Synthesis of 5-acetyl-2-arylamino-4-methylthiazole thiosemicarbazones under microwave irradiation and their in vitro anticancer activity

Article abstract of DOI:10.3184/174751916X14519928918516

A series of 21 new tri- and tetra-cyclic thiosemicarbazone derivatives were prepared via the condensation of morpholine, piperazine or N-(4-methoxyphenyl)piperazine with seven methyl hydrazine-carbodithioate derivatives of 5-acetyl-2-arylamino-4-methylthiazoles under microwave irradiation. All compounds were tested for their cytotoxic activity in vitro against human gastric, lung and breast cancer cell lines. The results showed that some of the compounds displayed moderate anticancer activity. The most potent compound, a morpholinosubstituted analogue, exhibited significant activity against human breast cancer cells.

Full text of DOI:10.3184/174751916X14519928918516

JOURNAL OF CHEMICAL RESEARCH 2016
VOL. 40 FEBRUARY, 67–72
RESEARCH PAPER 67
Synthesis of 5-acetyl-2-arylamino-4-methylthiazole thiosemicarbazones under
microwave irradiation and their in vitro anticancer activity
Hai-Bo Shia,b*, Wei-Xiao Huc, Wei-Mao Zhangb and Yan-Fei Wub
aChemical Engineering College, Ningbo Polytechnic, Ningbo 315800, P.R. China
bInstitute of Pharmaceutical Chemistry, Zhejiang Pharmaceutical College, Ningbo 315100, P.R. China
cCollege of Chemical Engineering and Materials Science, Zhejiang University of Technology, Hangzhou 310032, P.R. China
A series of 21 new tri- and tetra-cyclic thiosemicarbazone derivatives were prepared via the condensation of morpholine, piperazine or
N-(4-methoxyphenyl)piperazine with seven methyl hydrazine-carbodithioate derivatives of 5-acetyl-2-arylamino-4-methylthiazoles under
microwave irradiation. All compounds were tested for their cytotoxic activity in vitro against human gastric, lung and breast cancer cell
lines. The results showed that some of the compounds displayed moderate anticancer activity. The most potent compound, a morpholino-
substituted analogue, exhibited significant activity against human breast cancer cells.
Keywords: thiazole, thiosemicarbazone, synthesis, anticancer activity, microwave
The thiosemicarbazone (TSC) is considered as one of the most
important scaffolds and is embedded in many biologically
active compounds.1 In 1956, Brockman et al. first showed that
2-formylpyridine TSC possesses antileukemic activity in mice.2
Since then, various aliphatic, aromatic and heteroaromatic
carbaldehydeTSCsweresynthesisedandmanyofthemexhibited
a broad range of biological activities such as antimalarial,3,4
antiviral,5 antibacterial,6 and antitumour activities.7–11 To date,
the most significant progress in the treatment of cancer by this
class of compounds has been made with 3-aminopyridine-2-
carboxaldehyde TSC (3-AP or triapine) which is currently in
phase II clinical trials.12 TSCs were considered to suppress
tumour growth by virtue of their ability to chelate iron (Fe).
They are capable of removing Fe from biological systems
and inhibit the activity of Fe-requiring proteins, including
ribonucleotide reductase (RRa), a key enzyme involved in DNA
synthesis and repair.13 Therefore, there is increasing interest in
the structural modification of TSC derivatives with the aim of
improving the pharmaceutical profile of existing candidates or
of discovering novel derivatives.
process.14 Heterocyclic compounds with a variety of shapes
and electronic and physicochemical properties provide fertile
ground for optimisation of drug candidates. Thiazole TSCs are
known to possess a wide range of pharmacological activities
including antibacterial, antifungal,15,16 and anti-inflammatory17
properties. They are also anti-hypertension,18 anti-convulsion,19
anti-Parkinson’s disease,20 anti-Alzheimer’s disease,21 anti-
HIV22 and anticancer23–27 agents. The work in this paper is an
extension of our ongoing efforts towards the synthesis and
biological evaluation of new aminothiazole derivatives,28,29 and
is concerned with the synthesis of novel thiosemicarbazone
derivatives of 5-acetyl-2-arylamino-4-methylthiazoles and
determination of their antiproliferative activity in vitro against
three human cancer cell lines.
Results and discussion
Synthesis
We designed
a series of novel 5-acetyl-2-arylamino-4-
methylthiazole thiosemicarbazone derivatives TSC1–21 and
prepared them by the series of reactions shown in Scheme 1. The
first step, the preparation of aminothiazoles 3a–g was adapted
from the Hantzsch method described previously by us,30 and
Heterocycles are the most common structural units present in
marketed drugs and in target molecules in the drug discovery
H
N
H
N
O
O
N
NH2
(i)
(ii)
R
+
S
R
S
H
3C
CH3
S
O
H2NHN
C
4
SCH3
Br
2
3a–g
1a–g
H
N
S
N
(iii)
R
S
N
TSC1–TSC7
TSC8–TSC14
NNHC
O
H
N
H
N
N
N
R
R
S
(iv)
(v)
S
S
S
NNHC SCH3
NNHC N
NH
5a–g
H
N
N
R
S
S
NNHC N
N
OCH3
TSC15–TSC21
R: a = H; b = o-CH3; c = m-CH3; d = p-CH3; e = o-Cl; f = m-Cl; g = p-Cl;
Reagents and conditions: (i) NBS/C6H6,Benzoyl peroxide, reflux, K2CO3; (ii) i-PrOH, HCl, reflux; (iii) morpholine, i-PrOH, MW, 100 °C, 45 min
(iv) piperazine, i-PrOH, MW, 100 °C, 45 min;(v) N4-(4-methoxyphenyl)piperazine, i-PrOH, MW, 100 °C, 60 min;
Scheme 1
* Correspondent. E-mail: nbblconba_shb@163.com

68 JOURNAL OF CHEMICAL RESEARCH 2016
Table 1 Antiproliferative activity of compounds TSC1–21 (Scheme 1)
against human gastric (SGC-7901), lung (H446) and breast cancer
(MCF-7) cell lines
involved reaction of appropriate thioureas 1a–g and 3-bromo-
acetylacetone 2. Despite the success of this preparation, the
method suffered from an intricate and tedious work-up. Therefore,
it was necessary to develop a more convenient preparation. We
found that we could prepare 3-bromo-acetylacetone in situ by
treatment of acetylacetone 2 with N-bromosuccinimide and
benzoylperoxide and, by this means, we were able in a one-pot
reaction to convert a series of N-arylthioureas 1a–g into a series
of arylaminothiazoles 3a–g in good yield. Compared with the
previous one, our method is much simpler with more general
applicability. Reaction of arylaminothiazoles 3a–g with methyl
hydrazinecarbodithioate 4 (prepared by a literature method8)
in the presence of concentrated hydrochloric acid gave the
thiosemicarbazone derivatives 5a–g. The catalytic amount of
hydrochloric acid that was used is believed to readily drive the
reaction to completion thus improving the yield of the reaction.
