A convenient synthesis of 2H-pyran-2-ones, fused pyran-2-ones, and pyridones bearing a thiazole moiety

Article abstract of DOI:10.1002/jhet.1677

The versatile enaminonitrile, 2-cyano-3-(dimethylamino)-N-(4-phenylthiazol- 2-yl)-acrylamide (2), reacts with some C,O-binucleophiles (acetylacetone and dimedone) in refluxing acetic acid to afford the pyranone 4, the chromene 6 derivatives, and with C,N-

Full text of DOI:10.1002/jhet.1677

Month 2013
A Convenient Synthesis of 2H-Pyran-2-ones, Fused Pyran-2-ones,
and Pyridones Bearing a Thiazole Moiety
a
a
Samir Bondock,a,b Abd El-Gaber Tarhoni, and Ahmed A. Fadda
*
aChemistry Department, Faculty of Science, Mansoura University, ET-35516 Mansoura, Egypt
bChemistry Department, Faculty of Science, King Khalid University, 9004 Abha, Saudi Arabia
*
E-mail: bondock@mans.edu.eg
Received December 13, 2011
DOI 10.1002/jhet.1677
Published online 00 Month 2013 in Wiley Online Library (wileyonlinelibrary.com).
The versatile enaminonitrile, 2-cyano-3-(dimethylamino)-N-(4-phenylthiazol-2-yl)-acrylamide (2), reacts
with some C,O-binucleophiles (acetylacetone and dimedone) in refluxing acetic acid to afford the pyranone 4,
the chromene 6 derivatives, and with C,N-binucleophiles (2-(benzothiazol-2-yl)acetonitrile and 2-(1H-
benzimidazol-2-yl)acetonitrile) to afford the respective 1H-pyrido[2,1-b]benzothiazole 8 and pyrido
[1,2-a]benzimidazole 10 derivatives. Similar treatment of 2 with phenol, resorcinol, a-naphthol and
b-naphthol in boiling acetic acid gave the coumarin derivatives 12, 14, 16, and 18, respectively. The
utility of enaminonitrile 2 for the synthesis of 6H-pyrano[3,2-d]isoxazole 20, pyrano[2,3-c]pyrazole 22, and
pyrano[2,3-d]pyrimidine 24 derivatives was also explored via its reaction with 3-phenylisoxazol-5(4H)-one,
3-methyl-1-phenyl-1H-pyrazol-5(4H)-one, and barbituric acid, respectively. The mechanistic aspects for the
formation of the new compounds were also discussed.
J Hetercoyclic Chem., 00, 00 (2013).
INTRODUCTION
attracted a great interest because many of them are nonpeptide
HIV protease inhibitors [14–16].
2H-Pyran-2-ones and fused pyran-2-ones are important
biologically active compounds [1–6]. Among fused 2H-
pyran-2-one derivatives, 2H-1-benzopyran-2-one, coumarin,
plays an important role in the field of synthetic and medicinal
chemistry. Coumarin derivatives have exhibited various
pharmacological activities as bactericides [7,8], fungicides
[9], anti-inflammatory [10], anticoagulant [11], and antitu-
mor agents [12,13]. Recently, the synthesis of various
derivatives of pyran-2-one and fused pyran-2-one has
On the other hand, the 2-pyridone moiety is found to be
present in a large number of pharmaceuticals, agrochemicals,
and fine chemicals [17,18]. It is also a versatile synthon that
can act as a common intermediate for the synthesis of a wide
variety of alkaloids [18–20]. The presence of 3-(thiazole-2-
yl)carboxamido group in 2H-pyran-2-ones, fused 2H-pyra-
nones, and pyridones opens additional possibilities for their
utilization as building blocks in pharmaceutical chemistry.
© 2013 HeteroCorporation

S. Bondock, A. E-G Tarhoni, and A. A. Fadda
Vol 000
We have recently reviewed the chemistry of the synthesis
and application of heterocycles derived from enaminonitriles
[21] and described the behavior of 2-cyano-3-(dimethylamino)-
N-(4-phenylthiazol-2-yl)acrylamide towards some nitro-
gen nucleophiles as a possible synthetic route to attain
azoles, azines, diazepine, and azoloazines [22]. In contin-
uation of our interest in the synthesis of heterocycles
containing a thiazole moiety [23–28], we report herein the
results of our study of the reactions of 2-cyano-3-(dimethyla-
mino)-N-(4-phenylthiazol-2-yl)acrylamide with some C,O-
binucleophiles and C,N-binucleophiles. The aim of the
present paper is to present an efficient synthesis of novel
2H-pyran-2-ones, fused pyran-2-ones, and pyridones bear-
ing a thiazole moiety, which have not been reported hitherto.
and a broad singlet signal at d 12.85 ppm characteristic to
the NH proton. Its mass spectrum showed a molecular ion
peak at m/z = 394, which agrees with its molecular formula
C21H18N2O4S.
