Efficient one-pot four-component synthesis and X-ray crystallographic structure of 2-pyridone derivatives

Article abstract of DOI:10.1002/jhet.1632

A series of 3-cyano-2-pyridone derivatives were synthesized by one-pot four-component condensation reaction involving a benzaldehyde derivative, alkyl cyanoacetate, acyclic or cyclic ketones, and ammonium acetate in reflux condition. The X-ray structure of the products 5a and 5d confirm symmetric dimers via hydrogen bonding interactions between individual pyridine molecules showing, in addition, also π-π stacking interactions.

Full text of DOI:10.1002/jhet.1632

Month 2013
Efficient One-Pot Four-Component Synthesis and X-ray Crystallographic
Structure of 2-Pyridone Derivatives
Saeed Balalaie, Mohammed M. Hashemi, S. Hadi Khezri, Frank Rominger, Elmira Ghabraie, and Thomas Oeser
a
b
b
c
a
c
*
aPeptide Chemistry Research Center, K. N. Toosi University of Technology, P.O. Box 15875-4416, Tehran, Iran
bDepartment of Chemistry, Sharif University of Technology, P.O. Box 11365-9516, Tehran, Iran
cOrganisch-Chemisches Institut der Universität Heidelberg, Im Neuenheimer Feld 270, D-69120 Heidelberg, Germany
*
E-mail: balalaie@kntu.ac.ir
Received October 9, 2011
DOI 10.1002/jhet.1632
Published online 00 Month 2013 in Wiley Online Library (wileyonlinelibrary.com).
Dedicated to Professor Mohammad Hadi Khorghami on the occasion of his 75th birthday.
R3
H
R3
R2
O
R2
R1
CN
O
CN
2
Method A or B
CO2R4
R1
O
N
H
4
1
CH3CO2NH4
5 a-q
3
A: EtOH, Reflux, O2 Yields =18-95%
B: Solvent-free condition Yields =52-96%
A series of 3-cyano-2-pyridone derivatives were synthesized by one-pot four-component condensation
reaction involving a benzaldehyde derivative, alkyl cyanoacetate, acyclic or cyclic ketones, and ammonium
acetate in reflux condition. The X-ray structure of the products 5a and 5d confirm symmetric dimers via
hydrogen bonding interactions between individual pyridine molecules showing, in addition, also p–p stack-
ing interactions.
J. Heterocyclic Chem., 00, 00 (2013).
INTRODUCTION
The 2-pyridone skeleton with the cis-amide substructure
provides an ideal structure for bifunctional catalysis and
also supramolecular structures. In addition, the 2-pyridone
exists in two tautomeric forms as an amide (A) and as
2-hydroxypyridine (B). The ratio of these forms depends
to the surrounding medium [10] (Scheme 1).
These facts led us to develop a new synthetic method for
the synthesis of a new series of highly substituted 3-cyano-
2-(1H)-pyridone derivatives and to study the crystalline
structure of differently substituted compounds.
There are several methods for the synthesis of 2-pyridones
[11], and they can be categorized by the following types: (1)
condensation of cyanoacetamide with 1,3-diketones [12], (2)
condensation of enamines with alkyl acetylenecarboxylates
[13], (3) oxidation of pyridine compounds [10], and (4)
diazotation of 2-aminopyridine derivatives [14]. However,
these methods show limitations, and none o them is suitable
for the synthesis of 3-cyano-4-aryl-5,6-dialkyl(aryl)-2-
(1H)-pyridone derivatives. Some methods involve harsh
conditions and can be incompatible with sensitive
functional groups.
The synthesis of 3-cyano-2-(1H)-pyridone derivatives
has been reported in a series of publications [4,15] dealing
with Michael condensation of alkyl cyanoacetate or
cyanoacetamide [3,16] with a, b-unsaturated ketones.
Multistep reactions, complex synthetic materials, using of
2-Pyridones as heteroaromatic compounds play an
important role in bioactive systems and are of significant
interest in current medicinal chemistry [1]. These
compounds show diverse pharmacological activities such
as anti-inflammatory, analgestic, antipyretic, b-adrenolytic,
antimicrobial, and antihypertensive activities [2–4].
Some of 2-pyridone derivatives reveal calcium antago-
nistic activity and are Ikappa B kinase (IKK) inhibitors.
Current medical research shows that substituted 2-(1H)
pyridones act as inhibitor of DNA-dependent protein
kinase [5] and also were identified as a primary hit of
IKK-b inhibitors [6]. Some of the 2-pyridone deriva-
tives were developed with high affinity for the benzodi-
azepine binding site of human g-amino butyric acid
receptor ion channels [7]. Meanwhile, 2-pyridones are
important and useful intermediates in preparing a variety
of heterocyclic compounds, and they are versatile
synthetic intermediates for the synthesis of alkaloids,
drugs, and herbicides. Many 2-pyridone derivatives have
been reported to exhibit antiproliferative activity against
intraperitoneally implanted P388 or L1210 lymphocyclic
leukemia in mice [8]. 2-Pyridones were proposed as an
advantageous alternative to classic digitalis glycosides for
the acute treatment of congestive heart failure [9].
© 2013 HeteroCorporation

S. Balalaie, M. M. Hashemi, S. H. Khezri, F. Rominger, E. Ghabraie, and T. Oeser
Vol 000
Table 1
Scheme 1
Four-component reaction of cyclohexanone, benzaldehyde, ammonium
acetate, and methyl cyanoacetate for the synthesis of 2-pyridone 5q.
N
H
O
N
OH
Entry
Solvent
Yield (%)
1
2
3
4
5
Solvent-free
EtOH
MeCN
Dioxan
THF
82
78
60
67
–
A
B
harmful organic solvents, harsh reaction conditions, and
tedious work-up procedures and also doing of reaction on
the surface of Wang’s resin were reported in other methods
[17,3]. Thus, there is a great need to develop a more effec-
tive and milder process with good functional compatibility.
In continuation of our interest on the one-pot multicompo-
nent reactions for the synthesis of various heterocyclic
compounds of biological importance [18], 3-cyano-4-aryl-
5,6-alkyl- or -aryl 2-(1H)-pyridones were simply constructed
using a one-pot coupling reaction of four components, alkyl
cyanoacetate, aromatic and heteroaromatic aldehyde deriva-
tives, alkyl ketones, and ammonium acetate in ethanol under
reflux or solvent-free conditions (Scheme 2). Meanwhile, the
X-ray structure of these compounds has been investigated.
