Synthesis and in vitro study of novel Bis-[3-(2- Arylmethylidenimino-1,3- thiazol-4-yl)-4-hydroxy-2H-chromen-2- one-6-yl]methane and Bis-[3-(2- arylidenhydrazo-1,3-thiazol-4-yl)- 4-hydroxy-2H-chromen-2-one-6-yl]methane as potential antimicrobial agents

Article abstract of DOI:10.1002/jhet.63

A series of novel bis-[3-(2-arylmethylidenimino-1,3-thiazol-4-yl)-4- hydroxy-2H-chromen-2-one-6- yl]methane 7a-f and bis-[3-(2-arylidenhydrazo-1,3- thiazol-4-yl)-4-hydroxy-2H-chromen-2-one-6-yl]- methane 8a-f were synthesized in good yields from bis-[3-(2-bromoacetyl-4-hydroxy-2H-chromen-2- one-6-yl]methane 5. The chemical structures of the newly synthesized compounds were elucidated by their IR, 1H NMR, MS, and elemental analyses. Further, all the compounds were screened for their antimicrobial activity against Gram-positive, Gram-negative bacteria, and fungi. Among the synthesized compounds, 7c, 7e, and 8c were found to be the most active against almost all the test bacteria. The compound 8c displayed notable antibacterial activity against Bacillus subtilis (ATCC 6633), Staphylococcus aureus (ATCC6538p), Micrococcus luteus (IFC 12708), Proteus vulgaris (ATCC 3851) and Salmonella typhimurium (ATCC 14028), equal to that of ampicillin. Similarly these compounds also showed potent antifungal effect against Candida albicans (ATCC 10231), Aspergillus fumigatus (HIC 6094), Trichophyton rubrum (IFO 9185), and Trichophyton mentagrophytes (IFO 40996).

Full text of DOI:10.1002/jhet.63

March 2009
Synthesis and in Vitro Study of Novel Bis-[3-(2-
arylmethylidenimino-1,3-thiazol-4-yl)-4-hydroxy-2H-chromen-2-
one-6-yl]methane and Bis-[3-(2-arylidenhydrazo-1,3-thiazol-4-yl)-
4-hydroxy-2H-chromen-2-one-6-yl]methane as Potential
Antimicrobial Agents
261
M. Raghu, A. Nagaraj, and Ch. Sanjeeva Reddy*
Department of Chemistry, Kakatiya University, Warangal 506009, India
*E-mail: chsrkuc@yahoo.co.in
Received June 10, 2008
DOI 10.1002/jhet.63
Published online 13 April 2009 in Wiley InterScience (www.interscience.wiley.com).
A series of novel bis-[3-(2-arylmethylidenimino-1,3-thiazol-4-yl)-4-hydroxy-2H-chromen-2-one-6-
yl]methane 7a-f and bis-[3-(2-arylidenhydrazo-1,3-thiazol-4-yl)-4-hydroxy-2H-chromen-2-one-6-yl]-
methane 8a-f were synthesized in good yields from bis-[3-(2-bromoacetyl-4-hydroxy-2H-chromen-2-
one-6-yl]methane 5. The chemical structures of the newly synthesized compounds were elucidated by
1
their IR, H NMR, MS, and elemental analyses. Further, all the compounds were screened for their anti-
microbial activity against Gram-positive, Gram-negative bacteria, and fungi. Among the synthesized
compounds, 7c, 7e, and 8c were found to be the most active against almost all the test bacteria. The
compound 8c displayed notable antibacterial activity against Bacillus subtilis (ATCC 6633), Staphylo-
coccus aureus (ATCC6538p), Micrococcus luteus (IFC 12708), Proteus vulgaris (ATCC 3851) and Sal-
monella typhimurium (ATCC 14028), equal to that of ampicillin. Similarly these compounds also
showed potent antifungal effect against Candida albicans (ATCC 10231), Aspergillus fumigatus (HIC
6094), Trichophyton rubrum (IFO 9185), and Trichophyton mentagrophytes (IFO 40996).
J. Heterocyclic Chem., 46, 261 (2009).
INTRODUCTION
There is a real perceived need for the discovery of new
compounds endowed with antimicrobial activity, possi-
bly acting through mechanism of action, which are dis-
tinct from those of well-known classes of antibacterial
agents to which many clinically relevant pathogens are
now resistant. Similarly in the recent decades, an
increased incidence of fungal infections has been
observed as a consequence of the growing number of
immunocompromised patients and the frequent use of
antibacterial and cytotoxic drugs. For many fungal
The treatment of infectious diseases still remains an
important and challenging problem because of a combi-
nation of factors including emerging infectious diseases
and the increasing number of multidrug resistant micro-
bial pathogens. Despite a large number of antibiotics
and chemotherapeutics available for medical use, at the
same time the emergence of old and new antibiotic re-
sistance created in the last decades revealed a substantial
medical need for new classes of antimicrobial agents.