The preparation of thiosemicarbazone derivatives TSC1–21
was carried out by condensations between compounds 5a–g
and morpholine, piperazine or N4-substituted piperazine, the
latter prepared by the literature method.31 We first carried out
the reaction of compound 5a with morpholine by conventional
heating and found that the reaction was completed in 24 h. When
the reaction was repeated under microwave (MW) conditions, the
reaction time was reduced to 45 min. We thus adopted the latter
method to prepare TSC1–21.
Substituent
R
H
2-CH3
3-CH3
4-CH3
2-Cl
3-Cl
4-Cl
H
2-CH3
3-CH3
4-CH3
2-Cl
3-Cl
4-Cl
Cell lines (IC50, µM)a,b
Compounds
SGC-7901
17.54
45.91
64.06
33.29
25.09
16.55
26.47
> 100
18.25
33.04
71.99
> 100
31.03
> 100
65.95
18.54
30.21
21.35
16.50
38.49
11.58
1.74
H446
54.00
48.37
> 100
40.32
21.13
10.33
34.05
> 100
> 100
> 100
> 100
> 100
> 100
> 100
> 100
56.13
71.19
81.79
> 100
83.95
35.03
2.23
MCF-7
13.94
20.52
57.07
53.97
17.74
5.49
11.11
> 100
> 100
> 100
> 100
> 100
> 100
> 100
38.28
15.04
39.51
49.61
34.65
45.43
23.29
6.53
TSC1
TSC2
TSC3
TSC4
TSC5
TSC6
TSC7
TSC8
TSC9
TSC10
TSC11
TSC12
TSC13
TSC14
TSC15
TSC16
TSC17
TSC18
TSC19
TSC20
TSC21
Cisplatin
H
2-CH3
3-CH3
4-CH3
2-Cl
3-Cl
4-Cl
The synthesised compounds (TSC1–21) were characterised
by their 1H NMR, MS, and IR spectra and by elemental analysis
or HRMS. The IR spectra of all compounds showed absorption
peaks at 1023–1138 cm–1 which are attributed to the C=S group,
while the bands at 1552–1600 cm–1 are due to the C=N group.
–
aIC50, compound concentration required to inhibit tumour cell proliferation by 50%.
bValues are the mean of three experiments.
1
In addition, the H NMR spectra of the compounds showed
signals within the range of δ 7.87–10.52 for the –NHCS– group.
against three human cancer cell lines in vitro and some of them
showed high or moderate cytotoxic activities. Among them,
the most potent compound TSC6 exhibited significant activity
against breast cancer cell line MCF-7. The preliminary structure-
activity relationships showed that an electron-withdrawing
group R on the benzene ring increased the cytotoxic inhibitory
effect and introduction of a 4-methoxyphenyl group into the N4
position in piperazine ring also enhanced inhibitory activity.
Anticancer activity
A preliminary evaluation of compounds TSC1–21 was
performed by MTT assays32 in vitro against three human
cancer cell lines including human gastric cancer cell SGC-
7901, human lung cancer cell H446 and human breast cancer
cell MCF-7. Cisplatin was employed as a positive control in the
assay. The data shown in Table 1 are IC50 values against tested
tumour cells.
Experimental
As shown in Table 1, most of the tested compounds showed
moderate antiproliferative activity against some or all of
SGC-7901, H446 and MCF-7. Compound TSC6 exhibited the
highest anticancer activity against MCF-7 cells with an IC50
value of 5.49 µM, comparable with that of cisplatin (6.53 µM).
Comparing the results of compounds TSC1–7 bearing the same
morpholine ring but different substituents R, it can be seen that
the three compounds TSC5–7 with a chloro group showed
better antitumour activity than the three compounds TSC2–4
with a methyl group against SGC-7901, H446 and MCF-7.
Compound TSC6 also has the best antitumour activity against
H446 with an IC50 value of 10.33 µM. The results implied
that when the R group is an electron-withdrawing group such
as a 3-Cl moiety and there is a morpholine ring, this feature
enhances the inhibitory activity.
The compounds which contain a piperazine ring TSC8–14
were only active towards SGC-7901 cells. The activities of
compounds TSC15–21 which have a 4-methoxyphenyl group
in the N4 position in the piperazine ring showed higher activities
against all cell lines than compounds unsubstituted at this
position. It is clear that a N4-(4-methoxyphenyl) substituent on
the piperazine enhances anticancer activity.
Reagents and solvents were purchased from the SinoPharm Chemical
Reagent Co., Ltd and were used without further purification. Melting
points were taken on a X-4 apparatus and were uncorrected (Shanghai
Optical instrument, China). IR spectra (KBr pellets) were obtained on
a Bruker TENSOR27 spectrometer. 1H NMR spectra were recorded on
a Bruker AVANCE spectrometer operating at 400 MHz in CDCl3 using
TMS as the internal standard. Chemical shifts (δ) are given in ppm and
coupling constants (J) in Hz. High resolution mass spectra (HRMS)
were obtained on an Agilent 6210 TOF LC/MS instrument. MS spectra
were obtained on an Agilent 1260 Ion Trap LC/MS 500 analysis
system. Elemental analyses were performed on a Flash EA1112
Elemental analyser (CE, Thermo Finnigan). Progress of reaction was
monitored by thin layer chromatography (TLC). The microwave-
assisted reactions were performed in an Initiator EXPmicrowave
system (Biotage, Inc.) at the specified temperatures using the standard
mode of operation.
Anticancer assays
The anticancer activities of compounds TSC1–21 were evaluated
against human cell lines by the MTT (3-(4,5-dimethylthiazol-2-
yl)-2,5-diphenyltetrazolium bromide) method.32 MTT solution
(10.0 µL/well) in RPMI-1640 (Roswell Park Memorial Institute,
Sigma, St. Louis, MO, USA) was added after cells were treated with
the test compound for 72 h and cells were incubated for a further
3 h at 37 °C. The purple formazan crystals were dissolved in DMSO
In conclusion, we have designed and synthesised a series of
novel compounds TSC1–TSC21 and evaluated their activities

JOURNAL OF CHEMICAL RESEARCH 2016 69
150 µL. After 5 min, the plates were read on an automated microplate
spectrophotometer (Bio-Tek Instruments, Winooski, VT, USA) at
λ = 570 nm. Assays were performed in triplicate in three independent
experiments. The concentration required for 50% inhibition of
cell viability (IC50) was calculated using the software, Dose-Effect
Analysis with Microcomputers. The tumour cell line panel consisted
of human gastric (SGC-7901), lung (H446) and breast cancer (MCF-7)
cell lines. In all of these experiments, three replicate wells were used to
determine each point.
with an ice–water bath and then carbon disulfide (57.5 g, 0.75 mol)
was added dropwise over the course of 100 min. After the addition
was completed, the reaction was allowed to proceed for 2 h. Dimethyl
sulfate (94.5 g, 0.75 mol) was then added to the mixture at 15 °C and
the mixture was stirred for 1 h. The resulting precipitate was filtered
off, washed with water and dried in vacuum. The crude product was
recrystallised from methylene dichloride to give 55.0 g of compound
(4): White platelets; yield 60.1%; m.p. 81–82 °C (lit.3 81–83 °C).
