Synthesis, characterization and antibacterial activity of some new thiazole and thiazolidinone derivatives containing phenyl benzoate moiety

Article abstract of DOI:10.1080/00397911.2018.1482349

4-Formylphenyl benzoate was utilized as a versatile precursor for the construction of new series of heterocyclic scaffolds that contain thiazole and thiazolidin-5-one rings. The antibacterial activity of these scaffolds against two types of bacteria was screened and most of them exhibited good activity. Among the synthesized thiazole derivatives, compounds 5, 6, and 8a showed antibacterial activity close to the standard chemotherapeutic (Ampicillin).

Full text of DOI:10.1080/00397911.2018.1482349

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: http://www.tandfonline.com/loi/lsyc20
Synthesis, characterization and antibacterial
activity of some new thiazole and thiazolidinone
derivatives containing phenyl benzoate moiety
Ebrahim Abdel-Galil, Evelin B. Moawad, Ahmed El-Mekabaty & Gehad E. Said
To cite this article: Ebrahim Abdel-Galil, Evelin B. Moawad, Ahmed El-Mekabaty & Gehad E.
Said (2018): Synthesis, characterization and antibacterial activity of some new thiazole and
thiazolidinone derivatives containing phenyl benzoate moiety, Synthetic Communications, DOI:
10.1080/00397911.2018.1482349
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https://doi.org/10.1080/00397911.2018.1482349
Synthesis, characterization and antibacterial activity of
some new thiazole and thiazolidinone derivatives
containing phenyl benzoate moiety
Ebrahim Abdel-Galil , Evelin B. Moawad, Ahmed El-Mekabaty, and Gehad E. Said
Chemistry Department, Faculty of Science, Mansoura University, Mansoura, Egypt
ABSTRACT
ARTICLE HISTORY
Received 12 March 2018
4-Formylphenyl benzoate was utilized as a versatile precursor for the
construction of new series of heterocyclic scaffolds that contain thia-
zole and thiazolidin-5-one rings. The antibacterial activity of these
scaffolds against two types of bacteria was screened and most of
them exhibited good activity. Among the synthesized thiazole deriva-
tives, compounds 5, 6, and 8a showed antibacterial activity close to
the standard chemotherapeutic (Ampicillin).
KEYWORDS
Antibacterial activity;
cyanoacetamide; phenyl
benzoate; thiazole;
thiazolidine
GRAPHICAL ABSTRACT
Me
OH
Ph
O
Ph
O
Ph
O
NH2
S
N
N
O
N
O
N
O
N
N
S
N
S
N
H
H
H
8a
5
6
Introduction
Thiazoles are a class of heterocyclic compounds which merit special attention because of
their vital role in the medicinal chemistry. They demonstrated wide spectrum of
pharmacological applications such as anticancer,[1] antimicrobial,[2] anti-inflammatory,[3]
antitubercular,[4] anti-allergic,[5] anticonvulsant,[6] anti-tumor,[7] antischizophrenic,[8]
anti-HIV,[9] tyrosinase inhibitors,[10] anti-trypanosoma cruzi,[11] and antioxidant.[12]
Thiazoles are aromatic five-membered heterocyclic compounds that contain sulfur and
nitrogen at position 1 and 3, respectively. They are involved in many of the natural
products for example, the thiazolium nucleus is a component of vitamin thiamin (B1)
and thiamine pyrophosphate (TPP).[13–15] The construction of thiazole ring was first
described in the literature by Hantzsch and Weber.[16] Many reports developed these
traditional methods for the synthesis of thiazole as the using chemoenzymatic one-pot
multicomponent synthesis[17] and application of microwave irradiation in the Hantzsch
reaction.[18–20] Thiazole derivatives could be utilized in various chemical reactions such
as Knoevenagel reaction[21]. Due to the importance of the core of thiazole and
CONTACT Ebrahim Abdel-Galil
msebrahim2002@gmail.com
Chemistry Department, Faculty of Science, Mansoura
University, El-Gomhoria Street, ET-35516 Mansoura, Egypt.
Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/lsyc.
Supplemental data for this article can be accessed publisher’s website.
ß 2018 Taylor & Francis

2
E. ABDEL-GALIL ET AL.
thiazolidinone rings in antimicrobial agents, different compounds incorporating these
moieties have been synthesized in our research article to test their antibacterial activity.
