Efficient oxidation of hantzsch 1,4-dihydropyridines with tetrabutylammonium peroxomonosulfate catalyzed by manganese(III) schiff base complexes: The effect of schiff base complex on the product selectivity

Article abstract of DOI:10.1080/00397910902838995

Efficient and rapid oxidation of Hantzsch 1,4-dihydropyridine with tetrabutylammonium peroxomonosulfate (TBAO) is reported. The Mn(salophen)/monopersulfate catalytic system efficiently converts 1,4-dihydropyridines (DHPs) to their corresponding pyridine d

Full text of DOI:10.1080/00397910902838995

This article was downloaded by: [Universita degli Studi di Torino]
On: 30 May 2013, At: 19:08
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
Efficient Oxidation of
Hantzsch 1,4-Dihydropyridines
with Tetrabutylammonium
Peroxomonosulfate Catalyzed
by Manganese(III) Schiff Base
Complexes: The Effect of Schiff
Base Complex on the Product
Selectivity
a
b
Masoud Nasr-Esfahani , Majid Moghadam
&
a
Ghasem Valipour
a
Department of Chemistry, Yasouj University,
Yasouj, Iran
b
Department of Chemistry, Catalysis Division,
University of Isfahan, Isfahan, Iran
Published online: 07 Oct 2009.
To cite this article: Masoud Nasr-Esfahani , Majid Moghadam & Ghasem
Valipour (2009): Efficient Oxidation of Hantzsch 1,4-Dihydropyridines with
Tetrabutylammonium Peroxomonosulfate Catalyzed by Manganese(III) Schiff Base
Complexes: The Effect of Schiff Base Complex on the Product Selectivity, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 39:21, 3867-3879
To link to this article: http://dx.doi.org/10.1080/00397910902838995

PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-
and-conditions
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.
The publisher does not give any warranty express or implied or make any
representation that the contents will be complete or accurate or up to
date. The accuracy of any instructions, formulae, and drug doses should be
independently verified with primary sources. The publisher shall not be liable
for any loss, actions, claims, proceedings, demand, or costs or damages
whatsoever or howsoever caused arising directly or indirectly in connection
with or arising out of the use of this material.

1
Synthetic Communications , 39: 3867–3879, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910902838995
Efficient Oxidation of Hantzsch
,4-Dihydropyridines with Tetrabutylammonium
1
Peroxomonosulfate Catalyzed by Manganese(III)
Schiff Base Complexes: The Effect of Schiff Base
Complex on the Product Selectivity
1
2
Masoud Nasr-Esfahani, Majid Moghadam, and Ghasem Valipour
1
1
Department of Chemistry, Yasouj University, Yasouj, Iran
Department of Chemistry, Catalysis Division, University of Isfahan,
Isfahan, Iran
2
Abstract: Efficient and rapid oxidation of Hantzsch 1,4-dihydropyridine with
tetrabutylammonium peroxomonosulfate (TBAO) is reported. The Mn(salophen)=
monopersulfate catalytic system efficiently converts 1,4-dihydropyridines (DHPs)
to their corresponding pyridine derivatives under mechanical stirring and micro-
wave irradiation in CH Cl . The ability of various Schiff base complexes to oxidize
2 2
DHPs was also investigated. The results showed that in the presence of manganese
Schiff complex, no by-product was obtained.
Keywords: Biomimetic oxidation, 1,4-dihydropyridine, manganese(III) Schiff
base, tetrabutylammonium peroxomonosulfate
INTRODUCTION
[
,4-Dihydropyridines (DHPs) are calcium antagonists, neuropeptide Y
1]
1
Y1 receptor antagonists, and antitubercular agents. They possess
[2]
[3]
[
4]
platet anti-aggregration, neuroprotective, and antidiabetic activities.
Aromatization of DHPs has received considerable attention because
Received January 23, 2009.
Address correspondence to Masoud Nasr-Esfahani, Department of Chemistry,
Yasouj University, Yasouj 75918-74831, Iran. E-mail: manas@mail.yu.ac.ir
3
867

