Synthesis and biological activities of thio-triazole derivatives as novel potential antibacterial and antifungal agents

Article abstract of DOI:10.1007/s11426-012-4602-1

A series of novel thio-triazole derivatives including thiols, thioethers and thiones as well as some corresponding triazolium compounds were conveniently and efficiently synthesized from commercially available halobenzyl halides and thiosemicarbazide. All the new compounds were characterized by 1H NMR, 13C NMR, FTIR, MS and HRMS spectra. Their antibacterial and antifungal activities in vitro were evaluated against four Gram-positive bacteria, four Gram-negative bacteria and two fungi by two-fold serial dilution technique. The preliminary bioassay indicated that some prepared triazoles exhibited effective antibacterial and antifungal activities. Especially, 3,4-dichlorobenzyl triazole-thione and its triazolium derivatives displayed the most potent activities against all the tested strains. Science China Press and Springer-Verlag Berlin Heidelberg 2012.

Full text of DOI:10.1007/s11426-012-4602-1

SCIENCE CHINA
Chemistry
October 2012 Vol.55 No.10: 2134–2153
doi: 10.1007/s11426-012-4602-1
• ARTICLES •
Synthesis and biological activities of thio-triazole derivatives as
novel potential antibacterial and antifungal agents
WANG QingPeng1, ZHANG JingQing2, DAMU Guri L. V.1†, WAN Kun1,
ZHANG HuiZhen1 & ZHOU ChengHe1*
1School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China
2Chongqing Key Laboratory of Biochemical & Molecular Pharmacology, Medicine Engineering Research Center, Chongqing Medical
University, Chongqing 400016, China
Received November 27, 2011; accepted January 9, 2012; published online May 30, 2012
A series of novel thio-triazole derivatives including thiols, thioethers and thiones as well as some corresponding triazolium
compounds were conveniently and efficiently synthesized from commercially available halobenzyl halides and thiosemicarba-
zide. All the new compounds were characterized by 1H NMR, 13C NMR, FTIR, MS and HRMS spectra. Their antibacterial and
antifungal activities in vitro were evaluated against four Gram-positive bacteria, four Gram-negative bacteria and two fungi by
two-fold serial dilution technique. The preliminary bioassay indicated that some prepared triazoles exhibited effective antibac-
terial and antifungal activities. Especially, 3,4-dichlorobenzyl triazole-thione and its triazolium derivatives displayed the most
potent activities against all the tested strains.
triazole, triazolium, antibacterial, antifungal, cyclization
antibacterial agents was relatively rare. In recent years,
1 Introduction
some novel 1,2,4-triazoles have been reported to demon-
strate remarkable antibacterial properties, especially against
Methicillin-Resistant Staphylococcus aureus [13, 15–17]. It
is well known that the increasing amount of multi-drug re-
sistant microorganisms has become serious threatens to
human health [18, 19], especially the very recent outbreaks
of New Delhi metallo-β-lactamase 1 (NDM-1) superbugs
[20] and enterohemorrhage Escherichia coli (EHEC)
O104:H4 [21], which have resulted in weak efficacy for
most of the first-line clinical antibiotics in the treatment of
infectious diseases. Therefore, development of more effec-
tive triazole agents with broader antimicrobial spectrum in
antibacterial and antifungal fields which are possibly help-
ful in overcoming drug-resistance has become an interesting
topic for researchers [1, 22].
Triazole compounds have been attracting considerable at-
tention due to their wide potential [1, 2] in the treatment of
various diseases as antibacterial [3, 4], antifungal [5, 6],
anti-tubercular [7, 8], anti-cancer [9, 10], anti-inflammatory
[11], anti-convulsant [12] and other medicinal drugs. Nu-
merous efforts have been directed toward the development
of 1,2,4-triazole derivatives as antifungal agents due to their
low toxicity, favorable safety profile and beneficial phar-
macokinetic characteristics. A large amount of excellent
triazole-based drugs, like Fluconazole and Itraconazole
which were proved to target on P450-dependent sterol
14a-demethylase [13, 14], have been successfully marketed
and widely used in clinics. In contrast to the well developed
triazoles as antifungal agents, the exploration of triazoles as
A large amount of literature has manifested that structur-
al modification of the triazole ring with various substituents
represents a practical strategy to explore new types of bio-
*Corresponding author (email: zhouch@swu.edu.cn)
†Postdoctoral fellow from Indian Institute of Chemical Technology (IICT), India
© Science China Press and Springer-Verlag Berlin Heidelberg 2012
chem.scichina.com www.springerlink.com

Wang QP, et al. Sci China Chem October (2012) Vol.55 No.10
2135
active agents that could affect the interactions of triazoles
with cells and tissues, thereby improving the biological ef-
fects [23–25]. In our previous work, halobenzyloxy and
alkoxy groups were introduced into the 1,2,4-triazole ring to
successfully improve bioactivities and broaden the antimi-
crobial spectrum [26]. As an extension of our study on nov-
el potent bioactive compounds, it is of our great interest to
incorporate thio-containing groups into the triazole ring
replacing the oxyl moiety to investigate how these new
1,2,4-triazole derivatives affect the antimicrobial efficacy.
Many researches have revealed that introduction of the
sulfur atom into the triazole ring could effectively enhance
the bioactivities of target compounds [27, 28]. The presence
of the sulfur moiety as an electron-rich center is able to im-
prove lipophilicity and modulate electron density of the
triazole ring, thereby influencing its transmembrane diffu-
sion ability to the anticipant targets, as well as its interaction
with hydrogen bond donors of the organism [29, 30]. As a
result, investigation of 1,2,4-triazole-3-thiol and its deriva-
tives as potential antimicrobial candidates [31, 32], which
can be easily prepared by diverse methods, has become in-
creasingly attractive. Furthermore, the mercapto group of
triazoles as a nucleophilic center could conveniently react
with electrophiles to produce corresponding triazole-
thioethers [33, 34] and thione derivatives [35]. Moreover,
modification of diverse triazole-thiols was demonstrated as
a good treasure to increase antimicrobial activities and ex-
tend their biological spectrum [36, 37]. Recently, a great
number of triazole-thioether and triazole-thione compounds
have been reported to demonstrate efficient antibacterial
and antifungal activities [38, 39].
of the aliphatic chain and aromatic substituents remarkably
affected antimicrobial potency [26]. Therefore, a series of
alkyl and halobenzyl triazoles were synthesized.
(4) Aromatic 1,2,4-triazole ring could exert multiple
non-covalent interactions such as hydrogen bond, -
stacking, ion-dipole, coordination bond, hydrophobic effect
and van der Waals force with biological molecules and
modulate physicochemical properties, thereby improving
and broadening biological activities [47, 48]. Herein, a se-
cond triazole moiety was introduced into the target com-
pounds through different linkers to prepare a series of
bis-triazole compounds.
(5) Triazolium ring with a permanent positive charge on
the triazole ring has been reported to affect the diffusion and
interaction with biological tissues which could result in the
enhancement of antimicrobial abilities [49]. Thereby, a se-
ries of triazolium derivatives were prepared to examine their
effects on antimicrobial activities.
(6) Coumarin ring, with the benzopyrone skeleton struc-
turally similar to the benzopyridone backbone of antibacte-
rial drug quinolones, has received specific interests in me-
dicinal chemistry as a new type of potential antibiotics. So
far an increasing number of coumarin derivatives have been
reported to exhibit good antimicrobial competence [50].
Therefore, the coumarin moiety was introduced into the
triazoles to survey its contribution to antimicrobial activi-
ties.
All the structures of the synthesized triazole-thiol 2, thi-
oethers and thiones 3–8 and triazoliums 9–11 are shown in
Scheme 1.
Inspired by these observations and in continuation of our
ongoing interests in the development of new antimicrobial
agents [40, 41], herein a series of novel triazole-thiols, thi-
oethers and thiones as well as some triazoliums were de-
signed and synthesized. Their antibacterial and antifungal
activities were evaluated, and some important effect factors
on antimicrobial activities were also investigated. The target
molecular structures were designed based on the following
considerations:
(1) Halobenzyl and thiol moieties on the triazole ring
were helpful in enhancing the bioactivities by improving
lipid solubility which might result in the enhancement of the
penetration of the agents into cells [42–44]. To this end, the
3,4-dichlorobenzyl, 2,4-difluorobenzyl, and thiol moieties
were introduced into the triazole ring to yield halobenzyl
triazole-thiol 2.
(2) It was confirmed that thioethers and thiones could ef-
fectively increase the biological activities and broaden an-
timicrobial spectrum in a large number of reported litera-
tures [45, 46]. In order to investigate the effects of the thiol
substituent in the triazole ring on antibacterial and antifun-
gal activities, some new thioethers and thiones were pre-
pared.
2 Experimental
2.1 Materials and measurements
Melting points were recorded on X-6 melting point appa-
ratus and were uncorrected. TLC analysis was done using
pre-coated silica gel plates. FT-IR spectra were carried out
on a Bruker RFS100/S spectrophotometer (Bio-Rad, Cam-
bridge, MA, USA) using KBr pellets in the 400–4000 cm–1
range. NMR spectra were recorded on a Bruker AV 300
spectrometer using TMS as an internal standard; Ph = phe-
nyl ring and Ar = aromatic ring. The chemical shifts were
reported in parts per million (ppm), the coupling constants
(J) are expressed in hertz (Hz) and singlet (s), doublet (d)
and triplet (t) as well as multiplet (m). The mass spectra
(MS) were recorded on LCMS-2010A and the high-resolu-
tion mass spectra (HRMS) were recorded on an IonSpec
FT-ICR mass spectrometer with ESI resource. All chemi-
cals and solvents were commercially available, and used
without further purification.
2.2 Synthesis
1-(3,4-Dichlorobenzyl)-1H-1,2,4-triazole-3-thiol (2a)
(3) Our previous investigation evidenced that alteration
To a stirred mixture of thiosemicarbazide (11.01 g, 0.12

2136
Wang QP, et al. Sci China Chem October (2012) Vol.55 No.10
mol) in ethanol (30 mL), 3,4-dichlorobenzyl chloride (21.62
g, 0.11 mol) was added dropwise at 40 °C. Upon comple-
tion of the reaction (monitored by TLC, eluent, chloro-
form/methanol, 30/1, v/v), the solvent was evaporated under
vacuum to give the crude 1-halobenzyl thiosemicarbazide as
a white solid. Subsequently, this solid was dissolved in dis-
tilled water (30 mL) with stirring at 60 °C, followed by ad-
dition of formic acid (6.82 g, 0.15 mol) and concentrated
sulfuric acid (0.5 mL). The reaction temperature was raised
to 100 °C for 12 h until the reaction completed (monitored
by TLC, eluent, chloroform/methanol, 30/1, v/v). The re-
sulting solution was quenched with saturated sodium bicar-
bonate and extracted with chloroform (3 × 50 mL). The
organic phase was dried over anhydrous sodium sulfate and
concentrated. The residue was purified via silica gel column
chromatography (eluent, chloroform/methanol, 30/1, v/v) to
give compound 2a (23.01 g) as a white solid. Yield: 82.3%;
mp 86–89 °C; IR (KBr) ν: 3114, 3061 (Ar–H), 2915, 2848
(CH2), 2668 (SH), 1609, 1572, 1513, 1468 (aromatic frame),
1123, 1077, 1032, 1000, 907, 883, 820, 714 cm–1; 1H NMR
(300 MHz, CDCl3) δ: 8.15 (s, 1H, S-triazole H), 7.46–7.31
(m, 2H, 3,4-Cl2Ph 2,5-H), 6.20–6.17 (m, 1H, 3,4-Cl2Ph
6-H), 4.30 (s, 2H, 3,4-Cl2Ph-CH2) ppm; 13C NMR (75 MHz,
CDCl3) δ: 156.6 (S-triazole S-C), 146.6 (S-triazole 5-C),
137.4 (3,4-Cl2Ph 1-C), 132.4 (3,4-Cl2Ph 3-C), 131.6
(3,4-Cl2Ph 4-C), 130.7 (3,4-Cl2Ph 2-C), 130.4 (3,4-Cl2Ph
5-C), 128.2 (3,4-Cl2Ph 6-C), 37.8 (CH2) ppm; ESI-MS (m/z):
261 [M+H]+; HRMS (ESI) calcd. for C9H7Cl2N3S [M+H]+,
259.9816; found, 259.9819.
min, and then 1-bromooctane (0.46 g, 2.4 mmol) was added.
After the reaction completed in about 12 h (monitored by
TLC, eluent, chloroform/petroleum ether, 3/1, v/v), the sol-
vent was evaporated under vacuum and the residue was
treated with water (50 mL) and extracted with chloroform
(3 × 50 mL). The organic layers were combined, dried over
anhydrous sodium sulfate, and concentrated. The crude
product was purified via silica gel column chromatography
(eluent, chloroform/petroleum ether, 1/1, v/v) to afford
compound 3a (0.35 g) as a helvolus oil. Yield: 47.1%; IR
(KBr) ν: 3116 (Ar–H), 2927, 2858 (CH2), 1601, 1502, 1468
(aromatic frame), 1358, 1181, 1134, 1029, 890, 722
1
(CSC) cm–1; H NMR (300 MHz, CDCl3) δ: 7.89 (s, 1H,
S-triazole H), 7.45 (s, 1H, 3,4Cl2Ph 2-H), 7.34–7.15 (m,
2H, 3,4-Cl2Ph 5,6-H), 4.36 (s, 2H, 3,4-Cl2Ph-CH2), 3.97 (t,
2H, J = 7.5 Hz, CH3(CH2)6CH2), 1.73–1.71 (m, 2H,
CH3(CH2)5CH2), 1.30–1.20 (m, 10H, CH3(CH2)5), 0.88 (t,
3H, J = 6.0 Hz, CH3) ppm; 13C NMR (75 MHz, CDCl3) δ:
152.6 (S-triazole S-C), 144.5 (S-triazole 5-C), 137.1
(3,4-Cl2Ph 1-C), 132.8 (3,4-Cl2Ph 3-C), 131.6 (3,4-Cl2Ph
4-C), 130.6 (3,4-Cl2Ph 2-C), 130.4 (3,4-Cl2Ph 5-C), 128.1
(3,4-Cl2Ph 6-C), 46.1, 34.3, 30.2, 29.6, 29.3, 29.1, 26.5,
23.2 (CH2), 14.4 (CH3) ppm; ESI-MS (m/z): 373 [M+H]+;
HRMS (ESI) calcd. for C17H23Cl2N3S [M+H]+, 372.1068;
found, 372.1072.
1-(3,4-Dichlorobenzyl)-3-(3,4-dichlorobenzylthio)-1H-1,2,4-
triazole (3b)
Compound 3b was synthesized employing a procedure
similar to that used to synthesize compound 3a, starting
from compound 2a (0.52 g, 2.0 mmol), 1,2-dichloro-4-
(chloromethyl)benzene (0.47 g, 2.4 mmol) and potassium
carbonate (0.33 g, 2.4 mmol). The crude product was ob-
tained and purified via silica gel column chromatography
(eluent, chloroform/petroleum ether, 1/1, v/v) to give pure
compound 3b (0.32 g) as a yellow oil. Yield: 38.3%; IR
(KBr) ν: 3087, 3059 (ArH), 2933 (CH2), 1612, 1491, 1446
(aromatic frame), 1356, 1134, 1061, 1030, 883, 819, 764,
1-(2,4-Difluorobenzyl)-1H-1,2,4-triazole-3-thiol (2b)
Compound 2b was prepared employing a procedure similar
to that used to synthesize compound 2a, starting from
thiosemicarbazide (10.10 g, 0.11 mol), 2,4-difluorobenzyl
bromide (21.01 g, 0.10 mol) and formic acid (9.21 g, 0.21
mol). The pure product 2b (17.82 g) was obtained as a
white solid. Yield: 72.9%; mp 128–129 ºC; IR (KBr) ν:
3113, 3077 (Ar–H), 2998, 2775 (CH2), 2709 (SH), 1602,
1584, 1503, 1458 (aromatic frame), 1381, 1139, 1065, 1027,
1
710 (C–S–C) cm–1; H NMR (300 MHz, CDCl3) δ: 7.93 (s,
1
995, 865, 834, 777, 720 cm–1; H NMR (300 MHz, CDCl3)
1H, S-triazole H), 7.41–7.32 (m, 4H, 3,4-Cl2Ph 2,5-H),
7.15–6.94 (m, 2H, 3,4-Cl2Ph 6-H), 5.13 (s, 2H, S-CH2),
4.36 (s, 2H, 3,4-Cl2Ph-CH2-triazole) ppm; 13C NMR (75
MHz, CDCl3) δ: 152.7 (S-triazole S-C), 146.1 (S-triazole
5-C), 137.8 (2C, 3,4-Cl2Ph 1-C), 131.5 (2C, 3,4-Cl2Ph 3-C),
130.9 (2C, 3,4-Cl2Ph 4-C), 130.5 (2C, 3,4-Cl2Ph 2-C),
130.2 (2C, 3,4-Cl2Ph 5-C), 127.3 (2C, 3,4-Cl2Ph 6-C), 45.6,
35.9 (CH2) ppm; ESI-MS (m/z): 420 [M+H]+; HRMS (ESI)
calcd. for C16H11Cl4N3S [M+H]+, 417.9506; found,
417.9520.
δ: 8.16 (s, 1H, S-triazole H), 7.39–7.26 (m, 1H, 2,4-F2Ph
6-H), 6.82–6.76 (m, 2H, 2,4-F2Ph 3,5-H), 4.37 (s, 2H,
2,4-F2Ph-CH2) ppm; 13C NMR (75 MHz, CDCl3) δ: 164.1,
163.9 (2,4-F2Ph 2-C), 160.5, 160.1 (2,4-F2Ph 4-C), 152.7
(S-triazole S-C), 145.6 (S-triazole 5-C), 130.5 (2,4-F2Ph
6-C), 117.9, 117.7 (2,4-F2Ph 1-C), 110.4, 110.2 (2,4-F2Ph
5-C), 104.1, 103.7 (2,4-F2Ph 3-C), 36.7 (CH2) ppm;
ESI-MS (m/z): 228 [M+H]+; HRMS (ESI) calcd. for
C9H7F2N3S [M+H]+, 228.0407; found, 228.0409.
1-(3,4-Dichlorobenzyl)-3-(octylthio)-1H-1,2,4-triazole (3a)
1-(3,4-Dichlorobenzyl)-3-(2,4-difluorobenzylthio)-1H-1,2,4-
triazole (3c)
A mixture of compound 2a (0.52 g, 2.0 mmol), potassium
carbonate (0.33 g, 2.4 mmol), and tetrabutylammonium
iodide (5 mg) in acetone (10 mL) was stirred at 40 °C for 20
Compound 3c was prepared employing a procedure simi-
lar to that used to synthesize compound 3a, starting from

