Synthesis, characterization and anti-microbial studies of some novel 2,4-disubstituted thiazoles

Article abstract of DOI:10.1016/j.ejmech.2010.07.048

In the present study a series of novel 2,4-disubstituted thiazole derivatives containing substituted pyrazole moiety was synthesized by the reaction of 3-Aryl-1H-pyrazole-4-carbaldehyde thiosemicarbazone with 6-Bromo/H-3-(bromoacetyl)-2H-chromen-2-one/phenacyl chloride. Structures of newly synthesized compounds were characterized by spectral studies. New compounds were screened for their antibacterial studies against Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa. The results revealed that compounds 7c, 8e, and 8f having 2,5-dichlorothiophene substituent and 8c, 8d having 2,4-dichlorophenyl substituent showed significant antibacterial activity against all tested microorganisms.

Full text of DOI:10.1016/j.ejmech.2010.07.048

European Journal of Medicinal Chemistry 45 (2010) 5460e5464
Contents lists available at ScienceDirect
European Journal of Medicinal Chemistry
journal homepage: http://www.elsevier.com/locate/ejmech
Short communication
Synthesis, characterization and anti-microbial studies of some novel
2,4-disubstituted thiazoles
,
,
c
c
b
A.M. Vijesh a b, Arun M. Isloor b , Vivek Prabhu , Shaoib Ahmad , Shridhar Malladi
*
a SeQuent Scientific Ltd., No: 120 A & B, Industrial Area, Baikampady, New Mangalore 575 011, Karnataka, India
b Organic Chemistry Division, Department of Chemistry, National Institute of Technology-Karnataka, Surathkal, Mangalore 575 025, India
c Department of Microbiology, Veterinary College, KVAFSU, Hebbal, Bangalore 560 002, India
a r t i c l e i n f o
a b s t r a c t
Article history:
In the present study a series of novel 2,4-disubstituted thiazole derivatives containing substituted pyr-
azole moiety was synthesized by the reaction of 3-Aryl-1H-pyrazole-4-carbaldehyde thiosemicarbazone
with 6-Bromo/H-3-(bromoacetyl)-2H-chromen-2-one/phenacyl chloride. Structures of newly synthe-
sized compounds were characterized by spectral studies. New compounds were screened for their
antibacterial studies against Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Pseudomonas
aeruginosa. The results revealed that compounds 7c, 8e, and 8f having 2,5-dichlorothiophene substituent
and 8c, 8d having 2,4-dichlorophenyl substituent showed significant antibacterial activity against all
tested microorganisms.
Received 31 March 2010
Received in revised form
21 July 2010
Accepted 27 July 2010
Available online 6 August 2010
Keywords:
Thiazoles
Pyrazoles
Ó 2010 Elsevier Masson SAS. All rights reserved.
Anti-microbial studies
1. Introduction
2. Chemistry
In the recent years, thiazoles and their derivatives have attracted
medicinal chemists because of their varied biological activities such
as recently found application in drug development for the treat-
ment of allergies [1], hypertension [2], inflammation [3], schizo-
phrenia [4], antibacterial [5], HIV infections [6], hypnotics [7] and
more recently for the treatment of pain [8], as fibrinogen receptor
antagonists with antithrombotic activity [9] and as new inhibitors
of bacterial DNA gyrase B [10].
Further, pyrazole derivatives have showed significant biological
activities, such as anti-microbial [11], analgesic [12], anti-inflam-
matory [13]. Since several years the emergence of multi-drug
resistant bacteria such as methicillin-resistant Staphylococcus
aureus or vancomycin-resistant enterococci and also resistant fungi
is reported worldwide, increasing the complexity of anti-infective
therapies. Therefore novel, effective anti-microbial drugs are
urgently required. Keeping in view of this and in continuation of
our search on biologically potent molecules [14e16] we hereby
report the synthesis and anti-microbial property of novel, thiazoles
containing pyrazole nucleus. These compounds were evaluated for
their antibacterial properties against S. aureus, Bacillus subtilis,
Escherichia coli and Pseudomonas aeruginosa bacteria.
3-(Bromoacetyl)-2H-chromen-2-ones (4a,b) were synthesized
as reported in the literature [17] and 3-substituted-1H-pyrazole-
4-carbaldehydes (5aed) were synthesized by the Vilsmayer Haack
reaction of semicarbazones [18]. The targeted thiazoles (7aed
and 8aeh) were obtained in good yield by refluxing substituted
thiosemicarbazones (6aed) with various phenacyl chlorides/bro-
moacetyl coumarins in ethanol for 8 h. The starting material 6aed
in turn were synthesized by refluxing equimolar amount of 3-aryl-
1-H-pyrazole-4-carbaldehyde with thiosemicarbazide in the pres-
ence of anhydrous sodium acetate in ethanol. The reaction pathway
has been summarized in Scheme 1. Newly synthesized compounds
(7aed and 8aeh) were characterized by IR, NMR, mass spectral and
C, H, N elemental analyses.
