Simple and efficient synthesis of 3-aminopropenones and 3-aminopropenoates catalyzed by copper(II) nitrate trihydrate under solvent-free conditions

Article abstract of DOI:10.1007/s00706-007-0832-x

A simple, efficient and environmentally begin method has been developed for the synthesis of 3-aminopropenones and 3-aminopropenoates through the reaction of 1,3-dicarbonyl compounds with amines in the presence of Cu(NO ₃)₂ · 3H₂O under solvent-free conditions.

Full text of DOI:10.1007/s00706-007-0832-x

Monatsh Chem 139, 789–792 (2008)
DOI 10.1007/s00706-007-0832-x
Printed in The Netherlands
Simple and efficient synthesis of 3-aminopropenones and 3-aminopropenoates
catalyzed by copper(II) nitrate trihydrate under solvent-free conditions
Geng-Chen Li
School of Material Science and Engineering, Shijiazhuang Railway Institute, Shijiazhuang, China
Received 16 October 2007; Accepted 21 October 2007; Published online 9 June 2008
# Springer-Verlag 2008
Abstract A simple, efficient and environmentally be- silica chloride [22], silica gel [23], natural clays
gin method has been developed for the synthesis of [24], and sulfated zirconia [25]. Recently, [EtNH3]-
3-aminopropenones and 3-aminopropenoates through NO3 [26] and HClO4 ꢀ SiO2 [27] have also been used
the reaction of 1,3-dicarbonyl compounds with amines to promote this transformation. However, some of
in the presence of Cu(NO3)2 ꢀ 3H2O under solvent-free these methodologies have not been entirely satis-
conditions.
factory with disadvantage, such as low yields of
products, longer reaction times, harsh reaction con-
ditions, use of harmful organic solvents, and require-
ment of excess of catalysts and special apparatus.
Hence, there is a need to develop an efficient, practi-
cally potential, and environmentally benign method
for the synthesis of 3-aminopropenones and 3-ami-
nopropenoates under mild and economically cheaper
conditions.
Recently, copper salts have emerged as efficient
Lewis acids in organic synthesis because these com-
pounds are relatively non-toxic, easy to handle, of
low cost, and good stability [28]. Among these,
copper(II) nitrate has gained special attention be-
cause this compound not only is commercially avail-
able and inexpensive, but also of high stability.
Copper(II) nitrate has been reported to be an efficient
reagent for many important organic reactions, such as
deprotection of 1,3-dithianes and 1,3-dithiolanes [29],
chemoselective synthesis of 1,1-diacetates [30], aro-
matization of Hantzsch 1,4-dihydrpyridines [31], syn-
thesis of bis(indolyl)methanes [32], etc. Inspired by
reports of continuation of interest in catalytic appli-
cations of Cu(NO3)2 ꢀ 3H2O for various organic trans-
formations, we report herein a simple and convenient
solvent-free method for the synthesis of 3-aminopro-
Keywords 3-Aminopropenones; 3-Aminopropenoates; 1,3-
Dicarbonyl compounds; Amines; Copper(II) nitrate trihydrate.
Introduction
3-Aminopropenones and 3-aminopropenoates, also
known as ꢀ-enaminones and ꢀ-enamino esters are
versatile intermediates for the synthesis of various
heterocycles [1], natural products [2], ꢁ- and ꢀ-ami-
no acid compounds [3], alkaloids [4], and peptides
[5]. Some synthetic approaches have been reported
but the direct condensation of amines with 1,3-dicar-
bonyl compounds is one of most preferred synthe-
sis approaches, which is usually catalyzed by protic
acid [6], Lewis acid such as Zn(ClO4)2 ꢀ 6H2O [7],
CeCl3 ꢀ 7H2O [8], NaAuCl4 [9], Bi(OTf)3 [10],
InBr3 [11], CoCl2 ꢀ 6H2O [12], CAN [13], Yb(OTf)3
[14], SnCl4 ꢀ 5H2O [15], ZrCl4 [16], ZrOCl2 ꢀ 8H2O
[17], Zn(Ac)2 ꢀ 2H2O [18], Sc(OTf)3 [19], I2 [20],
and solid acids such as montmorillonite K10 [21],
Correspondence: Geng-Chen Li, School of Material Science
and Engineering, Shijiazhuang Railway Institute, Shijiazhuang
050043, China. E-mail: gengchenli@sina.com.cn

