Aromatization of hantzsch 1,4-dihydropyridine with bismuth(III) chloride supported onto wet HZSM-5 zeolite under microwave irradiation in solventless system

Article abstract of DOI:10.1080/104265090508415

Hantzsch 1,4-dihydropyridines (1,4 DHPs) can be aromatized to pyridines by bismuth(III) chloride supported onto wet HZSM-5 zeolite under microwave irradiation in high yields and in a short time. Copyright Taylor & Francis Inc.

Full text of DOI:10.1080/104265090508415

This article was downloaded by: [University of Louisville]
On: 28 December 2014, At: 21:36
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
Phosphorus, Sulfur, and Silicon
and the Related Elements
Publication details, including instructions for
authors and subscription information:
http://www.tandfonline.com/loi/gpss20
Aromatization of Hantzsch
1,4-Dihydropyridine with
Bismuth(III) Chloride Supported
onto Wet HZSM-5 Zeolite
Under Microwave Irradiation in
Solventless System
Majid M. Heravi a & Mitra Ghassemzadeh b
a Department of Chemistry , School of Sciences,
Azzahra University, Vanak, Tehran, Iran , Vanak,
Tehran, Iran
b Chemistry & Chemical Engineering Research Center
of Iran Tehran, Iran , Tehrran, Iran
Published online: 21 Dec 2010.
To cite this article: Majid M. Heravi & Mitra Ghassemzadeh (2005) Aromatization of
Hantzsch 1,4-Dihydropyridine with Bismuth(III) Chloride Supported onto Wet HZSM-5
Zeolite Under Microwave Irradiation in Solventless System , Phosphorus, Sulfur, and
Silicon and the Related Elements, 180:2, 347-351, DOI: 10.1080/104265090508415
To link to this article: http://dx.doi.org/10.1080/104265090508415
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

Phosphorus, Sulfur, and Silicon, 180:347–351, 2005
Copyright © Taylor & Francis Inc.
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/104265090508415
Aromatization of Hantzsch 1,4-Dihydropyridine
with Bismuth(III) Chloride Supported onto Wet
HZSM-5 Zeolite Under Microwave Irradiation
in Solventless System
Majid M. Heravi
Department of Chemistry, School of Sciences, Azzahra University,
Vanak, Tehran, Iran
Mitra Ghassemzadeh
Chemistry & Chemical Engineering Research Center of Iran,
Tehran, Iran
Hantzsch 1,4-dihydropyridines (1,4 DHPs) can be aromatized to pyridines by bis-
muth(III) chloride supported onto wet HZSM-5 zeolite under microwave irradiation
in high yields and in a short time.
Keywords Aromatization; bismuth(III) chloride; hantzsch 1,4-dihydropyridines;
microwave irradiation; pyridines; solventless system
INTRODUCTION
Aromatization of Hantzsch 1,4-dihydropyridines has attracted much at-
tention due to the fact that some of them are hypertensive drugs (Ca2+
channel blockers)1 and they can be oxidatively converted to pyridine
derivatives by the action of cytochrome P-450 in the liver. The reaction
has also been used to investigate the NADH redox processes.2 Further-
more, the oxidation of Hantzsch 1,4-DHPs is a common and easy way
to pyridine derivatives.
Consequently, this oxidation reaction continues to attract the at-
tention of synthetic organic chemists for the introduction of milder,
faster, and eco-friendly protocols applicable to a wide range of 1,4-
dihydropyridines.
Received April 30, 2004; in final form July 6, 2004.
Partial financial support from the research council of Azzahra University is
appreciated.
Address correspondence to Majid M. Heravi, Department of Chemistry, School of Sci-
ences, Azzahra University, Vanak, Tehran, Iran. E-mail: mmheravi@azzahra.ac.ir
347