3. Results and discussion
Formation of 3-aryl-1H-pyrazole-4-carbaldehyde(4-aryl-1,3-
thiazol-2-yl)hydrazones was confirmed by recording their IR, 1H
NMR, 13C NMR and mass spectra. All compounds are characterized
after purification by column chromatography. IR spectrum of
thiazole 7a showed absorption at 3422 cmꢀ1 which is due to the NH
stretching. Band appeared at 1627 cmꢀ1 is due to C]N. The CeS
stretching frequency appeared at 1108 cmꢀ1 further confirms the
structure of the thiazole. The 1H NMR spectrum of 7a showed
* Corresponding author. Tel.: þ91 824 2474000; fax: þ91 824 2474033.
E-mail address: isloor@yahoo.com (A.M. Isloor).
a singlet at
d 2.53 is due to SCH3 protons. A doublet at d 7.60
0223-5234/$ e see front matter Ó 2010 Elsevier Masson SAS. All rights reserved.
doi:10.1016/j.ejmech.2010.07.048

A.M. Vijesh et al. / European Journal of Medicinal Chemistry 45 (2010) 5460e5464
5461
X
COCH3
O
COCH3
X
CHO
OH
Piperidine
Ethanol
Br2 , CHCl3
+
COOC2H5
2
O
3a,b
1
X
COCH2Br
O
O
4a,b
Where X = H, Br
NH2
NH
Ar
Ar
O
N
NH2NHCSNH2
S
N
N
N
H
N
H
5a-d
6a-d
PhCOCH2Cl
Ethanol
4a,b
Ethanol
Ar
O
N
Ph
N
NH
NH
N
O
N
Ar
N
N
S
N
H
S
N
H
7a-d
8a-h
X
Scheme 1. Synthetic route for the 2,4-disubstituted thiazoles.
(J ¼ 4.8 Hz) is due to aromatic protons of p-thioanisyl moiety. A
singlet at 7.89 is due to thiazole 5H proton. Pyrazole-5H appeared
as a singlet at 8.0. Similarly a doublet appeared at 7.41
(J ¼ 4.8 Hz) is due to aromatic protons of p-thioanisyl group and
doublet of doublet at
7.48 (J ¼ 2.0 Hz) is due to aromatic protons of
2,4-dichlorophenyl moiety. A singlet appeared at 11.83 is due to
pyrazole-NH protons. eN]CH Protons appeared as a singlet at
8.12 further confirmed the structure. The mass spectrum of 7a
showed molecular ion peak at m/z ¼ 462 (mþ), which is in
agreement with the molecular formula C20H15Cl2N5S5. Similarly the
spectral values for all the compounds and C, H, N analyses are given
in the experimental part and the characterization is provided in
Table 1.
PBS. This gives a 108 cfu/mL suspension. The working inoculums of
aforementioned four different microorganisms containing 105 cfu/
mL suspension was prepared by diluting the 108 cfu/mL suspen-
sion, 103 times in trypticase soya broth.
d
d
d
d
d
4.1. Preparation of anti-microbial suspension (1 mg/mL)
d
Dissolved 10 mg of each compound in 10 mL of Dimethyl
formamide to get 1 mg/mL concentration.
4.2. Preparation of dilutions
In all, for each of the 12 anti-microbial compounds and standard
anti-microbial i.e. Ceftriaxone, 24 tubes of 5 mL capacity were
arranged in 4 rows with each row containing 6 tubes. Then 1.9 mL
of trypticase soya broth was added in the first tube in each row and
4. Anti-microbial studies
All the newly synthesized compounds were screened for their
antibacterial activity. For this, S. aureus, B. subtilis, E. coli and
P. aeruginosa microorganisms were employed. Anti-microbial study
was assessed by Minimum Inhibitory Concentration (MIC) by serial
dilution method [19]. Several colonies of S. aureus, B. subtilis, E. coli
and P. aeruginosa were picked off a fresh isolation plate and inoc-
ulated in corresponding tubes containing 5 mL of trypticase soya
broth. The broth was incubated for 6 h at 37 ꢁC until there was
visible growth. Mc Farland No.5 standard was prepared by adding
0.05 mL of 1% w/v BaCl2.2H2O in Phosphate Buffered saline (PBS) to
9.95 mL of 1% v/v H2SO4 in PBS. The growth of all the four cultures
was adjusted to Mc Farland No.5 turbidity standard using sterile
then 1 mL in the remaining tubes. Now, 100 mL of anti-microbial
suspension dissolved in Dimethyl formamide was added to the first
tube in each row and then after mixing the content, 1 mL was
serially transferred from these tubes to the second tube in each of
the rows. Then the contents in the second tube of each of the rows
were mixed and transferred to the third tube in each of the rows.