C
V
2009 HeteroCorporation

262
M. Raghu, A. Nagaraj, and C. S. Reddy
Vol 46
Scheme 1
infections, polyenes, such as amphotericin B, represent
the standard therapy. Polyenes bind to membrane ster-
ols, leading to membrane permeability, leakage, and cell
death. However, the clinical use of amphotericin B is
limited by a high frequency of renal toxicity, and sev-
eral adverse effects [1]. Although the various molecules
were designed and synthesized for the above aim and to
reduce the adverse effects, it was demonstrated that
azoles and thiazoles, such as fluconazole, which act on
ergosterol biosynthesis, offer several advantages in
terms of decreased toxicity after oral or intravenous [2]
administration and are often employed in the treatment
of fungal infections, therefore the thiazoles, azoles, and
their derivatives could be considered as possible antimi-
crobial agents [3].
the synthesis of the title compounds with the view to
obtain certain new chemical entities with both active
pharmacophores in a single molecular frame work for
the potential intensified biological activities.
In this article, we wish to report the synthesis of
novel bis-[3-(2-arylmethylidenimino-1,3-thiazol-4-yl)-4-
hydroxy-2H-chromen-2-one-6-yl]methane
7
in good
yields, from bis-[3-(2-amino-1,3-thiazol-4-yl)-4-hydroxy-
2H-chromen-2-one-6-yl]methane 6, which in tern is syn-
thesized by the reaction of bis-[3-(2-bromoacetyl-4-
hydroxy-2H-chromen-2-one-6-yl]methane 5 with thio-
urea, and also the synthesis of novel bis-[3-(2-aryliden-
hydrazo-1,3-thiazol-4-yl)-4-hydroxy-2H-chromen-2-one-
6-yl]methane 8 in good yields, from compound 5 and
arylthiosemicarbazone (Schemes 1 and 2). The antibac-
terial and antifungal activities of the compounds 7a-f
and 8a-f have also been evaluated.
The thiazole nucleus also appears frequently in the
structure of various natural products and biologically
active compounds, notably thiamine (vitamin-B), antibi-
otics such as penicillin, micrococcin [4], troglitazone
[5], and many metabolic products of fungi and primitive
marine animals, including 2-(aminoalkyl)thiazole-4-car-
boxylic acids [6]. Similarly coumarins are a class of
compounds with biological activity [7], such as analge-
sics [8], anticoagulant [9], specific inhibitors of a-chy-
motripsin [10], human leukocyte elastase [11], diuretics
[12], platelet aggregation [13], anticancer [14], inhibitor
of HIV-1 protease [15], and antibacterial agents [16].
Following the successful introduction of antimicrobial
agents, inspired by the biological profile of thiazole and
coumarin and their increasing importance in pharmaceu-
tical and biological fields, and in continuation of our
research on biologically active heterocycles [17] consid-
ering the scope to introduce thiazolyl moiety into the
coumarin ring, it was thought worthwhile to undertake
RESULTS AND DISCUSSION
The key intermediate 5, required for the synthesis of
the title compounds was prepared according to the pro-
cedure outlined in the Scheme 1. Condensation of the
salicylic acid 1 and formaldehyde in the presence of sul-
furic acid gave bis-(4-hydroxy-3-carboxyphenyl)methane
2 in good yield [18]. Compound 2 was then reacted
with ethyl alcohol in presence of catalytic amount of
sulfuric acid to afford bis-(4-hydroxy-3-carbethoxyphe-
nyl)methane 3 in good yield [17b], subsequently cyclo-
condensation of compound 3 with ethylacetoacetate in
presence of sodium ethoxide gave bis-(3-acetyl-4-
hydroxy-2H-chromen-2-one-6-yl)methane 4 [17b]. a-
Bromination of compound 4 with bromine in chloroform
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DOI 10.1002/jhet

March 2009
Bis-[3-(1,3-thiazol-4-yl)-4-hydroxy-2H-chromen-2-one-6-yl]methane
263
Scheme 2
at low temperature afforded bis-[3-(2-bromoacetyl-4-
hydroxy-2H-chromen-2-one-6-yl] methane 5 in 85%
yield. The cyclocondensation of compound 5 with thiou-
rea in refluxing ethanol gave bis-[3-(2-amino-1,3-thia-
Antibacterial activity. The in vitro antibacterial ac-
tivity of the newly prepared compounds was screened
against three representative gram-positive bacteria viz.
