Recyclization of ethyl 1-alkyl-5-benzoyl-6-methylsulfanyl-2-oxo-1,2-dihydropyridine-3-carboxylates into Bicyclic N-alkyl-5-benzoyl-2-oxo-1,2-dihydropyridine-3-carboxamide derivatives by the action of nitrogen-containing 1,4- and 1,5-binucleophiles

Article abstract of DOI:10.1134/S1070428009120148

Reactions of ethyl 1-alkyl-5-benzoyl-6-methylsulfanyl-2-oxo-1,2-dihydropyridine-3-carboxylates with nitrogen-containing 1,4- and 1,5-binucleophiles (o-phenylenediamine, o-aminobenzenethiol, ethane-1,2-diamine, and propane-1,3-diamine) involved recyclizati

Full text of DOI:10.1134/S1070428009120148

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2009, Vol. 45, No. 12, pp. 1834–1842. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © V.N. Britsun, A.N. Esipenko, A.V. Gutov, A.N. Chernega, M.O. Lozinskii, 2009, published in Zhurnal Organicheskoi Khimii, 2009,
Vol. 45, No. 12, pp. 1837–1844.
Recyclization of Ethyl 1-Alkyl-5-benzoyl-6-methylsulfanyl-
2-oxo-1,2-dihydropyridine-3-carboxylates into Bicyclic N-Alkyl-
5-benzoyl-2-oxo-1,2-dihydropyridine-3-carboxamide Derivatives
by the Action of Nitrogen-Containing 1,4- and 1,5-Binucleophiles
V. N. Britsun, A. N. Esipenko, A. V. Gutov, A. N. Chernega, and M. O. Lozinskii
Institute of Organic Chemistry, National Academy of Sciences of Ukraine, ul. Murmanskaya 5, Kiev, 02660 Ukraine
e-mail: bvn1967@rambler.ru
Received December 11, 2008
Abstract—Reactions of ethyl 1-alkyl-5-benzoyl-6-methylsulfanyl-2-oxo-1,2-dihydropyridine-3-carboxylates
with nitrogen-containing 1,4- and 1,5-binucleophiles (o-phenylenediamine, o-aminobenzenethiol, ethane-1,2-
diamine, and propane-1,3-diamine) involved recyclization, leading to the formation of fused N-alkyl-5-ben-
zoyl-2-oxo-1,2-dihydropyridine-3-carboxamides, diethyl 6,6′-oxybis(1-alkyl-5-benzoyl-2-oxo-1,2-dihydropyri-
dine-3-carboxylates), and diethyl 6,6′-[ethane-1,2-diyl(or propane-1,3-diyl)diimino]bis(1-alkyl-5-benzoyl-2-
oxo-1,2-dihydropyridine-3-carboxylates), depending on the reactant ratio. The sequence of formation of inter-
mediate recyclization products was determined.
DOI: 10.1134/S1070428009120148
We recently developed a procedure for the synthe-
sis of ethyl 1-alkyl-5-benzoyl-6-methylsulfanyl-2-oxo-
1,2-dihydropyridine-3-carboxylates Ia and Ib [1]. Un-
like methods reported previously [2–4], the developed
procedure ensures high selectivity and utilizes acces-
sible initial compounds. 2-Oxo-1,2-dihydropyridines I
were used as substrates in cyclocondensations with
nitrogen-containing 1,2-, 1,3-, and 1,5-binucleophiles
[1, 2, 5]. The reactions of dihydropyridines Іa and Ib
with propane-1,3-diamine involved recyclization [5].
The goal of the present work was to estimate the
scope of application of the above recyclization and
examine how the ratio of initial 1,2-dihydropyridin-2-
one Ia or Ib and difunctional nucleophile [o-phenyl-
enediamine (IIa), o-aminobenzenethiol (IIb), ethane-
1,2-diamine (Va), and propane-1,3-diamine (Vb)] af-
fects the reaction direction. We were also interested in
elucidating the reaction mechanism (i.e., the trans-
formation sequence and structure of intermediate prod-
ucts) and unambiguously determining the structure of
recyclization products. Recyclizations with participa-
tion of o-phenylenediamine (IIa) and o-aminobenzene-
thiol (IIb), leading to the formation of benzimidazole,
quinoxaline, and 1,4-benzothiazine derivatives, were
the subjects of recent publications [6–8], which dem-
onstrated increased interest in such reactions.
Compounds Ia and Ib were found to react with
nucleophiles IIa, IIb, Va, and Vb along two pathways.
When the reactant ratio was 1:1 or 1:2, the products
were not substituted 2H-pyran-2-ones (as we presumed
previuously [5]) but mixtures of fused N-alkyl-5-ben-
zoyl-2-oxo-1,2-dihydropyridine-3-carboxamide deriva-
tives ІІІa–IIId or VIa–VId and diethyl 6,6′-oxybis(1-
alkyl-5-benzoyl-2-oxo-1,2-dihydropyridine-3-carbox-
ylates) IVa and IVb. The yields of compounds ІІІa–
IIId, VIa–VId, and IVa, IVb were 57–70, 39–69, and
24–49%. respectively. The reactions of compounds Ia
and Ib with diamines Va and Vb at a ratio of 2:1 led
to the formation of the corresponding diethyl 6,6′-[eth-
ane-1,2-diyl(or propane-1,3-diyl)diimino]bis(1-alkyl-
5-benzoyl-2-oxo-1,2-dihydropyridine-3-carboxylates)
VIIa–VIId (Scheme 1). Dihydropyridine Ia reacted
with butane-1,4-diamine (Vc) to give 6,6′-(butane-1,4-
diyldiimino)bis(1-alkyl-5-benzoyl-2-oxo-1,2-dihydro-
pyridine-3-carboxylate) (VIIe) as the only product
even when the amount of diamine Vc was 3 equiv.
