One-pot synthesis of thiazoles via Hantzsch thiazole reaction and their antimicrobial activity

Article abstract of DOI:10.14233/ajchem.2016.19603

In this work, substituted 2-bromo-1-phenylethanone compounds (1a-c) synthesized by reaction of bromine and various subtituted acetophenone. Compounds (1a-c) treated with thiosemicarbazide and several carbonyl species to gave corresponding substituted 4-ph

Full text of DOI:10.14233/ajchem.2016.19603

Asian Journal of Chemistry; Vol. 28, No. 4 (2016), 927-932
A
SIAN
J
OURNAL OF HEMISTRY
C
http://dx.doi.org/10.14233/ajchem.2016.19603
One-Pot Synthesis of Thiazoles via Hantzsch Thiazole Reaction and Their Antimicrobial Activity
1,*
1
2
2
1
PRABHUNATH YOGI , MOHAMMAD ASHID , NASIR HUSSAIN , SABA KHAN and AJIT JOSHI
1Organic Chemistry Laboratory, Department of Chemistry, Mewar University, Gangrar-312 901, India
2Organic Chemistry Laboratory, Vidya Bhawan Rural Institute, Udaipur-313 011, India
*Corresponding author: E-mail: prabhunath1987@gmail.com
Received: 7 September 2015;
Accepted: 23 November 2015;
Published online: 30 December 2015;
AJC-17718
In this work, substituted 2-bromo-1-phenylethanone compounds (1a-c) synthesized by reaction of bromine and various subtituted
acetophenone. Compounds (1a-c) treated with thiosemicarbazide and several carbonyl species to gave corresponding substituted 4-
phenyl-1,3-thiazole derivatives (2a-c to 6a-c) via multicomponent reaction and Hantzsch thiazole synthesis.All the synthesized compound
tested for their antimicrobial activity.
Keywords: Hantzsch thiazole synthesis, Pyrazolone, Thiazolidione, Isatine.
[24], antifungal [25], antibacterial [26,27], anticonvulsant [28-
31], antitumor [32] and antitubercular [33] properties.
INTRODUCTION
Nitrogen and sulfur containing nucleus have played a
crucial part in the history of heterocyclic chemistry and also
been used extensively as important synthons in organic
synthesis. Owing to the versatile medicinal activities of azoles,
a significant amount of research activity has been directed
towards this class. Thiazole linked molecule have a broad
spectrum of pharmacological activities, such as antiinfla-
mmatory [1], antihypertensive properties [2], antibacterial [3],
antifungal [4] and as well as being used as cystic fibrosis
transmembrane conductance regulator [5] (CFTR). Thiazo-
lidinediones nucleus play important role in antihyperglycemic
activity [6], anti-HIV activity [7], antihyperglycemic activity
[8] and peroxisome proliferator activated receptors (PPARs)
activity [9]. Isatine containing candidates are important
classes of nitrogen containing heterocycles and they constitute
useful intermediates in organic synthesis [10]. They have been
discovered for their applications in dyes, building blocks for the
synthesis of organic semiconductors and medicinal functions
such as antioxidant properties [11]. The furan derivatives has
attracted much attention in recent studies due to their biological
evaluation such as neuroprotection [12], oxytocin antagonism
[13], antioxidant, anti-inflammatory, antibacterial [14], β-
aggregate specific effect forAlzheimer’s disease treatment [15],
cholinesterase inhibition [16], H-3 receptor antagonism
with dyes function improvement [17], anticonvulsant [18],
antidepressant [19] and anticancer against different types of
carcinoma [20-23]. Pyrazole conjugated moieties have proved
for their effective pharmaceutical activities like anti-inflammatory
EXPERIMENTAL
All melting points were determined in open capillary tube
and are uncorrected. The IR spectra were recorded on Perkin-
Elmer-1800 spectrometer. The 1H NMR spectra (CDCl3) were
scanned on a DRX-300 (300 MHz) spectrometer using TMS
as internal standard and chemical shifts are expressed in δ,
ppm. The mass spectra were recorded on Jeol SX-102 (FAB)
spectrometer. Microwave induced reaction were carried out
in CATA scientific microwave synthesis system (2450 MHz,
catalyst system, India). Purity of synthesized compounds was
checked by elemental analysis and homogeneity was checked
by TLC using silica gel-G, as adsorbent and visualization was
accomplished by iodine.