Bacillus subtilis (ATCC 6633), Staphylococcus aureus
(ATCC 6538p), and Micrococcus luteus (IFC 12708),
three Gram-negative bacteria viz. Proteus vulgaris
(ATCC 3851), Salmonella typhimurium (ATCC 14028),
and Escherichia coli (ATCC 25922) by the broth dilu-
tion method, recommended by National Committee for
Clinical Laboratory Standards (NCCLS) [19]. Bacteria
were grown over night in Luria Bertani (LB) broth at
37ꢀC, harvested by centrifugation, and then washed
twice with sterile distilled water. Stock solutions of the
series of compounds were prepared in DMSO. Each
stock solution was diluted with standard method broth
(Difco) to prepare serial two-fold dilutions in the range
of 50–0.8 lg/mL. Ten microtiters of the broth contain-
ing about 105 colony forming units (cfu)/mL of test
bacteria was added to each well of 96-well microtiter
plate. Culture plates were incubated for 24 h at 37ꢀC,
and the growth was monitored visually and
zol-4-yl)-4-hydroxy-2H-chromen-2-one-6-yl]methane
6
in 78% yield. Subsequently condensation of compound
6 with various aromatic aldehydes in refluxing ethanol
gave the title compound bis-[3-(2-arylmethylidenimino-
1,3-thiazol-4-yl)-4-hydroxy-2H-chromen-2-one-6-yl]me-
thane 7a-f in good to excellent yields (Scheme 2).
Further, the intermediate 5 was treated with the vari-
ous arylthiosemicarbazone (prepared by the reaction of
aromatic aldehydes with thiosemicarbazide in presence
of sodium acetate in acetic acid) in refluxing isopropyl
alcohol to give the other title compound bis-[3-(2-aryli-
den-hydrazo-1,3-thiazol-4-yl)-4-hydroxy-2H-chromen-2-
one-6-yl]methane 8a-f in good yields (Scheme 2). The
structures of all the synthesized compounds were con-
1
firmed by their IR, H NMR, MS, and elemental analy-
ses and further screened for their antibacterial and anti-
fungal activities.
Journal of Heterocyclic Chemistry
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264
M. Raghu, A. Nagaraj, and C. S. Reddy
Vol 46
Table 1
Antibacterial activity of compounds 7a-f and 8a-f.
Minimum inhibitory concentration (MIC, lg/mL)
Compound
B. subtilis
S. aureus
M. luteus
P. vulgaris
S. typhimurium
E. coli
7a
7b
25.0
12.5
3.12
12.5
6.25
25.0
25.0
6.25
1.56
12.5
3.12
12.5
1.56
25.0
12.5
6.25
12.5
6.25
12.5
25.0
12.5
1.56
12.5
3.12
12.5
1.56
—
12.5
1.56
6.25
3.12
3.12
50.0
12.5
1.56
12.5
3.12
6.25
1.56
—
12.5
1.56
—
25.0
12.5
3.12
12.5
12.5
6.25
50.0
12.5
1.56
12.5
3.12
12.5
3.12
—
25.0
6.25
25.0
12.5
25.0
—
7c
7d
7e
12.5
12.5
—
7f
8a
8b
8c
25.0
1.56
12.5
6.25
6.25
3.12
25.0
12.5
—
6.25
12.5
12.5
8d
8e
8f
Ampicillin
—Indicates bacteria are resistant to the compound >50 lg/mL concentration. Standard deviation 0.05.
spectrophotometrically. Amphicillin was used as a
standard drug, the lowest concentration (highest dilu-
tion) required to arrest the growth of bacteria was
regarded as minimum inhibitory concentration (MIC,
lg/mL), was determined for all the compounds and
compared with the control. The MIC values of the com-
pounds screened are given in Table 1.
and resuspended in distilled water to obtain an initial
inoculum size of 105 spores/mL. Each test compound
was dissolved in DMSO and diluted with potato dex-
trose broth (Difco) to prepare serial two-fold dilutions
in the range of 100 to 0.8 lg/mL. Ten microtiters of
the broth containing about 103 (for yeast) and 104 (for
filamentous fungi) cells/mL of test fungi was added to
each well of a 96-well microtiter plate. Culture plates
were incubated for 48 ꢁ 72 h at 28ꢀC. The fungal ac-
tivity of each compound was compared with standard
drug Amphotericin B. Minimum inhibitory concentra-
tion (MIC, lg/mL) were measured and compared with
controls; the MIC values of the compounds screened
are given in Table 2.
