Silica chromate as a novel oxidizing agent for the oxidation of 1,4-dihydropyridines

Article abstract of DOI:10.1080/00397910701316276

Silica chromate easily converts 1,4-dihydropyridines to their corresponding pyridines in the presence of NaHSO4·H2O and wet SiO2 in dichloromethane at room temperature in good to excellent yields. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910701316276

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Silica Chromate as a Novel Oxidizing Agent
for the Oxidation of 1,4‐Dihydropyridines
a
b
c
Mohammad Ali Zolfigol , Peyman Salehi , Arash Ghorbani-Choghamarani
a
a
,
Maliheh Safaiee & Mozhgan Shahamirian
a
Faculty of Chemistry , Bu‐Ali Sina University , Hamadan, Iran
b
Department of Chemistry , Medicinal Plants and Drugs Research Institute,
Shahid Beheshti University , Evin, Tehran, Iran
c
Department of Chemistry, Faculty of Science , Ilam University , Ilam, Iran
Published online: 30 Jun 2007.
To cite this article: Mohammad Ali Zolfigol , Peyman Salehi , Arash Ghorbani-Choghamarani , Maliheh
Safaiee & Mozhgan Shahamirian (2007) Silica Chromate as a Novel Oxidizing Agent for the Oxidation of
1,4‐Dihydropyridines, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 37:11, 1817-1823, DOI: 10.1080/00397910701316276
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Synthetic Communications , 37: 1817–1823, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701316276
Silica Chromate as a Novel Oxidizing Agent
for the Oxidation of 1,4-Dihydropyridines
Mohammad Ali Zolfigol
Faculty of Chemistry, Bu-Ali Sina University, Hamadan, Iran
Peyman Salehi
Department of Chemistry, Medicinal Plants and Drugs Research Institute,
Shahid Beheshti University, Evin, Tehran, Iran
Arash Ghorbani-Choghamarani
Department of Chemistry, Faculty of Science, Ilam University, Ilam, Iran
Maliheh Safaiee and Mozhgan Shahamirian
Faculty of Chemistry, Bu-Ali Sina University, Hamadan, Iran
Abstract: Silica chromate easily converts 1,4-dihydropyridines to their corresponding
.
pyridines in the presence of NaHSO
temperature in good to excellent yields.
4 2 2
H O and wet SiO in dichloromethane at room
4
Keywords: 1,4-dihydropyridines, NaHSO , oxidation, pyridines, silica chromate,
sodium hydrogen sulfate
Hantzsch 1,4-dihydropyridines, a class of model compounds of nicotine amid
adenine dinucleotide (NADH) coenzyme, have been extensively studied in
view of the biological pertinence of these compounds to the NADH redox
[
1,2]
process.
diabetic activities. Some representative, such as nifedipine, niguldipine,
They process neuroprotective, platet anti-aggregration, and anti-
[
3]
[4]
nicardipine, and amlodipine, are widely used for treatment of hypertension.
Received in the U.K. November 23, 2005
Address correspondence to Mohammad Ali Zolfigol, Faculty of Chemistry, Bu-Ali
Sina University, P.O.Box 6517838483, Hamadan, Iran. E-mail: zolfi@basu.ac.ir
1
817