The formation of compounds 4 and 6 was assumed to
take place via the addition of the active methylene group
of acetylacetone and dimedone to the activated double
bond in the enaminonitrile 2 to give the nonisolable inter-
mediates 3 and 5 those underwent in situ cyclization via
the nucleophilic addition of the enolic hydroxyl group to
the nitrile function followed by hydrolysis and loss of a
dimethylamine molecule to give target compounds 4 and
6 (Scheme 1).
The reaction of enaminones with heterocyclic compounds
containing active methylene group attached at a-position in
respect to the ring nitrogen atom represents a simple
synthetic route to achieve polyfunctionally substituted fused
pyridine derivatives. With this context, we investigated the
reactivity of enaminonitrile 2 towards each of 2-(benzothiazol-
2-yl)acetonitrile and 2-(benzimidazol-2-yl)acetonitrile to obtain
fused pyridone derivatives.
RESULTS AND DISCUSSION
The starting 2-cyano-3-(dimethylamino)-N-(4-phenylthia-
zol-2-yl)acrylamide (2) [22] was prepared as previously
described from our laboratory via condensation of 2-cyano-
N-(4-phenylthiazol-2-yl)acetamide (1) [29] with dimethylfor-
mamide-dimethylacetal in refluxing toluene. Treatment of 2
with acetylacetone, as C,O-binucleophile, in glacial acetic
acid under reflux, led to the formation of 5-acetyl-6-methyl-
2-oxo-N-(4-phenylthiazol-2-yl)-2H-pyran-3-carboxamide
(4). The structure of 4 was inferred from elemental analysis
and spectral data. The IR spectrum revealed the disappear-
ance of absorption band characteristic to CꢀN function and
the presence of absorption bands at 3238, 1719, 1672, and
1644 cmÀ1 assignable to NH, pyrone C═O, and amidic
C═O functions, respectively. Its 1H NMR spectrum showed
three singlet signals at d 2.12, 2.26, and 8.64 ppm specific
for methyl, acetyl, and pyran (H4) protons, respectively, and
a broad singlet at d 13.01 ppm, exchangeable with D2O,
distinctive for NH proton. The 13C NMR spectrum revealed
16 carbon types; the most important signals were displayed
at d 18.9, 31.4, 162.3, 162.8, and 197.4 ppm characteristics
for methyl, methyl of acetyl, pyrone carbonyl, amidic
carbonyl, and ketonic carbonyl carbons, respectively. The
mass spectrum showed a molecular ion peak at m/z = 354
(M+) corresponding to a molecular formula C18H14N2O4S.
Next, we investigated the reactivity of enaminonitrile 2
towards dimedone as candidates for a facile synthetic route
to attain coumarin analogues. Thus, heating 2 with dimedone
in glacial acetic acid gave one isolable product that was iden-
tified as 7,7-dimethyl-2,5-dioxo-N-(4-phenylthiazol-2-yl)-
5,6,7,8-tetrahydro-2H-chromene-3-carboxamide (6). The
assignment of structure 6 was based on IR spectrum that
revealed the absorption bands at 3380, 1720, 1690, and
1655cmÀ1 assignable to NH, cyclic ester, cyclic C═O, and
amidic C═O functions, respectively. The 1H NMR spectrum
displayed five singlet signals at d 1.21, 1.23, 2.42, 2.68, and
8.73ppm owing to two germinal methyl, coumarin (2H8),
coumarin (2H6), and coumarin (H4) protons, respectively,
Thus, when the enaminonitrile 2 was subjected to react
with 2-(benzothiazol-2-yl)acetonitrile, as C,N-binucleophile,
in boiling glacial acetic acid, it afforded the 1H-pyrido[2,1-b]
benzothiazole derivative 8. The structure of the latter product
was confirmed on the basis of elemental analysis and spectral
data. The IR spectrum exhibited absorption bands at 3360,
2219, 1695 and 1656 cmÀ1 characteristic to NH, C ꢀ N,
1
and two amidic C═O groups, respectively. Its H NMR
spectrum revealed an aromatic multiplet in the region d
6.90–7.96 ppm, a singlet at d 8.72 ppm due to fused pyridine
(H3) proton and a broad singlet at d 12.71 ppm attributed
to NH proton. The mass spectrum showed a molecular ion
peak at m/z = 428 corresponding to a molecular formula
C22H12N4O2S2.
