Microwave-induced aza-michael reaction in water: A remarkably simple procedure

Article abstract of DOI:10.1080/00397910903134634

Microwave-induced fast addition of several amines to conjugated carbonyl compounds has been carried out in water very efficiently in the absence of any catalyst. Copyright

Full text of DOI:10.1080/00397910903134634

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Microwave-Induced Aza-Michael
Reaction in Water: A Remarkably Simple
Procedure
a
a
a
Andrea Kall , Debasish Bandyopadhyay & Bimal K. Banik
a
Department of Chemistry, University of Texas–Pan American,
Edinburg, Texas, USA
Version of record first published: 17 May 2010.
To cite this article: Andrea Kall , Debasish Bandyopadhyay & Bimal K. Banik (2010): Microwave-
Induced Aza-Michael Reaction in Water: A Remarkably Simple Procedure, Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry, 40:12, 1730-1735
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1
Synthetic Communications , 40: 1730–1735, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903134634
MICROWAVE-INDUCED AZA-MICHAEL REACTION IN
WATER: A REMARKABLY SIMPLE PROCEDURE
Andrea Kall, Debasish Bandyopadhyay, and Bimal K. Banik
Department of Chemistry, University of Texas–Pan American, Edinburg,
Texas, USA
Microwave-induced fast addition of several amines to conjugated carbonyl compounds has
been carried out in water very efficiently in the absence of any catalyst.
Keywords: Amine; aza-Michael; enone; green synthesis; microwave irradiation
Michael reaction of nucleophiles to unsaturated carbonyl compounds requires
[
1]
[2]
basic or acidic conditions. Methods classified as Michael reactions require
stoichiometric amounts or excess of acids and bases in organic solvents, and side
reactions can occur if the reactive partners are sensitive to nucleophiles, such as
[3]
amino compounds. The most important feature of these reagents is their ability
[
4]
to limit the catalysts used to catalytic amounts. Despite their tremendous advan-
tage, however, the literature reveals that the success of the reaction depends on
the choice of the catalyst and organic solvent. For example, indium salts are
[
5]
[6]
extremely effective for Michael reactions with indoles and pyrroles, but they
[
are not excellent promoters in catalyzing a similar reaction with carbamates. In
7]
[
7]
contrast, platinum salts are very effective for this purpose. These reactions were
performed in organic solvents. An alternative attractive method using either an effec-
tive catalyst or no catalyst in aqueous medium would be highly desirable, timely, and
challenging. The use of bismuth-derived reagents in several organic transformations
[8]
has been demonstrated by our group. The present communication describes the
development of a remarkably simple, fast, and environmentally benign microwave-
induced aza-Michael reaction of amines with unsaturated carbonyl compounds in
water in the absence of any catalysts.
Organic reactions in water have received significant attention because of their
environmental acceptability and selectivity. The rate acceleration in water has also
been observed in many cases. Development of an efficient and simple procedure in
water without any catalyst is difficult but important.
[9]
Many procedures have been developed for aza-Michael reaction. Transition
metals, lanthanide halides, triflates, silica gel, hetereogeneous solid salts,
Received April 16, 2009.
Address correspondence to Bimal K. Banik, Department of Chemistry, University of Texas–Pan
American, 1201 West University Drive, Edinburg, TX 78539, USA. E-mail: banik@panam.edu
1
730