Wang QP, et al. Sci China Chem October (2012) Vol.55 No.10
2137
compound 2a (0.52 g, 2.0 mmol), 1-(bromomethyl)-
2,4-difluorobenzene (0.49 g, 2.4 mmol) and potassium car-
bonate (0.33 g, 2.4 mmol). The desired pure compound 3c
(0.15 g) was obtained as a yellow oil. Yield: 20.0%; IR
(KBr) ν: 3078 (ArH), 2936, 2857 (CH2), 1613, 1581, 1507,
1441 (aromatic frame), 1179, 1135, 1094, 969, 853, 780,
728 (CSC) cm–1; 1H NMR (300 MHz, CDCl3) δ: 7.94 (s,
1H, S-triazole H), 7.40–7.33 (m, 3H, 3,4-Cl2Ph 2,5-H,
2,4-F2Ph 6-H), 7.21–6.97 (m, 3H, 3,4-Cl2Ph 6-H, 2,4-F2Ph
3,5-H), 5.18 (s, 2H, S-CH2), 4.36 (s, 2H, 2,4-F2Ph-CH2)
ppm; 13C NMR (75 MHz, CDCl3) δ: 164.7, 164.5 (2,4-F2Ph
2-C), 161.9, 158.6 (2,4-F2Ph 4-C), 153.7 (S-triazole S-C),
151.9 (S-triazole 5-C), 137.0 (3,4-Cl2Ph 1-C), 131.9
(3,4-Cl2Ph 3-C), 131.5, 131.4 (2,4-F2Ph 6-C), 130.9
(3,4-Cl2Ph 4-C), 130.8 (3,4-Cl2Ph 2-C), 130.5 (3,4-Cl2Ph
5-C), 128.3 (3,4-Cl2Ph 1-C), 118.1 (2,4-F2Ph 1-C), 112.0,
111.7 (2,4-F2Ph 5-C), 104.5, 104.1, 103.8 (2,4-F2Ph 3-C),
45.3, 38.6 (CH2) ppm; ESI-MS (m/z): 387 [M+H]+; HRMS
(ESI) calcd. for C16H11Cl2F2N3S [M+H]+, 386.0097; found,
386.0099.
2,4-F2Ph 6-H), 7.32–7.23 (m, 2H, 3,4-Cl2Ph 2,5-H),
7.00–6.98 (m, 1H, 3,4-Cl2Ph 6-H), 6.83–6.74 (m, 2H,
2,4-F2Ph 3,5-H), 5.12 (s, 2H, S-CH2), 4.41 (s, 2H,
3,4-Cl2Ph-CH2) ppm; 13C NMR (75 MHz, CDCl3) δ: 164.4,
163.7 (2,4-F2Ph 2-C), 160.8, 160.2 (2,4-F2Ph 4-C), 152.4
(S-triazole S-C), 148.2 (S-triazole 5-C), 137.1 (3,4-Cl2Ph
1-C), 132.2 (3,4-Cl2Ph 3-C), 131.3 (2,4-F2Ph 6-C), 130.8
(3,4-Cl2Ph 4-C), 130.7 (3,4-Cl2Ph 2-C), 130.3 (3,4-Cl2Ph
5-C), 128.2 (3,4-Cl2Ph 6-C), 117.9 (2,4-F2Ph 1-C), 111.5,
111.3 (2,4-F2Ph 5-C), 104.4, 104.0 (2,4-F2Ph 3-C), 48.3,
36.5 (CH2) ppm; ESI-MS (m/z): 386 [M]+; HRMS (ESI)
calcd. for C16H11Cl2F2N3S [M+H]+, 386.0097; found,
386.0092.
1-(2,4-Difluorobenzyl)-3-(2,4-difluorobenzylthio)-1H-1,2,4-
triazole (3f)
Compound 3f was prepared employing a procedure similar
to that used to synthesize compound 3a, starting from com-
pound 2b (0.45 g, 2.0 mmol), 1-(bromomethyl)-2,4-
difluorobenzene (0.49 g, 2.4 mmol) and potassium car-
bonate (0.33 g, 2.4 mmol). The pure product 3f (0.25 g) was
obtained as a yellow oil. Yield: 35.1%; IR (KBr) ν: 3107,
3081 (ArH), 2933, 2857 (CH2), 1613, 1504, 1430 (aro-
matic frame), 1361, 1183, 1138, 1093, 969, 852, 723
1-(2,4-Difluorobenzyl)-3-(octylthio)-1H-1,2,4-triazole (3d)
Compound 3d was prepared employing a procedure similar
to that used to synthesize compound 3a, starting from com-
pound 2b (0.45 g, 2.0 mmol), 1-bromooctane (0.46 g, 2.4
mmol) and potassium carbonate (0.33 g, 2.4 mmol). The
pure product 3d (0.26 g) was obtained as a yellow oil. Yield:
38.2%; IR (KBr) ν: 3121, 3078 (ArH), 2928, 2856 (CH2),
1613, 1506, 1449 (aromatic frame), 1357, 1180, 1136, 968,
1
(CSC) cm–1; H NMR (300 MHz, CDCl3) δ: 7.92 (s, 1H,
S-triazole H), 7.32–7.30 (m, 2H, 2,4-F2Ph 6-H), 6.90–6.72
(m, 4H, 2,4-F2Ph 3,5-H), 5.19 (s, 2H, S-CH2), 4.42 (s, 2H,
2,4-F2Ph-CH2-triazole) ppm; 13C NMR (75 MHz, CDCl3) δ:
164.9, 161.8 (2C, 2,4-F2Ph 2-C), 161.4, 160.5 (2C, 2,4-F2Ph
4-C), 153.3 (S-triazole S-C), 147.7 (S-triazole 5-C), 132.1,
130.8 (2C, 2,4-F2Ph 6-C), 118.2, 117.7 (2C, 2,4-F2Ph 1-C),
111.6, 111.3 (2C, 2,4-F2Ph 5-C), 104.7, 104.1 (2C, 2,4-F2Ph
3-C), 46.9, 38.7 (CH2) ppm; ESI-MS (m/z): 353 [M]+;
HRMS (ESI) calcd. for C16H11F4N3S [M+H]+, 354.0688;
found, 354.0692.
1
852, 731 (CSC), 665 cm–1; H NMR (300 MHz, CDCl3)
δ: 7.88 (s, 1H, S-triazole H), 7.38–7.30 (m, 1H, 2,4-F2Ph
6-H), 6.89–6.73 (m, 2H, 2,4-F2Ph 3,5-H), 4.41 (s, 2H,
2,4-F2Ph-CH2), 3.95 (t, 2H, J = 7.5 Hz, CH3(CH2)6CH2),
1.74–1.72 (m, 2H, CH3(CH2)5CH2), 1.28–1.24 (m, 10H,
CH3(CH2)5), 0.88 (t, 3H, J = 6.0 Hz, CH3) ppm; 13C NMR
(75 MHz, CDCl3) δ: 164.8, 162.2 (2,4-F2Ph 2-C), 161.7,
160.9 (2,4-F2Ph 4-C), 151.9 (S-triazole S-C), 145.3
(S-triazole 5-C), 128.7 (2,4-F2Ph 6-C), 117.5 (2,4-F2Ph 1-C),
111.6, 111.2 (2,4-F2Ph 5-C), 104.5, 104.1 (2,4-F2Ph 3-C),
45.7, 40.1, 32.6, 30.1, 29.3, 29.2, 26.7, 22.9 (CH2), 14.5
(CH3) ppm; ESI-MS (m/z): 339 [M]+; HRMS (ESI) calcd.
for C17H23F2N3S [M+H]+, 340.1659; found, 340.1661.
1-(3,4-Dichlorobenzyl)-2-octyl-1H-1,2,4-triazole-3(2H)-
thione (4a)
Pure compound 4a (0.32 g) was prepared as a yellow oil
according to the procedure described for compound 3a.
Yield: 43.2%; IR (KBr) ν: 3111, 3058 (Ar–H), 2923, 2853
(CH2), 1564, 1496, 1460 (aromatic frame), 1354, 1264
(C=S), 1184, 1133, 1032, 989, 891, 820, 668 cm–1; 1H NMR
(300 MHz, CDCl3) δ: 7.96 (s, 1H, S-triazole H), 7.49–7.35
(s, 2H, 3,4-Cl2Ph 2,5-H), 7.26–7.22 (m, H, 3,4-Cl2Ph 6-H),
4.26 (s, 2H, 3,4-Cl2Ph-CH2), 4.07 (t, 2H, J = 7.5 Hz,
CH3(CH2)6CH2), 1.86–1.82 (m, 2H, CH3(CH2)5CH2),
1.29–1.25 (m, 10H, CH3(CH2)5), 0.89 (t, 3H, J = 6.0 Hz,
CH3) ppm; 13C NMR (75 MHz, CDCl3) δ: 156.7 (S=C),
144.9 (S-triazole 5-C), 138.1 (3,4-Cl2Ph 1-C), 132.5
(3,4-Cl2Ph 3-C), 131.2 (3,4-Cl2Ph 4-C), 130.8 (3,4-Cl2Ph
2-C), 130.5 (3,4-Cl2Ph 5-C), 128.4 (3,4-Cl2Ph 6-C), 48.7,
46.2, 31.4, 29.3, 29.0, 27.4, 26.7, 22.2 (CH2), 14.7 (CH3)
ppm; ESI-MS (m/z): 372 [M]+; HRMS (ESI) calcd. for
C17H23Cl2N3S [M+H]+, 372.1068; found, 372.1066.
3-(3,4-Dichlorobenzylthio)-1-(2,4-difluorobenzyl)-1H-1,2,4-
triazole (3e)
Compound 3e was prepared employing a procedure simi-
lar to that used to synthesize compound 3a, starting from
compound 2b (0.45 g, 2.0 mmol) and 3,4-dichloro-1-
(chloromethyl) benzene (0.46 g, 2.4 mmol). The pure prod-
uct 3e (0.24 g) was obtained as a yellow syrup. Yield:
31.3%; IR (KBr) ν: 3107, 3074 (ArH), 2932, 2856 (CH2),
1611, 1505, 1453 (aromatic frame), 1352, 1180, 1136, 1061,
967, 853, 763, 715 (CSC), 663 cm–1; 1H NMR (300 MHz,
CDCl3) δ: 7.94 (s, 1H, S-triazole H), 7.38–7.36 (m, 1H,

