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

Article abstract of DOI:10.1134/S0023158410020096

The novel efficient procedure has been developed for the conjugate addition of amines to electron deficient alkenes. The results showed that the catalyst was very efficient for the reactions with the excellent yields in several minutes. Operational simplicity, without need of any solvent, low cost of the catalyst used, high yields, reusability, excellent chemoselectivity, applicability to large-scale reactions are the key features of this methodology. The article is published in the original.

Full text of DOI:10.1134/S0023158410020096

ISSN 0023ꢀ1584, Kinetics and Catalysis, 2010, Vol. 51, No. 2, pp. 225–228. © Pleiades Publishing, Ltd., 2010.
Published in Russian in Kinetika i Kataliz, 2010, Vol. 51, No. 2, pp. 240–243.
Highly Efficient Procedure for the Conjugate Addition
of Amines to Electron Deficient Alkenes1
,b
Liao Anꢀpinga , Lan Pingb, Li Meib, and Lan Liꢀhongb
a School of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004, China
b School of Chemistry and Ecology Engineering, Guangxi University for Nationalities, Nanning 530006, China
eꢀmail: gxanping@sohu.com
Received December 3, 2008
Abstract—The novel efficient procedure has been developed for the conjugate addition of amines to electron
deficient alkenes. The results showed that the catalyst was very efficient for the reactions with the excellent
yields in several minutes. Operational simplicity, without need of any solvent, low cost of the catalyst used,
high yields, reusability, excellent chemoselectivity, applicability to largeꢀscale reactions are the key features
of this methodology.
DOI: 10.1134/S0023158410020096
1
The addition of nitrogen compounds across carꢀ
The catalyst was synthesized through the polymerꢀ
bonꢀcarbon multiple bonds is an unsolved synthetiꢀ ization of pꢀtoluenesulfonic acid (PTSA) and
cally important problem for both basic research and paraformaldehyde catalyzed by sulfuric acid
for the chemical industry [1]. An alternative method (Scheme 1). In the typical procedure: The mixture of
for preparing these compounds is via Michael addiꢀ pꢀtoluenesulfonic acid (10 g), paraformaldehyde (2 g),
tion. It is a very straightforward approach for the synꢀ and sulfuric acid (0.2 g) was heated to 100–110°C in a
thesis of substituted amines and their derivatives with three necked round bottomed flask equipped with a
100% atom efficiency and without any byproduct forꢀ magnetic stirrer, a thermometer, and a funnel. The
mation [2]. Although a number of alternative proceꢀ reaction was kept in the range of 100–110°C for 48 h
dures have been reported recently using a variety of to form black solid. The solid was washed with hot
water (>80°C) and filtrated until no SO24– was
reagents such as Pd compounds, InCl3, CeCl3,
Yb(OTf)3, Bi(NO3)3, Bi(OTf)3, Cu(OAc)2, LiClO4
,
detected in the filtrate. The catalyst was obtained after
Clay, Silica gel, SmI2, FeCl3, CrCl3, SnCl4, et al. [3–
23]. Many suffer from limitations such as the requireꢀ
ment for a large excess of reagents, long reaction
times, harsh reaction conditions and also involvement
of toxic solvents such as acetonitrile or 1,2ꢀdichloroetꢀ
hane. Hence, the development of less expensive, simꢀ
pler, “greener” catalysts for the reactions is still highly
desirable. Aiming to these advantages, we developed a
solventꢀfree protocol for the conjugate addition of
amines to electron deficient alkenes using a novel hetꢀ
erogeneous acid catalyst. The catalyst has been synꢀ
thesized through the copolymerization of pꢀtolueneꢀ
sulfonic acid (PTSA) and paraformaldehyde with sulꢀ
furic acid as catalyst (Scheme 1). The results showed
that the catalysts were efficient for the reaction with
the excellent yields.
drying at 120°C overnight in an oven.
The Conjugate Addition of Amines
to Electron Deficient Alkenes
Typical procedure for the conjugate addition of
amines: To a mixture of amines (20 mmol), alkenes
(24 mmol) and the catalyst (50 mg) was stirred 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
(2 × 20 ml) and the combined extract was dried over
Na2SO4 and evaporated to leave a crude product, the
product was separated by column chromatography
CH3
CH3
EXPERIMENTAL
CH2
Sulfuric acid
HCHO 100–110°C, 48 h
n
+
n
+ nH2O
n
All organic reagents were commercial products
with the highest purity available (>98%) and used for
the reaction without further purification.
SO3H
SO3H
1
The article is published in the original.
Scheme 1. The synthetic route of the novel catalyst.
225

