Zn[aminoacid]2 hybrid materials applied as heterogeneous catalysts in the synthesis of β-enaminones

Article abstract of DOI:10.1016/j.tetlet.2014.05.122

Hybrid materials have seized attention from scientific community mainly as heterogenic catalysts in organic reactions on a large scale succeeding in some organic compounds with high yields. One of the most important classes of hybrid materials used for this purpose involves the complexation of Zn and aminoacids. Herein, we introduced Zn[Pro]₂ and Zn[Gly]₂ in the synthesis of several β-enaminones via solvent free protocol and using an ultrasound device.

Full text of DOI:10.1016/j.tetlet.2014.05.122

Accepted Manuscript
Zn[aminoacid]2 hybrid materials applied as heterogeneous catalysts in the syn-
thesis of β-enaminones
Cristiane R. Winck, Mariana P. Darbem, Roberto S. Gomes, Andrelson W.
Rinaldi, Nelson Luís C. Domingues
PII:
S0040-4039(14)00955-1
DOI:
http://dx.doi.org/10.1016/j.tetlet.2014.05.122
TETL 44713
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
3 April 2014
27 May 2014
29 May 2014
Please cite this article as: Winck, C.R., Darbem, M.P., Gomes, R.S., Rinaldi, A.W., Domingues, N.C.,
Zn[aminoacid]2 hybrid materials applied as heterogeneous catalysts in the synthesis of β-enaminones, Tetrahedron
Letters (2014), doi: http://dx.doi.org/10.1016/j.tetlet.2014.05.122
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Zn[aminoacid]2 hybrid materials applied as
heterogeneous catalysts in the synthesis of
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β-enaminones.
Cristiane R. Winck, Mariana P. Darbem, Roberto da Silva Gomes, Andrelson W. Rinaldi, and Nelson Luís C.
Domingues*.

1
Tetrahedron Letters
journal homepage: www.els evier.com
Zn[aminoacid]2 hybrid materials applied as heterogeneous catalysts in the
synthesis of β-enaminones.
Cristiane R. Winck,[a] Mariana P. Darbem,[a] Roberto S. Gomes,[a] Andrelson W. Rinaldi,[b] and Nelson
Luís C. Domingues*[a].
a Hybrid Materials Laboratory-LMH, Federal University of Grande Dourados – UFGD, Dourados/Itahúm rod. km 12 s/n°, Dourados-MS, Brazil, Fax: +55 (67)
3410 2072, Tel: + 55 (67) 3410 2081, E-mail: nelsondomingues@ufgd.edu.br ; nelsonluis.domingues@hotmail.com
b Departament of Chemistry, State University of Maringá-UEM, Av. Colombo 5790, zona 7, Maringá/PR, Brazil.
ARTICLE INFO
ABSTRACT
Article history:
Received
Hybrid materials have seized attention from scientific community mainly as heterogenic
catalysts in organic reactions on a large scale succeeding in some organic compounds with
high yields. One of the most important classes of hybrid materials used to this purpose
involves the complexation of Zn and aminoacids. Herein, we introduced Zn[Pro]2 and
Zn[Gly]2 in the synthesis of several β-enaminones via solvent free protocol and using
ultrasound device.
Received in revised form
Accepted
Available online
Keywords:
2009 Elsevier Ltd. All rights reserved.
Zinc hybrid materials
aminoacids
ultrasound
β-enaminones
1. Introduction
their structure, for example, the proteins. Therefore, there have
been a growing interest in synthesized compounds containing
[23]
There have been a growing interest in hybrid materials
because of their application as heterogenic catalysts in various
nitrogen for example as starting point in library design.
Among the compounds containing nitrogen, the most used ones
in organic chemistry as synthetic intermediates are the β-
enaminones which are widely applied mainly in organic reactions
because of their versatile reactivity, as electrophiles and
nucleophiles. [24] Because of this remarkable property, nowadays,
there are many researchers groups that have developed several
numbers of preparations. The shortcoming of this procedure is
that, in many cases, the catalysts are constituted of heavy metals,
which is not in accordance with the principles of Green
Chemistry. All in all, we proposed the insertion of Zn[Pro]2 and
bis[glycinate-N,O]Zn or Zn[Gly]2 as a heterogenic catalyst on β-
enaminones via solvent free synthesis using ultrasound protocol,
aiming the acceleration of the process once it comes to an
ecofriend procedure.
types of organic reactions, for example, in Prins condensation [1]
,
esters
synthesis
from
alkyl
aromatic
compounds [2], enantioselective catalysis [3], inter alia, as for
other reactions applied in industry [4-6]. Hybrid materials are
classified in the literature according to the analysis of their
structures and one of their most important classes is constituted
by the interaction of both organic and inorganic fractions. One
can classify two classes of organic/inorganic hybrid materials by
the interaction between these two fractions: the hybrid materials
with strong chemical bonds (ionic or covalent) inside its structure
or the ones with week bonds (van der Walls or hydrogens
bonds).[7] Another example of class included in strong chemical
bonds that has seized attention recently is the bis[prolinate-
N,O]Zn or Zn[Pro]2. This hybrid is an efficient, stable,
inexpensive, recyclable, non-toxic Lewis acid catalyst which is
soluble in water but insoluble in almost all the other organic
solvents, enabling a simple and quantitative recovery of the
catalyst. It has been extensively applied to various catalytic
reactions including Aldol condensation [8], direct nitro aldol
2. Results and Discussion
Firstly, we exposed the efficiency of the catalyst by carring
out the reaction involving the aniline and ethyl acetoacetate in
four situations: (I) in the absence of catalyst using magnetic
stirrer procedure (blank), (II) in the absence of catalyst but using
the ultrasound device (US), (III) by inserting the catalyst
Zn[Pro]2, in 10 % mol, using ultrasound device and finally (IV)
by inserting the catalyst Zn[Gly]2, in 10 % mol, using the
ultrasound device as well (Fig. 1).
[9]
,
[11]
[10]
,
[12]
condensation
condensation
condensation
Hantzsch reaction
Mannich reaction
Knoevenagel
, Friedlander
etc. It has also been used for the synthesis of
,
[13]
1,5-benzodiazepines [14], 1,2-disubstituted benzimidazoles [15] and
pyrazoles [16], inter alia. [17-25]. These heterogenic catalysts, as
Zn[Pro]2, are mainly applied on the synthesis of compounds that
present biological activity. Many of them presented nitrogen(s) in