Conventional synthesis of 2-bromo-1-phenyl ethanone
(1a): Acetophenone (0.55 mmol) and 100 mL glacial acetic
acid taken in beaker. Similarly, bromine (0.125 mmol) and
100 mL glacial acetic acid taken in another beaker and it added
drop by drop in the solution of acetophenone and glacial acetic
acid with occasionally shaking. Reaction mass stay for 30 min,
poured in ice water, isolated the solid and recrystallized from
ethanol. Physico-chemical data of the synthesized compounds
are given in Table-1.
Microwave assisted synthesis of 2-bromo-1-phenyl-
ethanone (1a):Acetophenone (0.55 mmol) and 100 mL glacial
acetic acid taken in beaker. Similarly, bromine (0.125 mmol)
and 100 mL glacial acetic acid taken in another beaker and it

928 Yogi et al.
Asian J. Chem.
added drop by drop in the solution of acetophenone and glacial
acetic acid with occasionally shaking. Reaction mixture
was transferred in an Erlenmeyer flask and irradiated under
microwave irradiation for 15 min with a time interval of 35 s,
after the completion of reaction indicated by TLC, poured in
ice water, isolated the solid and recrystallized from ethanol
(Scheme-I). Physico-chemical data of the synthesized com-
pounds are given in Table-1. IR (KBr, νmax, cm-1): 3055 (Ar-H
Microwave assisted synthesis of 2-(5-ethoxy-3-methyl-
1H-pyrazol-1-yl)-4-phenyl-1,3-thiazole (2a): Take an equi-
molar mixture of compound (1a) 2-bromo-1-phenylethanone
(0.01 M), thiosemicarbazide (0.01 mmol) and ethyl aceto-
acetate (0.01 mmol) and add 10 % HBr sol as a catalysis in
Erlenmeyer flask and irradiated under microwave irradiation
for 15 min with a time interval of 40 s, after the completion of
reaction indicated by TLC, then poured in crushed ice, solid
appear which was isolated, washed with cold methanol and
recrystallized from ethanol (Scheme-II). Physico-chemical
data of the synthesized compounds are given in Table-1.
IR (KBr, νmax, cm-1): 3077 (Ar-H, str.), 2973 (CH2, str.),
1620 (C=N thiazole, str.), 1601(C=N, pyrazole, str.), 1363
(N-N), 1262 (C-O-C, str.); 1H NMR (CDCl3) δ: 7.43-7.70 (m,
5 H, Ar-H), 7.24 (s, 1H, thiazole), 6.72 (s, 1H, pyrazole), 3.39
(s, 3H, CH3); MS: m/z 285 [M]+., 240, 225, 160, 77.
1
str), 2950 (CH2, str.), 1685 (C=O str.), H NMR (CDCl3) δ:
7.04-8.16 (m, 5H, Ar-H), 3.06 (s, 2H, CH2); MS: m/z 199 [M]+.,
119, 103, 77.
O
O
Stirring 25 min
Br /CH COOH,
2
3
Br
Me
R
R
m.w. 15 min
1(a-c)
Similarly compounds 2b-c were prepared with some
changes in reflux time and work up process.
R:
a = C6H5; b = p-Br-C6H4; c = p-F-C6H4
Scheme-I
4-(4-Bromophenyl)-2-(5-ethoxy-3-methyl-1H-pyrazol-
1-yl)-1,3-thiazole (2b): IR (KBr, νmax, cm-1): 3086 (Ar-H, str.),
2977 (CH2, str.), 1626 (C=N thiazole, str.), 1607(C=N,
Similarly compounds 1b-c were prepared with minor
changes in stirring time and work up process.
1
pyrazole, str.), 1369 (N-N), 1268 (C-O-C, str.); H NMR
2-Bromo-1-(4-bromophenyl)ethanone (1b): IR (KBr,
(CDCl3) δ: 7.53-7.80 (m, 4H, Ar-H), 7.34 (s, 1H, thiazole),
6.75 (s, 1H, pyrazole), 3.42 (s, 3H, CH3); MS: m/z 365 [M]+.,
367, 319, 304, 239, 156, 76.