2138
Wang QP, et al. Sci China Chem October (2012) Vol.55 No.10
1,2-Bis(3,4-dichlorobenzyl)-1H-1,2,4-triazole-3(2H)-thione
(4b)
143.5 (S-triazole 5-C), 129.7 (2,4-F2Ph 6-C), 123.0
(2,4-F2Ph 1-C), 111.5, 111.2 (2,4-F2Ph 5-C), 104.7, 104.5
(2,4-F2Ph 3-C), 48.6, 34.2, 30.4, 29.8, 29.2, 27.2, 27.0, 22.1
(CH2), 14.7 (CH3) ppm; ESI-MS (m/z): 339 [M]+; HRMS
(ESI) calcd. for C17H23F2N3S [M+H]+, 340.1659; found,
340.1664.
Pure compound 4b (0.41 g) was prepared as a yellow
syrup according to the procedure described for compound
3b. Yield: 31.0%; IR (KBr) ν: 3112 (ArH), 2930, 2853
(CH2), 1601, 1575, 1461 (aromatic frame), 1358, 1267
(C=S), 1196, 1135, 1028, 886, 820, 761, 683 cm–1; 1H NMR
(300 MHz, CDCl3) δ: 8.04 (s, 1H, S-triazole H), 7.47–7.31
(m, 4H, 3,4-Cl2Ph 2,5-H), 7.22–7.03 (m, 2H, 3,4-Cl2Ph
6-H), 5.21 (s, 2H, triazole-thione N2-CH2), 4.25 (s, 2H, tri-
azole-thione N1-CH2) ppm; 13C NMR (75 MHz, CDCl3) δ:
157.7 (S=C), 147.4 (S-triazole 5-C), 137.6 (2C, 3,4-Cl2Ph
1-C), 131.2 (2C, 3,4-Cl2Ph 3-C), 130.9 (2C, 3,4-Cl2Ph 4-C),
130.8 (2C, 3,4-Cl2Ph 2-C), 130.5 (2C, 3,4-Cl2Ph 5-C),
128.1 (2C, 3,4-Cl2Ph 6-C), 47.2, 44.3 (CH2) ppm; ESI-MS
(m/z): 419 [M]+; HRMS (ESI) calcd. for C16H11Cl4N3S
[M+H]+, 417.9506; found, 417.9509.
2-(3,4-Dichlorobenzyl)-1-(2,4-difluorobenzyl)-1H-1,2,4-
triazole-3(2H)-thione (4e)
Pure compound 4e (0.23 g) was prepared as a yellow
syrup according to the procedure described for compound
3e. Yield: 34.1%; IR (KBr) ν: 3110 (Ar–H), 2938, 2857
(CH2), 1611, 1500, 1451 (aromatic frame), 1358, 1272
(C=S), 1185, 1128, 967, 853, 763, 660 cm–1; 1H NMR (300
MHz, CDCl3) δ: 8.05 (s, 1H, S-triazole H), 7.46–7.43 (m,
1H, 2,4-F2Ph 6-H), 7.35–7.32 (m, 2H, 3,4-Cl2Ph 2,5-H),
7.09–7.06 (m, 1H, 3,4-Cl2Ph 6-H), 6.81–6.72 (m, 2H,
2,4-F2Ph 3,5-H), 5.22 (s, 2H, triazole-thione N2-CH2), 4.32
(s, 2H, 2,4-F2Ph-CH2) ppm; 13C NMR (75 MHz, CDCl3) δ:
163.8, 162.9 (2,4-F2Ph 2-C), 161.1, 160.6 (2,4-F2Ph 4-C),
158.6 (S=C), 148.5 (S-triazole 5-C), 137.2 (3,4-Cl2Ph 1-C),
132.5 (3,4-Cl2Ph 3-C), 131.7 (3,4-Cl2Ph 4-C), 131.4
(2,4-F2Ph 6-C), 130.5 (3,4-Cl2Ph 2-C), 129.9 (3,4-Cl2Ph
5-C), 128.1 (3,4-Cl2Ph 6-C), 118.0 (2,4-F2Ph 1-C), 111.7,
111.4 (2,4-F2Ph 5-C), 104.1, 103.7 (2,4-F2Ph 3-C), 47.7,
43.6 (CH2) ppm; ESI-MS (m/z): 386 [M]+; HRMS (ESI)
calcd. for C16H11Cl2F2N3S [M+H]+, 386.0097; found,
386.0096.
1-(3,4-Dichlorobenzyl)-2-(2,4-difluorobenzyl)-1H-1,2,4-tria
zole-3(2H)-thione (4c)
Pure compound 4c (0.24 g) was prepared as a yellow
syrup according to the procedure described for compound
3c. Yield: 31.1%; IR (KBr) ν: 3111, 3083 (ArH), 2937,
2854 (CH2), 1616, 1503, 1458 (aromatic frame), 1359, 1269
(C=S), 1182, 1137, 1093, 1026, 969, 853, 764, 674 cm–1; 1H
NMR (300 MHz, CDCl3) δ: 8.04 (s, 1H, S-triazole H),
7.46–7.34 (m, 3H, 2,4-F2Ph 6-H, 3,4-Cl2Ph 2,5-H),
7.25–6.95 (m, 3H, 2,4-F2Ph 3,5-H, 3,4-Cl2Ph 6-H), 5.25 (s,
2H, triazole-thione N2-CH2), 4.24 (s, 2H, 3,4-Cl2Ph-CH2)
ppm; 13C NMR (75 MHz, CDCl3) δ: 164.7, 164.5 (2,4-F2Ph
2-C), 161.5, 160.2 (2,4-F2Ph 4-C), 158.9 (S=C), 151.8
(S-triazole 5-C), 138.2 (3,4-Cl2Ph 1-C), 132.1 (3,4-Cl2Ph
3-C), 131.6, 131.2 (2,4-F2Ph 6-C), 131.1 (3,4-Cl2Ph 4-C),
130.9 (3,4-Cl2Ph 2-C), 130.5 (3,4-Cl2Ph 5-C), 128.3
(3,4-Cl2Ph 6-C), 117.7 (2,4-F2Ph 1-C), 112.1, 111.9
(2,4-F2Ph 5-C), 104.7, 104.3, 104.1 (2,4-F2Ph 3-C), 46.8,
45.3 (CH2) ppm; ESI-MS (m/z): 386 [M]+; HRMS (ESI)
calcd. for C16H11Cl2F2N3S [M+H]+, 386.0097; found,
386.0094.
1,2-Bis(2,4-difluorobenzyl)-1H-1,2,4-triazole-3(2H)-thione
(4f)
Compound 4f (0.26 g) was prepared as a yellow syrup
according to the procedure described for compound 3f.
Yield: 32.7%; IR (KBr) ν: 3111 (Ar–H), 2931, 2857 (CH2),
1614, 1505, 1440 (aromatic frame), 1364, 1273 (C=S), 1184,
1138, 1092, 968, 851, 675 cm–1; 1H NMR (300 MHz,
CDCl3) δ: 8.05 (s, 1H, S-triazole H), 7.35–7.33 (m, 2H,
2,4-F2Ph 6-H), 6.90–6.73 (m, 4H, 2,4-F2Ph 3,5-H), 5.27 (s,
2H, triazole-thione N2-CH2), 4.30 (s, 2H, triazole-thione
N1-CH2) ppm; 13C NMR (75 MHz, CDCl3) δ: 165.0, 162.4
(2C, 2,4-F2Ph 2-C), 160.2, 159.1 (2C, 2,4-F2Ph 4-C), 158.7
(S=C), 149.4 (S-triazole 5-C), 131.8, 131.6 (2C, 2,4-F2Ph
6-C), 117.7, 117.3 (2C, 2,4-F2Ph 1-C), 111.4, 110.7 (2C,
2,4-F2Ph 5-C), 104.6, 104.2 (2C, 2,4-F2Ph 3-C), 45.8, 41.5
(CH2) ppm; ESI-MS (m/z): 353 [M]+; HRMS (ESI) calcd.
for C16H11F4N3S [M+H]+, 354.0688; found, 354.0691.
1-(2,4-Difluorobenzyl)-2-octyl-1H-1,2,4-triazole-3(2H)-
thione (4d)
Pure compound 4d (0.29 g) was prepared as a yellow
syrup according to the procedure described for compound
3d. Yield: 43.5%; IR (KBr) ν: 3112 (Ar–H), 2927, 2859
(CH2), 1612, 1576, 1502, 1442 (aromatic frame), 1362,
1274 (C=S), 1186, 1025, 967, 852, 670 cm–1; 1H NMR (300
MHz, CDCl3) δ: 7.98 (s, 1H, S-triazole H), 7.36–7.29 (m,
1H, 2,4-F2Ph 6-H), 6.90–6.74 (m, 2H, 2,4-F2Ph 3,5-H), 4.32
(s, 2H, 2,4-F2Ph-CH2), 4.06 (t, 2H, J = 7.5 Hz,
CH3(CH2)6CH2), 1.88–1.82 (m, 2H, CH3(CH2)5CH2),
1.30–1.24 (m, 10H, CH3(CH2)5), 0.89 (t, 3H, J = 6.0 Hz,
CH3) ppm; 13C NMR (75 MHz, CDCl3) δ: 163.5, 161.7
(2,4-F2Ph 2-C), 160.1, 159.7 (2,4-F2Ph 4-C), 159.2 (S=C),
3-(2-Bromoethylthio)-1-(3,4-dichlorobenzyl)-1H-1,2,4-
triazole (5a)
A
mixture of 1-(3,4-dichlorobenzyl)-1H-1,2,4-triazole-
3-thiol 2a (2.00 g, 7.7 mmol) and potassium carbonate (1.21
g, 8.3 mmol) in acetone (10 mL) was stirred at 50 °C for 20
min, cooled to room temperature, and added 1,2-dibromo-
ethane (1.73 g, 9.2 mmol). The resulting mixture was stirred

Wang QP, et al. Sci China Chem October (2012) Vol.55 No.10
2139
at 40 °C for 12 h. Upon completion of the reaction (moni-
tored by TLC, eluent, chloroform/methanol, 30/1, v/v), the
mixture was cooled to room temperature. The solvent was
removed under vacuum and the residue was extracted with
chloroform. The organic extracts were collected, dried over
anhydrous sodium sulfate and concentrated. The crude
product was purified by silica gel column chromatography
(eluent, chloroform/methanol, 50/1, v/v) to afford pure
compound 5a (1.10 g) as a yellow oil. Yield: 40.5%; IR
(KBr) ν: 3110, 3060 (Ar–H), 2967, 2930, 2853 (CH2), 1562,
1499, 1473 (aromatic frame), 1356, 1176, 1133, 1060, 1032,
(1.20 g) was obtained as a yellow oil. Yield: 37.6%; IR
(KBr) ν: 3111, 3062 (Ar–H), 2965, 2934 (CH2), 1560, 1495,
1472 (aromatic frame), 1362, 1182, 1130, 1032, 885, 730
(C–S–C), 681 cm–1; 1H NMR (300 MHz, CDCl3) δ: 7.95 (s,
1H, S-triazole H), 7.45–7.33 (m, 2H, 3,4-Cl2Ph 2,5-H),
7.13–7.11 (m, 1H, 3,4-Cl2Ph 6-H), 4.35 (s, 2H,
3,4-Cl2Ph-CH2), 3.97 (t, 2H, J = 6.0 Hz, Br(CH2)5CH2),
3.44 (t, 2H, J = 6.0 Hz, BrCH2), 1.97–1.91 (m, 2H,
Br(CH2)4CH2), 1.84–1.75 (m, 2H, BrCH2CH2), 1.34–1.21
(m, 4H, Br(CH2)2CH2CH2) ppm; 13C NMR (75 MHz,
CDCl3) δ: 155.1 (S-triazole S-C), 142.8 (S-triazole 5-C),
137.2 (3,4-Cl2Ph 1-C), 132.4 (3,4-Cl2Ph 3-C), 131.8
(3,4-Cl2Ph 4-C), 130.7 (3,4-Cl2Ph 2-C), 130.5 (3,4-Cl2Ph
5-C), 128.1 (3,4-Cl2Ph 6-C), 47.2, 34.7, 34.5, 29.6, 28.9,
25.9, 25.8 (CH2) ppm; ESI-MS (m/z): 424 [M+H]+; HRMS
(ESI) calcd. for C15H18BrCl2N3S [M+H]+, 421.9860; found,
421.9862.
1
884, 823, 767, 724 (C–S–C) cm–1; H NMR (300 MHz,
CDCl3) δ: 7.94 (s, 1H, S-triazole H), 7.45–7.35 (m, 2H,
3,4-Cl2Ph 2,5-H), 7.19–7.16 (m, 1H, 3,4-Cl2Ph 6-H),
4.39–4.36 (m, 4H, BrCH2CH2, 3,4-Cl2Ph-CH2), 3.63 (t, 2H,
J = 6.0 Hz, BrCH2) ppm; 13C NMR (75 MHz, CDCl3) δ:
151.8 (S-triazole S-C), 144.8 (S-triazole 5-C), 137.2
(3,4-Cl2Ph 1-C), 132.3 (3,4-Cl2Ph 3-C), 131.4 (3,4-Cl2Ph
4-C), 130.8 (3,4-Cl2Ph 2-C), 130.4 (3,4-Cl2Ph 5-C), 128.1
(3,4-Cl2Ph 6-C), 47.7, 36.5, 32.4 (CH2) ppm; ESI-MS (m/z):
368 [M+H]+; HRMS (ESI) calcd. for C11H10BrCl2N3S
[M+H]+, 365.9234; found, 365.9238.
3-(2-Bromoethylthio)-1-(2,4-difluorobenzyl)-1H-1,2,4-
triazole (5d)
Compound 5d was prepared employing a procedure similar
to that used to synthesize compound 5a, starting from
1-(2,4-difluorobenzyl)-1H-1,2,4-triazole-3-thiol 2b (2.01 g,
8.9 mmol), 1,2-dibromoethane (2.04 g, 10.8 mmol) and po-
tassium carbonate (1.24 g, 8.3 mmol). The pure product 5d
(0.73 g) was obtained as a yellow oil. Yield: 23.7%; IR
(KBr) ν: 3111, 3076 (Ar–H), 2995 (CH2), 1603, 1548, 1478
(aromatic frame), 1359, 1188, 1138, 1088, 967, 852, 724
3-(4-Bromobutylthio)-1-(3,4-dichlorobenzyl)-1H-1,2,4-
triazole (5b)
Compound 5b was prepared employing a procedure similar
to that used to synthesize compound 5a, starting from
1-(3,4-dichlorobenzyl)-1H-1,2,4-triazole-3-thiol 2a (2.01 g,
7.8 mmol), 1,4-dibromobutane (2.02 g, 9.4mmol) and po-
tassium carbonate (1.21 g, 8.3 mmol). The pure product 5b
(1.22 g) was obtained as a yellow oil. Yield: 38.4%; IR
(KBr) ν: 3113, 3062 (Ar–H), 2960, 2933, 2847 (CH2), 1604,
1566, 1485, 1442 (aromatic frame), 1353, 1178, 1132, 1066,
1033, 884, 823, 759, 719 (CSC), 674 cm–1; 1H NMR (300
MHz, CDCl3) δ: 7.94 (s, 1H, S-triazole H), 7.46–7.30 (m,
2H, 3,4-Cl2Ph 2,5-H), 7.21–7.16 (m, 1H, 3,4-Cl2Ph 6-H),
4.36 (s, 2H, 3,4-Cl2Ph-CH2), 3.96 (t, 2H, J = 7.5 Hz,
Br(CH2)3CH2), 3.47 (t, 2H, J = 7.5 Hz, BrCH2), 2.14–2.06
(m, 2H, Br(CH2)2CH2), 1.99–1.92 (m, 2H, BrCH2CH2) ppm;
13C NMR (75 MHz, CDCl3) δ: 149.9 (S-triazole S-C), 143.6
(S-triazole 5-C), 137.0 (3,4-Cl2Ph 1-C), 132.1 (3,4-Cl2Ph
3-C), 131.5 (3,4-Cl2Ph 4-C), 130.6 (3,4-Cl2Ph 2-C), 130.5
(3,4-Cl2Ph 5-C), 127.8 (3,4-Cl2Ph 6-C), 46.6, 35.6, 31.7,
28.2, 27.6 (CH2) ppm; ESI-MS (m/z): 396 [M+H]+; HRMS
(ESI) calcd. for C13H14BrCl2N3S [M+H]+, 393.9547; found,
393.9545.
1
(C–S–C) cm–1; H NMR (300 MHz, CDCl3) δ: 7.93 (s, 1H,
S-triazole H), 7.38–7.29 (m, 1H, 2,4-F2Ph 6-H), 6.81–6.75
(m, 2H, 2,4-F2Ph 3,5-H), 4.57 (t, 2H, J = 6.0 Hz,
BrCH2CH2), 4.29 (s, 2H, 2,4-F2Ph-CH2), 3.56 (t, 2H, J = 6.0
Hz, BrCH2) ppm; 13C NMR (75 MHz, CDCl3) δ: 164.1,
162.8 (2,4-F2Ph 2-C), 160.8, 160.1 (2,4-F2Ph 4-C), 152.5
(S-triazole S-C), 142.2 (S-triazole 5-C), 131.5 (2,4-F2Ph
6-C), 120.6, 120.3 (2,4-F2Ph 1-C), 110.4, 110.2 (2,4-F2Ph
5-C), 103.6, 103.2 (2,4-F2Ph 3-C), 47.3, 33.4, 31.4 (CH2)
ppm; ESI-MS (m/z): 334 [M]+; HRMS (ESI) calcd. for
C11H10BrF2N3S [M+H]+, 333.9825; found, 333.9822.
3-(4-Bromobutylthio)-1-(2,4-difluorobenzyl)-1H-1,2,4-
triazole (5e)
Compound 5e was prepared employing a procedure similar
to that used to synthesize compound 5a, starting from
1-(2,4-difluorobenzyl)-1H-1,2,4-triazole-3-thiol 2b (2.12 g,
9.2 mmol) and 1,4-dibromobutane (2.31 g, 10.7 mmol) and
potassium carbonate (1.21 g, 8.3 mmol). The pure product
5e (1.12 g) was obtained as a yellow oil. Yield: 33.2%; IR
(KBr) ν: 3113 (Ar–H), 2998, 2987 (CH2), 1607, 1501, 1481
(aromatic frame), 1361, 1192, 1139, 1079, 967, 852, 722
(C–S–C), 691 cm–1; 1H NMR (300 MHz, CDCl3) δ: 7.92 (s,
1H, S-triazole H), 7.45–7.36 (m, 1H, 2,4-F2Ph 6-H),
6.81–6.75 (m, 2H, 2,4-F2Ph 3,5-H), 4.41 (s, 2H,
2,4-F2Ph-CH2), 3.97 (t, 2H, J = 6.0 Hz, Br(CH2)3CH2), 3.36
3-(6-Bromohexylthio)-1-(3,4-dichlorobenzyl)-1H-1,2,4-
triazole (5c)
Compound 5c was prepared employing a procedure similar
to that used to synthesize compound 5a, starting from
1-(3,4-dichlorobenzyl)-1H-1,2,4-triazole-3-thiol 2a (2.02 g,
7.8 mmol), 1,6-dibromohexane (2.43 g, 9.9mmol) and po-
tassium carbonate (1.24 g, 8.3 mmol). The pure product 5c

