Ecofriendly and facile Nano ZnO catalyzed solvent-free enamination of 1,3-dicarbonyls

Article abstract of DOI:10.1016/j.tetlet.2012.05.048

Nano zinc oxide (Nano-ZnO) was explored as a reusable catalyst for the enamination of 1,3-dicarbonyls using diverse amines. To make the process environmentally viable, the reaction was carried out under solvent-free conditions and found to give good yield of desired products. The catalyst was characterized by various analytical techniques such as UV-spectroscopy, XRD, and TEM. The catalyst was found to be reusable up to four catalytic cycles without any appreciable loss in activity.

Full text of DOI:10.1016/j.tetlet.2012.05.048

Tetrahedron Letters 53 (2012) 3857–3860
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Ecofriendly and facile Nano ZnO catalyzed solvent-free enamination of
1,3-dicarbonyls
Utkarsha U. Indulkar a, Sandip R. Kale a, Manoj B. Gawande b, Radha V. Jayaram a,
⇑
a Department of Chemistry, Institute of Chemical Technology, Matunga, Mumbai 400 019, India
b REQUIMTE, Department of Chemistry, Faculty of Science and Technology, New University of Lisbon, Quinta da Torre 2829-516, Lisbon, Portugal
a r t i c l e i n f o
a b s t r a c t
Article history:
Nano zinc oxide (Nano-ZnO) was explored as a reusable catalyst for the enamination of 1,3-dicarbonyls
using diverse amines. To make the process environmentally viable, the reaction was carried out under
solvent-free conditions and found to give good yield of desired products. The catalyst was characterized
by various analytical techniques such as UV-spectroscopy, XRD, and TEM. The catalyst was found to be
reusable up to four catalytic cycles without any appreciable loss in activity.
Received 9 April 2012
Revised 9 May 2012
Accepted 10 May 2012
Available online 16 May 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Nanomaterials
Zinc oxide
Solvent free reaction
Enamination
Green synthesis
Enamination of 1,3-dicarbonyl compounds to b-enamino
ketones and esters is an important organic transformation as
b-enaminones are important intermediates in the synthesis of het-
erocyclic compounds.1 They are also known to have medicinal
applications as anticonvulsant, anti-inflammatory, and analgesic
agents.2 Several homogeneous catalysts such as Ca(CF3COO)2,3a
BF3ÁOEt2,3b Zn(ClO4)Á6H2O,3c ceric ammonium nitrate,3d and Bi
(OTf)3,3e have been reported for the enamination of 1,3-dicarbonyl
compounds, but suffer from one or the other drawbacks associated
with homogeneous catalysis. Heterogeneous catalysts such as
clays,4 supported tungstophosphoric acid,5 silica supported per-
chloric acid,6 and silica chloride7 have been used in enamination
reaction and some other protocol as well.8
However, many of these catalysts suffer from disadvantages
such as long reaction times, high catalyst loading, use of solvents,
and deactivation of catalyst on repeated use. Thus, there is a need
to develop an environmentally benign protocol for the synthesis of
b-enamino ketones and esters using a heterogeneous reusable
catalyst.
R2
O
R3
NH2
O
O
NH
ZnO NPs
R2
R3
+
solvent-free,
80 oC
R1
R1
Yiled 70 - 98 %
R1 = -CH3, -F etc
R2=R3= -CH3, -Ph
Scheme 1. Nano ZnO catalyzed synthesis of b-enaminones.
In continuation of our efforts on nanomaterials,11 green synthe-
sis,12 heterogeneous catalysis, and its application in organic syn-
thesis,13 we herein present a green and efficient method for the
synthesis of b-enaminones and enaminoesters via enamination of
1,3-dicarbonyl compounds using nano zinc oxide as a catalyst un-
der solvent-free condition (Scheme 1).
The catalyst was prepared by a simple precipitation method.
External morphology and particle size of the catalyst were deter-
mined by the TEM image (Fig. 1). It can be seen from the image that
the zinc oxide has a polymorphic geometry and the size of the par-
ticles range from 50 to 70 nm. Powder X-ray diffraction pattern of
the zinc oxide shows 2h values at 31.8, 34.5, 36.2, 39, 47, 49, 56, 63,
and 68, corresponding to (100), (002), (101), (102), (110), (103),
(200), (112), (201), and (202) planes, respectively (Fig. 2).
The results confirm that the ZnO nano particles are of Wurtzite
hexagonal type structure.14 The crystallite size was calculated to be
43 nm from the Scherrer’s equation, d = 0.9(Kk)/b (cos h).
Zinc oxide is a non-hygroscopic, inexpensive, non-toxic mate-
rial, which has been utilized as a heterogeneous catalyst for various
organic reactions.9 Of late, catalysis by nano materials has become
an area of interest, as these materials exhibit better catalytic activ-
ity compared to their bulk sized counterparts.10
⇑
Corresponding author. Tel.: +91 22 3361 2607; fax: +91 22 3361 1020.
E-mail address: rv.jayaram@ictmumbai.edu.in (R.V. Jayaram).
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.05.048