This serial dilution was repeated till the sixth tube in each of the
rows. This provided anti-microbial concentrations of 50, 25, 12.5,
6.25, 3.125, 1.6125 mg/mL in the first to sixth tube respectively in
each row. Finally, 1 mL of 105 cfu/mL of S. aureus, B. subtilis, E. coli
and P. aeruginosa suspension were added to the first, second, third
and fourth rows of tubes respectively. Along with the test samples

5462
A.M. Vijesh et al. / European Journal of Medicinal Chemistry 45 (2010) 5460e5464
Table 1
Characterization data of the compounds 7aed and 8aeh.
Comp-ounds
Ar
Ph or X
Molecular formula (Mol. wt.)
Yield (%)
M.p. (ꢁC)
7a
7b
7c
7d
8a
8b
8c
8d
8e
8f
4-SCH3eC6H4
2,4-Dichlorophenyl
2,4-Dichlorophenyl
2,4-Dichlorophenyl
2,4-Dichlorophenyl
H
Br
H
Br
H
Br
H
C20H15Cl2N5S2 (461)
C19H11Cl4N5S (483)
C18H9Cl4N5S2 (501)
C25H17Cl2N5S (491)
C23H17N5O2S2 (459)
C23H16BrN5O2S2 (539)
C22H13Cl2N5O2S (483)
C21H12BrCl2N5O2S (549)
C20H11Cl2N5O2S2 (489)
C20H10BrCl2N5O2S (567)
C28H19N5O2S (489)
82
85
78
81
83
76
84
77
79
75
80
76
220e222
210e212
236e238
226e228
202e204
244e246
250e252
240e242
218e220
234e236
238e240
254e256
2,4-Dichlorophenyl
2,5-dichlorothiophene
Biphenyl
4-SCH3eC6H4
4-SCH3eC6H4
2,4-Dichlorophenyl
2,4-Dichlorophenyl
2,5-dichlorothiophene
2,5-dichlorothiophene
Biphenyl
8g
8h
Biphenyl
Br
C28H18BrN5O2S (569)
and Ceftriaxone (standard), the inoculums control (without anti-
microbial compound) and broth control (without anti-microbial
compound and inoculum) were maintained. All the test sample and
control tubes were then incubated for 16 h at 37 ꢁC.
a certain change of activity. Compounds 8e and 8f have 2,5-
dichlorothiophene moiety, which is accounted for the enhanced
antibacterial activity against all the four tested microorganisms.
Similarly compounds 7c, 8c and 8d have showed significant
activity against the four bacteria, which are active at the same
concentration as that of the standard drug. Compound 7c has
2,5-dichlorothiophene and 8c and 8d have 2,4-Dichlorophenyl
subsistent respectively, which is accounted for the activity of the
compounds. On the other hand, for the remaining compounds
have not showed any activity against any of the four tested
bacterial strains. From the obtained results, it is clear that the
major role for antibacterial activity is played by the substituent
present on pyrazole and aromatic rings bonded to thiazole moiety.
It is evident that thiazoles with 2,5-dichlorothiophene and
2,4-Dichlorophenyl are the most active compounds.
4.3. Interpretation
After incubation, the tubes showing no visible growth were
considered to be representing the MIC. The details of results are
furnished in Table 2. Inoculums control showed visible growth,
where as the broth control showed no growth.
5. Conclusion
A series of novel 2,4-disubstituted thiazole derivatives were
synthesized in reasonably good yields. They were characterized by
1H NMR, 13C NMR, mass spectrometry, IR studies and elemental
analyses. All the newly synthesized compounds were screened for
antibacterial activity by MIC method. Among the screened samples,
8e and 8f have showed excellent antibacterial activity at 1.6125 mg/
mL concentration against S. aureus bacteria as compared to the
standard drug Ceftriaxone which is active at 3.125 mg/mL
concentration. They also showed similar activity as that of standard,
against B. subtilis, E. coli and P. aeruginosa, at 1.6125 mg/mL
concentration.
6. Experimental
6.1. Chemistry
Melting points were determined by open capillary method and
were uncorrected. The IR spectra (in KBr pellets) were recorded on
a JASCO FT/IR-4100 spectrophotometer. 1H NMR and 13C NMR
spectra were recorded (DMSO-d6) on a Bruker (400 MHz) and
Varian (400 MHz) spectrometer using TMS as internal standard.