2140
Wang QP, et al. Sci China Chem October (2012) Vol.55 No.10
(t, 2H, J = 7.5 Hz, BrCH2), 2.04–1.96 (m, 2H, BrCH2CH2),
1.85–1.77 (m, 2H, Br(CH2)2CH2) ppm; 13C NMR (75 MHz,
CDCl3) δ: 164.0, 163.4 (2,4-F2Ph 2-C), 160.9, 160.7
(2,4-F2Ph 4-C), 151.1 (S-triazole S-C), 145.5 (S-triazole
5-C), 130.7, 130.5 (2,4-F2Ph 6-C), 118.8, 117.9 (2,4-F2Ph
1-C), 110.3, 110.1 (2,4-F2Ph 5-C), 103.2, 103.0 (2,4-F2Ph
3-C), 46.6, 34.6, 31.5, 27.1, 26.8 (CH2) ppm; ESI-MS (m/z):
362 [M]+; HRMS (ESI) calcd. for C13H14BrF2N3S [M+H]+,
362.0138; found, 362.0138.
cording to the procedure described for compound 5b. Yield:
34.9%; IR (KBr) ν: 3111, 3059 (Ar–H), 2961, 2933 (CH2),
1602, 1558, 1496, 1447 (aromatic frame), 1360, 1272 (C=S),
1179, 1131, 1037, 885, 825, 771 cm–1; 1H NMR (300 MHz,
CDCl3) δ: 7.98 (s, 1H, S-triazole H), 7.45–7.33 (m, 2H,
3,4-Cl2Ph 2,5-H), 7.23–7.17 (m, 1H, 3,4-Cl2Ph 6-H), 4.26 (s,
2H, 3,4-Cl2Ph-CH2), 4.08 (t, 2H, J = 6.0 Hz, Br(CH2)3CH2),
3.39 (t, 2H, J = 6.0 Hz, BrCH2), 2.13–2.06 (m, 2H,
Br(CH2)2CH2), 1.99–1.91 (m, 2H, BrCH2CH2) ppm; 13C
NMR (75 MHz, CDCl3) δ: 157.2 (S=C), 141.9 (S-triazole
5-C), 137.4 (3,4-Cl2Ph 1-C), 132.5 (3,4-Cl2Ph 3-C), 131.7
(3,4-Cl2Ph 4-C), 130.9 (3,4-Cl2Ph 2-C), 130.6 (3,4-Cl2Ph
5-C), 127.7 (3,4-Cl2Ph 6-C), 47.6, 36.5, 31.1, 27.7, 27.4
(CH2) ppm; ESI-MS (m/z): 396 [M+H]+; HRMS (ESI) calcd.
for C13H14BrCl2N3S [M+H]+, 393.9547; found, 393.9550.
3-(6-Bromohexylthio)-1-(2,4-difluorobenzyl)-1H-1,2,4-
triazole (5f)
Compound 5f was prepared employing a procedure similar
to that used to synthesize compound 5a, starting from
1-(2,4-difluorobenzyl)-1H-1,2,4-triazole-3-thiol 2b (2.01 g,
9.0 mmol), 1,2-dibromoethane (2.64 g, 10.7 mmol) and po-
tassium carbonate (1.21 g, 8.3 mmol). The pure product 5f
(0.91 g) was obtained as a yellow oil. Yield: 25.5%; IR
(KBr) ν: 3112 (Ar–H), 2988, 2834 (CH2), 1610, 1508, 1471
(aromatic frame), 1351, 1166, 1114, 968, 853, 710 (C–S–C)
cm–1; 1H NMR (300 MHz, CDCl3) δ: 7.93 (s, 1H, S-triazole
H), 7.37–7.30 (m, 1H, 2,4-F2Ph 6-H), 6.84–6.75 (m, 2H,
2,4-F2Ph 3,5-H), 4.42 (s, 2H, 2,4-F2Ph-CH2), 3.98 (t, 2H, J
= 7.5 Hz, Br(CH)5CH2), 3.41 (t, 2H, J = 6.0 Hz, BrCH2),
1.96–1.88 (m, 2H, Br(CH2)4CH2), 1.80–1.72 (m, 2H,
2-(6-Bromohexyl)-1-(3,4-dichlorobenzyl)-1H-1,2,4-triazole-
3(2H)-thione (6c)
Compound 6c (1.32 g) was prepared as a yellow oil accord-
ing to the procedure described for compound 5c. Yield:
46.5%; IR (KBr) ν: 3113, 3060 (Ar–H), 2962, 2931 (CH2),
1561, 1491, 1452 (aromatic frame), 1361, 1267 (C=S), 1179,
1131, 1031, 887, 819, 765 cm–1; 1H NMR (300 MHz,
CDCl3) δ: 7.97 (s, 1H, S-triazole H), 7.43–7.31 (m, 2H,
3,4-Cl2Ph 2,5-H), 7.17–7.14 (m, 1H, 3,4-Cl2Ph 6-H), 4.28 (s,
2H, 3,4-Cl2Ph-CH2), 4.07 (t, 2H, J = 7.5 Hz, Br(CH2)5CH2),
3.46 (t, 2H, J = 7.5 Hz, BrCH2), 2.01–1.92 (m, 2H,
Br(CH2)4CH2), 1.87–1.77 (m, 2H, BrCH2CH2), 1.28–1.19
(m, 4H, Br(CH2)2CH2CH2) ppm; 13C NMR (75 MHz,
CDCl3) δ: 157.1 (S=C), 142.5 (S-triazole 5-C), 137.3
(3,4-Cl2Ph 1-C), 132.4 (3,4-Cl2Ph 3-C), 131.4 (3,4-Cl2Ph
4-C), 130.7 (3,4-Cl2Ph 2-C), 130.5 (3,4-Cl2Ph 5-C), 128.1
(3,4-Cl2Ph 6-C), 46.6, 35.7, 30.9, 29.8, 29.2, 25.3, 25.2
(CH2) ppm; ESI-MS (m/z): 424 [M+H]+; HRMS (ESI) calcd.
for C15H18BrCl2N3S [M+H]+, 421.9860; found, 421.9862.
BrCH2CH2), 1.28–1.17 (m, 4H, Br(CH2)2CH2CH2) ppm; 13
C
NMR (75 MHz, CDCl3) δ: 164.1, 162.8 (2,4-F2Ph 2-C),
160.7, 160.2 (2,4-F2Ph 4-C), 152.4 (S-triazole S-C), 146.0
(S-triazole 5-C), 130.2, 130.0 (2,4-F2Ph 6-C), 119.7, 119.5
(2,4-F2Ph 1-C), 110.6, 110.4 (2,4-F2Ph 5-C), 103.5, 103.2
(2,4-F2Ph 3-C), 47.5, 33.2, 32.1, 29.8, 29.2, 25.6, 25.4 (CH2)
ppm; ESI-MS (m/z): 390 [M]+; HRMS (ESI) calcd. for
C15H18BrF2N3S [M+H]+, 390.0451; found, 390.0453.
2-(2-Bromoethyl)-1-(3,4-dichlorobenzyl)-1H-1,2,4-triazole-
3(2H)-thione (6a)
Compound 6a (1.00 g) was prepared as a yellow oil ac-
cording to the procedure described for compound 5a. Yield:
37.6%; IR (KBr) ν: 3110, 3059 (Ar–H), 2968, 2938 (CH2),
1555, 1499, 1470 (aromatic frame), 1367, 1268 (C=S), 1185,
1133, 1031, 885, 823, 777 cm–1; 1H NMR (300 MHz,
CDCl3) δ: 7.99 (s, 1H, S-triazole H), 7.49–7.33 (m, 2H,
3,4-Cl2Ph 2,5-H), 7.23–7.21 (m, 1H, 3,4-Cl2Ph 6-H), 4.47 (t,
2H, J = 6.0 Hz, BrCH2CH2), 4.26 (s, 2H, 3,4-Cl2Ph-CH2),
3.70 (t, 2H, J = 6.0 Hz, BrCH2) ppm; 13C NMR (75 MHz,
CDCl3) δ: 155.8 (S=C), 149.6 (S-triazole 5-C), 137.2
(3,4-Cl2Ph 1-C), 132.3 (3,4-Cl2Ph 3-C), 131.4 (3,4-Cl2Ph
4-C), 130.8 (3,4-Cl2Ph 2-C), 130.4 (3,4-Cl2Ph 5-C), 128.1
(3,4-Cl2Ph 6-C), 48.2, 34.5, 32.4 (CH2) ppm; ESI-MS (m/z):
368 [M+H]+; HRMS (ESI) calcd. for C11H10BrCl2N3S
[M+H]+, 365.9234; found, 365.9230.
2-(2-Bromoethyl)-1-(2,4-difluorobenzyl)-1H-1,2,4-triazole-
3(2H)-thione (6d)
Compound 6d (1.01 g) was prepared as a yellow oil ac-
cording to the procedure described for compound 5d. Yield:
35.1%; IR (KBr) ν: 3111 (Ar–H), 2996 (CH2), 1604, 1503,
1459 (aromatic frame), 1369, 1266 (C=S), 1186, 1138, 1088,
1
967, 852, 731, 663 cm–1; H NMR (300 MHz, CDCl3) δ:
7.95 (s, 1H, S-triazole H), 7.41–7.33 (m, 1H, 2,4-F2Ph 6-H),
6.83–6.76 (m, 2H, 2,4-F2Ph 3,5-H), 4.51 (t, 2H, J = 6.0 Hz,
BrCH2CH2), 4.32 (s, 2H, 2,4-F2Ph-CH2), 3.68 (t, 2H, J = 6.0
Hz, BrCH2) ppm; 13C NMR (75 MHz, CDCl3) δ: 163.8,
162.7 (2,4-F2Ph 2-C), 160.5, 160.3 (2,4-F2Ph 4-C), 155.6
(S=C), 143.4 (S-triazole 5-C), 130.4 (2,4-F2Ph 6-C), 118.2
(2,4-F2Ph 1-C), 109.8, 109.6 (2,4-F2Ph 5-C), 102.4, 102.1
(2,4-F2Ph 3-C), 45.6, 43.5, 37.7 (CH2) ppm; ESI-MS (m/z):
334 [M]+; HRMS (ESI) calcd. for C11H10BrF2N3S [M+H]+,
333.9825; found, 333.9825.
2-(4-Bromobutyl)-1-(3,4-dichlorobenzyl)-1H-1,2,4-triazole-
3(2H)-thione (6b)
Compound 6b (1.51 g) was prepared as a yellow oil ac-

