Synthesis and antibacterial activity of 2-(3-acylphenyl)amino-4-phenylthiazole

Article abstract of DOI:10.1134/S1070363215030275

Abstract 2-(3-acylphenyl)amino-4-phenylthiazoles were synthesized from 1-(3-acetylphenyl)thiourea and 2-bromo-1-substituted phenylethanones in presence of triethylamine upon heating. The newly synthesized compounds were characterized by IR, ¹H

Full text of DOI:10.1134/S1070363215030275

ISSN 1070-3632, Russian Journal of General Chemistry, 2015, Vol. 85, No. 3, pp. 686–688. © Pleiades Publishing, Ltd., 2015.
Synthesis and Antibacterial Activity
of 2-(3-Acylphenyl)amino-4-phenylthiazole1
N. J. P. Subhashinia, Jampaiah Amanagantia, and Shivarajb
a Department of Chemistry, University College of Technology, Osmania University, Hyderabad, India
b Department of Chemistry, University College of Science, Osmania University, Hyderabad, India
e-mail: njsubhashini@yahoo.co.in
Received November 26, 2014
Abstract—2-(3-acylphenyl)amino-4-phenylthiazoles were synthesized from 1-(3-acetylphenyl)thiourea and 2-
bromo-1-substituted phenylethanones in presence of triethylamine upon heating. The newly synthesized
1
compounds were characterized by IR, H NMR, MS spectrometry. All products were evaluated for their
antibacterial activity against Gram positive (Staphylococcus aureus and Bacillus subtilis) and Gram negative
(Escherichia coli, Klebsiella pnemoniae) strains.
Keywords: thiazoles, 1-(3-acetylphenyl)thiourea, 2-bromo-1-phenylethanone, antibacterial activity
DOI: 10.1134/S1070363215030275
INTRODUCTION
tested by TLC (silica gel 60 F254, Merck). IR (KBr)
spectra were recorded by Perkin-Elmer FT-IR spectro-
photometer BX. H NMR spectra were measured on
Bruker AMX-400 (400 MHz) spectrometer with TMS
as an internal reference. Mass spectra were measured
on Quatro Lc Micromas (Waters, UK) (70 eV).
Elemental analysis was carried out by a Thermo
Finnigan CHNS analyzer.
Development of antibiotic resistant bacterial and
fungal strains over the recent decades resulted in
substantial need of new classes of antimicrobial agents.
Thiazole and its derivatives are important components
of various biologically and pharmacologically active
compounds such as antifungal [1], antibacterial [2],
anti-inflammatory [3], antimicrobial [4–6], anti-HIV
[7, 8], hypertension [9, 10], anticancer [11], anticon-
vulsant [12], anti-inflammatory [13], antidepressant,
and antitubercular [14]. Thiazolium cycle present in
vitamin B1 serves as an electron sink and its coenzyme
form is important for decarboxylation of α-keto acids
[15]. Herein we report the synthesis of novel 2-(3-
acylphenyl)amino-4-phenylthiazoles (Scheme 1).
1
Synthesis of 1-(3-Acetylphenyl)thiourea (II). A
mixture of 3-aminoacetophenone (0.05 mol), ammo-
nium thiocyanate (0.05 mol) and dilute hydrochloric
acid (20 mL) was stirred at 85°C for 12 h. The reaction
progress was monitored by TLC. Upon completion of
the reaction the mixture was poured into ice cold water
and neutralized by a base. The resulting solid was
filtered off, dried and recrystallized from methanol to
produce pure crystals of the compound II.
Antibacterial activity. The newly synthesized
thiazole derivatives were screened for their anti-
bacterial activity against Gram positive bacteria viz.
Staphylococcus aureus and Bacillus subtilis and Gram
negative bacteria viz. Escherichia coli, Klebsiella
pnemoniae. The products IVe–IVg demonstrated high
activity at concentration 50 μg/mL in the disc diffusion
method (Table 2).
Synthesis of 2-(3-acylphenyl)amino-4-phenyl-
thiazole (IVa–IVj). The mixture of 1-(3-acetylphenyl)-
thiourea (II) (0.01 mol), aryl substituted 2-bromo-1-
phenylethanone (IIIa–IIIj) (0.01 mol) and NEt3 in
ethanol was refluxed for 3–4 h at room temperature.
The reaction progress was monitored by TLC. Upon
completion of the process the reaction mixture was
poured into ice cold water. The resulting solid was
filtered off, dried and purified by column chromato-
graphy using EtOAc : pet ether (4 : 10) eluent to yield
the compounds IVa–IVj (Table 1).
EXPERIMENTAL
Melting points were measured by the Boetieus
micro heating apparatus. Purity of compounds was
1 The text was submitted by the authors in English.
686