Table 2
Synthesis of 2-pyridone derivatives via one-pot four-component conden-
sation refluxing in ethanol.
Entry
R1
R2
R3
R4
Yield (%)a
5a
5b
5c
5d
5e
5f
5g
5h
5i
5j
5k
5l
5m
5n
5o
5p
5q
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Ph
Ph
Ph
Ph
Ph
Ph
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Et
Et
Et
Et
Me
Me
57
38
21
35
32
88
74
54
94
81
95
34
27
18
22
89
78
4-Cl-C6H4
4-Me-C6H4
3-NO2-C6H4
4-NO2-C6H4
Ph
4-Cl-C6H4
2-furyl
2-pyridyl
4-pyridyl
2-thienyl
Ph
3-NO2-C6H4
Ph
Ph
RESULTS AND DISCUSSION
i-Bu
i-Bu
Pr
Initially, we began our studies with four-component
reaction of cyclohexane, ammonium acetate, benzaldehyde,
and methyl cyanoacetate as model reaction. The model
reaction was carried out in different solvents and also
solvent-free conditions. The experimental results are
summarized in Table 1.
As can be seen in Table 1, carrying out the reaction in
EtOH had better yield, and because of this result, we used
it as reaction media for one-pot four-component reaction of
different ketones (1), aromatic aldehydes (2), ammonium
acetate (3), and alkyl cyanoacetates (4) refluxing. The
results are given in Table 2. Because of the potential inter-
est in finding versatile procedures, a solvent-free reaction
condition approach was investigated, and the model reaction
for the synthesis of 5q was checked at 80ꢀC in solvent-free
conditions. The product was obtained after 2 h with 82%.
The results for some 2-pyridones (5) are summarized in
Pr
3-NO2-C6H4
4-Cl-C6H4
Ph
À CH2CH2CH2 À
À CH2(CH2)2CH2 À
aYields refer to those of pure isolated products characterized by IR, H
NMR, and 13C NMR spectroscopic data. Reaction time in all reactions
was between 2 and 4 h.
1
Table 3
Synthesis of 2-pyridone derivatives via one-pot four-component
condensation in solvent-free conditions.
Entry
R1
R2
R3
R4
Yield (%)a
5a
5c
5e
5f
5g
5h
5i
5j
5p
5q
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Ph
Ph
Ph
Ph
Ph
Ph
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
74
52
59
92
84
73
96
87
93
82
4-Me-C6H4
4-NO2-C6H4
Ph
4-Cl-C6H4
2-furyl
2-pyridyl
4-pyridyl
4-Cl-C6H4
Ph
Scheme 2
R3
H
À CH2CH2CH2 À
R3
À CH2(CH2)2CH2 À
R2
O
R2
R1
CN
O
CN
aIsolated yields of products.
2
Method A or B
CO2R4
R1
O
N
H
4
Table 3. The model reaction in solvent-free conditions was
investigated at temperatures 40 and 60ꢀC, but the yields
were 50 and 65%, respectively.
One-pot four-component reactions were carried out in
refluxing ethanol. The structures of the products were
1
CH3CO2NH4
5 a-q
3
A: EtOH, Reflux, O2 Yields =18-95%
B: Solvent-free condition Yields =52-96%
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2013
Synthesis of Novel 2-Pyridones
1
established by their IR, H NMR, 13C NMR, HR mass
spectrometry data and by X-ray crystallography. The IR
spectra showed characteristic bands at about 3450 cmÀ1
O2 or further single electron transfer chemistry or even com-
bination with an oxygen species, followed by elimination
[16]. A second possible mechanism is shown in Scheme 4
and involves oxidation of dihydropyridone (11) with reduc-
tion of benzylidene methylcyanoacetate (7) to 2-cyano-3-
phenyl-propionic acid methyl ester (14) [17].
(N-H), 2220 cmÀ1 (CN), 1630–1670 cmÀ1 (CO). The H
1
NMR spectra revealed a broad singlet in the region
d12.5–13 ppm because of the N-H proton. 13C NMR spec-
tra exhibit in the region 117–119 ppm signals for the CN
group and in the region d 160–170 ppm for the CO group.
X-ray crystallography.
Investigation of the X-ray
structure of pyridine derivatives has been studied, and there
are some reports about it [19]. We were able to crystallize
the compounds from chloroform/methanol (1/1) to obtain
crystals of suitable quality for X-ray structural analysis.
The structures of the compounds 5a and 5d were
confirmed by X-ray crystal structure determination. As
shown in Figures 1 and 2, hydrogen atoms in the structures
can be located bonded to the nitrogen atoms, and this
indicates clearly that we have -NH-(C═O), units (1), rather
than -N-(C-OH), units (2). The results show that in both
molecules, the amide structure is prevailing (Scheme 5).
This observation is supported by the bond lengths and
angles found in the hetero ring of structure 5a. The
comparison of the C3-N4-C5 angle (125.3ꢀ) with this angle
for pyridinium (mean 122.5ꢀ) and pyridine (mean 117.3ꢀ)
skeletons shows that the nitrogen atom in the C-N-C unit
is carrying a hydrogen atom, and the comparison of the
C2-C3(O)-N4 angle (114.1ꢀ) with this for phenolate or
ketone (mean 116.0ꢀ) and phenol (mean 120.4ꢀ) skeletons
[19] shows unequivocally that we do not have a phenol
group here.
Mechanism. To understand the reaction mechanism, the
four-component condensation reaction of benzaldehyde,
methyl cyanoacetate, ammonium acetate, and benzyl methyl
ketone was chosen as a model. The reaction may be assumed
to proceed via (1) initial formation of the benzylidene methyl
cyanoacetate (7) (Knoevenagel reaction) which then react
with the benzyl methyl ketone (8) to give the intermediate (9)
or (2) initial formation of chalcone (10) (Aldol condensation
reaction, chalcone product) which then reacts with the methyl
cyanoacetate (6) to give again the intermediate (9) which in
both reaction pathways cyclized with ammonia (from
ammonium acetate) to give the dihydropyridone ring (11)
(Scheme 3).
