Catalytic oxidation of 1,4-dihydropyridins by tetrabutylammonium periodate in the presence of manganese amino acid Schiff base

Article abstract of DOI:10.3184/030823407X227615

The amino acid Schiff base manganese complex (Tryp-Mn); 1, was prepared with L-tryptophan, salicylaldehyde and Mn(OAc)₂.4H₂O in methanol. In the presence of 1, 1,4-dihydropyridines (1,4-DHPs) were oxidised by n-Bu₄NIO

Full text of DOI:10.3184/030823407X227615

JOURNAL OF CHEMICAL RESEARCH 2007
JULY, 415–417
RESEARCH PAPER 415
Catalytic oxidation of 1,4-dihydropyridins by tetrabutylammonium
periodate in the presence of manganese amino acid Schiff base
Gholam Reza Karimipour*, Masoud Nasr-Esfahani and Ghasem Valipour
Department of Chemistry, Yasouj University, Yasouj 75914-353, Iran
The amino acid Schiff base manganese complex (Tryp–Mn); 1, was prepared with L-tryptophan, salicylaldehyde
and Mn(OAc)2.4H2O in methanol. In the presence of 1, 1,4-dihydropyridines (1,4-DHPs) were oxidised by n-Bu4NIO4
to the corresponding pyridine derivatives in high yields. Imidazole was used as an additive to improve the catalytic
oxidation.
Keywords: amino acid Schiff base, 1,4-dihydropyridine, tetrabutylammonium periodate, oxidation
O
Hantzsch 1,4-dihydropyridines (1,4-DHPs) are the
O
N
analogues of NADH coenzymes known as Ca2+ channel
blockers.1 They have received most attention because of
their relevant applications in various cardiovascular diseases
and hypertension, and of their pharmacological activity in
antioxidant protective effects.2 4-substituted-2,6-dimethyl-
3,5-pyridine dicarboxylic acid diethyl esters have anti-
hypoxic and anti-ischemic behaviours. Moreover, Hantzsch
1,4-DHPs are important agents for organic synthesis. For
example, various novel dihydroindolizine-based compounds
were synthesised using 2-formyl-1,4-DHP by the Michael
addition/intramolecular amino-nitrile cyclisation method.3
The oxidation of 1,4-DHPs is also one of the ubiquitous
issues in organic chemistry. Various methods were employed
for this purpose including oxidation with ferric nitrate on a
solid support,4 ceric ammonium nitrate,5 Claycop,6 pyridinium
chlorochromate,7 nitric acid,8 nitric oxide and N-methyl-N-
nitrosotoluene-P-sulfonamide.9 Recently, periodate has been
used extensively in oxidation of 1,4-DHPs in the presence of
metalloporphyrin catalysts.10-13
H2N CH C OH
OHC
HO
OH
O
H2C
MeOH
+
HN
HN
OAc
Mn
O
N
O
Mn(OAc)2.4H2O
MeOH
O
HN
1
Scheme 1 Synthesis of the Schiff base ligand and the
Tryp–Mn complex (1).
Oxidative dehydrogenation of 1,4-DHPs
Tetrabuthylammonium periodate (n-Bu4NIO4), soluble in
chlorinated organic solvents, is used as a neutral weak oxidant
for sulfides, α-bromoketones and α-hydroxycarboxylic
acids.15 However, it can serve as a potent monooxygen donor
by combining with metalloporphyrin catalysts, simulating the
function of P-450.16
We now report the room temperature oxidation of 1,4-
DHPs with tetrabutylammonium periodate (n-Bu4NIO4)
to their corresponding pyridine derivatives catalysed by a
L-tryptophan-base manganese(III) complex (Tryp–Mn);
1 (Fig. 1) in CH2Cl2.
As a continuation of our studies on the oxidative
decarboxylation of diphenylacetic acid17 and epoxidation of
alkenes with periodates,18 we now report the oxidation of
Hantzsch 1,4-DHPs to the corresponding pyridine derivatives
by n-Bu4NIO4 in the presence of 1 as catalyst. By control
experiments employing different solvents and their selected
mixtures, CH2Cl2/DMF (90/10) was chosen as the expedient
solvent due to the facile solvation of starting materials,
oxidant and 1 in this mixed solvent. DMF is necessary because
CH2Cl2 has very little capability to solve the complex. We first
confirmed that the oxidative dehydrogenation of 1,4-DHPs
does not proceed by n-Bu4NIO4 alone. Furthermore, the
reactions are not affected even if performed in the presence
of the simple Mn(OAc)3.2H2O and Mn(OAc)2.4H2O salts.
The efficiency of 1 as catalyst was then tested by changing its
concentration in the reaction mixture. We found that the yields
reach in a maximum value when the 1/DHP ratio was 1/2.
It is notable that the catalytic activity of 1 increased during
the reactions. It seems that the produced pyridine derivatives
act as axial ligands for the catalyst, leading to acceleration
of the oxidation during the course of the reactions. This
hypothesis was confirmed by adding a nitrogenous donor
such as imidazole into the reaction mixture. We found that the
oxidation rate was 1.3 times that of no imidazole. Nitrogenous
ligands such as imidazoles and pyridines are reported to
improve selectivity, reactivity and turnover number of
metalloporphyrin-mediated reactions, leading to weakening of
the M–O bond in the oxidised form of the porphyrin catalysts
by donating electron density into the M–O antibonding
orbitals, which can account for the improved reactivity.19
Results and discussion
The ligand and manganese(III) complex (Tryp–Mn) (1) were
synthesised according to Wong et al. (Scheme 1).14 The IR
spectrum (KBr) of 1 was compared with that of the free ligand
to determine the changes that might have taken place during the
complexation. The results show that vibration absorption bands
appear at 1616 cm-1(υas COO), 1410 cm-1 (υs COO), 1635 (υ C=N
and 1249 cm-1 (υ Ph-O) for the amino acid Schiff base ligand.
)
The metal ion coordination caused a dramatic change in
COO, C=N and Ph-O vibrations, leading to changes of their
characteristic frequencies to 1600, 1376, 1625 and 1236 cm-1
respectively. Moreover, bands at 548 cm-1 and 441 cm-1 appear
in the complex and are attributed to the Mn–N and Mn–O
stretching vibrations, respectively. These structural data are
nicely consistent with the results obtained by Wong et al.14
OAc
O
Mn
O
N
O
HN
1
* Correspondent. E-mail:ghkar@mail.yu.ac.ir
PAPER: 07/4658