3868
M. Nasr-Esfahani, M. Moghadam, and G. Valipour
DHP-based calcium-channel blockers are oxidatively converted to
[
5]
pyridine derivatives by the action of cytochrome P-450 in the liver.
Transition-metal complexes with Schiff base and porphyrin ligands
have been extensively used as models for the heme containing
[6]
cytochrome P-450. Cytochorome P-450 catalyzes a wide variety of
reactions, including oxygen transfer to heteroatoms, epoxidation of
olefins, hydroxylation of aromatic hydrocarbons, and oxidative
degradation of chemically inert xenobiotics such as drugs and environ-
[7]
mental contaminants. Metal complexes of salen and salophen ligands
have been used as reagents and catalysts in many reactions including
olefin epoxidation, nucleic acid modification, electrochemical reduction,
alkane hydroxylation, Diels–Alder transformations, carboxylic acid
decarboxylation, amine oxidation, and medicinal studies as models for
[8]
mimicking the superoxide dismutase. For mimicking the function of
cytochrome P-450, the transition-metal Schiff base systems have several
advantages, such as ready availability, simple preparation, low cost, and
high activity.
Mn(III) complexes of salen-type ligands have attracted much interest
in the past few decades because of their unique catalytic activity, espe-
cially as epoxidation catalysts, in the presence of terminal oxidants such
as iodosylbenzene, sodium hypochlorite, tert-butylhydroperoxide, and
[9]
hydrogen peroxide. These complexes catalyze the transfer of oxygen
atoms to organic substrates, and the nature of products depends on
several factors such as substrate, oxidant, counterion, solvent, structure
[
10]
of salen ligands, and the kind of axial ligand.
DHPs can easily be synthesized by Hantzsch condensation of aldehydes,
[
5b,11]
b-keto esters, and ammonia or ammonium acetate.
DHPs have been aro-
matized to pyridines by various reagents such as pyridinium chlorochromate
[12]
PCC);
[13]
[14]
(
Co ;
Zr(NO ) ;
(NH ) Ce(NO ) ;
4 4
urea nitrate and K S O –
2 2
3
[16]
4
3 6
8
ꢀ
2
þ [15]
[17]
Pd=C;
photochemical oxidation;
Mn porphyrin=IO ,
[18]
4
inorganic acidic
[20]
ꢀ
Mn(salophen)=IO , silver salts=iodine monochloride;
4
salts, sodium nitrite, or nitrate; and O -activated carbon. Despite these
[19]
2
intensive efforts, most of the reported oxidation procedures require long
reaction time, utilize strong oxidants in large excess, and afford products with
only modest yields. In particular, the aromatization reaction with these
reagents leads to dealkylation of the 4-position or formation of side
[
21]
products.
aromatization of DHPs is still necessary.
The tetrabutylammonium salt acts as a phase-transfer catalyst,
Therefore, the development of more effective methods for
[
22]
changing the solubility properties of a reagent so that two reactants (an
organic compound and a salt) that normally do not dissolve in the
same solvent can be brought together. The commercial potassium salt of

1
,4-Dihydropyridine Oxidation by TBAO–Schiff Base
3869
Scheme 1. Catalytic oxidation of 1,4-dihydropyridines with tetrabutylammonium
peroxomonosulfate at room temperature in CH
microwave irradiation conditions.
2 2
Cl under mechanical stirring or
oxone is not soluble in organic solvents; the corresponding salt, tetrabutyl-
ammonium monopersulfate [2(Bu N)HSO (Bu N)HSO (Bu N) SO ]
4
5
4
4
4
2
4
[
23]
(
TBAO) is easily prepared and soluble in many organic solvents.
Oxone has been used for hydrocarbon epoxidation and hydroxyl-
[24]
ation with metalloporphyrin catalysts
as with platinum catalysts.
radicals as peroxides and usually acts as a single oxygen atom donor like
iodosylbenzene.
TBAO act as an efficient oxidant for the selective transformation of
in a two-phase systems as well
As a peracid, it is not as likely to form
[25]
[
26]
[27]
imines to oxaziridines. Its use in oxyfunctionalization of hydrocarbons
required activation by Mn–porphyrin
[28]
and biomimetic oxidation of
organosulfur. TBAO has also been introduced as a very sluggish oxy-
[
29]
[
30]
gen source for the oxidation of sulfides to sulfones.
In this article, we report the rapid and efficient catalytic oxidation of
DHPs with TBAO to their corresponding pyridine derivatives at room
temperature in CH Cl (Scheme 1).
2
2
EXPERIMENTAL
[
11b]
All Hantzsch DHPs were synthesized by the reported procedures.
Schiff base complexes 1–10 (Table 1) were prepared as described by
[
31]
[32]
Boucher
or by the more recently modified methods.
Infrared (IR)
1
spectra were recorded on a Jasco IR-680 spectrophotometer. H NMR
spectra were obtained with Brucker AW 80 (80-MHz) or Bruker-Arance
AQS 300-MHz spectrometers. The microwave (MW) system used for
these experiments includes the following items: Micro-Synth labstation,
complete with glass door, dual magnetron system with pyramid-shaped
diffuser, 1000 W delivered power, exhaust system, magnetic stirrer,