Dihydropyridone (11) must be oxidized to give pyridone
(5f) as final product. Two possible mechanisms for this
oxidation are discussed in the literature [16,17]. First, as
shown in Scheme 4, dihydropyridone (11) is converted in
alkali media to dianion (12). Single electron transfer from
the dianion (12) to O2 yields the radical anion (13),
aromatization of which involves either H atom transfer to
Scheme 3
O
NC
Ph
NC
Ph
8
PhCHO
O
O
CH3CO2NH4
OMe
Ph
OMe
CN
Ph
7
6
O
O
MeO
O
CN
O
Ph
O
MeO
PhCHO
9
6
CH3CO2NH4
Ph
Ph
8
10
CH3CO2NH4
Ph
Ph
Ph
CN
Ph
CN
-H2
Oxidation
N
H
O
N
H
O
5f
11
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

S. Balalaie, M. M. Hashemi, S. H. Khezri, F. Rominger, E. Ghabraie, and T. Oeser
Vol 000
Scheme 4
Ph
Ph
Ph
Ph
Ph
CN
O
Ph
CN
O
Ph
CN
O
Ph
CN
O
(base)
O2 O2
N
H
N
N
H
N
13
12
5f
11
Ph
Ph
Ph
CN
Ph
CN
N
O
N
O
H
H
5f
Ph
NC
Ph
NC
11
CO2Me
CO2Me
7
14
Scheme 5
Ph
Ph
Ph
4
CN
OH
CN
O
CN
5
3
6
N
N
H
N
H
O
2
1
15
16
5a
Focusing on the bond length pattern of the hetero ring can
reveal more about the mesomeric structure. The carbonyl
bond length (1.25Å) is longer than in a normal carbonyl
group (ꢁ1.20 Å) [19]. The recorded bond lengths in the
heterocycle correspond to a resonance between 5a (pyridone)
and 16 (aromatic zwitterion mesomer) given in Scheme 5.
They show a substantial differentiation, even though they
do, of course, not respond to isolated single and double
bonds. Short C-C bonds are the bonds C3-C4 (1.39 Å) and
C5-C6 (1.38 Å) at the positions of the double bonds in the
mesomer 5a; long C-C bonds are the bonds C2-C3 (1.44 Å)
and C4-C5 (1.42 Å) at the positions of the single bonds in
mesomer 5a. The nitrogen–carbon bonds N1-C2 and N1-C6
are with 1.37 Å and 1.36 Å nearly equal and fit much better
to a C(sp2)-NH-C(sp2) single bond (mean 1.37 Å) than to
an aromatic pyridinium bond (mean 1.34 Å) [18]. Thus, we
can state that the mesomeric structure 5a is the best one to
describe the found structure, although there are, of course,
contributions of the aromatic mesomer 16.
Figure 1. ORTEP structure of compound 5a. [Color figure can be viewed
in the online issue, which is available at wileyonlinelibrary.com.]
Structure 5d (Fig. 2) has a C-N-C angle (125.5ꢀ), C-C-N
angle (114.5ꢀ), a C═O carbonyl bond length (1.25 Å), single
C8-C9 bond length (1.43 Å), single C7-C12 bond (1.41 Å),
single N10-C11 and C9-N10 bonds (1.36 Å and 1.37 Å), double
C7═C8 bond (1.39 Å), and double C11═C12 bond (1.38 Å),
which show clearly that structure 5d is similar to structure 5a.
Figure 2. ORTEP structure of compound 7d. [Color figure can be viewed
in the online issue, which is available at wileyonlinelibrary.com.]
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2013
Synthesis of Novel 2-Pyridones
We can see a deviation from 180ꢀ for the nitrile group,
177.4ꢀ for compound 5a, and 177.3ꢀ for compound 5d.
The torsion angle between the aromatic and the pyridone
rings for compound 5a is 122ꢀ and for compound 5d is
118ꢀ, and in compound 5d, the torsion between the
aromatic ring and the nitro group is 14ꢀ.
Hydrogen bonding interactions in 2-pyridones are very
crucial not only because of their strength but also because
of their importance in bifunctional catalysis. Two of the
more important hydrogen bonding parameters are depicted
for all systems: the distance r(NH. . .O) and its correlation
with angle a(C═O..H). Because of difficulties in localizing
the position of the hydrogen atoms accurately, the N. . .O
distance has most often been used in the past in analyzing
hydrogen bonding interactions. However, with larger
deviations of the N-H-O fragment from linearity, the direct
N. . .O distance becomes less and less descriptive.
As shown in Figures 3 and 4, the N-H and C-O moieties
form pairs of N-H. . .O hydrogen bridge to connect the
molecules to coplanar (with respect to the hetero rings)
molecule pairs. The N. . .O distances amount to 2.772 Å
Figure 4. ORTEP structure of compound 5d. [Color figure can be viewed
in the online issue, which is available at wileyonlinelibrary.com.]
and 2.763 Å for compounds 5a and 5d, respectively. In
these compounds, the hetero rings stack parallel to pairs
with a symmetry equivalent ring with close distances of
3.58 Å for compound 5a and even 3.35 Å for compound
5d indicating p–p interactions.[20] There is also a hydrogen
bonding interaction between two molecules of 5a forming
symmetrical dimmers with r(NH + OH) = 2.772 Å and
a(C═O..H) = 121.87ꢀ. Again, two molecules of 5d form a
symmetrical dimmer with r(NH + OH) = 2.771 Å and
a(C═O. . .H)= 123.23ꢀ. The hydrogen bond is almost linear
with the NH. . .O angle178.59 in 5d (Figs 5, and 6).
Table 4 shows selected structural parameters for the
crystals 5a and 5d.
From the aforementioned discussion of structural data, it
is clear that three types of intramolecular interactions
appear to exist in the crystals: (1) hydrogen bonding inter-
actions between the pyridone carbonyl oxygen and the
pyridone N-H group forming either cyclic dimer and (2)
interactions between the cyano nitrogen atom and also
Figure 3. Intermolecular hydrogen bonding for compound 5a. [Color figure
can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

S. Balalaie, M. M. Hashemi, S. H. Khezri, F. Rominger, E. Ghabraie, and T. Oeser
Vol 000
Figure 5. Intermolecular hydrogen boding and p–p interaction for compound 5a. [Color figure can be viewed in the online issue, which is available at
wileyonlinelibrary.com.]