ν
max, cm-1): 3065 (Ar-H str), 2980 (CH2, str.), 1690 (C=O str.),
1H NMR (CDCl3) δ: 7.12-8.23 (m, 4H, Ar-H), 3.14 (s, 1H,
CH2); MS: m/z 277[M]+., 198, 182, 156, 76.
2-(5-Ethoxy-3-methyl-1H-pyrazol-1-yl)-4-(4-fluoro-
phenyl)-1,3-thiazole (2c): IR (KBr, νmax, cm-1): 3094 (Ar-H,
str.), 2985 (CH2, str.), 1633 (C=N, thiazole, str.), 1615 (C=N,
pyrazole, str.), 1376 (N-N, str.), 1277 (C-O-C, str.); 1H NMR
(CDCl3) δ: 7.63-7.91 (m, 4H, Ar-H), 7.39 (s, 1H, thiazole),
6.77 (s, 1H, pyrazole), 3.46 (s, 3H, CH3); MS: m/z 303 [M]+.,
258, 243, 178, 95, 76.
Conventional synthesis of 2-[-2-(5-methyl-2,4-dihydro-
3H-pyrazol-3-ylidene)hydrazino]-4-phenyl-1,3-thiazole
(3a): Take an equimolar mixture of compound (1a) 2-bromo-
1-phenylethanone (0.01 mmol), thiosemicarbazide (0.01
mmol) and methanolic solution of methyl pyrazole (0.01
mmol) and add 10 % HBr sol as a catalysis in conical flask
2-Bromo-1-(4-fluorophenyl)ethanone (1c): IR (KBr,
ν
max, cm-1): 3072 (Ar-H str), 2990 (CH2, str.), 1696 (C=O str.),
1H NMR (CDCl3) δ: 7.17-8.33 (m, 4H, Ar-H), 3.23 (s, 2H,
CH2); MS: m/z 217[M]+., 137, 121, 95, 76.
Conventional synthesis of 2-(5-ethoxy-3-methyl-1H-
pyrazol-1-yl)-4-phenyl-1,3-thiazole (2a): Take an equimolar
mixture of compound (1a) 2-bromo-1-phenylethanone (0.01
mmol), thiosemicarbazide (0.01 mmol) and ethyl aceto acetate
(0.01 mmol) in conical flask and add 10 % HBr sol as a catalysis
than stirrer at room temperature for about 25 min gave the
solid. It was filtered, washed with cold methanol and recrysta-
llized from ethanol. Physico-chemical data of the synthesized
compounds are given in Table-1.
TABLE-1
PHYSICAL AND ANALYTICAL DATA OF NEW SYNTHESIZED COMPOUNDS 1a-c TO 6a-c
Elemental analysis (%): Found (calcd.)
m.p.
(°C)
Yield (%):
Conven. (M.W.)
Compd.
m.f.
C8H7BrO
C8H6Br2O
C8H6BrFO
m.w.