SYNTHESIS AND ANTIBACTERIAL ACTIVITY
687
Scheme 1. Synthesis of 2-(3-acylphenyl)amino-4-phenylthiazole (IVa–IVj)
O
Br
R1
R
S
O
O
O
R1
H
NH2
NH
N
NH2
N
NH4SCN
IIIa−IIIj
R
S
HCl
12−14 h
Et3N/EtOH
3−4 h
I
IVa−IVj
II
IIIa: R = H R1 = H; IIIb: R = CH3, R1 = H; IIIc: R = OCH3, R1 = H; IIId: R = NO2, R1 = H; IIIe: R = F, R1 = H; IIIf: R =
Cl, R1 = H; IIIg: R = Br, R1 = H; IIIh: R = H R1 = CH3; IIIi: R = CN, R1 = H; IIIj: R = H R1 = NO2.
Spectral data. Compound IVa. IR spectrum, ν,
cm–1: 1678 (C=O); 3445 (N–H). 1H NMR spectrum, δ,
ppm: 2.65 s (3H, –CH3); 6.74 s (1H, Th-H); 7.50–7.53
m (3H, Ar-H); 7.61–7.62 m (2H, Ar-H); 7.80–7.82 d
(2H, Ar-H); 7.89–7.90 d (Ar-H); 8.01 s (Ar-H). Found,
%: C 69.37, H 4.80, N 9.53, S 10.90. C17H14ON2S.
Calculated, %: C 69.36, H 4.79, N 9.52, S 10.89. M
295 [M + H]+.
Calculated, %: C 65.37, H 4.19, F, 6.08, N 8.97, S
10.27. M 313 [M + H]+.
Compound IVf. IR spectrum, ν, cm–1: 1672 (C=O);
1
3442 (N–H). H NMR spectrum, δ, ppm: 2.64 s (3H,
–CH3); 6.79 s (Th-H); 7.40–7.44 d (2H, Ar-H); 7.51–
7.56 m (Ar-H ); 7.66–7.69 d (Ar-H); 7.75–7.78 m (3H,
Ar-H); 8.05 s (Ar-H). Found, %: C 62.12, H 3.99, N
8.53, S 9.76. C17H13ON2ClS. Calculated, %: C 62.10,
H 3.98, N 8.52, S 9.75. M 329 [M + H]+.
Compound IVb. IR spectrum, ν, cm–1: 1684 (C=O);
1
3600 (N–H). H NMR spectrum, δ, ppm: 2.40 s (3H,
Compound IVg. IR spectrum, ν, cm–1: 1670 (C=O);
–CH3); 2.65 s (3H, –CH3), 6.68 s (Th-H); 7.30 d (2H,
Ar-H); 7.60 m (2H, Ar-H); 7.69 d (2H, Ar-H); 7.89 m
(1H, Ar-H); 7.99 s (Ar-H). Found, %: C 70.13, H 5.25,
N 9.11; S 10.42 C18H16N2OS. Calculated, %: C 70.10,
H 5.23, N 9.08, S 10.40. M 309 [M + H]+.
1
3448 (N–H). H NMR spectrum, δ, ppm: 2.65 s (3H,
–CH3); 6.78 s (Th-H); 7.59–7.72 m (6H, Ar-H); 7.88–
7.90 d (Ar-H); 8.02 s (Ar-H). Found, %: C 54.71, H
3.52, N 7.51, S 8.60. C17H13BrN2OS. Calculated, %: C
54.70, H 3.51, N 7.50, S 8.59. M 373 [M + H]+.
Compound IVc. IR spectrum, ν, cm–1: 1678 (C=O);
3668 (N–H). H NMR spectrum, δ, ppm: 2.63 s (3H,
Compound IVh. IR spectrum, ν, cm–1: 1669 (C=O);
3438 (N–H); H NMR spectrum, δ, ppm: 2.41 s (3H,
1
1
–CH3); 3.87 s (3H, –OCH3); 6.61 s (Th-H); 7.02 d (2H,