Figure 6. Intermolecular hydrogen boding and p–p interaction for compound 5d. [Color figure can be viewed in the online issue, which is available at
wileyonlinelibrary.com.]
Table 4
studied and provided the basis for the formation of two dif-
Structural parameters for the crystals 5a and 5d.
ferent supramolecular structures in the solid state. According
to the X-ray crystallographic data, intermolecular hydrogen
bonding and p–p stacking interaction were observed.
5a
5d
r(N. . .O)
rA(N. . .H)
rB(H. . .O)
2.765
0.952
1.820
2.771
0.925
1.846
EXPERIMENTAL
r(NH + HO)
a(N-H. . .O)
a(C═O. . .H)
2.772
172.01
121.87
2.763
178.59
123.23
Melting points were obtained on Electrothermal 9100 appara-
tus and are uncorrected. The 1H NMR and 13C NMR spectra were
measured in DMSO-d6 with Bruker AS 300 spectrometer (1H at
300 MHz and 13C at 75 MHz) and with Bruker DRX-500
AVANCE spectrometer (1H at 500 MHz and 13C at 125 MHz).
The chemical shifts are quoted in ppm on the d scale, with the
residual protonated solvent as internal standard. IR spectra were
recorded on a Unicam/Mattson 8700 FTIR spectrometer in KBr
disks. High resolution mass spectra (HRMS) were obtained with
a ZAB high resolution mass spectrometer (Vacuum Generators).
X-ray diffraction analyses: The reflections were collected on a
Bruker Smart CCD diffractometer using Mo-Ka radiation and a
graphite monochromator. Intensities were corrected for Lorentz
and polarization effects; an empirical absorption correction was
applied based on the Laue symmetry of the reciprocal space
[21]. Full matrix least squares refinement was carried out against
F2. The nonhydrogen atoms were refined anisotropically as well
as the hydrogen atoms at the nitrogen atoms. The other hydrogen
atoms were treated using appropriate ring models. Structure
hydrogen atoms located either in aryl skeleton in C-4 of the
pyridine ring. Strength of hydrogen bonding can affect on
the bifunctional catalysis activity of 2-pyridones.
CONCLUSION
Some novel 3-cyano-2-pyridone derivatives were effi-
ciently synthesized via a one-pot four component reaction.
Carrying out the reaction under (multicomponent reactions)
condition, using of simple starting materials, good yields,
and high diversity of pyridine derivatives are advantages of
this method compared with reported methods. The cis-amide
motifs present in the 3-cyano-4,6-dialkyl-2-pyridones were
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2013
Synthesis of Novel 2-Pyridones
solution and refinement were carried out with the SHELXTL
(5.0) software package [22].
(brs, 1H, HAr), 8.36 (d, 1H, J = 9.0 Hz, HAr), 12.69 (brs, 1H, NH);
13C NMR (75MHz, DMSO-d6): d 13.9, 18.1, 101.0, 111.8, 116.1,
122.7, 124.0, 130.7, 134.5, 137.8, 147.9, 151.3, 158.6, 159.8;
HRMS(EI+): C14H11N3O3, found 269.0810, Calcd 269.0800.
General procedure for the synthesis of 2-pyridones 5a–q.
Alkylcyanoacetate (10 mmol), aromatic and heteroaromatic
aldehyde (10 mmol), ketone (5 mmol), and ammonium acetate
(1.5g) in ethanol 95% (20 mL) were stirred at reflux for 2–4 h.
The progress of reaction was monitored by TLC. Work-up
process was performed in two different ways: (1) for compounds
5a–5i, after cooling to room temperature, the solvent was
evaporated under reduced pressure. Ethyl acetate was added to the
residue, the organic phase was washed with water, dried over
MgSO4, filtered, and concentrated under reduced pressure. The
residue was recrystallized from acetonitrile or THF. (2) For
compounds 5j–5s, two-thirds of the solvent was evaporated under
reduced pressure. The solid formed was collected by filtration,
washed with ethanol (minimum amount), dried at room
temperature, and recrystallized from acetonitrile or THF. In the
case of solvent-free reaction condition, after completion of
reaction, 10mL water was added to the mixture and after
decantation, the mixture was crystalized by EtOH.
X-ray: C14H11N3O3, M= 269.265 g molÀ1, monoclinic, a= 5.7992
(5), b= 17.2087(14), c= 12.8130(11) Å, a = 90, b = 90.877(2),
g =90ꢀ, V= 1278.55(19) Å3, Space groupP21/c, Z = 4, density
(calculated) = 1.40 g cmÀ3
.
Crystal size 0.40 Â 0.20 Â 0.15 mm3,
T= 296(2) K, m [mmÀ1] = 0.10, tmin = 0.96, tmax = 0.98, hmin/hmax
=
À7/7, kmin/kmax =À22/22, lmin/lmax =À16/17, Refl. Collected =
13112, Refl. unique = 3182, Refl. observed = 2539, Parameter = 187,
S (Gof) on F2 =1.04, R(F) = 0.051, Rw(F2) = 0.138, (Δr)max =0.32e.
Å
À3, (Δr)min =À0.21 e.ÅÀ3. CCDC 635910 contains the supplemen-
tary crystallographic data for this article. These data can be obtained
free of charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
3-Cyano-4-(4-nitrophenyl)-5,6-dimethyl-2(1H)-pyridone
(5e). Yield: 32%; mp (Dec) 262–264ꢀC; IR(KBr): 3461, 2846,
2223, 1646, 1530, 1338 cmÀ1; 1H NMR (300 MHz, DMSO-d6):
d 1.69 (s, 3H, CH3), 2.34 (s, 3H, CH3), 7.65 (d, 2H, J = 8.7 Hz,
H
Ar), 8.38 (d, 2H, J = 8.7 Hz, HAr), 12.71 (brs, 1H, NH); 13C
Selected data for compounds 5a–5q. 3-Cyano-4-phenyl-5,6-
dimethyl-2(1H)-pyridone (5a).
Yield: 57%; mÀp1 (Dec) 260–
NMR (75 MHz, DMSO-d6): d 13.9, 18.1, 99.4, 111.0, 116.0,
124.0, 129.4, 142.8, 147.8, 151.4, 159.7, 159.8; HRMS(EI+):
C14H11N3O3, found 269.0808, Calcd 269.0801.
