Synthesis of some new azole, pyrimidine, pyran, and benzo/naphtho[b]furan derivatives incorporating thiazolo[3,2-a]benzimidazole moiety

Article abstract of DOI:10.1002/jhet.584

Reaction of E-3-(N,N-dimethylamino)-1-(3-methylthiazolo[3,2-a]benzimidazol- 2-yl)prop-2-en-1-one (1) with some N-nucleophiles, such as anilines 2a-c, 4-amino-N-pyridin-2-yl-benzenesulfonamide (4a), 4-amino-N-pyrimidin-2-yl- benzenesulfonamide (4b), hydrazine, hydroxylamine, thiourea, and guanidine afforded the corresponding arylaminoprop-2-en-1-one derivatives 3a-c, 5a,b, the pyrazole, isoxazole, pyrimidinethione and aminopyrimidine derivatives 7a, 7b, 9a, and 9b, respectively. The utility of compound 1, as a versatile building block, for the synthesis of the pyranone 13, benzo[b]furan 17a, and naphtho[1,2-b]furan 17b was also explored via its reaction with 2-benzamidoacetic acid (10), 1,4-benzoquinone (14a), and 1,4-naphthoquinone (14b), respectively.

Full text of DOI:10.1002/jhet.584

March 2011
Synthesis of Some New Azole, Pyrimidine, Pyran, and Benzo/
Naphtho[b]furan Derivatives Incorporating
355
Thiazolo[3,2-a]benzimidazole moiety
Ahmad M. Farag,a* Kamal M. Dawood,a Hatem A. Abdel-Aziz,b,c
Nehal A. Hamdy,b and Issa M. I. Fakhrb
aDepartment of Chemistry, Faculty of Science, Cairo University, Giza 12622, Egypt
bDepartment of Applied Organic Chemistry, National Research Centre, Dokki, Cairo 12613, Egypt
cDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud University,
Riyadh 11451, Saudi Arabia
*E-mail: afarag49@yahoo.com
Received March 19, 2010
DOI 10.1002/jhet.584
Published online 22 December 2010 in Wiley Online Library (wileyonlinelibrary.com).
Reaction of E-3-(N,N-dimethylamino)-1-(3-methylthiazolo[3,2-a]benzimidazol-2-yl)prop-2-en-1-one
(1) with some N-nucleophiles, such as anilines 2a-c, 4-amino-N-pyridin-2-yl-benzenesulfonamide (4a),
4-amino-N-pyrimidin-2-yl-benzenesulfonamide (4b), hydrazine, hydroxylamine, thiourea, and guanidine
afforded the corresponding arylaminoprop-2-en-1-one derivatives 3a-c, 5a,b, the pyrazole, isoxazole,
pyrimidinethione and aminopyrimidine derivatives 7a, 7b, 9a, and 9b, respectively. The utility of com-
pound 1, as a versatile building block, for the synthesis of the pyranone 13, benzo[b]furan 17a, and
naphtho[1,2-b]furan 17b was also explored via its reaction with 2-benzamidoacetic acid (10), 1,4-benzo-
quinone (14a), and 1,4-naphthoquinone (14b), respectively.
J. Heterocyclic Chem., 48, 355 (2011).
INTRODUCTION
As a part of our ongoing research program directed
towards developing new approaches to a variety of het-
erocyclic ring systems for biological screening [20–37]
specially those containing thiazolo[3,2-a]benzimidazole
moiety [20,29,37], we report herein on the utility of E-
3-(N,N-dimethylamino)-1-(3-methylthiazolo[3,2-a]benzi-
midazol-2-yl)prop-2-en-1-one (1) [20] for the synthesis
of title compounds.
