Ionic liquid promoted synthesis of β-enamino ketones at room temperature

Article abstract of DOI:10.1055/s-2006-939042

β-Enamino ketones have been synthesised in excellent yield at room temperature in the absence of any added catalyst by the reaction of aromatic or aliphatic amines with 1,3-dicarbonyl compounds in ionic liquid. The ionic liquid is recycled and reused several times. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-939042

LETTER
933
Ionic Liquid Promoted Synthesis of b-Enamino Ketones at Room Temperature
Ionic
L
iquid Prom
a
oted Synt
j
e
b
-Enamino
s
K
etonesh S. Bhosale,a Padmakar A. Suryawanshi,a Sachin A. Ingle,a Mahendra N. Lokhande,a Sandeep P. More,a
Sandeep B. Mane,a Sidthanath V. Bhosale,b Rajendra P. Pawar*a
a
Organic Chemistry Synthesis Laboratory, Dnyanopasak College, Parbhani – 431401, India
b
Institute of Chemistry – Organic Chemistry, Freie Universität, Takustr. 3, 14195 Berlin, Germany
Fax +91(2452)242466; E-mail: rsbhosale03@yahoo.co.in
Received 27 October 2005
Most of these reported methods suffer from several draw-
Abstract: b-Enamino ketones have been synthesised in excellent
yield at room temperature in the absence of any added catalyst by
the reaction of aromatic or aliphatic amines with 1,3-dicarbonyl
compounds in ionic liquid. The ionic liquid is recycled and reused
several times.
backs like prolonged reaction period, low yields, harsh
reaction conditions and expensive catalyst. Consequently,
there is scope for further innovation towards milder reac-
tion conditions, absence of catalyst, shorter reaction times
and better yields. This could be achieved through the use
of green ionic liquid solvents.
Key words: amination, ionic liquid, 1,3-dicarbonyl compounds, b-
enaminone
O
O
O
[EtNH3]NO3
r.t., 3–4.2 h
b-Enaminones are useful intermediates in organic synthe-
sis as synthons for the construction of biologically active
compounds such as dopamine auto-receptor agonists,1
acetylcholinestersase inhibitors,2 oxytocin antagonists3
and anticonvulsants.4 Recently, the enamino ketone
moiety has attracted much attention because of its use as
an intermediate for the preparation of part of the side
chain of taxol.5
R
NH2
+
R
N
H
OH
O
2
3
1
Scheme 1
In recent times, the use of room temperature ionic liquids
(ILs) as green solvents in organic synthetic process has
gained considerable importance due to its negligible va-
pour pressure, solvating ability and easy recyclibility.12
Several reactions have been reported recently using ionic
liquids as reaction media13 and as rate enchancers.14
Several methods for the preparation of b-enamino ketones
have been reported. The common method used for the
preparation of b-enamino ketones is the reaction between
b-dicarbonylic compounds and amines in the presence of
benzene by azeotropic removal of water. However, sever-
al problems are associated with the use of low boiling
amines as starting materials.6 It is necessary either to pass
a rapid stream of gaseous amine through the refluxing
diketone solution, or to operate a reaction in an autoclave
at 130–150 °C. Moreover, the former procedure requires
an excess amount of amine. For the latter the reaction can-
not be easily monitored and the yields are not quantitative.
Some successful modifications have been reported for
these methods such as the use of ammonium or alkyl-
ammonium acetate, Lewis acids like boron trifluoride
etherate, alumina (neutral) or Montmorillonite K-10 as a
solid catalyst in benzene or as solid supports.7 Other syn-
thetic methods reported for b-enamino ketones are addi-
tion of an amine to b-halovinyl ketones, hydrogenation of
isoxazoles,8 palladium-catalyzed amination of electron-
deficient olefins9 and palladium-induced dehydro-
genation of a b-amine ketone.10 Recently, some improved
methods have been also reported for the synthesis of b-
enamino ketones.11
Herein, we wish to report an efficient method for the syn-
thesis of b-enamino ketones 3 from 1,3-dicarbonyl com-
pounds 1 and amine 2 in ionic liquid ethylammonium
nitrate [EtNH3]NO3 at room temperature in the absence of
any additional catalyst (Scheme 1). Excellent yields were
obtained and the ionic liquid can be recycled and reused
several times. The ionic liquid [EtNH3]NO3 was prepared
as described in the literature.15
In a typical condensation reaction, the dimedone 1a and
aniline 2a in ionic liquid [EtNH3]NO3 was stirred at room
temperature. The progress of reaction was monitored by
TLC. After completion of reaction, aqueous work up
afforded b-enamino ketone 3a in 88% yield. To evaluate
the synthetic utility of the procedure, various amines in-
cluding aromatic and aliphatic ones were chosen to be
condensed with different 1,3-dicarbonyl compounds. The
results are shown in Table 1.
The reaction proceeds very cleanly at room temperature
and no undesirable side reactions are observed. This pro-
tocol offers advantages in terms of its simple procedure
and work up, mild reaction conditions and excellent
yields. The protocol neither required any additional cata-
lyst nor azeotropic conditions and proceeded without the
formation of any by-products except water. From Table 1
SYNLETT 2006, No. 6, pp 0933–0935
0
4.
0
4.
2
0
0
6
Advanced online publication: 14.03.2006
DOI: 10.1055/s-2006-939042; Art ID: D32605ST
© Georg Thieme Verlag Stuttgart · New York