As regards the relationships between the structure of the
heterocyclic scaffold and the detected antibacterial properties, it
showed varied biological activity. Probably in this case the nature
of the heterocyclic ring is not so important for anti-microbial
activity. Moreover, the presence of different substituents causes
Chemical shift values are given in
d scales. The mass spectra were
recorded on a JEOL JMS-D 300 spectrometer operating at 70 eV.
Elemental analyses were performed on a Flash EA 1112 series
CHNS-O Analyzer. The completion of the reaction was checked by
thin layer chromatography (TLC) on silica gel coated aluminium
sheets (silica gel 60 F254). Commercial grade solvents and reagents
were used without further purification.
Table 2
Antibacterial activity data in MIC (mg/mL).
6.2. General procedure for the synthesis of 3-acetyl-6-H/Br-2H-
chromen-2-one (3aeb)
Comp. No.
S. aureus
B.subtilis
E.coli
P.aeruginosa
7a
7b
7c
7d
8a
8b
8c
8d
8e
8f
***
50.00
***
1.6125
***
***
***
1.6125
3.125
1.6125
1.6125
***
50.00
50.00
1.6125
***
***
***
1.6125
1.6125
3.125
1.6125
***
50.00
***
1.6125
***
***
***
1.6125
1.6125
1.6125
1.6125
***
3.125
3.125
***
***
***
3.125
3.125
1.6125
1.6125
***
A mixture of salicylaldehyde/bromosalicylaldehyde (0.5 mol)
and ethylacetoacetate (0.5 mol) were stirred in 20 ml of ethanol and
cooled. To this mixture 10 g of piperidine was added with shaking.
The mixture was maintained at freezing temperature for 2e3 h,
which resulted in yellow colored solid mass, which was separated
out. It was recrystalised from ethanol to get the target compounds.
8g
8h
6.3. General procedure for the synthesis of 6-Bromo/H-3-
***
***
***
***
(bromoacetyl)-2H-chromen-2-one (4a,b)
Ceftriaxone (Standard) 3.125
1.6125
***
1.6125
***
1.6125
***
Inoculum control
Broth control
***
No growth No growth No growth No growth
To a solution of compound 3a-b (0.25 mol) in 200 ml of chlo-
roform, bromine (0.25 mol) in 25 mL of chloroform was added
*** Indicates growth in all concentrations.

A.M. Vijesh et al. / European Journal of Medicinal Chemistry 45 (2010) 5460e5464
5463
under stirring [20]. The mixture was stirred for 1 h at room
temperature and then warmed to decompose the addition product.
The mixture was heated to 55 ꢁC for 15 min, cooled and filtered to
get a solid mass, further which was washed with diethyl ether to
get the desired product. It was recrystalised from acetic acid to give
pale yellow colored needles.
J ¼ 4.8 Hz, p-thioanisyl), 7.48 (dd, 1H, J ¼ 2.0 Hz, 2,4-dichlor-
ophenyl), 7.6 (d, 2H, J ¼ 4.8 Hz, p-thioanisyl), 7.68 (d, 1H, J ¼ 2.4 Hz,
2,4-dichlorophenyl), 7.89 (s, 1H, thizole-5H), 8.0 (s, 1H, pyrazole-
5H), 8.12 (s, 1H, N]CH), 11.83 (s, 1H, pyrazole-NH); MS (m/z, %):
462.0 (Mþ, 64), 464.0 (M þ 2), 466.0 (M þ 4). Anal. calcd. for
C20H15Cl2N5S2: C, 52.06; H, 3.25; N, 15.18. Found: C, 52.04; H, 3.23;
N, 15.20%
6.3.1. Characterization of synthesized compounds
6.3.1.1. 3-(2-Bromoacetyl)-2H-chromen-2-one
(4a). 1H
NMR
6.7.2. 3-(2,4-Dichlorophenyl)-1H-pyrazole-4-carbaldehyde [4-(2,4-
dichlorophenyl)-1,3-thiazol-2-yl]hydrazone (7b)
(DMSO-d6): 4.41 (s, 2H, COCH2), 7.4e7.8 (m, 4H, aromatic H), 8.13
d
(s, 1H, Coumarin 4H).