Synthesis of compounds 5a–g; general procedure
Synthesis
1–2 Drops of hydrochloric acid were added to a solution of
2-phenylamino-4-methyl-5-acetyl-thiazole 3a (4.64 g, 0.02 mol) and
methyl hydrazinecarbodithioate 4 (2.928 g, 0.024 mol) in isopropanol
(60 mL). The reaction mixture was heated to reflux for 18 h (monitored
by TLC, EtOAc/toluene, 1:2). After concentration of the reaction
mixture, the crude solid was filtered off and washed with cold
isopropanol. Recrystallisation of the crude product from 95% ethanol
afforded the title compound 5a as a dark-yellow solid.
Compounds 1a–g was prepared according to the reported method.33, 34
Aminothiazoles 3a–g; general procedure
A mixture of N-arylthiourea 1a–g (0.01 mol), acetylacetone 2 (1 g, 0.01
mol), N-bromosuccinimide (1.79 g, 0.01 mol) and benzoyl peroxide
(0.12 g) in anhydrous benzene (40 mL) was heated to reflux for 6 h
(completion indicated by TLC). The solvent was evaporated and the
residue was dissolved in water and basified with 5% aqueous K2CO3 to
pH 9. The resulting precipitate was filtered off and washed thoroughly
with ethanol and water. Recrystallisation of the crude product from
ethyl acetate afforded the title compound 3a.
5-Acetyl-4-methyl-2-phenylaminothiazole (3a): Pale yellow needles;
yield 78%; m.p. 153–154 °C (EtOH) (lit.29 154–155 °C); IR (νmax cm–1):
3279 (NH), 3095 (benzene ring), 1617 (C=O); 1H NMR: δ 7.42 (t, J =
8.0 Hz, 2H, ArH), 7.34 (d, J = 8.0 Hz, 2H, ArH), 7.20 (t, J = 7.2 Hz, 1H,
ArH), 2.61 (s, 3H, CH3), 2.47 (s, 3H, CH3CO); APCI-MS: m/z (%): 232
([M + H]+, 100).
Methyl
2-{1-[4-methyl-2-(phenylamino)thiazol-5-yl]ethylidene}
hydrazinecarbodithioate (5a): Yellow powder; yield 81.9%; m.p.
179–180°C (i-PrOH); IR (υmax cm–1): 3172 (NH), 2913 (benzene ring),
1531 (C=N), 1049 (C=S); 1H NMR: δ 9.84 (bs, 1H, –NHCS–), 7.41 (t,
2H, J = 7.8 Hz, ArH), 7.33 (d, 2H, J = 7.6 Hz, ArH), 7.17 (t, 1H, J = 7.4
Hz, ArH), 2.65 (s, 3H, –SCH3), 2.58 (s, 3H, thiazole–CH3), 2.30 (s, 3H,
–N=C–CH3); APCI-MS: m/z (%): 337.0 ([M + H]+, 32). Anal. calcd
for C14H16N4S3: C, 49.97; H, 4.79; N, 16.65; found: C, 49.92; H, 4.71; N,
16.61%.
Methyl
2-{1-[4-methyl-2-(o-tolylamino)thiazol-5-yl]ethylidene}
5-Acetyl-4-methyl-2-(o-methylphenylamino)thiazole (3b): White
needles; yield 75%; m.p. 156–157 °C (EtOH) (lit.35 169–170 °C); IR
hydrazinecarbodithioate (5b): Yellow powder; yield 77.4%; m.p.
181–182 °C (i-PrOH); IR (υmax cm–1): 3154 (NH), 2914 (benzene ring),
(ν cm–1): 3167 (NH), 3060 (benzene ring), 1596 (C=O); H NMR:
1
1
δ m7.a5x 0 (d, J = 8.0 Hz, 1H, ArH), 7.32–7.27 (m, 2H, ArH), 7.20 (d, J =
7.6 Hz, 1H, ArH), 2.52 (s, 3H, CH3), 2.41 (s, 3H, CH3CO), 2.33 (s, 3H,
ArCH3); APCI-MS: m/z (%): 246 ([M + H]+, 100).
1566 (C=N), 1048 (C=S); H NMR: δ 9.85 (bs, 1H, –NHCS–), 7.53
(d, 1H, J = 7.6 Hz, ArH), 7.31–7.27 (m*, 2H, ArH), 7.17 (t, 1H, J = 7.6
Hz, ArH), 2.63 (s, 3H, –SCH3), 2.57 (s, 3H, thiazole–CH3), 2.34 (s, 3H,
–N=C–CH3), 2.27 (s, 3H, ArCH3) (*overlapped with CHCl3); APCI-
MS: m/z (%): 351.3 ([M + H]+, 100). Anal. calcd for C15H18N4S3: C,
51.40; H, 5.18; N, 15.98; found: C, 51.48; H, 5.24; N, 16.02%.
5-Acetyl-4-methyl-2-(m-methylphenylamino)thiazole (3c): Grey
white needles; yield 92%; m.p. 162–164 °C (EtOH) (lit.29 165–166 °C);
IR (νmax cm–1): 3220 (NH), 3071 (benzene ring), 1613 (C=O); 1H NMR:
δ 7.29 (t, J = 7.6 Hz, 1H, ArH), 7.14 (d, J = 8.4 Hz, 2H, ArH), 7.00 (d, J
= 7.2 Hz, 1H, ArH), 2.56 (s, 3H, CH3), 2.44 (s, 3H, CH3O), 2.38 (s, 3H,
ArCH3); APCI-MS: m/z (%): 246 ([M + H]+, 92).