416 JOURNAL OF CHEMICAL RESEARCH 2007
n-Bu4NIO4, Im
H
R
R
EtOOC
Me
COOEt
(Tryp-Mn) / n-Bu4NIO4, Im
COOEt
Me
EtOOC
O
O
N
O
N
Me
N
H
N
O
Mn
Me
O
Mn
CH2Cl2/DMF, RT
O
O
Im
I
HN
HN
H
EtOOC
Me
COOEt
Me
1,4-DHP's
H
R
COOEt
Me
EtOOC
+
R
N
N
EtOOC
Me
COOEt
Me
Me
N
H
II
O
Scheme 2
O
N
Mn
Im
O
O
When acetic acid was added as the additive into the oxidation
systems, formation of the pyridine products is completely
retarded. It seems that the nitrogenous ligand is bound to the
Mn centre during the course of the reactions.
The coordinated nitrogenous bases (i.e. imidazole and/or
produced pyridines) aid the possible electronic changes in the
Mn centre in the proposed catalytic cycle shown in Scheme 3,
leading to facile formation of the pyridine products. Addition
of n-Bu4NIO4 and imidazole into the reaction mixture caused
the generation of an imidazolated, high-valent, manganese
oxo complex.
The oxidation was preceded by an electrophilic attack of oxo
ligand to the N–H hydrogen atom, followed by a concomitant
elimination of the hydrogen atom on the 4-position of the 1,4-
DHPs as shown in Scheme 3.
It is important to note that dealkylation of 4-alkyl substituted
1,4-DHPs can be explained by this simple catalytic cycle. So,
the elimination of the R groups on 4-position of 1,4-DHPs
could lead the formation of dealkylated pyridine derivatives
(Scheme 2).
HN
Scheme 3 A simple proposed catalytic cycle for oxidation of
1,4-DHPs by the n-Bu4NIO4/Tryp–Mn/Im system.
Initially, in order to show the periodate anion activation
by 1, the catalytic oxidation of 4-phenyl derivative of 1,4-
dihydropyridine with n-Bu4NIO4 in the presence of imidazole
was investigated. The obtained results showed that this
complex is an efficient catalyst in the oxidation of 4-phenyl
derivative of 1,4-dihydropyridine with n-Bu4NIO4 at room
temperature.
The Tryp–Mn/n-Bu4NIO4 catalytic system can be used for
oxidising a wide variety of 1,4-dihydropyridine derivatives
bearing an alkyl or aryl group to their corresponding pyridine
derivatives in good to excellent yields at room temperature
in the presence of imidazole as axial ligand. As shown in
Table 1, oxidation of a 4-(1-methyl-1-phenyl) derivative (alkyl
moiety may be responsible for generating stable carbocation) was
Table 1 Oxidation of Hantzsch 1, 4-dihydropyridines with n-Bu4NIO4 catalysed by Tryp–Mn (1)a
Entry
R
Time/min
Yield/%c
92
1
H
10
2
CH3
15
95
3
4
120
45
94
92
Cl
5
6
20
25
91
93
O2N
NO2
O2N
7
8
9
70
180b
70
95
93
92
CH3
MeO
10
11
50
48
94
95
N
O
aAll products were identified by comparison with authentic samples (IR, 1H NMR, m.p.).
bThe product is a dealkylated pyridine derivative.
cIsolated yields.
PAPER: 07/4658