C
H
N
S
-
-
-
1a
1b
1c
2a
2b
2c
3a
3b
3c
4a
4b
4c
5a
5b
5c
6a
6b
6c
199
277
217
285
364
303
271
350
289
320
399
338
283
362
301
290
369
308
49
51
54
80 (86)
75 (80)
82 (85)
86 (90)
84 (89)
81 (85)
76 (80)
87 (90)
83 (87)
70 (80)
71 (75)
69 (78)
65 (70)
67 (75)
68 (80)
78 (85)
79 (87)
77 (86)
48.25 (48.27)
34.60 (34.57)
44.25 (44.27)
63.10 (63.13)
44.48 (44.46)
59.35 (59.39)
57.50 (57.54)
44.60 (44.58)
53.95 (53.97)
63.70 (63.73)
51.17 (51.14)
60.31 (60.34)
63.55 (63.58)
49.75 (49.73)
59.75 (59.79)
49.60 (49.64)
39.05 (39.03)
46.70 (46.74)
3.50 (3.54)
2.19 (2.18)
2.78 (2.79)
5.26 (5.30)
3.88 (3.87)
4.64 (4.65)
4.82 (4.83)
3.46 (3.45)
4.17 (4.18)
3.76 (3.78)
2.80 (2.78)
3.25 (3.28)
4.60 (4.62)
3.36 (3.34)
4.00 (4.01)
3.45 (3.47)
2.47 (2.46)
2.93 (2.94)
-
-
-
C15H15N3OS
C15H14N3OSBr
C15H14N3OSBrF
C13H13N5S
C13H12N5SBr
C13H12N5SF
C17H12N4OS
C17H11N4OSBr
C17H11N4OSF
C15H13N3OS
C15H12N3OSBr
C15H12N3OSF
C12H10N4OS2
C12H9N4OS2Br
C12H9N4OS2F
248
249
253
256
261
263
272
275
277
189
192
194
298
307
313
14.70 (14.73)
11.56 (11.54)
13.83 (13.85)
25.79 (25.81)
20.02 (20.00)
24.19 (24.21)
17.45 (17.49)
14.05 (14.03)
16.53 (16.56)
14.80 (14.83)
11.63 (11.60)
13.91 (13.94)
19.25 (19.30)
15.19 (15.17)
18.13 (18.17)
11.22 (11.24)
8.82 (8.80)
10.56 (10.57)
11.80 (11.82)
9.17 (9.16)
11.06 (11.08)
09.99 (10.01)
8.05 (8.03)
9.45 (9.48)
11.29 (11.32)
8.88 (8.85)
10.60 (10.64)
22.06 (22.09)
17.40 (17.37)
20.76 (20.80)

Vol. 28, No. 4 (2016)
One-Pot Synthesis of Thiazoles via Hantzsch Thiazole Reaction and Their Antimicrobial Activity 929
EtO
N
R
N N
S
2(a-c)
Stirrer 25 min
N
N
R
R
O
NH
N
NH
N
Me
S
M.W. 15
S
S
N
H
N N
H
O
O
3(a-c)
6(a-c)
O
OEt
Stirrer 50 min
Stirrer 60 min
M.W.40
M.W. 35
O
S
N
H
N N
H
O
CH OH
C H OH
2 5
3
H N
O
NH
2
NH
Br
2
+
R
S
1(a-c)
C H OH
2 5
O
M.W. 30
M.W. 20
O
O
O
Me
N
H
Stirrer 20 min
Stirrer 55 min
N
N
R
NH
O
N
R
NH
N
O
S
S
Me
N
H
5(a-c)
4(a-c)
Scheme-II
and stirrer at room temperature for about 50 min gave the solid.
It was filtered, washed with cold methanol and recrystallized
from ethanol. Physico-chemical data of the synthesized com-
pounds are given in Table-1.
CH2, ring), 1.24 (s, 3H, CH3); MS: m/z 271 [M]+., 256, 189,
160, 77.
Similarly compounds 3b-c were prepared with some
change in stirring time and work up process.
4-(4-bromophenyl)-2-[-2-(5-methyl-2,4-dihydro-3H-
pyrazol-3-ylidene)hydrazino]-1,3-thiazole (3b): IR (KBr,
Microwave assisted synthesis of 2-[-2-(5-methyl-2,4-
dihydro-3H-pyrazol-3-ylidene) hydrazino]-4-phenyl-1,3-
thiazole (3a): Take an equimolar mixture of compound (1a)
2-bromo-1-phenylethanone (0.01 mmol), thiosemicarbazide
(0.01 mmol) and methanolic solution of methyl pyrazole (0.01
mmol) and add 10 % HBr sol. as a catalysis in Erlenmeyer
flask and irradiated under microwave irradiation for 35 min
with a time interval of 45 s, after the completion of reaction
indicated by TLC, then poured in crushed ice, solid appear
which was isolated, washed with cold methanol and recrysta-
llized from ethanol (Scheme-II). Physico-chemical data of the
synthesized compounds are given in Table-1.
