Calcined Mg-Al hydrotalcite as a heterogeneous base catalyst for gewald aminothiophene synthesis

Article abstract of DOI:10.1081/SCC-100105884

Calcined Mg-Al hydrotalcite (Mg/Al=4) has been conveniently employed as a heterogeneous base catalyst in the synthesis of 2-amino-3-cyanothiophenes adopting a one pot Gewald aminothiophene methodology.

Full text of DOI:10.1081/SCC-100105884

This article was downloaded by: [Moskow State Univ Bibliote]
On: 18 February 2014, At: 06:54
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer
House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and subscription information:
http://www.tandfonline.com/loi/lsyc20
CALCINED Mg-Al HYDROTALCITE AS A
HETEROGENEOUS BASE CATALYST FOR GEWALD
AMINOTHIOPHENE SYNTHESIS
R. Rajagopal , T. M. Jyothi , Thomas Daniel , K. V. Srinivasan & B. S. Rao
Published online: 16 Aug 2006.
To cite this article: R. Rajagopal , T. M. Jyothi , Thomas Daniel , K. V. Srinivasan & B. S. Rao (2001) CALCINED
Mg-Al HYDROTALCITE AS A HETEROGENEOUS BASE CATALYST FOR GEWALD AMINOTHIOPHENE SYNTHESIS, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry, 31:20, 3113-3117,
DOI: 10.1081/SCC-100105884
To link to this article: http://dx.doi.org/10.1081/SCC-100105884
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained
in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no
representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of
the Content. Any opinions and views expressed in this publication are the opinions and views of the authors,
and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied
upon and should be independently verified with primary sources of information. Taylor and Francis shall
not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other
liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or
arising out of the use of the Content.
This article may be used for research, teaching, and private study purposes. Any substantial or systematic
reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any
form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http://
www.tandfonline.com/page/terms-and-conditions

SYNTHETIC COMMUNICATIONS, 31(20), 3113–3117 (2001)
CALCINED Mg-Al HYDROTALCITE
AS A HETEROGENEOUS BASE
CATALYST FOR GEWALD
AMINOTHIOPHENE SYNTHESIS
R. Rajagopal, T. M. Jyothi, Thomas Daniel,
K. V. Srinivasan, and B. S. Rao*
National Chemical Laboratory, Pune 411 008, India
ABSTRACT
Calcined Mg-Al hydrotalcite (Mg/Al ¼ 4) has been conveni-
ently employed as a heterogeneous base catalyst in the syn-
thesis of 2-amino-3-cyanothiophenes adopting a one pot
Gewald aminothiophene methodology.
The Gewald reaction constitutes a very useful and versatile method for
the synthesis of 2-aminothiophene with an electron withdrawing substituent
in the 3-position and alkyl and/or aryl groups in the 4- and 5-positions.1
Aminothiophenes found their way as very important diazo components for
azo dyes which give exotic colours with high tinctorial strength. The devel-
opment of Gewald reaction for the synthesis of 2-amino-3-cyano, 2-amino-
3-carbethoxy and 2-amino-3-carbonyl substituted thiophenes has been made
*Corresponding author.
3113
Copyright & 2001 by Marcel Dekker, Inc.
www.dekker.com