Results and discussion
Cyanoacetyl hydrazone 1 was synthesized by refluxing of 4-formylphenyl benzoate[22]
with 2-cyanoacetohydrazide[23] in ethanol. Assignment of compound 1 was based on IR,
1H NMR, and elemental analysis. IR spectrum showed characteristic bands at 3199 cmꢀ1
for (NH), 2260 cmꢀ1 for (CN), and 1733 cmꢀ1 for (C¼O ester) functions. Then, a base
catalyzed addition reaction of cyanoacetyl hydrazone 1 with phenyl isothiocyanate was
achieved in DMF to afford the non-isolable intermediate potassium salt 2 which
sequently, underwent heterocyclization with chloroacetonitrile and chloroacetone to
yield the corresponding thiazole derivatives 3 and 4, respectively (Scheme 1). Spectral
and analytical analyses have been utilized to establish the chemical structures of both 3
and 4. IR spectra of compound 3 revealed absorption bands at the region
3331–3439 cmꢀ1 for (br, NH, NH2), 2182 cmꢀ1 for (CN), 1734 cmꢀ1 for (C¼O(ester)).
The mass spectrum of 3 showed a molecular ion peak at m/z ¼ 481 which was agreed
completely with the predicted formula (C26H19N5O3S). Figure 1 illustrates some decom-
position processes of thiazole 3, fragmentation includes the elimination of an NH2 group
[M-16]þ followed by the elimination of OH radical to produce the ion at m/z 448. The
thiazole ring opening with the following release of an acetylene to produce the ion at
m/z 423, which underwent loss HCN and N2 molecules to give the base peak at m/z 368
1
with 100% intensity. H NMR of compound 4 assigned the appearance of new singlet
signals at 1.92, 6.49, and 9.09 ppm characteristic for CH3, CH(thiazole), and NH protons,
respectively.
Into our target to synthesize new thiazole derivatives, six thiazoles 6–9 were resulted
via
a
heterocyclization reaction of 4-((2-carbamothioylhydrazono)methyl)phenyl
Ph
O
O
H2N
CN
O
+
N
CHO
H
EtOH
heat
Ph
O
O
N
Ph
O
O
N
CN
S
ClCH2CN
O
N
H
O
N
N
CN
Ph
H
3
1
H2N
PhNCS
DMF/ KOH
Ph
O
Ph
O
O
O
O
N
CN
S
O
N
CN
CH3COCH2Cl
N
H
N
H
Ph
N
PhHN
S K
4
2
Me
Scheme 1. Synthesis of thiazole derivatives 3 and 4.

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SYNTHETIC COMMUNICATIONSV
3
benzoate (5) that was synthesized according to the reported method[24] with a-halo car-
bonyl compounds and hydrazonyl halides namely; ethyl bromoacetate, bromodiethylmal-
onate, chloroacetone, phenacylchloride, 2-oxo-2-phenyl-N’-p-tolylacetohydrazonoyl
chloride, and N’-(4-methoxyphenyl)-2-oxo-2-phenylacetohydrazonoyl chloride,[25–27]
respectively in refluxing commercial ethanol containing anhydrous AcONa (Scheme 2).
Assignment of the newly synthesized compounds was based on both spectral and analyt-
ical analyses (cf. Experimental section).
To extend our work, we synthesized three thiazolidin-5-one derivatives 10 (a–c) using
the reported method in literature.[28,29] Furthermore, the reactivity of these derivatives
as active methylene compounds was tested via a Knoevenagel condensation reaction
with 4-formylphenyl benzoate in ethyl alcohol containing a catalytic amount of piperi-
dine (three drops) to afford the corresponding arylidine products 11 (a–c) (Scheme 3).
The chemical structures of these products were confirmed using both spectral and ana-
lytical analyses. For example, IR spectra of compound 11b assigned absorptions at
2208 cmꢀ1 for (CN), 1714 and 1744 cmꢀ1 for (2C¼O(ester)) and 1692 cmꢀ1 for
(C¼O(cyclic)). 1H NMR spectrum exhibited two singlet signals at 1.36 and 4.34 ppm
assignable to CH3 and CH2 protons, respectively. 13C NMR spectrum also confirmed
the structure of 11b through the appearance of signals at 62.31 and 14.22 ppm related to
OCH2 and CH3 carbons.