ν
max, cm-1): 3341 (N-H, ring, str.), 3217 (N-H, str.), 3046 (Ar-
H, str.), 2941 (CH2, str.), 1640 (C=N, thiazole, str.), 1559 (C=N,
1
pyrazole, str.), 1493 (N-N, str.); H NMR (CDCl3) δ: 7.32-
8.10 (m, 4H, Ar-H), 6.81 (s, 1H, C-H, thiazole ring), 5.34 (s,
1H, N-H), 4.75 (s, 1H, N-H ring), 3.51 (s, 2H, CH2, ring),
1.30 (s, 3H, CH3); MS: m/z 351 [M]+., 353, 335, 268, 239,
156, 76.
4-(4-Fluorophenyl)-2-[-2-(5-methyl-2,4-dihydro-3H-
pyrazol-3-ylidene)hydrazino]-1,3-thiazole (3c): IR (KBr,
ν
max, cm-1): 3346 (N-H, ring, str.), 3222 (N-H, str.), 3049 (Ar-
IR (KBr, νmax, cm-1): 3336 (N-H, ring, str.), 3210 (N-H,
str.), 3045 (Ar-H, str.), 2931 (CH2, str.), 1632 (C=N, thiazole,
H, str.), 2950 (CH2, str.), 1646 (C=N, thiazole, str.), 1565 (C=N,
1
pyrazole, str.), 1498 (N-N, str.); H NMR (CDCl3) δ: 7.34-
1
str.), 1551 (C=N, pyrazole, str.), 1483 (N-N, str.), H NMR
8.15 (m, 4H, Ar-H), 6.85 (s, 1H, C-H, thiazole ring), 5.38 (s,
1H, N-H), 4.80 (s, 1H, N-H ring), 3.54 (s, 2H, CH2, ring),
1.34 (s, 3H, CH3); MS: m/z 289 [M]+., 274, 207, 178, 95, 76.
(CDCl3) δ: 7.21-7.80 (m, 5H,Ar-H), 6.77 (s, 1H, C-H, thiazole
ring), 5.30 (s, 1H, N-H), 4.70 (s, 1H, N-H ring) 2.26 (s, 2H,

930 Yogi et al.
Asian J. Chem.
Conventional synthesis of 3-[(4-phenyl-1,3-thiazol-2-
IR (KBr, νmax, cm-1): 3431 (N-H, str.), 3131 (Ar-H, str.),
1615 (C=N, str.), 1494 (N-N, str.), 1360 (C=N, ring, str.), 1284
(C-O-C, str.); 1H NMR (CDCl3) δ: 7.15-8.05 (m, 8H, Ar-H),
6.50 (s, 1H, C-H, thiazole), 4.99 (s, 1H, NH), 3.40 (s, 3H,
CH3); MS: m/z 283 [M]+., 268, 201, 160, 78.
4-(4-Bromophenyl)-2-[-2-(1-furan-2-ylethylidene)-
hydrazino]-1,3-thiazole (5b): IR (KBr, νmax, cm-1): 3441 (N-
H, str.), 3138 (Ar-H, str.), 1624 (C=N, str.), 1499 (N-N, str.),
1366 (C=N, ring, str.), 1295 (C-O-C, str.); 1H NMR (CDCl3)
δ: 7.20-8.10 (m, 7H, Ar-H), 6.54 (s, 1H, C-H, thiazole), 5.04
(s, 1H, NH), 3.45 (s, 3H, CH3); MS: m/z 363 [M]+., 365, 347,
280, 239, 156, 76.
4-(4-Fluorophenyl)-2-[-2-(1-furan-2-ylethylidene)-
hydrazino]-1,3-thiazole (5c): IR (KBr, νmax, cm-1): 3445 (N-H,
str.), 3142 (Ar-H, str.), 1630 (C=N, str.), 1510 (N-N, str.), 1371
(C=N, ring, str.), 1301(C-O-C, str.); 1H NMR (CDCl3) δ: 7.22-
8.13 (m, 7H, Ar-H), 6.57 (s, 1H, C-H, thiazole), 5.10 (s, 1H,
NH), 3.50 (s, 3H, CH3); MS: m/z 301[M]+., 286, 219, 178, 95, 76.