Presumably, recyclization of N,N′-disubstituted 1,4-di-
aminobutane VIIe into 1,3-diazepine derivative does
not occur because of difficult closure of seven-mem-
bered ring.
Fused pyridobenzimidazoles IIIa and IIIb, pyrido-
benzothiazoles IIIc and IIId, imidazopyridines VIa
1834

RECYCLIZATION OF ETHYL 1-ALKYL-5-BENZOYL-6-METHYLSULFANYL-...
1835
Scheme 1.
O
NH2
NHR
O
Ph
Ph
O
O
XH
O
O
N
X
IIa, IIb
EtO
OEt
+
Ph
N
N
O
O
O
O
R
R
IIIa–IIId
IVa, IVb
O
NHR
O
H2N
NH2
O
O
Ph
( )n
Va, Vb
(excess)
N
O
EtO
O
( )n–1
+
IVa, IVb
N
H
N
R
SMe
Ph
Ia, Ib
VIa–VId
O
Ph
Ph
O
Va, Vb (0.5 equiv)
Vc (excess)
EtO
O O
( )n
OEt
O
N
R
N
N
H
N
O
H
R
VIIa–VIIe
O
O
O
Me
N
Ac2O, pyridine
Me
N
IIIa
N
H
Ph
O
VIII
I, IV, R = Me (a), Et (b); II, X = NH (a), S (b); III, VI, VII, R = Me (a, c), Et (b, d); III, X = NH (a, b), S (c, d);
V, n = 2 (a), 3 (b), 4 (c); VI, VII, n = 2 (a, b), 3 (c, d), 4 (e)..
9.24 ppm), and a singlet from the endocyclic NH
group (the position of the latter signal depended on the
heteroring nature). The presence of benzoyl groups in
molecules IIIa–IIId, IVa, IVb, VIa–VId, and VIIa–
VIIe clearly followed from the 13C NMR spectra of
IIIa, IVa, VIb, and VIIa–VIIc, which, as well as the
spectra of initial compounds Ia and Ib [1], contained
a signal at δC 191.0–193.2 ppm typical of carbonyl
carbon atom in benzoyl group.
and VIb, and pyridopyrimidines VIc and VId are yel-
lowish high-melting substances that are poorly soluble
in polar organic solvents. Their structure was con-
1
firmed by IR and H and 13C NMR spectra, as well as
by the transformation of compound IIIa into N-acetyl-
4-benzoyl-1-oxo-1,5-dihydropyrido[1,2-a]benzimid-
azole-2-carboxamide (VІII) by the action of acetic an-
hydride in pyridine (Scheme 1).
Compounds IIIa–IIId and VІa–VId characteris-
tically showed in the 1H NMR spectra a doublet signal
from methyl protons in the CH3NH groups (IIIa, IIIc,
VІa, VIc; δ 2.75–2.85 ppm, J = 2.7–4.5 Hz), a broad-
ened singlet from the amide AlkNH proton (δ 8.90–
9.15 ppm), a multiplet from 6-H (IIIa–IIId, δ 8.70–
The molecular and crystalline structures of diethyl
6,6′-(ethane-1,2-diyldiimino)bis(5-benzoyl-1-methyl-
2-oxo-1,2-dihydropyridine-3-carboxylate) (VIIa) and
6,6′-(propane-1,3-diyldiimino)bis(5-benzoyl-1-methyl-
2-oxo-1,2-dihydropyridine-3-carboxylate) (VIIc) were
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 12 2009

BRITSUN et al.
and interesting that the central ethanediamine fragment
1836
C14
C13
C13
2
15
C15
C
adopts clearly unfavorable synclinal conformation
(Fig. 2): the torsion angle N2C17C17'N2' is 63.8°, and
the interatomic distance N2···N2′ is 2.910(2) Å (cf. the
double van der Waals radius of the nitrogen atom
3.0 Å). The N1C1C2C3C4C5 ring is slightly nonplanar:
deviations of atoms from the corresponding mean-
square plane reach 0.078 Å). The N1 atom is charac-
terized by planar–trigonal bond configuration, whereas
the configuration of the N2 atom is an appreciably
flattened pyramid (the sums of the bond angles at N1
and N2 are 359.6 and 349.5°, respectively). Effective
conjugation between the lone electron pairs on N1 and
N2 with π-electron system of the C4=C5 bond induces
considerable shortening of formally single N1–C5 and
N2–C5 bonds [1.359(2) and 1.333(2) Å, respectively]
against the distance 1.43–1.45 Å typical of purely
single Nsp2–Csp2 bond [9, 10]. The dihedral angle be-
tween the N1C1–C5 and C11–C16 ring planes is 53.5°.
One more specificity of the molecular structure of
compound VIIa is formation of a quite strong [11]
intramolecular hydrogen bond N2H2···O4 [O···N
2.631(2), O···H 1.87(3) Å; ∠OHN 143(2)°] closing
six-membered N2C5C4C10O4H2 ring. Molecules VIIa
in crystal are arranged to form infinite stacks (Fig. 3),
and neither inside the stacks nor between them short-
ened intermolecular contacts are observed.