Thiazolo[3,2-a]benzimidazoles have been reported to
possess interesting biological and pharmacological activ-
ities where several derivatives of this fused ring system
are used as antibacterial [1–3], anti-inflammatory [4],
antiulcer [5,6], and antiviral [7,8] agents. Moreover, cer-
tain thiazolo[3,2-a]benzimidazoles, such as 6-amino-N-
cyclohexyl-N,3-dimethyl-thiazolo[3,2-a]benzimidazole-
2-carboxamide (YM-298,198) has been reported as
potent selective and noncompetitive metabotropic gluta-
mate receptor type 1 (mGluR1) antagonist [9,10]. On
the other hand, tilomisole (WY-18,251) was largely
studied [11,12] demonstrating its anti-inflammatory [13]
and immunomodulatory [14] activities. Additionally, the
gastric antisecretory activity of thiazolo[3,2-a]benzimi-
dazol-1-oxide (WY-26,769) was reported [15]. Also,
some of these derivatives are used for treatment of can-
cer [16], cerebral infarction [17], neurogenic pain [18],
and bone diseases [19].
RESULTS AND DISCUSSION
Recently, we have reported the synthesis of the enam-
inone 1 by the reaction of 1-(3-methylthiazolo[3,2-
a]benzimidazol-2-yl)ethanone with [3-(dimethylamino)-
2-azaprop-2-en-1-ylidene]dimethylammonium chloride
(Gold’s reagent) [20] or with dimethylformamide dime-
thylacetal (DMF-DMA) [29]. Treatment of 1 with ani-
line derivatives 2a-c gave the corresponding acyclic sec-
ondary amines 3a-c (Scheme 1). The structures of the
C
V
2010 HeteroCorporation

356
A. M. Farag, K. M. Dawood, H. A. Abdel-Aziz, N. A. Hamdy, and I. M. I. Fakhr
Vol 48
Scheme 1
later products were assigned on the basis of their analyt-
ical and spectral data. For example, the IR spectra of
the reaction products exhibited, in each case, NH
absorption band in the region 3333–3179 cmꢀ1. Their
mass spectra revealed, in each case, molecular ion peaks
at the corresponding m/z value. The enaminone 1 reacted
also with 4-amino-N-pyridin-2-yl-benzenesulfonamide (4a)
and 4-amino-N-pyrimidin-2-yl-benzenesulfonamide (4b),
in refluxing acetic acid to afford the corresponding sulfon-
amide derivatives 5a, and 5b, respectively (Scheme 1).
The IR spectra of the reaction products showed, in each
case, two absorption bands corresponding to 2NH func-
tions in the region 3233–3105 cmꢀ1, in addition to a car-
The enaminone 1 reacted also with hydrazine and
afforded a white product that was identified as 3-
methyl-2-(2H-pyrazol-3-yl)thiazolo[3,2-a]benzimidazole
1
(7a) (Scheme 2). The H-NMR spectrum of later prod-
uct revealed a pair of doublet signals duo to pyrazole
protons at d 6.65 and 7.62 with J ¼ 2.4 Hz, in addition
to D2O-exchangeable broad singlet at d 13.82 due to
pyrazole NH proton.
When compound 1 was treated with hydroxylamine in
refluxing ethanol, it afforded a single product identified
as 2-(isoxazol-5-yl)-3-methylthiazolo[3,2-a]benzimida-
zole (7b) (Scheme 2).
Treatment of compound 1 with thiourea in refluxing
ethanol, in the presence of sodium ethoxide, afforded
the pyrimidine-2-thione derivative 9a (Scheme 2). Com-
pound 9a is assumed to be formed via the addition of
the NH2 group of thiourea to the activated exocyclic
double bond in compound 1 with subsequent elimination
bonyl absorption band in the region 1643–1639 cmꢀ1
.
Their mass spectra revealed, in each case, a peak corre-
1
sponding to the molecular ion and their H NMR spectra
were free of signals characteristic for the dimethylamino
protons [cf. Experimental part].
Scheme 2
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

March 2011
Synthesis of Some New Azole, Pyrimidine, Pyran, and Benzo/Naphtho[b]furan
Derivatives Incorporating Thiazolo[3,2-a]benzimidazole moiety
357
Scheme 3
of dimethylamine molecule to give the nonisolable inter-
mediate 8a, which underwent intramolecular cyclization
to form the final product 9a via loss of a water molecule.
Compound 1 reacted also with guanidine and gave the
corresponding pyrimidine derivative 9b (Scheme 2). The
structures of compounds 9a and 9b were deduced from
their elemental analyses and 1H NMR data. The mass
spectra of these compounds displayed molecular ion
peaks at appropriate m/z values [cf. Experimental part].