2
Tetrahedron Letters
CO2Et
N
O
Zn+2
OEt
O
O
O
O
(2)
CO2Et
N
+
δ
O
Zn+2
O
O
(3)
NH
NH2R
O
Figure 1. Yields obtained for each methodology during β-
enaminones synthesis.
Zn+2
O
CO2Et
N
(1)
It is important to evidence that all the reactions were
performed in solvent free procedures. So, as expected, the
changes in the systems resulted in substantial modifications of
the β-enaminones yields. We observed, for the blank reaction,
that β-enaminone was not obtained without the catalyst neither
the ultrasound device. Therefore, when we used it in the same
synthesis, for 1 hour, we observed the resulting β-enaminone in
12 % /yield. On the other hand, when we inserted in the reaction
the Zn[Pro]2 or the Zn[Gly]2 we obtained the β-enaminone in
good yields in 1 hour (70 and 90% respectively). We attributed
this difference to the frame of the catalyst. The hybrid catalyst
constituted by glycine is a bit smaller than the one with proline.
So, compared to proline, the access to the Lewis acid (Zinc
cation) happened much more likely with the hybrid material from
glycine, what explains the increasing on the yield. Accordingly,
we performed the β-enaminone synthesis using other amines
keeping dicarbonyl compound as being ethyl acetoacetate (Table
1).
O
N
HR
Zn+2
O
R
OH
-H2O
(4)
N
O
OEt
O
NH
NH
Zn+2
O
R
corresponds to
Zn
O
O
N
H
O
HN
O
O
OEt
Figure 2. Purposed mechanism for the β-enaminones synthesis using
Zn[Pro]2.
Besides, it was not possible to observe the substituted effect of
the phenyl group on the β-enaminones' yield. For this reason, we
concluded that the size of the catalyst was a determinant point
linked to the yields as previously mentioned.
Table 1. Yields for the β-enaminones synthesis using some amines,
ethyl acetoacetate and Zn[Gly]2 and Zn[Pro]2 as catalyst.
For this reason, we decided to change the dicarbonyl
compound to acetylacetone and carry out the β-enaminone
synthesis with same amines previously used. The data are
presented in Table 2 in which we obtained the highest yields for
almost all the β-enaminones except for the cases involving the p-
anisidine and p-toluidine (entries 2 and 3) in which we obtained
the lowest yields in the set because of the difficulty in separating
the amine precursor and the corresponding β-enaminones.
a
Entry
Amine
Yield (%)
Zn[Gly]2 Zn[Pro]2
1
2
3
4
5
6
Aniline
90
65
72
92
99
96
70
75
80
65
70
67
p-Anisidine
p-Toluidine
Benzylamine
Butylamine
Table 2. The yields for the use of hybrids catalysts Zn[Pro]2 and
Zn[Gly]2 on the β-enaminones synthesis with some amines and
acetylacetone.
Ciclohexylamine
a
Entry
Amine
Yield (%)
a Yields obtained after purification on chromatographic column.
Zn[Gly]2 Zn[Pro]2
As previously mentioned, the reactions using Zn[Gly]2
presented the best yields when we compare them to the ones with
Zn[Pro]2. To the best of our knowledge, we purposed a
mechanism as presented in Figure 2. This mechanism was based
on the one described by Siddiqui [26]. In our mechanism there is a
nucleophilic attack of the nitrogen from the catalyst (red
nitrogen, structure 1 – Figure 2) on the ketone carbonyl. This
attack produced the iminium ion (structure 3) which was attacked
by the amine (blue nitrogen). The obtained N,N acetal (structure
4) produced the corresponding imine which finally rearranged
itself resulting in the β-enaminone. It is worth mentioning that in
both hybrids catalysts, we didn’t observe the nucleophylic attack
on the ester carbonyl group.
1
2
3
4
5
6
Aniline
93
87
83
94
96
98
93
60
70
92
91
93
p-Anisidine
p-Toluidine
Benzylamine
Butylamine
Ciclohexylamine
a Yields obtained after purification on chromatographic column.