IR (KBr, ymax cmꢀ1): 3420 (NeH-str), 2923 (CeH-str), 1644(C]
N), 1575 (C]C), 1105 (CeS), 1029 (CeCl); 1H NMR (DMSO-d6):
d 7.26e7.77 (m, 6H, 2,4-dichlorophenyl), 7.84 (s, 1H, thizole-5H),
6.3.1.2. 6-Bromo-3-(2-bromoacetyl)-2H-chromen-2-one
(4b). 1H
NMR (DMSO-d6):
7H, 8H), 8.12 (s, 1H, Coumarin 4H), 8.19 (s, 1H, coumarin 5H).
d
4.43 (s, 2H, COCH2), 7.31e7.62 (m, 2H, Coumarin
7.86 (s, 1H, pyrazole-5H), 8.08 (s, 1H, N]CH), 11.75 (s,1H, pyrazole-
NH); MS (m/z, %): 484.0 (Mþ, 100), 486.0 (M þ 2), 488.0 (M þ 4),
490.0 (M þ 6), 492.0 (M þ 8). Anal. calcd. for C19H11Cl4N5S: C, 47.20;
H, 2.28; N, 14.49. Found: C, 47.16; H, 2.26; N, 14.45%.
6.4. General procedure for the synthesis of 3-aryl-1H-pyrazole-4-
carbaldehyde thiosemicarbazone (6aed)
6.7.3. 3-(2,5-Dichloro-3-thienyl)-1H-pyrazole-4-carbaldehyde [4-
(2,4-dichlorophenyl)-1,3-thiazol-2-yl]hydrazone (7c)
An equimolar mixture of 3-aryl-1H-pyrazole-4-carbaldehyde
(0.143 mol) and thiosemicarbazide (0.143 mol) in ethanol (25 mL)
and sodium acetate (0.07 mol) was refluxed for 8 h. The solid
separated was filtered, dried and recrystalised using ethanoleDMF
mixture.
IR (KBr, ymax cmꢀ1): 3443 (NeH-str), 2931 (CeH-str), 1631(C]
N), 1573 (C]C), 1111 (CeS), 948, 816, 735 (CeCl); 1H NMR (DMSO-
d6):
d
7.31 (s, 1H, 2,4-dichlorophenyl), 7.46 (d, 1H, J ¼ 2.0 Hz
2,4-dichlorophenyl), 7.48 (d, 1H, J ¼ 2.4 Hz, 2,4-dichlorothiophene),
7.65 (d, 1H, J ¼ 2.0 Hz, 2,4-dichlorophenyl), 7.85 (s, 1H, thizole-5H),
7.97 (s, 1H, pyrazole-5H), 8.09 (s, 1H, N]CH), 11.88 (s, 1H, pyrazole-
NH); 13C NMR: 167.2, 145.5, 135.1, 132.4, 132.1, 132.0, 131.5, 129.6,
128.9, 127.3, 124.8, 123.7, 115.3, 108.6. MS (m/z, %): 502.0 (Mþ, 100),
504.0 (M þ 2), 506.0 (M þ 4), 508.0 (M þ 6), 510.0 (M þ 8). Anal.
calcd. for C18H9Cl4N5S2: C, 43.11; H, 1.79; N, 13.97. Found: C, 43.10;
H, 1.75; N, 13.94%.
6.5. Characterization of synthesized compounds
6.5.1. 3-(2,4-Dichlorophenyl)-1H-pyrazole-4-carbaldehyde
thiosemicarbazone (6a)
IR (KBr, ymax cmꢀ1): 3451, 3324 (NeH-str), 1603 (C]N), 1537
(C]C), 1109 (C]S), 948, 835 (CeCl). Yield 82%, M.p. 212e214 ꢁC.
6.5.2. 3-[4-(Methylthio)phenyl]-1H-pyrazole-4-carbaldehyde
thiosemicarbazone (6b)
6.7.4. 3-Biphenyl-4-yl-1H-pyrazole-4-carbaldehyde [4-(2,4-
dichlorophenyl)-1,3-thiazol-2-yl]hydrazone (7d)
IR (KBr, ymax cmꢀ1): 3424, 3282 (NeH-str), 1591 (C]N), 1559
(C]C), 1128 (C]S). Yield 76%, M.p. 238e240 ꢁC.