5-Acetyl-4-methyl-2-(p-methylphenylamino)thiazole (3d): White
needles; yield 92%; m.p. 190–191 °C (EtOH) (lit.29 190–192 °C); IR
(νmax cm–1): 3282 (NH), 3084 (benzene ring), 1611 (C=O); 1H NMR: δ
7.23–7.06 (m, 4H, ArH), 2.59 (s, 3H, CH3), 2.45 (s, 3H, CH3CO), 2.35
(s, 3H, ArCH3); APCI-MS: m/z (%): 246 ([M + H]+, 100).
5-Acetyl-4-methyl-2-(o-chlorophenylamino)thiazole (3e): White
needles; yield 79%, m.p. 163–164 °C (EtOH) (lit.29 163–165 °C); IR
(νmax cm–1): 3236 (NH), 3001 (benzene ring), 1634 (C=O); 1H NMR: δ
7.94 (d, J = 8.0 Hz, 1H, ArH), 7.44 (d, J = 8.0 Hz, 1H, ArH), 7.34 (t, J =
8.0 Hz, 1H, ArH), 7.06 (t, J = 7.8 Hz, 1H, ArH), 2.65 (s, 3H, CH3), 2.46
(s, 3H, CH3CO); APCI-MS: m/z (%): 266 ([M + H]+, 75).
Methyl
2-{1-[4-methyl-2-(m-tolylamino)thiazol-5-yl]ethylidene}
hydrazinecarbodithioate (5c): Yellow powder; yield 43.7%; m.p.
169–170 °C (i-PrOH); IR (υmax cm–1): 3189 (NH), 2916 (benzene
1
ring), 1564 (C=N), 1047 (C=S); H NMR: δ 9.91 (bs, 1H, –NHCS–),
7.30–7.28 (m*, 1H, ArH), 7.16–7.09 (m, 2H, ArH), 6.96 (d, 1H, J =
6.8 Hz, ArH), 2.65 (s, 3H, –SCH3), 2.55 (s, 3H, thiazole–CH3), 2.38
(s, 3H, –N=C–CH3), 2.30 (s, 3H, ArCH3) (*overlapped with CHCl3);
APCI-MS: m/z (%): 351.1 ([M + H]+, 20). Anal. calcd for C15H18N4S3:
C, 51.40; H, 5.18; N, 15.98; found: C, 51.45; H, 5.21; N, 16.03%.
Methyl
2-{1-[4-methyl-2-(p-tolylamino)thiazol-5-yl]ethylidene}
hydrazinecarbodithioate (5d): Yellow powder; yield 63.6%; m.p.
177–178 °C (i-PrOH); IR (υmax cm–1): 3114 (NH), 2917 (benzene
ring), 1560 (C=N), 1048 (C=S); 1H NMR: δ 9.87 (bs, 1H, –NHCS–),
7.25–7.18 (m, 4H, ArH), 2.64 (s, 3H, –SCH3), 2.54 (s, 3H, thiazole–
CH3), 2.35 (s, 3H, –N=C–CH3), 2.28 (s, 3H, ArCH3); APCI-MS: m/z
(%): 351.1 ([M + H]+, 60). Anal. calcd for C15H18N4S3: C, 51.40; H, 5.18;
N, 15.98; found: C, 51.32; H, 5.13; N, 15.93%.
5-Acetyl-4-methyl-2-(m-chlorophenylamino)thiazole (3f): Pale
yellow needles; yield 76%, m.p. 192–193 °C (EtOH) (lit.29 m.p.
191–193 °C); IR (νmax cm–1): 3290 (NH), 3129 (benzene ring), 1615
Methyl
2-{1-[4-methyl-2-(o-chlorophenylamino)thiazol-5-yl]
1
(C=O); H NMR: δ 7.42 (s, 1H, ArH), 7.34 (t, J = 8.0 Hz, 1H, ArH),
ethylidene}hydrazinecarbodithioate (5e): Yellow powder; yield
50.7%; m.p. 173–74 °C (i-PrOH); IR (υmax cm–1): 3126 (NH), 2918
(benzene ring), 1543 (C=N), 1050 (C=S); 1H NMR: δ 9.87 (bs, 1H, –
NHCS–), 8.02 (d, 1H, J= 8.4 Hz, ArH), 7.42 (d, 1H, J= 8.4 Hz, ArH),
7.35–7.32 (t, 1H, J = 7.2 Hz, ArH), 7.05–7.01 (t, 1H, J = 7.8 Hz, ArH),
2.65 (s, 3H, –SCH3), 2.60 (s, 3H, thiazole–CH3), 2.32 (s, 3H, –N=C–
CH3); APCI-MS: m/z (%): 371.3 ([M + H]+, 100). Anal. calcd for
C14H15ClN4S3: C, 45.33; H, 4.08; N, 15.10; found: C, 45.38; H, 4.15; N,
15.16%.
7.25 (d, J = 7.8 Hz, 1H, ArH), 7.15 (d, J = 7.5 Hz, 1H, ArH), 2.62 (s, 3H,
CH3), 2.46 (s, 3H, CH3CO); APCI-MS: m/z (%): 266 ([M + H]+, 86);
HRMS (APCI) calcd for C12H11ClN2OS + H: 267.0359; found: 267.0359.
5-Acetyl-4-methyl-2-(p-chlorophenylamino)thiazole (3g): Grey
white needles; yield 65%; m.p. 193–194 °C (EtOH) (lit.29 195–197 °C);
IR (νmax cm–1): 3278 (NH), 3085 (benzene ring), 1610 (C=O); 1H NMR:
δ 7.38 (d, J = 8.8 Hz, 2H, ArH), 7.34 (d, J = 8.8 Hz, 2H, ArH), 2.62 (s,
3H, CH3), 2.46 (s, 3H, CH3CO); APCI-MS: m/z (%): 266 ([M + H]+,
90).
Methyl
2-{1-[4-methyl-2-(m-chlorophenylamino)thiazol-5-yl]
Methyl hydrazinecarbodithioate 4; general procedure
ethylidene}hydrazine carbodithioate (5f): Yellow powder; yield
34.3%; m.p. 177–178 °C (i-PrOH); IR (υmax cm–1): 3231 (NH), 2914
(benzene ring), 1554 (C=N), 1030 (C=S); 1H NMR: δ 9.84 (bs, 1H, –
NHCS–), 7.41 (s, 1H, ArH), 7.35–7.31 (t, 1H, J = 8.0 Hz, ArH), 7.23
Hydrazine hydrate (39.0 g, 0.75 mol) was added to a mixture of distilled
water (60 mL), isopropyl alcohol (50 mL) and potassium hydroxide
(49.5 g, 0.75 mol) at 20°C. The resulting mixture was cooled to 10 °C

70 JOURNAL OF CHEMICAL RESEARCH 2016
(m*, 1H, ArH), 7.12 (d, 1H, J= 7.2 Hz, ArH), 2.66 (s, 3H, –SCH3), 2.60
(s, 3H, thiazole–CH3), 2.32 (s, 3H, –N=C–CH3) (*overlapped with
CHCl3); APCI-MS: m/z (%): 371.3 ([M + H]+, 100). Anal. calcd for
C14H15ClN4S3: C, 45.33; H, 4.08; N, 15.10; found: C, 45.41; H, 4.19; N,
15.14%.