Moreover, the reactivity of some known cyanoacetamide thiazole derivatives 12 (a–c)
which were obtained through the synthetic routes reported in literature[30–32] and a new
cyanoacetamide derivative 12d which was prepared by refluxing of 2-amino-6-ethoxy-
benzothiazole with 3,5-dimethyl-1-cyanoacetyl pyrazole[33] in dioxane was studied
toward the Aldol condensation reaction with 4-formylphenyl benzoate to afford aryli-
dine thiazole compounds 13 (a–d) through refluxing in ethanol with adding few drops
of piperidine (3–4 drops) (Scheme 4). Chemical structures of compounds 13 (a–d) were
Figure 1. Possible mass fragmentation pattern of compound 3.

4
E. ABDEL-GALIL ET AL.
OH
OH
R
Ph
O
Ph
O
BrCH2COOEt
N
O
N
O
S
N
CHO
H
6
7
NH2NHCSNH2
EtOH
Ph
O
N
BrCH(COOEt)2
COOEt
O
N
S
N
H
Ph
O
NH2
O
N
Ph
O
S
N
N
H
RCOCH2Cl
5
O
N
S
N
H
8a: R = Me
8b: R = Ph
O
Ph
N
N
Ar
Ph
O
Ph
N
H
Cl
N
O
N
S
N
H
N
Ar
9a: Ar = 4-MeC6H4
9b:
Ar = 4-MeOC6H4
Scheme 2. Synthesis of thiazole derivatives 6–9.
Ph
Ph
Y
CHO
N
Y
X
N
O
Ph
EtOH
Piperdine
+
X
S
S
Ph
O
O
O
O
O
10(a-c)
11a: X, Y = CN
11b:
X = CN, Y = COOEt
11c: X = COMe, Y = COOEt
Scheme 3. Synthesis of thiazolidin-5-one derivatives 11 (a–c).
elucidated using both elemental and spectral analyses. For example, IR of 13c revealed
absorptions at 3226 cmꢀ1 for (NH), 2227 cmꢀ1 for (CN), and 1730 cmꢀ1 for (C¼O(ester)
)
1
groups, while H NMR spectrum assigned a singlet signal at 3.80 ppm assignable for
(OCH3) protons.
To further explore the synthetic potentially of compounds 13 (a–d), the reactivity of
13 (a–d) towards Michael addition with malononitrile as a possible synthetic route to
get pyridinone derivatives 15 (a–d) was examined. Compounds 15 (a–d) were achieved
by refluxing compounds 13 (a–d) with malononitrile and TEA in ethyl alcohol to fur-
nish the non-isolable intermediate 14 which then underwent intramolecular heterocycli-
zation to give the corresponding products. In a similar manner, the reaction of
compounds 13 (a–c) with ethyl cyanoacetate and TEA in refluxing EtOH gave the inter-
mediate 16 which underwent an intramolecular heterocyclization to afford pyridinone
derivatives 17 (a–c). Elucidation of the new synthesized derivatives 15 (a–d) and 17

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SYNTHETIC COMMUNICATIONSV
5
O
C
O
O
NC
O
O
NC
NC
O
Ph
NH Ar
Ph
- EtOH
Air [O]
N
Ar
COOEt
NC
OH
17a-c
16
NC CH2 COOEt
EtOH, Et3N
O
O
NC
O
N
O
Ph
O
EtOH
Piperdine
Ph
NC
Ar
+
O
N
Ar
H
CHO
H
12a-d
13a-d
NC CH2 CN
EtOH, Et3N
O
O
NC
NC
O
O
C
O
O
NC
Ph
Ph
NH Ar
N
Air [O]
N
Ar
C
NH2
NC
15a-d
14
N
S
N
N
S
N
,
,
,
Ar =
S
S
EtO
MeO
(c)
(d)
(a)
(b)
Scheme 4. Synthesis of thiazole derivatives 13–17.
1
(a–c) was based on elemental analysis, IR, H NMR, 13C NMR, and mass spectroscopy
(cf. Experimental Section).
Biological activity
All new investigated thiazole derivatives 3–17 were subjected to antibacterial screening
in vitro against Gram (ꢀve) (Escherichia coli) (MTCC-443) and Gram (þve)
(Staphylococcus aureus) (MTCC-96) bacteria and were compared with ampicillin as a
standard chemotherapeutic. Then, the results are tabulated in Table 1. Most of the syn-
thesized compounds showed high antibacterial activity against the selected bacteria.