O2
O
C8
C12
C16
C8
C16
CC712
11
CC11
CC9 9
C3
C3
3
O3
O
C2
C11
0
C 0
C2
O4
O4
C4
C4
1
C1
C
5
O1
C5
C
O1
N1
H2
N1
H2
N2
N2
N2'
C6
C17
C17′
C6
Fig. 1. Structure of the molecule of diethyl 6,6′-(ethane-1,2-
diyldiimino)bis(5-benzoyl-1-methyl-2-oxo-1,2-dihydropyri-
dine-3-carboxylate) (VIIa) according to the X-ray diffraction
data. Intramolecular hydrogen bonds are shown with dotted
lines. Atoms related to the initial ones through the 2 axis are
denoted with primed numbers. Principal bond lengths (Å)
and bond angles (deg): C1–O1 1.214(2), C1–N1 1.426(2),
C1–C2 1.439(3), C2–C3 1.366(3), C3–C4 1.396(3), C4–C5
1.421(2), C4–C10 1.462(3), C5–N1 1.359(2), C5–N2 1.333(2),
N2–C17 1.463(3), C17–C17' 1.516(4); C1N1C5 124.3(2),
C5N2C17 125.9(3).
determined by X-ray analysis. The structure of mole-
cule VIIa and its principal geometric parameters are
given in Fig. 1. Molecule VIIa is symmetric; it is ex-
tended along the crystallographic 2 axis. It is unusual
The structure of molecule VIIc and its principal
geometric parameters are presented in Fig. 4. Exten-
sion of the (CH2)n central bridging fragment from n = 2
in molecule VIIa to n = 3 in VIIc (i.e., increase of the
distance between the dihydropyridine fragments) con-
siderably changes the molecular conformation: the tor-
sion angles N2C17C18C19 and N4C19C18C17 are –158.7
and 178.6°, respectively. The dihydropyridine rings
N2C1–C5 and N3C20–C24 are almost planar (deviations
of atoms from the corresponding mean-square planes
do not exceed 0.010 and 0.028 Å, respectively. The
bond configurations at the N1, N2, N3, and N4 approach
planar–trigonal (the sums of the bond angles at these
nitrogen atoms range from 355.5 to 359.9°). Effective
conjugation between lone electron pairs on the N1, N2,
N3, and N4 atoms, on the one hand, and π-electron
systems of the C4=C5 and C20=C24 bonds is observed:
the N1–C5 [1.380(5) Å], N2–C5 [1.336(5) Å], N3–C20
[1.363(5) Å], and N4–C20 bonds [1.352(5) Å] are ap-
preciably shorter than standard purely single Nsp2–Csp
3
bond (1.43–1.45 Å) [9, 10]. Like compound VIIa,
molecules VIIc in crystal are characterized by strong
intramolecular hydrogen bond N4–H4 · · · O8 with
the following parameters: O ···N 2.651(5), O···H
Fig. 2. A projection demonstrating synclinal conformation of
the central ethylene fragment in molecule VIIa.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 12 2009

RECYCLIZATION OF ETHYL 1-ALKYL-5-BENZOYL-6-METHYLSULFANYL-...
1837
1.99(5) Å; ∠OHN 141(5)°; as a result, six-membered
H-chelate ring N4C20C24C29O8H4 is formed. Molecules
VIIc in crystal are linked through medium-strength
intermolecular hydrogen bonds N2–H2 ···O1 [O···N
2.905(5), O···H 2.02(3) Å; ∠OHN 142(5)°] to form
zigzag chains as shown in Fig. 5. Thus compounds
VIIa and VIIc are characterized by considerably dif-
ferent molecular structures and crystal packings.
c
c
Some model reactions were performed to elucidate
the transformation sequence leading to compounds
IIIa–IIId, IVa, IVb, VIa–VId, and VIIa–VIIe
(Scheme 2). Hydrolysis of 1,2-dihydropyridin-2-one Іa
by the action of an aqueous–alcoholic solution of tri-
ethylamine was accompanied by elimination of the
methylsulfanyl group, and the product was dipyridyl
ether IVa. The latter readily reacted with ethane-1,2-
diamine (Va) to give compound VIIa in 83% yield,
and the reaction of VIIa with excess diamine Va
afforded 81% of N-methyl-8-benzoyl-5-oxo-1,2,3,5-
tetrahydroimidazo[1,2-a]pyridine-6-carboxamide
(VIa). Compound VIa was also synthesized by reac-
tion of ethyl 5-benzoyl-1-methyl-2-oxo-6-phenyl-
amino-1,2-dihydropyridine-3-carboxylate (IX) with
diamine Va, but the yield did not exceed 47%. We can
conclude that high thermodynamic stability of fused
heterocycles VIa–VId also favors the observed re-
cyclization.
a
a
0
b
Fig. 3. Packing of molecules VIIa in crystal.
most favorable for subsequent intramolecular cycliza-
tion to fused 3-alkylcarbamoyl-5-benzoylpyridin-2-one
derivatives VIa–VId.
Unlike reactions of ethyl 5-cyano-4-methyl-2-
methylsulfanyl-6-oxo-1-phenyl-1,6-dihydropyridine-3-
carboxylate with ethane-1,2-diamine and propane-1,3-
Scheme 2.