3870
M. Nasr-Esfahani, M. Moghadam, and G. Valipour
Table 1. Oxidation of 4-phenyl derivative of 1,4-dihydropyridines with TBAO
a
catalyzed by various metal Schiff base complexes
b
Catalyst
M
Z
X
Y
Yields (%)
I
I
I
I
I
I
I
II
II
II
Fe
Co
Mn
Mn
Ni
Mn
Fe
Fe
C H
6
H
H
H
NO2
H
H
Cl
—
Cl
Cl
—
Cl
Cl
Cl
Cl
Cl
9
11
95
42
8
20
15
6
4
4
4
4
4
C
C
6
H
H
6
C H
6
6
C H
(CH
(CH2)2
2
)
2
H
C
6
H
4
—
—
—
Mn
Fe
(CH
(CH2)2
2
)
2
24
13
a
Reaction conditions: 4-phenyl derivative of 1,4-dihydropyridines (1 mmol),
TBAO (2 mmol), catalyst (0.067 mmol), and CH Cl (10 mL).
2
2
b
Isolated yield.
‘‘quality pressure’’ sensor for flammable organic solvents, and Atcfo
fiber-optic system for automatic temperature control.
General Procedure for Oxidation of 1,4-Dihydropyridines (DHPs) with
TBAO Catalyzed by Manganese(III) Schiff Base Complex Under
Mechanical Stirring at Room Temperature
All reactions were carried out at room temperature in a 25-mL flask
equipped with a magnetic stirring bar. A solution of TBAO (2 mmol)
in CH Cl (5 mL) was added to a mixture of Hantzsch DHPs (1 mmol)
2
2
and Mn–salophen (0.067 mmol) in CH Cl (5 mL). The progress of
2
2
the reaction was monitored by thin-layer chromatography (TLC). After
the reaction was complete, the reaction mixture was filtered and purified
on a silica-gel plate or a silica-gel column (eluent: CCl –Et O). The
4
2
identities of products were confirmed by melting point (mp), IR, and
1
H NMR spectral data.

1
,4-Dihydropyridine Oxidation by TBAO–Schiff Base
3871
General Procedure for Oxidation of 1,4-Dihydropyridines (DHPs) with
TBAO Catalyzed by Manganese(III) Schiff Base Complex Under
Microwave Irradiation
ꢁ
All reactions were carried out at 53–56 C, with 180 W applied power in a
100-mL, round-bottom flask provided with two openings and equipped
with a glass condenser.
TBAO (2 mmol) and Mn–salophen (0.067 mmol) were added to a
mixture of Hantzsch DHP (1 mmol) in CH Cl (10 mL), and the mixture
2
2
was irradiated with MW for the appropriate time. After completion of
the reaction (monitored by TLC), the mixture was filtered and purified
on a silica-gel column.
RESULTS AND DISCUSSION
Oxidation of 1,4-Dihydropyridines (DHPs) with TBAO Catalyzed by
Different Metal Schiff Base Complexes
To show the peroxomonosulphate anion activation by metal Schiff base
complexes, we have investigated the influence of the metal center on the
activity of catalysts. Oxidation reactions were carried out with metallosa-
lophen having the same ligand but different metals: Mn, Fe, Co, and Ni
(
Table 1).
The results of the catalytic oxidation of 4-phenyl derivative of DHP
with TBAO in the presence of different Schiff base complexes indicates
that the nature of the metal ion has an important role on the catalytic
0
activity. The most active catalyst is Mn-salophene [N,N -(1,2-
phenylene)bis(salicylaldiminato)manganese(III) chloride] complex, which
showed greater activity in the oxidation of 4-phenyl derivative of DHP
than the Ni, Fe, and Co analog (Table 1).
Effect of Solvent and Oxidant on the Oxidation of 4-Phenyl
Derivative of 1,4-Dihydropyridine (DHP)
Of the dichloromethane, acetonitrile alone, and aqueous solution of metha-
nol, ethanol, acetone, acetonitrile (single-phase systems), chloroform,
dichloromethane, and carbon tetrachloride (two-phase systems in which
TBAO acts as phase-transfer catalyst), CH Cl was chosen as the reaction
2
2
medium because the metal Schiff base complex is highly soluble in this
solvent, and greater pyridine derivative yields were obtained (Fig. 1). The
effects of other oxidants were also studied in the oxidation of the DHP.

3872
M. Nasr-Esfahani, M. Moghadam, and G. Valipour
Figure 1. Effect of solvent and oxidant on the oxidation of 4-phenyl derivative of
,4-dihydropyridine. Reaction conditions: 4-phenyl derivative of DHP (1 mmol),
oxidant (2 mmol), and catalyst (0.067 mmol).
1
The obtained results showed that TBAO is more effective than H O ,
2
2
NaOCl, t-BuOOH, and ureahydrogen peroxide (UHP) adduct (Fig. 1).
Effect of Axial Ligand on the Oxidation of 4-Phenyl Derivative of
1
,4-Dihydropyridine (DHP)
Addition of a small amount of a nitrogen base as cocatalyst improves the
catalytic ability of Mn Schiff bases in the oxidation reactions. Addition of
an axial base in biomimetic systems using metalloporphyrins and Schiff
base complexes as catalysts is necessary to obtain high catalytic
[
33]
activity.
Interestingly, in this catalytic system [Mn(III)–salophen=TBAO],
more catalytic activity is observed in the absence of imidazole. Indeed,
when imidazole is added as axial ligand to this catalytic system, the
reaction times become longer in the oxidation of DHPs. For instance,
the oxidation of 4-phenyl and 4-chlorophenyl derivatives was completed
in 50 and 40 min, respectively. Addition of imidazole as cocatalyst led to
longer reaction times: 85 and 70 min for 4-phenyl and 4-chlorophenyl
derivatives, respectively. These observations show that DHP can play
the axial ligand role.
Oxidation of 1,4-Dihydropyridine (DHP) Derivatives with TBAO
Catalyzed by Mn(III)–Salophen Complex Under Mechanical Stirring
Initially, the catalytic oxidation of 4-phenyl derivative of DHP with TBAO
in CH Cl was investigated. The results show that Mn(III)–salophen
2
2