Wang QP, et al. Sci China Chem October (2012) Vol.55 No.10
2141
2-(4-Bromobutyl)-1-(2,4-difluorobenzyl)-1H-1,2,4-triazole-
3(2H)-thione (6e)
product was purified via silica gel column chromatography
(eluent, chloroform/methanol, 40/1, v/v) to afford com-
pound 7a (0.32 g) as a yellow syrup. Yield: 90.9%; IR (KBr)
ν: 3110, 3058 (Ar–H), 2956, 2851 (CH2), 1557, 1504, 1471
(aromatic frame), 1360, 1178, 1136, 1012, 961, 882, 739
(C–S–C), 685 cm–1; 1H NMR (300 MHz, CDCl3) δ: 7.92 (s,
1H, triazole 3-H), 7.90 (s, 1H, S-triazole H), 7.74 (s, 1H,
triazole 5-H), 7.40–7.34 (m, 2H, 3,4-Cl2Ph 2,5-H),
7.12–7.10 (m, 1H, 3,4-Cl2Ph 6-H), 4.60 (t, 2H, J = 6.0 Hz,
SCH2CH2), 4.43 (t, 2H, J = 4.5 Hz, SCH2), 4.24 (s, 2H,
3,4-Cl2Ph-CH2) ppm; 13C NMR (75 MHz, CDCl3) δ: 152.1
(S-triazole S-C), 151.6 (triazole 3-C), 143.9 (S-triazole 5-C),
143.5 (triazole 5-C), 137.0 (3,4-Cl2Ph 1-C), 132.3
(3,4-Cl2Ph 3-C), 131.7 (3,4-Cl2Ph 4-C), 130.7 (3,4-Cl2Ph
2-C), 130.6 (3,4-Cl2Ph 5-C), 128.4 (3,4-Cl2Ph 6-C), 47.7,
46.8, 30.7 (CH2) ppm; ESI-MS (m/z): 355 [M]+; HRMS
(ESI) calcd. for C13H12Cl2N6S [M+H]+, 355.0299; found,
355.0291.
Compound 6e (1.10 g) was prepared as a yellow oil accord-
ing to the procedure described for compound 5e. Yield:
34.9%; IR (KBr) ν: 3112, 3065 (Ar–H), 2993, 2789 (CH2),
1603, 1581, 1506, 1453 (aromatic frame), 1367, 1259 (C=S),
1181, 1139, 1087, 1014, 967, 852, 762 cm–1; 1H NMR (300
MHz, CDCl3) δ: 7.99 (s, 1H, S-triazole H), 7.46–7.39 (m,
1H, 2,4-F2Ph 6-H), 6.82–6.74 (m, 2H, 2,4-F2Ph 3,5-H), 4.32
(s, 2H, 2,4-F2Ph-CH2), 4.09 (t, 2H, J = 7.5 Hz,
Br(CH2)3CH2), 4.04 (t, 2H, J = 7.5 Hz, BrCH2), 2.15–2.10
(m, 2H, Br(CH2)2CH2), 1.97–1.90 (m, 2H, BrCH2CH2) ppm;
13C NMR (75 MHz, CDCl3) δ: 164.7, 164.2 (2,4-F2Ph 2-C),
161.5, 160.8 (2,4-F2Ph 4-C), 156.6 (S=C), 140.1 (S-triazole
5-C), 131.4, 131.1 (2,4-F2Ph 6-C), 117.5 (2,4-F2Ph 1-C),
111.1, 110.7 (2,4-F2Ph 5-C), 104.1, 103.6 (2,4-F2Ph 3-C),
47.8, 39.6, 34.5, 25.8, 25.6 (CH2) ppm; ESI-MS (m/z): 362
[M]+; HRMS (ESI) calcd. for C13H14BrF2N3S [M+H]+,
362.0138; found, 362.0141.
3-(4-(1H-1,2,4-Triazol-1-yl)butylthio)-1-(3,4-dichlorobenzyl)-
1H-1,2,4-triazole (7b)
2-(6-Bromohexyl)-1-(2,4-difluorobenzyl)-1H-1,2,4-triazole-
3(2H)-thione (6f)
Compound 7b was prepared employing a procedure similar
to that used to synthesize compound 7a, starting from bro-
mide 5b (0.39 g, 1.0 mmol), 1H-1,2,4-triazole (0.07 g, 1.2
mmol) and potassium carbonate (0.17 g, 1.2 mmol). The
pure product 7b (0.33 g) was obtained as a yellow syrup.
Yield: 85.1%; IR (KBr) ν: 3111, 3062 (Ar–H), 2941, 2856
(CH2), 1612, 1505, 1475 (aromatic frame), 1355, 1176,
Compound 6f (1.31 g) was prepared as a yellow oil accord-
ing to the procedure described for compound 5f. Yield:
39.3%; IR (KBr) ν: 3117, 3068 (Ar–H), 2941, 2792 (CH2),
1603, 1509, 1434 (aromatic frame), 1361, 1262 (C=S), 1185,
1144, 1093, 972, 848, 679 cm–1; 1H NMR (300 MHz,
CDCl3) δ: 7.96 (s, 1H, S-triazole H), 7.39–7.29 (m, 1H,
2,4-F2Ph 6-H), 6.80–6.74 (m, 2H, 2,4-F2Ph 3,5-H), 4.31 (s,
2H, 2,4-F2Ph-CH2), 4.10 (t, 2H, J = 6.0 Hz, Br(CH2)5CH2),
4.03 (t, 2H, J = 7.5 Hz, BrCH2), 1.99–1.93 (m, 2H,
Br(CH2)4CH2), 1.84–1.76 (m, 2H, BrCH2CH2), 1.26–1.16
(m, 4H, Br(CH2)2CH2CH2) ppm; 13C NMR (75 MHz,
CDCl3) δ: 164.1, 162.8 (2,4-F2Ph 2-C), 160.3, 159.7
(2,4-F2Ph 4-C), 156.8 (S=C), 142.6 (S-triazole 5-C), 130.8,
130.6 (2,4-F2Ph 6-C), 118.3 (2,4-F2Ph 1-C), 110.5, 110.1
(2,4-F2Ph 5-C), 104.5, 103.8 (2,4-F2Ph 3-C), 46.1, 41.5,
35.3, 28.8, 28.6, 25.7, 25.6 (CH2) ppm; ESI-MS (m/z): 390
[M]+; HRMS (ESI) calcd. for C15H18BrF2N3S [M+H]+,
390.0451; found, 390.0456.
1
1137, 1011, 961, 882, 737 (C–S–C), 676 cm–1; H NMR
(300 MHz, CDCl3) δ: 8.04 (s, 1H, triazole 3-H), 7.94 (s, 1H,
triazole 5-H), 7.88 (s, 1H, S-triazole H), 7.44–7.34 (m, 2H,
3,4-Cl2Ph 2,5-H), 7.17–7.14 (m, 1H, 3,4-Cl2Ph 6-H), 4.35 (s,
2H, 3,4-Cl2Ph-CH2), 4.12 (t, 2H, J = 7.5 Hz, S(CH2)3CH2),
3.96 (t, 2H, J = 6.0 Hz, SCH2), 1.90–1.83 (m, 2H,
S(CH2)2CH2), 1.79–1.71 (m, 2H, SCH2CH2) ppm; 13C NMR
(75 MHz, CDCl3) δ: 152.0 (S-triazole S-C), 149.5 (triazole
3-C), 142.6 (S-triazole 5-C), 142.1 (triazole 5-C), 137.4
(3,4-Cl2Ph 1-C), 132.8 (3,4-Cl2Ph 3-C), 132.0 (3,4-Cl2Ph
4-C), 130.9 (3,4-Cl2Ph 2-C), 130.6 (3,4-Cl2Ph 5-C), 127.6
(3,4-Cl2Ph 6-C), 48.1, 47.8, 35.2, 27.7, 27.4 (CH2), ppm;
ESI-MS (m/z): 383 [M]+; HRMS (ESI) calcd. for
C15H16Cl2N6S [M+H]+, 383.0612; found, 383.0613.
3-(2-(1H-1,2,4-Triazol-1-yl)ethylthio)-1-(3,4-dichlorobenzyl)-
1H-1,2,4-triazole (7a)
3-(6-(1H-1,2,4-Triazol-1-yl)hexylthio)-1-(3,4-dichlorobenzyl)-
1H-1,2,4-triazole (7c)
To a stirred solution of 1H-1,2,4-triazole (0.07 g, 1.2
mmol) in acetonitrile (5 mL) was added potassium car-
bonate (0.17 g, 1.2 mmol). The mixture was heated at 60 ºC
for 20 min, cooled to room temperature, and added com-
pound 5a (0.37 g, 1.0 mmol). The resulting mixture was
stirred at 40 ºC until the reaction was completed (monitored
by TLC, eluent, chloroform/methanol, 30/1, v/v). The sol-
vent was evaporated under vacuum and the residue was
treated with water (50 mL) and extracted with chloroform
(3 × 50 mL). The organic layers were combined, dried over
anhydrous sodium sulfate and concentrated. The crude
Compound 7c was prepared employing a procedure similar
to that used to synthesize compound 7a starting from
3-(6-bromohexylthio)-1-(3,4-dichlorobenzyl)-1H-1,2,4-triaz
ole 5c (0.42 g, 1.0 mmol), 1H-1,2,4-triazole (0.07 g, 1.2
mmol) and potassium carbonate (0.17 g, 1.2 mmol). The
pure product 7c (0.34 g) was obtained as a yellow syrup.
Yield: 83.4%; IR (KBr) ν: 3113, 3059 (Ar–H), 2936, 2859
(CH2), 1562, 1506, 1471 (aromatic frame), 1356, 1179,
1
1139, 1014, 959, 879, 738 (C–S–C), 680 cm–1; H NMR

2142
Wang QP, et al. Sci China Chem October (2012) Vol.55 No.10
(300 MHz, CDCl3) δ: 8.02 (s, 1H, triazole 3-H), 7.93 (s, 1H,
triazole 5-H), 7.85 (s, 1H, S-triazole H), 7.43–7.34 (m, 2H,
3,4-Cl2Ph 2,5-H), 7.19–7.15 (m, 1H, 3,4-Cl2Ph 6-H), 4.33 (s,
2H, 3,4-Cl2Ph-CH2), 4.15 (t, 2H, J = 6.0 Hz, S(CH2)5CH2),
3.95 (t, 2H, J = 7.5 Hz, SCH2), 1.89–1.79 (m, 2H,
S(CH2)4CH2), 1.74–1.65 (m, 2H, SCH2CH2), 1.29–1.18 (m,
4H, S(CH2)2CH2CH2) ppm; 13C NMR (75 MHz, CDCl3) δ:
151.8 (S-triazole S-C), 151.3 (triazole 3-C), 148.1
(S-triazole 5-C), 142.8 (triazole 5-C), 137.2 (3,4-Cl2Ph 1-C),
132.6 (3,4-Cl2Ph 3-C), 131.8 (3,4-Cl2Ph 4-C), 130.7
(3,4-Cl2Ph 2-C), 130.5 (3,4-Cl2Ph 5-C), 128.2 (3,4-Cl2Ph
6-C), 49.4, 48.3, 36.6, 29.5, 29.0, 25.8, 25.7 (CH2) ppm;
ESI-MS (m/z): 411 [M]+; HRMS (ESI) calcd. for
C17H20Cl2N6S [M+H]+, 411.0925; found, 411.0925.
SCH2CH2CH2) ppm; 13C NMR (75 MHz, CDCl3) δ: 164.7,
162.0 (2,4-F2Ph 2-C), 160.9, 160.3 (2,4-F2Ph 4-C), 152.2
(S-triazole S-C), 151.7 (triazole 3-C), 144.5 (S-triazole 5-C),
143.2 (triazole 5-C), 130.7, 130.4 (2,4-F2Ph 6-C), 118.5,
118.1 (2,4-F2Ph 1-C), 111.3, 111.0 (2,4-F2Ph 5-C), 104.1,
103.6 (2,4-F2Ph 3-C), 48.0, 45.3, 34.5, 27.3, 26.8 (CH2)
ppm; ESI-MS (m/z): 351 [M+H]+; HRMS (ESI) calcd. for
C15H16F2N6S [M+H]+, 351.1203; found, 351.1203.
3-(6-(1H-1,2,4-Triazol-1-yl)hexylthio)-1-(2,4-difluorobenzyl)-
1H-1,2,4-triazole (7f)
Compound 7f was prepared employing a procedure similar
to that used to synthesize compound 7a, starting from bro-
mide 5f (0.39 g, 1.0 mmol), 1H-1,2,4-triazole (0.07 g, 1.2
mmol) and potassium carbonate (0.17 g, 1.2 mmol). The
pure product 7f (0.30 g) was obtained as a yellow syrup.
Yield: 78.7%; IR (KBr) ν: 3113, 3076 (Ar–H), 2942, 2860
(CH2), 1603, 1505, 1476 (aromatic frame), 1359, 1178,
3-(2-(1H-1,2,4-Triazol-1-yl)ethylthio)-1-(2,4-difluorobenzyl)-
1H-1,2,4-triazole (7d)
Compound 7d was prepared employing a procedure similar
to that used to synthesize compound 7a starting from bro-
mide 5d (0.33 g, 1.0 mmol), 1H-1,2,4-triazole (0.07 g, 1.2
mmol) and potassium carbonate (0.17 g, 1.2 mmol). The
pure product 7d (0.24 g) was obtained as a yellow syrup.
Yield: 75.4%; IR (KBr) ν: 3115, 3078 (Ar–H), 2956 (CH2),
1603, 1504, 1479 (aromatic frame), 1358, 1177, 1138, 1087,
1
1139, 1014, 968, 853, 736 (C–S–C), 681 cm–1; H NMR
(300 MHz, CDCl3) δ: 8.06 (s, 1H, triazole 3-H), 7.95 (s, 1H,
triazole 5-H), 7.87 (s, 1H, S-triazole H), 7.35–7.30 (m, 1H,
2,4-F2Ph 6-H), 6.86–6.77 (m, 2H, 2,4-F2Ph 3,5-H), 4.37 (s,
2H, 2,4-F2Ph-CH2), 4.13 (t, 2H, J = 6.0 Hz, S(CH2)5CH2),
3.97 (t, 2H, J = 7.5 Hz, SCH2), 1.90–1.79 (m, 2H,
S(CH2)4CH2), 1.76–1.71 (m, 2H, SCH2CH2), 1.27–1.16 (m,
4H, S(CH2)2CH2CH2) ppm; 13C NMR (75 MHz, CDCl3) δ:
164.5, 163.8 (2,4-F2Ph 2-C), 160.4, 160.1 (2,4-F2Ph 4-C),
151.6 (S-triazole S-C), 151.4 (triazole 3-C), 145.7
(S-triazole 5-C), 143.6 (triazole 5-C), 131.5, 131.3
(2,4-F2Ph 6-C), 117.8 (2,4-F2Ph 1-C), 111.0, 109.8
(2,4-F2Ph 5-C), 104.5, 104.4 (2,4-F2Ph 3-C), 48.6, 48.1,
36.2, 33.2, 29.8, 25.7, 25.5 (CH2) ppm; ESI-MS (m/z): 479
[M+H]+; HRMS (ESI) calcd. for C17H20F2N6S [M+H]+,
379.1516; found, 379.1512.
1
1024, 967, 853, 719 (C–S–C) cm–1; H NMR (300 MHz,
CDCl3) δ: 7.95 (s, 1H, triazole 3-H), 7.93 (s, 1H, S-triazole
H), 7.80 (s, 1H, triazole 5-H), 7.29–7.23 (m, 1H, 2,4-F2Ph
6-H), 6.82–6.77 (m, 2H, 2,4-F2Ph 3,5-H), 4.60 (t, 2H, J =
6.0 Hz, SCH2CH2), 4.42 (t, 2H, J = 6.0 Hz, SCH2), 4.31 (s,
2H, 2,4-F2Ph-CH2) ppm; 13C NMR (75 MHz, CDCl3) δ:
164.2, 161.1 (2,4-F2Ph 2-C), 160.9, 159.2 (2,4-F2Ph 4-C),
152.6 (S-triazole S-C), 152.2 (triazole 3-C), 143.8
(S-triazole 5-C), 143.6 (triazole 5-C), 131.8, 131.7
(2,4-F2Ph 6-C), 119.9, 119.8 (2,4-F2Ph 1-C), 111.5, 111.2
(2,4-F2Ph 5-C), 104.4, 104.1, 103.7 (2,4-F2Ph 3-C), 48.0,
47.4, 30.6 (CH2) ppm; ESI-MS (m/z): 323 [M+H]+; HRMS
(ESI) calcd. for C13H12F2N6S [M+H]+, 323.0890; found,
323.0892.
2-(2-(1H-1,2,4-Triazol-1-yl)ethyl)-1-(3,4-dichlorobenzyl)-1H-
1,2,4-triazole-3(2H)-thione (8a)
Compound 8a was prepared employing a procedure similar
to that used to synthesize compound 7a, starting from bro-
mide 6a (0.37 g, 1.0 mmol), 1H-1,2,4-triazole (0.07 g, 1.2
mmol) and potassium carbonate (0.17 g, 1.2 mmol). The
pure product 8a (0.24 g) was obtained as a yellow syrup.
Yield: 71.8%; IR (KBr) ν: 3112 (Ar–H), 2964, 2857 (CH2),
1558, 1506, 1472 (aromatic frame), 1354, 1263 (C=S), 1177,
1139, 1007, 972, 886, 681 cm–1; 1H NMR (300 MHz,
CDCl3) δ: 7.97 (s, 1H, triazole 3-H), 7.66 (s, 2H, S-triazole
H, triazole 5-H), 7.51–7.36 (m, 2H, 3,4-Cl2Ph 2,5-H),
7.23–7.21 (m, 1H, 3,4-Cl2Ph 6-H), 4.61–4.57 (m, 4H,
S-triazole N2-CH2CH2), 4.24 (s, 2H, 3,4-Cl2Ph-CH2) ppm;
13C NMR (75 MHz, CDCl3) δ: 158.7 (S=C), 151.0 (triazole
3-C), 142.9 (S-triazole 5-C), 142.2 (triazole 5-C), 137.1
(3,4-Cl2Ph 1-C), 132.7 (3,4-Cl2Ph 3-C), 131.5 (3,4-Cl2Ph
4-C), 130.7 (3,4-Cl2Ph 2-C), 130.5 (3,4-Cl2Ph 5-C), 128.1
(3,4-Cl2Ph 6-C), 48.4, 46.4, 36.1 (CH2) ppm; ESI-MS (m/z):
3-(4-(1H-1,2,4-Triazol-1-yl)butylthio)-1-(2,4-difluorobenzyl)-
1H-1,2,4-triazole (7e)
Compound 7e was prepared employing a procedure similar
to that used to synthesize compound 7a, starting from bro-
mide 5e (0.36 g, 1.0 mmol), 1H-1,2,4-triazole (0.07 g, 1.2
mmol) and potassium carbonate (0.17 g, 1.2 mmol). The
pure product 7e (0.29 g) was obtained as a yellow syrup.
Yield: 82.0%; IR (KBr) ν: 3113, 3077 (Ar–H), 2946, 2865
(CH2), 1603, 1505, 1477 (aromatic frame), 1357, 1181,
1
1139, 1013, 967, 852, 735 (C–S–C), 681 cm–1; H NMR
(300 MHz, CDCl3) δ: 8.03 (s, 1H, triazole 3-H), 7.94 (s, 1H,
triazole 5-H), 7.89 (s, 1H, S-triazole H), 7.35–7.30 (m, 1H,
2,4-F2Ph 6-H), 6.84–6.76 (m, 2H, 2,4-F2Ph 3,5-H), 4.40 (s,
2H, 2,4-F2Ph-CH2), 4.13 (t, 2H, J = 6.0 Hz, S(CH2)3CH2),
3.96 (t, 2H, J = 7.5 Hz, SCH2), 1.94–1.76 (m, 4H,