By studying the results of the disc diffusion test that are summarized in Table 1, we
found that compounds 3, 5, 6, and 8a showed potent activity against S. aureus bacteria
and compounds 6 and 8a showed excellent activity against E. coli bacteria. On the other
hand, compounds 4, 9a, 9b, and 13d showed good activity against S. aureus bacteria
and compounds 3 and 5 showed good activity against E. coli, while all the other tested
compounds showed moderate or low activity against the selected bacteria.
According to the above-mentioned results, we may apply the following SARs (struc-
ture–activity relationships) and compare between the tested compounds. A comparison
of antibacterial activity of compounds with their structures revealed that antibacterial

6
E. ABDEL-GALIL ET AL.
Table 1. Antibacterial activity of compounds 3–17 against Escherichia coli and Staphylococcus aureus bacteria.
E. coli (mg/ml) S. aureus (mg/ml)
Diameter of inhibition Diameter of inhibition
Compound no.
zone (mm)
% Activity index
zone (mm)
% Activity index
3
4
5
6
7
8a
8b
9a
20
16
18
22
NA
23
10
14
17
11
NA
NA
7
13
3
5
9
NA
2
76.9
61.5
69.2
84.6
–
88.5
38.5
53.8
65.4
42.3
–
21
20
23
23
8
24
7
18
20
14
2
87.5
83.3
95.8
95.8
33.3
100.0
29.2
75.0
83.3
58.3
8.3
9b
11a
11b
11c
13a
13b
13c
13d
15a
15b
15c
15d
17a
17b
17c
Ampicillin
–
2
8.3
26.9
50.0
11.5
19.2
34.6
–
7.7
11.5
–
15
15
5
17
10
NA
11
6
62.5
62.5
20.8
70.8
41.7
–
45.8
25.0
–
3
NA
NA
2
NA
3
6
–
7.7
100
12.5
25.0
100
26
24
NA: no activity.
Table 2. Minimum inhibitory concentration (mg/ml) of
compounds 3, 4, 5, 6, 8a, and 9b against Escherichia coli
and Staphylococcus aureus bacteria.
Compounds
E. coli
S. aureus
3
4
5
6
500
375
250
375
62.5
750
125
500
250
62.5
187.5
46.9
375
8a
9b
Ampicillin
187.5
activity of the evaluated compounds is related to the attached groups with thiazole
derivatives. The presence of amino, hydroxyl, methyl, methoxy, azo, or ethoxy groups
incorporated with cyanoacetyl hydrazone or carbamothioyl hydrazone and phenyl
benzoate moiety in thiazole derivatives gave significant antibacterial activity against the
two bacteria while introducing of electron withdrawing group (phenyl group) instead of
electron donating group (methyl group) in compound 8b decreased the activity as
shown in Table 1. Compound 8a gave the best antibacterial activity against E. coli and
S. aureus bacteria, this may be attributed to the presence of methyl group on the fourth
position of thiazole forced to higher activity.
In addition, the minimum inhibitory concentration (MIC) of the most active com-
pounds 3, 4, 5, 6, 8a, and 9b was tested against E. coli and S. aureus bacteria and the
results are reported in Table 2. Most of the tested compounds exhibited high MIC as

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SYNTHETIC COMMUNICATIONSV
7
shown in Table 2. On the other hand, compound 8a revealed low MIC (62.5 mg/ml)
against E. coli and compounds 5 and 8a exhibited low MIC (62.5, 46.9 mg/ml), respect-
ively against S. aureus.
Conclusion
In this paper, we synthesized various series of thiazole derivatives using 4-formylphenyl
benzoate as a starting material. The reactivity of some of these thiazoles towards
Knoevenagel condensation reaction was studied. All the newly synthesized products
were screened against their in vitro antibacterial activity, compound 8a which contains
the phenyl benzoate moiety with 4-methylthiazolyl substituent has the highest antibac-
terial activity. By applying SARs, we found that the presence of electron donating groups
(i.e. methyl group in compound 8a) gave significant antibacterial activities against the
two types of bacteria.