1
818
M. A. Zolfigol et al.
Hantzsch 1,4-dihydropyridines are easily prepared from the Hantzsch reaction
[
5–8]
or its modifications. In recent years, it was found that drugs such as nifedi-
pine and niguldipine undergo redox processes due to the catalysis of cytochrome
[9]
P-450 in the liver during their metabolism. Therefore, the oxidation of 1,4-
dihydropyridines has attracted considerable attention. Several oxidation
reagents have been reported for the oxidation of 1,4-dihydropyridines, such
[
1a]
[3]
[4]
[9]
as isoxazolones, SeO2, lead (IV) tetraacetate, FeCl /KMnO , triazo-
3
4
[
10]
linediones, ferric or cupric nitrates on a solid support (clayfen or claycop),
ceric ammonium nitrate, clay-supported cupric nitrate accompanied by ultra-
[
11]
[12]
[13]
sound-promotion NO gas,
Pd/C,
O /activated carbon,
2
manganese
dioxide or DDQ, nitric oxide, bismuth nitrate pentahydrate, pyridinum
chloro chromate (PCC), tetrakis-pyridine cobalt(II) dicromate (TPCD), nicoti-
[
14]
[15]
nium dichromate,
gluthathione, diphenylpicrylhydrazyl and benzoyl peroxide as free-radical
the N O complex of 18-crown-6,
S-nitroso-
2
4
oxidizing agents, KMnO , CrO , HNO , HNO , tert-butylhydroperoxide,
2
4
3
3
silica-gel-supported ferric nitrate (silfen), N O , MCl /NaNO /wet SiO
2
2
3
x
2
[
16]
and silica chloride/NaNO wet SiO ,
2
photochemical and voltammetric
[19]
2
[
17]
[18]
oxidation,
H O /Co(OAc) ,
NaHSO /Na Cr O /wet SiO ,
peroxy-
Co(II)-
inorganic acidic salts and sodium nitrite or
2
2
2
4
2
2
7
2
[
20]
[21]
[22]
disulfate-cobalt(II),
catalyzed auto oxidation,
Zr(NO ) ,
hypervalent iodine reagents,
3
4
[
23]
[
24–28]
[29]
[30]
nitrate,
Mn(TPP)Cl],
Our goal in undertaking this line of work was twofold: (i) to overcome the
I -MeOH and I -ultrasound,
KBrO /MCl ,
(n-Bu) IO /
2
31]
2
3
n
4 4
[
[32]
[
and heteropolyacid/NaNO /wet SiO .
2 2
limitations and drawbacks of the reported methods such as tedious workup,
acidic media, and safety problems, and moreover (ii) to develop a high-
yielding conversion of 1,4-dihydropyridines to their corresponding pyridines
by using a novel synthetic silica-based oxidant.
In continuation of our studies on the synthesis of new inorganic
[
33]
silica-based resins, we found that silica gel reacts with dichloro
chromium oxide to give silica chromate (I). It is interesting to note that the
reaction is easy and clean without any workup procedure because HCl gas
[34]
is evolved from the reaction vessel immediately (Scheme 1).
report a simple, cheap, and mild method for the effective oxidation of
,4-dihydropyridines using silica chromate in the presence of
NaHSO4 H O and wet SiO in dichloromethane at room temperature.
Here, we
1
I
.
2
2
Scheme 1.

Silica Chromate Oxidizes 1,4-Dihydropyridines
1819
A good range of dihydropyridines (1) was subjected to the oxidation
.
reaction in the presence of silica chromate I, NaHSO4 H O, and wet SiO
2
2
(50% w/w) in dichloromethane (Scheme 2). The oxidation reactions were
performed under mild and completely heterogeneous conditions at room
temperature and took place with good to excellent yields. The reaction was
mild and the workup was straightforward, requiring simple filtration of the
silica-based reagents. Highly pure pyridine derivatives 2 could be obtained
by passing the filtrate through a short pad of silica gel and evaporation of
the solvent. The results and reaction conditions are give in Table 1. The
Scheme 2.
1
2
1
a
,2
R
R
COOEt
COOEt
COOEt
COOEt
COOEt
COOEt
COOEt
COOEt
COOEt
COOEt
COOMe
COOMe
COOMe
COOMe
COOMe
COOMe
COOMe
COOMe
COOMe
COOMe
H
b
c
d
e
f
Me
Et
n-Pr
Ph
2-Thienyl
2-Furyl
g
h
i
3-NO
4-NO
2
-C
-C
6
6
H
H
4
-
-
2
4
j
4-Br-C H -
6 4
k
l
Me
Et
m
n
o
p
q
r
s
n-Pr
Ph
2-Thienyl
2-Furyl
3-NO -C H -
2
6 4
4- NO
2
-C
6
H
-
4
-
6 4
2-Br-C H
t
4-Br-C H -
6 4