Et3N, H2O, EtOH
Va
C14
C13
C15
CC1166
IIa
IVa
VIIa
C13
C12
O
Ph
C11
5
C11
C25
C25
C12
O5
O
C9
C9
C10
EtO
O
O4
Va
Va
O4
C10
VIa
N3
O6
O6
21
C21
C22C26
C8
19
C3 3C4
O3 3
N3
C
C
C19
O
O
N
NHPh
18
C
C4
5
C5
C
C18
C
4
N4
N
C7
C20
C
27C2
C26
Me
C22
C7
C2
N2
C1717
C20
C24
C2
C
O7
O7
4
IX
H4
23
H
C23
NN11
2
O2
C
H2
H2
C24
C28
O
C
C1
C1
29
C29
C
The above experimental data led us to propose the
following recyclization mechanism (Scheme 3). Pre-
sumably, the first step is hydrolysis or aminolysis of
dihydropyridines Ia and Ib with formation of com-
pounds IVa and IVb or intermediates XIa–XId, re-
spectively. Hydrolysis products IVa and IVb are also
capable of undergoing aminolysis by the action of
diamines Va and Vb to give the same intermediates
XIa–XId. Itramolecular transamination of XIa–XId
with opening of the pyridine ring leads to dihydro-
imidazole (tetrahydropyrimidine) derivatives XIIa–
XIId which undergo isomerization at the double C=C
bond to adopt conformation XIІIa–XIIId which is the
8
C6
O
C30
O8
31
C31
C
O1 1
O
C6
C30
C35
C32
C32
C35
C34
C33
C34
Fig. 4. Structure of the molecule of diethyl 6,6′-(propane-
1,3-diyldiimino)bis(5-benzoyl-1-methyl-2-oxo-1,2-dihydro-
pyridine-3-carboxylate) (VIIc) according to the X-ray dif-
fraction data. Intramolecular hydrogen bonds are shown with
dotted lines. Principal bond lengths (Å) and bond angles
(deg): O1–C1 1.242(5), N1–C1 1.411(5), N1–C5 1.380(5),
N2–C5 1.336(5), N2–C17 1.433(5), O5–C21 1.228(5), N3–C20
1.363(5), N3–C21 1.424(5), N4–C19 1.481(5), N4–C20 1.352(5);
C1N1C5 124.5(3), C5N2C17 128.0(4), C20N3C21 123.8(3),
C19N3C20 132.0(4).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 12 2009

BRITSUN et al.
1838
Scheme 3.
O
O
Ph
HO–
Ia, Ib
–MeSH
Va, Vb
EtO
O
IVa, IVb
XIa–XId
–MeSH
N
O–
Ph
R
Xa, Xb
Ia, Ib
Ph
O
O
O
O
Va, Vb
EtO
O
EtO
RNH
–MeSH
NH2
NH
( )n
N
R
N
H
N
( )n
O
XIa–XId
XIIa–XIId
O
OEt
N
O
( )n
VIa–VId
R
NH
N
H
Ph
O
XIIIa–XIIId
R = Me, Et.
diamine, reported previously [12], the described recy-
clization of ethyl 1-alkyl-5-benzoyl-6-methylsulfanyl-
2-oxo-1,2-dihydropyridine-3-carboxylates involves
the ethoxycarbonyl group in the substrate, while no
elimination of the alkylamino group occurs, so that the
process is possible only via cleavage of the N–C6 bond
in the pyridine ring. As a result, bicyclic 5-benzoyl-
pyridin-2-one derivatives having a carboxamide func-
tionality can be obtained.
Thus the examined recyclization of ethyl 1-alkyl-5-
benzoyl-6-methylsulfanyl-2-oxo-1,2-dihydropyridine-
3-carboxylates is general, and it provides a new syn-
thetic route to previously unknown fused 3-alkylcar-
bamoyl-5-benzoylpyridin-2(1H)-one derivatives.
EXPERIMENTAL
1
The H and 13C NMR spectra were recorded on
a Varian Unity 300 spectrometer at 300 and 75 MHz,
respectively, using DMSO-d6 as solvent and tetrameth-
ylsilane as internal reference. The IR spectra were
measured in KBr on a UR-20 instrument. Ethyl 5-ben-
zoyl-1-methyl-2-oxo-6-phenylamino-1,2-dihydropyri-
dine-3-carboxylate (IX) was synthesized according to
the procedure described in [1].
The principal crystallographic parameters of com-
pounds VIIa and VIIc and details of the X-ray diffrac-
tion data acquisition and structure solution and refine-
ment are collected in table. The structures of both com-
Fig. 5. A fragment of crystal packing of compound VIIc
(phenyl and ethyl substituents are not shown).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 12 2009

RECYCLIZATION OF ETHYL 1-ALKYL-5-BENZOYL-6-METHYLSULFANYL-...
1839
Principal crystallographic parameters of compounds VIIa
and VIIc
pounds were solved by the direct method and were
refined by the least-squares procedure in full-matrix
anisotropic approximation using CRYSTALS software
package [13]. All hydrogen atoms were visualized by
difference syntheses of electron density and were in-
volved in the refinement procedure with fixed posi-
tional and thermal parameters. The positions of the H2
atom in molecule VIIa and of H2 and H4 in VIIc (these
hydrogen atoms participate in H bonding) were refined
in isotropic approximation. Chebyshev’s weight scheme
was applied [14]. The complete sets of crystallographic
data for compounds VIIa and VIIc were deposited to
the Cambridge Crystallographic Data Centre (entry
nos. CCDC 671856 and CCDC 710260).