Conventional synthesis of 4-[(4-phenyl-1,3-thiazol-2-
yl)hydrazono]-1,3-thiazolidin-2-one (6a): Take an equimolar
mixture of compound (1a) 2-bromo-1-phenylethanone (0.01
mmol), thiosemicarbazide (0.01 mmol) and ethanolic solution
of thiazolidione (0.01 mmol) and add 10 % HBr sol as a
catalysis in conical flask and stirrer at room temperature for
about 60 min gave the solid. It was filtered, washed with cold
methanol and recrystallized from ethanol. Physico-chemical
data of the synthesized compounds are given in Table-1.
Microwave assisted synthesis 4-[(4-phenyl-1,3-thiazol-
2-yl)hydrazono]-1,3-thiazolidin-2-one (6a): Take an equi-
molar mixture of compound (1a) 2-bromo-1-phenylethanone
(0.01 mmol), thiosemicarbazide (0.01 mmol) and ethanolic
solution of thiazolidione (0.01 mmol) and add 10 % HBr sol
as a catalysis in Erlenmeyer flask and irradiated under
microwave irradiation for 40 min with a time interval of 55 s,
after the completion of reaction indicated by TLC, than poured
in crushed ice, solid appear which was isolated, washed with
cold methanol and recrystallized from ethanol (Scheme-II).
Physico-chemical data of the synthesized compounds are given
in Table-1.
yl)hydrazono]-1,3-dihydro-2H-indol-2-one (4a):Take an equi-
molar mixture of compound (1a) 2-bromo-1-phenylethanone
(0.01 mmol), thiosemicarbazide (0.01 mmol) and ethanolic
solution of isatine (0.01 mmol) and add 10 % HBr sol as a
catalysis in conical flask and stirrer at room temperature for
about 55 min gave the solid. It was filtered, washed with cold
methanol and recrystallized from ethanol. Physico-chemical
data of the synthesized compounds are given in Table-1.
Microwave assisted synthesis of 3-[(4-phenyl-1,3-thiazol-
2-yl)hydrazono]-1,3-dihydro-2H-indol-2-one (4a): Take an
equimolar mixture of compound (1a) 2-bromo-1-phenylethanone
(0.01 mmol), thiosemicarbazide (0.01 mmol) and ethanolic
solution of isatine (0.01 mmol) and add 10 % HBr sol as a
catalysis in Erlenmeyer flask and irradiated under microwave
irradiation for 30 min with a time interval of 35 s, after the
completion of reaction indicated by TLC, than poured in crushed
ice, solid appear which was isolated, washed with cold methanol
and recrystallized from ethanol (Scheme-II). Physico-chemical
data of the synthesized compounds are given in Table-1.
IR (KBr, νmax, cm-1): 3403 (N-H, ring, str.), 3315 (N-H,
str.), 3162 (Ar-H, str.), 1676 (C=O, str.), 1618 (C=N, ring,
str.), 1463 (N-N, str.); 1H NMR (CDCl3) δ: 7.02-8.84 (m, 9H,
Ar-H), 6.51 (s, 1H, C-H, thiazole), 4.90 (s, 1H, NH), 3.80 (s,
1H, NH, ring); MS: m/z 320 [M]+., 304, 189, 160, 77.
3-{[4-(4-Bromophenyl)-1,3-thiazol-2-yl]hydrazono}-
1,3-dihydro-2H-indol-2-one (4b): IR (KBr, νmax, cm-1): 3414
(N-H, ring, str.), 3327 (N-H, str.), 3176 (Ar-H, str.), 1683 (C=O,
str.), 1624 (C=N, ring, str.), 1476 (N-N); 1H NMR (CDCl3) δ:
7.11-7.91 (m, 8H, Ar-H), 6.60 (s, 1H, C-H, thiazole), 4.95 (s,
1H, NH), 3.86 (s, 1H, NH, ring); MS: m/z 400 [M]+., 402, 383,
268, 239, 156, 76.
3-{[4-(4-Fluorophenyl)-1,3-thiazol-2-yl]hydrazono}-
1,3-dihydro-2H-indol-2-one (4c): IR (KBr, νmax, cm-1): 3417
(N-H, ring, str.), 3332 (N-H, str.), 3179 (Ar-H, str.), 1685 (C=O,
str.), 1628 (C=N, ring, str.), 1480 (N-N, str.); 1H NMR (CDCl3)
δ: 7.14-7.95 (m, 8H, Ar-H), 6.64 (s, 1H, C-H, thiazole), 4.97
(s, 1H, NH), 3.89 (s, 1H, NH, ring); MS: m/z 338 [M]+., 322,
207, 178, 95, 76.