1H, NH), 7.25–7.18 (m, 4H, ArH), 3.99 (t, J = 4.6 Hz, 4H, 2OCH2), 3.69
(t, J = 4.4 Hz, 4H, 2NCH2), 2.65 (s, 3H, thiazole–CH3), 2.54 (s, 3H,
–N=C–CH3), 2.36 (s, 3H, ArCH3); APCI-MS: m/z (%): 390.2 ([M +
H]+, 38); HRMS (APCI) calcd for C18H23N5OS2 + H: 390.1422; found:
390.1429.
Methyl 2-{1-[4-methyl-2-(p-chlorophenylamino)thiazol-5-yl]ethyl-
idene}hydrazine carbodithioate (5g): Yellow powder; yield 69.1%;
m.p. 187–189 °C (i-PrOH); IR (υmax cm–1): 3175 (NH), 2925 (benzene
N’- (1-{2-[(2-Chlorophenyl) amino]-4-methylthiazol-5-yl}
ethylidene)morpholine-4-carbothiohydrazide
(TSC5):
Yellow
powder; yield 37.9%; m.p. 159–161 °C (i-PrOH); IR (υmax cm–1): 3424
(NH), 2966 (benzene ring), 1593 (C=N), 1025 (C=S); 1H NMR: δ 8.07
(bs, 1H, NH), 7.95 (d, 1H, J = 8.0 Hz, ArH), 7.46 (d, 1H, J = 7.6 Hz,
ArH), 7.30 (t, 1H, J = 8.0 Hz, ArH), 7.09 (t, 1H, J = 7.2 Hz, ArH), 4.03
(t, J = 4.8 Hz, 4H, 2OCH2), 3.73 (t, J = 4.4 Hz, 4H, 2NCH2), 2.70 (s, 3H,
thiazole–CH3), 2.68 (s, 3H, –N=C–CH3); APCI-MS: m/z (%): 410.2
([M + H]+, 45). Anal. calcd for C17H20ClN5OS2: C, 49.81; H, 4.92; N,
17.08; found: C, 49.76; H, 4.89; N, 17.04%.
1
ring), 1536 (C=N), 1045 (C=S); H NMR: δ 9.83 (bs, 1H, –NHCS–),
7.33 (dd, 4H, J1 = 8.8 Hz, J2 = 9.2 Hz, ArH), 2.65 (s, 3H, –SCH3), 2.57
(s, 3H, thiazole–CH3), 2.31 (s, 3H, –N=C–CH3); APCI-MS: m/z (%):
371.4 ([M + H]+, 100). Anal. calcd for C14H15ClN4S3: C, 45.33; H, 4.08;
N, 15.10; found: C, 45.38; H, 4.14; N, 15.13%.
Synthesis of compounds TSC1–21; general procedure
N’- (1-{2-[(3-Chlorophenyl) amino]-4-methylthiazol-5-yl}
ethylidene)morpholine-4-carbothiohydrazide (TSC6): Dark-yellow
powder; yield 55.0%; m.p. 178–180 °C (i-PrOH); IR (υmax cm–1): 3425
(NH), 2969 (benzene ring), 1597 (C=N), 1026 (C=S); 1H NMR: δ 7.64
(bs, 1H, NH), 7.48 (s, 1H, ArH), 7.30 (t, 1H, J = 8.0 Hz, ArH), 7.17 (d,
1H, J = 8.0 Hz, ArH), 7.12 (d, 1H, J = 7.6 Hz, ArH), 4.04 (t, J = 4.8 Hz,
4H, 2OCH2), 3.75 (t, J = 4.8 Hz, 4H, 2NCH2), 2.71 (s, 3H, thiazole–
CH3), 2.69 (s, 3H, –N=C–CH3); APCI-MS: m/z (%): 410.3 ([M + H]+,
35). Anal. calcd for C17H20ClN5OS2: C, 49.81; H, 4.92; N, 17.08; found:
C, 49.78; H, 4.88; N, 17.01%.
Conventional heating
Morpholine (0.957 g, 0.011 mol) was added to a stirred mixture of 5a
(3.36 g, 0.01 mol) in isopropanol (60 mL). The mixture was heated to
reflux under N2 for 24 h and TLC showed the reaction was completed.
After concentration, the residue was filtered off and washed with cold
isopropanol to give a crude product. Recrystallisation from methanol/
propan-2-ol afforded the title compound TSC1 as a light-yellow
powder.
Microwave heating
Morpholine (0.55 mmol) was added to a suspension of 5a (0.5 mmol)
and propan-2-ol (5 mL) in a 10 mL glass vial equipped with a small
magnetic stirring bar at room temperature under air. After 0.5 h
(arrested N2 bubbles), the reaction vial was sealed with an aluminium/
Teflon crimp top and stirred at 100 °C for 45 min under microwave-
irradiation. After completion of the reaction, the vial was cooled to
50 °C by air jet cooling before it was opened. The precipitated product
was collected by filtration and washed with cold propan-2-ol to give a
crude product. Recrystallisation of which from methanol/propan-2-ol
afforded the title compound TSC1 as a light-yellow powder.
N’- (1-{2-[(4-Chlorophenyl) amino]-4-methylthiazol-5-yl}
ethylidene)morpholine-4-carbothiohydrazide
(TSC7):
Yellow
powder; yield 50.4%; m.p. 173–174 °C (i-PrOH); IR (υmax cm–1): 3422
(NH), 2920 (benzene ring), 1598 (C=N), 1044 (C=S); 1H NMR: δ 7.96
(bs, 1H, NH), 7.34 (dd, J1 = 8.8 Hz, J2 = 9.2 Hz, 4H, ArH), 4.03 (t, J
= 4.6 Hz, 4H, 2OCH2), 3.73 (t, J = 4.6 Hz, 4H, 2NCH2), 2.69 (s, 3H,
thiazole–CH3), 2.66 (s, 3H, –N=C–CH3); APCI-MS: m/z (%): 410.1
([M + H]+, 47). Anal. calcd for C17H20ClN5OS2: C, 49.81; H, 4.92; N,
17.08; found: C, 49.79; H, 4.91; N, 17.03%.