In a similar manner, the reaction of 2 with 2-(1H-
benzimidazol-2-yl)acetonitrile in refluxing acetic acid
afforded a single product that was identified as 4-cyano-
1-oxo-N-(4-phenylthiazol-2-yl)-1,5-dihydropyrido[1,2-a]
benzimidazole-2-carboxamide (10) based on elemental
analysis and spectral data (see experimental).
The plausible mechanism for the formation of compounds
8 and 10 may be attributed to the nucleophilic addition of the
active methylene group of both 2-(benzothiazol-2-yl)aceto-
nitrile and 2-(benzimidazol-2-yl)acetonitrile to the b-carbon
of the enaminonitrile 2 to give the nonisolable intermediates
7 and 9, those underwent in situ intramolecular cyclization
via the nucleophilic addition of the ring nitrogen atom to
the nitrile function followed by hydrolysis and elimination
of a dimethylamine molecule to give the target products
8 and 10.
The forgoing results prompted us to study the reactivity
of the enaminonitrile 2 towards some aromatic C,O-
binucleophiles as a possible synthetic route to attain fused
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Synthesis of 2H-Pyran-2-ones, Fused Pyran-2-ones, and Pyridones
Scheme 1. Reaction of enaminonitrile 2 with some C,O-binucleophiles and C,N-binucleophiles.
2H-pyran-2-ones. Phenols and their annulated naphthols
are well known to be used as C,O-binucleophiles in the
synthesis of condensed system of 2H-pyran-2-ones. In this
context, we investigated the reactivity of enaminonitrile 2
to some phenols and naphthols. Thus, when 2 was
subjected to react with phenol in refluxing glacial acetic acid,
the reaction mixture followed up by TLC. After some time,
approximately 48 h, a little pale yellow crystals got depos-
ited, and it was identified as 2-oxo-N-(4-phenylthiazol-2-
yl)-2H-chromene-3-carboxamide (12). The assignment of
the structure of the latter product was based on its elemental
analysis and spectral data (see Experimental section).
Furthermore, the structure of the product 12 was confirmed
by its alternative synthesis by reaction of 2-cyano-N-(4-
phenylthiazol-2-yl)acetamide (1) with salicylaldehyde in
refluxing ethanol containing a catalytic amount of piperidine
(Scheme 2).
to coumarin (H8) and (H4) protons, respectively, two doub-
lets at d 6.94 (J = 5.6 Hz) and 7.65ppm (J = 5.6 Hz) due to
coumarin (H5) and (H6) protons, and two broad singlets at
d 10.41 and 13.04 ppm owing to NH and OH protons,
respectively. The mass spectrum showed a molecular ion
peak at m/z = 364 (M+) corresponding to a molecular formula
C19H12N2O4S.
The reactivity of enaminonitrile 2 towards some
naphthols was also examined. Thus, reaction of 2 with
a-naphthol in acetic acid under reflux yielded a single
product identified as 2-oxo-N-(4-phenylthiazol-2yl)-2H-
benzo[h]chromene-3-carboxamide (16).
In a similar manner, treatment of 2 with b-naphthol
under the same reaction condition afforded the respective
3-oxo-3H-benzo[f]chromene-2-carboxamide derivative 18.
The structure of the products 16 and 18 was elucidated on
the basis of their spectra and elemental analyses. For exam-
ple, the IR spectrum of 16 showed absorption bands at
3368, 1728, and 1661cmÀ1 assignable to NH, cyclic C═O
ester, and amidic C═O functions, respectively. The 1H
Similar treatment of 2 with resorcinol in glacial acetic acid
under reflux afforded only one isolable product that was
identified, on the basis of its spectral data and elemental
analysis, as the coumarin derivative 14. Its IR spectrum
displayed the absence of CꢀN stretching absorption band
and the presence of absorption bands characteristic to OH,
NH, cyclic ester, and amidic C═O stretching at 3450,
NMR spectrum exhibited two doublets at
d 7.77
(J = 4.8 Hz) and 8.50 ppm (J = 4.8 Hz) assignable to benzo-
chromene (H5) and benzochromene (H6) protons, a multiplet
signal at d 7.29–8.02 ppm region due to aromatic protons, a
singlet at d 8.81ppm characteristic to benzochromene (H4)
proton, and a broad singlet signal at d 11.12 ppm assignable
1
3365, 1719, and 1658 cmÀ1, respectively. The H NMR
spectrum showed two singlets at d 6.81 and 8.48 ppm owing
Journal of Heterocyclic Chemistry
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S. Bondock, A. E-G Tarhoni, and A. A. Fadda
Vol 000
Scheme 2. Reactions of enaminonitrile 2 with some phenols and naphthols.
to NH proton. Its 13C NMR spectrum revealed 21 carbon
types; the most important signals were displayed at d 158.4
and 164.2 ppm specific for cyclic carbonyl and acyclic
carbonyl carbons. The mass spectrum showed a molecular
ion peak at m/z = 398 (M+) corresponding to a molecular
formula C23H14N2O3S.