The investigation of antibacterial screening data
revealed that all the tested compounds exhibited inter-
esting biological activity however, with a degree of vari-
ation. Compound 8c is highly active against all the
microorganisms employed, except E. coli, at 1.56 lg/
mL concentration, it is almost equal to the standard.
Compound 7c is also highly active but only against
M.luteus and P. vulgaris at the same concentration as
8c. The compound 8e also showed good antibacterial ac-
tivity against B.subtilis, S. aureus, M. Luteus, and S.
typhimurium.
The antifungal screening data showed only moderate
activity of the test compounds. Among the screened
compounds, compound 7c is highly active against T.
rubrum, T. mentagrophytes, compound 7e is also active
against only C. albicans and compound 8c is highly
active against C. albicans, T. mentagrophytes, the activ-
ity of these compounds are almost equal to the standard,
it is interesting to note that compounds 7e and 8c
showed good antifungal activity toward C. albicans at
the concentration of 3.12 lg/mL, it is less than the con-
centration of standard.
Compound 7a is almost inactive towards M. luteus, P.
vulgaris, and E. coli. The remaining compounds showed
moderate to good activity.
Antifungal activity. The newly prepared com-
pounds were screened for their antifungal activity
against four fungal organism viz. Candida albicans
(ATCC 10231), Aspergillus fumigatus (HIC 6094),
Trichophyton rubrum (IFO 9185), and Trichophyton
mentagrophytes (IFO 40996). C. albicans was grown
for 48 h at 28ꢀC in YPD broth (1% yeast extract, 2%
peptone, and 2% dextrose), harvested by centrifuga-
tion and then washed twice with sterile distilled
water. A. fumigatus, T. rubrum, and T. mentagro-
phytes were plated in potato dextrose agar (PDA)
(Difco) and incubated at 28ꢀC for two weeks. Spores
were washed three times with sterile distilled water
In conclusion, a series of novel bis-[3-(2-arylmethyl-
lidenimino-1,3-thiazol-4-yl)-4-hydroxy-2H-chromen-2-
one-6-yl]methane 7 and novel bis-[3-(2-arylidenhydrazo-
1,3-thiazol-4-yl)-4-hydroxy-2H-chromen-2-one-6-yl]me-
thane 8 has been designed and synthesized. The antimi-
crobial activity of these compounds was evaluated
against various Gram-positive, Gram-negative bacteria
and fungi. Among the synthesized compounds, 7c, 7e,
and 8c showed good activity against bacteria and fungi
Journal of Heterocyclic Chemistry
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March 2009
Bis-[3-(1,3-thiazol-4-yl)-4-hydroxy-2H-chromen-2-one-6-yl]methane
265
Table 2
Antifungal activity of compounds 7a-f and 8a-f.
Minimum inhibitory concentration (MIC, lg/mL)
Compound
C. albicans
A. fumigatus
T. rubrum
T. mentagropytes
7a
7b
—
25.0
12.5
25.0
3.12
50.0
25.0
6.25
3.12
50.0
12.5
25.0
6.25
—
25.0
6.25
12.5
12.5
25.0
25.0
12.5
6.25
50.0
25.0
6.25
3.12
—
25.0
3.12
6.25
12.5
12.5
12.5
25.0
6.25
50.0
6.25
6.25
3.12
25.0
25.0
7c
7d
3.12
12.5
25.0
12.5
25.0
12.5
7e
7f
8a
8b
8c
3.12
8d
8e
8f
25.0
25.0
12.5
Amphotericin B
3.12
—Indicates fungi are resistant to the compound >50 lg/mL concentration. Standard deviation 0.05.
Synthesis of bis-[3-(2-amino-1,3-thiazol-4-yl)-4-hydroxy-
2H-chromen-2-one-6-yl]methane (6). To a stirred solution of
thiourea (3 mmol) in 1-propanol (20 mL), was added drop
wise a solution of 5 (1 mmol) in 1-propanol (20 mL) over a
period of 30 min. The mixture was refluxed for 3 h, and then
pyridine (5 mL) was added and continued reflux for 5 h. After
completion of the reaction, monitored by TLC, the solvent was
removed in vacuo. The crude product was dried and crystal-
lized from ethanol to give compound 6 in 78% of yield as
brown solid, mp 224-26ꢀC; IR (KBr): m 3480-3275, 1720,
and emerged as potential molecules for further
development.