348
M. M. Heravi and M. Ghassemzadeh
Several oxidizing agents and a variety of methods have been reported
in the literature.3 Each method has its merits and drawbacks. However
the aromatization reaction with most of these methods lead to dealky-
lation at the 4-position or formation of side products.4
Bismuth compounds are environmentally friendly reagents for or-
ganic synthesis.5 They are relatively nontoxic, readily available, in-
expensive, and fairly insensitive to small amounts of water.6 The
biochemistry,7 toxicology,8 and environmental effects of bismuth com-
pounds have been well documented and show that they are attractive
candidates for use in green chemistry.
Prompted by stringent environment protection laws in recent years
there has been increasing emphases on the use and design of eco-
friendly reagents and solid and solvent free reactions.9 Applica-
tion of microwave heating technique is currently under intensive
examination.10 Dry technique has attracted much attention recently
since organic solvents are expensive and hazardous and open vessels
can be used.11 Due to the importance of Hantzsch 1,4 dihydropyridines,
advantages of bismuth compounds, and merits of coupling of microwave
irradiation with dry technique, in this communication we wish to re-
port our results on an expeditious supported BiCl3 mediated oxidation
of 1,4-dihydropyridine.
RESULTS AND DISCUSSION
The reagent impregnated on solid supports, especially that are efficient
in dry media, have gained popularity in organic synthesis because of
their selectivity and ease of manipulation. During the course of the
study of organic reaction in solvent-free conditions, we have observed
the usefulness of HZSM-5 zeolite∗ and microwave irradiation in en-
hancing of the reaction.12 In connection with these observations, we
became interested in developing a rapid and eco-friendly condition to
effect conversion of 1,4-dihydropyridines to pyridines under microwave
irradiation in solventless system. Our initial attempts to induce oxi-
dation of the simple Hantzsch 1,4-dihydropyridine as a test case with
(R H) and bismuth chloride under microwave irradiation and without
solvent was not very promising as considerable amounts of inchanged
starting material was recovered after a relatively long reaction period of
up to 10 min. However, when BiCl3 was supported onto equal amounts
of HZSM-5 zeolite and the mixture was made wet by addition of a few
∗HZSM-5 zeolite was prepared by calcination of NH4ZSM-5 zeolite at 500◦C for 8 hrs.
˚
Si:Al = 40:1 and pore diameters are 5.1 × 5.5 A. We are grateful to Dr. A. R. Garakani
for a gift of zeolite.

Aromatization of Dihydropyridines
349
drops of water, under microwave irradiation, the oxidation was per-
formed rapidly in (12 min) in the case of the oxidation of 1 (R H).
It is noteworthy to mention that in the absence of water the reac-
tion is sluggish. To establish the generality of the method a variety
of 1,4-dihydropyridines 1–10 were oxidized under similar conditions
(Table I).
The salient features of this reaction are mild reaction conditions,
short time, eco-friendly conditions, excellent yields, and the stability of
the substituents at the 4-position, which are normally dealkylated dur-
13
ing aromatization by existing methods. i.e., oxidant such as KMnO4
and MnO14 in addition, BiCl3 does not show the disadvantage of giving
nitrated side products, was observed in the reaction with bismuth(III)
nitrate.15
The oxidation of 1,4-dihydropyridine was initated by a three electron
transfer to Bi(III) to produce Bi0. A radical cation subsequently looses
a proton to afford a radical II. The second mole of Bi(III) then oxidizes
radical II to the protonated pyridine III. At the end, the pyridinium
species III loses a proton to give the corresponding pyridine derivative
(Scheme 1).
In summary, we have found BiCl3 supported onto HZSM-5 zeolite
can serve as a mild and clean oxidant under microwave irradiation
in solvent free conditions for aromatization of 1,4-dihydropyridines to
pyridines in high yield, giving the additional benift of easy work up and
eco-friendly conditions.
TABLE I Aromatization of Hantzsch 1,4-Dihydropyridines with
BiCl3 Supported onto HZSM-5 Zeolite Under Microwave Irradiation
in Solventless System
Mp (◦C)
Entry
R
Reaction time (s)
Yielda (%)
Observed Reported
1
2
3
4
5
6
7
8
9
H
CH3
CH3CH2CH3
(CH3)2CH
4-Cl-C5H4
2-NO2-C6H4
3-NO2-C6H4
4-NO2-C6H4
4-CH3O-C8H4
2-furyl
180
120
120
120
180
180
270
210
120
120
92
90
65
77
82
80
81
80
78
85
68–9
Oil
Oil
69–70
65–6
75–6
62–3
114–5
49–50
Oil
70–117
Oil18
Oil18
69–7017
66–717
7519
61-317
114–617
5020
10
Oil19
aYields refer to isolated pure product. Products exhibited physical and spectral
properties in accordance with the assigned structure.