Wang QP, et al. Sci China Chem October (2012) Vol.55 No.10
2143
355 [M]+; HRMS (ESI) calcd. for C13H12Cl2N6S [M+H]+,
355.0299; found, 355.0297.
(3,4-Cl2Ph 6-C), 49.6, 49.4, 35.2, 29.5, 29.3, 25.8, 25.5
(CH2) ppm; ESI-MS (m/z): 411 [M]+; HRMS (ESI) calcd.
for C17H20Cl2N6S [M+H]+, 411.0925; found, 411.0928.
2-(4-(1H-1,2,4-Triazol-1-yl)butyl)-1-(3,4-dichlorobenzyl)-1H-
1,2,4-triazole-3(2H)-thione (8b)
2-(2-(1H-1,2,4-Triazol-1-yl)ethyl)-1-(2,4-difluorobenz-yl)-1H-
1,2,4-triazole-3(2H)-thione (8d)
Compound 8b was prepared employing a procedure similar
to that used to synthesize compound 7a starting from bro-
mide 6b (0.39 g, 1.0 mmol), 1H-1,2,4-triazole (0.07 g, 1.2
mmol) and potassium carbonate (0.17 g, 1.2 mmol). The
pure product 8b (0.29 g) was obtained as a yellow syrup.
Yield: 79.6%; IR (KBr) ν: 3110 (Ar–H), 2943, 2859 (CH2),
1555, 1503, 1467 (aromatic frame), 1352, 1268 (C=S), 1180,
1142, 1013, 961, 880, 677 cm–1; 1H NMR (300 MHz,
CDCl3) δ: 8.08 (s, 1H, triazole 3-H), 7.96 (s, 1H, S-triazole
H), 7.95 (s, 1H, triazole 5-H), 7.49–7.33 (m, 2H, 3,4-Cl2Ph
2,5-H), 7.24–7.22 (m, 1H, 3,4-Cl2Ph 6-H), 4.24 (s, 2H,
3,4-Cl2Ph-CH2), 4.16 (t, 2H, J = 6.0 Hz, S-triazole
N2-(CH2)3CH2), 4.08 (t, 2H, J = 6.0 Hz, S-triazole N2-CH2),
1.95–1.84 (m, 4H, S-triazole N2-CH2CH2CH2) ppm; 1H
NMR (300 MHz, DMSO-d6) δ: 8.51 (s, 1H, triazole 3-H),
8.49 (s, 1H, S-triazole H), 7.95 (s, 1H, triazole 5-H),
7.62–7.51 (m, 2H, 3,4-Cl2Ph 2,5-H), 7.36–7.32 (m, 1H,
3,4-Cl2Ph 6-H), 4.28 (s, 2H, 3,4-Cl2Ph-CH2), 4.18–4.12 (m,
4H, S-triazole N2-CH2(CH2)2CH2), 1.80–1.57 (m, 4H,
S-triazole N2-CH2CH2CH2) ppm; 13C NMR (75 MHz,
DMSO) δ: 157.6 (S-triazole S=C), 151.3 (triazole 3-C),
143.4 (S-triazole 5-C), 142.6 (triazole 5-C), 138.6
(3,4-Cl2Ph 1-C), 132.7 (3,4-Cl2Ph 3-C), 132.3 (3,4-Cl2Ph
4-C), 130.6 (3,4-Cl2Ph 2-C), 130.3 (3,4-Cl2Ph 5-C), 128.1
(3,4-Cl2Ph 6-C), 49.3, 48.5, 35.3, 27.4, 27.3 (CH2) ppm;
ESI-MS (m/z): 383 [M]+; HRMS (ESI) calcd. for
C15H16Cl2N6S [M+H]+, 383.0612; found, 383.0603.
Compound 8d was prepared employing a procedure sim-
ilar to that used to synthesize compound 7a starting from
bromide 6d (0.33 g, 1.0 mmol) and 1H-1,2,4-triazole (0.07
g, 1.2 mmol) and potassium carbonate (0.17 g, 1.2 mmol).
The pure product 8d (0.21 g) was obtained as a yellow syr-
up. Yield: 66.8%; IR (KBr) ν: 3114, 3078 (Ar–H), 2960
(CH2), 1603, 1503, 1437 (aromatic frame), 1358, 1262
(C=S), 1189, 1137, 1087, 967, 853, 679 cm–1; H NMR
1
(300 MHz, CDCl3) δ: 7.97 (s, 1H, triazole 3-H), 7.82 (s, 1H,
S-triazole H), 7.79 (s, 1H, triazole 5-H), 7.40–7.34 (m, 1H,
2,4-F2Ph 6-H), 6.83–6.78 (m, 2H, 2,4-F2Ph 3,5-H),
4.62–4.59 (m, 4H, S-triazole N2-CH2CH2), 4.31 (s, 2H,
2,4-F2Ph-CH2) ppm; 13C NMR (75 MHz, CDCl3) δ: 163.5,
162.8 (3,4-F2Ph 2-C), 160.8, 159.6 (3,4-F2Ph 4-C), 159.1
(S=C), 151.9 (triazole 3-C), 146.9 (S-triazole 5-C), 143.0
(triazole 5-C), 130.7, 130.6, 130.5 (2,4-F2Ph 6-C), 121.3
(2,4-F2Ph 1-C), 110.4, 110.1 (3,4-F2Ph 5-C), 103.3, 102.9,
102.8 (3,4-F2Ph 3-C), 47.5, 47.2, 37.9 (CH2) ppm; ESI-MS
(m/z): 323 [M+H]+; HRMS (ESI) calcd. for C13H12F2N6S
[M+H]+, 323.0890; found, 323.0895.
2-(4-(1H-1,2,4-Triazol-1-yl)butyl)-1-(2,4-difluorobenzyl)-1H-
1,2,4-triazole-3(2H)-thione (8e)
Compound 8e was prepared employing a procedure similar
to that used to synthesize compound 7a starting from bro-
mide 6e (0.36 g, 1.0 mmol), 1H-1,2,4-triazole (0.07 g, 1.2
mmol) and potassium carbonate (0.17 g, 1.2 mmol). The
pure product 8e (0.26 g) was obtained as a yellow syrup.
Yield: 74.6%; IR (KBr) ν: 3112 (Ar–H), 2946, 2866 (CH2),
1603, 1564, 1503, 1446 (aromatic frame), 1358, 1265 (C=S),
1187, 1138, 1087, 1015, 967, 853, 681 cm–1; 1H NMR (300
MHz, CDCl3) δ: 8.06 (s, 1H, triazole 3-H), 7.98 (s, 1H,
S-triazole H), 7.96 (s, 1H, triazole 5-H), 7.42–7.34 (m, 1H,
2,4-F2Ph 6-H), 6.81–6.75 (m, 2H, 2,4-F2Ph 3,5-H), 4.31 (s,
2H, 2,4-F2Ph-CH2), 4.18 (t, 2H, J = 6.0 Hz, S-triazole
N2-(CH2)3CH2), 4.10 (t, 2H, J = 6.0 Hz, S-triazole N2-CH2),
2.05–1.94 (m, 4H, S-triazole N2-CH2CH2CH2) ppm; 13C
NMR (75 MHz, CDCl3) δ: 164.1, 163.8 (2,4-F2Ph 2-C),
161.1, 160.9 (2,4-F2Ph 4-C), 159.9 (S=C), 151.1 (triazole
3-C), 143.6 (S-triazole 5-C), 142.2 (triazole 5-C), 130.1,
129.9 (2,4-F2Ph 6-C), 119.1, 118.9 (2,4-F2Ph 1-C), 111.5,
111.3 (2,4-F2Ph 5-C), 104.7, 104.4 (2,4-F2Ph 3-C), 48.0,
47.7, 33.4, 27.4, 27.2 (CH2) ppm; ESI-MS (m/z): 351
[M+H]+; HRMS (ESI) calcd. for C15H16F2N6S [M+H]+,
351.1203; found, 351.1203.
2-(6-(1H-1,2,4-Triazol-1-yl)hexyl)-1-(3,4-dichlorobenzyl)-1H-
1,2,4-triazole-3(2H)-thione (8c)
Compound 8c was prepared employing a procedure similar
to that used to synthesize compound 7a starting from bro-
mide 6c (0.42 g, 1.0 mmol), 1H-1,2,4-triazole (0.07 g, 1.2
mmol) and potassium carbonate (0.17 g, 1.2 mmol). The
pure product 8c (0.32 g) was obtained as a yellow syrup.
Yield: 76.9%; IR (KBr) ν: 3112 (Ar–H), 2940, 2860 (CH2),
1553, 1504, 1470 (aromatic frame), 1356, 1271 (C=S), 1179,
1
1138, 1014, 959, 879, 680 cm–1; H NMR (300 MHz,
CDCl3) δ: 8.06 (s, 1H, triazole 3-H), 7.96 (s, 1H, S-triazole
H), 7.94 (s, 1H, triazole 5-H), 7.48–7.32 (m, 2H, 3,4-Cl2Ph
2,5-H), 7.25–7.22 (m, 1H, 3,4-Cl2Ph 6-H), 4.21 (s, 2H,
3,4-Cl2Ph-CH2), 4.15 (t, 2H, J = 6.0 Hz, S-triazole
N2-(CH2)5CH2), 4.05 (t, 2H, J = 7.5 Hz, S-triazole N2-CH2),
1.90–1.81 (m, 4H, S-triazole N2-CH2CH2(CH2)2CH2),
1.35–1.25 (m, 4H, S-triazole N2-(CH2)2CH2CH2) ppm; 13C
NMR (75 MHz, CDCl3) δ: 159.8 (S=C), 151.9 (triazole
3-C), 144.9 (S-triazole 5-C), 142.9 (triazole 5-C), 138.2
(3,4-Cl2Ph 1-C), 132.1 (3,4-Cl2Ph 3-C), 130.9 (3,4-Cl2Ph
4-C), 130.2 (3,4-Cl2Ph 2-C), 128.3 (3,4-Cl2Ph 5-C), 126.9
2-(6-(1H-1,2,4-Triazol-1-yl)hexyl)-1-(2,4-difluorobenzyl)-1H-
1,2,4-triazole-3(2H)-thione (8f)
Compound 8f was prepared employing a procedure sim-