1671 cmÀ1 specific for pyrone C═O and amidic C═O
functions, respectively. Its H NMR spectrum displayed a
1
singlet at d 8.89 ppm due to fused pyran (H4) proton and
a broad singlet at d 12.51 ppm, exchangeable with D2O,
specific for the NH proton. In addition, the mass spectrum
showed
a
molecular ion peak at m/z = 415 (M+)
To account for the formation of the products 12, 14, 16,
and 18, it is suggested as depicted in Scheme 2 that the
studied reactions started with Michael-type addition of the
carbon atom adjacent to hydroxyl group of each of the
phenols and naphthols used to the activated double bond of
2 followed by in situ tandem elimination of dimethylamine
and deaminative cyclization (Scheme 2).
Finally, reactions of the enaminonitrile 2 with an active
methylene group incorporated into heterocyclic system,
latent C,O-binucleophiles, were examined. Thus, reaction
of 2 with 3-phenylisoxazol-5(4H)-one in refluxing glacial
acetic acid afforded the corresponding 6H-pyrano[3,2-d]
isoxazole derivative 20 (Scheme 3). The chemical structure
of 20 was elucidated on the basis of its elemental analysis
and spectral data. The IR spectrum was free of a nitrile
function and showed absorption band for NH function at
3372 cmÀ1 and two sharp absorption bands at 1724 and
corresponding to a molecular formula C22H13N3O4S.
Similar treatment of 2 with 3-methyl-1-phenyl-1H-
pyrazol-5(4H)-one and barbituric acid under the same
reaction conditions afforded the respective pyrano[2,3-c]
pyrazole and pyrano[2,3-d]pyrimidine derivatives 22 and
24, respectively. The structures of the products 22 and 24
were elucidated on the basis of their spectra and elemental
analyses. For example, the IR spectrum of compound 24
exhibited the absence of absorption band due to a nitrile
function and the presence of absorption bands at 3369–
3232, 1722, 1683, 1669, and 1654 cmÀ1 characteristic for
three NH, pyrone C═O and three amidic C═O functions,
1
respectively. Its H NMR spectrum displayed a singlet at
d 8.61 ppm assignable to fused pyran (H5) proton, in addi-
tion to three broad signals at d 7.74, 9.84, and 12.76 ppm,
exchangeable with D2O, assignable to three NH protons.
Its 13C NMR spectrum revealed 15 carbon types, the most
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Synthesis of 2H-Pyran-2-ones, Fused Pyran-2-ones, and Pyridones
Scheme 3. Reactions of enaminonitrile 2 with some heterocyclic C,O-binucleophiles.
ionizing voltage was 70 eV, at the Faculty of Science, Cairo Univer-
sity. Elemental analyses were carried out by the Microanalytical Unit
of Faculty of Science, Cairo University, Giza, Egypt, and the results
were in a good agreement (Æ0.3%) with the calculated values. All
reactions were followed by TLC (silica gel, aluminum sheets
60 F254, Merk). 2-Cyano-N-(4-phenylthiazol-2-yl)acetamide (1)
[29] and 2-cyano-3-(dimethylamino)-N-(4-phenylthiazol-2-yl)
acrylamide (2) [22] were prepared according to previously
reported procedure.
important signals being displayed at d 165.4, 162.9, 162.6,
and 160.2 ppm specific for pyrone carbonyl, pyrimidine
two carbonyl, and amidic carbonyl carbons, respectively.
In addition, the mass spectrum showed a molecular ion
peak at m/z = 382 (M+) corresponding to a molecular
formula C17H10N4O5S.
Here also, it is suggested that the formation of the
products 20, 22, and 24 seems to start with Michael addition
of the active methylene group of heterocycles to the activated
double bond of 2 to give the nonisolable intermediates 19,
21, and 23, those underwent tandem cyclization, elimination
of dimethylamine, hydrolysis, and deamination to give 20,
22, and 24 as end products.
In conclusion, the results of the present study indicate
that the enaminonitrile, C,O-binucleophile, and C,N-
binucleophile are useful precursors for the facile and
convenient synthesis of different functionalized 2H-pyran-
2-one, fused 2H-pyran-2-ones, and pyridones bearing a
thiazole moiety. In addition, they indicate that reactions of
the studied enaminonitrile are regiospecific as they yielded,
in each case, one product in good yield. The compounds
prepared are expected to be of pharmacological interest.