226
LIAO ANꢀPING et al.
TChoenjcuognajtuegaadtediatdiodnitsioonf svaorfiovuarsioamusinamesiwneitshwailtkheanleksenes
Entry
Amines
Alkenes
COOCH3
Reaction ttime, min
YYiieelldd,, %%b
*
H
1
5
98
N
H
N
2
3
4
5
6
10
10
15
25
5
96
97
94
92
97
COOCH3
COOCH3
NH2
COOCH3
COOCH3
COOC2H5
H2N
OH
NH2
NH2
H
N
H
7
8
20
10
25
5
95
96
92
98
COOC2H5
COOC2H5
N
NH2
9
COOC2H5
OH
NH2
H
N
10
H3COOC
COOCH3
COOCH3
COOCH3
H
N
11
12
13
14
15
16
17
18
25
15
20
25
30
5
93
94
95
92
92
98
94
92
91
H3COOC
H3COOC
NH2
H3COOC
H3COOC
H3COOC
C4H9OOC
C4H9OOC
C4H9OOC
COOCH3
COOCH3
COOCH3
COOC4H9
COOC4H9
COOC4H9
H3CO
OH
NH2
NH2
H2N
NH2
H
N
H
20
15
25
N
NH2
19
H3CO
NH2
C4H9OOC
COOC4H9
a
b
Note: RTeahcetiroenacctoionndictoionndsi:tiaomnsin: aem20inme m20oml, malkoel,naelsk2e0nems m24oml, mcaotal,lycsatt5al0ysmt g5,0Rm.Tg.,(R2.5T°.C(2).5°C).
* Isolated yield.
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2010

HIGHLY EFFICIENT PROCEDURE FOR THE CONJUGATE ADDITION OF AMINES
227
using neutral alumina as stationary phase and (petroꢀ
leum ether/ethyl acetate 95 : 5) as eluent to give the
corresponding products.
Weight, mg
16
14
12
RESULTS AND DISCUSSION
Characterization of the Catalyst
The acidity of the catalyst determined through the
neutralization titration gave the results of 224 mg
(KOH)/g. The acid strength of the catalyst was deterꢀ
mined by thermodesorption of chemisorbed ammonia
(NH3ꢀTPD). The results showed that the catalyst had
high acid strength in which ammonia desorbed rangꢀ
ing from 673 to 873 K. The elemental analyst gave the
results: C 59.7%; H 7.3%; S 12.8%; O 20.2%. The
results indicating that almost all the element S existed
in the catalyst in the form of sulfuric groups. The IR
spectra of the catalyst showed the sulfuric group
absorbability at 1030 and 970 cm–1 which confirmed
the existence of the sulfuric groups. The BET surface
area using nitrogen adsorptionꢀdesorption isotherms
at the temperature of liquid nitrogen which gave the
result of 23 m2/g. The TG analysis gives the decomꢀ
10
100 200 300 400 500 600 700 800
T, °C
Fig. 1. The TG curve of the novel catalyst.
(Entries 1, 6, 10, 16). The yields slightly dropped with
the carbon atomicity of the amines added because of
the steric hinderance (Entries 2, 3, 7, 8, 11, 12, 17, 18).
Here the catalyst was also efficient for the multiꢀ
amino compound such as ethanediamine (Entries 4,
15). Both amino groups reacted with the alkenes the
yield over 90% in short time. The primary amines
underwent the single substitution reaction under the
reaction condition (Entries 3, 8, 12, 18). These results
indicated the usefulness of the novel catalyst for the
reactions and the reaction conditions are mild and not
sufficient to cause double substitution reaction. The
multiꢀsubstitution reaction could also be activated
when more alkenes and high temperature applied,
then the double substituted products were obtained
with high yields. Ethanolamine and 3ꢀmethoxy ethyꢀ
lamine also converted to the corresponding products
without destroy the hydroxyl and methoxy groups
(Entries 5, 9, 13, 14, 19). As to the alkenes, the reacꢀ
tivity was affected by the EWG and the steric hinꢀ
posed temperature of 200°C, which showed that the
catalyst holds great potential for the high temperature
reactions (Fig. 1).
Catalytic Procedure for the Conjugate Addition
The conjugate additions of various amines with
alkenes under solventꢀfree condition were investigated
first (Table 1). The results showed that the reactions
underwent smoothly at room temperature within sevꢀ
eral minutes. The dimethylamine showed extremely
high activity for all kinds of electron deficient alkenes
with almost complete conversion within 5 min drance also had the certain effect on the reaction.
R1
R2
R1
R2
EWG
EWG cat
+
NH
N
R.T.
MS:
72, 58, 42, 30.
m
/
z
159 (M+ –1), 144, 130, 116, 102, 86 (100%),
The other separated products were then tested by
1H NMR and results agreed well with that of authentic
samples.
δ
, ppm): 3.685 (
s,
Entry 2:
1H NMR (CDCl3, 500 MHz,
δ
, ppm): 3.68 (
, 4H, = 7.18 Hz),
, 3H, = 7.18 Hz).
s, 3H),
The Reuse of the Catalyst
2.80 (
t
, 2H,
J
J
= 7.30 Hz), 2.52 (
q
J
2.46 (
t
, 2H,
= 7.30 Hz), 1.03 (
t
J
One property of the catalyst is the heterogeneous
catalytic process. Thus, recovery of the catalyst is very
convenient. After reactions, the catalyst was recovered
by filtration. The recovered activities were investigated
through the reaction of dibutylamine and methyl acryꢀ
late carefully (Fig. 2). The yield remained unchanged
even after the catalyst had been recycled for a sixth
13C NMR (CDCl3, 125 MHz,
48.2, 47.1, 32.1, 12.2.
δ
, ppm): 173.5, 51.8,
Entry 7:
1H NMR (CDCl3, TMS):
7.2 Hz), 2.426 ( , 2H, = 7.2 Hz), 2.477 (
7.2 Hz), 2.765 ( , 2H, = 7.2 Hz), 3.649 (
δ
(0.993 (
t
, 6H,
J
=
=
t
t
J
J
q, 4H, J
s
, 3H). GC– time.
KINETICS AND CATALYSIS Vol. 51
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2010