Experimental
All melting points were measured in degree Celsius on an electrothermal Gallenkamp
(Germany) apparatus. The infrared spectra t cmꢀ1 (KBr) were determined on a Mattson
1
5000 FTIR Spectrometer (USA). The H NMR and 13C NMR spectra were run on a
Bruker Avance III spectrophotometer at 400 and 100 MHz, respectively. The mass meas-
urements were recorded on Kratos MS apparatus by EI mode with ionizing voltage
70 eV. Elemental (C, H, and N) analyses were measured on Perkin-Elmer 2400. The
results were favorably agree with the calculated values.
Reaction of a-halo derivatives with cyanoacetyl hydrazone 1
General procedure: A 0.005 mole of cyanoacetyl hydrazone 1 (0.49 g), 0.005 mole of phe-
nylisothiocyanate (0.59 ml), and 0.005 mole of KOH (0.28 g) were dissolved in 15 ml
DMF, then were stirred overnight. After that, 0.005 mole of a-halo derivatives namely;
2-chloroacetonitrile (0.31 ml) or chloroacetone (0.40 ml) were added drop by drop with
stirring for 4 h. After completion of the reaction, the previous mixtures were poured
onto ice-water with stirring and the formed precipitates after settling down of the mix-
tures were filtered off. EtOH was utilized as a recrystallizing solvent to afford com-
pounds 3 and 4, respectively.
4-((2-(2-(4-Amino-3-phenylthiazol-2(3H)-ylidene)-2-cyanoacetyl)hydrazono)methyl)-
phenyl benzoate (3)
Reddish brown powder, m.p. ¼ 214–216 ꢁC, yield 33%. IR (ꢀmax/cmꢀ1): 3331–3439 (br,
NH, NH2), 2182 (CN), 1734 (C¼O(ester)), 1636 (C¼O(amidic)), 1600 (C¼N). MS m/z (%):
481 (Mþ) (38.24), 448 (97.19), 424 (26.01), 423 (39.13), 369 (57.92), 368 (100), 104
(30.01), 43 (19.20). Analysis for C26H19N5O3S (481.53): Calcd: C ¼ 64.85%; H ¼ 3.98%;
N ¼ 14.54%. Found: C ¼ 64.88%; H ¼ 3.11%; N ¼ 14.50%.

8
E. ABDEL-GALIL ET AL.
4-((2-(2-Cyano-2-(4-methyl-3-phenylthiazol-
2(3H)ylidene)acetyl)hydrazono)methyl)phenyl benzoate (4)
Yellow crystals, m.p. ¼ 240–242 ꢁC, yield 67%. IR (ꢀmax/cmꢀ1): 3311 (NH), 2185 (CN),
1
1738 (C¼O(ester)), 1640 (C¼O(amidic)). H NMR (CDCl3): d (ppm) ¼ 1.92 (s, 3H, CH3),
6.49 (s, 1H, CH(thiazole)), 7.24 (d, 2H, J ¼ 8.4 Hz, Ar–H), 7.28–7.67 (m, 8H, Ar–H), 7.79
(d, 2H, J ¼ 8.4 Hz, Ar–H), 7.91 (s, 1H, CH¼N), 8.20 (d, 2H, J ¼ 7.2 Hz, Ar–H), 9.09 (s,
1H, NH, D2O exchangeable). 13C NMR (DMSO-d6, 100 MHz): d (ppm) ¼ 26.21 (1C,
CH3), 69.71 (1C, C–CN), 96.34 (1C, CH(thiazole)), 115,75 (1C, CN), 121.10 (1C), 122.81
(2C), 128.44 (2C), 128.60 (1C), 129.25 (1C), 129.35 (1C), 129.78 (2C), 129.86 (1C),
130.12 (2C), 130.29 (1C), 130.59 (2C), 134.60 (1C), 145.02 (1C, C¼N), 151.93 (1C,
C–O), 163.45 (1C, C¼O(ester)), 164.92 (1C, C¼O(amidic)), 171.30 (1C, S–C–N). Analysis
for C27H20N4O3S (480.54): Calcd: C ¼ 67.48%; H ¼ 4.20%; N ¼ 11.66%. Found:
C ¼ 67.53%; H ¼ 4.18%; N ¼ 11.69%.
Microbiological procedure for the activity study
Materials and method
Each of the compounds was dissolved in DMSO and solution of the concentration
1 mg/ml were prepared separately. Paper discs of Whatman filter paper were prepared
with standard size (5 cm) were cut and sterilized in an autoclave. The paper discs soaked
in the desired concentration of the complex solution were placed aseptically in the petri
dishes containing nutrient agar media (agar 20 g þ beef extract 3 g þ peptone 5 g) seeded
with S. aureus and E. coli. The petri dishes were incubated at 36 ꢁC and the inhibition
zones were recorded after 24 h of incubation. Each treatment was replicated three times.