3858
U. U. Indulkar et al. / Tetrahedron Letters 53 (2012) 3857–3860
R2
O
R3
NH2
O
O
NH
ZnO NPs
R2
R3
+
Scheme 2. Nano ZnO catalyzed synthesis of b-enaminones.
Table 1
Effect of catalyst loading of nano ZnO and bulk ZnOa
Entry
Catalyst (mol %)
Yieldb (%)
Nano ZnO
Bulk ZnO
1
2
3
4
1
2
5
7
78
87
94
95
71
77
79
81
a
Reaction conditions: aniline (5 mmol), ethyl acetoacetate (5 mmol) tempera-
ture (80 °C), time (3 h), no solvent.
Figure 1. TEM image of Nano ZnO at 100 nm.
b
Isolated yield.
UV absorption spectrum of bulk and nano zinc oxide dispersed
in distilled water was analyzed (Fig. 3, see Supplementary data). It
was observed that as compared to bulk zinc oxide (417 nm), nano
zinc oxide particles absorb at a lower wavelength (380 nm). This
blue shift in UV absorption confirms size reduction.15 The surface
area of nano ZnO and bulk ZnO was found to be 35.6 m2/g and
6.2 m2/g, respectively.
In order to optimize the reaction conditions for the enamination
of ethyl acetoacetate using aniline was chosen as the model reac-
tion (Scheme 2).
Initially, bulk zinc oxide was used as a catalyst and it was found
to give 79% yield of ethyl 3-(phenylamino) but-2-enoate. With
nano zinc oxide the yield increased to 94%. (Table 1, entry 3). On
increasing the catalyst loading from 1 to 5 mol %, the yield of prod-
uct was found to increase, however on further increasing the
catalyst loading no effective increase in the yield was observed (Ta-
ble 1). Similar trend was also observed with bulk ZnO but the
yields were comparatively lower than that for nano ZnO. The high-
Table 2
Influence of reaction temperature on nano ZnO catalyzed enamination of 1,3-
dicarbonyl compoundsa
Entry
Temperature (°C)
Yieldb (%)
1
2
3
4
30
60
80
100
32
68
94
95
a
Reaction conditions: aniline (5 mmol), ethyl acetoacetate (5 mmol), nano ZnO
(5 mol %), temperature (80 °C), time (3 h), no solvent.
b
Isolated yield.
er yield with nano ZnO can be attributed to the increase in the sur-
face area due to size reduction.
In order to study the effect of temperature, the enamination
reaction was carried out at four different temperatures (30, 60,
80, and 100 °C). Notably, optimum results were obtained at 80 °C
Figure 2. XRD spectra of nano ZnO.

U. U. Indulkar et al. / Tetrahedron Letters 53 (2012) 3857–3860
3859
Table 3
To determine the effect of solvent on the product yield, reac-
tions were studied in various solvents (Table 3, entries 1–4). It
can be seen from the results that in polar solvents such as THF
and acetonitrile better yields were obtained as compared to non-
polar solvents. However the yield was maximum under solvent-
free conditions (Table 2, entry 5).
In order to generalize the above catalytic protocol, enamination
of 1,3-dicarbonyls with various amines was studied as depicted in
Table 4. When 1,3-dicarbonyl compounds were reacted with ani-
line, the corresponding products were obtained in 74–96% yield
(Table 4, entries 1–4). While an aryl amine with an electron donat-
ing substituent such as –CH3 gave good yield, (Table 4, entry 5),
with 2,5-dimethyl aniline a slightly lower yield of 70% was ob-
served even when the reaction was carried out for a longer reaction
time (Table 4, entry 6). This may be due to steric hindrance by the
Effect of solvent on enamination reactiona
Entry
Solvent
Time (h)
Yieldb (%)
1
2
3
4
5
THF
ACN
DCE
Toluene
None
4
4
6
8
3
90
85
70
65
94
a
Reaction conditions: aniline (5 mmol), ethyl acetoacetate (5 mmol), nano ZnO
(5 mol %), temperature (80 °C).
b
Isolated yield.
(Table 2, entry 3). With further increase in temperature, no consid-
erable increase in yield was observed (Table 2, entry 4). Hence all
other reaction parameters were studied at 80 °C.
Table 4
Nano ZnO catalyzed synthesis of b-enaminones
Entry
1
Amine
1,3-Dicarbonyl compound
Product
Time (h)
3
Isolated yielda (%)
94
O
O
NH
NH2
O
O
O
O
O
NH
NH
NH2
NH2
O
O
2
3
3
3
96
90
O
O
Ph
Ph
O
O
NH2
NH
O
O
O
4
5
6
7
4
3
7
5
75
96
70
83
O
O
O
O
O
O
O
NH2
NH
O
O
O
NH
O
NH2
O
O
O
O
O
O
NH2
NH
F
F
O
O
O
NH
O
8
2.5
97
NH2
O
O
O
NH2
NH
O
9
2
2
1
98
90
94
O
O
O
O
O
O
NH
O
NH2
10
11
O
O
O
NH
O
NH2
O
O
O
O
O
NH
O
12
2
98
N
O
O
a
Reaction conditions: amine (5 mmol), 1,3-diacarbonyl compound (5 mmol), nano ZnO (5 mol %), temperature (80 °C), no solvent.