261ꢀC; IR (KBr): 3453, 2923, 2223, 1653 cm
;
1H NMR
(300 MHz, DMSO-d6): d 1.68 (s, 3H, CH3), 2.30 (s, 3H, CH3),
7.26–7.29 (m, 2H, HAr), 7.46–7.53 (m, 3H, HAr), 12.6 (brs, 1H,
NH); 13C NMR (75 MHz, DMSO-d6): d 13.9, 18.0, 99.6, 111.4,
116.3, 127.6, 128.7, 129.0, 136.4, 150.5, 160.1, 161.9; HRMS
(EI+): C14H12N2O, found 224.0958, Calcd 224.0949.
3-Cyano-4,5-diphenyl-6-methyl-2(1H)-pyridone (5f).
Yield:
88%; mp (Dec) 318–320ꢀC; IR (KBr): 3461, 2831, 2223,
1
1646 cmÀ1; H NMR (DMSO-d6, 500 MHz): d 2.04 (s, 3H, CH3),
6.91–7.22 (m, 10H, HAr), 12.78 (brs, 1H, NH); 13C NMR
(125 MHz, DMSO-d6): d 24.7, 103.4, 112.3, 122.2, 133.4, 133.6,
134.4, 135.9, 136.1, 141.7, 142.0, 160.6, 165.6, 167.3.; HRMS
(EI+): C19H14N2O, found 286.1099, Calcd 286.1106.
X-ray: C14H12N2O, M = 224.269 g molÀ1, triclinic, a = 7.3862
(3), b = 9.4458(1), c = 9.6700(3) Å, a = 62.669(2), b = 82.671(2),
g = 89.980(2)ꢀ, V = 593.15(3) Å3, Space group Pī, Z = 2, density
(calculated) = 1.26 g cmÀ3. Crystal size 0.50 Â 0.24 Â 0.03 mm3,
3-Cyano-4-(4-chlorophenyl)-5-phenyl-6-methyl-2(1H)-pyridone
T = 200(2) K, m [mmÀ1] = 0.08, tmin = 0.96, tmax = 0.99, hmin
/
(5g). Yield: 74%; mp (Dec) 310–312ꢀC; IR (KBR): 3546, 2910,
1
2223, 1654 cmÀ1; H NMR (500 MHz, DMSO-d6): d 2.10 (s, 3H,
hmax = À9/9, kmin/kmax = À11/11, lmin/lmax = À12/11, Refl.
CH3), 7.03 (d, 2H, J=7.7Hz, HAr), 7.15–7.24 (m, 5H, HAr), 7.88 (d,
2H, J=7.7Hz, HAr), 12.89 (brs, 1H, NH); 13C NMR (125 MHz,
DMSO-d6): d 18.0, 105.7, 121.7, 124.5, 133.0, 133.6, 133.8, 134.6,
135.9, 136.5, 139.0, 140.5, 156.3, 165.5, 165.8.; HRMS(EI+):
C19H13N2O35Cl, found 320.0723, Calcd 322.0716. C19H13N2O37Cl,
found 322.0706, calc 322.0687.
3-Cyano-4-(2-furyl)-5-phenyl-6-methyl-2(1H)-pyridone
(5h). Yield: 54%; mp (Dec) 263–264ꢀC; IR(KBr): 3431, 2784,
2215, 1646 cmÀ1; 1H NMR (500 MHz, DMSO-d6): d 2.04 (s, 3H,
CH3), 6.02 (d, 1H, J = 1.6Hz, Hfuryl), 6.47 (d, 1H, J = 3.6,
Hfuryl), 7.14 (m, 2H, HAr), 7.35 (m, 3H, HAr), 7.69 (d, 1H,
J = 3.6 Hz, Hfuryl), 12.72 (brs, 1H, NH); 13C NMR (125MHz,
DMSO-d6): d 24.4, 107.5, 117.6, 121.7, 133.4, 133.5, 134.6,
136.0, 141.4, 150.8, 152.3, 155.8, 158.3, 163.3, 166.6. HRMS
(EI+): C17H12N2O2, found 276.0899, Calcd 276.0900.
Collected = 4760, Refl. unique = 2360, Refl. observed = 1457,
Parameter = 160,
(F2) = 0.104, (Δr)max = 0.2 e.ÅÀ3
S
(Gof) on F2 = 0.97, R(F) = 0.045, Rw
,
(Δr)min = 593.15(3) e.ÅÀ3
.
CCDC 635909 contains the supplementary crystallographic data
for this article. These data can be obtained free of charge from
The Cambridge Crystallographic Data Centre via www.ccdc.
cam.ac.uk/data_request/cif.
3-Cyano-4-(4-chlorophenyl)-5,6-dimethyl-2(1H)-pyridone
(5b). Yield: 38%; mp (Dec) 258–260ꢀC; IR (KBr): 3561, 2754,
2223, 1654 cmÀ1; 1H NMR (300 MHz, DMSO-d6): d 1.69 (s, 3H,
CH3), 2.31 (s, 3H, CH3), 7.34 (d, 2H, J = 8.4 Hz, HAr), 7.58 (d,
2H, J = 8.4 Hz, HAr), 12.55 (brs, 1H, NH); 13C NMR (75 MHz,
DMSO-d6): d 13.9, 18.0, 100.0, 111.3, 116.2, 125.8, 128.8,
128.7, 129.6, 129.9, 133.9, 135.1, 150.7, 159.9, 160.6; HRMS
(EI+): C14H11ClN2O37Cl found 260.0526, Calcd 260.0530, mmu
À0.4, C14H11ClN2O 35Cl found 258.0558, Calcd 258.0560.
3-Cyano-4-(4-methylphenyl)-5,6-dimethyl-2(1H)-pyridone
(5c). Yield: 21%; mp (Dec) 253–255ꢀC; IR (KBr): 3446, 2753,
2223, 1654cmÀ1; 1H NMR (300MHz, DMSO-d6): d 1.71 (s, 3H,
CH3), 2.31 (s, 3H, CH3), 2.50 (s, 3H, CH3), 7.18 (d, 2H,
J = 7.9Hz, HAr), 7.33 (d, 2H, J = 7.9 Hz, HAr),, 12.63 (brs, 1H,
NH); 13C NMR (75MHz, DMSO-d6): d 14.0, 18.0, 20.9, 99.4,
111.8, 116.4, 127.5, 129.2, 133.4, 138.5, 150.6, 160.1, 162.3;
HRMS(EI+): C15H14N2O, found 238.1089, Calcd 238.1106.