Parameter
Diffractometer
Irradiation
VIIa
VIIc
Bruker Smart ApexII
MoKα
Scan range
–30 ≥ h ≥ 33
–11 ≥ k ≥ 11
–14 ≥ h ≥ 14
–11 ≥ k ≥ 14
–2334 ≥ l ≥ 8000 –15 ≥ l ≥ 12
28.7 26.4
0.25×0.30×0.51 0.19×0.40×0.47
θmax, deg
Crystal habit, mm
Crystal system
Space group
a, Å
Monoclinic
C2/c
Monoclinic
Pc
26.396(3)00
8.8113(7)
17.614(2)00
131.58(2)
3064.5(7)
8
12.2098(9)
11.4144(8)
12.0720(8)
108.732(2)
1593.3(2)
2
Recyclization of ethyl 1-alkyl-5-benzoyl-6-meth-
ylsulfanyl-2-oxo-1,2-dihydropyridine-3-carbox-
ylates Ia and Ib (general procedure). A solution of
1 mmol of 1,2-dihydropyridin-2-one Ia or Ib and
1.0 mmol of amine IIa or IIb (or 1.5 mmol of diamine
Va or Vb) in 4 ml of propan-2-ol was heated for 2–6 h
under reflux. The mixture was cooled, and the precip-
itate of compound IIIa–IIId or VIa–VId was filtered
off. Dipyridyl ether IVa or IVb was isolated by evap-
oration of the filtrate.
b, Å
c, Å
β, deg
V, Å3
Z
d
calc, g/cm3
1.36
1.33
μ, cm–1
0.98
0.96
F(000)
1320
624
Total number
of reflections
6984
9303
4-Benzoyl-N-methyl-1-oxo-1,5-dihydropyrido-
[1,2-a]benzimidazole-2-carboxamide (IIIa). Yield
70%, mp 283–285°C (from DMSO). IR spectrum, ν,
cm–1: 3330, 3000, 1675, 1620, 1600, 1560, 1540, 1470,
Number of independent
reflections
3689
2048
4484
3261
Number of reflections
1
1450, 1390, 1370. H NMR spectrum, δ, ppm: 2.85 d
with I ≥ 3σ(I)
(3H, NHCH3, J = 3.6 Hz), 7.48 m (1H, Harom), 7.63–
7.69 m (6H, Harom), 7.84 m (1H, 6-H), 8.68 s (1H,
3-H), 8.70 m (1H, 9-H), 9.00 br.s (1H, NHMe), 13.71 s
(1H, 5-H). 13C NMR spectrum, δC, ppm: 25.7 (NMe),
99.4, 105.6, 113.0, 116.4, 123.5, 126.8, 126.9, 128.4,
128.5, 131.2, 131.5, 138.5, 144.1, 144.9, 159.4 (C=O),
163.8 (C=O), 191.2 (PhC=O). Found, %: C 69.74;
H 4.31; N 12.13. C20H15N3O3. Calculated, %: C 69.56;
H 4.38; N 12.17.
Rmerge
0.020
0.044
0.047
1.077
0.010
0.044
0.046
1.209
R1 (F)
Rw (F)
Goodness of fit
Weight coefficients
0.23, –0.12, 1.28, –0.70, 1.14,
–0.11, –0.16
–0.30, 0.28
Residual electron den-
0.23/–0.20
0.60/–0.41
sity, max/min, e/cm3
4-Benzoyl-N-ethyl-1-oxo-1,5-dihydropyrido-
[1,2-a]benzimidazole-2-carboxamide (IIIb). Yield
63%, mp 272–275°C (from DMSO). IR spectrum, ν,
cm–1: 3330, 3000, 1685, 1610, 1560, 1470, 1440, 1390,
4-Benzoyl-N-methyl-1-oxo-1H-pyrido[2,1-b][1,3]-
benzothiazole-2-carboxamide (IIIc). Yield 61%,
mp 250–252°C (from DMSO). IR spectrum, ν, cm–1:
3350, 3000, 1670, 1615, 1560, 1490, 1460, 1420,
1
1370, 1340, 1320, 1260. H NMR spectrum, δ, ppm:
1
1.16 t (3H, CH2CH3, J = 6.3 Hz), 3.36 m (2H,
NHCH2), 7.49 m (1H, Harom), 7.62–7.76 m (6H, Harom),
7.88 m (1H, 6-H), 8.69 s (1H, 3-H), 8.71 m (1H, 9-H),
9.11 br.s (1H, NHEt), 13.73 s (1H, 5-H). Found, %:
C 69.89; H 4.56; N 11.85. C21H17N3O3. Calculated, %:
C 70.18; H 4.77; N 11.69.
1380, 1330. H NMR spectrum, δ, ppm: 2.87 d (3H,
NHCH3, J = 2.7 Hz), 7.66 m (7H, Harom), 8.23 m
(1H, 6-H), 8.74 s (1H, 3-H), 9.02 br.s (1H, NHCH3),
9.20 m (1H, 9-H). Found, %: C 66.02; H 4.15; N 7.48;
S 8.64. C20H14N2O3S. Calculated, %: C 66.29; H 3.89;
N 7.73; S 8.85.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 12 2009

BRITSUN et al.
1840
4-Benzoyl-N-ethyl-1-oxo-1H-pyrido[2,1-b][1,3]-
Yield 39%, mp 257–259°C (from nitromethane). IR
benzothiazole-2-carboxamide (IIId). Yield 57%,
mp 241–243°C (from DMSO). IR spectrum, ν, cm–1:
3300, 3000, 1690, 1620, 1570, 1500, 1470, 1385,
1310. 1H NMR spectrum, δ, ppm: 1.18 t (3H, CH2CH3,
J = 6.6 Hz), 3.34 m (2H, NHCH2), 7.68–7.83 m (7H,
spectrum, ν, cm–1: 3300, 3100, 3000, 1670, 1640,
1
1580, 1540, 1510, 1470, 1380. H NMR spectrum, δ,
ppm: 1.07 t (3H, CH2CH3, J = 6.6 Hz), 2.06 br.m (2H,
3-H), 3.47 br.m (2H, CH2CH3), 3.53 br.m (2H, 2-H),
3.98 br.m (2H, 4-H), 7.40–7.61 m (5H, Ph), 8.32 s
(1H, 8-H), 9.05 br.t (1H, NHCH2), 10.87 br.s (1H,
1-H). Found, %: C 66.64; H 5.68; N 13.15.