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Figure 3. Reusability of nano ZnO in the enamination of ethylacetoacetate with
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were studied, excellent yields of products were obtained in 1–2 h
(Table 4, entries 8–11). Encouraged by the results obtained, mor-
pholine, an heterocyclic amine was treated with the carbonyl com-
pound and in this case, yield of the product was 98% (Table 4, entry
1).
In order to check the reusability of nano ZnO, the reaction be-
tween aniline and ethyl acetoacetate was repeated several times.
The catalyst was filtered off after each run and washed thoroughly
with ethyl acetate. It was then dried at 120 °C for 3 h and used for
the next catalytic cycle. The catalyst was found to be reusable up to
four catalytic cycles without any significant loss in catalytic activ-
ity (Fig. 3).
Nano ZnO showed good catalytic activity as compared to bulk
ZnO for the enamination of 1,3-dicarbonyls under mild reaction
conditions.17 The catalyst was found to give good to excellent
yields for the reaction of various amines under solvent free condi-
tions. Hence, we have reported a procedure for the enamination of
carbonyl compounds with nano ZnO as a green, cost effective, and
reusable catalyst.
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1, 47–58; (b) Gawande, M. B.; Pandey, R. K.; Jayaram, R. V. Catal. Sci. Technol.
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17. All materials were purchased from S.D. Fine Chem. Ltd, India, were of analytical
grade and were used without any further purification. XRD studies were
performed with a conventional powder diffractometer (Philips 1050) using Cu-
K
a radiation (k = 1.5406Ao). Microscopic image of nanocatalyst was obtained
using Transmission Electron Microscope (Philips CM 200).
Preparation of catalyst: Bulk zinc oxide was prepared by simple precipitation
method wherein aqueous ammonia solution (30%) was added dropwise to zinc
nitrate solution under vigorous stirring (till pH of solution reached 7.5–8). The
white precipitate of Zn(OH)2 was filtered and washed several times with
distilled water till the washings were neutral. The precipitate was then dried
overnight at 100 °C in an oven and calcined at 600 °C for 3 h. Nano zinc oxide
catalyst was prepared by the gel combustion method as described by Riahi-
Noori et al.16 An appropriate molar ratio of citric acid and zinc nitrate (2:1) was
mixed in a minimum amount of distilled water. The aqueous solution was
homogenized and further concentrated on a hot plate to a viscous liquid, which
was further heated at 100 °C for complete removal of water to obtain a dry
mass. This mass was then further heated gradually till its combustion occurred
giving a white fluffy powder.
Acknowledgement
The financial assistance from Technical Education Quality
Improvement Programme (TEQIP), Government of India is kindly
acknowledged.
Supplementary data
The powder obtained was annealed at 600 °C for 3 h to give nano ZnO. The
oxide was further characterized by various analytical techniques to confirm its
structural properties.
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2012.05.
048.
General procedure for enamination reaction: A mixture of amine (5 mmol), 1,3-
dicarbonyl compound (5 mmol), and the catalyst (5 mol %) was taken in a
25 mL round bottom flask. This reaction mixture was stirred at 80 °C and the
progress of reaction was monitored by TLC (10% ethyl acetate in PET ether) at
regular time intervals, till the complete conversion of amine was observed.
After completion of the reaction, ethyl acetate was added to the reaction
mixture and the catalyst was filtered off. The reaction mixture was analyzed
using GC (Shimadzu, column BP-10) and products were confirmed by GC-MS
(Shimadzu 2010). The filtered catalyst was washed with ethyl acetate (3–4
times), dried at 120 °C for 3 h, and used for the next catalytic cycle.
References and notes
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