MICROWAVE-INDUCED AZA-MICHAEL REACTION IN WATER
1731
Cu(acac) =ionic liquid, quarternary ammonium salt=ionic liquid=H O, boric acid
2
2
in H O, and b-cyclodextrin in H O all have been used for the aza-Michael reac-
2
2
tion. Despite much progress, many of these methods used heavy-metal salts and
hazardous organic solvents.
Our microwave-induced reaction (Scheme 1) in water has been tested with several
amines, unsaturated ketones, unsaturated nitriles, and unsaturated ester, the results of
which have been very encouraging (Table 1). The reactions are efficient and completed
within 1 to 3 min. The products are isolated in excellent yields. All the reactions in
water were very rapid compared to reactions in organic solvents under identical
conditions (microwaves). No catalysts were necessary to complete the reaction.
Primary, secondary (cyclic, heterocyclic, and acyclic), benzylic, and aromatic
amines produce excellent yields. This method suggests that it is not necessary to
use a large excess of corrosive acid, catalytic amounts of Lewis acids, or solid acidic
surfaces in Michael reactions of amines with unsaturated ketones, esters, and nitriles.
Primary amines produced monoaddition products (entries 10–14) selectively, and no
bis-addition product could be detected. The presence of water accelerates the reac-
tion, probably through hydrogen bond formation with the carbonyl group, and this
may increase the electrophilic character at the b-carbon of the unsaturated com-
pounds. As a result, nucleophilic attack by the amine may increase significantly.
On the other hand, hydrogen bond formation between the oxygen atom of water
and the H atom of the amine may also increase the nucleophilic power of the N atom
of the amine. Water has a very high dielectric constant and dipole moment, and
therefore the role of water in the presence of microwave is unique. Water activates
the amine as well as the enone system through hydrogen bond formation and thereby
greatly facilitates the addition through a brief microwave exposure.
Several years ago, our laboratory demonstrated the aza-Michael reaction in the
[
9a]
presence of bismuth nitrate in organic solvent.
We proposed that the role of
bismuth nitrate in this type of reaction results in a coordinating power with the
carbonyl group. Later, we also demonstrated that bismuth nitrate–catalyzed Michael
[
10]
reactions have proceeded remarkably well in aqueous media.
In conclusion, this method is completely devoid of the use of any metallic,
enzymatic, or corrosive catalysts. The present procedure has notable advantages that
include simple operational procedure, environmentally benign reaction conditions,
faster (1–3 min) reactions, and good yields of products.
Scheme 1. Microwave-induced aza-Michael reaction in water.

1732
A. KALL, D. BANDYOPADHYAY, AND B. K. BANIK
Table 1. Microwave-assisted aza-Michael reaction in water
Time Yield
a
(min) (%)
Entry
1
Amine
Enone
Product
Ref.
9c
1
2
1
97
93
93
2
3
(1a)
(1a)
9c
9d
4
5
6
(2a)
(2b)
1
1
3
97
98
88
9b
9b
9a
(1b)
(1b)
7
8
9
(2a)
(2b)
(2d)
1
1
3
90
99
88
9a
9a
9d
(1c)
(1c)
1
1
0
1
(2b)
3
2
82
92
9c
9c
12
(2e)
1
95
9c
(
Continued )

MICROWAVE-INDUCED AZA-MICHAEL REACTION IN WATER
1733
Table 1. Continued
Time Yield
a
(min) (%)
Entry
Amine
Enone
Product
Ref.
9b
n
1
3
4
BuNH
2
(1e)
(2a)
1
1
92
96
1
(1e)
(2b)
(2a)
9b
9b
15
2
90
Note. ‘‘Ref.’’ indicates the corresponding literature syntheses.
a
Isolated yield.
EXPERIMENTAL
A representative experimental procedure for the aza-Michael reaction (Table 1,
entry 13) is as follows: methyl acrylate (1 mmol) was added to n-butyl amine
(
1 mmol) in water (1 mL), and the heterogeneous mixture was irradiated in a dom-
estic microwave oven. Thin-layer chromatography (TLC) was checked after every
0-s interval. During the microwave exposure, a beaker (250 mL) containing cold
3
water (100 mL) was kept next to the reaction vessel (as heat sink) to absorb excess
heat. The mixture was then extracted with dichloromethane (2 Â 5 mL), washed with
brine solution (10 mL), and dried over Na SO . The extracts were then concentrated,
2
4
and the crude product was purified using flash chromatography (silica gel, 30%
EtOAc–70% hexane) to afford pure compound (92%). This procedure was followed
for all the reactions listed in Table 1. All the products are known compounds and
were easily identified by comparison of their spectroscopic data with those reported.
This procedure was also effective for gram-scale reactions.
ACKNOWLEDGMENT
We gratefully acknowledge the funding support from the National Institutes of
Health SCORE Program (Grant 2S06M008038-37).
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