1
,4-Dihydropyridine Oxidation by TBAO–Schiff Base
3873
efficiently catalyzes the oxidation of 4-phenyl derivatives of DHP with
TBAO at room temperature. The Mn(III)–salophen=TBAO catalytic sys-
tem was used for oxidation of a wide variety of DHP derivatives (1) bear-
ing an alkyl or an aryl group to their corresponding pyridine derivatives
in excellent yields at room temperature. The results are summarized in
Table 2.
Oxidation of 4-isopropyl and 1-methyl benzyl derivatives (alkyl
moiety may be responsible for generating stable carbocation) was
accompanied by leaving of this substituent and gave dealkylated pyridine
derivatives (3) (entries 9 and 12 in the Table 2), which were previously
reported by Ortiz de Montellano in the oxidation of DHPs by
[34]
cytochrome P-450.
This approach shows that this synthetic model behaves as cyto-
chrome P-450. All reactions were completed during the appropriate time
(
5–60 min as indicated in Table 2) and gave only the corresponding
pyridine derivative. In the absence of Mn(III)–salophen catalyst, TBAO
has poor ability to oxidize DHPs at room temperature (9–14% yields).
Recently, oxidation of DHPs using benzyltriphenylphosphonium
peroxymonosulfate as an oxidant in the presence of BiCl under nearly
3
[
35]
neutral reaction conditions at ambient temperature has been reported.
The obtained results show that when a biomimetic catalyst is used
for oxidation of DHPs, the reaction times decrease and the product
yields increase. This feature show the importance of biomimetic cata-
lyst in the increasing the catalyst efficiency. On the other hand, the
reaction conditions in the presence of these catalysts are milder, which
makes these systems useful in studying the action of cytochrome P-450
enzymes.
In another report, in the oxidation of 4-substituted Hantzsch DHPs
with oxone, a ring-contraction reaction took place, and polysubstituted
[36]
furans were obtained. In the presence of Mn(III) Schiff base complex,
no by-product was observed. This shows the effect of a biomimetic
catalyst that moderates the reaction conditions without producing any
by-product.
Oxidation of 1,4-Dihydropyridine (DHP) Derivatives with TBAO
Catalyzed by Mn(III)–Salophen Complex Under Microwave Irradiation
When the reaction mixture was exposed to MW irradiation, the corre-
sponding pyridine derivatives were obtained in 25–50 s. When the same
reaction was carried out in the absence of catalyst, the reaction times
were longer. For example, the oxidation of 4-phenyl derivatives was
completed in 50 s, whereas in the absence of catalyst this reaction was

3874
M. Nasr-Esfahani, M. Moghadam, and G. Valipour
Table 2. Oxidation of Hantzsch 1,4-dihydropyridines with TBAO catalyzed by
a
Mn(III)–salophen under mechanical stirring and microwave irradiation
Mechanical stirring
Microwave irradiation
Time Yields Yields
b
Time
(s)
Yields
b
(%)
c
Entry DHP
R
(min)
(%)
(%)
1
2
1a
1b
H
30
10
90
96
12
14
50
25
91
95
CH
3
3
1c
50
94
10
50
92
4
5
6
1d
1e
1f
60
40
20
97
91
94
13
9
50
35
25
95
90
91
10
7
8
1g
1h
15
45
89
92
9
25
50
90
93
10
d
d
9
0
1i
1j
12
95
92
12
12
25
92
90
1
40
5
50
25
1
1
1
1
2
3
1k
1l
94
95
96
13
10
14
95
94
94
d
20
d
30
1m
15
10
25
30
1
4
1n
93
12
90
a 1
All products were identified by comparison with authentic samples (IR, H
NMR, mp). Reaction conditions are TBAO (2 mmol), DHP (1 mmol), and
Mn–salophen (0.067 mmol) in CH Cl (10 mL).
2
2
b
Isolated yields.
The yields are in the absence of catalyst.
The product is a dealkylated pyridine derivative.
c
d