General procedure for the reaction of enaminonitrile 2 with
C,O-binucleophiles and C,N-binucleophiles. To a solution of
enaminonitrile 2 (0.298 g, 0.001 mol) in glacial acetic acid (3–5mL),
an equimolar amount of the appropriate C,O-binucleophiles and
C,N-binucleophiles was added, the mixture was heated in oil bath
under reflux for 10–48h, and then evaporated in vacuo. The
residue was triturated with ethanol, and the resulting solid
product was collected by filtration, dried well, and recrystallized
from the appropriate solvent to give compounds 4, 6, 8, 10, 12,
14, 16, 18, 20, 22, and 24.
5-Acetyl-6-methyl-2-oxo-N-(4-phenylthiazol-2-yl)-2H-pyran-
3-carboxamide (4). This compound was prepared from
acetylacetone (0.13 g) by heating for 10 h under reflux and
recrystallized from a mixture of ethanol and dimethylformamide
(1:1).
White powdered; yield 57%; mp 269–270ꢁC; IR (KBr): vmax.
/
cmÀ1 = 3238 (NH), 1719 (pyrone C═O), 1672 (amidic C═O). 1H
NMR (DMSO–d6): dppm = 2.12 (s, 3H, CH3), 2.26 (s, 3H, COCH3),
7.30–7.95 (m, 5H, Ar-H), 7.57 (s, 1H, thiazole H-5), 8.64 (s,
1H, pyran H-4), 13.01 (s, br, 1H, NH). 13C NMR (DMSO–d6):
EXPERIMENTAL
All melting points were determined on an electrothermal 9100
Gallenkamp apparatus (Germany). The IR spectra were measured
on a Mattson 5000 FTIR spectrometer (USA) in potassium bro-
d
ppm = 18.9 (CH3), 31.4 (CH3), 105.5 (thiazole C-5), 116.4 (pyran
C-3), 125.6 (2CHAr), 127.7 (pyran C-5), 128.5 (2CHAr), 129.6
(CHAr), 131.4 (CAr), 153.7 (pyran C-2), 155.6 (pyran C-6), 159.9
(thiazole C-4), 162.6 (thiazole C-2), 162.8 (CONH), 163.2 (pyran
C═O), 197.4 (C═O). MS m/z (%): 354 (M+, 36.4), 339 (37.8),
310 (22.5), 268 (28.6), 202 (54.9), 179 (36.6), 175 (23.2), 160
(16.7), 151 (100.0), 137 (19.1), 108 (36.6), 77 (19.8), 54 (21.6).
1
mide disks. The H NMR and 13C NMR spectra were recorded
in DMSO-d6 or CDCl3 on a Bruker WP spectrometer (USA)
(300 MHz for 1H NMR and 75 MHz for 13C NMR) and the chemical
shifts d downfield from TMS as an internal standard. The mass spec-
tra were recorded on Finnigan MAT 212 instrument (USA), and the
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S. Bondock, A. E-G Tarhoni, and A. A. Fadda
Vol 000
Anal. Calcd for C18H14N2O4S (354.38): C 61.01; H 3.98; N 7.90%,
Found: C 61.24; H 3.83; N 7.86%.
(19.7), 203 (24.9), 175 (46.6) 173 (100), 160 (14.8), 145 (28.3),
77 (19.9), 51(28.8). Anal. Calcd for C19H12N2O3S (348.38): C
7,7-Dimethyl-2,5-dioxo-N-(4-phenylthiazol-2-yl)-5,6,7,8-
tetrahydro-2H-chromene-3-carboxamide (6). This compound
was prepared from dimedone (0.14) by heating for 10 h under
65.51; H 3.47; N 8.04%, found: C 65.34; H 3.43; N 8.20%.
7-Hydroxy-2-oxo-N-(4-phenylthiazol-2-yl)-2H-chromene-3-
carboxamide (14). This compound was prepared from resorcinol
(0.11 g) by heating for 15 h under reflux and recrystallized from a
mixture of ethanol and dimethylformamide (1:1).
reflux and recrystallized from
a mixture of ethanol and
dimethylformamide (1:1).
Brown powdered; yield 62%; mp 287–288ꢁC; IR (KBr): vmax.
/
Pale yellow crystal; Yield 55%; mp 279–280ꢁC; IR (KBr): vmax.