Conventional synthesis of 2-[-2-(1-furan-2-ylethylidene)-
hydrazino]-4-phenyl-1,3-thiazole (5a): Take an equimolar
mixture of compound (1a) 2-bromo-1-phenylethanone (0.01
mmol), thiosemicarbazide (0.01 mmol) and acetyl furan (0.01
mmol) and add 10 % HBr sol as a catalysis in conical flask
and stirrer at room temperature for about 20 min gave the solid.
It was filtered, washed with cold methanol and recrystallized
from ethanol. Physico-chemical data of the synthesized com-
pounds are given in Table-1.
Microwave assisted synthesis of 2-[-2-(1-furan-2-ylethyli-
dene)hydrazino]-4-phenyl-1,3-thiazole (5a): Take an equi-
molar mixture of compound (1a) 2-bromo-1-phenylethanone
(0.01 mmol), thiosemicarbazide (0.01 mmol) and acetyl furan
(0.01 mmol) and add 10 % HBr sol as a catalysis in Erlenmeyer
flask and irradiated under microwave irradiation for 20 min
with a time interval of 50 s, after the completion of reaction
indicated by TLC, than poured in crushed ice, solid appear
which was isolated, washed with cold methanol and recrysta-
llized from ethanol (Scheme-II). Physico-chemical data of the
synthesized compounds are given in Table-1.
IR (KBr, νmax, cm-1): 3336 (N-H, ring, str.), 3212 (N-H,
str.), 3103 (Ar-H, str.), 2945 (CH2, str.), 1633 (C=O, str.), 1553
(C=N, str. ring), 1484 (N-N, str.); 1H NMR (CDCl3) δ: 7.24-
7.77 (m, 5H, Ar-H), 6.81 (s, 1H, C=C-H, ring), 5.54 (s, 1H,
N-H), 4.80 (s, 1H, N-H, ring), 2.01 (s, 2H, CH2, ring); MS:
m/z 290 [M]+., 274, 189, 160, 77.
4-{[4-(4-Bromophenyl)-1,3-thiazol-2-yl]hydrazono}-
1,3-thiazolidin-2-one (6b): IR (KBr, νmax, cm-1): 3347 (N-H,
ring, str.), 3223 (N-H, str.), 3112 (Ar-H, str.), 2955 (CH2, str.),
1642 (C=O, str.), 1565 (C=N, str. ring), 1493 (N-N, str.); 1H
NMR (CDCl3) δ: 7.34-7.81 (m, 4H, Ar-H), 6.85 (s, 1H, C=C-
H, ring), 5.60 (s, 1H, N-H), 4.86 (s, 1H, N-H, ring), 2.05 (s,
2H, CH2, ring); MS: m/z 370[M]+., 372, 353, 268, 239, 156, 76.
4-{[4-(4-Fluorophenyl)-1,3-thiazol-2-yl]hydrazono}-
1,3-thiazolidin-2-one (6c): IR (KBr, νmax, cm-1): 3352 (N-H,
ring, str.), 3228 (N-H, str.), 3116 (Ar-H, str.), 2965 (CH2, str.),
1650 (C=O, str.), 1571 (C=N, str. ring), 1497 (N-N, str.); 1H
NMR (CDCl3) δ: 7.38-7.86 (m, 4H, Ar-H), 6.89 (s, 1H, C=C-
H, ring), 5.68 (s, 1H, N-H), 4.89 (s, 1H, N-H, ring), 2.10 (s,
2H, CH2, ring); MS: m/z 308 [M]+., 292, 207, 178, 95, 76.

Vol. 28, No. 4 (2016)
One-Pot Synthesis of Thiazoles via Hantzsch Thiazole Reaction and Their Antimicrobial Activity 931
TABLE-2
ANTIMICROBIAL ACTIVITY OF SYNTHESIZED COMPOUNDS ON 200 ppm 2a-c TO 6a-c [ZONE OF INHIBITION (mm)]
Antibacterial activity
Antifungal activity
Compd.