3-Cyano-4-(3-nitrophenyl)-5,6-dimethyl-2(1H)-pyridone
3-Cyano-4-(2-pyridyl)-5-phenyl-6-methyl-2(1H)-pyridone
(5i).
Yield: 94%; mp (Dec) 312–313ꢀC; IR (KBr): 3469,
1638cmÀ1; 1H NMR (500 MHz, DMSO-d6): d 2.13 (s, 3H, CH3),
7.01 (d, 1H, J = 6.3 Hz, Hpyridyl), 7.16 (m, 5H, HAr), 7.25 (m, 1H,
Hpyridyl), 7.64 (m, 1H, Hpyridyl), 8.50 (d, 1H, J = 4.7Hz,
Hpyridyl),12.94 (brs, 1H, NH); 13C NMR (125MHz, DMSO-d6): d
24.2, 105.4, 121.3, 124.1, 129.1, 129.5, 132.9, 133.6, 136.4,
140.3, 141.8, 154.6, 156.8, 159.7, 165.0, 165.8.; HRMS(EI+)
C18H13N3O, found 287.1026, Calcd 287.1058.
3-Cyano-4-(4-pyridyl)-5-phenyl-6-methyl-2(1H)-pyridone
(5j). Yield: 81%; mp (Dec) 290–293ꢀC; IR (KBr): 3454, 2950,
2215, 1677 cmÀ1; 1H NMR (500 MHz, DMSO-d6): d 2.11 (s, 3H,
CH3), 7.06 (d, 2H, J = 5.7 Hz, Hpyridyl), 7.20 (m, 5H, HAr), 8.47
(5d).
Yield: 35%; mp (Dec) 243–244ꢀC; IR (KBr): 3469, 2900,
2223, 1646, 1538, 1361 cmÀ1; 1H NMR (300MHz, DMSO-d6): d
1.71 (s, 3H, CH3), 2.34 (s, 3H, CH3), 7.80 (m, 2H, HAr), 8.21
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

S. Balalaie, M. M. Hashemi, S. H. Khezri, F. Rominger, E. Ghabraie, and T. Oeser
Vol 000
(d, 2H, J = 5.7 Hz, Hpyridyl) 12.98 (brs, 1H, NH); 13C NMR
(125 MHz, DMSO-d6): d 25.0, 103.3, 114.8, 120.1, 123.0, 128.5,
133.1, 133.8, 136.4, 140.1, 147.6, 154.9, 164.1, 165.0.; HRMS
(EI+) C18H14N3O, found 288.1113, Calcd 288.1137.
3-Cyano-4-(2-thienyl)-5-phenyl-6-methyl-2(1H)-pyridone
(5k). Yield: 95%; mp (Dec) 242–243ꢀC; IR (KBr): 3446, 2215,
1646cmÀ1; 1H NMR (500 MHz, DMSO-d6): d 2.07 (s, 3H, CH3),
6.97 (d, 1H, J = 4.8 Hz, Hthienyl), 7.08 (m, 2H, HAr), 7.15 (quint,
1H, Hthienyl), 7.26 (m, 3H, HAr), 7.59 (d, 1H, J = 4.2Hz, Hthienyl),
12.87 (brs, 1H, NH); 13C NMR (125MHz, DMSO-d6): d 24.5,
105.7, 122.0, 124.6, 132.4, 133.4, 133.9, 134.5, 135.7, 136.0,
136.5, 137.5, 140.7, 142.3, 159.2, 165.9.; HRMS(EI+)
C17H12N2OS, found 292.0646, Calcd 292.0671.
CH2), 1.67 (m, 2H, CH2), 2.03 (t, 2H, J = 5.9 Hz, CH2), 2.64
(t, 2H, J = 6.1 Hz, CH2),7.31 (m, 2H, HAr), 7.50 (m, 3H, HAr),
12.44 (brs, 1H, NH); 13C NMR (125 MHz, DMSO-d6): d 26.2,
27.4, 30.5, 32.9, 106.0, 117.9, 121.7, 133.1, 134.3, 134.7, 141.2,
155.9, 165.5, 167.5.; HRMS(EI+): C16H14N2O, found 250.1085,
Calcd 250.1106.
Acknowledgments. S.B. is grateful to the Alexander von
Humboldt foundation for the research fellowship and equipment
donation. Partial support of this work by the K. N. Toosi
University of Technology Research Council is gratefully
acknowledged.
3-Cyano-4-phenyl-6-iso-butyl-2-(1H)-pyridone (5l).
34%; mp (Dec) 238–239ꢀC; IR (KBr): 3623, 2954, 2215,
1654cmÀ1 1H NMR (500 MHz, DMSO-d6): d 0.89 (d, 6H,
Yield:
;
REFERENCES AND NOTES
J = 5.8Hz, 2CH3), 2.01 (m, 1H, CH), 2.45 (d, 2 H, J = 5.9Hz,
CH2), 6.33 (s, 1H, CH),7.55 (m, 3H, HAr), 7.61 (m, 2H, HAr),
12.61 (brs, 1H, NH); 13C NMR (125MHz, DMSO-d6): d 27.5,
33.7, 47.1, 103.3, 112.2, 122.2, 133.6, 134.4, 135.9, 141.7, 160.6,
165.6, 167.2. HRMS(EI+): C16H16N2O, found 252.3152, Calcd
252.3164.
3-Cyano-4-(3-nitrophenyl)-6-iso-butyl-2(1H)-pyridone
(5m). Yield: 27%; mp (Dec) 205–206ꢀC; IR(KBr): 3415, 2961,
2223, 1654, 1538, 1353 cmÀ1; 1H NMR (500MHz, DMSO-d6): d
0.89 (brs, 6H, 2CH3), 2.01 (m, 1H, CH), 2.46 (brs, 2H, CH2),
6.45 (s, 1H, CH),7.85 (m, 1H, HAr), 8.08 (m, 1H, HAr), 8.40 (m,
2H, HAr), 12.76 (brs, 1H, NH); 13C NMR (125MHz, DMSO-d6):
d 27.5, 33.8, 47.1, 103.8, 112.1, 121.8, 128.5, 130.5, 136.1,
140.3, 143.1, 153.4, 161.5, 163.2, 166.9. HRMS(EI+)
C16H15N3O3, found 297.1113, Calcd 297.1116.