C18H19N3O3. Calculated, %: C 66.45; H 5.89; N 12.91.
H
arom), 8.26 m (1H, 6-H), 8.78 s (1H, 3-H), 9.15 br.s
(1H, NHEt), 9.24 m (1H, 9-H). Found, %: C 66.73;
H 4.42; N 7.29; S 8.40. C21H16N2O3S. Calculated, %:
C 67.01; H 4.28; N 7.44; S 8.52.
Compounds IVa and IVb (general procedure).
A solution of 1 mmol of 1,2-dihydropyridine Ia or Ib
and 3 mmol of triethylamine in 3 ml of 75% aqueous
ethanol was heated for 10 h under reflux. The solvent
was evaporated, the oily residue was dissolved in 3 ml
of water, 0.2 ml of acetic acid was added, the mixture
was cooled to 5°C, and the precipitate was filtered off.
8-Benzoyl-N-methyl-5-oxo-1,2,3,5-tetrahydro-
imidazo[1,2-a]pyridine-6-carboxamide (VIa). Yield
69%, mp 335–337°C (from DMSO). IR spectrum, ν,
cm–1: 3380, 3300, 3050, 2970, 1680, 1640, 1600, 1580,
1500. 1H NMR spectrum, δ, ppm: 2.75 d (3H, NHCH3,
J = 4.2 Hz), 3.91 m (2H, 2-H), 4.14 t (2H, 3-H, J =
9.3 Hz), 7.52 m (5H, Ph), 8.31 s (1H, 7-H), 8.90 br.s
(1H, NHCH3), 9.39 br.s (1H, 1-H). Found, %: C 64.37;
H 4.98; N 14.30. C16H15N3O3. Calculated, %: C 64.64;
H 5.09; N 14.13.
Diethyl 6,6′-oxybis(5-benzoyl-1-methyl-2-oxo-
1,2-dihydropyridine-3-carboxylate) (IVa). Yield
52%, mp 100–101°C (from propan-2-ol). IR spectrum,
ν, cm–1: 3100, 3000, 1730, 1680, 1600, 1530, 1460,
1
8-Benzoyl-N-ethyl-5-oxo-1,2,3,5-tetrahydro-
imidazo[1,2-a]pyridine-6-carboxamide (VIb). Yield
63%, mp 300–303°C (from DMSO). IR spectrum, ν,
cm–1: 3400, 3300, 3100, 3000, 1680, 1640, 1610, 1580,
1400, 1380, 1310. H NMR spectrum, δ, ppm: 1.24 t
(6H, CH2CH3, J = 6.9 Hz), 3.29 s (6H, NCH3), 4.19 q
(4H, OCH2, J = 6.9 Hz), 7.56–7.67 m (10H, Ph), 8.18 s
(2H, 4-H). 13C NMR spectrum, δC, ppm: 14.0
(CH2CH3), 26.6 (NCH3), 60.3 (OCH2), 104.4 (C4),
105.5 (C3), 128.5, 128.8, 132.3, 135.2, 144.1 (C5),
160.3 (C6), 164.8 (C2), 166.5 (CO2Et), 191.0 (PhC=O).
Found, %: C 65.94; H 4.66; N 4.64. C32H28N2O9. Cal-
culated, %: C 65.75; H 4.83; N 4.79.
1
1500, 1450, 1380, 1330. H NMR spectrum, δ, ppm:
1.08 t (3H, CH2CH3, J = 7.2 Hz), 3.21 m (2H,
NHCH2), 3.92 m (2H, 2-H), 4.13 t (2H, 3-H, J =
9.0 Hz), 7.53 m (5H, Ph), 8.32 s (1H, 7-H), 9.02 br.s
(1H, NHEt), 9.37 br.s (1H, 1-H). 13C NMR spectrum,
δC, ppm: 14.8 (CH2CH3), 33.2 (C2), 43.1 (CH2CH3),
43.4 (C3), 97.7, 106.5, 127.8, 128.3, 130.7, 138.8,
146.4, 156.3, 160.3 (C=O), 162.8 (C=O), 191.3
(PhC=O). Found, %: C 65.60; H 5.58; N 13.61.
C17H17N3O3. Calculated, %: C 65.58; H 5.50; N 13.50.
Diethyl 6,6′-oxybis(5-benzoyl-1-ethyl-2-oxo-1,2-
dihydropyridine-3-carboxylate) (IVb). Yield 45%,
mp 75–77°C (from propan-2-ol). IR spectrum, ν, cm–1:
3100, 3000, 1720, 1680, 1610, 1530, 1450, 1400,
1
1370, 1320. H NMR spectrum, δ, ppm: 1.28 m (12H,
9-Benzoyl-N-methyl-6-oxo-2,3,4,6-tetrahydro-
1H-pyrido[1,2-a]pyrimidine-7-carboxamide (VIc).
Yield 43%, mp 253–256°C (from nitromethane). IR
spectrum, ν, cm–1: 3300, 3100, 2950, 1670, 1640,
CH2CH3), 4.18 q (4H, OCH2, J = 7.1 Hz), 4.37 q (4H,
NCH2, J = 6.4 Hz), 7.52–7.65 m (10H, Ph), 8.17 s (2H,
4-H). Found, %: C 66.43; H 4.99; N 4.86. C34H32N2O9.
Calculated, %: C 66.66; H 5.26; N 4.57.