Treatment compound with 2-benzamidoacetic acid
(10) in refluxing acetic anhydride led to the formation
molecular cyclization in situ under the reaction condi-
tions into the oxazolone intermediate 11, which then
reacts with the enaminone 1, yielding the nonisolable in-
termediate 12, that further rearranges into the final pyra-
none structure 13 (Scheme 3).
When the enaminone 1 was treated with p-benzoqui-
none (14a) in acetic acid at room temperature, it
afforded a single product that was formulated as the
benzo[b]furan derivative 17a on the basis of its elemen-
tal analysis and spectral data. For example, its IR spec-
trum showed a broad band at 3475 cmꢀ1 due to OH
group and revealed a carbonyl absorption band at 1636
cmꢀ1. Its 1H NMR spectrum showed a characteristic
downfiled singlet signal at d 8.90 due to the furan ring
proton and revealed a broad D2O-exchangeable signal at
d 9.55 due to OH proton. Compound 17a is suggested
to be formed via an initial addition of the electron-rich
C2 of the enaminone 1 to the activated electron-poor
double bond of the quinone 14a to form the
of
N-[6-(3-methylthiazolo[3,2-a]benzimidazol-2-yl)-2-
1
oxo-2H-pyran-3-yl]benzamide (13) (Scheme 3). The H
NMR spectrum of compound 13 showed two doublets
corresponding to pyran protons at d 6.83 and 7.81 with
J ¼ 7.8 Hz, in addition to a broad D2O-exchangeable
signal at d 9.61 due to NH proton. Compound 13 was
assumed to be formed according to the following
sequence; 2-benzamidoacetic acid (10) undergoes intra-
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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A. M. Farag, K. M. Dawood, H. A. Abdel-Aziz, N. A. Hamdy, and I. M. I. Fakhr
Vol 48
63.65; H, 4.01; N, 11.13; S, 8.50%. Found: C, 63.38; H,
3.92; N, 11.30; S, 8.73%.
intermediate 16a, which undergoes intramolecular cycli-
zation into the final product via elimination of dimethyl-
amine (Scheme 3).
(E)-1-(3-Methylbenzo[d]thiazolo[3,2-a]imidazol-2-yl)-3-(4-
nitrophenylamino)prop-2-en-1-one (3b). Orange crystals,
yield (86%); mp 270–272ꢁC; IR (KBr) mmax/cmꢀ1: 3124 (NH),
In a similar manner, the enaminone 1 reacted with
1,4-naphthoquinone (14b) and afforded 2-(5-hydroxy-
naphtho[1,2-b]furan-3-oyl)-3-methylthiazolo[3,2-a]benz-
imidazole (17b) (Scheme 3).
The proposed reaction sequence of the enaminone 1
with p-benzoquinone (14a) and 1,4-naphthoquinone
(14b) is analogous to Nenitzescu reaction of enaminones
with quinones, which has proven to be highly efficient
method for the synthesis of 5-hydroxyindole-based
derivatives with a wide range of substituents at various
positions of the ring system [38–49].
1
1643 (C¼¼O), 1546 (C¼¼N); H NMR (DMSO-d6): d 3.15 (s, 3H,
CH3), 6.38 (d, 1H, J ¼ 12.0 Hz, ACOACH¼¼), 7.30–8.28 (m,
9H), 10.90 (br. s, 1H, NH, D2O-exchangeable); MS m/z (%): 379
(Mþþ1, 4.9%), 378 (Mþ, 100%), 241 (18.2%), 135 (43.0%), 77
(7.4%). Anal. Calcd for C19H14N4O3S: C, 60.31; H, 3.73; N,
14.81; S, 8.47%. Found: C, 60.57; H, 3.49; N, 14.95; S, 8.33%.