1
820
M. A. Zolfigol et al.
Table 1. Oxidation of 1,4-dihydropyridines (1) to their corresponding pyridine
.
derivatives (2) with a combination of silica chromate (I), NaHSO4 H O (II), and
2
wet SiO
2
(50% w/w) in dichloromethane at room temperature
Reagents/
a
substrate
b
Time
(min)
Yield
(%)
Entry
Substrate
Product
I
II
1
2
3
4
5
6
7
8
9
1a
1b
1c
1d
1e
1f
2a
2b
2c
2d
2e
2f
1.05
1.125
1.05
1.05
1.125
1.2
7
20
35
76
98
97
85
88
97
95
91
98
89
80
83
91
90
83
91
94
92
85
91
7.5
7
50
35
7
7.5
8
150
75
1g
1h
1i
2g
2h
2i
1.2
1.2
8
100
65
8
1.2
8
60
50
1
1
1
1
1
1
1
1
1
1
2
0
1
2
3
4
5
6
7
8
9
0
1j
2j
1.05
1.125
1.05
1.05
1.125
1.2
7
1k
1l
2k
2l
7.5
7
45
40
1m
1n
1o
1p
1q
1r
1s
2m
2n
2o
2p
2q
2r
2s
7
75
7.5
8
125
90
1.2
1.2
8
60
8
100
105
50
1.2
8
1.05
1.05
7
1t
2t
7
120
a
Wet SiO :substrate (0.3 g:1 mmol); I and II refer to gram of the silica chromate and
2
.
mmol of NaHSO
b
Isolated yields.
4 2
H O respectively.
pyridine derivatives were characterized by comparison of their spectral (IR,
1
H NMR) and physical data with the authentic samples (Table 1).
The application of silica-gel-supported chromium trioxide in the aroma-
[
35]
tization of 1,4-dihydropyridines has already been reported.
our knowledge, silica chromate is the first example of silica-chromium-
To the best of
based oxidant with covalent linkages (silica vulcanized with CrO
34]
2
[
linkages).
the previously reported chromium-based oxidants
Thus, we hoped that the silica chromate I would be superior to
because (i) toxic
[36–41]
chromium cations could be collected from the reaction mixture easily, (ii)
workup is very simple and pure products are obtained solely by filtration
and removing of solvent, and (iii) there is no need for any chelating agents
[
41]
such as pyridine in pyridinium chlorochromate (PCC).
older procedures, isolation of the oxidation products from reaction mixture
Moreover, in
[
36,41]
and chelating agents such as pyridine in PCC was difficult.

Silica Chromate Oxidizes 1,4-Dihydropyridines
1821
In conclusion, the low cost and the availability of the reagents, easy and
clean workup, and high yields make this method attractive for chemists. We
believe that the present methodology could be an important addition to
the existing methodologies.
EXPERIMENTAL
General
Chemicals were purchased from Fluka, Merck, and Aldrich chemical
companies. The pyridine derivatives were characterized by comparison of
1
their spectral (IR, H NMR) and physical data with those of the authentic
[
1,33]
samples.
our recent published procedure.
All Hantzsch 1,4-dihydropyridines were easily prepared by
[
5]
Preparation of Silica Chromate
A 500-mL suction flask was equipped with a constant-pressure dropping
funnel containing dichloro chromium oxide (23.2 g, 0.15 mol) and gas inlet
tube for conducting HCl gas over an adsorbing solution (i.e., water). Silica
gel (100 g) was charged into the flask. Dichloro chromium oxide was added
dropwise over a period of 20 min at room temperature. HCl gas evolved
from the reaction vessel immediately (Scheme 1). After the addition was
complete, the mixture was shaken for 90 min. A brown solid (silica
[34]
chromate) was obtained quantitatively.
General Procedure for the Oxidation of 1,4-Dihydropyridines
A suspension of compound 1, silica chromate, and wet SiO [(50% w/w)] in
2
CH Cl (10 mL) was stirred at room temperature for a specific time (molar
2
2
ratio of reagents and needed reactions times indicated in Table 1). The
progress of the reaction was monitored by thin-layer chromatography
(TLC). After disappearing the spot of starting material 1 on TLC, the
reaction mixture was filtered off. The residue was washed with CH Cl2
2
(
2 Â 10 mL). Anhydrous Na SO (1 g) was added to the filtrate and filtered
2
4
off after 20 min. Dichloromethane was removed, and product 2 was obtained.
ACKNOWLEDGMENT
Financial support of this work by the Management and Programming Organ-
ization of Iran (award of the selection by ESI) and Research Affair, Bu-Ali
Sina University, Hamadan, Iran, is gratefully acknowledged.