The antibacterial activity of a common standard antibiotic ampicillin was also recorded
using the same procedure as above at the same concentration and solvents. The % activ-
ity index for the complex was calculated by the formula as under:
Zone of inhibition by test compound ðdiametreÞ
% Activity index ¼
ꢂ 100
ð
Þ
Zone of inhibition by standard diametre
MIC (minimum inhibitory concentration) values for the selected compounds were
determined using the previously reported procedure.[34]
ORCID
Ebrahim Abdel-Galil
http://orcid.org/0000-0002-1960-9583
References
[1] Kaminskyy, D.; den Hartog, G. J. M.; Wojtyra, M.; Lelyukh, M.; Gzella, A.; Bast, A.; Lesyk,
R. Antifibrotic and Anticancer Action of 5-Ene Amino/Iminothiazolidinones. Eur. J. Med.
Chem. 2016, 112, 180–195. doi:10.1016/j.ejmech.2016.02.011
[2] Reddy, G. M.; Garcia, J. R.; Reddy, V. H.; de Andrade, A. M.; Camilo, A.; Pontes Ribeiro,
R. A.; de Lazaro, S. R. Synthesis, Antimicrobial Activity and Advances in

R
SYNTHETIC COMMUNICATIONSV
9
Structure–Activity Relationships (SARs) of Novel Tri-Substituted Thiazole Derivatives.
Eur. J. Med. Chem. 2016, 123, 508–513. doi:10.1016/j.ejmech.2016.07.062
[3] Ottana, R.; Maccari, R.; Barreca, M. L.; Bruno, G.; Rotondo, A.; Rossi, A.; Chiricosta, G.;
Di Paola, R.; Sautebin, L.; Cuzzocrea, S.; Vigorita, M. G. 5-Arylidene-2-Imino-4-
Thiazolidinones: Design and Synthesis of Novel anti-Inflammatory Agents. Bioorg. Med.
Chem. 2005, 13, 4243–4252. doi:10.1016/j.bmc.2005.04.058
[4] Chandraprabha, V. J.; Prasad, D. J.; Kumar, C.; Nayak, P. J. Med. Sci. Clin. Res. 2016, 4,
759–767.
[5] Hargrave, K. D.; Hess, F. K.; Oliver, J. T. N-(4-Substituted-Thiazolyl)Oxamic Acid
Derivatives, a New Series of Potent, Orally Active Antiallergy Agents. J. Med. Chem. 1983,
26, 1158–1163. doi:10.1021/jm00362a014
[6] Ghabbour, H. A.; Kadi, A. A.; ElTahir, K. E. H.; Angawi, R. F.; El-Subbagh, H. I.
Synthesis, Biological Evaluation and Molecular Docking Studies of Thiazole-Based
Pyrrolidinones and Isoindolinediones as Anticonvulsant Agents. Med. Chem. Res. 2015,
24, 3194–3211. doi:10.1007/s00044-015-1371-3
[7] Hassan, G. S.; El-Messery, S. M.; Al-Omary, F. A. M.; El-Subbagh, H. I. Substituted
Thiazoles VII. Synthesis and Antitumor Activity of Certain 2-(Substituted Amino)-4-
Phenyl-1,3-Thiazole Analogs. Bioorg. Med. Chem. Lett. 2012, 22, 6318–6323. doi:10.1016/
j.bmcl.2012.08.095
[8] Jaen, J. C.; Wise, L. D.; Caprathe, B. W.; Tecle, H.; Bergmeier, S.; Humblet, C. C.; Heffner,
T. G.; Meltzer, L. T.; Pugsley, T. A. 4-(1,2,5,6-Tetrahydro-1-Alkyl-3-Pyridinyl)-2-
Thiazolamines: A Novel Class of Compounds with Central Dopamine Agonist Properties.