(E)-3-(4-Methoxyphenylamino)-1-(3-methylbenzo[d]-thia-
zolo[3,2-a]imidazol-2-yl)prop-2-en-1-one (3c). Yellow fine
crystals, yield (77%); mp 181–183ꢁC; IR (KBr) mmax/cmꢀ1
:
1
3134 (NH), 1633 (C¼¼O), 1569 (C¼¼N); H NMR (DMSO-d6):
d 3.12 (s, 3H, CH3), 3.75 (s, 3H, AOCH3), 6.1 (d, 1H, J ¼
12.3 Hz, ACOACH¼¼), 6.94–8.07 (m, 9H), 10.20 (br. s, 1H,
NH, D2O-exchangeable); MS m/z (%): 365 (Mþþ2, 18.5%),
364 (Mþþ1, 4.0%), 363 (Mþ, 100%), 319 (53.5%), 242
(26.9%), 133 (30.9%), 77 (15.0%). Anal. Calcd for
C20H17N3O2S: C, 66.10; H, 4.71; N, 11.56; S, 8.82%. Found:
C, 65.84; H, 4.86; N, 11.54; S, 8.94%.
In conclusion, the utility of E-3-(N,N-dimethylamino)-
1-(3-methylthiazolo[3,2-a]benzimidazol-2-yl)prop-2-en-1-
one (1) was explored, as a versatile synthon, in rapid
and efficient experiments for the synthesis of the title
compounds from simple and accessible materials.
(E)-4-(3-(3-Methylbenzo[d]thiazolo[3,2-a]imidazol-2-yl)-3-
oxoprop-1-enylamino)-N-(pyridin-2-yl)benzenesulfonamide
(5a). Yellow fine crystals, yield (77%); mp 268–270ꢁC; IR
(KBr) mmax/cmꢀ1: 3225, 3115 (2NH), 1628 (C¼¼O), 1593
(C¼¼N); 1H NMR (DMSO-d6): d 3.12 (s, 3H, CH3), 6.24 (d,
1H, J ¼ 12.3 Hz, ACOACH¼¼), 6.86–8.21 (m, 13H, 12
ArAH), 10.50 (br. s, 1H, NH, D2O-exchangeable), 11.70 (br.
s, 1H, NH, D2O-exchangeable); MS m/z (%): 490 (Mþþ1,
5.7%), 489 (Mþ, 7.2%), 240 (26.3%), 187 (43.8%), 184
(100%), 106 (18.4%). Anal. Calcd for C24H19N5O3S2: C,
58.88; H, 3.91; N, 14.30; S, 13.10%. Found: C, 58.54; H,
3.73; N, 14.62; S, 13.33%.
(E)-4-(3-(3-Methylbenzo[d]thiazolo[3,2-a]imidazol-2-yl)-3-
oxoprop-1-enylamino)-N-(pyridin-2-yl)benzenesulfonamide
(5b). Yellow fine crystals, yield (72%); mp 277–279ꢁC; IR
(KBr) mmax/cmꢀ1: 3233, 3105 (2NH), 1639 (C¼¼O), 1578
(C¼¼N); 1H NMR (DMSO-d6): d 3.13 (s, 3H, CH3), 6.24 (d,
1H, J ¼ 12.3 Hz, ACOACH¼¼), 7.03–8.52 (m, 12H), 10.50
(br. s, 1H, NH, D2O-exchangeable), 11.69 (br. s, 1H, NH,
D2O-exchangeable); MS m/z (%): 491 (Mþþ1, 3.0%), 490
(Mþ, 12.4%), 240 (16.8%), 186 (76.8%), 185 (100%), 150
(15.1%), 108 (29.9%), 92 (47.2%), 65 (70.8%). Anal. Calcd
for C23H18N6O3S2: C, 56.31; H, 3.70; N, 17.13; S, 13.07%.
Found: C, 56.50; H, 3.53; N, 17.00; S, 12.88%.