3
6. C.R. Winck, A.C. Lima, P.V.S. Rizzo, A.W. Rinaldi, N.L.C.
3. Conclusion
Domingues, Orbital - The Electronic Journal of Chemistry, 4
(2012), 96.
7. F.A. Beleze, A.J.G. Zarbin, J. Braz. Chem. Soc. 12 (2001), 542.
In short, synthetically versatile β-enaminones were prepared
with the use of the hybrid catalysts Zn[Pro]2 and Zn[Gly]2 in a
green protocol and using the ultrasound and solvent free
conditions. This extension of the scope for the use of Zn[Pro]2
and Zn[Gly]2 here underlined their ability to promote the
synthesis of β-enaminones with high yields, assuring the
maintenance of other groups like esters.
8. J. Kofoed, J.L. Reymond, T. Darbre, Org. Biomol. Chem.
(2005), 1850.
3
9. V.R. Sivamurugan, S. Kumar, M. Palanichamy, V. Murugesan,
J. Heterocycl. Chem. 42 (2005) 969.
10. V. Sivamurugan, A. Vinu, M. Palanichamy, V. Murugesan,
Heteroat. Chem. 17 (2006), 267.
11. Z.N. Siddiqui, T.N.M. Musthafa, S. Praveen, F. Farooq, Med.
Chem. Res. 20 (2011), 1438.
Acknowledgments
12. M. Kidwai, A. Jain, R. Poddar, S. Bhardwaj, Appl. Organomet.
Chem. 25 (2011), 335.
13. Z.N. Siddiqui, Tetrahedron. Lett. 53 (2012), 4974.
14. V. Sivamurugan, K. Deepa, M. Palanichamy, V. Murugesan,
Synth. Commun. 34 (2004), 3833.
Brazilian author (M.P.D) thanks to Conselho Nacional de
Desenvolvimento Científico e Tecnológico for scholarship and
the author C.R.W thanks to Coordenação de Aperfeiçoamento de
Pessoal de Nível Superior (CAPES) for financial support.
15. M.M. Heravia, A. Ghodsa, K. Bakhtiaria, F. Derikvanda, Synth.
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16. M. Kidwai, A. Jain, R.J. Poddar, J. Organomet. Chem. 696
(2011), 1939.
Supplementary data
17. M. Kidwai, A. Jain, S. Bhardwaj, Catal. Lett. 141(2011), 183.
18. M. Kidwai, A. Jain, R. Poddar, S. Bhardwaj, Appl. Organometal.
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Supplementary data (general experimental procedures and
spectral data) associated with this article can be found, in the
online version, at http://
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The article’s highlights:
•
•
•
•
Hybrid materials containing zinc and proline or glycine in β-enaminone synthesis;
The reactions were carried out without any solvent using the ultrasound device;
The optimal protocol was guided by green chemistry principles;
The use of ultrasound device allowed the increasing in the reaction time.
1