EXPERIMENTAL
Research chemicals were purchased from either Aldrich
Company or Fluka and used without further purification, or
were prepared according to the procedure described in the lit-
erature. Reactions were monitored by thin layer chromatogra-
phy (TLC) on silica gel plates (60 F254; Merck) visualizing
with ultraviolet light or iodine vapors. The yields of the prod-
ucts reported here are unoptimized. Melting points were deter-
mined on a Fisher-Johns apparatus and are uncorrected. IR
spectra were recorded on a Perkin-Elmer FTIR 5000 spectrom-
eter, using KBr pellets. 1H NMR spectra were recorded on a
Varian Gemini spectrometer, operating at 300 MHz. Chemical
shifts (d) are reported in parts per million down field from tet-
ramethylsilane. Mass spectra were obtained on a VG micro
mass 7070H spectrometer operating at 70 eV. Elemental analy-
ses were performed on a Perkin-Elmer 240 CHN elemental
analyzer.
1
1614, 1582, 758, 638 cm-1; H NMR (DMSO-d6): d 7.78 (2H,
s, ArH), 7.63 (2H, s, ArH), 7.40 (4H, bs, NH2), 7.32 (2H, s,
OH), 7.23 (2H, d, J ¼ 8.72 Hz, ArH), 7.14 (2H, d, J ¼ 8.72
Hz, ArH), 3.98 (2H, s, CH2); MS: m/z 532 (Mþ). Anal. calcd
for C25H16N4O6S2: C, 56.39; H, 3.03; N, 1052. Found: C,
55.82; H, 3.09; N, 10.44.
Synthesis of bis-[3-(2-arylmethylidenimino-1,3-thiazol-4-
yl)-4-hydroxy-2H-chromen-2-one-6-yl]methane (7a-f). A mi-
xture of aromatic aldehyde (2 mmol) and compound 6
(1 mmol) in ethanol (20 mL) was refluxed for 1 h. After com-
pletion of the reaction (monitored by TLC), the mixture was
cooled and the solvent evaporated. The formed crude product
was washed with cold aq. ethanol and then the product was
purified by recrystallization from ethanol to afford pure com-
pound 7.
Bis-[3-(2-phenylmethylidenimino-1,3-thiazol-4-yl)-4-hydr-
oxy-2H-chromen-2-one-6-yl]methane (7a). This compound
was obtained as yellow solid; Yield 81%; Mp 254-56ꢀC; IR
(KBr): m 3410, 3062, 1720, 1615, 1580, 1471, 1180, 638 cm-1;
1H NMR (DMSO-d6): d 11.07 (2H, s, OH), 8.47 (2H, s, ArH),
8.26 (2H, s, CH), 7.62 (2H, s, ArH), 7.38 (4H, d J ¼ 7.2 Hz,
ArH), 7.30 (4H, d, J ¼ 7.2 Hz, ArH), 7.19 (2H, d, J ¼ 8.72
Hz, ArH), 7.17 (4H, s, ArH), 3.99 (2H, s CH2); MS: m/z 532
(Mþ). Anal. calcd. for C39H24N4O6S2: C, 66.09; H, 3.41; N,
7.90. Found: C, 66.00; H, 3.36; N, 7.92.
Synthesis of bis-[3-(2-bromoacetyl-4-hydroxy-2H-chro-
men- 2-one-6-yl] methane (5). To a stirred solution of 4 (1
mmol) in chloroform (20 mL), was added drop wise a solution
of bromine (3 mmol) dissolved in chloroform (20 mL) at 0–
5ꢀC. The mixture was further stirred for 4 h. After completion
of the reaction, monitored by TLC, the mixture was then
poured into ice cold water. Crude product was collected by fil-
tration, washed with water, dried, and recrystallized from etha-
nol to give pure compound 5 in 85% of yield as red solid, mp
208–210ꢀC; IR (KBr): m 3480, 1728, 1680, 1587, 1180, 586
1
cm-1; H NMR (DMSO-d6): d 15.07 (2H, s, OH), 7.50 (2H, s,
ArH), 7.18 (2H, d, J ¼ 8.62 Hz, ArH), 7.14 (2H, d, J ¼ 8.62
Hz, ArH), 4.21 (4H, s, CH2Br), 3.98 (2H, s, CH2); MS: m/z
578 (Mþ). Anal. calcd for C23H14Br2O8: C, 47.78; H, 2.44.