[1] (a) Manna, F.; Chimenti, F.; Bolasco, A.; Filippelli, A.;
Lampa, E. Pharmacol Res 1992, 26, 267; (b) Presti, E. L.; Boggia, R.;
Feltrin, A.; Menozzi, G.; Dorigo, P.; Mosti, L. Farmaco 1999, 54, 465;
(c) Su, Y.; Zhao, M.; Han, K.; Song, G.; Li, X. Org Lett 2010, 12,
5462; (d) Nadin, A.; Harrison, T. Tetrahedron Lett 1999, 40, 4073 and
references cited therein.
[2] (a) Dejohn, D.; Domogala, J. M.; Kaltenbronn, J. S.; Krolls, U.
J Heterocycl Chem 1983, 20, 1295; (b) Takahashi, T.; Tsai, F.-Y.; Li, Y.;
Wang, H.; Kondo, Y.; Yamanaka, M.; Nakajima, K.; Kotora, M. J Am
Chem Soc 2002, 124, 5059; (c) Lam, P. Y. S.; Clark, C. G.; Saubern,
S.; Adams, J.; Averill, K.; Chan, D. M. T.; Comb, A. P. Synlett 2000,
674; (d) Chiba, T.; Takahashi, T. Chem Pharm Bull 1985, 33, 2731.
[3] (a) Witzel, B. E. Chem Abstr 1972, 77, 39226t; (b) Manna, F.;
Chimenti, F.; Bolasco, A.; Filippeli, A.; Palla, A.; Filippeli, W.; Lampa, E.;
Mercantini, R. Eur J Med Chem 1992, 27, 627.
[4] Attia, A.; Michael, M. Pharmazie 1982, 37, 551.
3-Cyano-4-phenyl-6-propyl-2(1H)-pyridone (5n).
18%; mp (Dec) 238–239ꢀC; IR (KBr): 3623, 2954, 2215,
1654 cmÀ1 1H NMR (500 MHz, DMSO-d6): d 0.89 (d, 6H,
Yield:
[5] Stockley, M.; Clegg, W.; Fontana, G.; Golding, B. T.; Martin,
N.; Rigoreau, L. J. M.; Smith, G. C. M.; Griffin, R. J. Bioorg Med Chem
Lett 2001, 11, 2837.
;
J = 5.8 Hz, 2CH3), 2.01 (m, 1H, CH), 2.45 (d, 2H, J = 5.9 Hz,
CH2), 6.33 (s, 1H, CH),7.55 (m, 3H, HAr), 7.61 (m, 2H, HAr),
12.61 (brs, 1H, NH); 13C NMR (125 MHz, DMSO-d6): d 27.5,
33.7, 47.1, 103.3, 112.2, 122.2, 133.6, 134.4, 135.9, 141.7,
160.6, 165.6, 167.2. HRMS(EI+): C15H14N2O, found 238.2884,
Calcd 238.2876.
[6] (a) Murata, T.; Shimada, M.; Sakakibara, S.; Yoshino, T.;
Kadono, H.; Masuda, T.; Shimazaki, M.; Shintani, T.; Fuchikami, K.;
Sakai, K.; Inbe, H.; Takeshita, K.; Niki, T.; Umeda, M.; Bacon, K. B.;
Ziegelbauer, K. B.; Lowinger, T. B. Bioorg Med Chem Lett 2003, 13, 913
[7] Collins, J.; Moyes, C.; Davey, W. B.; Rowley, M. F. A.;
Bromidge, F. A.; Qurik, K.; Atack, J. R.; McKernan, R. M.; Thompson, S.
A.; Wafford, K.; Dawson, G. R.; Pike, A.; Sohal, B.; Tsou, N. N.; Ball, R. G.;
Castro, J. L. J Med Chem 2002, 45, 1887.
[8] (a)Abdi, A.H.; Al-Khames, H. A. ArchPharm Pharm Med Chem
1998, 331, 319; (b) Abdi, A.; Al-Deeb, O.; Al-Afify, A.; El-Kashef, H. Il
Farmaco 1999, 54, 195.
[9] (a) Bekhit, A. A.; Baraka, A. M. Eur J Med Chem 2005, 40,
1405; (b) Dorigo, P.; Gaion, R. M.; Belluco, P.; Fraccarollo, D.; Maragno,
I.; Bombieri, G.; Benetollo, F.; Mosti, L.; Orsini, F. J Med Chem 1993,
36, 2475; (c) Neo, A. G.; Carrillo, R. M.; Barriga, S.; Moman, E.;
Marcaccini, S.; Marcos, C. F. Synlett 2007, 327.
[10] (a) Rybakov, V. B.; Bush, A. A.; Babaev, E. U.; Aslanov, L.
A. Acta Cryst E 2004, 60, 160; (b) Glidewell, C.; Low, J. N.; Skakle, J.
M. S.; Wardell, S.M.S.V., Wardell, J. L. Acta Cryst B 2004, 60, 472;
(c) Eicher, T.; Hauptmann, S. The Chemistry of Heterocycles:
Structure, Reactions, Syntheses and Applications; Wiley: New York,
2003; p 310.
[11] (a) McKillop, A.; Boulton, A. In Comprehensive Heterocy-
clic Chemistry; Katritzky, A. R.; Rees, C. W., Eds.; Pergamon Press:
New York, 1984; Vol 2, Part 2, p 67; (b) Carles, L.; Narkunan, K.;
Penlou, S.; Rousset, L.; Bouchu, D.; Ciufolini, M. A. J Org Chem
2002, 67, 4304.
[12] (a) Balalaie, S.; Kowsari, E.; Hashtroudi, M. S. Monatsh Chem
(Chemical Monthly) 2003, 134, 435; (b) Rodriguez, H.; Suarez, M.;
Perez, R.; Petit, A.; Loupy, A.; Tetrahedron Lett 2003, 44, 3709.
[13] Xiong, X.; Bagley, M.; Chapaneri, K. Tetrahedron Lett 2004,
45, 6121.