IR (KBr, ymax cmꢀ1): 3419 (NeH-str), 2924 (CeH-str), 1626(C]
N), 1573 (C]C), 1104 (CeS), 953, 838, 729 (CeCl); 1H NMR (DMSO-
d6):
d 7.34 (s, 1H, 2,4-dichlorophenyl), 7.39e7.51 (m, 4H,
6.5.3. 3-(2,5-Dichloro-3-thienyl)-1H-pyrazole-4-carbaldehyde
thiosemicarbazone (6c)
2,4-dichlorophenyl, biphenyl), 7.66 (d, 1H, J ¼ 2.4 Hz, 2,4-dichlor-
ophenyl), 7.73e7.82 (m, 7H,biphenyl), 7.88 (s, 1H, thizole-5H), 8.02
(s, 1H, pyrazole-5H), 8.18 (s, 1H, N]CH), 11.87 (s, 1H, pyrazole-NH);
13C NMR: 167.2, 139.9, 139.4, 136.0, 132.3, 132.1, 132.0, 131.5, 129.6,
128.9, 128.6, 127.6, 127.4, 126.8, 126.6, 113.9, 108.7. MS: (m/z, %):
492.0 (Mþ, 60), 494.0 (M þ 2), 496.0 (M þ 4). Anal. calcd. for
C25H17Cl2N5S: C, 61.10; H, 3.46; N, 14.26. Found: C, 61.07; H, 3.44; N,
14.23%.
IR (KBr, ymax cmꢀ1): 3432, 3272 (NeH-str), 3030 (CeH-str),
1606 (C]N), 1559 (C]C), 1036 (C]S), 945, 823, 706 (CeCl). Yield
78%, M.p. 228e230 ꢁC.
6.5.4. 3-Biphenyl-4-yl-1H-pyrazole-4-carbaldehyde
thiosemicarbazone (6d)
IR (KBr, ymax cmꢀ1): 3471, 3309 (NeH-str), 3046 (CeH-str), 1590
(C]N), 1576 (C]C), 1104 (C]S). Yield 81%, M.p. 234e236 ꢁC.
6.7.5. 3-[4-(Methylthio)phenyl]-1H-pyrazole-4-carbaldehyde [4-
(2-oxo-2H-chromen-3-yl)-1,3-thiazol-2-yl]hydrazone (8a)
IR (KBr, ymax cmꢀ1): 3311 (NeH-str), 2920 (CeH-str), 1728(C]O
6.6. General procedure for the synthesis of 3-aryl-1H-pyrazole-4-
carbaldehyde (4-aryl-1,3-thiazol-2-yl)hydrazone (7aed and 8aeh)
a
-Pyrone), 1605(C]N), 1562 (C]C); 1095 (CeS), 1H NMR
(DMSO-d6):
d 2.53 (s, 3H, SCH3), 7.29e7.75 (m, 9H, coumarin,
An equimolar mixture of 3-Aryl-1H-pyrazole-4-carbaldehyde
thiosemicarbazone 4a-d (0.01 mol) and substituted phenacyl
bromide/chlorides (0.01 mol) in ethanol was refluxed for 4 h. After
completion of the reaction, the reaction mixture was allowed to
cool. The solid thus separated was collected by filtration and
recrystalised using ethanoleDMF mixture.
p-anisyl), 7.92 (s, 1H, thizole-5H), 8.09 (s, 1H, pyrazole-5H), 8.46 (s,
1H, N]CH), 11.79 (s, 1H, pyrazole-NH); MS (m/z, %): 460.0 (Mþ,
100). Anal. calcd. for C23H17N5O2S2: C, 60.13; H, 3.70; N, 15.25.
Found: C, 60.12; H, 3.68; N, 15.23%.
6.7.6. 3-[4-(Methylthio)phenyl]-1H-pyrazole-4-carbaldehyde [4-
(6-bromo-2-oxo-2H-chromen-3-yl)-1,3-thiazol-2-yl]hydrazone
(8b)
6.7. Characterization of synthesized compounds
IR (KBr, ymax cmꢀ1): 3320 (NeH-str), 2919 (CeH-str), 1731(C]O
6.7.1. 3-[4-(Methylthio)phenyl]-1H-pyrazole-4-carbaldehyde [4-
(2,4-dichlorophenyl)-1,3-thiazol-2-yl]hydrazone (7a)
a
-Pyrone), 1631(C]N), 1573 (C]C); 1096 (CeS), 1H NMR (DMSO-
d6):
d 2.53 (s, 3H, SCH3), 7.36 (s, 1H, coumarin), 7.40 (d, 2H,
IR (KBr, ymax cmꢀ1): 3422 (NeH-str), 2852 (CeH-str), 1627(C]
J ¼ 4.4 Hz p-thioanisyl), 7.59 (d, 2H, J ¼ 4.8 Hz, p-thioanisyl),
7.72e7.75 (m, 2H, coumarin), 7.79 (s, 1H, thizole-5H), 8.12 (s, 1H,
coumarin 4H), 8.13 (s, 1H, pyrazole-5H), 8.45 (s, 1H, N]CH), 11.84
N), 1579 (C]C), 1108 (CeS), 956, 838 (CeCl); 1H NMR (DMSO-d6):
d
2.53 (s, 3H, SCH3), 7.36 (s, 1H, 2,4-dichlorophenyl), 7.41 (d, 2H,

5464
A.M. Vijesh et al. / European Journal of Medicinal Chemistry 45 (2010) 5460e5464
(s,1H, pyrazole-NH); 13C NMR: 167.5, 136.5, 133.7, 130.6, 128.5,
125.9, 121.1, 118.0, 111.0, 14.5. MS (m/z, %): 540.0 (Mþ, 82), 542.0
(M þ 2). Anal. calcd. for C23H16BrN5O2S2: C, 51.21; H, 2.97; N, 12.99.