350
M. M. Heravi and M. Ghassemzadeh
SCHEME 1
EXPERIMENTAL
All dihydropyridines were prepared in the same manner, using the ap-
propriate aldehyde, ammonia, and ethyl acetoacetate. All compounds
were known and identified by comparison of their spectral data with
those of authentic samples.
Oxidation of Dihydropyridines. General Procedure
Bismuth(III) chloride (1 mmol) was mixed thoroughly with HZSM-5 ze-
olite (0.5 g). The appropriate Hantzsch 1,4-dihydropyridine was added
to the above reagent in a beaker and mixed thoroughly using a spat-
ula. The beaker was placed in a microwave oven and irradiated for the
specified time (Table I). After completion of the reaction (monitored by
TLC) chloroform was added and the solid filtered off. The filtrate was
evaporated to dryness and the residue was crystallized from ethanol to
afford the corresponding pyridine (Table I).
CAUTION
Although we did not have any accident during this work, use of the
microwave oven in an efficient hood is highly recommended.
REFERENCES
[1] a) R. H. Bocker and F. P. Guengerich, J. Med. Chem., 29, 1596 (1986); b) F. P.
Guengerich, W. R. Brian, M. Iwasaki, M. A. Sari, C. Baarnhielm, and P. Bernisson,
J. Med. Chem., 34, 1838 (1991).

Aromatization of Dihydropyridines
351
[2] M. F. Gordeev, D. V. Patel, and E. M. Gordon, J. Org. Chem., 61, 924 (1996).
[3] a) R. S. Varma and D. Kumar, Tetrahedron Lett., 40, 21 (1999); b) H. R. Memarian,
M. M. Sadeghi, and A. R. Momeni, Synth. Commun., 31, 2241 (2001).
[4] a) J. J. Van den Eynde, A. Mayence, and A. Maquestiau, Tetrahedron, 48, 463 (1992);
b) M. Tajbakhsh, M. M. Heravi, A. Hosseini, and A. Shahrezaiee, Phosphorus, Sulfur
and Silicon, 178, 773 (2003).
[5] H. Suzuki, T. Ikegami, and Y. Matano, Synthesis, 249, (1997).
[6] B. A. Nattier, K. J. Eash, and R. S. Mehan, Synthesis, 2, 1010 (2001).
[7] K. Dill and E. L. McGreen, Chemistry of Organic Arsenic, Antimony and Bismuth
Compounds, S. Patai (ed.) (New York: John Wiley, 1994), pp. 695–713.
[8] U. Worsner and L. Nir, Ibid., 715 (1994).
[9] C. B. Khouv, C. Parth, J. A. Lalenger, and M. E. Davis, J. Catal., 149, 195 (1994).
[10] S. Caddick, Tetrahedron, 51, 10403 (1995).
[11] a) M. M. Heravi, D. Ajami, K. Aghapoor, and M. Ghassemzadeh, Chem. Commun.,
833 (1999); b) M. M. Heravi, D. Ajami, M. M. Mojtahedi, and M. Ghassemzadeh,
Tetrahedron Lett., 40, 561 (1999).
[12] M. M. Heravi, D. Ajami, B. Mohajerani, K. Tabar-Hydar, and M. Ghassemzadeh,
Synth. Commun., 32, 3325 (2002).
[13] J. J. Van den Eynde, R. D’Orazio, and H. Yves van, Tetrahedron, 50, 2479 (1994).
[14] F. Delgado, C. Alvarez, O. Garcia, G. Penieres, and C. Marquez, Synth. Commun.,
21, 2137 (1991).
[15] S. H. Marquez and M. A. Karnik, Synthesis, 7 13 (1998).
[16] J. J. Van den Eynde, F. Delfasse, A. Majence, and Y. Van Haveriene, Tetrahedron,
51, 6511 (1995).
[17] B. Loer and K. M. Snader, J. Org. Chem., 30, 1914 (1965).
[18] L. E. Henkel, E. E. Ayling, and W. H. Margan, J. Chem. Soc., 1835 (1931).
[19] D. Emmert, E. Diefenbach, and R. Eck, Ber., 2220 (1927).