3-Cyano-4-(3-nitrophenyl)-6-propyl-2(1H)-pyridone (5o). Yield:
22%; mp (Dec) 213–215ꢀC; IR (KBr): 2980, 2223, 1654, 1530,
1353 cmÀ1 1H NMR (500 MHz, DMSO-d6): d 0.91 (t, 3H,
;
J=7.3Hz, CH3), 1.66 (m, 2H, CH2), 2.57 (t, 2H, J=7.6Hz, CH2),
6.46 (s, 1H, CH), 7.85 (t, 1H, J=7.9Hz, HAr), 8.10 (d, 1H,
J=7.7Hz, HAr), 8.41 (m, 2H, HAr), 12.77 (brs, 1H, NH); 13C NMR
(125 MHz, DMSO-d6): d 19.0, 27.2, 40.2, 103.8, 111.4, 121.8,
128.5, 130.6, 136.1, 140.3, 143.1, 153.4, 162.2, 163.4, 166.9.;
HRMS(EI+): C15H13N3O3, found 283.0936, Calcd 269.0957.
3-Cyano-4-(4-chlorophenyl)-5,6-(1,3-propanediyl)-2(1H)-
pyridone (5p).
Yield: 89%; mp (Dec) 256–266ꢀC; IR (KBr):
3453, 2938, 2223, 1646 cmÀ1; 1H NMR (500MHz, DMSO-d6): d
2.00 (m, 2H, CH2), 2.52 (t, 2H, J = 7.1Hz, CH2), 2.88 (t, 2H,
J = 7.6Hz, CH2),7.53 (d, 2H, J = 8.0Hz, HAr), 7.61 (d, 2H,
J = 8.0Hz, HAr), 12.87 (brs, 1H, NH); 13C NMR (125 MHz,
DMSO-d6): d 27.7, 34.3, 37.3, 103.6, 122.4, 123.3, 134.3, 134.5,
135.6, 139.7, 140.2, 162.0, 163.1, 167.2.; HRMS(EI+):
C15H11N2O35Cl, found 270.0561, Calcd 270.0562, mmu= +0.1.,
C15H11N2O37Cl, found 272.0519, Calcd 270.0507.
3-Cyano-4-phenyl-5,6-(1,4-butanediyl)-2(1H)-pyridone
(5q). Yield: 78%; mp 256–259ꢀC; IR(KBr): 3415, 2938, 2215,
1623cmÀ1 1H NMR (500 MHz, DMSO-d6): d 1.55 (m, 2H,
;
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2013
Synthesis of Novel 2-Pyridones
[14] (a) Gilchrist, T. L. Heterocyclic Chemistry; Addison Wesley
3299; (e) Bararjanian, M.; Balalaie, S.; Rominger, F.; Movassagh, B.;
Bijanzadeh, H. R. J Org Chem 2010, 75, 2806; (f) Bararjanian, M.;
Balalaie, S.; Rominger, F.; Barouti, S. Helv Chim Acta 2010, 93, 777;
(g) Balalaie, S.; Abdolmohammadi, S.; Soleimanifard, B. Helv Chim Acta
2009, 92, 932; (h) Khoshkholgh, M. J.; Lotfi, M.; Balalaie, S.; Rominger,
F. Tetrahedron 2009, 65, 4228; (i) Bararjanian, M., Hosseinzadeh, S.;
Balalaie, S.; Bijanzadeh, H. R. Tetrahedron 2011, 67, 2644; (j) Hadjebi,
M.; Hashtroudi, M. S.; Bijanzadeh, H. R.; Balalaie, S. Helv Chim Acta
2011, 94, 382.
[19] (a) Fischer, C. B.; Polborn, K.; Steininger, H.; Zipse, H. Z
Naturforschung 2004, 59b, 1121; (b) Maverick, E. F.; Wash, P. L.;
Lightner, D. A. Cryst Struct Commun 2001, 57, 284; (c) Wheeler, G.;
Ammon, H. L. Acta Cryst 1974, B30, 680; (d) Kvick, A.; Booles, S. S.
Acta Cryst 1972, B28, 680; (e) Allen, F. H. Acta Cryst 2002, B 58, 380.
[20] Werz, D. B.; Fischer, F. R.; Kornmayer, S. C.; Rominger, F.;
Gleiter, R. J Org Chem 2008, 73, 8021 and refernces cited therein.
[21] Sheldrick G. M. Program SADABS V2.03 for absorption
correction; Bruker Analytical X-ray-Division: Madison, Wisconsin, 2001.
[22] Sheldrick G. M. Software package SHELXTL V5.10 for
structure solution and refinement; Bruker Analytical X-ray-Division:
Madison, Wisconsin, 1997.
Longman: Harlow, 1997; p 156 and references cited therein; (b) Jessen,
H. J.; Gademann, K. Nat Prod Rep 2010, 27, 1168; (c) Joule, J. A.; Mills,
K. Heterocyclic Chemistry, 4th ed.; Blackwell Science Ltd.: Oxford, 2000.
[15] (a) Sammour, A.; Akhnookh, Y.; Yahine, H. UARR J Chem
1970, 13, 421; (b) Soto, J.; Seoane, C.; Mansilla, A. Org Prep Proc Int
1981, 13, 331.
[16] (a) Jain, R.; Rochangar, F.; Ciufolini, A. Tetrahedron Lett
1995, 36, 3307; (b) Wang, S.; Tan, T.; Li, J.; Hu, H. Synlett 2005,
2658; (c) Murata, T.; Sakakibara, S.; Yoshino, T.; Ikegami, Y.; Masuda,
T.; Shimada, M.; Shimazaki, M.; Lowinger, T.; Ziegelbauer, K.; Fuchi-
kami, K.; Umeda, M.; Komura, H.; Yoshida, N. WO Patent 02/44153
A1 2002.
[17] (a) Kambe, S.; Saito, K. Synthesis 1980, 366; (b) Shintani, T.;
Kadono, H.; Kikuchi, T.; Schubert, T.; Shogase, Y.; Shimazaki, M.
Tetrahedron Lett 2003, 44, 6567.
[18] (a) Balalaie, S.; Bararjanian, M.; Amani, M. A.; Movassagh,
B. Synlett 2006, 263; (b) Balalaie, S.; Bararjanian, M.; Rominger, F. J
Heterocycl Chem 2006, 43, 821; (c) Balalaie, S.; Bararjanian, M.;
Hekmat, S.; Sheikh-Ahmadi, M.; Salehi, P. Synth Commun 2007, 37,
1097; (d) Abdolmohammadi, S.; Balalaie, S. Tetrahedron Lett 2007, 45,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet