. 5
2010

NOVEL EFFICIENT PROCEDURE FOR THE CONJUGATE ADDITION OF AMINES
COOCH3
655
NH2
N
10 mmol
cat, R.T.
25 min
94%
+
COOCH3
12 mmol
NH2
NH2
10 mmol
Scheme 2. The chemoselectivity of the catalyst.
RESULTS AND DISCUSSION
The Reuse of the Catalyst
One property of the catalyst is the heterogeneous
catalytic process. Thus, recovery of the catalyst is very
convenient. After reactions, the reaction mixture was
Catalytic Procedure for the Conjugate Addition
The conjugate additions of various amines with
alkenes under solventꢀfree conditions were investiꢀ
gated first (table). The results showed that the reacꢀ
tions underwent smoothly at room temperature just
within several minutes. The methylamine showed
extremely high activity for all kinds of electron defiꢀ
cient alkenes with almost complete conversion within
extracted with ethyl acetate (2 × 20 ml) and the lower
phase, the ionic liquid, could be reused without any
disposal. The recovered activities were investigated
through the reaction of cyclohexamine and methyl
acrylate carefully (figure). The yield remained
unchanged even after the catalyst had been recycled
for six times.
5
min (entries 1, 6, 11). The yields slightly dropped
with the increasing carbon atomicity of the amines
because of the steric hindrance (entries 2, 3, 7, 8, 12,
The Chemoselectivity of the Catalyst
1
3). The primary amines underwent the single substiꢀ
It is noteworthy that aromatic amines could not be
tution reaction under the reaction condition. These transformed to the corresponding products under the
results indicated the usefulness of the novel catalyst for same reaction conditions (Scheme 2). This result indiꢀ
cated that the present protocol could be applicable to
the chemoselective addition of aliphatic amines in the
presence of aromatic amines.
In conclusion, a novel efficient procedure has been
developed for the conjugate addition of amines to
electron deficient alkenes. Operational simplicity,
without need of any solvent, low cost of the catalyst
used, high yields, excellent chemoselectivity, wide
applicability are the key features of this methodology.
the reactions and the reaction conditions are mild and
not sufficient enough to cause double substitution
reaction. The multusubstitution reactions could also
be activated when more alkenes and high temperature
applied, then the double substituted products were
obtained with high yields. As to the alkenes, the reacꢀ
tivity was affected by the electronic withdrawing
groups (EWG) and the steric hindrance also had the
certain effect on the reaction.
ACKNOWLEDGMENTS
Yield, %
This work was supported by the Shaoxing Key Disꢀ
cipline Foundation, China.
100
80
60
40
20
0
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