1
,4-Dihydropyridine Oxidation by TBAO–Schiff Base
3875
carried out in 80 s. This shows that the Mn catalyst can accelerate the
reaction. The results are summarized in Table 2.
CONCLUSION
Mn(III)–salophen=TBAO catalytic system has the following advantages
in the oxidation of Hantzsch DHPs to their corresponding pyridine
derivatives: (i) short reaction time, (ii) high efficiency, (iii) mild reaction
conditions, (iv) low cost and stability of the oxidant, and (v) solubility of
the oxidant in organic solvents. Therefore, the present method could be a
useful addition to the available methods in organic synthesis.
ACKNOWLEDGMENT
The partial support of this work by Yasouj University Council of
Research is acknowledged.
REFERENCES
1
. (a) Zamponi, G. W.; Stotz, S. C.; Staples, R. J.; Andro, T. M.; Nelson, J. K.;
Hulubei, V.; Blumenfeld, A.; Natale, N. R. Unique structure–activity rela-
tionship for 4-isoxazolyl-1,4-dihydropyridines. J. Med. Chem. 2003, 46, 87–
96; (b) Zarghi, A.; Sadeghi, H.; Fassihi, A.; Faizi, M.; Shafiee, A. Synthesis
and calcium antagonist activity of 1,4-dihydropyridines containing phenyla-
minoimidazolyl substituents. Farmaco 2003, 58, 1077–1081; (c) Peri, R.;
Padmanabhan, S.; Rutledge, A.; Singh, S.; Triggle, D. J. Permanently
charged chiral 1,4-dihydropyridines: Molecular probes of L-type calcium
channels: Synthesis and pharmacological characterization of methyl (x-
trimethylalkylammonium) 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-
pyridinedicarboxylate iodide, calcium channel antagonists. J. Med. Chem.
2000, 43, 2906–2914.
2
. (a) Poindexter, G. S.; Bruce, M. A.; Breitenbucher, J. G.; Higgins, M. A.; Sit,
S. Y.; Romine, J. L.; Martin, S. W.; Ward, S. A.; McGovern, R. T.; Clarke,
W.; Russell, J.; Antal-Zimanyi, I. Dihydropyridine neuropeptide Y Y1 recep-
tor antagonists 2: Bioisosteric urea replacements. Bioorg. Med. Chem. 2004,
12, 507–521; (b) Poindexter, G. S.; Bruce, M. A.; LeBoulluec, K. L.;
Monkovic, I.; Martin, S. W.; Parker, E. M.; Ben, L. G.; McGovern, R. T.;
Ortiz, A. A.; Stanley, J. A.; Mattson, G. K.; Kozlowski, M.; Arcuri, M.;
Antal-Zimanyi, I. Dihydropyridine neuropeptide Y Y1 receptor antagonists.
Bioorg. Med. Chem. Lett. 2002, 12, 379–382.
3
. Eharkar, P. S.; Desai, B.; Gaveria, H.; Varu, B.; Loriya, R.; Naliapara, Y.;
Shah, A.; Kulkarni, V. M. Three-dimensional quantitative structure–activity

3876
M. Nasr-Esfahani, M. Moghadam, and G. Valipour
relationship of 1,4-dihydropyridines as antitubercular agents. J. Med. Chem.
002, 45, 4858–4867.
2
4
. (a) McCormack, J. G.; Westergaard, N.; Kristiansen, M.; Brand, C. L.;
Lau, J. Pharmacological approaches to inhibit endogenous glucose production
as a means of anti-diabetic therapy. Curr. Pharm. Des. 2001, 7, 1451–1474; (b)
Ogawa, A. K.; Willoughby, C. A.; Raynald, B.; Ellsworth, K. P.; Geissler,
W. M.; Myer, R. W.; Yao, J.; Georgianna, H.; Chapman, K. T.
Glucose-lowering in a db=db mouse model by dihydropyridine diacid glyco-
gen phosphorylase inhibitors. Bioorg. Med. Chem. Lett. 2003, 13, 3405–3408.
. (a) Boer, R.; Gekeler, V. Chemosensitizers in tumor therapy: New
compounds promise better efficacy. Drugs Fut. 1995, 20, 499–509; (b)
Sabitha, G.; Kiran Kumar Reddy, G. S.; Srinivas Reddy, C.; Yadav, J. S.
A novel TMSI-mediated synthesis of Hantzsch 1,4-dihydropyridines at
ambient temperature. Tetrahedron Lett. 2003, 44, 4129–4131.
5
6
. (a) Katsuki, T. Mn–salen catalyst, competitor of enzymes, for asymmetric
epoxidation. J. Mol. Catal. A: Chem. 1996, 113, 87–107; (b) Katsuki, T. Cat-
alytic asymmetric oxidations using optically active (salen) manganese(III)
complexes as catalysts. Coord. Chem. Rev. 1995, 140, 189–214.
7. Ortiz de Montellano, P. R. Cytochrome P-450: Structure, Mechanism, and
Biochemistry, 2nd ed.; Plenum Press: New York, 1995.
8
. (a) Routier, S. B.; Bernier, J. L.; Catteau, M. P.; Bailly, C. Highly preferential
cleavage of unpaired guanines in DNA by a functionalized salen–nickel com-
plex. Bioorg. Med. Chem. Lett. 1997, 7, 63–66; (b) Muller, J. G.; Paikoff, S. J.;
Rokita, S. E.; Burrow, C. J. DNA modification promoted by water-soluble
nickel(II) salen complexes: A switch to DNA alkylation. J. Inorg. Biochem.
1994, 54, 199–206; (c) Samide, M. J.; Peters, D. G. Electrochemical reduction
of copper(II) salen at carbon cathodes in dimethylformamide. J. Electroanal.
Chem. 1998, 443, 95–102; (d) Mirkhani, V.; Tangestaninejad, S.; Moghadam,
M.; Moghbel, M. Rapid and efficient oxidative decarboxylation of carboxylic
acids with sodium periodate catalyzed by manganese(III) Schiff base com-
plexes. Bioorg. Med. Chem. 2004, 12, 903–906; (e) Puglisi, A.; Tabbi, G.;
Vecchio, G. Bioconjugates of cyclodextrins of manganese salen-type ligand
with superoxide dismutase activity. J. Inorg. Biochem. 2004, 98, 969–976.
. (a) Palucki, M.; McCormick, G. J.; Jacobsen, E. N. Low temperature
asymmetric epoxidation of unfunctionalized olefins catalyzed by (salen)-
Mn(III) complexes. Tetrahedron Lett. 1995, 36, 5457–5460; (b) Adam, W.;
Jeco, J.; Levai, A.; Nemes, C.; Patonay, T.; Sebok, P. Enantioselective epox-
idation of 2,2-dimethyl-2H-chromenes by dimethyldioxirane and Jacobsen’s
Mn(III) salen catalysts. Tetrahedron Lett. 1995, 36, 3669–3672; (c) Linker,
T. The Jacobsen-Katsuki epoxidation and its controversial mechanism.
Angew. Chem., Int. Ed. Engl. 1997, 36, 2060–2062; (d) Irie, R.; Hashihayata,
T.; Katasuki, T.; Akita, M.; Moro-oka, M. X-ray structures of chiral (sale-
n)manganese(III) complexes: Proof of pliability of the salen ligand. Chem.
Lett. 1998, 1041–1042; (e) Hamada, T.; Fukuda, H.; Katsuki, T. Mechanism
of one oxygen atom transfer from oxo (salen)manganese(V) complex to ole-
fins. Tetrahedron 1996, 52, 515–530.
9