Found: C, 51.18; H, 2.95; N, 12.96%.
(s, 1H, pyrazole-5H), 8.43 (s, 1H, N]CH), 11.84 (s, 1H, pyrazole-NH);
MS (m/z, %): 490.2 (Mþ,100). Anal. calcd. for C28H19N5O2S: C, 68.71; H,
3.88; N, 14.31. Found: C, 68.69; H, 3.86; N, 14.30%.
6.7.12. 3-(Biphenyl)-1H-pyrazole-4-carbaldehyde [4-(6-bromo-2-
6.7.7. 3-(2,4-Dichlorophenyl)-1H-pyrazole-4-carbaldehyde [4-(2-
oxo-2H-chromen-3-yl)-1,3-thiazol-2-yl]hydrazone (8c)
oxo-2H-chromen-3-yl)-1,3-thiazol-2-yl]hydrazone (8h)
IR (KBr, ymax cmꢀ1): 3326 (NeH-str), 1733 (C]O
a-Pyrone), 1633
IR (KBr, ymax cmꢀ1): 3445 (NeH-str), 2925 (CeH-str), 1722 (C]O
(C]N), 1574 (C]C), 1105 (CeS); 1H NMR (DMSO-d6):
d
7.37e7.82
a
-Pyrone), 1633(C]N), 1558 (C]C); 1099 (C-S), 1H NMR (DMSO-
(m, 12H, coumarin, biphenyl), 8.02 (s, 1H, thizole-5H), 8.11 (d, 1H,
J ¼ 2.4 Hz coumarin), 8.20 (s, 1H, pyrazole-5H), 8.45 (s, 1H, N]CH),
11.88 (s, 1H, pyrazole-NH); 13C NMR: 167.6, 158.2, 151.2,143.5, 139.9,
139.4, 136.5, 136.2, 133.7, 130.6, 129.8, 128.9, 128.6, 127.6, 126.8,
126.6, 121.4, 121.1, 118.0, 116.2, 113.9, 111.0. MS (m/z, %): 570.0 (Mþ,
82), 572.0 (M þ 2). Anal. calcd. for C28H18BrN5O2S: C, 59.05; H, 3.16;
N, 12.30. Found: C, 59.03; H, 3.14; N, 12.27%.
d6):
d 7.34e7.47 (m, 3H, coumarin, 2,4-dichlorophenyl), 7.55 (dd,
1H, J ¼ 2.0 Hz 2,4-dichlorophenyl), 7.60e7.63 (m, 2H, coumarin),
7.76 (d, 1H, J ¼ 2.0 Hz 2,4-dichlorophenyl), 7.81e7.83 (dd, 1H,
J ¼ 6.4 Hz coumarin), 7.88 (s, 1H, thizole-5H), 8.08 (s, 1H, pyrazole-
5H), 8.47 (s, 1H, N]CH), 11.78 (s,1H, pyrazole-NH); 13C NMR: 167.5,
159.0, 152.4, 138.0, 135.2, 134.0, 133.2, 131.5, 129.1, 128.7, 127.2,
124.6, 120.4, 115.8, 115.4, 110.0. MS (m/z, %): 484.0 (Mþ, 68), 486.0
(M þ 2), 488.0 (M þ 4). Anal. calcd. for C22H13Cl2N5O2S: C, 54.66; H,
2.69; N, 14.49. Found: C, 54.64; H, 2.66; N, 14.47%.
Acknowledgements
AMI thank Prof. A.V. Adhikari, HOD Chemistry and Prof. Sandeep
Sancheti, Director, National Institute of Technology-Karnataka,
India for providing the research facilities. Also thank Board for
research in Nuclear Sciences, Government of India for ‘Young
Scientist’ award. AMV thankful to the management, SEQUENT
SCIENTIFIC LTD, New Mangalore, India for their invaluable support
and allocation of resources for this work. The authors are also
thankful to Head, NMR Research center, IISc, Bangalore for
providing spectral data.
