Montmorillonite K10 clay: An efficient catalyst for Hantzsch synthesis of 1,4-dihydropyridine derivatives

Article abstract of DOI:10.1080/00397910701750003

An efficient, solid-catalyst-mediated Hantzsch synthesis of 1,4-dihydropyridines is described. This procedure has such advantages as short reaction time, high yields, and simple workup. The catalyst could be reused several times and keeps its initial acti

Full text of DOI:10.1080/00397910701750003

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Montmorillonite K10 Clay: An Efficient
Catalyst for Hantzsch Synthesis of
1,4‐Dihydropyridine Derivatives
Adeleh Moshtaghi Zonouz a & Sahar Baradaran Hosseini a
a Faculty of Science, Chemistry Department, Azarbaijan University of
Tarbiat Moallem, Tabriz, Iran
Published online: 18 Jan 2008.
To cite this article: Adeleh Moshtaghi Zonouz & Sahar Baradaran Hosseini (2008): Montmorillonite K10 Clay:
An Efficient Catalyst for Hantzsch Synthesis of 1,4‐Dihydropyridine Derivatives, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 38:2, 290-296
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Synthetic Communicationsw, 38: 290–296, 2008
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701750003
Montmorillonite K10 Clay: An Efficient
Catalyst for Hantzsch Synthesis of 1,4-
Dihydropyridine Derivatives
Adeleh Moshtaghi Zonouz and Sahar Baradaran Hosseini
Faculty of Science, Chemistry Department, Azarbaijan University of
Tarbiat Moallem, Tabriz, Iran
Abstract: An efficient, solid-catalyst-mediated Hantzsch synthesis of 1,4-dihydro-
pyridines is described. This procedure has such advantages as short reaction time,
high yields, and simple workup. The catalyst could be reused several times and
keeps its initial activity in the subsequent reactions.
Keywords: montmorillonite K10, 1,4-dihydropyridine, solid catalyst, Hantzsch esters
INTRODUCTION
4-Aryl-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate (1,4-DHP) deriva-
tives are widely used for the treatment of cardiovascular diseases (hypertension,
angina pectoris, infarction).[1] The pharmacology of 1,4-dihydropyridine
derivatives is at the eve of a novel boom. After the synthesis, study, and devel-
opment of a set of antihypertensive and antiangina drugs,[2,3] interest is growing
in pharmacological activities that are not connected with their calcium antagon-
ist properties, such as neurotropic (antiamnestic, anticonvulsant, neuroregula-
tory), antidiabetic, membrane-protecting, anticancer, and anti-inflammatory
activities.[4–9]
Received in the U.K. January 12, 2007
Address correspondence to Adeleh Moshtaghi Zonouz, Faculty of Science,
Chemistry Department, Azarbaijan University of Tarbiat Moallem, Tabriz, Iran.
E-mail: adelehmz@yahoo.com
290

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Montmorillonite K10 Clay
291
The first synthesis of a dihydropyridine was performed by Arthur
Hantzsch in 1881.[10,11] The synthesis, which now bears his name, consists
of the cyclocondensation of an aldehyde with an active methylene carbonyl
compound (e.g., ethyl acetoacetate) and ammonia or a primary amine.[12,13]
The standard conditions are heating under reflux for 6–72 h in a lower
alcohol solvent. The yields of 1,4-dihydropyridines obtained by this
method are generally low, but the Hantzsch synthesis remains the most
common method for the synthesis of a wide variety of 1,4-dihydropyri-
dines. The usefulness of 1,4-dihydropyridine derivatives has led to the
development of novel synthetic strategies to improve classical methods of
preparation.[14–16]
In recent years, clay catalysts, particularly montmorillonite, have
received considerable attention in chemical synthesis.[17] They are inex-
pensive, noncorrosive, and recyclable. Thus, montmorillonite-catalyzed
procedures have many advantages, such as environmental compatibility
and easy handling. As a commercial product, montmorillonite K10 clay
has been widely studied and found to be useful in many reactions,
such as the synthesis of b-acetamido ketones,[18] the synthesis of bio-
markers,[19] (2,5)-intramolecular ene cyclization,[20] Michael addition,[21]
Friedel–Craft reaction,[22] Diels–Alder reaction,[23] synthesis of polyhy-
droquinoline derivatives,[24] and also microwave-mediated aromatization
of 1,4-dihydropyridine (DHPs) on the bentonite clay (montmorillonite
K10 clay).[25] Herein, we report our preliminary results on the synthesis
of 1,4-dihydropyridine derivatives catalyzed by montmorillonite K10, as
shown in Scheme 1.
RESULTS AND DISCUSSION
Initially, 2-methoxybenzaldehyde and 3-nitrobenzaldehyde were selected as
probe aldehydes to optimize the reaction conditions, and the results are
listed in Tables 1 and 2. Obviously, the results show that the amount of
Scheme 1.

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292
A. M. Zonouz and S. B. Hosseini
Table 1. Effect of temperature and amount of catalyst on the
reactiona
Amount
of catalyst
(wt.%)
Temp.
(8C)
Time
(min)
Yield of 2b
(%)
Entry
1
2
3
4
5
20
20
20
10
5
80
50
25
80
80
40
80
83
80
70
77
77
120
60
70
aAll reactions were conducted with 2-methoxybenzaldehyde
(2 mmol), ethyl aceto acetate (4 mmol), and ammonium acetate
(3 mmol).
catalyst and temperature had important effects on the reactions, and the best
conditions were 20 wt.% of catalyst montmorillonite K10 and temperature
of 808C.
Encouraged by these results, other aromatic aldehydes have been
reacted with an active methylene carbonyl compound (e.g., ethyl acetoace-
tate, benzoyl acetone) and ammonium acetate. Different aromatic
aldehydes with ethyl acetoacetate and ammonium acetate could be
converted to the corresponding products in good to excellent yields over
the montmorillonite K10 catalyst (Table 3, entries 1–5). When benzoyl
acetone was performed, moderate yields were obtained (Table 3, entries
6–8). Various substituents on the aromatic aldehydes including electron-
donating groups (such as hydroxyl and alkoxyl groups) and electron-with-
drawing groups (such as nitro or chloro groups) did not detrimentally
affect the yields.
Table 2. Effect of temperature and amount of catalyst on the reactiona
Amount of
catalyst
(wt.%)
Temp.
(8C)
Time
(min)
Yield of 2c
(%)
Entry
1
2
3
4
5
20
20
20
10
5
80
50
25
80
80
30
100
120
60
75
70
50
73
65
70
aAll reactions were conducted with 3-nitro benzaldehyde (2 mmol), ethyl aceto
acetate (4 mmol), and ammonium acetate (3 mmol).