1
,4-Dihydropyridine Oxidation by TBAO–Schiff Base
3877
1
0. (a) Adam, W.; Roschmann, K. J.; Saha-Moller, C. R.; Seebach, D.
cis-Stilbene and (1a,2b,3a)-(2-ethenyl-3-methoxycyclopropyl)benzene as
mechanistic probes in the Mn(III)(salen)-catalyzed epoxidation: Influence of
the oxygen source and the counterion on the diastereoselectivity of the com-
petitive concerted and radical-type oxygen transfer. J. Am. Chem. Soc. 2002,
124, 5068–5073; (b) Campbell, K. M.; Lashley, M. R.; Wayatt, J. K.; Nantz,
M. H.; Britt, R. D. Dual-mode EPR study of Mn(III) salen and the Mn(III)
salen-catalyzed epoxidation of cis-b-methylstyrene. J. Am. Chem. Soc. 2001,
123, 5710–5719.
¨
1. (a) Ohberg, L.; Westman, J. An efficient and fast procedure for the Hantzsch
dihydropyridine synthesis under microwave conditions. Synlett 2001, 1296–
1
1298; (b) Zolfigol, M. A.; Safaiee, M. Synthesis of 1,4-dihydropyridines under
solvent-free conditions. Synlett 2004, 827–828.
1
1
2. Vanden Eynde, J. J.; Mayence, A.; Maquestiau, A. A novel application of the
oxidizing properties of pyridinium chlorochromate: Aromatization of
Hantzsch 1,4-dihydropyridines. Tetrahedron 1992, 48, 463–468.
3. Sabitha, G.; Kumar Reddy, G. S. K.; Reddy, C. S.; Fatima, N.; Yadav, J. S.
3 4
Zr(NO ) : A versatile oxidizing agent for aromatization of Hantzsch 1,4-
dihydropyridines and 1,3,5-trisubstituted pyrazolines. Synthesis 2003, 1267–1271.
4. Pfister, J. R. Rapid, high-yield oxidation of Hantzsch-type 1,4-dihydropyri-
dines with ceric ammonium nitrate. Synthesis 1990, 689–690.
5. Anniyappan, M.; Muralidharan, D.; Paramasivan, P. T. A novel application
of the oxidizing properties of urea nitrate and peroxydisulfate–cobalt(II):
Aromatization of NAD(P)H model Hantzsch 1,4-dihydropyridines. Tetrahe-
dron 2002, 58, 5069–5073.
1
1
1
6. Nakamichi, N.; Kawashita, Y.; Hayashi, M. Oxidative aromatization of
1,3,5-trisubstituted pyrazolines and Hantzsch 1,4-dihydropyridines by Pd=C
in acetic acid. Org. Lett. 2002, 4, 3955–3957.
7. (a) Memarian, H. R.; Sadeghi, M. M.; Aliyan, H. Photochemistry of some
1
1,4-dihydropyridine derivatives: Part I. Indian J. Chem. 1998, 37B, 219–
223; (b) Memarian, H. R.; Abdoli-Senejani, M.; Tangestaninejad, S. Photo-
sensitized oxidation of unsymmetrical 1,4-dihydropyridines. J. Iran. Chem.
Soc. 2006, 3, 285–292; (c) Zhang, D.; Wu, L. Z.; Zhou, L.; Han, X.; Yang,
Q. Z.; Zhang, L. P.; Tung, C. J. Photocatalytic hydrogen production from
Hantzsch 1,4-dihydropyridines by platinum(II) terpyridyl complexes in
homogeneous solution. J. Am. Chem. Soc. 2004, 126, 3440–3441.
1
8. (a) Nasr-Esfahani, M.; Moghadam, M.; Tangestaninejad, S.; Mirkhani, V.
Biomimetic oxidation of Hantzsch 1,4-dihydropyridines with tetra-n-buty-
lammonium periodate catalyzed by tetraphenyl porphyrinatomanganese(III)
chloride [Mn(TPP)Cl]. Bioorg. Med. Chem. Lett. 2005, 15, 3276–3278; (b)
Nasr-Esfahani, M.; Moghadam, M.; Tangestaninejad, S.; Mirkhani, V.;
Momeni, A. R. Rapid and efficient oxidation of Hantzsch 1,4-dihydropyri-
dines with sodium periodate catalyzed by manganese(III) Schiff base com-
plexes. Bioorg. Med. Chem. 2006, 14, 2720–2724; (c) Moghadam, M.;
Nasr-Esfahani, M.; Tangestaninejad, S.; Mirkhani, V.; Zolfigol, M. A. Bio-
mimetic aromatization of Hantzsch 1,4-dihydropyridines with sodium