B. subtilis
++
++
E. coli
S. typhi
++
++
+
P. aeruginosa
A. fumigatus
C. albicans
++
+
++
++
++
++
++++
++
++
+
+++
++
++
+
++
++
+
2a
2b
2c
3a
3b
3c
4a
4b
4c
5a
5b
5c
6a
6b
6c
STD1
STD2
+
++
++
++
+
++
+
++
++
++
++
++
+
+
++
+
++
+
++
++++
+++
+
++
+
+
+
++
+
++
++
++
+
++
+
++
++
+
++
+
+++
++
+
+
+
++
+
++
++
+
+
++
++
+++
++
--
+++
+
++
++
+
++
+++
++
+++
--
+++
++++
+
++
+
++
+++
--
+++
--
++
--
--
+++
+++
+ = 10-14 (poor activity), ++ = 15-18 (moderate activity), +++ = 19-22 (good activity), ++++ = 23-26 (strong activity).
Standard: STD1 = Ciprofloxacin, STD2 = Flucanazole,
against C. albicans. Hence, the conclusion can be drawn that
synthesized compounds are better antibacterial and antifungal.
The screening have been summarized in Table-2.
RESULTS AND DISCUSSION
Compound 1a was achieved by reaction with acetophenone
and bromine. The structure of this compound is confirmed by
1H NMR, presence of a singlet at δ 3.02 due to (CH2) group and
IR absorptions at 1685 cm-1 due to the C=O group. Compounds
2a-6a is synthesized by multicomponent reaction via Hantzsch
thiazole process. In this reaction compound 1a reacts with
thiosemicarbazide and ethyl acetoacetate to give compound 2a
and it confirmed by disappear of C=O group peak at 1685 cm-1
and appear of two C=N group peak at 1620 and 1601 cm-1.
Similarly, compound 3a achieved by reaction with compound
1a, thiosemicarbazide and pyrazolone it exhibit singlet at δ
4.70 due to the N-H group of pyrazole. In another path compound
1a, thiosemicarbazide and isatin stirrer to give compound 4a
which is confirmed by IR absorptions at 1676 cm-1 due to the
Conclusion
In this work, thiazole and their derivatives were synthe-
sized using multicomponent conventional and microwave
method. This clearly indicates that synthesis of thiazole deri-
vatives in microwave afforded better yield in short time and
eco-friendly route. The multicomponent process also takes less
time and give excellent yield compare to another conventional
process and this method supported to the development of green
chemistry.
Synthesized compounds are tested for antibacterial and
antifungal activity. Compound 4a exhibit strong activity against
B. subtilis and compound 6a show moderate to good against
both microbial. Compounds 2a and 5a show good activity
against fungi.All over result is that compound 3b shows strong
activity against P. aeruginosa bacterial strains and 6b exhibit
strong activity against C. albicans fungal strains as compared
to the standard drugs (STD).
1
C=O group and H NMR singlet at δ 3.80 due to the N-H
group of isatine. In next path compound 1a, thiosemicarbazide
and acetyl furan cyclized and give final compound 5a, it show
sharp singlet at δ 3.40 corresponding to the CH3 group and IR
absorptions at 1284 cm-1 due to the C-O-C group of the furan.
In last path compound 1a, treated with thiosemicarbazide and
thiazolidione to give compound 6a, which is confirmed by IR
absorptions at 1633 cm-1 due to the C=O group and 1H NMR
singlet at δ 4.80 due to the N-H group of thiazolodione.All the
synthesized compound are tested for their antimicrobial activity.
Biological activity:All the synthesized compounds were
tested against four bacterial strains viz., B. subtilis, S. typhi,
P. aeruginosa, E. coli and two fungal strains A. fumigatus and
C. albicans by using cup and well method at 200 ppm concen-
trations in DMF. It is clear that compounds 4a exhibit strong
activity and 6a show good activity against B. subtilis. Similarly,
compound 3b possesses strong activity and 6b show good
activity against P. aeruginosa. Compound 2a exhibit good
activity against A. fumigatus and 6b show strong activity
ACKNOWLEDGEMENTS
The authors are thankful to the Head, Department of
Chemistry, Mewar University, Chittorgarh, India for providing
the laboratory facilities.
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