/
cmÀ1 = 3450 (OH), 3365 (NH),1719 (cyclic ester), 1658 (amidic
C═O). 1H NMR (DMSO–d6): dppm = 6.81 (s, 1H, chromene
H-8), 6.94 (d, J = 5.6 Hz, 1H, chromene H-5), 7.65 (d, J = 5.6 Hz,
1H, chromene H-6), 7.28–7.77 (m, 9H, Ar-H),7.52 (s, 1H, thiazole
H-5), 8.48 (s, 1H, chromene H-4), 10.41 (s, br, 1H, NH), 13.04
(s, br, 1H, OH). MS m/z (%): 364 (M+, 31.8), 320 (39.7), 287
(19.7), 203 (45.3), 189 (100), 175 (18.3), 160 (26.3), 77 (28.3),
58 (20.3). Anal. Calcd for C19H12N2O4S (364.37): C 62.63; H
3.32; N 7.69%, found: C 62.42; H 3.43; N 7.52%.
cmÀ1 = 3380 (NH), 1720 (cyclic ester), 1665 (cyclic C═O), 1655
1
(amidic C═O). H NMR (DMSO–d6): dppm = 1.21 (s, 3H, CH3),
1.23 (s, 3H, CH3), 2.42 (s, 2H, chromene 8-CH2), 2.68 (s, 2H,
chromene 6-CH2), 7.29–7.96 (m, 5H, Ar-H), 7.57 (s, 1H, thiazole
H-5), 8.73 (s, 1H, chromene H-4), 12.85 (s, br, 1H, NH). MS m/z
(%): 394 (M+, 36.5), 350 (19.6), 324 (30.2), 252 (26.3), 229
(33.2), 220 (46.6), 203 (16.3), 191 (100), 175 (34.6), 160 (15.8),
123 (21.4), 77 (23.6), 58 (18.3). Anal. Calcd for C21H18N2O4S
(394.44): C 63.94; H 4.60; N 7.10%, found: C 64.04; H 4.51;
2-Oxo-N-(4-phenylthiazol-2-yl)-2H-benzo[h]chromene-3-
carboxamide (16). This compound was prepared from a-naphthol
(0.144 g) by heating for 16 h under reflux and recrystallized from a
mixture of ethanol and dimethylformamide (1:1).
N 7.02%.
4-Cyano-1-oxo-N-(4-phenylthiazol-2-yl)-1H-pyrido[2,1-b]
benzothiazole-2-carboxamide (8). This compound was prepared
from (benzothiazol-2-yl)acetonitrile (0.174 g) by heating for 10h
under reflux and recrystallized from a mixture of ethanol and
dimethylformamide (1:1).
Deep brown powdered; yield 59%; mp 298–299ꢁC; IR (KBr):
vmax./cmÀ1 = 3368 (NH), 1728 (cyclic ester), 1661 (amidic C═O).
1H NMR (DMSO–d6): dppm = 7.29–8.02 (m, 9H, Ar-H), 7.52 (s,
1H, thiazole H-5), 7.77 (d, J = 4.8 Hz, 1H, benzochromene H-5),
8.50 (d, J = 4.8 Hz, 1H, benzochromene H-6), 8.81 (s, 1H, benzo-
chromene H-4), 11.12 (s, br, 1H, NH). 13C NMR (DMSO–d6):
Brown powdered; yield 54%; mp 281–282ꢁC; IR (KBr): vmax.
/
cmÀ1 = 3360 (NH), 2219 (CꢀN), 1695, 1656 (2 amidic C═O).
1H NMR (DMSO–d6): dppm = 6.9–7.96 (m, 9H, Ar-H), 7.49
(s, 1H, thiazole H-5), 8.72 (s, 1H, pyridobenzothiazole H-3),
12.71 (s, br, 1H, NH). MS m/z (%): 428 (M+, 39.7), 376 (27.8),
320 (19.2), 253 (26.9), 225 (43.3), 203 (28.4), 175 (34.6), 160
(100), 134 (53.3), 77 (33.8), 58 (17.3). Anal. Calcd for
C22H12N4O2S2 (428.49): C 61.67; H 2.82; N 13.08%, found: C
d
ppm = 105.5 (thiazole C-5), 117.5 (benzopyran C-3), 119.3,
120.8, 121.6, 123.3, 125.3, 125.5, 126.2, 127.3, 127.7, 128.3,
128.8, 129.3, 131.0, 131.1, 133.6 (CHAr + CAr), 150.5 (thiazole C-
4), 155.1 (thiazole C-2), 158.4 (CONH), 165.4 (benzopyran
C═O). MS m/z (%): 398 (M+, 24.3), 354 (33.5), 223 (100), 203
(31.3), 195 (36.6), 175 (29.9), 160 (21.3), 152 (24.8), 77 (30.4),
58 (18.6). Anal. Calcd for C23H14N2O3S (398.43): C 69.33; H
61.48; H 2.91; N 13.22%.