1
1590, 1550, 1510, 1440, 1400, 1380. H NMR spec-
Compounds VIIa–VIIe (general procedure). A so-
lution of 0.5 mmol of amine Va–Vc in 3 ml of propan-
2-ol was added dropwise under stirring to a solution of
1 mmol of dihydropyridine Іa or Ib in 3 ml of propan-
2-ol. The mixture was kept for 3 h at 20°C, and the
precipitate was filtered off.
trum, δ, ppm: 2.04 br.m (2H, 3-H), 2.75 d (3H,
NHCH3, J = 4.5 Hz), 3.52 br.m (2H, 2-H), 3.99 br.m
(2H, 4-H), 7.39–7.65 m (5H, Ph), 8.31 s (1H, 8-H),
8.92 q (1H, NHCH3, J = 4.5 Hz), 10.88 br.s (1H, 1-H).
13C NMR spectrum, δC, ppm: 18.7 (C3), 26.1 (NCH3),
38.7 (C2), 39.9 (C4), 98.8, 104.6, 128.5, 128.9, 131.1,
140.0, 146.8, 155.0, 161.4 (C=O) , 164.4 (C=O), 194.1
(PhC=O). Found, %: C 65.73; H 5.32; N 13.74.
C17H17N3O3. Calculated, %: C 65.58; H 5.50; N 13.50.
Diethyl 6,6′-(ethane-1,2-diyldiimino)bis(5-ben-
zoyl-1-methyl-2-oxo-1,2-dihydropyridine-3-carbox-
ylate) (VIIa). Yield 73%, mp 220–222°C (from nitro-
methane). IR spectrum, ν, cm–1: 3400, 3200, 3050,
9-Benzoyl-N-ethyl-6-oxo-2,3,4,6-tetrahydro-
1H-pyrido[1,2-a]pyrimidine-7-carboxamide (VId).
1
1720, 1680, 1580, 1540, 1500, 1660, 1440. H NMR
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 12 2009

RECYCLIZATION OF ETHYL 1-ALKYL-5-BENZOYL-6-METHYLSULFANYL-...
1841
methane). IR spectrum, ν, cm–1: 3100, 3000, 2900,
1720, 1680, 1570, 1600, 1500, 1470, 1450, 1410.
1H NMR spectrum, δ, ppm: 1.15 t (6H, CH2CH3, J =
7.2 Hz), 1.71 br.s (4H, CH2), 3.48 br.s (10H, NMe,
CH2), 4.08 q (4H, OCH2, J = 7.2 Hz), 7.42–7.65 m
(10H, Ph), 8.12 s (2H, 4-H), 9.90 s (2H, NH). Found,
%: C 65.76; H 6.03; N 8.69. C36H38N4O8. Calculated,
%: C 66.04; H 5.85; N 8.56.
spectrum, δ, ppm: 1.15 t (6H, CH2CH3, J = 6.9 Hz),
3.40 s (6H, NCH3), 3.65 br.s (4H, NCH2), 4.07 q (4H,
OCH2, J = 6.9 Hz), 7.45–7.56 m (10H, Ph), 8.04 s (2H,
4-H), 9.34 s (2H, NH). 13C NMR spectrum, δC, ppm:
14.7 (CH2CH3), 33.4 (NCH3), 48.0 (NCH2), 60.1
(OCH2), 101.5, 104.5, 128.8, 129.1, 132.0, 138.9,
148.2, 159.0, 160.2, 164.6 (C=O), 193.1 (PhC=O).
Found, %: C 65.32; H 5.22; N 9.07. C34H34N4O8. Cal-
culated, %: C 65.17; H 5.47; N 8.94.
N-Acetyl-4-benzoyl-1-oxo-1,5-dihydropyrido-
[1,2-a]benzimidazole-2-carboxamide (VІII). A solu-
tion of 1 mmol of compound IIIa and 2 mmol of
pyridine in 10 mmol of acetic anhydride was heated
for 8 h under reflux. The mixture was cooled, and the
precipitate was filtered off. Yield 75%, mp 245–247°C
(from DMSO). IR spectrum, ν, cm–1: 3250, 3000,
2950, 1690, 1670, 1620, 1560, 1540, 1490, 1460, 1390.
1H NMR spectrum, δ, ppm: 2.28 s (3H, CH3CO),
3.16 s (3H, NCH3), 7.51 m (1H, Harom), 7.55–7.72 m
(6H, Harom), 7.87 m (1H, 6-H), 8.18 (1H, 3-H), 8.70
(1H, 9-H), 13.78 (1H, 5-H). Found, %: C 68.06;
H 4.33; N 11.09. C22H17N3O4. Calculated, %: C 68.21;
H 4.42; N 10.85.
Diethyl 6,6′-(ethane-1,2-diyldiimino)bis(5-ben-
zoyl-1-ethyl-2-oxo-1,2-dihydropyridine-3-carbox-
ylate) (VIIb). Yield 69%, mp 155–158°C (from etha-
nol). IR spectrum, ν, cm–1: 3300, 3100, 3000, 1720,
1
1660, 1620, 1590, 1520, 1460, 1420. H NMR spec-
trum, δ, ppm: 1.14 m (12H, CH2CH3), 3.46 br.s (4H,
NCH2), 4.05 m (8H, CH2CH3), 7.48–7.57 m (10H,
Ph), 8.05 s (2H, 4-H), 8.76 s (2H, NH). 13C NMR spec-
trum, δC, ppm: 12.8 (NCH2CH3), 14.2 (OCH2CH3),
37.9 (NCH2CH3), 47.3 (NCH2), 59.5 (OCH2), 101.1,
103.6, 128.4, 128.8, 131.9, 138.1, 147.8, 157.4, 157.8,
164.2 (C=O), 191.3 (PhC=O). Found, %: C 65.83;
H 6.02; N 8.65. C36H38N4O8. Calculated, %: C 66.04;
H 5.85; N 8.56.