1
822
M. A. Zolfigol et al.
REFERENCES
1
2
. (a) Han, B.; Liu, Q.; Liu, Z.; Mu, R.; Zhang, W.; Liu, Z. L.; Yu, W. Synlett 2005,
333; (b) Liu, Z. G.; Han, B.; Liu, Q.; Zhang, W.; Yang, L.; Liu, Z. L.; Yu, W.
Synlett 2005, 1579.
2
. (a) Simon, C.; Constantieux, T.; Rodriguez, J. Eur. J. Org. Chem. 2004, 4957;
(
b) Tewari, N.; Dwivedi, N.; Tripathi, R. P. Tetrahedron Lett. 2004, 45, 9011.
3
. Cai, X.; Yang, H.; Zhang, G. Can. J. Chem. 2005, 83, 273.
. Litvic, M.; Cepanec, I.; Filipan, M.; Kos, K.; Bartolincic, A.; Druskovic, V.;
Tibi, M. M.; Vinkovic, V. Heterocycles 2005, 65, 23.
4
5
6
7
8
. Zolfigol, M. A.; Safaiee, M. Synlett 2004, 827.
. Chari, M. A.; Syamasundar, K. Catal. Commun. 2005, 6, 624.
. Ji, S. J.; Jiang, Z. Q.; Lu, J.; Loh, T. P. Synlett 2004, 831.
. Sabitha, G.; Reddy, G. S. K. K.; Reddy, C. S.; Yadav, J. S. Tetrahedron Lett. 2003,
4
. Xia, J. J.; Wang, G. W. Synthesis 2005, 2379.
4, 4129.
9
1
0. Zolfigol, M. A.; Ghorbani Choghamarani, A.; Shahamirian, M.; Safaiee, M.;
Mohammadpoor-Baltork, I.; Mallakpour, S.; Abdollahi-Alibeik, M. Tetrahedron
Lett. 2005, 46, 5581.
1
1. Itoh, T.; Nagata, K.; Matsuya, Y.; Miyazaki, M.; Ohsawa, A. J. Org. Chem. 1997,
6
2, 3582, and references cited therein.
12. Nakamichi, N.; Kawashita, Y.; Hayashi, M. Org. Lett. 2002, 4, 3955.
13. Nakamichi, N.; Kawashita, Y.; Hayashi, M. Synthesis 2004, 1015.
14. Sadeghi, M. M.; Mohammadpoor-Baltork, I.; Memarian, H. R.; Sobhani, S. Synth.
Commun. 2000, 30, 1661, and references cited therein.
1
5. Zolfigol, M. A.; Zebarjadian, M. H.; Sadeghi, M. M.; Mohammadpoor-Baltork, I.;
Memarian, H. R.; Shamsipur, M. Synth. Commun. 2001, 31, 929.
6. (a) Zolfigol, M. A.; Ghorbani Choghamarani, A.; Dialameh, S.; Sadeghi, M. M.;
Mohammadpoor-Baltork, I.; Memarian, H. R. J. Chem. Res-S. 2003, 18, and refer-
ences cited therein; (b) Zolfigol, M. A.; Shirin, F.; Ghorbani Choghamarani, A.;
Mohammadpoor-Baltork, I. Phosphorus. Sulfur. 2003, 178, 1709, and references
cited therein.
1
17. (a) Memarian, H. R.; Sadeghi, M.; Aliyan, H. Indian J. Chem. 1998, 37B, 219;
(
b) Arguello, J.; Nunez-Vergara, L. J.; Sturm, J. C.; Squella, J. A. Electrochim.
Acta 2004, 49, 4989.
1
8. Hashemi, M. M.; Ahmadibeni, Y.; Ghafuri, H. Monatsh. Chem. 2003, 134, 107.
9. Zolfigol, M. A.; Sadeghi, M. M.; Mohammadpoor-Baltork, I.; Ghorbani
Choghamarani, A.; Taqian-Nasab, A. Asian J. Chem. 2001, 13, 887.
0. Anniyappan, M.; Muralidharan, D.; Perumal, P. T. Tetrahedron 2002, 58, 5069.
1. Sabitha, G.; Kumar Reddy, G. S. K.; Reddy, C. S.; Fatima, N.; Yadav, J. S.
Synthesis 2003, 1267.
1
2
2
22. Lee, J. W.; Ko, K. Y. B. Kor. Chem. Soc. 2004, 25, 19.
23. Chavan, S. P.; Kharul, R. K.; Kalkote, U. R.; Shivakumar, I. Synth. Commun. 2003,
3
8, 1333.
2
2
2
4. Zolfigol, M. A.; Kiany-Borazjani, M.; Sadeghi, M. M.; Memarian, H. R.; Moham-
madpoor-Baltork, I. J. Chem. Res-S. 2000, 167.
5. Zolfigol, M. A.; Kiany-Borazjani, M.; Sadeghi, M. M.; Memarian, H. R.; Moham-
madpoor-Baltork, I. Synth. Commun. 2000, 30, 2945.
6. Zolfigol, M. A.; Kiany-Borazjani, M.; Sadeghi, M. M.; Mohammadpoor-
Baltork, I; Memarian, H. R. Synth. Commun. 2000, 30, 3919.