934
R. S. Bhosale et al.
LETTER
Table 1 Synthesis of b-Enamino Ketones (3a–m)16
Entry
a
1,3-Diketones 1
Amines 2
Products (3a–m)
Time (h)
3
Yield (%)a
O
O
NH2
88
90
87
82
N
H
O
O
O
Me
OMe
Cl
NH2
b
c
d
3.5
3.6
4
N
H
Me
O
O
O
NH2
MeO
N
H
O
O
O
Cl
NH2
N
H
O
Cl
Cl
O
O
O
NH2
NH2
e
3.8
85
N
H
O
O
Br
f
4
84
82
80
85
87
Br
N
H
O
O
O
O
O
NH2
OH
g
h
i
4.2
3.7
3.4
3.6
HO
N
H
O
O
NH2
N
H
O
O
Me
NH2
N
H
Me
O
O
O
NH2
OMe
j
MeO
N
H
O
NH2
O
O
O
O
k
l
3.8
4
83
85
H
H
O
O
N
N
NH2
NH2
O
O
m
4.1
82
H
O
N
EtO
EtO
a Isolated yield.
Synlett 2006, No. 6, 933–935 © Thieme Stuttgart · New York

LETTER
Ionic Liquid Promoted Synthesis of b-Enamino Ketones
935
Table 2 Recycle Use of Ionic Liquid in b-Enamino Ketone Synthesis
Entry
1,3-Diketone
Amine
Product
Time (h)
Yield (%)
Recycle 1
Recycle 2
Recycle 3
1
2
3
1a
1i
2a
2i
3a
3i
3
88
85
87
84
82
85
84
82
85
3.4
3.6
1j
2j
3j
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it is evident that both aliphatic as well as substituted
aromatic amines participate well in the reaction. The
protocol is also applicable for the synthesis of b-enamino
ester (entry m).
Similarly, the reaction of dimedone 1a with aniline 2a was
also carried out using 1,3-dibutyl imidazolium bromide
[bbim]Br ionic liquid for comparison. The resulting b-
enamino ketone 3a forms with same yield. The ionic liq-
uid used in b-enamino ketones synthesis was recovered
and reused with identical results. Thus, the recyclibility
was conformed as listed in Table 2.
In summary, we have demonstrated an efficient and mild
protocol for the condensation of 1,3-dicarbonyl com-
pounds and different amines (aliphatic and aromatic) to b-
enamino ketones at room temperature in ionic liquid with-
out adding any catalyst. The procedure is simple and can
be used as an alternative to the existing producers.
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Chem. Commun. 2001, 1544. (b) Ohara, H.; Kiyokane, H.;
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(c) Sugden, S.; Wilkins, H. J. Chem. Soc. 1929, 1291.
(16) General Experimental Procedure for the Synthesis of
b-Enamino Ketones:
References and Notes
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A mixture of 1,3-diketones 1 (2 mmol) and amine 2 (2
mmol) in ionic liquid [EtNH3]NO3 (4 mmol) was stirred at
r.t. The progress of the reaction was monitored by TLC.
After completion of reaction, the reaction mixture was
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Synlett 2006, No. 6, 933–935 © Thieme Stuttgart · New York