6.7.8. 3-(2,4-Dichlorophenyl)-1H-pyrazole-4-carbaldehyde [4-(6-
bromo-2-oxo-2H-chromen-3-yl)-1,3-thiazol-2-yl]hydrazone (8d)
IR (KBr, ymax cmꢀ1): 3420 (NeH-str), 1715 (C]O
a
-Pyrone), 1627
(C]N), 1576 (C]C); 1105 (CeS), 1H NMR (DMSO-d6):
d
7.38e7.77
(m, 7H, coumarin, 2,4-dichlorophenyl), 7.88 (s, 1H, thizole-5H), 8.07
(s, 1H, pyrazole-5H), 8.11 (d, 1H, J ¼ 2.0 Hz coumarin), 8.41 (s, 1H,
N]CH), 11.77 (s, 1H, pyrazole-NH); 13C NMR: 167.6, 158.2, 151.2,
143.5, 136.5, 135.3, 133.9, 133.2, 130.6, 129.1, 127.2, 121.4, 121.1, 118.0,
116.2,115.3,110.8. MS (m/z, %): 550.0 (Mþ,100), 552.0 (M þ 2), 554.0
(M þ 4), 556.0 (M þ 6). Anal. calcd. for C21H12BrCl2N5O2S: C, 45.90;
H, 2.18; N, 12.79. Found: C, 45.87; H, 2.15; N, 12.76%.
References
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6.7.9. 3-(2,5-Dichloro-3-thienyl)-1H-pyrazole-4-carbaldehyde [4-
(2-oxo-2H-chromen-3-yl)-1,3-thiazol-2-yl]hydrazone (8e)
IR (KBr, ymax cmꢀ1): 3420 (NeH-str), 1698 (C]O
a
-Pyrone), 1636
(C]N), 1576 (C]C); 1111 (CeS), 1H NMR (DMSO-d6):
d
7.2e7.8 (m,
6H, coumarin, 2,5-dichlorothiophene), 7.90 (s, 1H, thizole-5H), 8.02
(s, 1H, pyrazole-5H), 8.42 (s, 1H, N]CH), 11.78 (s, 1H, pyrazole-NH);
13C NMR: 167.5, 158.7, 152.2, 138.0, 135.2, 131.6, 128.9, 128.7, 124.9,
124.6, 120.5, 119.1, 115.8, 115.3, 110.1, 85.6. MS (m/z, %): 490.0 (Mþ,
100), 492.0 (M þ 2), 494.0 (M þ 4). Anal. calcd. for C20H11Cl2N5O2S2:
C, 49.08; H, 2.25; N, 14.31. Found: C, 49.07; H, 2.23; N, 14.28%.
6.7.10. 3-(2,5-Dichloro-3-thienyl)-1H-pyrazole-4-carbaldehyde [4-
(6-bromo-2-oxo-2H-chromen-3-yl)-1,3-thiazol-2-yl]hydrazone (8f)
IR (KBr, ymax cmꢀ1): 3316 (NeH-str), 2924 (CeH-str), 1715 (C]O
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a
-Pyrone), 1629(C]N), 1573 (C]C), 1109 (CeS), 949, 816 (CeCl); 1H
NMR (DMSO-d6):
d 7.20e7.65 (m, 3H, coumarin), 7.67 (d, 1H,
J
¼
2.4 Hz 2,5-dichlorothiophene), 7.91 (s, 1H, thizole-5H),
8.02e8.04 (m, 2H, coumarin), 8.36 (s, 1H, pyrazole-5H), 8.86 (s, 1H,
N]CH), 11.80 (s, 1H, pyrazole-NH); 13C NMR: 167.5, 158.2, 151.2,
143.5, 136.5, 135.3, 133.7, 130.6, 128.9, 124.9, 121.4, 121.1, 118.0, 116.2,
15.3,110.9. MS (m/z, %): 567.9 (Mþ, 27), 570.0 (M þ 2), 572.0 (M þ 4),
574.0 (M þ 6). Anal. calcd. for C20H10BrCl2N5O2S2: C, 42.33; H, 1.76;
N, 12.35. Found: C, 42.31; H, 1.75; N, 12.33%.
6.7.11. 3-(Biphenyl)-1H-pyrazole-4-carbaldehyde [4-(2-oxo-2H-
chromen-3-yl)-1,3-thiazol-2-yl]hydrazone (8g)
IR (KBr, ymax cmꢀ1): 3420 (NeH-str), 2923 (CeH-str), 1729 (C]O
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a
d
-Pyrone),1633 (C]N),1564 (C]C),1100 (CeS); 1H NMR (DMSO-d6):
7.35e7.81 (m,14H, coumarin, biphenyl), 8.01 (s,1H, thizole-5H), 8.17