Ar-H); 7.48–7.49 m (2H, Ar-H); 7.76 d (2H, Ar-H);
8.07–8.09 m (2H, Ar-H). Found, %: C 66.65, H 4.98,
N 9.65, S 9.89. C18H16N2O2S. Calculated, %: C 66.64,
H 4.97, N 8.64, S 9.88. M 325 [M + H]+.
Table 1. Experimental data for the synthesis of 2-(3-acyl-
phenyl)amino-4-phenylthiazole (IVa–IVj)
Comp.
no.
mp,
°C
Reaction time,
h
Yield,
%
Compound IVd. IR spectrum, ν, cm–1: 1660 (C=O);
3360 (N–H). H NMR spectrum, δ, ppm: 2.62 s (3H,
–CH3); 6.94 s (Th-H); 7.52–7.58 m (3H, Ar-H); 7.71–
7.74 m (2H, Ar-H); 7.83–7.85 m (2H, Ar-H); 8.41 s
(Ar-H). Found, %: C 60.18, H 3.87, N 12.39, S 9.46.
C17H13N3O3S. Calculated, %: C 60.17, H 3.86, N
12.38, S 9.45. M 340 [M + H]+.
IVa
IVb
IVc
IVd
IVe
IVf
IVg
IVh
IVi
158
231
183
162
177
170
214
242
203
178
3.0
4.0
3.0
4.0
3.0
4.0
4.0
4.5
3.5
4.0
86
88
90
82
84
76
80
75
90
78
1
Compound IVe. IR spectrum (KBr), ν, cm–1: 1682
1
(C=O); 3450 (N–H). H NMR spectrum, δ, ppm: 2.62
s (3H, –CH3); 6.71 s (Th-H); 7.15–7.18 m (2H, Ar-H);
7.52–7.57 m (2H, Ar-H); 7.67–7.69 m (Ar-H), 7.78–
7.82 m (2H, Ar-H); 8.05 s (Ar-H). Found: C 65.39, H
4.20, F, 6.09, N 8.98, S 10.28. C17H13ON2FS.
IVj
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 85 No. 3 2015

688
SUBHASHINI et al.
Table 2. Antibacterial data of compounds IVa–IVj
37°C for 24 h. The growth inhibition zones around the
discs were measured. Each assay was repeated three
times.
Antibacterial activity zone of inhibition,
mm
Comp. no.
B.
K.
ACKNOWLEDGMENTS
S. aureus E.coli
subtilis pnemoniae
IVa
IVb
IVc
IVd
IVe
IVf
IVg
IVh
IVi
06
05
07
06
08
08
07
05
06
06
10
–
–
06
07
–
–
–
One of us (JA) is thankful to CSIR, New Delhi, for
the award of research fellowship and also thankful to
the Head, Department of Chemistry, Osmania
University, Hyderabad for providing the laboratory
facilities and also thankful to the CFRD, Osmania
University for providing Analytical data.
–
–
–
08
07
08
08
06
07
–
–
06
07
08
-
07
08
08
–
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–CH3); 7.02 s (Th-H); 7.54–7.56 d (2H, Ar-H); 7.71–
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1
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