ORDER
REPRINTS
3114
RAJAGOPAL ET AL.
possible the synthesis of an enormous number of thieno-fused heterocycles
of great medicinal interest such as thienopyrimidines and thienodiazepines.
In one version of Gewald reaction aliphatic aldehydes, ketones or
b-dicarbonyl compounds react with active nitriles and sulfur in presence
of amines. Amines such as diethyl amine and morpholine have been
employed as catalysts. Both one step and two step routes have been adopted
with numerous ketones and aldehydes or their Knoevanagel – Cope
condensation products (Scheme 1). In particular, cyclic and heterocyclic
saturated ketones have been used extensively.
A
Scheme 1.
Herein we report our preliminary results on the application of calcined
Mg-Al htdrotalcite as a heterogeneous catalyst in the Gewald aminothio-
phene synthesis. Hydrotalcites are interesting class of materials, which can
be utilized as precursors for mixed metal oxides with pronounced basic
properties. They can be efficiently used as basic heterogeneous catalysts in
many organic transformations such as aldol and Knoevenagel condensa-
tions,2 epoxidation,3 cyanoethylation4 and Meerwein–Ponndorf–Verley
reduction.5 Mg-Al hydrotalcites having Mg : Al ¼ 4 : 1 was synthesized
using the procedure reported by Miyata et al.6 Typical XRD, IR, TGA
and DTA patterns have substantiated the formation of hydrotalcites.
We have chosen methyl ethyl ketone and three cyclic ketones viz.
cyclopentanone, cyclohexanone and cylcoheptanone for condensation with
malononitrile in presence of sulfur to yield 2-amino-3-cyano-thiophenes
(Scheme 2).
Results of Gewald reaction of cyclic ketones with malononitrile and
sulfur are summarized in Table 1. The lower yield of the product in the case
of cycloheptanone is attributed to the increasing nonbonded repulsive inter-
action between methylene protons in the middle and large sized rings fused
to a planar five membered ring.7

ORDER
REPRINTS
GEWALD AMINOTHIOPHENE SYNTHESIS
3115
Scheme 2.
Table 1. Gewald Aminothiophene Synthesis over Calcined Mg-
Al (Mg/Al ¼ 4) Hydrotalcite Catalysta
Substrate
Reaction time (h)
Yield (%)
Cyclopentanone
Cyclohexanone
Cycloheptanone
Ethyl Methyl Ketone
Cyclohexanoneb
Cyclohexanonec
Cyclohexanoned
12
8
14
8
12
14
9
85
91
56
61
88
86
90
aReaction conditions: cyclic ketone (0.002 moles), malononitrile
(0.002 moles), sulfur (0.003 moles) and ethanol (7 ml), catalyst
calcined in air at 450ꢀC for 6 h (50 mg). b–cSecond and third
recycling. Used catalyst reactivated in air at 450ꢀC.
d
In the first step of the reaction, ketone reacts with malononitrile to
form a,b-unsaturated nitrile by Knoevanagel – Cope condensation. In the
second step, sulfur reacts with the intermediate compound formed in the
first step to complete the cyclization (Scheme 3). To investigate the catalytic
influence in detail, we separately carried out the reaction of cyclohexanone
and malononitrile with hydrotalcite (first step). The condensed product
formed was isolated and made to react with sulfur in presence of the catalyst
under same experimental conditions (second step). We found that the first
step of the reaction is completed in 3 h and no condensation takes place in
the absence of catalyst. The second step of the reaction proceeded smoothly
in presence of catalyst whereas, in the absence of catalyst reaction was very
slow and never attained completion. From the rate of reaction of both the
steps, it can be concluded that the reaction proceeds essentially through the
intermediate A.
The reusability of the catalyst was examined by using the filtered
catalyst for subsequent reactions. The catalyst was found to be reusable
without appreciable loss in activity.

ORDER
REPRINTS
3116
RAJAGOPAL ET AL.
Scheme 3.
In conclusion, we have demonstrated that calcined Mg-Al hydrotalcite
catalysts can be successfully employed to replace secondary amines in
Gewald synthesis of aminothiophenes. Hope this will open new vistas in
the field of recyclable heterogeneous base catalysis in heterocyclic synthesis.
EXPERIMENTAL
Preparation of Mg-Al Hydrotalcite Catalyst
To an aqueous solution containing Mg(NO3)2ꢀ 6H2O and
Al(NO3)3ꢀ 9H2O mixed at the required ratio, an aqueous solution of
NaOH and Na2CO3 was added dropwise with stirring, until the pH reached
10. The slurry was stirred at 313 K for 13 h, filtered and washed with deio-
nised water to the neutral pH and dried at 373 K for 24 h. Finally the
catalyst was calcined at 723 K in air for 12 h.
Characterization of Catalysts
The physico-chemical characterization of the catalysts has been done
by XRD, thermogravimetry and BET surface area measurements. The
ICPES method was adopted to estimate the ratio of MII and MIII ions in
calcined hydrotalcite.
Reaction Procedure
All the reactions were carried out batch wise in a 100 ml R.B. flask
fitted with a reflux condenser with constant stirring. One equivalents of
cyclic ketone (0.002 moles), malononitrile (0.002 moles) and 1.1 equivalents
of sulfur (0.003 moles) and 7 ml ethanol as solvent were taken in a round
bottom flask. 50 mg of freshly activated hydrotalcite catalyst was added to
this suspension and temperature slowly raised to 60ꢁC. Reaction was mon-