J. Med. Chem. 1990, 33, 311–317. doi:10.1021/jm00163a051
[9] Khan, M.; Hameed, S.; Akhtar, T.; Al-Masoudi, N. A.; Al-Masoudi, W. A.; Jones, P. G.;
Pannecouque, C. Synthesis, Crystal Structure, Anti-HIV, and Antiproliferative Activity of
New Oxadiazole and Thiazole Analogs. Med. Chem. Res. 2016, 25, 2399–2409. doi:10.1007/
s00044-016-1669-9
[10] Hamidian, H.; Tagizadeh, R.; Fozooni, S.; Abbasalipour, V.; Taheri, A.; Namjou, M.
Synthesis of Novel Azo Compounds Containing 5(4H)-Oxazolone Ring as Potent
Tyrosinase Inhibitors. Bioorg. Med. Chem. 2013, 21, 2088–2092. doi:10.1016/
j.bmc.2013.01.014
[11] Andr, P.; Gomes, T.; Barbosa, M.; Santiago, E. F.; Cardoso, M. V.; Costa, N. T. C.;
Hernandes, M. Z.; Moreira, D. R. M.; Caroline da Silva, A.; Ramos dos Santos, T. A.; et al.
New 1,3-Thiazole Derivatives and Their Biological and Ultrastructural Effects on
Trypanosoma Cruzi. Eur. J. Med. Chem. 2016, 121, 387–398.
[12] Jaishree, V.; Ramdas, N.; Sachin, J.; Ramesh, B. In Vitro Antioxidant Properties of New
Thiazole Derivatives. J. Saudi Chem. Soc. 2012, 16, 371–376. doi:10.1016/j.jscs.2011.02.007
[13] Breslow, R. On the Mechanism of Thiamine Action. IV. 1 Evidence from Studies on
Model Systems. J. Am. Chem. Soc. 1958, 80, 3719–3726. doi:10.1021/ja01547a064
[14] Glotova, T. E.; Dvorko, M. Y.; Albanov, A. I.; Kazheva, O. N.; Shilov, G. V.; D’yachenko,
O. A. 1,3-Dipolar Cycloaddition of 3-Phenylamino-5-Phenylimino-1,2,4-Dithiazole to 1-
Acyl-2-Phenylacetylenes – A New Route to Functionalized 1,3-Thiazole Derivatives. Russ.
J. Org. Chem. 2008, 44, 1532–1537. doi:10.1134/S1070428008100230
[15] Yadlapalli, R. K.; Chourasia, O. P.; Jogi, M. P.; Podile, A. R.; Perali, R. S. Design, Synthesis
and in Vitro Antimicrobial Activity of Novel Phenylbenzamido-Aminothiazole-Based
Azasterol Mimics. Med. Chem. Res. 2013, 22, 2975–2983. doi:10.1007/s00044-012-0314-5
[16] Hantzsch, A. R.; Weber, H. J. Berichte. Ueber Verbindungen des Thiazols (Pyridins der
Thiophenreihe). Ann. Chem. 1887, 20, 3118–3132. doi:10.1002/cber.188702002200
[17] Zheng, H.; Mei, Y.; Du, K.; Cao, X.; Zhang, P. One-Pot Chemoenzymatic Multicomponent
Synthesis of Thiazole Derivatives. Molecules 2013, 18, 13425–13433. doi:10.3390/
molecules181113425
[18] Mohanty, S. K.; Khuntia, A.; Harika, M. S.; Sarangi, S. P.; Susmitha, D. Synthesis,
Characterization and Antimicrobial Activity of Some Oxazole and Thiazole Derivatives.

10
E. ABDEL-GALIL ET AL.
J. Int J Pharm Pharm. Res. 2015, 2, 60–66. http://ijppr.humanjournals.com/synthesis-char-
acterization-and-antimicrobial-activity-of-some-oxazole-and-thiazole-derivatives/
[19] Singh, S. K.; Singh, K. N. Glycine-Catalyzed Easy and Efficient One-Pot Synthesis of
Polyhydroquinolines Through Hantzsch Multicomponent Condensation under Controlled
Microwave. J. Heterocycl. Chem. 2010, 47, 194–198. doi:10.1002/jhet.308
€
[20] Ohberg, L.; Westman, J. An Efficient and Fast Procedure for the Hantzsch
Dihydropyridine Synthesis under Microwave Conditions. J. Synlett. 2001, 2001, 1296–1298.
doi:10.1055/s-2001-16043
[21] Sundaram, K.; Ravi, S. Microwave Assisted Synthesis of 3-α-Carboxy ethylrhodanine
Derivatives and Their in vitro Antibacterial Activity. J. Appl. Pharm. Sci. 2013, 3, 133–135.
doi:10.7324/JAPS.2013.3725
[22] Agrawal, Y. P.; Agrawal, M. Y.; Gupta, A. K. Design, Synthesis and Evaluation of
Rhodanine Derivatives as Aldose Reductase Inhibitors. Chem. Biol. Drug. Des. 2015, 85,
172–180. doi:10.1111/cbdd.12369
[23] Gorobets, N. Y.; Yousefi, B. H.; Belaj, F.; Kappe, C. O. Rapid Microwave-Assisted Solution
Phase Synthesis of Substituted 2-Pyridone Libraries. Tetrahedron 2004, 60, 8633–8644.
doi:10.1016/j.tet.2004.05.100
[24] Saeed, A.; Al-Masoudi, N. A.; Latif, M. Arch. Pharm. Chem. Life Sci. 2013, 346, 618–625.
doi:10.1002/ardp.201300057
[25] Eweiss, N. F.; Osman, A. O. Synthesis of Heterocycles. Part II. New Routes to
Acetylthiadiazolines and Alkylazothiazoles. J. Heterocycl. Chem. 1980, 17, 1713–1717.
doi:10.1002/jhet.5570170814
[26] Wolkoff, P. A New Method of Preparing Hydrazonyl Halides. Can. J. Chem. 1975, 53,
1333–1335. doi:10.1139/v75-183
[27] Shawali, A. S.; Albar, H. A. Kinetics and Mechanism of Dehydrochlorination of N-Aryl-C
-Ethoxycarbonylformohydrazidoyl Chlorides. Can. J. Chem. 1986, 64, 871–875.
doi:10.1139/v86-144
[28] Metwally, M. A.; Abdel-Latif, E.; Amer, F. A. Synthesis and Reactions of Some
Thiocarbamoyl
Derivatives.
Sulfur
Lett.
2003,
26,
119–126.
doi:10.1080/
0278611031000095322
[29] Mohareb, R. M.; Sherif, M. Heterocyclic Synthesis with Isothiocyantes: Synthesis of Several
New Polyfunctionally Substituted Thiophene, D4-Thiazoline and Thiazolidinone
Derivatives. Arch. Pharm. Pharm. Med. Chem. 2010, 324, 469–471. doi:10.1002/
ardp.2503240801
[30] Ibrahim, H. M.; Makhseed, S.; Abdel-Motaleb, R. M.; Makhlouf, A. A.; Elnagdi, M. H.
Utility of Cyanoacetamides as Precursors to Pyrazolo[3,4-d]Pyrimidin-4-Ones, 2-Aryl-6-
Substituted
1,2,3
Triazolo[4,5-d]Pyrimidines
and
Pyrazolo[1,5-a]Pyrimidine-3-
Carboxamides. Heterocycles 2007, 71, 1951–1966.
ꢀ
ꢁ
ꢀ
ꢁ
[31] Stetinova, J.; Kada, R.; Lesko, J.; Zalibera, L.; Ilavsky, D.; Bartovic, A. Synthesis and
Properties of Substituted 1-(2-Benzothiazolyl)-2-Pyridones. Collect. Czech. Chem. Commun.
1995, 60, 999–1008. doi:10.1135/cccc19950999
ꢀ
ꢁ
ꢀ
ꢁ
ꢁ
ꢁ
[32] Stetinova, J.; Kada, R.; Lesko, J.; Dandarova, M.; Krublova, M. Synthesis and Spectral
Properties of 1-(6-Methoxy-2-Benzothiazolyl)-2-Pyridones. Collect. Czech. Chem. Commun.
1996, 61, 921–929. doi:10.1135/cccc19960921
[33] Chigorina, E. A.; Dotsenko, V. V. The First Example of 3,7-Diazabicyclo[3.3.1]Nonane
Synthesis by Aminomethylation of Guareschi Imide Salts. Chem. Heterocycl. Comp. 2013,
48, 1722–1236. doi:10.1007/s10593-013-1200-x
[34] Refat, H. M.; Fadda, A. A. Synthesis and Antimicrobial Activity of Some Novel Hydrazide,
Benzochromenone, Dihydropyridine, Pyrrole, Thiazole and Thiophene Derivatives. Eur. J.
Med. Chem. 2013, 70, 419–426. doi:10.1016/j.ejmech.2013.09.003