228
LIAO ANꢀPING et al.
O
O
NH
N
O
Cat., RT
10 min
99%
10 mmol
+
O
12 mmol
NH2
10 mmol
NH2
Scheme 2. The chemoselectivity of the catalyst.
4. Xu, L.W., Yang, M.S., Qiu, H.Y., Lai, G.Q., and
Jiang, J.X., Synth. Commun., 2008, vol. 38, p. 1011.
5. Miao, T. and Wang, L., Tetrahedron Lett., 2008, vol. 49,
Yield, %
100
p. 2173.
80
60
40
20
6. Wang, Y., Li, P., Liang, X., Zhang, T.Y., and Ye, J.,
Chem. Commun., 2008, p. 1232.
7. Bhanushali, M.J., Nandurkar, N.S., Jagtap, S.R., and
Bhanage, B.M., Catal. Commun., 2008, vol. 9, p. 1189.
8. Shirakawa, S. and Shimizu, S., Synlett., 2007, p. 3160.
9. Zhu, S., Yu, S., and Ma, D., Angew. Chem. Int. Ed.
Engl., 2008, vol. 47, p. 545.
10. Chen, F.X., Shao, C., Wang, Q., Gong, P., and
0
1
Zhang, D.Y., Tetrahedron Lett., 2008, vol. 49, p. 1282.
2
3
4
5
6
Run
11. Ni, B., Zhang, Q., and Headley, A.D., Tetrahedron
Lett., 2008, vol. 49, p. 1249.
Fig. 2. The reuse of the catalyst.
12. Azim, Z.H. and Saidi, M.R., Tetrahedron Lett., 2008,
vol. 49, p. 1244.
13. Li, X., Cun, L., Lian, C., Zhong, L., Chen, Y., Liao, J.,
Zhu, J., and Deng, J., Org. Biomol. Chem., 2008, vol. 6,
p. 349.
The Chemoselectivity of the Catalyst
It is noteworthy that aromatic amines did not
14. Attanasi, O.A., Favi, G., Filippone, P., Golobic, A.,
undergo the reaction under the same reaction condiꢀ
tions (Scheme 2). This result indicated that the
present protocol could be applicable to the chemoseꢀ
lective addition of aliphatic amines in the presence of
aromatic amines.
Perrulli, F.R., Stanovnik, B., and Svete, J., Synlett.
2007, p. 2971.
,
15. Micheletti, G., Pollicino, S., Ricci, A., Berionni, G.,
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16. Esteban, J., Costa, A.M., Gomez, A., and Vilarrasa, J.,
Org. Lett., 2008, vol. 10, p. 65.
17. Bi, X., Zhang, J., Liu, Q., Tan, J., and Li, B., Adv.
Synth. Catal., 2007, vol. 349, p. 2301.
CONCLUSIONS
In conclusion, a novel efficient procedure has been
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19. Luo, S., Zhang, L., Mi, X., Qiao, Y., and Cheng, J.,
electron deficient alkenes. Operational simplicity,
without need of any solvent, low cost of the catalyst
used, high yields, excellent chemoselectivity, applicaꢀ
bility to largeꢀscale reactions are the key features of
this methodology.
J. Org. Chem., 2007, vol. 72, p. 9350.
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KINETICS AND CATALYSIS Vol. 51
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2010