EXPERIMENTAL
Melting points were taken on Electrothermal IA 9000 series
digital melting point apparatus. Elemental analytical data were
obtained from the microanalytical unit, Cairo University,
Cairo, Egypt, their results were found to be in good agreement
with the calculated values. The IR spectra (KBr) were
recorded on a Shimadzu CVT-04 spectrophotometer. The
NMR spectra were recorded on a Varian Mercury VX-300
NMR spectrometer. 1H spectra were run at 300 MHz in deu-
terated dimethylsulfoxide [D6] DMSO. Mass spectra were
measured on a Varian MAT CH-5 spectrometer (70 eV). E-3-
(N,N-dimethylamino)-1-(3-methylthiazolo[3,2-a]benzimidazol-
2-yl)prop-2-en-1-one (1) [20,29] was prepared according to
reported methods. 4-Amino-N-(pyridin-2-yl)benzenesulfona-
mide (4a), 4-amino-N-(pyrimidin-2-yl)benzenesulfonamide (4b),
2-benzamidoacetic acid (10), 1,4-bezoquinone (14a), and 1,4-
naphthoquinone (14b) were obtained commercially.
General procedure for the synthesis of the enaminones
3a-c and 5a,b A mixture of E-3-(N,N-dimethylamino)-1-(3-
methylthiazolo[3,2-a]benzimidazol-2-yl)prop-2-en-1-one
(1)
[20] (1.43 g, 5 mmol) and the appropriate amine [2-aminoben-
zoic acid (2a), 4-nitroaniline (2b), 4-methoxyaniline (2c), 4-
amino-N-(pyridin-2-yl)benzenesulfonamide (4a) or 4-amino-N-
(pyrimidin-2-yl)benzenesulfonamide (4b)] (5 mmol) in acetic
acid (20 mL) was refluxed for 0.5 h (2 h in case of 4a and
4b). The precipitated product was collected by filtration,
washed with ethanol, and dried. Recrystallization from DMF/
H2O afforded the corresponding derivatives 3a-c and 5a,b.
(E)-2-(3-(3-Methylbenzo[d]thiazolo[3,2-a]imidazol-2-yl)-3-
oxoprop-1-enylamino)benzoic acid (3a). Yellow crystals,
yield (76%); mp 290–292ꢁC; IR (KBr) mmax/cmꢀ1: 3450
(OH), 3115 (NH), 1693, 1630 (2C¼¼O), 1605 (C¼¼N); 1H
NMR (DMSO-d6): d 3.01 (s, 3H, CH3), 6.39 (d, 1H, J ¼ 12.3
Hz, ACOACH¼¼), 7.27–8.14 (m, 9H), 10.84 (br. s, 1H, NH,
D2O-exchangeable) 11.96 (br. s, 1H, OH, D2O-exchange-
able); MS m/z (%): 378 (Mþþ1, 16.4%), 377 (Mþ, 100%),
240 (17.2%), 77 (8.5%). Anal. Calcd for C20H15N3O3S: C,
3-Methyl-2-(2H-pyrazol-3-yl)thiazolo[3,2-a]benzimidazole
(7a). A mixture of the enaminone (1) (1.43 g, 5 mmol) and
hydrazine hydrate (1 mL, 99%) in acetic acid (20 mL) was
refluxed for 1 h, then left to cool. The precipitated product
was collected by filtration, washed with ethanol, and dried.
Recrystallization from EtOH afforded the pyrazole derivative
7a as white powder in 74% yield, mp 243–245ꢁC; IR (KBr)
1
m
max/cmꢀ1: 3125 (NH), 1624 (C¼¼N); H NMR (DMSO-d6): d
2.96 (s, 3H, CH3), 6.65 (d, 1H, J¼ 2.4 Hz, pyrazole), 7.23–
7.55 (m, 2H, ArAH), 7.62 (D, 1H, J ¼ 2.4 Hz, pyrazole), 7.7–
8.03 (m, 2H, ArAH), 9.82 (br. s, 1H, NH, D2O-exchangeable);
MS m/z (%): 256 (Mþþ2, 28.1%), 255 (Mþþ1, 100%), 254
(Mþ, 50.4%), 65 (22.5%). Anal. Calcd for C13H10N4S: C,
61.40; H, 3.96; N, 22.03; S, 12.61%. Found: C, 61.64; H,
4.12; N, 21.85; S, 12.80%.
Journal of Heterocyclic Chemistry
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Synthesis of Some New Azole, Pyrimidine, Pyran, and Benzo/Naphtho[b]furan
Derivatives Incorporating Thiazolo[3,2-a]benzimidazole moiety
359
2-(Isoxazol-5-yl)-3-methylthiazolo[3,2-a]benzimidazole (7b). A
mixture of the enaminone 1 (2.85 g, 10 mmol), hydroxylamine
hydrochloride (10 mmol), and anhydrous potassium carbonate
(0.5 g) in absolute ethanol (25 mL) was refluxed for 5 h, then
left to cool. The reaction mixture was poured into cold water
and the solid product was filtered off, washed with water,
dried, and finally recrystallized from ethanol to afford the iso-
xazole derivative 7b as white powder in 56% yield, mp 191–
General procedure for the synthesis of the furan deriva-
tives 17a,b. To a stirred solution of the enaminone 1 (2.85 g,
10 mmol) in acetic acid (50 mL), 1,4-benzoquinone 14a or
1,4-naphthoquinone 14b (10 mmol) was added and the reac-
tion mixture was stirred overnight at room temperature. The
solvent was evaporated in vacuo, and solid product obtained
was filtered off, washed with EtOH, dried and recrystallized
from EtOH/DMF to afford the corresponding furan derivatives
17a and 17b, respectively.
a2-(5-Hydroxybenzofuran-3-oyl)-3-methylthiazolo[3,2-a]benz-
imidazole (17a). White powder, yield (61%); mp 268–270ꢁC;
IR (KBr) mmax/cmꢀ1: 3475 (OH), 1636 (C¼¼O), 1543 (C¼¼N);
13C NMR (DMSO-d6): d 14.9 (ACH3), 106.3, 112.2, 112.6,
114.9, 118.7, 120.1, 121.2, 121.3, 124.3, 125.1, 130.2, 137.6,
148.3, 149.1, 153.9, 154.0, 154.9, 180.6 (C¼¼O); 1H NMR
(DMSO-d6): d 3.01 (s, 3H, CH3), 6.88–8.10 (m, 7H, ArAH),
8.90 (s, 1H, furan), 9.55 (br. s, 1H, OH, D2O-exchangeable);
MS m/z (%): 349 (Mþþ1, 26.5%), 348 (Mþ, 53.9%), 264
(18.0%), 201 (21.6%), 144 (100%), 118 (44.8%), 77 (65%).
Anal. Calcd for C19H12N2O3S: C, 65.51; H, 3.47; N, 8.04; S,
9.20%. Found: C, 65.35; H, 3.35; N, 8.22; S, 9.04%.
1
193ꢁC; IR (KBr) mmax/cmꢀ1: 1616 (C¼¼N); H NMR (DMSO-
d6): d 3.01 (s, 3H, CH3), 6.66 (d, 1H, J ¼ 2.7 Hz, isoxazole),
7.24–7.7.57 (m, 2H, ArAH), 7.68 (d, 1H, J ¼ 2.7 Hz, isoxa-
zole), 7.73–8.01 (m, 2H, ArAH); MS m/z (%): 256 (Mþþ1,
3.6%), 255 (Mþ, 100%), 240 (45.2%), 118 (Mþ, 16.4%). Anal.
Calcd for C13H9N3OS: C, 61.16; H, 3.55; N, 16.46; S,
12.56%. Found: C, 61.40; H, 3.53; N, 16.67; S, 12.38%.
Reaction of 1 with thiourea and guanidine. The enami-
none 1 (2.85 g, 10 mmol) was added to an ethanolic sodium
ethoxide solution [prepared from sodium metal (0.23 g, 10
mmol) and absolute ethanol (50 mL)] then thiourea (0.076 g,
10 mmol) or guanidine nitrate (0.12 g, 10 mmol) was added.
The reaction mixture was refluxed for 16 h, then left to cool
and poured into crushed ice and neutralized with diluted hy-
drochloric acid in case of thiourea. The precipitated product
was collected by filtration, washed with ethanol, and dried.
Recrystallization from EtOH/DMF afforded the pyrimidine
derivatives 9a and 9b, respectively.