Found: C, 47.72; H, 2.46.
Bis-[3-(2-(4-nitrophenyl)methylidenimino-1,3-thiazol-4-yl)-
4-hydroxy-2H-chromen-2-one-6-yl]methane (7b). This com-
pound was obtained as brown solid; Yield 76%; Mp 247-49ꢀC;
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M. Raghu, A. Nagaraj, and C. S. Reddy
Vol 46
IR (KBr): m 3410, 3065, 1728, 1612, 1580, 1472, 1345, 1180,
m 3400-3300, 3065, 1720, 1614, 1580, 1471, 1180, 638 cm-1;
1H NMR (DMSO-d6): d 11.20 (2H, s, OH), 9.52 (2H, s, NH),
8.19 (2H, s, CH), 7.67 (2H, s, ArH), 7.56 (2H, s, ArH), 7.35-
7.25 (10H, m, ArH), 7.23 (2H, d, J ¼ 8.7 Hz, ArH), 7.10 (2H,
d, J ¼ 8.7 Hz, ArH), 4.00 (2H, s, CH2); MS: m/z 738 (Mþ).
Anal. calcd. for C39H26N6O6S2: C, 63.41; H, 3.55; N, 11.38.
Found: C, 63.45; H, 3.49; N, 11.29.
Bis-[3-(2-(4-nitrophenyliden)hydrazo-1,3-thiazol-4-yl)-4-
hydroxy-2H-chromen-2-one-6-yl]methane (8b). This com-
pound was obtained as red solid; Yield 72%; Mp 272-74ꢀC;
IR (KBr): m 3400-3300, 3065, 1720, 1614, 1580, 1471, 1365,
1180, 638 cm-1; 1H NMR (DMSO-d6): d 11.20 (2H, s, OH),
9.52 (2H, s, NH), 8.30 (2H, d, J ¼ 8.4 Hz, ArH), 8.21 (2H, s,
CH), 7.81 (2H, d, J ¼ 8.4 Hz, ArH), 7.67 (2H, s, ArH), 7.52
(2H, s, ArH), 7.23 (2H, d, J ¼ 8.7 Hz, ArH), 7.12 (2H, d, J ¼
8.7 Hz, ArH), 4.00 (2H, s, CH2); MS: m/z 828 (Mþ). Anal.
calcd. for C39H24N8O10S2: C, 56.52; H, 2.92; N, 13.52. Found:
C, 56.46; H, 2.98; N, 13.46.
1
638 cm-1; H NMR (DMSO-d6): d 11.72 (2H, s, OH), 8.46 (2H,
s, ArH), 8.28 (2H, s, CH), 8.24 (4H, d, J ¼ 8.5 Hz, ArH), 7.72
(4H, d, J ¼ 8.5 Hz, ArH), 7.62 (2H, s, ArH), 7.20 (2H, d, J ¼
8.72 Hz, ArH), 7.17 (2H, d, J ¼ 8.7 Hz, ArH), 4.00 (2H, s CH2);
MS: m/z 799 (Mþ þ1). Anal. calcd. for C39H22N6O10S2: C,
58.65; H, 2.78; N, 10.52. Found: C, 58.60; H, 2.80; N, 10.46.
Bis-[3-(2-(4-bromophenyl)methylidenimino-1,3-thiazol-4-yl)-
4-hydroxy-2H-chromen-2-one-6-yl]methane (7c). This com-
pound was obtained as yellow solid; Yield 75%; Mp 223-
25ꢀC; IR (KBr): m 3410, 3065, 1720, 1616, 1582, 1474, 1180,
638, 586 cm-1; 1H NMR (DMSO-d6): d 11.72 (2H, s, OH),
8.46 (2H, s, ArH), 8.28 (2H, s, CH), 7.62 (2H, s, ArH), 7.49
(4H, d, J ¼ 8.5 Hz, ArH), 7.38 (4H, d, J ¼ 8.3 Hz, ArH), 7.20
(2H, d, J ¼ 8.72 Hz, ArH), 7.17 (2H, d, J ¼ 8.7 Hz, ArH),
4.00 (2H, s CH2); MS: m/z 866 (Mþ). Anal. calcd. for
C39H22Br2N4O6S2: C, 54.06; H, 2.56; N, 6.47. Found: C,
54.00; H, 2.51; N, 6.50.