4-Cyano-1-oxo-N-(4-phenylthiazol-2-yl)-1,5-dihydropyrido
[1,2a]benzimidazole-2-carboxamide (10). This compound was
prepared from (benzimidazol-2-yl)acetonitrile (0.157g) by heating
for 12h under reflux and recrystallized from a mixture of ethanol
and dimethylformamide (1:1).
3.54; N 7.03%, found: C 69.24; H 3.62; N 7.19%.
3-Oxo-N-(4-phenylthiazol-2-yl)-3H-benzo[f]chromene-2-
carboxamide (18). This compound was prepared from b-naphthol
(0.144 g) by heating for 16 h under reflux and recrystallized from a
mixture of ethanol and dimethylformamide (1:1).
Yellowish brown powdered; yield 56%; mp 293–294ꢁC; IR
(KBr): vmax./cmÀ1 = 3410–3378 (2NH), 2215 (CꢀN), 1690, 1658
(2 amidic C═O). 1H NMR (DMSO–d6): dppm = 7.05–7.96 (m,
9H, Ar-H), 7.49 (s, 1H, thiazole H-5), 8.75 (s, 1H, pyridobenzimi-
dazole H-3), 9.18 (s, br, 1H, NH), 12.79 (s, br, 1H, NH). MS m/z
(%): 411(M+, 33.9), 383 (23.3), 336 (20.2), 258 (29.7), 236
(19.8), 208 (100), 203 (36.6), 175 (20.3), 160 (23.1), 133 (50.2),
77 (27.9), 54 (16.7). Anal. Calcd for C22H13N5O2S (411.44): C
64.22; H 3.18; N 17.02%, found: C 64.04; H 3.23; N 17.14%.
2-Oxo-N-(4-phenylthiazol-2-yl)-2H-chromene-3-carboxamide
Reddish brown powdered; yield 82%; mp > 300ꢁC; IR (KBr):
vmax./cmÀ1 = 3362 (NH), 1726 (cyclic ester), 1659 (amidic C═O).
1H NMR (DMSO–d6): dppm = 7.87–8.01 (m, 9H, Ar-H), 7.52
(s, 1H, thiazole H-5), 7.64 (d, J = 4.6 Hz, 1H, benzochromene
H-5), 8.38 (d, J = 4.6 Hz, 1H, benzochromene H-6), 9.92
(s, 1H, benzochromene H-1), 11.22 (s, br, 1H, NH). Anal. Calcd
for C23H14N2O3S (398.43): C 69.33; H 3.54; N 7.03%, found:
C 69.56; H 3.44; N 7.11%.
(12).
This compound was prepared from phenol (0.094 g) by
6-Oxo-3-phenyl-N-(4-phenylthiazol-2-yl)-6H-pyrano[3,2-d]
isoxazole-5-carboxamide (20). This compound was prepared
from 3-phenylisoxazol-5-one (0.161 g) by heating for 6 h under
reflux and recrystallized from a mixture of ethanol and
dimethylformamide (1:1).
heating for 48 h under reflux and recrystallized from a mixture of
methanol and dimethylformamide (1:1).
Alternative method for the synthesis of compound 12. A
mixture of compound 1 (0.243 g, 0.001 mol) and salicylaldehyde
(0.122 g, 0.001 mol) in ethanol (30 mL) containing a little amount of
piperidine (3 drops) was refluxed for 3 h. The reaction mixture was
allowed to cool to room temperature and then pour onto ice cold
water (25 mL) containing few drops of conc. HCl. The precipitated
product was filtered off, dried well, and crystallized from a mixture of
Yellow powdered; yield 62%; mp 275–276ꢁC; IR (KBr): vma1x.
/
cmÀ1 = 3372 (NH), 1724 (cyclic ester), 1671 (amidic C═O). H
NMR (DMSO–d6): dppm = 6.98–7.87 (m, 10H, Ar-H), 7.52
(s, 1H, thiazole H-5), 8.89 (s, 1H, pyranoisoxazole H-4), 12.51
(s, br, 1H, NH). MS m/z (%): 415 (M+, 35.7), 371(50.6), 240
(26.6), 212 (100), 203 (54.4), 175 (36.3), 160 (17.8), 77 (18.3),
58 (22.3). Anal. Calcd for C22H13N3O4S (415.42): C 63.61; H
methanol and dimethylformamide (1:1) to give compound 12.
Pale yellow crystals; yield 48%; mp 269–270ꢁC; IR (KBr):
vmax./cmÀ1 = 3378 (NH), 1725 (cyclic easter), 1657 (amidic
3.15; N 10.12%, found: C 63.44; H 3.23; N 10.21%.