N’-{1-[4-Methyl-2- (phenylamino)thiazol-5-yl]ethylidene}
piperazine-1-carbothiohydrazide (TSC8): Yellow powder; yield
70.4%; m.p. 216–217 °C (i-PrOH); IR (υmax cm–1): 3425 (NH), 2923
N’-{1-[4-Methyl-2- (phenylamino)thiazol-5-yl]ethylidene}
morpholine-4-carbothiohydrazide (TSC1): Light-yellow powder;
yield 69.3%; m.p. 176–178 °C (i-PrOH); IR (υmax cm–1): 3425 (NH),
1
(benzene ring), 1562 (C=N), 1074 (C=S); H NMR: δ 10.47 (bs, 1H,
1
2916 (benzene ring), 1562 (C=N), 1106 (C=S); H NMR: δ 7.87 (bs,
NH), 7.47–7.39 (m, 4H, ArH), 7.23 (t, 1H, J = 6 Hz, ArH), 4.15 (t, J
= 4.6 Hz, 4H, 2NCH2), 3.71 (t, J = 4.6 Hz, 4H, 2NCH2), 2.68 (s, 3H,
thiazole–CH3), 2.61 (s, 3H, –N=C–CH3); APCI-MS: m/z (%): 375.0
([M + H]+, 100); HRMS (APCI) calcd for C17H22N6S2 + H: 375.1426;
found: 375.1431.
1H, NH), 7.41–7.34 (m, 4H, ArH), 7.18 (t, 1H, J = 6 Hz, ArH), 4.01 (t,
J = 4.6 Hz, 4H, 2OCH2), 3.71 (t, J = 4.6 Hz, 4H, 2NCH2), 2.68 (s, 3H,
thiazole–CH3), 2.66 (s, 3H, –N=C–CH3); APCI-MS: m/z (%): 376.2
([M + H]+, 60); HRMS (APCI) calcd for C17H21N5OS2 + H: 376.1266;
found: 376.1272.
N’-{1-[4-Methyl-2- (o-tolylamino)thiazol-5-yl]ethylidene}
piperazine-1-carbothiohydrazide (TSC9): Yellow powder; yield
35.9%; m.p. 210–211 °C (i-PrOH); IR (υmax cm–1): 3431 (NH), 3174
N’-{1-[4-Methyl-2- (o-tolylamino)thiazol-5-yl]ethylidene}
morpholine-4-carbothiohydrazide (TSC2): Light-yellow powder;
yield 51.7%; m.p. 164–166 °C (i-PrOH); IR (υmax cm–1): 3418 (NH),
1
(benzene ring), 1555 (C=N), 1138 (C=S); H NMR: δ 10.05 (bs, 1H,
1
2914 (benzene ring), 1561 (C=N), 1113 (C=S); H NMR: δ 8.09 (bs,
NH), 7.29–7.19 (m, 4H, ArH), 4.16 (t, J = 4.8 Hz, 4H, 2NCH2), 3.90 (s,
1H, NH, pip), 3.75 (t, J = 4.8 Hz, 4H, 2NCH2), 2.68 (s, 3H, thiazole–
CH3), 2.62 (s, 3H, –N=C–CH3), 2.33 (s, 3H, ArCH3); APCI-MS: m/z
(%): 389.1 ([M + H]+, 100). Anal. calcd for C18H24N6S2: C, 55.64; H,
6.23; N, 21.63; found: C, 55.58; H, 6.19; N, 21.61%;
N’-{1-[4-Methyl-2- (m-tolylamino)thiazol-5-yl]ethylidene}
piperazine-1-carbothiohydrazide (TSC10): Light-yellow powder;
yield 55.9%; m.p. 199–200 °C (i-PrOH); IR (υmax cm–1): 3439 (NH),
2923 (benzene ring), 1563 (C=N), 1133 (C=S); 1H NMR: δ 10.11
(bs, 1H, NH), 7.49–7.36 (m, 2H, ArH), 7.30 (t, J = 7.6 Hz, 1H, ArH),
7.24–7.19 (m, 1H, ArH), 4.16 (t, J = 4.8 Hz, 4H, 2NCH2), 3.98 (s, 1H,
NH, pip), 3.75 (t, J = 4.8 Hz, 4H, 2NCH2), 2.68 (s, 3H, thiazole–CH3),
2.62 (s, 3H, –N=C–CH3), 2.33 (s, 3H, ArCH3); APCI-MS: m/z (%):
389.1 ([M + H]+, 52). Anal. calcd for C18H24N6S2: C, 55.64; H, 6.23; N,
21.63; found: C, 55.62; H, 6.21; N, 21.59%.
1H, NH), 7.49 (d, J = 7.6 Hz, 1H, ArH), 7.31–7.19 (m*, 3H, ArH), 4.00
(t, J = 4.6 Hz, 4H, 2OCH2), 3.72 (t, J = 4.6 Hz, 4H, 2NCH2), 2.65 (s,
3H, thiazole–CH3), 2.59 (s, 3H, –N=C–CH3), 2.33 (s, 3H, ArCH3)
(*overlapped with CHCl3); APCI-MS: m/z (%): 390.2 ([M + H]+, 100);
Anal. calcd for C18H23N5OS2: C, 55.50; H, 5.95; N, 17.98; found: C,
55.45; H, 5.89; N, 17.93%.
N’-{1-[4-Methyl-2- (m-tolylamino)thiazol-5-yl]ethylidene}
morpholine-4-carbothiohydrazide (TSC3): Light-yellow powder;
yield 56.6%; m.p. 157 °C (i-PrOH); IR (υmax cm–1): 3425 (NH), 2909
1
(benzene ring), 1554 (C=N), 1115 (C=S); H NMR: δ 8.07 (bs, 1H,
NH), 7.29–7.25 (m*, 1H, ArH), 7.17–7.10 (m, 2H, ArH), 7.00–6.94 (m,
1H, ArH), 4.02 (t, J = 4.6 Hz, 4H, 2OCH2), 3.69 (t, J = 4.4 Hz, 4H,
2NCH2), 2.68 (s, 3H, thiazole–CH3), 2.64 (s, 3H, –N=C–CH3), 2.38 (s,
3H, ArCH3) (*overlapped with CHCl3); APCI-MS: m/z (%): 390.2 ([M
+ H]+, 42). Anal. calcd for C18H23N5OS2: C, 55.50; H, 5.95; N, 17.98;
found: C, 55.43; H, 5.90; N, 17.91%.
N’-{1-[4-Methyl-2- (p-tolylamino)thiazol-5-yl]ethylidene}
morpholine-4-carbothiohydrazide (TSC4): Yellow powder; yield
46.9%; m.p. 177–179 °C (i-PrOH); IR (υmax cm–1): 3424 (NH), 2917
(benzene ring), 1560 (C=N), 1076 (C=S), 1049; 1H NMR: δ 8.30 (bs,
N’-{1-[4-Methyl-2- (p-tolylamino)thiazol-5-yl]ethylidene}
piperazine-1-carbothiohydrazide (TSC11): Yellow powder; yield
56.1%; m.p. 236–237 °C (i-PrOH); IR (υmax cm–1): 3440 (NH), 2918
1
(benzene ring), 1555 (C=N), 1126 (C=S); H NMR: δ 10.17 (bs, 1H,
NH), 7.48 (d, J = 8.4 Hz, 2H, ArH), 7.13 (d, J = 8.0 Hz, 2H, ArH), 4.37
(t, J = 4.8 Hz, 4H, 2NCH2), 4.11 (s, 1H, NH, pip), 3.61 (t, J = 4.8 Hz,

JOURNAL OF CHEMICAL RESEARCH 2016 71
4H, 2NCH2), 2.65 (s, 3H, thiazole–CH3), 2.61 (s, 3H, –N=C–CH3),
2.32 (s, 3H, ArCH3); APCI-MS: m/z (%): 389.3 ([M + H]+, 41); HRMS
(APCI) calcd for C18H24N6S2 + H: 389.1582; found: 389.1585.
ArH), 7.08 (d, J = 8.0 Hz, 1H, ArH), 7.94 (d, J = 8.8 Hz, 2H, ArH), 6.85
(d, J = 6.8 Hz, 2H, ArH), 4.36 (t, J = 4.4 Hz, 4H, 2NCH2), 3.71 (s, 3H,
OCH3), 3.47 (t, J = 5.2 Hz, 4H, 2NCH2), 2.71 (s, 3H, thiazole–CH3),
2.65 (s, 3H, –N=C–CH3), 2.46 (s, 3H, ArCH3); APCI-MS: m/z (%):
495.1 ([M + H]+, 35). Anal. calcd for C25H30N6OS2: C, 60.70; H, 6.11; N,
16.99; found: C, 60.69; H, 6.09; N, 16.97%.
N’- (1-{2-[(2-Chlorophenyl) amino]-4-methylthiazol-5-yl}
ethylidene)-4-(4-methoxyphenyl)piperazine-1-carbothiohydrazide
(TSC19): Yellow powder; yield 39.2%; m.p. 161–162 °C (i-PrOH);
IR (υmax cm–1): 3440 (NH), 2920 (benzene ring), 1585 (C=N), 1027
(C=S); 1H NMR: δ 9.91 (bs, 1H, NH), 7.89 (d, 1H, J = 8.0 Hz, ArH),
7.59 (d, 1H, J = 7.6 Hz, ArH), 7.48 (t, 1H, J = 6.4 Hz, ArH), 7.09 (t,
1H, J = 7.2 Hz, ArH), 6.97–6.84 (m, 4H, ArH), 4.36 (t, J = 4.8 Hz, 4H,
2NCH2), 3.70 (s, 3H, OCH3), 3.45 (t, J = 6.0 Hz, 4H, 2NCH2), 2.70 (s,
3H, thiazole–CH3), 2.63 (s, 3H, –N=C–CH3); APCI-MS: m/z (%):
515.3 ([M + H]+, 60). Anal. calcd for C24H27ClN6OS2: C, 55.96; H, 5.28;
N, 16.32; found: C, 55.91; H, 5.22; N, 16.31%.
N’- (1-{2-[(2-Chlorophenyl) amino]-4-methylthiazol-5-y})
ethylidene)piperazine-1-carbothiohydrazide (TSC12): Light-yellow
powder; yield 56.7%; m.p. 200–201 °C (i-PrOH); IR (υmax cm–1): 3444
1
(NH), 3167 (benzene ring), 1586 (C=N), 1140 (C=S); H NMR: δ
10.24 (bs, 1H, NH), 7.85 (d, 1H, J = 8.0 Hz, ArH), 7.58 (d, J = 7.6 Hz,
1H, ArH), 7.46 (t, 1H, J = 6.4 Hz, ArH), 7.09 (t, 1H, J = 7.2 Hz, ArH),
4.37 (t, J = 4.8 Hz, 4H, 2NCH2), 4.03 (s, 1H, NH, pip), 3.61 (t, J = 4.8
Hz, 4H, 2NCH2), 2.70 (s, 3H, thiazole–CH3), 2.65 (s, 3H, –N=C–CH3);
APCI-MS: m/z (%): 409.5 ([M + H]+, 58); HRMS (APCI) calcd for
C17H21ClN6S2 + H: 409.1036; found: 409.1046.
N’- (1-{2-[(3-Chlorophenyl) amino]-4-methylthiazol-5-yl}
ethylidene)piperazine-1-carbothiohydrazide (TSC13): Light-yellow
powder; yield 59.3%; m.p. 201–202 °C (i-PrOH); IR (υmax cm–1): 3424
1
(NH), 2923 (benzene ring), 1596 (C=N), 1097 (C=S); H NMR: δ
10.24 (bs, 1H, NH), 7.61 (s, 1H, ArH), 7.43–7.32 (m, 3H, ArH), 4.35 (t,
J = 4.8 Hz, 4H, 2NCH2), 4.07 (s, 1H, NH, pip), 3.62 (t, J = 4.8 Hz, 4H,
2NCH2), 2.69 (s, 3H, thiazole–CH3), 2.63 (s, 3H, –N=C–CH3); APCI-
MS: m/z (%): 409.2 ([M + H]+, 100). Anal. calcd for C17H21ClN6S2: C,
49.93; H, 5.18; N, 20.55; found: C, 49.91; H, 5.17; N, 20.52%.
N’- (1-{2-[(3-Chlorophenyl) amino]-4-methylthiazol-5-yl}
ethylidene)-4-(4-methoxyphenyl)piperazine-1-carbothiohydrazide
(TSC20): Yellow powder; yield 41.3%; m.p. 163–165 °C (i-PrOH);
IR (υmax cm–1): 3441 (NH), 2921 (benzene ring), 1595 (C=N), 1044
1
(C=S); H NMR: δ 9.96 (bs, 1H, NH), 7.86 (t, 1H, J = 8.0 Hz, ArH),
N’- (1-{2-[(4-Chlorophenyl) amino]-4-methylthiazol-5-yl}
ethylidene)piperazine-1-carbothiohydrazide (TSC14): Light-yellow
powder; yield 73.1%; m.p. 226–227 °C (i-PrOH); IR (υmax cm–1): 3429
7.52–7.30 (m, 2H, ArH), 7.00 (d, 1H, J = 8.0 Hz, ArH), 6.94 (d, 2H,
J = 8.8 Hz, ArH), 6.85 (d, 2H, J = 8.4 Hz, ArH), 4.36 (t, J = 4.8 Hz,
4H, 2NCH2), 3.70 (s, 3H, OCH3), 3.45 (t, J = 6.0 Hz, 4H, 2NCH2), 2.74
(s, 3H, thiazole–CH3), 2.70 (s, 3H, –N=C–CH3); APCI-MS: m/z (%):
515.1 ([M + H]+, 86); HRMS (APCI) calcd for C24H27ClN6OS2+ H:
515.1455; found: 515.1463.