Bis-[3-(2-(4-methoxyphenylmethylidenimino-1,3-thiazol-4-
(7d). This
Bis-[3-(2-(4-bromophenyliden)hydrazo-1,3-thiazol-4-yl)-4-
hydroxy-2H-chromen-2-one-6-yl]methane (8c). This com-
pound was obtained as brown solid; Yield 70%; Mp 239-41ꢀC;
IR (KBr): m 3400-3300, 3062, 1720, 1615, 1580, 1471, 1180,
638, 586 cm-1; 1H NMR (DMSO-d6): d 11.20 (2H, s, OH),
9.52 (2H, s, NH), 8.21 (2H, s, CH), 7.67 (2H, s, ArH), 7.52
(2H, s, ArH), 7.42 (4H, d, J ¼ 8.3 Hz, ArH), 7.38 (4H, d, J ¼
8.3 Hz, ArH), 7.23 (2H, d, J ¼ 8.7 Hz, ArH), 7.12 (2H, d, J ¼
8.7 Hz, ArH), 4.00 (2H, s, CH2); MS: m/z 896 (Mþ). Anal.
calcd. for C39H24Br2N6O6S2: C, 52.25; H, 2.70; N, 9.37.
Found: C, 52.20; H, 2.72; N, 9.31.
yl)-4-hydroxy-2H-chromen-2-one-6-yl]methane
compound was obtained as red solid; Yield 74%; Mp 252-
54ꢀC; IR (KBr): m 3410, 3065, 1728, 1615, 1584, 1472, 1250,
1180, 638 cm-1; 1H NMR (DMSO-d6): d 11.42 (2H, s, OH),
8.49 (2H, s, ArH), 8.34 (2H, s, CH), 7.62 (2H, s, ArH), 7.21
(2H, d, J ¼ 8.52 Hz, ArH), 7.14 (2H, d, J ¼ 8.52 Hz, ArH),
7.09 (4H, d, J ¼ 8.51 Hz, ArH), 6.72 (4H, d, J ¼ 8.51 Hz,
ArH), 4.00 (2H, s CH2), 3.79 (6H, s, OCH3); MS: m/z 768
(Mþ). Anal. calcd. for C41H28N4O8S2: C, 64.05; H, 3.67; N,
7.29. Found: C, 64.09; H, 3.64; N, 7.22.
Bis-[3-(2-(3,4-methylendioxyphenyl)methylidenimino-1,3-
thiazol-4-yl)-4-hydroxy-2H-chromen-2-one-6-yl]methane
(7e). This compound was obtained as black solid; Yield 76%;
Mp 262-64ꢀC; IR (KBr): m 3415, 3062, 1728, 1615, 1584, 638
Bis-[3-(2-(4-methoxyphenyliden)hydrazo-1,3-thiazol-4-yl)-
4-hydroxy-2H-chromen-2-one-6-yl]methane (8d). This com-
pound was obtained as brown solid; Yield 79%; Mp 238-40ꢀC;
IR (KBr): m 3400-3300, 3062, 1728, 1619, 1580, 1471, 1270,
1180, 640 cm-1; 1H NMR (DMSO-d6): d 11.20 (2H, s, OH),
9.52 (2H, s, NH), 8.21 (2H, s, CH), 7.67 (2H, s, ArH), 7.52
(2H, s, ArH), 7.23 (6H, m, ArH), 7.12 (2H, d, J ¼ 8.7 Hz,
ArH), 6.67 (4H, d, J ¼ 8.5 Hz, ArH), 4.00 (2H, s, CH2), 3.76
(6H, s, OCH3); MS: m/z 798 (Mþ). Anal. calcd. for
C41H30N6O8S2: C, 61.65; H, 3.79; N, 10.52. Found: C, 61.70;
H, 3.71; N, 10.46.
1
cm-1; H NMR (DMSO-d6): d 11.59 (2H, s, OH), 8.52 (2H, s,
ArH), 8.30 (2H, s, CH), 7.62 (2H, s, ArH), 7.20-7.18 (2H, m,
ArH), 7.12 (2H, d, J ¼ 8.52 Hz, ArH), 6.87 (2H, d, J ¼ 7.56
Hz, ArH), 6.80 (2H, d, J ¼ 7.56 Hz, ArH), 5.81 (4H, s, CH2),
4.00 (2H, s, CH2); MS: m/z 796 (Mþ). Anal. calcd. for
C41H24N4O10S2: C, 61.81; H, 3.04; N, 7.03. Found: C, 61.76;
H, 2.99; N, 7.08.