6-(3-Methylthiazolo[3,2-a]benzimidazol-2-yl)pyrimidine-
2(1H)-thione (9a). Yellow crystals, yield (71%); mp 266–
268ꢁC; IR (KBr) mmax/cmꢀ1: 3190 (NH), 1608 (C¼¼N); 1H
NMR (DMSO-d6): d 3.04 (s, 3H, CH3), 7.12–8.08 (m, 6H,
ArAH), 8.65 (br. s, 1H, NH, D2O-exchangeable); MS m/z (%):
299 (Mþþ1, 4.2%), 298 (Mþ, 14.0%), 240 (100%), 188
(11.3%), 118 (16.1%), 111 (5.8%), 56 (18.2%). Anal. Calcd
for C14H10N4S2: C, 56.35; H, 3.38; N, 18.78; S, 21.49%.
Found: C, 56.03; H, 3.44; N, 18.53; S, 21.20%.
2-Amino-4-(3-methylthiazolo[3,2-a]benzimidazol-2-yl)pyri-
midine (9b). Yellow powder, yield (58%); mp >300ꢁC; IR
(KBr) mmax/cmꢀ1: 3240, 3126 (NH2), 1608 (C¼¼N); 1H NMR
(DMSO-d6): d 3.02 (s, 3H, CH3), 6.75 (br. s, 2H, NH, D2O-
exchangeable), 7.20–8.07 (m, 6H, ArAH); MS m/z (%): 283
(Mþþ2, 3.1%), 282 (Mþþ1, 8.6%), 281 (Mþ, 6.4%), 242
(100%), 188 (6.0%), 94 (3.3%), 51 (14.8%). Anal. Calcd for
C14H11N5S: C, 59.77; H, 3.94; N, 24.89; S, 11.40%. Found: C,
60.13; H, 3.68; N, 24.66; S, 11.25%.
N-[6-(3-Methylthiazolo[3,2-a]benzimidazol-2-yl)-2-oxo-2H-
pyran-3-yl]benzamide (13). A solution of the enaminone 1
(2.85 g, 10 mmol) and 2-benzamidoacetic acid (10) (1.7 g, 10
mmol) in acetic anhydride (20 mL) was heated under reflux
for 2 h. The reaction mixture was concentrated in vacuo and
the solid product obtained upon cooling was filtered off,
washed with water, and recrystallized from DMF/H2O to
afford the pyran derivative 13 as yellow powder in 63% yield,
mp >300ꢁC; IR (KBr) mmax/cmꢀ1: 3109 (NH), 1717, 1670
(2C¼¼O), 1628(C¼¼N); 1H NMR (DMSO-d6): d 3.03 (s, 3H,
CH3), 6.83 (d, 1H, J ¼ 7.8 Hz, pyran), 7.31–7.74 (m, 5H,
ArAH), 7.81 (d, 1H, J ¼ 7.8 Hz, pyran), 7.85–8.22 (m, 4H,
Ar-H), 9.61 (br. s, 1H, NH, D2O-exchangable); MS m/z (%):
402 (Mþþ1, 43.6%), 401 (Mþ, 100%), 314 (46.1%), 264
(20.0%), 211 (42.8%), 109 (61%), 77 (34.5%). Anal. Calcd for
C22H15N3O3S: C, 65.82; H, 3.77; N, 10.47; S, 7.99%. Found:
C, 66.11; H, 3.91; N, 10.25; S, 8.07%.
2-(5-Hydroxynaphtho[1,2-b]furan-3-oyl)-3-methylthiazolo[3,2-
a]benzimidazole (17b). White powder, yield (56%); mp 290–
292ꢁC; IR (KBr) mmax/cmꢀ1: 3414 (OH), 1670 (C¼¼O), 1620
1
(C¼¼N); H NMR (DMSO-d6): d 3.03 (s, 3H, CH3), 7.31–8.29
(m, 9H, ArAH), 8.99 (s, 1H, furan), 10.27 (br. s, 1H, OH,
D2O-exchangeable); MS m/z (%): 400 (Mþþ2, 18.1%), 399
(Mþþ1, 46.2%), 398 (Mþ, 100%), 331 (68.5%), 245 (99%),
210 (37.6%), 98 (10.2%). Anal. Calcd for C23H14N2O3S: C,
69.33; H, 3.54; N, 7.03; S, 8.05%. Found: C, 69.62; H, 3.52;
N, 6.86; S, 7.93%.
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