1
(NH), 2922 (benzene ring), 1554 (C=N), 1091 (C=S); H NMR: δ
10.52 (bs, 1H, NH), 7.67 (d, J = 8.8 Hz, 2H, ArH), 7.38 (d, J = 8.8 Hz,
2H, ArH), 4.37 (t, J = 4.8 Hz, 4H, 2NCH2), 3.93 (s, 1H, NH, pip), 3.61
(t, J = 4.8 Hz, 4H, 2NCH2), 2.70 (s, 3H, thiazole–CH3), 2.65 (s, 3H, –
N=C–CH3); APCI-MS: m/z (%): 409.1 ([M + H]+, 52). Anal. calcd for
C17H21ClN6S2: C, 49.93; H, 5.18; N, 20.55; found: C, 49.85; H, 5.13; N,
20.53%.
N’- (1-{2-[(4-Chlorophenyl) amino]-4-methylthiazol-5-yl}
ethylidene)-4-(4-methoxyphenyl)piperazine-1-carbothiohydrazide
(TSC21): Yellow powder; yield 36.3%; m.p. 178–180 °C (i-PrOH);
IR (υmax cm–1): 3440 (NH), 2922 (benzene ring), 1552 (C=N), 1026
N’-{1-[4-Methyl-2-(phenylamino)thiazol-5-yl]ethylidene}-4-(4-
methoxyphenyl)piperazine-1-carbothiohydrazide (TSC15): Yellow
powder; yield 50.7%; m.p. 170–171 °C (i-PrOH); IR (υmax cm–1): 3440
1
(C=S); H NMR: δ 9.94 (bs, 1H, NH), 7.66 (dd, J1 = 8.8 Hz, J2 = 8.8
Hz, 2H, ArH), 7.43 (d, J = 8.8 Hz, 1H, ArH), 7.34 (d, J = 8.4 Hz, 1H,
ArH), 6.94 (d, J = 8.8 Hz, 2H, ArH), 6.85 (d, J = 9.2 Hz, 2H, ArH), 4.36
(t, J = 4.8 Hz, 4H, 2NCH2), 3.70 (s, 3H, OCH3), 3.73 (t, J = 6.0 Hz, 4H,
2NCH2), 2.73 (s, 3H, thiazole–CH3), 2.68 (s, 3H, –N=C–CH3); APCI-
MS: m/z (%): 515.5 ([M + H]+, 72). Anal. calcd for C24H27ClN6OS2: C,
55.96; H, 5.28; N, 16.32; found: C, 56.01; H, 5.32; N, 16.35%.
1
(NH), 2924 (benzene ring), 1600 (C=N), 1080 (C=S); H NMR: δ
9.92 (bs, 1H, NH), 7.63–7.62 (m, 4H, ArH), 7.33 (t, 3H, J = 6 Hz, ArH),
7.01–6.86 (m, 2H, ArH), 4.36 (t, J = 5.2 Hz, 4H, 2NCH2), 3.70 (s, 3H,
OCH3), 3.45 (t, J = 6.2 Hz, 4H, 2NCH2), 2.49 (s, 3H, thiazole–CH3),
2.38 (s, 3H, –N=C–CH3); APCI-MS: m/z (%): 481.3 ([M + H]+, 41);
HRMS (APCI) calcd for C24H28N6OS2+ H: 481.1844; found: 481.1852.
N’-{1-[2-(o-tolylamino)-4-methylthiazol-5-yl]ethylidene}-4-(4-
methoxyphenyl)piperazine-1-carbothiohydrazide (TSC16): Yellow
powder; yield 41.5%; m.p. 166–167 °C (i-PrOH); IR (υmax cm–1): 3445
(NH), 2922 (benzene ring), 1595 (C=N), 1044 (C=S); 1H NMR: δ 9.58
(bs, 1H, NH), 7.49 (d, J = 8.4 Hz, 2H, ArH), 7.26–7.20 (m*, 4H, ArH),
7.08 (t, J = 7.6 Hz, 2H, ArH), 4.36 (t, J = 5.0 Hz, 4H, 2NCH2), 3.71
(s, 3H, OCH3), 3.45 (t, J = 6.0 Hz, 4H, 2NCH2), 2.68 (s, 3H, thiazole–
CH3), 2.62 (s, 3H, –N=C–CH3), 2.34 (s, 3H, ArCH3) (*overlapped
with CHCl3); APCI-MS: m/z (%): 495.4 ([M + H]+, 34). Anal. calcd
for C25H30N6OS2: C, 60.70; H, 6.11; N, 16.99; found: C, 60.61; H, 6.05;
N, 16.97%.
N’-{1-[2-(m-Tolylamino)-4-methylthiazol-5-yl]ethylidene}-4-(4-
methoxyphenyl)piperazine-1-carbothiohydrazide (TSC17): Yellow
powder; yield 55.3%; m.p. 184–185 °C (i-PrOH); IR (υmax cm–1): 3444
(NH), 2920 (benzene ring), 1565 (C=N), 1024 (C=S); 1H NMR: δ 9.91
(bs, 1H, NH), 7.47–7.34 (m, 2H, ArH), 7.27 (t, J = 7.8 Hz, 1H, ArH),
7.22–7.17 (m, 1H, ArH), 6.94–6.79 (m, 4H, ArH), 4.36 (t, J = 4.8 Hz,
4H, 2NCH2), 3.70 (s, 3H, OCH3), 3.47 (t, J = 5.2 Hz, 4H, 2NCH2),
2.68 (s, 3H, thiazole–CH3), 2.63 (s, 3H, –N=C–CH3), 2.32 (s, 3H,
ArCH3); APCI-MS: m/z (%): 495.3 ([M + H]+, 40). Anal. calcd for
C25H30N6OS2: C, 60.70; H, 6.11; N, 16.99; found: C, 60.65; H, 6.09; N,
16.96%.
We thank the Natural Science Foundation of Ningbo City (grant
No. 2014A610210) for financial support and the Nantong Centre
for Disease Control and Prevention, Jiangsu, P.R. China for
drug screening.
Received 17 November 2015; accepted 15 December 2015
Paper 1503720 doi: 10.3184/174751916X14519928918516
Published online 27 January 2016
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