ORDER
REPRINTS
GEWALD AMINOTHIOPHENE SYNTHESIS
3117
itored by T.L.C. (eluent 10% ethylacetate in petroleum ether). After the
reaction, the catalyst was filtered off, filtrate extracted with ethylacetate
and finally purified by column chromatography. Physico-chemical charac-
terization of the products were performed using NMR, MS, IR, elemental
analysis and melting point determination. In the case of methyl ethyl ketone,
the ketone itself was used as solvent instead of ethanol.
ACKNOWLEDGMENT
R.R. thanks CSIR, New Delhi for the award of Senior Research
Fellowhip.
REFERENCES
1. Gewald, K.; Schinke, E.; Bottcher, H. Chem. Ber. 1966, 99, 94.
2. Lakshmi Kantam, M.; Choudary, B.M.; Venkat Reddy, Koteswara
Rao, K.; Figueras, F. Chem. Commun. 1998, 1033.
3. Ueno, S.; Yamaguchi, K.; Yoshida, K.; Ebitani, K.; Kaneda, K. Chem.
Commun. 1998, 295.
4. Kumbhar, P.S.; Sanchez-valente, J.; Figueras, F. Chem. Commun. 1998,
1091.
5. Kumbhar, P.S.; Sanchez-valente, J.; Lopez, J.; Figueras, F. Chem.
Commun. 1998, 535.
6. Miyata, S.; Kumura, T.; Shimada, M. U.S. Pat. 1975, 3, 879523.
7. Rosowsky, A.; Chaykowsky, M.; Chan, K.K.N.; Lin, M.; Modest, E.J.
J. Med. Chem. 1973, 16, 185.
Received in the Netherlands December 20, 2000

Request Permission or Order Reprints Instantly!
Interested in copying and sharing this article? In most cases, U.S. Copyright
Law requires that you get permission from the article’s rightsholder before
using copyrighted content.
All information and materials found in this article, including but not limited
to text, trademarks, patents, logos, graphics and images (the "Materials"), are
the copyrighted works and other forms of intellectual property of Marcel
Dekker, Inc., or its licensors. All rights not expressly granted are reserved.
Get permission to lawfully reproduce and distribute the Materials or order
reprints quickly and painlessly. Simply click on the "Request
Permission/Reprints Here" link below and follow the instructions. Visit the
U.S. Copyright Office for information on Fair Use limitations of U.S.
copyright law. Please refer to The Association of American Publishers’
(AAP) website for guidelines on Fair Use in the Classroom.
The Materials are for your personal use only and cannot be reformatted,
reposted, resold or distributed by electronic means or otherwise without
permission from Marcel Dekker, Inc. Marcel Dekker, Inc. grants you the
limited right to display the Materials only on your personal computer or
personal wireless device, and to copy and download single copies of such
Materials provided that any copyright, trademark or other notice appearing
on such Materials is also retained by, displayed, copied or downloaded as
part of the Materials and is not removed or obscured, and provided you do
not edit, modify, alter or enhance the Materials. Please refer to our Website
User Agreement for more details.
Order now!
Reprints of this article can also be ordered at
http://www.dekker.com/servlet/product/DOI/101081SCC100105884