1
3-Methyl-6-oxo-1-phenyl-N-(4-phenylthiazol-2-yl)-1,6-
C═O). H NMR (DMSO–d6): dppm = 7.13–7.79 (m, 9H, Ar-H),
dihydropyrano [2,3-c]pyrazole-5-carboxamide (22). This
compound was prepared from 3-methyl-1-phenyl-1H-pyrazol-5
7.52 (s, 1H, thiazole H-5), 8.43 (s, 1H, chromene H-4), 10.68
(s, br, 1H, NH). MS m/z (%): 348 (M+, 40.1), 304 (49.2), 271
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet.1677

Month 2013
Synthesis of 2H-Pyran-2-ones, Fused Pyran-2-ones, and Pyridones
(4H)-one (0.174 g) by heating for 10 h under reflux and recrystallized
Katritzky, A. R.; Rees, C. W.; Scriven, E. F. V. Eds.; Pergamon Press: Oxford,
1996; Vol. 5, pp 469–500.
[4] Afarinkia, K.; Vinader, M. V. In: Science of Synthesis;
Thomas, E. J. Ed.; Thieme: Stuttgart, 2003; Vol. 14, pp 275–346.
from a mixture of ethanol and dimethylformamide (1:1).
Deep yellow crystal; yield 51%; mp 284–285ꢁC; IR (KBr): vma1x.
/
cmÀ1 = 3386 (NH), 1725 (cyclic ester), 1665 (amidic C═O). H
NMR (DMSO–d6): dppm = 2.21 (s, 3H, CH3), 7.29–7.92 (m, 10H,
Ar-H), 7.52 (s, 1H, thiazole H-5), 8.67 (s, 1H, pyranopyrazole H-
4), 12.33 (s, br, 1H, NH). MS m/z (%): 428 (M+, 43.6), 413
(29.8), 336 (22.5), 253 (100), 225 (36.4), 203 (30.2), 175 (40.6),
160 (23.7), 77 (30.3), 54 (18.3). Anal. Calcd for C23H16N4O3S
(428.46): C 64.47; H 3.76; N 13.08%, found: C 64.65; H 3.68;
ꢀ
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N 13.14%.
2,4,7-Trioxo-N-(4-phenylthiazol-2-yl)-2,3,4,7-tetrahydro-
1H-pyrano[2,3-d]pyrmidine-6-carboxamide (24). This compound
was prepared from barbituric acid (0.128 g) by heating for 12 h
under reflux and recrystallized from a mixture of ethanol and
dimethylformamide (1:1).
Yellowish brown powdered; yield 49%; mp 122–123ꢁC; IR
(KBr): vmax./cmÀ1 = 3369–3232 (3NH), 1722 (cyclic ester),
[13] Raev, L.; Voinov, E.; Ivanov, I.; Popov, D. Pharmazie 1990, 45, 696.
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B.; Pochet, L. J Med Chem 2007, 50, 3645.
1683, 1669, 1654 (3amidic C═O). 1H NMR (DMSO–d6): dppm
=
7.20–7.96 (m, 5H, Ar-H), 7.59 (s, 1H, thiazole H-5), 7.74 (s, br,
1H, NH), 8.61 (s, 1H, pyranopyrimidine H-5), 9.84 (s, br, 1H,
NH), 12.76 (s, br, 1H, NH). 13C NMR (DMSO–d6): dppm = 85.8
(C-4a), 108.6 (thiazole C-5),119.5 (C-6), 125.2 (2CHAr), 127.8
(2CHAr), 129.5 (CHAr), 131.9 (CAr), 149.3 (C-5), 155.7 (C-8a),
152.8 (thiazole C-4), 159.6 (thiazole C-2), 160.2 (CONH),
162.6 (pyrimidine C═O), 162.9 (pyrimidine C═O), 165.4 (pyran
C═O). MS m/z (%): 382 (M+, 27.9), 354 (36.6), 305 (23.3), 207
(100), 203 (23.3), 175 (31.6), 160 (23.7), 111 (19.5), 77 (26.3),
58 (19.9). Anal. Calcd for C17H10N4O5S (382.35): C 53.40; H
2.64; N 14.65%, found: C 53.26; H 2.73; N 14.47%.
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REFERENCES AND NOTES
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Heterocyclic Chemistry II: Pyrans and their Benzo Derivatives: Synthesis;
Katritzky, A. R.; Rees, C. W.; Scriven, E. F. V. Eds.; Pergamon Press:
Oxford, 1996; Vol. 5, pp 351–468.
[27] Abdel-Latif, E.; Bondock, S. Heteroatom Chem 2006 17, 299.
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Metwally, M. A. Sulfur Lett 2003, 26, 127.
[3] Geen, G. R.; Evans, J. M.; Vong, A. K. In Comprehensive
Heterocyclic Chemistry II: Pyrans and their Benzo Derivatives: Applications;
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet.1677