Recyclization of ethyl 5-benzoyl-1-methyl-2-oxo-
6-phenylamino-1,2-dihydropyridine-3-carboxylate
(IX) to 8-benzoyl-N-methyl-5-oxo-1,2,3,5-tetrahy-
droimidazo[1,2-a]pyridine-6-carboxamide (VIa).
A solution of 1 mmol of dihydropyridine IX and
1 mmol of diamine Va in 3 ml of propan-2-ol was
heated for 6 h under reflux. The mixture was cooled,
and the precipitate was filtered off. Yield 47%.
Diethyl 6,6′-(propane-1,3-diyldiimino)bis(5-ben-
zoyl-1-methyl-2-oxo-1,2-dihydropyridine-3-carbox-
ylate) (VIIc). Yield 67%, mp 215–218°C (from nitro-
methane). IR spectrum, ν, cm–1: 3400, 3200, 3000,
1
1720, 1660, 1580, 1520, 1450, 1370. H NMR spec-
trum, δ, ppm: 1.15 t (6H, CH2CH3, J = 7.2 Hz), 2.03 t
(2H, CH2, J = 6.6 Hz), 3.21 m (4H, NCH2), 3.43 s (6H,
NCH3), 4.08 q (4H, OCH2, J = 7.2 Hz), 7.44–7.61 m
(10H, Ph), 8.08 s (2H, 4-H), 9.43 s (2H, NH). 13C
NMR spectrum, δC, ppm: 14.7 (CH2CH3), 26.0 (CH2),
30.0 (NCH3), 48.0 (NCH2), 60.1 (OCH2), 101.5, 104.5,
128.8, 129.1, 132.0, 138.9, 148.2, 159.0, 160.2, 164.6,
193.1 (PhC=O). Found, %: C 65.45; H 5.84; N 9.02.
C35H36N4O8. Calculated, %: C 65.61; H 5.66; N 8.74.
REFERENCES
1. Britsun, V.N., Esipenko, A.N., Chernega, A.N., Rusa-
nov, E.B., and Lozinskii, M.O., Khim. Geterotsikl.
Soedin., 2007, p. 1660.
2. Britsun, V.N., Borisevich, A.N., Samoilenko, L.S., and
Lozinskii, M.O., Russ. J. Org. Chem., 2005, vol. 41,
p. 283.
3. Schirok, H., Alonso-Alija, C., and Michels, M.,
Synthesis, 2005, p. 3085.
4. Chacrabarti, S., Panda, K., Misra, N.C., Illa, H., and
Diethyl 6,6′-(propane-1,3-diyldiimino)bis(5-ben-
zoyl-1-methyl-2-oxo-1,2-dihydropyridine-3-carbox-
ylate) (VIId). Yield 62%, mp 123–125°C (from
propan-2-ol). IR spectrum, ν, cm–1: 3300, 3050, 3000,
1
1720, 1650, 1630, 1590, 1510, 1460, 1410. H NMR
Junjappa, H., Synlett, 2005, p. 1437.
spectrum, δ, ppm: 1.16 m (12H, CH2CH3), 1.99 t (2H,
CH2, J = 6.3 Hz), 3.17 m (4H, NCH2), 4.08 m (8H,
CH2CH3), 7.48–7.62 m (10H, Ph), 8.02 s (2H, 4-H),
8.89 s (2H, NH). Found, %: C 66.26; H 5.92; N 8.50.
C37H40N4O8. Calculated, %: C 66.45; H 6.03; N 8.38.
5. Britsun, V.N., Maiboroda, E.I., and Lozinskii, M.O.,
Khim. Geterotsikl. Soedin., 2008, p. 472.
6. Kalinin, A.A., Isaikina, O.G., and Mamedov, V.A.,
Khim. Geterotsikl. Soedin., 2007, p. 1539.
7. Tolmacheva, I.A., Mashevskaya, I.V., and Masli-
Diethyl 6,6′-(butane-1,4-diyldiimino)bis(5-ben-
zoyl-1-methyl-2-oxo-1,2-dihydropyridine-3-carbox-
ylate) (VIIe). Yield 60%, mp 233–236°C (from nitro-
vets, A.N., Russ. J. Org. Chem., 2001, vol. 37, p. 596.
8. Bozdyreva, K.S. and Maslivets, A.N., Russ. J. Org.
Chem., 2006, vol. 42, p. 463.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 12 2009

BRITSUN et al.
1842
9. Burke-Laing. M., and Laing, M., Acta Crystallogr.,
Sect. B, 1976, vol. 32, p. 3216.
12. Hehemann, D.G. and Winnik, W., J. Heterocycl. Chem.,
1994, vol. 31, p. 393.
10. Allen, F.H., Kennard, O., Watson, D.G., Brammer, L.,
Orpen, A.G., and Taylor, R., J. Chem. Soc., Perkin
Trans. 2, 1987, no. 12, p. S1.
13. Watkin, D.J., Prout, C.K., Carruthers, J.R., and Bet-
teridge, P.W., CRYSTALS. Issue 10, Chemical Crystal-
lography Laboratory, Univ. of Oxford, 1996.
11. Kuleshova, L.N. and Zorkii, P.M., Acta Crystallogr.,
Sect. B, 1981, vol. 37, p. 1363.
14. Carruthers, J.R. and Watkin, D.J., Acta Crystallogr.,
Sect. A, 1979, vol. 35, p. 698.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 12 2009