3878
M. Nasr-Esfahani, M. Moghadam, and G. Valipour
periodate catalyzed by a new polystyrene-bound manganese porphyrin. Can.
J. Chem. 2006, 84, 1–4; (d) Moghadam, M.; Nasr-Esfahani, M.;
Tangestaninejad, S.; Mirkhani, V. Mild and efficient oxidation of Hantzsch
1,4-dihydropyridines with sodium periodate catalyzed by a new polystyrene-
bound Mn(TPP)Cl. Bioorg. Med. Chem. Lett. 2006, 16, 2026–2030; (e)
Montazerozohori, M.; Karami, B.; Nasr-Esfahani, M.; Musavi, S. A. Silver
salts=iodine monochloride as a new oxidation system for the oxidative aro-
matization of 1,4-dihydropyridines. Heterocycl. Commun. 2007, 13, 289–295.
9. (a) Zolfigol, M. A.; Kiany-Borazjani, M.; Sadeghi, M. M.; Mohammadpoor-
Baltork, I.; Memarian, H. R. An efficient method for the oxidation of
Hantzsch 1,4-dihydropyridines to their corresponding pyridine derivatives
under mild and heterogeneous conditions. Synth. Commun. 2000, 30, 551–558;
1
(
d) Zolfigol, M. A.; Kiany-Borazjani, M.; Sadeghi, M. M.; Mohammadpoor-
Baltork, I.; Memarian, H. R. Aromatization of 1,4-dihydropyridines under mild
and heterogeneous conditions. Synth. Commun. 2000, 30, 3919–3923; (e)
Zolfigol, M. A.; Bagherzadeh, M.; Niknam, K.; Shirini, F.; Mohammadpoor-
Baltork, I.; Ghorbani Choghamarani, A.; Baghbanzadeh, M. Oxidation of
1,4-dihydropyridines under mild and heterogeneous conditions using solid
acids. J. Iran. Chem. Soc. 2006, 3, 73–80.
2
0. Nakamichi, N.; Kawashita, Y.; Hayashi, M. Activated carbon-promoted oxi-
dative aromatization of Hantzsch 1,4-dihydropyridines and 1,3,5-trisubsti-
tuted pyrazolines using molecular oxygen. Synthesis 2004, 1015–1020.
1. (a) Delgado, F.; Alvarez, C.; Garcia, O.; Penieres, G.; Marquez, C. Unusual
oxidative dealkylation of certain 4-alkyl-1,4-dihydropyridines with
2
MnO
(
2
=bentonite using microwave irradiation, in the absence of solvent
II). Synth. Commun. 1991, 21, 2137–2141; (b) B o¨ ker, R. H.; Guengerich,
F. P. Oxidation of 4-aryl- and 4-alkyl-substituted 2,6-dimethyl-3,5-
bis(alkoxycarbonyl)-1,4-dihydropyridines by human liver microsomes and
immunochemical evidence for the involvement of a form of cytochrome
P-450. J. Med. Chem. 1986, 29, 1596–1603.
2
2
2
2
2. Starks, C.; Liotta, C.; Halpern, M. Phase Transfer Catalysis: Fundamentals,
Applications, and Industrial Perspective; Chapman & Hall: New York, 1994.
3. Trost, B. M.; Braslau, R. Tetra-n-butylammonium oxone: Oxidations under
anhydrous conditions. J. Org. Chem. 1988, 53, 532–537.
4. Meunier, B. Metalloporphyrins as versatile catalysts for oxidation reactions
and oxidative DNA cleavage. Chem. Rev. 1992, 92, 1411–1456.
5. Strukul, G.; Sinigalia, R.; Zanardo, A.; Pinna, F.; Michelin, R. A. Selective
oxidations of olefins catalyzed by platinum(II) complexes: Use of tert-butyl
hydroperoxide and potassium caroate as oxidants: Ketone vs. epoxide forma-
tion. Inorg. Chem. 1989, 28, 554–559.
26. Wessel, J.; Crabtree, R. H. Nonradical tetrabutylammonium monopersulfate
3 4 4 2 2 4 4
oxidation of hydrocarbons catalyzed by [Mn O bipy (H O) ](ClO ) . J. Mol.
Cat. A: Chem. 1996, 113, 13–22.
7. Mohajer, D.; Iranpoor, N.; Rezaeifard, A. Simple and highly efficient synth-
2
esis of oxaziridines by tetrabutylammonium oxone. Tetrahedron Lett. 2004,
45, 631–634.

1
,4-Dihydropyridine Oxidation by TBAO–Schiff Base
3879
2
8. Mohajer, D.; Rezaeifard, A. Efficient oxygenation of hydrocarbons with
tetrabutylammonium monopersulfate catalyzed by manganese meso-
tetraphenylporphyrin in the presence of imidazole. Tetrahedron Lett. 2002,
43, 1881–1884.
2
9. Iranpoor, N.; Mohajer, D.; Rezaeifard, A. R. Rapid and highly chemoselective
biomimetic oxidation of organosulfur compounds with tetrabutylammonium
peroxymonosulfate in the presence of manganese meso-tetraphenylporphyrin
and imidazole. Tetrahedron Lett. 2004, 45, 3811–3815.
3
0. Trost, B. M.; Braslau, R. Tetra-n-butylammonium oxone: Oxidations under
anhydrous conditions. J. Org. Chem. 1988, 53, 532–537.
3
1. Boucher, L. J. Manganese Schiff’s base complexes (II): Synthesis and spectro-
scopy of chloro-complexes of some derivatives of (salicylaldehydeethylenedii-
mato)manganese(III). J. Inorg. Nucl. Chem. 1974, 36, 531–536.
3
2. (a) Srinivasa, K.; Michaud, P.; Kochi, J. K. Epoxidation of olefins with catio-
nic (salen)Mn(III) complexes: The modulation of catalytic activity by substi-
tuents. J. Am. Chem. Soc. 1986, 108, 2309–2320; (b) Rihter, B.; Masnovi, J.
0
Oxidation of alkynes and ylides by oxo(salen)chromium(V)(salen ¼ N,N -
ethylenebis-salicylideneiminato)trifluoromethane sulphonate. J. Chem. Soc.,
Chem. Commun. 1988, 35–37; (c) Chellamani, A.; Alhaji, N. M. I.; Rajagopal,
S.; Sevvel, R.; Srinivasan, C. Mechanism of oxidation of organic sulphides by
oxo(salen)manganese(V) complexes. Tetrahedron 1995, 51, 12677–12698; (d)
Chellamani, A.; Alhaji, N. M. I.; Rajagopal, S. Applicability and mathema-
tical verification of the reactivity–selectivity principle in the oxidation of
thioanisoles by oxo(salen)manganese(V) complexes. J. Chem. Soc., Perkin.
Trans. 2 1997, 299–302; (e) Koola, J.; Kochi, J. K. Nickel catalysis of olefin
epoxidation. Inorg. Chem. 1987, 26, 908–916; (f) Chen, D.; Martell, A. E.
Dioxygen affinities of synthetic cobalt Schiff base complexes. Inorg. Chem.
1987, 26, 1026–1030; (g) Trivedi, B. M.; Bhattacharya, P. K.; Ganeshpure,
P. A.; Satish, S. Epoxidation of olefins catalysed by Mn(III)-Schiff base
complexes. J. Mol. Cat. 1992, 5, 109–115.
3
3
3. (a) Collman, P. J.; Zeng, L.; Brauman, I. J. Donor ligand effect on the nature
of the oxygenating species in Mn(III)(salen)–catalyzed epoxidation of olefins:
Experimental evidence for multiple active oxidants. Inorg. Chem. 2004, 43,
2672–2679; (b) Gross, Z.; Ini, S. Remarkable effects of metal, solvent, and
oxidant on metalloporphyrin-catalyzed enantioselective epoxidation of ole-
fins. J. Org. Chem. 1997, 62, 5514–5521.
4. Ortiz de Montellano, P. R.; Beilan, H. S.; Kunze, K. L. N-
Alkylprotoporphyrin IX formation in 3,5-dicarbethoxy-1,4-dihydrocollidine
treated rats: Transfer of the alkyl group from the substrate to the porphyrin.
J. Biol. Chem. 1981, 256, 6708–6713.
3
5. Adibi, H.; Hajipour, A. R. 1,4-Dihydropyridines using benzyltriphenylpho-
sphonium peroxymonosulfate under almost neutral reaction conditions.
Bioorg. Med. Chem. Lett. 2007, 17, 1008–1012.
3
6. Liu, Z.; Yu, W.; Yang, L.; Liu, Z.-L. A novel oxidation–ring contraction of
Hantzsch 1,4-dihydropyridines to polysubstituted furans. Tetrahedron Lett.
2007, 48, 5321–5324.