790
G.-C. Li
Scheme 1
penones and 3-aminopropenoates in the presence of
a catalytic amount of Cu(NO3)2 ꢀ 3H2O (Scheme 1).
show significant influence on the rate of the reaction
as well as yield. Lower catalyst loading can be used
with only a marginal drop in reaction rate. Various
solvents such as EtOH, MeCN, CH2Cl2, THF, DMF,
and EtOAc were also screened for this reaction.
However, the best results were observed under sol-
vent-free conditions.
To explore the generality and scope of this meth-
od, a wide variety of amines including primary, ben-
zylic, and aromatic amines were reacted with various
1,3-dicarbonyl compounds and the results are sum-
marized in Table 1. In general, primary and benzylic
amines reacted with a broad range of structurally
diverse 1,3-dicarbonyl compounds to afford the cor-
Results and discussion
Initially, a model reaction of ethyl acetoacetate and
aniline was performed under solvent-free conditions
in the presence of a catalytic of Cu(NO3)2 ꢀ 3H2O
(10 mol%) at room temperature. To our delight, we
observed the formation of ethyl 3-(phenylamino)but-
2-enoate (3i) in 95% isolated yield after 50 min. In
the absence of the catalyst, only 30% of the product
was obtained even after 24 h stirring at room temper-
ature. Increasing the amount of the catalyst did not
Table 1 Synthesis of 3-aminopropenones and 3-aminopropenoates catalyzed by Cu(NO3)2 ꢀ 3H2O
Entry
R1
R2
R3
Time=min
Yielda=%
Ref.
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
p
q
r
s
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
OEt
OBn
OMe
OMe
OMe
OBn
OMe
OMe
OEt
OBn
OEt
OMe
OMe
OEt
OEt
Me
Me
Me
Me
Me
Me
Me
Me
Me
CH3(CH2)3
CH3(CH2)3
CH2¼CHCH2
C6H11
PhCH2
PhCH2
PhCH2CH2
(R)–PhCH(Me)
Ph
15
18
15
15
12
18
15
15
50
60
40
90
360
40
480
20
15
15
10
10
15
10
45
300
50
80
92
90
95
93
93
90
92
95
95
90
94
91
75
95
80
92
95b
96
92
95
90
91
90
80
85
80
[25]
[34]
[12]
[14b]
[25]
[34]
[11]
[12]
[19]
[34]
[12]
[12]
[11]
[25]
[12]
[12]
[11]
[15]
[15]
[25]
[25]
[15]
[11]
[25]
[15]
[25]
Ph
4-Me–C6H4
2-Me–C6H4
2,6-Et2–C6H3
4-OMe–C6H4
4-Cl–C6H4
CH3(CH2)3
H2NCH2CH2CH2
CH2¼CHCH2
Ph
4-Me–C6H4
2-Me–C6H4
4-OMe–C6H4
2-OEt–C6H4
4-Cl–C6H4
Ph
t
u
v
w
x
y
z
Ph
Ph
2-OEt–C6H4
a
b
Yield refer to pure, isolated products; Propane-1,3-diamine:methyl acetoacetate molar ratio ¼ 1:2

Simple and efficient synthesis of 3-aminopropenones
791
red vigorously at room temperature until the disappearance of
the starting amine. When the reaction was complete, 20 cm3 of
ethyl acetate was added and washed with brine (2ꢁ10cm3).
The combined organic layer was dried (MgSO4) and concen-
trated under vacuum. The residue was subjected to column
chromatography over alumina using ethyl acetate (10%) in n-
hexane to obtain the pure product. All compounds prepared
proved to be identical with those already reported (Table 1)
with respect to their spectroscopic properties.
responding ꢀ-enaminones or ꢀ-enamino esters in high
yields in short time. We have also observed delicate
electron effects for aromatic amine. Aniline with elec-
tron-rich groups (Table 1, entries 2k, 2n, 2t, and 2v)
reacted rapidly, while substitution ivolving electron-
withdrawing groups (Table 1, entries 2o and 2x) on
the benzene ring decreased the reactivity requiring
longer reaction times. It was also found that the
substituted groups (2l, 2m, 2w, and 2z) on the ortho
position in the anilines influenced the reaction rates.
Moreover, the optically active (R)-(þ)-ꢁ-methyl
benzyl amine (2h) was converted into the corre-
sponding 3-aminopropenoates without any race-
mization or inversion confirmed by measuring its
optical rotation. When 1,3-diaminopropane (2q) was
used as an amine, two equivalents of acetylacetone
were used and the product was formed with two
enaminone groups. It should be pointed out that
1,3-diketones with two different substituents, such
as 1-benzoylacetone, reacted with amines in a regio-
selective amination of the aliphatic carbonyl group
(2y and 2z).
The products with (Z)-configuration were favored
over the (E)-isomers. It is postulated that the forma-
tion of intramolecular hydrogen bonding could be
responsible for the observed shift towards the (Z)-
isomer [33].
In conclusion, Cu(NO3)2 ꢀ 3H2O was found to be an
efficient catalyst in the reaction of 1,3-dicarbonylic
compounds and amines to afford 3-aminopropenones
and 3-aminopropenoates. The main advantages of
this method are mild, clean, and solvent-free reaction
conditions, good to excellent yields, short reaction
times, and an environmentally begin reagent.
Acknowledgement
The financial support to this work from the Science and
Technology Research and Development Program in Hebei
Province (06213507D-2) is gratefully acknowledged.
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