Silica Chromate Oxidizes 1,4-Dihydropyridines
1823
2
2
2
7. Zolfigol, M. A.; Shirin, F.; Ghorbani Choghamarani, A.; Mohammadpoor-
Baltork, I. Green Chem. 2002, 4, 562.
8. Zolfigol, M. A.; Kiany-Borazjani, M.; Sadeghi, M. M.; Mohammadpoor-
Baltork, I.; Memarian, H. R. Synth. Commun. 2000, 30, 551.
9. (a) Yadav, J. S.; Reddy, B. V. S.; Sabitha, G.; Reddy, G. S. K. K. Synthesis 2000,
1532; (b) Zeynizadeh, B.; Dilmaghani, K. A.; Roozijoy, A. J. Chin. Chem. Soc.
2005, 52, 1001.
30. (a) Zeynizadeh, B.; Dilmaghani, K. A.; Roozijoy, A. J. Chem. Res. Synop. 2005,
675; (b) Zeynizadeh, B.; Dilmaghani, K. A.; Roozijoy, A. Synth. Commun.
2005, 35, 557.
31. Nasr-Esfahani, M.; Moghadam, M.; Tangestaninejad, S.; Mirkhani, V. Bioorg.
Med. Chem. Lett. 2005, 15, 3276.
3
2. (a) Niknam, K.; Zolfigol, M. A.; Razavian, S. M.; Mohammadpoor-Baltork, I. Het-
erocycles 2005, 65, 657; (b) Zolfigol, M. A.; Bagherzadeh, M.; Niknam, K.;
shirini, F.; Mohammadpoor-Baltork, I.; Ghorbani-Choghamarani, A.;
Baghbanzadeh, M. J. Iran. Chem. Soc. 2006, 3, 73; (c) Karami, B.;
Montazerozohori, M.; Habibi, M. H.; Zolfigol, M. A. Heterocycl. Commun.
2006, 11, 513; (d) Nikname, K.; Zolfigol, M. A.; Razavian, S. M.; Mohammad-
poor-Baltork, I. J. Heterocycl. Chem. 2006, 65, 199.
3
3
3. (a) Zolfigol, M. A. Tetrahedron 2001, 57, 9509; (b) Zolfigol, M. A.; Madrakian, T.;
Ghaemi, E.; Afkhami, A.; Azizian, S.; Afshar, S. Green Chem. 2002, 4, 611;
(
c) Zolfigol, M. A.; Shirini, F.; Zamani, K.; Ghofrani, E.; Ebrahimi, S. Phosphorus
Sulfur 2004, 179, 2177; (d) Madrakian, T.; Zolfigol, M. A.; Afkhami, A.;
Afshar, S. Asian J. Chem. 2005, 17, 1941; (e) Bamoniri, A.; Zolfigol, M. A.;
Mohammadpoor-Baltork, I.; Mirjalili, B. F. J. Iran. Chem. Soc. 2006, 3, 85.
4. Zolfigol, M. A.; Shirini, F.; Mohammadpoor-Baltork, I.; Ghorbani-
Choghamarani, A.; Hajjami, M.; Sedaghat, A. M. Mendeleev Commun. 2005,
15, 113.
35. Khadilkar, B.; Jaisinghani, H.; Khare, A. Indian. J. Chem. 1998, 37B, 817.
36. Salehi, P.; Firouzabadi, H.; Farrokhi, A.; Gholizadeh, M. Synthesis 2001, 2273.
37. Mahjoub, A. R.; Ghammami, S.; Kassaee, Z. Tetrahedron Lett. 2003, 44, 4555.
38. (a) Mirjalili, B. F.; Zolfigol, M. A.; Bamoniri, A.; Zarei, A. B. Kor. Chem. Soc.
2
2
003, 24, 400; (b) Shirini, F.; Zolfigol, M. A.; Khaleghi, M. B. Kor. Chem. Soc.
003, 24, 1021; (c) Shirini, F.; Zolfigol, M. A.; Mallakpour, B.;
Mallakpour, S. E.; Hajipour, A. R. Aust. J. Chem. 2001, 54, 405.
9. Yamato, T.; Shinoda, N. J. Chem. Res-S 2002, 400.
0. Bressette, A. R.; Glover IV, L. C. Synlett 2004, 738.
1. Fernandes, R. A. Synlett 2003, 741.
3
4
4