JOURNAL OF CHEMICAL RESEARCH 2007 417
2
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accompanied by expulsion of this substituent to give the dealkyl-
ated pyridine derivative (entry 8). All reactions were completed
during the appropriate time and gave only the corresponding
pyridine derivative. In the absence of Tryp–Mn catalyst,
n-Bu4NIO4 has poor ability to oxidise 1,4-dihydropyridines at
room temperature (7–12% yields; not shown).
3
4
5
6
Experimental
7
L-tryptophan, salicylaldehyde, Mn(OAc)2.4H2O and n-Bu4NIO4 were
obtained from Aldrich and were used without further purification.
All Hantzsch 1,4-dihydropyridines were synthesised by the reported
procedures.20 IR and NMR spectra were measured on Shimadzu IR-
435 and BruckerAW DPX 250 spectrometers, respectively. The Schiff
base ligand and Tryp–Mn 1 were synthesised in a manner similar to
that described by Wong et al.14 However, the complex synthesis was
achieved under Argon.
8
9
10 M. Nasr-Esfahani, M. Moghadam, S. Tangestaninejad and V. Mirkhani,
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2006, 605.
General procedure
In a 10 ml round bottom flask were added in order: 1,4-DHP
(0.5 mmol), Tryp–Mn 1 (0.001 mmol) imidazole (0.05 mmol) in
CH2Cl2/DMF (90/10). The reaction mixture was stirred until the
complete dissolution of chemicals. Tetrabutylammonium periodate
(0.55 mmol) was then added to began the oxidation. The mixture was
stirred thoroughly for the required time at ambient temperature in air.
The products were separated by a simple flash chromatography and
analysed.
18 D. Mohajer, G.R. Karimipour and M. Bagherzadeh, New J. Chem., 2004,
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Received 21 May 2007; accepted 4 July 2007
Paper 07/4658 doi: 10.3184/030823407X227615
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PAPER: 07/4658