Bis-[3-(2-(2-furyl)methylidenimino-1,3-thiazol-4-yl)-4-hy-
droxy-2H-chromen-2-one-6-yl]methane (7f). This compound
was obtained as black solid; Yield 82%; Mp 271-73 ꢀC; IR
(KBr): m 3400, 3065, 1728, 1615, 1584, 1130, 1070, 638 cm-1;
1H NMR (DMSO-d6): d 11.78 (2H, s, OH), 8.52 (2H, s, ArH),
8.12 (2H, s, CH), 7.62 (2H, s, ArH), 7.52 (2H, d, J ¼ 3.2 Hz,
ArH), 7.19 (2H, d, J ¼ 7.52 Hz, ArH), 7.17 (2H, d, J ¼ 7.52
Hz, ArH), 6.76 (2H, d, J ¼ 1.56 Hz, ArH), 6.47 (2H, m, ArH),
4.00 (2H, s, CH2); MS: m/z 688 (Mþ). Anal. calcd. for
C35H20N4O8S2: C, 61.04; H, 2.93; N, 8.14. Found: C, 61.00;
H, 3.05; N, 8.11.
Bis-[3-(2-(3,4-methylendioxyphenyliden)hydrazo-1,3-thia-
zol-4-yl)-4-hydroxy-2H-chromen-2-one-6-yl]methane
(8e). This compound was obtained as black solid; Yield 70%;
Mp 248-50 ꢀC; IR (KBr): m 3400-3300, 3065, 1720, 1620,
1580, 1471, 1365, 1180, 637 cm-1; 1H NMR (DMSO-d6): d
11.20 (2H, s, OH), 9.52 (2H, s, NH), 8.19 (2H, s, CH), 7.67
(2H, s, ArH), 7.52 (2H, s, ArH), 7.24 (2H, s, ArH), 7.17 (2H,
d, J ¼ 8.5 Hz, ArH), 7.12 (2H, d, J ¼ 8.5 Hz, ArH), 7.09-6.98
(4H, m, ArH), 5.84 (4H, s, CH2), 4.00 (2H, s, CH2); MS: m/z
826 (Mþ). Anal. calcd. for C41H26N6O10S2: C, 59.56; H, 3.17;
N, 10.16. Found: C, 59.46; H, 3.14; N, 10.20.
Bis-[3-(2-arylidenhydrazo-1,3-thiazol-4-yl)-4-hydroxy-2H-
chromen-2-one-6-yl]methane (8a-f). A mixture of arylthio-
semicarbazone (2 mmol) and compound 5 (1 m mol) in isopro-
pylalcohol (20 mL) was refluxed for 1.5 h. When the foaming
product was formed, the mixture was allowed to cool and the
solid filtered, purified by recrystallization from aq. ethanol
afforded pure compound 8.
Bis-[3-(2-phenylidenhydrazo-1,3-thiazol-4-yl)-4-hydroxy-
2H-chromen-2-one-6-yl]methane (8a). This compound was
obtained as yellow solid; Yield 76%; Mp 222-24ꢀC; IR (KBr):
Bis-[3-(2-(2-furyliden)hydrazo-1,3-thiazol-4-yl)-4-hydroxy-
2H-chromen-2-one-6-yl]methane (8f). This compound was
obtained as black solid; Yield 79%; Mp 286-88ꢀC; IR (KBr):
m 3400, 3065, 1720, 1620, 1180, 1030, 637 cm-1; 1H NMR
(DMSO-d6): d 11.20 (2H, s, OH), 9.52 (2H, s, NH), 7.72 (2H,
s, CH), 7.67 (4H, m, ArH), 7.52 (2H, s, ArH), 7.17 (2H, d, J
¼ 8.5 Hz, ArH), 7.12 (2H, d, J ¼ 8.5 Hz, ArH), 6.78-6.60
(4H, m, ArH), 4.00 (2H, s, CH2); MS: m/z 718 (Mþ). Anal.
calcd. for C35H22N6O8S2: C, 58.49; H, 3.09; N, 11.69. Found:
C, 58.41; H, 3.10; N, 11.61.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

March 2009
Bis-[3-(1,3-thiazol-4-yl)-4-hydroxy-2H-chromen-2-one-6-yl]methane
267
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Acknowledgments. The authors are grateful to the Director, In-
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NMR and MS spectral analysis, to the Head, Department of Bio-
technology, S.R. PG. Center, Warangal, India for providing
facilities for biological screening.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet