Facile and convenient synthesis of 2,4-disubstituted and 2,3,4-trisubstituted 1,3-thiazoles

Article abstract of DOI:10.1080/17415993.2015.1114621

An efficient route for the synthesis of (E)-2-(2-(2-nitrobenzylidene)-hydrazinyl)-4-phenylthiazol-3-ium bromide, (E)-2-(2(substituted benzylidene)hydrazinyl)-4-phenylthiazoles and (E)-4-(4-bromophenyl)-2-(cycloalkylidenehydrazono)-3-phenyl-2,3-dihydrothia

Full text of DOI:10.1080/17415993.2015.1114621

Journal of Sulfur Chemistry
ISSN: 1741-5993 (Print) 1741-6000 (Online) Journal homepage: http://www.tandfonline.com/loi/gsrp20
Facile and convenient synthesis of 2,4-
disubstituted and 2,3,4-trisubstituted 1,3-thiazoles
Alaa A. Hassan, Shaaban K. Mohamed, Nasr K. Mohamed, Kamal M.A. El-
Shaieb, Ahmed T. Abdel-Aziz, Joel T. Mague & Mehmet Akkurt
To cite this article: Alaa A. Hassan, Shaaban K. Mohamed, Nasr K. Mohamed, Kamal M.A. El-
Shaieb, Ahmed T. Abdel-Aziz, Joel T. Mague & Mehmet Akkurt (2015): Facile and convenient
synthesis of 2,4-disubstituted and 2,3,4-trisubstituted 1,3-thiazoles, Journal of Sulfur
Chemistry, DOI: 10.1080/17415993.2015.1114621
To link to this article: http://dx.doi.org/10.1080/17415993.2015.1114621
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Date: 31 December 2015, At: 04:34

JOURNAL OF SULFUR CHEMISTRY, 2015
http://dx.doi.org/10.1080/17415993.2015.1114621
Facile and convenient synthesis of 2,4-disubstituted and
2,3,4-trisubstituted 1,3-thiazoles
Alaa A. Hassana, Shaaban K. Mohameda,b, Nasr K. Mohameda, Kamal M.A. El-Shaieba,
Ahmed T. Abdel-Aziza, Joel T. Maguec and Mehmet Akkurtd
aChemistry Department, Faculty of Science, Minia University, El-Minia, Egypt; bFaculty of Science &
Engineering, Metropolitan University, Manchester, England; cDepartment of Chemistry, Tulane University,
New Orleans, LA, USA; dDepartment of Physics, Faculty of Sciences, Erciyes University, Kayseri, Turkey
ABSTRACT
ARTICLE HISTORY
Received 11 June 2015
Accepted 27 October 2015
An efficient route for the synthesis of (E)-2-(2-(2-nitrobenzylidene)-
hydrazinyl)-4-phenylthiazol-3-ium bromide, (E)-2-(2(substituted
benzylidene)hydrazinyl)-4-phenylthiazoles and (E)-4-(4-bromo-
phenyl)-2-(cycloalkylidenehydrazono)-3-phenyl-2,3-dihydrothiazol-
es by reaction of 1-aryl-2-bromoethanones with 2-(1-substituted
methylidene)hydrazinecarbothioamides and cycloalkylidene-N-phe-
nyl-hydrazinecarbothioamides. The structure of the products has
been confirmed by using IR, NMR, mass spectrometry and single-
crystal X-ray analyses.
KEYWORDS
Aryl-2-bromoethanones;
hydrazinecarbothioamides;
cyclo-alkylidenehydrazine
carbothioamides; Di- and
trisubstituted-1,3-thiazoles;
thiazolium bromide
derivative
Introduction
α-Haloketones are promising synthons for synthesizing carbo- and heterocyclic com-
pounds in preparative organic chemistry.[1] Although the Hantzch method, in which
α-haloketone is condensed with a thioamide, has been reported for decades as the method
of choice for the synthesis of thiazoles,[2] a great effort has been dedicated for more
CONTACT Alaa A. Hassan
alaahassan2001@mu.edu.eg.
Chemistry Department, Faculty of Science, Minia
University, El-Minia 61519, Egypt
Supplemental data for this article can be accessed here. http://dx.doi.org/10.1080/17415993.2015.1114621
© 2015 Taylor & Francis

2
A. A. HASSAN ET AL.
flexible procedures, and particularly to that of thiazole ring formation. One-pot syn-
thesis via a three-component reaction between aroylisothiocyanates, α-amino acids and
α-bromoketones in an ionic liquid was described as a synthesis of thiazole-2(3H)imines.[3]
It has been reported that, treatment of freshly prepared differently substituted
α-bromoacetophenones with thiourea, afforded the formation of 2-amino-4-phenyl-
1,3-thiazole- and 2-amino-4-(4-bromophenyl)-1,3-thiazole in 52% and 47% yields,
respectively.[4] Synthetic methods have also been reported for trisubstituted thiazoles.[5–
10] Trisubstituted thiazoles were synthesized using ligand-free, palladium-catalyzed, direct
5-arylation of 2,4-disubstituted thiazole and conventional or microwave-assisted heating
in low to moderate yields.[11]
In view of the emerging importance of thiazoles and their derivatives, several meth-
ods for their synthesis were developed using various catalysts,[12] conditions [13–15] and
strategies.[16–19] However, unsatisfactory yields, prolonged reaction times, tedious work
up procedures and use of expensive catalysts are still often encountered problems. There-
fore, the development of efficient and facile processes is a major challenge for chemists in
organic synthesis.
Many natural products [20] containing the thiazole ring have been isolated and most
of them exhibited, e.g. antimicrobial, antifungal, antihypertensive, anti-inflammatory and
antitumor cytotoxic activities.[21–25]
The 2-iminothiazolidine moiety is present in a large variety of physiologically active
compounds with applications varying from medicinal to agricultural use.[26] Some 2-
iminothiazolidines are useful as schistosomicides [27] and many applications in medicinal
chemistry.[28]
2-Imino-4-thiazolidines and 3,4-disubstituted-2-imino-4-thiazolines have been syn-
thesized via condensation α-chloromethyl and α-bromomethyl ketimines with potassium
thiocyanate.[29,30]
Recently, we have reported the synthesis of 1,3-thiazolylidenehydrazinylidene
ethylpyridinum bromide monohydrate, 1,3-thiazolylidenehydrazinum bromide, hemihy-
drate and 1,3-thiazolylidenehydrazine derivatives by heterocyclization of 2-(1-substituted
ethylidene)hydrazinecarbothioamides via reaction with 1-aryl-2-bromoethanones and
evaluated their antibacterial activity.[31]
Results and discussion
Herein, the behavior of 1-aryl-2-bromoethanones (2a,b) towards 2-(1-substituted methyli-
dene) hydrazinecarbothioamides 1a–g and cycloalkylidene-N-phenylhydrazinecarbothio
amides 4a–e will be investigated and compared to the behavior of the same compounds
2a,b toward 2-(1-substituted ethylidene) hydrazinecarbothioamides.
We also report a facile and efficient preparation of (E)-2-(2-(2-nitrobenzylidene)
hydrazinyl)-4-phenylthiazol-3-ium bromide 3a, (E)-2-(substituted arylidene)hydrazinyl-
4-phenylthiazoles 3b–g and (E)-4-(4-bromophenyl)-2-(cycloalkylidenehydrazono-3-
phenyl-2,3-dihydrothiazoles 5a–e in high yields under mild reaction conditions
(Schemes 1 and 2).
Cyclocondensation of 1-aryl-2-bromoethanone (2a) with 2(1-substituted methyli-
dene)hydrazinecarbothioamides 1a–g in absolute ethanol under reflux for 1 h afforded the
disubstituted 1,3-thiazoles 3b–g in 96–98% yields, except in the case of the reaction 2a with

JOURNAL OF SULFUR CHEMISTRY
3
Scheme 1. The reaction between 2-(1-substituted methylidene)hydrazinecarbonthioamides 1a–g and
1-aryl-2-bromoethanones (2a,b).
Scheme 2. The reaction between cycloalkylidene-N-phenylhydrazinecarbothio amides 4a–e and
4-bromophenyl-2-bromoethanone (2b).
1a, in which (E)-2-(2-(2-nitrobenzylidene)hydrazinyl)-4-phenylthiazol-3-ium bromide 3a
(98%) was formed.
A variety of analytical techniques, including IR, NMR, mass spectrometry, elemental
analysis and X-ray crystallography, were used to confirm the structural identity of the final
products. The target compounds were correctly analyzed for their molecular structure.
The infrared spectrum of 3a, as an example, shows a broad band at 3329 cm−1, which can
be attributed to the hydrazine-NH. The IR spectrum of 3a revealed sharp band at 1616
(C N), medium band at 1343 (NO2) and Ar–C C at 1595 cm−1. A new band at 1033 and
=
=
746 cm−1 in 3a was assigned to (C–S–C).[31,32]

4
A. A. HASSAN ET AL.
1
The H NMR spectrum of 3a contained two singlets at 7.31 and 8.45 ppm which
=
could be attributed to the thiazole-CH and azomethine CH N, respectively. A broad
exchangeable signal with (D2O) at 11.18 ppm is attributed to hydrazine-NH. In addition,
the presence of multiplets in the range 7.32–8.06 ppm is ascribed to nine aromatic protons.
Moreover, the 13C NMR spectrum showed a peak appearing at 167.69 ppm corresponds to
thiazole-C2. Signals at 150.42, 147.33 and 104.33 are due to thiazole-C5, azomethine-CH
and thiazole-CH, respectively. The aryl-C and aryl-CH were also observed (see experimen-
tal design section). In the mass spectra of 3a–g, molecular ion peaks of all compounds were
obtained from EI-MS, but the molecular ion peak abundances were not strong. The mass
Figure 1. The title compound 3a with labeling scheme and 50% probability ellipsoids. The N–H . . . Br
interactions are shown as dotted lines.
Figure 2. Packing viewed down the a-axis. The N–H . . . Br interactions are shown as dotted lines.

JOURNAL OF SULFUR CHEMISTRY
5
Figure 3. The asymmetric unit of 3b with the complementary N–H . . . N hydrogen bonds shown as
dotted lines. Ellipsoids are drawn at the 50% probability level.
+
=
spectrometry fragmentations are characterized by the fragments (M -Ar-CH N) and
(M+-C9H7N3S), and have a peak at 102 a.m.u due to [Ar–C≡N]+. The identities of (E)-2-
(2-substituted benzylidene)hydrazinyl)-4-phenylthiazoles 3a–g were further confirmed by
single-crystal X-ray crystallographic studies for compounds 3a and 3b. The ORTEP view
of the title compound (E)-2-2[2-(2-nitrobenzylidene)hydrazinyl]-4-phenylthiazole 3a and
packing viewed down the a-axis are shown in Figures 1 and 2, respectivly. H-atoms attached
to carbon were placed in calculated positions (C–H = 0.95−0.98 Å) while those attached
to nitrogen were placed in locations derived from a difference map and their parameters
adjusted to give N–H = 0.91 Å. All were included as riding contributions with isotropic
displacement parameters 1.2–1.5 times those of the attached atoms. Tables 5–7 in the sup-
plementary data show the values of the selected geometric parameters and they are normal.
The details of N–H . . . Br intramolecular interactions are given in Table 10 in the supple-
mentary data. The bromide ion is associated with both N–H groups. The cations pack in
columns in which adjacent pairs of cations are arranged in an anti-parallel fashion with the
thiazolidene rings eclipsed (Figure 2) and the separation of their mean planes is 3.32 (3)°.
The distance between the ring centroids is 3.50 (2)°.
The X-ray study of 3b showed that the asymmetric unit of the title compound 2-[(E)-2-
[2-chlorobenzylidene]hydrazin-1-yl]-4-phenyl-1,3-thiazole, C16H12ClN3S, contains two
independent molecules whose conformations differ primarily in the orientation of the
phenyl and chlorobenzene rings with respect to the thiazole ring.
In the crystal, the two independent molecules are associated via complementary
N–H . . . ..N hydrogen bands into a dimer. These dimers are associated through weak
C–H . . . .Cl and C–H . . . .S interactions into supramolecular chains propagating along
the a-axis direction (Figure 3).[33]
Compound 3a contains NO2 in the aryl group (strong electron withdrawing group).
This NO2 group increased the positive charge on the aromatic ring and consequently on the
NH group. This will facilitate the attraction forces between Br− and delta positive charge
on hydrogen atom.

6
A. A. HASSAN ET AL.
Figure 4. Thetitlecompound5awith50%probabilitydisplacementellipsoidsfornon-hydrogenatoms.
Interestingly, further application of our optimized reaction conditions to
Z-cycloalkylidene-N-phenylhydrazinecarbothioamides 4a–e and 4-bromophenyl-2-
bromoethanone (2b) provided the corresponding (E)-4-(4-bromophenyl)-2-
(cycloalkylidenehydrazono)-3-phenyl-2,3-dihydrothiazoles 5a–e in 95–97% yields.
Cycloalkylidene-N-phenylhydrazin ecarbothioamides 4a–e was prepared according to
published procedures.[34,35]
Reaction of 2b with cycloalkylidene -N-phenylhydrazinecarbothioamides 4a–e in a
molar ratio of (1:1) in absolute ethanol has been carried out under reflux with stirring
for 1 h. The progress of the reaction was monitored by TLC until completion, and a pale
yellow precipitate from 5a–e was separated (Scheme 2).
The results of combustion analyses and spectroscopic data of 5a–e suggested the pres-
ence of (E)-4-(4-bromophenyl)-2-(cycloalkylidenehydrazono)-3-phenyl-2,3-dihydrothia
zoles. The gross formula (C20H18BrN3S) of 5a, as an example, was confirmed by mass
spectrometry and exhibited its molecular ion peak at m/z = 411/413 (80%) which is in
agreement with the proposed structure and clearly shows the addition of one molecule of
2b to one molecule of 4a with elimination a molecule of HBr and H2O.
1H NMR of 5a showed the appearance of cyclo-pentylidene-CH2 at δ = 1.63 (4H),
H
=
2.20 (2H) and 2.32 (2H) as multiplets representing (CH2)2 and (CH2)2C N, respectively.
A sharp singlet at 6.62 due to thiazole-CH, another multiplets at 7.07–7.45 due to aryl
groups. The presence of cyclo-pentylidene-CH2 is evident from DEPT spectra exhibiting
negative signals at 24.08, 24.48, 29.78 and 31.12 ppm. In the 13C NMR spectrum of 5a,
thiazole-C2 and C4 resonate at 165.54 and 137.94 ppm, respectively, further peaks are at
=
δ = 171.79 (cyclopentyl-C N), and 101.78 (thiazole-CH).
C
Moreover, the structure of 5a was confirmed unambiguously by the single-crystal X-ray
structure analysis (Figure 4).[36] Figure 4 shows the structure of (2E)-4-(4-bromophenyl)-
2-[2-[(1E)-cyclo-pentylidene]hydrazin-1-ylidene]-3-phenyl-2,3-dihydro-1,3-thiazole 5a
in which the cyclopentyl ring adopts a half-chair conformation. The 4-bromophenyl and
phenyl rings are twisted out of the plane of the thiazole ring with dihedral angles of 34.6
(1)° and 68.32 (6)°, respectively.[36]

JOURNAL OF SULFUR CHEMISTRY
7
Scheme 3. Mechanistic rationale for the formation of compounds 3a–g and 5a–e.
The rational for the formation of 3a–g and 5a–e is depicted in scheme 3.
As a result, this synthesis allows much wider substrate scope and provides a general and
practical access to the target products. It was found that solvent, temperature and the molar
ratio of reactants may all play a critical role on the reaction efficiency. The influence of
different solvents has been studied and found that absolute ethanol was a superior solvent
compared with benzene, THF, DMF, ethyl acetate and ethylene chloride which gave traces
of products.
An increased amount of 2a as well as 2b was not necessary to obtain the products in
pure and high yields.
Therefore, applying the reactions in absolute ethanol under reflux and using equimolar
ratios of 1a–g with 2a or 4a–e with 2b is chosen as the optimized reaction conditions.
Conclusion
An efficient and facile process for the synthesis of di-and trisubstituted-1,3-thiazoles has
been reported. The advantage of this procedure is fast reaction time and high yields without
use of expensive catalysts.
Experimental design
Instruments
Melting points were determined using open glass capillaries on a Gallenkamp melting
point apparatus, and uncorrected. IR spectra were recorded from potassium bromide disks

8
A. A. HASSAN ET AL.
on Alpha, Bruker FT-IR. 1H- and 13C NMR spectra (300 MHz for 1H, 75 MHz for 13C)
were observed in CDCl3 and DMSO-d6 as a solvent, on Varian mercury plus 300 spectrom-
eter with tetramethylsilane as an internal standard. The 13C NMR signals were assigned
with the aid of DEPT experiments. Mass spectra were obtained in Varian MAT 311 dou-
bly focusing instrument using electron impact ionization (70 eV). X-ray diffractions were
measured using Bruker SMART APEXCCD diffractometer with Graphite monochroma-
tor and five-focus sealed tube as a Radiation source. TLC was performed as analytical
merck 9385 silica aluminum sheets (Kieselgel 60) with pf254 indicator; TLC’s were viewed
at λ
= 254 nm. The elemental analysis was carried out at the Microanalytical Center,
max
Cairo University, Egypt.
X-ray data were collected using a Bruker D8 VENTURE PHOTON 100 CMOS diffrac-
tometer using CuKα radiation in the ω-scan mode at 150(2) K. Data have been processed
using APEX2 and SAINT softwares.[37] The numerical absorption correction was applied
using the SADABS program.[37] The crystal structure was solved by direct methods using
SHELXT,[37] and refined by a full-matrix least-squares procedure based on F2 (SHELXL-
2014).[38] The molecular graphics were drawn using the DIAMOND [39] and SHELXT
programs.[37]
Starting materials
1-Aryl-2-bromoethanones (2a,b) were prepared according to Nobuta et al., [40] and
Salama and Novák [41] 2-(1-Substituted methylidene)hydrazinecarbonthioamides 1a–g
were prepared by condensation of phenyl thiosemicarbazide with appropriate aldehydes
according to the published procedure.[42] Cycloalkylidene-N-substituted hydrazinecar-
bothioamides 4a–e were prepared according to the published procedures.[34,35]
2-Cycloocytylidene-N-phenyl hydrazinecarbothioamides (4d)
Colorless crystals (0.269 g, 98%), m.p = 100–102°C, IR (KBr): υ = 3080 (Ar–CH), 2927
=
=
=
(Ali-CH), 1617 (C N), 1593 (Ar-C C), 1560 (NH def. and C–N str.), 1362, 990 (C S
and C–N). 1H NMR (CDCl3): δ = 1.53–1.54 (m, 2H, CH2), 1.55–1.56 (m, 4H, 2CH2),
H
1.79–1.81 (m, 4H, 2CH2), 2.41–2.42 (m, 4H, 2CH2), 7.19–7.23 (m, 1H, Ar-H), 7.36–7.40
(m, 2H, Ar–H), 7.68–7.72 (m, 2H, Ar–H), 8.62 (br, s, 1H, NH), 9.32 (br, s, 1H, NHPh); 13
C
NMR (CDCl3): δ = 24.56,24.92, 25.29, 26.55, 27.33, 28.09, 36.36 (CH2), 124.18, 125.93,
C
=
=
128.77 (Ar–CH), 138.13 (Ar–C), 158.85 (C N), 176.0 (C S). Anal. Calcd. for C15H21N3S:
C, 65.41; H, 7.69; N, 15.26; S, 11.64. Found: C, 65.27; H, 7.78; N, 15.41; S, 11.49.
(E)-2-(3,4-Dihydronaphthalen-1(2H)-ylidene)-N-phenylhydrazinecarbothioamide (4e)
Colorless crystals (0.286 g, 97%), m.p = 186–188°C, IR (KBr): υ = 3091 (Ar–CH), 2937
=
=
=
(Ali-CH), 1624 (C N), 1602 (Ar–C C),1556 (NH def. and C–N str.), 1360, 992 (C S
1
and C–N). H NMR (CDCl3): δ = 1.96–2.01 (m, 2H, CH2), 2.64–2.67 (m, 2H, CH2)
H
2.75–2.82 (m, 2H, CH2), 7.19–7.24 (m, 1H, Ar–H), 7.26–7.32 (m, 1H, Ar–H), 7.38–7.42
(m, 1H, Ar–H), 8.02–8.04 (m, 1H, Ar–H), 8.87 (br, s, 1H, NH), 9.45 (br, s, 1H, NHPh); 13
C
NMR (CDCl3): δ = 21.52, 25.71, 29.44 (CH2), 124.56, 126.77, 130.02 (Ar–CH), 138.01,
C
=
140.59 (Ar–C), 147.24 (C N), 176.16 (C=S). Anal. Calcd. for C17H17N3S (295.40): C,
69.12; H, 5.80; N, 14.22; S, 10.85. Found: C, 68.96; H, 5.88; N, 14.36; S, 11.03.

JOURNAL OF SULFUR CHEMISTRY
9
General procedure of synthesis of di-and trisubstituted thiazoles 3a–g and 5a–e
A mixture of (1.0 mmol) 1-aryl-2-bromoethanones (2a,b) and (1.0 mmol) from each
of 2-(1-substituted methylene)hydrazinecarbothioamides 1a–g or cycloalkylidene-N-
substituted hydrazinecarbothioamides (4a–e) in absolute ethanol (30 ml) was refluxed for
1 h, then cooled to room temperature. A yellow solid precipitate was filtered and washed
with a small amount of ethanol and recrystallized from ethanol to give pure crystals from
3a–g to 5a–e.
(E)-2-2[2-(2-Nitrobenzylidene)hydrazinyl]-4-phenylthiazole-3-ium bromide (3a)
Yellow crystals (ethanol) (0.317 g, 98%), m.p = 244–246°C, IR (KBr): υ = 3329 (NH),
1616 (C N), 1595 (Ar–C C), 1343 (NO2), 1033, 746 (C–S–C) cm−1. 1H NMR (DMSO-
=
=
d6): δ = 7.31 (s, 1H, thiazole-CH), 7.32–7.34 (m, 1H, Ar–H), 7.41–7.43 (m, 2H, Ar–H),
H
7.60–7.64 (m, 1H, Ar–H), 7.78–7.87 (m, 1H, Ar–H), 7.87–7.89 (m, 2H, Ar–H), 8.03–8.06
(m, 2H, Ar–H), 8.45 (s, 1H, CH N), 11.18 (s, br, 1H, NH); C NMR (DMSO-d6):
13
=
δ = 104.33 (thiazole-CH), 124.63, 125.47, 127.40, 127.86, 128.56, 129.65 (Ar–CH),
C
131.26, 133.43, 144.33 (Ar–C), 147.33 (CH=N), 150.42 (thiazole-C5), 167.69 (thiazole-
C2), EI-mass, m/z (%) 405/407 (M+,11), 324 (36), 278 (6), 175 (13), 135 (90), 102 (100),
76 (89). Anal. Calcd. for C16H13BrN4O2S (405.27): C, 47.42; H, 3.23; Br, 19.72; N, 13.82;
S, 7.91 Found: C, 47.58; H, 3.17; Br, 19.60, N, 13.94; S, 8.07.
(E)-2-[2-(2-Chlorobenzylidene)hydrazinyl]-4-phenylthiazole (3b)
Yellow crystals (ethanol, (0.300 g, 96%), m.p = 208–210°C, IR (KBr): υ = 3323 (NH),
1620 (C N), 1602 (Ar–C C), 1040, 750 (C–S–C) cm−1. 1H NMR (DMSO-d6): δ = 7.32
=
=
H
(s, 1H, thiazole-CH), 7.39–7.43 (m, 6H, Ar–H), 7.86–7.88 (m, 3H, Ar–H), 8.41 (s, 1H,
13
=
CH N), 11.08 (s, br, NH). C NMR (DMSO-d6): δ = 104.01 (thiazole-CH), 125.45,
C
126.10, 127.52, 128.25, 128.55, 129.73 (Ar–CH), 131.91, 133.11, 134.86 (Ar–C), 1+47.80
=
(CH N), 150.38 (thiazole-C5), 167.80 (thiazole-C2), EI-mass, m/z (%) 313/315 (M , 9),
175 (36), 135 (100), 125 (58), 89 (60), 77 (82). Anal. Calcd. for C16H12ClN3S (313.80): C,
61.24; H, 3.85; Cl, 11.30; N, 13.39; S, 10.22. Found: C, 61.07; H, 3.91; Cl, 11.42; N, 13.26; S,
10.32.
(E)-2-[2-(4-Chlorobenzylidene)hydrazinyl]-4-phenylthiazole (3c)
Yellow crystals (ethanol), (0.303 g, 97%), m.p = 216–218°C. IR (KBr): υ = 3321 (NH),
1621 (C N), 1600 (Ar–C=C), 1041, 749 (C–S–C) cm−1,1H NMR (DMSO-d6):
=
δ
= 7.30 (s, 1H, thiazole-CH), 7.31–7.33 (m, 1H, Ar–H), 7.41–7.45 (m,2H, Ar–H),
H
7.46–7.51 (m, 2H, Ar–H), 7.86–7.88 (m, 2H, Ar–H), 7.93–7.95 (m, 2H, Ar–H), 8.43 (s,1H,
CH N), 11.12 (s, br, NH), 13C NMR (DMSO-d6): δ = 104.16 (thiazole-CH), 123.59,
=
C
=
127.64, 127.68, 122.89, 128.36 (Ar–CH), 131.21, 133.35, 137.47 (Ar–C), 147.90 (CH N),
150.30 (thiazole-C5), 167.92 (thiazole-C2), EI-mass, m/z (%) 313/315 (M+,9), 175 (40),
135 (100), 125 (55), 89 (65), 77 (85). Anal. Calcd. for C16H12ClN3S (313.80): C, 61.24; H,
3.85; Cl, 11.30; N, 13.39; S, 10.22. Found: C, 61.13; H, 3.94; Cl, 11.46; N, 13.22; S, 10.09.
(E)-2-[2-(2-Methoxybenzylidene)hydrazinyl]-4-phenylthiazole (3d)
Yellow crystals (ethanol), (0.302 g, 98%), m.p = 248–250°C, IR (KBr): υ = 3339 (NH),
1617 (C N),1590 (Ar–C C), 1032, 744 (C–S–C) cm−1. 1H NMR (DMSO-d6): δ = 3.86
=
=
H

10
A. A. HASSAN ET AL.
(s, 3H, OCH3), 7.01–7.05 (m, H, Ar–H), 7.09–7.11 (m, 1H, Ar–H), 7.33 (s, 1H, thiazole-
CH), 7.35–7.41 (m, 2H, Ar–H), 7.43–7.45 (m, 2H, Ar–H), 7.81–7.86 (m, 3H, Ar–H), 8.44
(s, 1H, CH N), 11.05 (s, br, NH), 13C NMR (DMSO-d6): δ = 55.73 (OCH3), 103.78
=
C
(thiazole-CH), 122.17, 125.02, 125.72, 127.90, 128.36, 128.71 (Ar–CH), 131.06, 133.83
=
(Ar–C), 148.08 (CH N), 150.27 (thiazole-C5), 157.30 (Ar–C–O), 168.36 (thiazole-C2).
EI-mass, m/z (%) 309 (M+,10), 175 (35), 135 (79), 91 (39), 77 (100). Anal. Calcd. for
C17H15N3OS (309.39): C, 66.00; H, 4.89; N, 13.58; S, 10.36. Found: C, 65.84; H, 4.96; N,
13.66; S, 10.55.
(E)-2-[2-(3,4-Dimethoxybenzylidene)hydrazinyl]-4-phenylthiazole (3e)
Yellow crystals (ethanol), (0.328 g, 97%), m.p = 256–258°C. IR (KBr): υ = 3317 (NH),
1613 (C N), 1585 (Ar–C C), 1035,748 (C–S–C) cm−1. 1H NMR (DMSO-d6): δ = 3.80
=
=
H
(s, 3H, OCH3), 3.82 (s, 3H, OCH3), 7.00–7.03 (m,1H, Ar–H), 7.18–7.20 (m, 1H, Ar–H),
7.28–7.31 (m, 2H, Ar–H), 7.32 (s, 1H, thiazole-CH), 7.40–7.45 (m, 2H, Ar–H), 7.84–7.86
(m, 2H, Ar–H), 8.00 (s, 1H, CH N), 11.03 (s, br, 1H, NH). 13C NMR (DMSO-d6):
=
δ = 55.38, 55.58 (OCH3), 103.32 (thiazole-CH), 120.39, 125.59, 127.06, 127.69, 128.65
c
=
(Ar–CH), 131.22, 133.76 (Ar–C), 147.99 (CH N), 150.18 (thiazole-C5), 157.49, 158.12
(Ar–C–O), 168.35 (thiazole-C2). EI-mass, m/z (%): 339 (M+, 4), 175 (64), 135 (100), 106
(22), 77 (72). Anal. Calcd. for C18H17N3O2S (339.41): C, 63.70; H, 5.05; N, 12.38; S, 9.45.
Found: C, 63.86; H, 4.92; N, 12.26; S, 9.61.
(E)-2-[2-(Naphthalene-2-ylmethylene)hydrazinyl]-4-phenylthiazole (3f)
Yellow crystals (ethanol), (0.322 g, 98%),m.p. = 250–252°C, IR (KBr): υ = 3338 (NH),
−1
=
=
1619 (C N), 1608 (Ar–C C), 1037, 745 (C–S–C) cm
.
1H NMR (DMSO-d6):
δ
= 7.31, 7.34 (m, 1H, Ar–H), 7.39 (s, 1H, thiazole-CH), 7.41–7.43 (m, 1H, Ar–H),
H
7.44–7.46 (m, 2H, Ar–H), 7.61–7.63 (m, 2H, Ar–H), 7.69–7.72 (m, 2H, Ar–H), 7.88–7.90
=
(m, 1H, Ar–H), 7.99–8.01 (m, 1H, Ar–H), 8.71 (s, 1H, CH N), 8.73–8.78 (m, 2H, Ar-H),
11.0 (s, br, 1H, NH).13C NMR (DMSO-d6): δ = 103.84 (thiazole-CH), 125.62, 126.28,
C
127.29, 127.71, 128.68, 128.89, 129.91 (Ar–CH), 130.83, 132.66, 133.45 (Ar–C), 147.67
+
=
(CH N), 150.67 (thiazole-C5), 168.24 (thiazole-C2). EI-mass, m/z (%): 329 (M , 8), 175
(87), 135 (100), 82 (76), 77 (46). Anal. Calcd. for C20H15N3S (329.42): C, 72.92; H, 4.59;
N, 12.76; S, 9.73. Found: C, 73.11; H, 4.66; N, 12.69; S, 9.58.
(E)-2-[2-(Anthracen-2-ylmethylene)hydrzinyl]-4-phenylthiazole (3g)
Yellow crystals (ethanol), (0.363 g, 96%), m.p = 264–266°C, IR (KBr): υ = 3336 (NH),
−1
=
=
1621 (C N), 1591 (Ar C C), 1041, 749 (C–S–C) cm
.
1H NMR (DMSO-d6):
δ
= 7.27–7.30 (m, 4H, Ar–H), 7.33 (s, 1H, thiazole-CH), 7.57–7.60 (m, 2H, Ar–H),
H
7.68–7.70 (m,2H,Ar–H), 7.89–7.90 (m, 2H, Ar-H), 8.17–8.20 (m, 2H, Ar–H), 8.67 (s,
H, CH N), 8.70–8.74 (m, 2H, Ar-H), 10.97 (s, br, 1H, NH). 13C NMR (DMSO-d6):
=
δ = 103.84 (thiazole-CH), 125.80, 126.42, 127.20, 127.66, 127.88,128.24, 128.68, 128.84,
C
=
129.91 (Ar–CH), 130.83, 132.66, 133.45, 135.26 (Ar–C), 148.27 (CH N), 152.67 (thiazole-
C5), 168.88 (thiazole-C2). EI-mass, m/z (%): 379 (M+, 8), 19 (21), 134 (27), 77 (100). Anal.
Calcd. for C24H17N3S (379.48): C, 75.96; H, 4.52; N, 11.07; S, 8.45. Found: C, 76.13; H, 4.49;
N, 10.89; S, 8.38.

JOURNAL OF SULFUR CHEMISTRY
11
(E)-4-(4-Bromophenyl)-2-(cyclopentylidenehydrazono)-3-phenyl-2,3-dihydrothiazole
(5a)
Yellow crystals (ethanol), (0.332 g, 97%), m.p = 268–270°C, IR (KBr): υ = 3093 (Ar-
1
=
=
CH), 2958 (Ali-CH), 1628 (C N), 1579 (Ar C C). H NMR (DMSO-d6): δ = 1063 (m,
H
4H, 2CH2), 2.20 (m, 2H, CH2), 2.32 (m, 2H, CH2), 6.62 (s, 1H, thiazole-CH), 7.07–7.09
(m, 2H, Ar–H), 7.20–7.22 (m, 2H, Ar-H), 7.26–7.28 (m, 1H, Ar–H), 7.32–7.34 (m, 2H,
Ar–H), 7.43–7.45 (m, 2H, Ar–H). 13C NMR (DMSO-d6): δ = 24.08, 24.48, 29.78, 31.12
C
(CH2), 101.78 (thiazole-CH), 127.39, 128.29, 128.66, 129.89, 130.27 (Ar–CH), 131.22,
=
137.81 (Ar–C), 137.94 (thiazole-C4), 165.54 (cyclopenlyl-C N), 171.79 (thiazole-C2). EI-
mass, m/z (%) 411/413 (M+, 80), 331 (22), 257 (12), 135 (26), 77 (100). Anal. Calcd. for
C20H18BrN3S (412.35): C, 58.26; H, 4.40; Br, 19.38; N, 10.19; S, 7.78. Found: C, 58.40; H,
4.32; Br, 19.22; N, 10.32; S, 7.89.
(E)-4-(4-Bromophenyl)-2-(cyclohexylidenehydrazono)-3-phenyl-2,3-dihydrothiazole
(5b)
Yellow crystals (ethanol), (0.330 g, 95%), m.p = 247–249°C, IR (KBr): υ = 3086 (Ar-
1
=
=
CH), 2934 (Ali-CH), 1624 (C N), 1580 (Ar–C C). H NMR (CDCl3): δ = 1.57 (m,
H
4H, 2CH2), 1.70 (m, 2H, CH2), 2.38 (m, 2H, CH2), 2.49 (m, 2H, CH2), 6.10 (s, 1H,
thiazole-CH), 6.95–6.97 (m, 2H, Ar–H), 7.18–7.24 (m, 3H, Ar–H), 7.28–7.32 (m, 4H,
Ar–H);13C NMR (CDCl3): δ = 26.07, 26.35, 27.44, 28.60, 35.31 (CH2), 101.37 (thiazole-
C
CH), 122.21, 127.19, 128.22, 118.63, 129.39 (Ar–CH), 131.38, 137.84 (Ar-C), 138.69
=
(thiazole-C4), 166.42 (cyclohexyl-C N), 166.56 (thiazole-C2). EI-mass, m/z (%) 425/427
(M+,72), 401 (12), 271 (28), 135 (32), 77 (100). Anal. Calcd. for C21H20BrN3S (426.37):
C, 59.16; H, 4.73; Br, 18.74; N, 9.86; S, 7.52. Found: C, 58.98; H, 4.81; Br, 18.88; N, 9.73; S,
7.46.
(E)-4-(4-Bromophenyl)-2-(cycloheptylidenehydrazono)-3-phenyl-2,3-
dihydrothiazole(5c)
Yellow crystals (ethanol), (0.356 g, 96%), m.p = 240–242°C, IR (KBr): υ = 3080 (Ar-CH),
1
=
=
2919 (Ali-CH), 1611 (C N), 1573 (Ar–C C). H NMR (CDCl3): δ = 1.53–1.56 (m, 4H,
H
2CH2), 1.56–1.59 (m, 4H, 2CH3), 2.53–2.55 (m, 4H, 2CH2), 6.21 (s, 1H, thiazole-CH),
6.94–6.97 (m, 2H, Ar–H), 7.19–7.22 (m, 3H, Ar–H), 7.27–7.29(m, 2H, Ar–H), 7.30–7.31
(m, 2H, Ar–H); 13C NMR (CDCl3): δ = 25.15, 27.63, 30.55, 32.19, 36.91 (CH2), 101.51
C
(thiazole-CH), 122.36, 127.29, 128.30, 118.72, 129.52 (Ar–CH), 131.52, 138.02 (Ar–C),
=
138.82 (thiazole-C4), 165.42 (cycloheptylidene-C N), 165.58 (thiazole-C2). EI-mass, m/z
(%): 439/441 (M+, 64), 411 (29), 385 (12), 329 (33), 258 (17), 135 (24), 77 (100). Anal.Calcd.
for C22H22BrN3S (440.40): C, 60.00; H, 5.04; Br, 18.14; N, 9.54, S, 7.28. Found: 59.84; H,
4.96; Br, 17.98; N, 9.68; S, 7.16.
(E)-4-(4-Bromophenyl)-2-(cyclooctylidenehydrazono)-3-phenyl-2,3-
dihydrothiazole(5d)
Yellow crystals (ethanol), (0.369 g, 96%), m.p = 212–214°C, IR (KBr): υ = 3088 (Ar–CH),
1
=
=
2926 (Ali-CH), 1616 (C N), 1582 (Ar–C C). H NMR (CDCl3): δ = 1.54–1.56 (m,
H
4H, 2CH2), 1.88–1.90 (m, 2H, CH2), 2.38–2.41 (m, 4H, 2CH2), 6.08 (s, 1H, thiazole-CH),
6.98–7.00 (m, 3H, Ar–H), 7.20–7.23 (m, 2H, Ar–H), 7.30–7.32 (m, 4H, Ar–H), 7.30–7.31
(m, 2H,Ar–H); 13C NMR(CDCl3): δ = 24.37, 25.50, 25.73, 26.31, 27.79, 30.09, 36.40
C

12
A. A. HASSAN ET AL.
(CH2), 101.22 (thiazole-CH), 122.18, 127.06, 128.20, 128.49, 129.36 (Ar–CH), 131.40,
=
137.97 (Ar–C), 138.64 (thiazole-C4), 164.79 (cyclooctylidene-C N), 170.45 (thiazole-
C2). EI-mass, m/z: 453/455 (M+, 35), 425 (7), 329 (33), 315 (8), 135 (17), 77 (100). Anal.
Calcd. for C23H24BrN3S (454.43): C, 60.79; H, 5.32; Br, 17.58; N, 9.25; S, 7.06. Found: C,
60.91; H, 5.28; Br, 17.46; N, 9.37; S, 6.93.
(E)-4-(4-Bromophenyl)-2-[(E)-(3,4-dihydronaphthalen-1(2H)-ylidene)hydra-zono]-
3-phenyl-2,3-dihydrothiazole (5e)
Yellow crystals (ethanol), (0.399 g, 97%), m.p = 214–216°C, IR (KBr): υ = 3084 (Ar–CH),
1
=
=
2929 (Ali-CH), 1619 (C N), 1585 (Ar–C C). H NMR (CDCl3): δ = 1.82–1.83 (m,
H
4H, 2CH2), 2.73–2.75 (m, 4H, 2CH2), 6.17 (thiazole-CH), 6.97–6.99 (m, 1H, Ar–H),
7.09–7.11 (m, 1H, Ar–H), 7.23–7.25 (m, 1H,Ar–H) 7.30–7.32 (m,1H, Ar–H); 13C NMR
(CDCl3): δ = 22.22, 27.34, 30.14 (CH2), 102.31 (thiazole-CH), 126.12, 127.34, 128.23,
c
128.40, 128.48(Ar–CH), 128.68, 129.49, 137.22 (Ar–C), 138.72 (thiazole-C4), 157.32
+
=
(dihydronaphthalenylidene-C N), 168.36 (thiazole-C2). EI-mass, m/z: 473/475 (M , 13),
135 (12), 130 (41), 77 (100). Anal. Calcd. for C25H20BrN3S (474.42): C, 63.29; H, 4.25; Br,
16.84; N, 8.86; S, 6.76. Found: C, 63.41; H, 4.19; Br, 17.03; N, 9.02; S, 6.62.
Disclosure statement
No potential conflict of interest was reported by the authors.
Funding
This work was supported by NSF-MRI Grant #1228232 and Tulane University .
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