2144
Wang QP, et al. Sci China Chem October (2012) Vol.55 No.10
ilar to that used to synthesize compound 7a starting from
bromide 6f (0.39 g, 1.0 mmol), 1H-1,2,4-triazole (0.07 g,
1.2 mmol) and potassium carbonate (0.17 g, 1.2 mmol). The
pure product 8f (0.29 g) was obtained as a yellow syrup.
Yield: 75.1%; IR (KBr) ν: 3111 (Ar–H), 2941, 2861 (CH2),
1604, 1503, 1477 (aromatic frame), 1358, 1264 (C=S), 1187,
1139, 1088, 1019, 967, 853, 681 cm–1; 1H NMR (300 MHz,
CDCl3) δ: 8.08 (s, 1H, triazole 3-H), 7.97 (s, 1H, S-triazole
H), 7.94 (s, 1H, triazole 5-H), 7.44–7.36 (m, 1H, 2,4-F2Ph
6-H), 6.81–6.75 (m, 2H, 2,4-F2Ph 3,5-H), 4.32 (s, 2H,
2,4-F2Ph-CH2), 4.16 (t, 2H, J = 6.0 Hz, S-triazole
N2-(CH2)5CH2), 4.07 (t, 2H, J = 7.5 Hz, S-triazole N2-CH2),
1.97–1.87 (m, 4H, S-triazole N2-CH2CH2(CH2)2CH2),
1.34–1.23 (m, 4H, S-triazole N2-(CH2)2CH2CH2) ppm; 13C
NMR (75 MHz, CDCl3) δ: 164.2, 164.0 (2,4-F2Ph 2-C),
160.8, 160.5 (2,4-F2Ph 4-C), 159.5 (S=C), 152.0 (triazole
3-C), 145.0 (S-triazole 5-C), 143.1 (triazole 5-C), 130.6,
130.4 (2,4-F2Ph 6-C), 118.0, 117.9 (2,4-F2Ph 1-C), 111.2,
110.9 (2,4-F2Ph 5-C), 104.3, 104.1 (2,4-F2Ph 3-C), 48.2,
47.8, 36.5, 30.3, 28.5, 25.8, 25.7 (CH2) ppm; ESI-MS (m/z):
379 [M+H]+; HRMS (ESI) calcd. for C17H20F2N6S [M+H]+,
379.1516; found, 379.1520.
554.6422.
1-((2-(3,4-Dichlorobenzyl)-4-octyl-5-thioxo-2,5-dihydro-
1H-1,2,4-triazol-4-ium-1-yl)methyl)-4-octyl-1H-1,2,4-triazol-
4-ium bromide (9b)
Compound 9b was prepared employing a procedure similar
to that used to synthesize compound 9a starting from thione
8b (0.38 g, 1.0 mmol) and 1-bromooctane (0.46 g, 2.4
mmol). The pure compound 9b (0.51 g) was obtained as a
brown syrup. Yield: 65.2%; IR (KBr) ν: 3115 (Ar–H), 2927,
2850 (CH2), 1613, 1551, 1514, 1463 (aromatic frame), 1269
(C=S), 1142, 1091, 1023, 974, 848, 637 cm–1; H NMR
1
(300 MHz, DMSO-d6) δ: 10.38 (s, 1H, S-triazole H), 10.36
(s, 1H, triazole 3-H), 9.35 (s, 1H, triazole 5-H), 7.79−7.50
(m, 2H, 3,4-Cl2Ph 2,5-H), 7.42−7.27 (m, 1H, 3,4-Cl2Ph
6-H), 4.71−4.19 (m, 6H, S-triazole N2-CH2(CH2)2CH2,
S-triazole N1-CH2), 3.34−4.19 (m, 4H, triazole N4-CH2,
S-triazole N4-CH2), 2.33−1.75 (m, 8H, S-triazole
N2-CH2(CH2)2, triazole N4-CH2CH2, S-triazole N4-CH2CH2),
1.35−1.27 (m, 20H, triazole N4-CH2CH2 (CH2)5, S-triazole
N4-CH2CH2(CH2)5), 0.87 (t, 6H, J = 6.0 Hz, triazole
N4-(CH2)7CH3, S-triazole N4-(CH2)7CH3) ppm; 13C NMR
(75 MHz, DMSO-d6) δ: 159.4 (S=C), 155.5 (triazole 3-C),
147.1 (S-triazole 5-C), 143.5 (triazole 5-C), 137.1
(3,4-Cl2Ph 1-C), 132.6 (3,4-Cl2Ph 3-C), 131.8 (3,4-Cl2Ph
4-C), 131.0 (3,4-Cl2Ph 2-C), 130.7 (3,4-Cl2Ph 5-C), 128.5
(3,4-Cl2Ph 6-C), 56.6, 50.7, 47.4, 47.3, 32.0, 31.7, 30.1,
29.7, 29.6, 29.5, 29.3, 29.0, 28.1, 27.6, 25.5, 25.3, 23.2,
22.9 (CH2), 14.6, 14.3 (CH3) ppm; ESI-MS (m/z): 690
[M–Br]+, 609 [M–2Br]+; HRMS (ESI) calcd. for
C31H50Br2Cl2N6S [M–2Br+H]+, 609.3273; found, 609.3275.
1-(4-(2-(3,4-Dichlorobenzyl)-4-hexyl-5-thioxo-2,5-dihydro-
1H-1,2,4-triazol-4-ium-1-yl)butyl)-4-hexyl-1H-1,2,4-triazol-
4-ium bromide (9a)
A solution of thione 8b (0.38 g, 1.0 mmol) and 1-bro-
mooctane (0.40 g, 2.4 mmol) in anhydrous acetonitrile (5
mL) was stirred under reflux and monitored by TLC (eluent,
chloroform/methanol, 30/1, v/v). Upon completion of the
reaction, the solvent was evaporated under vacuum and the
residue was washed three times with petroleum ether
(30−60 ºC) and dried to afford pure compound 9a (0.54 g)
as a brown syrup. Yield: 76.2%; IR (KBr) ν: 3055 (Ar–H),
2928, 2858 (CH2), 1605, 1561, 1500, 1473 (aromatic frame),
1271 (C=S), 1146, 1097, 1029, 972, 889, 851, 764, 684
1-((2,4-Bis(3,4-dichlorobenzyl)-5-thioxo-2,5-dihydro-1H-
1,2,4-triazol-4-ium-1-yl)methyl)-4-(3,4-dichlorobenzyl)-1H-
1,2,4-triazol-4-ium chloride (10a)
Compound 10a was prepared employing a procedure simi-
lar to that used to synthesize compound 9a, starting from
thione 8b (0.38 g, 1.0 mmol) and 3,4-dichlorobenzyl chlo-
ride (0.47 g, 2.4 mmol). The pure product 10a (0.55 g) was
obtained as a brown syrup. Yield: 71.3%; IR (KBr) ν: 3123,
3084 (Ar–H), 2938 (CH2), 1609, 1568, 1467 (aromatic
1
cm–1; H NMR (300 MHz, DMSO-d6) δ: 10.39 (s, 1H,
S-triazole H), 10.35 (s, 1H, triazole 3-H), 9.34 (s, 1H, tria-
zole 5-H), 7.92−7.70 (m, 2H, 3,4-Cl2Ph 2,5-H), 7.61−7.43
(m, 1H, 3,4-Cl2Ph 6-H), 4.54−4.06 (m, 6H, S-triazole
N2-CH2(CH2)2CH2, S-triazole N1-CH2), 3.35−3.21 (m, 4H,
S-triazole N4-CH2, triazole N4-CH2), 1.95−1.64 (m, 8H,
S-triazole N2-CH2(CH2)2, S-triazole N4-CH2CH2, triazole
N4-CH2CH2), 1.39−1.20 (m, 12H, S-triazole N4-(CH2)2-
(CH2)3, triazole N4-(CH2)2(CH2)3), 0.87 (t, 6H, J = 6.0 Hz,
S-triazole N4-(CH2)5CH3, triazole N4-(CH2)5CH3) ppm; 13C
NMR (75 MHz, DMSO-d6) δ: 159.2 (S=C), 154.7 (triazole
3-C), 147.1 (S-triazole 5-C), 142.8 (triazole 5-C), 137.0
(3,4-Cl2Ph 1-C), 132.9 (3,4-Cl2Ph 3-C), 131.5 (3,4-Cl2Ph
4-C), 130.7 (3,4-Cl2Ph 2-C), 130.3 (3,4-Cl2Ph 5-C), 128.2
(3,4-Cl2Ph 6-C), 51.4, 46.2, 45.6, 36.5, 32.4, 31.8, 28.7,
28.4, 27.5, 27.1, 25.7, 25.6, 22.6, 22.4 (CH2), 14.3, 14.2
(CH3) ppm; ESI-MS (m/z): 553 [M–2Br]+; HRMS (ESI)
calcd. for C27H42Br2Cl2N6S [M–2Br+H]+, 554.6415; found,
frame), 1267 (C=S), 1140, 1032, 885, 625 cm–1; H NMR
1
(300 MHz, DMSO-d6) δ: 10.64 (s, 1H, S-triazole H), 10.52
(s, 1H, triazole 3-H), 9.43 (s, 1H, triazole 5-H), 7.92–7.52
(m, 6H, 3,4-Cl2Ph 2,5-H), 7.45–7.36 (m, 3H, 3,4-Cl2Ph
6-H), 5.60 (s, 2H, S-triazole N4-CH2), 5.44 (s, 2H, triazole
N4-CH2), 4.46–4.35 (m, 6H, S-triazole N1-CH2, triazole N1-
CH2(CH2)2CH2), 1.91–1.94 (m, 4H, triazole N1-CH2(CH2)2)
ppm; 13C NMR (75 MHz, DMSO-d6) δ: 161.5 (S=C), 155.7
(triazole 3-C), 146.6 (S-triazole 5-C), 144.7 (triazole 5-C),
138.9, 138.7 (3,4-Cl2Ph 1-C), 133.7, 133.5, 132.9
(3,4-Cl2Ph 3-C), 132.4, 132.1 (3,4-Cl2Ph 4-C), 131.5, 131.3
(3,4-Cl2Ph 2-C), 130.7, 130.5 (3,4-Cl2Ph 5-C), 128.3, 128.0
(3,4-Cl2Ph 6-C), 54.7, 51.5, 45.8, 45.1, 32.4, 26.3, 25.9

Wang QP, et al. Sci China Chem October (2012) Vol.55 No.10
2145
(CH2) ppm; ESI-MS (m/z): 702 [M−2Cl]+; HRMS (ESI)
calcd. for C29H26Cl8N6S [M−2Cl+H]+, 701.0149; found,
701.0156.
rin-CH3), 1.93−1.74 (m, 12H, coumarin O-CH2CH2(CH2)2-
CH2, triazole N1-CH2CH2CH2), 1.40−1.28 (m, 8H, couma-
rin O-(CH2)2CH2CH2) ppm; 13C NMR (75 MHz, DMSO-d6)
δ: 162.1 (2C, coumarin 2-C), 160.6 (2C, coumarin 7-C),
159.6 (S=C), 155.2 (2C, coumarin 9-C), 155.1 (triazole 3-C),
153.8 (2C, coumarin 4-C), 145.1 (S-triazole 5-C), 143.1
(triazole 5-C), 137.9 (3,4-Cl2Ph 1-C), 132.0 (3,4-Cl2Ph 3-C),
131.6 (3,4-Cl2Ph 4-C), 130.9 (3,4-Cl2Ph 2-C), 130.1
(3,4-Cl2Ph 5-C), 129.6 (3,4-Cl2Ph 6-C), 126.8 (2C, couma-
rin 5-C), 113.4 (2C, coumarin 3-C), 112.8 (2C, coumarin
10-C), 111.4 (2C, coumarin 6-C), 101.4 (2C, coumarin 8-C),
68.5, 61.0, 51.5, 51.2, 35.6, 33.1, 32.8, 32.6, 29.1, 28.7,
28.6, 28.3, 27.9, 27.7, 25.6, 25.2, 25.0 (CH2), 18.6 (2C, CH3)
ppm; ESI-MS (m/z): 901 [M–2Br]+; HRMS (ESI) calcd. for
C47H54Br2Cl2N6O6S [M–2Br+H]+, 901.3281; found,
901.3290.
1-((2-(3,4-Dichlorobenzyl)-4-(2,4-difluorobenzyl)-5-thioxo-
2,5-dihydro-1H-1,2,4-triazol-4-ium-1-yl)methyl)-4-(2,4-
difluorobenzyl)-1H-1,2,4-triazol-4-ium bromide (10b)
Compound 10b was prepared employing a procedure simi-
lar to that used to synthesize compound 9a, starting from
thione 8b (0.38 g, 1.0 mmol) and 2,4-difluorobenzyl bro-
mide (0.49 g, 2.4 mmol). The pure product 10b (0.57 g) was
obtained as a white solid. Yield: 75.1%; mp 166−168 ºC; IR
(KBr) ν: 3120, 3089 (Ar–H), 2997, 2931 (CH2), 1612, 1559,
1506, (aromatic frame), 1278 (C=S), 1142, 1093, 970, 857,
814, 641 cm–1; 1H NMR (300 MHz, DMSO-d6) δ: 10.35 (s,
2H, triazole 3-H, S-triazole H), 9.37 (s, 1H, triazole 5-H),
7.74−7.63 (m, 2H, 3,4-Cl2Ph 2,5-H), 7.54−7.48 (m, 2H,
2,4-F2Ph 6-H), 7.43−7.35 (m, 1H, 3,4-Cl2Ph 6-H),
7.24−7.05 (m, 4H, 2,4-F2Ph 3,5-H), 5.61 (s, 2H, S-triazole
N4-CH2), 5.43 (s, 2H, triazole N4-CH2), 4.48−4.45 (m, 6H,
S-triazole N1-CH2, S-triazole N2-CH2(CH2)CH2), 1.91−1.88
(m, 4H, triazole-CH2(CH2)2) ppm; 13C NMR (75 MHz,
DMSO-d6) δ: 164.2 (2,4-F2Ph 2-C), 162.7, 160.8 (2,4-F2Ph
4-C), 159.9 (S=C), 156.2 (triazole 3-C), 149.4 (S-triazole
5-C), 143.3 (triazole 5-C), 139.1 (3,4-Cl2Ph 1-C), 133.6
(3,4-Cl2Ph 3-C), 133.5 (3,4-Cl2Ph 4-C), 133.3 (3,4-Cl2Ph
2-C), 130.3 (3,4-Cl2Ph 5-C), 127.5 (3,4-Cl2Ph 6-C), 130.3,
130.0 (2,4-F2Ph 6-C), 119.8, 119.6 (2,4-F2Ph 1-C), 117.6,
117.4 (2,4-F2Ph 5-C), 104.9, 104.7, 104.3 (2,4-F2Ph 3-C),
51.7, 51.3, 44.8, 44.6, 30.7, 25.1, 25.0 (CH2) ppm; ESI-MS
(m/z): 637 [M–2Br]+; HRMS (ESI) calcd. for
C29H26Br2Cl2F4N6S [M–2Br+H]+, 637.1320; found,
637.1327.
2.3 Biological assays
All the new 1,2,4-triazole derivatives 2–11 were evaluated
for antimicrobial activities against MRSA (N315), S. aureus
(ATCC25923), B. subtilis and M. luteus (ATCC4698) as
Gram-positive bacteria, E. coli (DH52), S. dysenteriae, P.
aeruginosa and E. typhosa as Gram-negative bacteria, as
well as C. albicans (ATCC76615) and C. mycoderma as
fungi according to the NCCLS [51, 52]. The tested microbi-
al strains were provided by the School of Pharmaceutical
Sciences, Southwest University and the College of Phar-
macy, Third Military Medical University. Minimal inhibi-
tory concentration (MIC, μg/mL) is defined as the lowest
concentration of the tested compounds required to com-
pletely inhibit the growth of microbial strains, and deter-
mined by means of the standard two-fold serial dilution
method in 96-well microtest plates taking Chloromycin,
Norfloxacin and Fluconazole as reference drugs. To ensure
that the solvent had no effect on bacterial growth, a control
experiment was performed by testing the medium supple-
mented with DMSO at the same concentration used in the
experiment. All the bacteria and fungi growth was moni-
tored visually and spectrophotometrically. The antimicrobi-
al active data are summarized in Table 3.
1-(4-(2-(3,4-Dichlorobenzyl)-4-(6-(4-methyl-2-oxo-2H-chro
men-7-yloxy)hexyl)-5-thioxo-2,5-dihydro-1H-1,2,4-triazol-4-
ium-1-yl)butyl)-4-(6-(4-methyl-2-oxo-2H-chromen-7-yloxy)
hexyl)-1H-1,2,4- triazol-4-ium bromide (11)
Compound 11 was prepared employing a procedure similar
to that used to synthesize compound 9a starting from thione
8b (0.38 g, 1.0 mmol) and 7-(6-bromohexyloxy)-4-methyl-
2H-chromen-2-one (0.81 g, 2.4 mmol). The pure prod-
uct 11 (0.71 g) was obtained as a yellow syrup. Yield:
65.3%; IR (KBr) ν: 3127, 3067 (Ar–H), 2939, 2896 (CH2),
1613, 1504, 1442 (aromatic frame), 1288 (C=S), 1203, 1146,
1072, 1021, 864, 638 cm–1; 1H NMR (300 MHz, DMSO-d6)
δ: 10.28 (s, 1H, S-triazole H), 10.20 (s, 1H, triazole 3-H),
9.29 (s, 1H, triazole 5-H), 7.86−7.44 (m, 5H, 3,4-Cl2Ph
2,5,6-H, coumarin 5-H), 6.92−6.96 (m, 4H, coumarin
6,8-H), 6.19 (s, 2H, coumarin 3-H), 5.55 (s, 2H, S-triazole
N4-CH2), 5.41 (s, 2H, triazole N4-CH2), 4.51−4.46 (t, 2H, J
= 7.5 Hz, S-triazole N2-CH2), 4.40 (s, 2H, S-triazole
N1-CH2), 4.29−4.25 (t, 2H, J = 6.0 Hz, triazole N1-CH2),
4.09−4.03 (m, 4H, coumarin O-CH2), 2.38 (s, 6H, couma-
Antibacterial assays
The prepared compounds 2−11 were evaluated on their an-
tibacterial activities against MRSA (N315), S. aureus
(ATCC25923), B. subtilis and M. luteus (ATCC4698) as
Gram-positive bacteria, E. coli (DH52), S. dysenteriae, P.
aeruginosa and E. typhosa as Gram-negative bacteria. The
bacterial suspension was adjusted with sterile saline to a
concentration of 1 × 105
CFU. The tested compounds were
dissolved in DMSO to prepare the stock solutions. The
tested compounds and reference drugs were prepared in
Mueller–Hinton broth (Guangdong Huaikai Microbial Sci.&
Tech. Co., Ltd., Guangzhou, Guangdong, China) by

2146
Wang QP, et al. Sci China Chem October (2012) Vol.55 No.10
two-fold serial dilution to obtain the required concentrations
of 512, 256, 128, 64, 32, 16, 8, 4, 2, 1, 0.5 μg/mL. These
dilutions were inoculated and incubated at 37 ºC for 24 h.
azole-3-thiol 2 was prepared via a newly developed mul-
ti-component procedure without isolation of intermediates.
This method provided an efficient procedure for the synthe-
sis of triazole-thiols with easy and convenient operation,
short reaction time and high yield etc. A possible mecha-
nism is shown in Scheme 2. It could involve the generation
of halobenzyl hydrazinecarbothioamide A which was gen-
erated by the substitution of halobenzyl halide 1 with thio-
semicarbazide, and then further nucleophilic reaction of
intermediate A with formic acid could afford the intermedi-
ate B. Subsequent cyclization of compound A under acid
conditions could produce the desired triazole-thiol 2 whose
structure was confirmed by spectral analysis.
The experimental results manifested that the solvent and
base significantly affected the formation of the products 2a
and b (Table 1). It was noticed that ethanol led to relatively
high yields in contrast to acetonitrile because of the better
solubility of thiosemicarbazide in ethanol. On the other
hand, the presence of base resulted in lower yields of target
compounds owing to the formation of by-products. Conse-
quently, thiosemicarbazide and halobenzyl halides could
react to produce compounds 2a and b in satisfactory yields
(72.9% and 82.3% respectively) when dissolved in ethanol
in the absence of base.
Antifungal assays
Compounds 2−11 were evaluated for their antifungal activi-
ties against C. albicans (ATCC76615) and C. mycoderma.
A spore suspension in sterile distilled water was prepared
from 1-day old culture of the fungi growing on Sabouraud
agar (SA) media. The final spore concentration was 1−5 ×
103 spore mL–1. Using the stock solutions of the tested
compounds and reference antifungal Fluconazole, dilutions
in sterile RPMI 1640 medium (Neuronbc Laboraton Tech-
nology Co., Ltd, Beijing, China) were generated in eleven
desired concentrations (0.5 to 512 μg/mL) for each tested
compound. These dilutions were inoculated and incubated
at 35 ºC for 24 h.
3 Results and discussion
3.1 Synthesis of triazole-thioethers and thiones
The synthetic route of the target thio-triazole compounds
was outlined in Scheme 1. The 1-halobenzyl-1H-1,2,4-tri-
N
X
N
N
SH
S
S
N
N
N
N
N
N
n
n
a, b
Br
X1
e
N N
X1
X1
X1
d
1a b
N
X2
2a b
1, 2: a, X1 = 3-Cl, X2 = Cl
X2
7a f
5a f
X2
N
X2
b, X1 = 2-F, X2 = F
c
5 8: a, X1 = 3-Cl, X2 = Cl, n = 2
b, X1 = 3-Cl, X2 = Cl, n = 4
c, X1 = 3-Cl, X2 = Cl, n = 6
d, X1 = 2-F, X2 = F, n = 2
e, X1 = 2-F, X2 = F, n = 4
f, X1 = 2-F, X2 = F, n = 6
S
N
N
N
S
n
N
S
Br
N
N
X1
N N
R
R
6a f
X2
X1
X1
e
3a f
n CH3
S
N
N
X2
4a f
X2
N
N
N
2Br
4
S
3, 4: a, X1 = 3-Cl, X2 = Cl, R = (CH2)6CH3
b, X1 = 3-Cl, X2 = Cl, R = 3,4-Cl2Ph
c, X1 = 3-Cl, X2 = Cl, R = 2,4-F2Ph
d, X1 = 2-F, X2 = F, R = (CH2)6CH3
e, X1 = 2-F, X2 = F, R = 3,4-Cl2Ph
f, X1 = 2-F, X2 = F, R = 2,4-F2Ph
f
N
N N
n
N
N N
CH3
Cl
X1
n
Cl
N
g
9: a, n = 5; b, n = 7
h
X2 8a f
Cl
Cl
N
N
R3
2X
N
N
6 O
10: a, R1 = H, R2 = Cl,
N
N
S
R3 = Cl, X = Cl
b, R1 = F, R2 = H,
R3 = F, X = Br
R2
R1
N
4
2Br
CH3
O
S
N
O
4 N
N
N
N
Cl
R1
R3
H3C
O
O
O
Cl
R2
6
11
10a, b
Scheme 1 Synthetic route of triazole-thiols and their derivatives. Conditions and reagents: (a) NH2NHCSNH2, CH3CH2OH, 40 °C; (b) HCOOH, H2SO4,
H2O, 100 °C; (c) alkyl or aryl halide, K2CO3, TBAI, CH3COCH3, 40 °C; (d) alkyl dibromide, K2CO3, TBAI, CH3COCH3, 40 °C; (e) 1,2,4-triazole, K2CO3,
TBAI, CH3CN, 40 °C; (f) alkyl bromide, CH3CN, reflux; (g) aryl halide, CH3CN, reflux; (h) 7-(6-bromohexyloxy)-4-methyl-2H-chromen-2-one, CH3CN,
reflux.

Wang QP, et al. Sci China Chem October (2012) Vol.55 No.10
2147
Table 1 The effects of solvent and base on yields of triazole-thiols 2a–b
from 65.2% to 75.1% after purification by washing with
petroleum ether or dichloromethane. Notably, the formation
of halobenzyl triazolium 10 (12 h) was faster than the alkyl
triazolium 9 (24 h), while the preparation of the coumarin
derived triazolium 11 required a longer reaction time (> 48
h), probably due to the steric hindrance of the coumarin
moiety.
EtOH
CH3CN
Solvent
Base
NaOH K2CO3 Absence NaOH K2CO3 Absence
Yield (%)
2a
Yield (%)
10.5
12.7
34.9
40.1
82.3
72.9
9.3
21.3
18.5
57.2
63.4
10.8
2b
3.3 Spectral analysis
All the new compounds were characterized by 1H NMR, 13
C
NMR, FTIR, MS and HRMS spectra. The spectral data
were in accordance with the assigned structures and were
provided in the experimental protocol section. The mass
spectra of all the target compounds were in agreement with
their molecular formulas.
In the FTIR spectra of compounds 2a–b, characteristic
stretching frequencies of the thiol moiety at 2709–2668
cm–1 demonstrated the structure of the triazole-thiols, while
their absence in compounds 3–11 suggested that the thiol
group of triazole-thiols reacted with halides. Moreover, tri-
azole-thione compounds 4a–f, 6a–f and 8a–f gave strong
absorption peaks at 1288–1259 cm–1 due to the stretching
vibration of C=S in the triazole-thione moiety, while the
bending vibration of C–S–C in thioethers 3a–f, 5a–f and
7a–f gave absorption peaks at the region of 739–710 cm–1.
In addition, the moderate absorption bands at 3123–3055
cm–1 and 2998–2775 cm–1 were attributed to the stretching
vibration of aromatic and aliphatic C–H, respectively, while
the aromatic frame exhibited characteristic stretching fre-
quencies in the region between 1616 and 1430 cm–1. All the
other absorption bands were also observed at expected re-
gions.
Scheme 2 Possible mechanism for the synthesis of triazole-thiol 2.
Scheme 3 Tautomerism of triazole-thiols in the presence of potassium
carbonate.
Triazole-thioethers 3a–f were prepared via the alkylation
reaction of compounds 2a and b with a series of halides in
acetone using potassium carbonate as base and tetrabu-
tylammonium iodide as phase-transfer catalyst, while tria-
zole-thiones 4a–f were synthesized employing a procedure
similar to that used to synthesize compounds 3a–f. This
phenomenon was probably due to the existence of tauto-
meric forms C and D of triazole-thiols in the presence of
potassium carbonate (Scheme 3). The experiments revealed
that triazole-thione, the thermodynamic product [53], was
obtained as the major product at higher temperature (80 ºC)
via intermediate D and the thiol was generally converted
into thioether at room temperature. The reaction took place
at 40 ºC to give thioether 3 and thione 4 respectively in the
yields of 20.0%–49.7%. The bromides 5 and 6 were simul-
taneously produced according to the general procedure de-
scribed for the preparation of compounds 3 and 4 in the
yields of 23.7%–46.5%, and their further reactions with
1,2,4-triazole in the presence of potassium carbonate and
tetrabutylammonium iodide produced the bis-triazoles 7a–f
and 8a–f in good yields (66.8%–91.7%).
1
As for H NMR spectra, compounds 2–4, 7 and 8 gave
singlets at 4.42–4.24 ppm assigned to the methylene proton
Ha (Table 2). Triazole-thiones 4 and 8 (4.32–4.21 ppm) dis-
played relatively upfield shifts for Ha when compared with
triazole-thiol 2 and thioethers 3 and 7 (4.40–4.24 ppm) be-
cause of destruction of the conjugated system by the for-
mation of triazole-thione, which resulted in the decreased
electron-withdrawing ability of the triazole moiety. Fur-
thermore, substitution of triazole-thiol 2 (8.16–8.15 ppm) to
yield compounds 3, 4, 7 and 8 led to upfield shifts of Hb to
8.05–7.66 ppm. Moreover, in contrast to the thioethers 3
and 7, the corresponding triazole-thiones 4 and 8 gave rela-
tively downfield chemical shifts for Hb due to the elec-
tron-withdrawing character of C=S in the triazole-thione
structure, except for compounds 7a, 7d, 8a and 8d (Figure
1). This phenomenon was probably ascribed to the remote
interaction of the triazole ring with the triazole-thione moi-
ety with a short (CH2)2 linker and thus caused a decrease of
Hb in thiones 8a and 8d. Notably, proton Hb of halobenzyl
derivatives 3b–c, 3e–f, 4b–c and 4e–f with the elec-
tron-withdrawing halobenzyl groups on the triazole ring
gave higher chemical shifts than the corresponding alkyl-
3.2 Synthesis of triazoliums
The desired triazolium derivatives 9–11 were synthesized
through the reactions of thione 8b with excessive alkyl hal-
ides and aryl halides in acetonitrile under reflux. All the
triazoliums were synthesized in satisfactory yields ranging

2148
Wang QP, et al. Sci China Chem October (2012) Vol.55 No.10
Table 2 Some 1H NMR data (δ/ppm) of compounds 2–4 and 7, 8
Compds
2a
Ha
Hb
Hc
Compds
2b
4a
Ha
Hb
Hc
4.30
4.36
4.36
4.36
4.41
4.41
4.42
4.24
4.35
4.33
4.31
4.40
4.37
8.15
7.89
7.93
7.94
7.88
7.94
7.92
7.90
7.88
7.85
7.93
7.89
7.87
–
4.37
4.26
4.25
4.24
4.32
4.32
4.30
4.24
4.24
4.21
4.31
4.31
4.32
8.16
7.96
8.04
8.04
7.98
8.05
8.05
7.66
7.96
7.96
7.82
7.98
7.97
–
3a
3.97
5.13
5.18
3.95
5.12
5.19
4.43
3.95
3.95
4.42
3.96
3.97
4.07
5.21
5.25
4.06
5.22
5.27
4.59
4.08
4.05
4.60
4.18
4.16
3b
3c
4b
4c
3d
3e
4d
4e
3f
4f
7a
8a
7b
7c
8b
8c
7d
7e
8d
8e
7f
8f
1
Figure 2 Some H NMR data (δ/ppm) of compound 8b and its triazoli-
ums 9–11.
downfield 13C chemical shifts for C=S carbons of the
S-triazole rings in contrast to the carbons (CS) of the cor-
responding thioethers 3, 5 and 7. It was noticed that the
3-position carbons in the triazole and S-triazole rings gave
larger δ values than the 5-position carbons for compounds
3–8. In comparison with triazole thioethers 3, 5 and 7
(153.7–151.6 ppm), the thiones 4, 6 and 8 displayed rela-
tively large 13C signals at 160.1–155.6 ppm for the
3-position carbon of the S-triazole rings, which were as-
cribed to the electron-withdrawing characteristics of the
thione moieties. However, all the carbons in the halobenzyl
moieties linking with the N1-position of S-triazoles exhibit-
ed no significant changes of chemical shifts for the thi-
oethers and thiones. Moreover, the transformation of
bis-triazole 8b into its triazoliums 9–11 resulted in down-
field 13C shifts with 0.2–4.9 ppm for the carbons of triazole
rings due to the formation of positive charges on both tria-
zole and S-triazole groups, while all the other carbons gave
13C peaks in the expected regions.
Figure 1 1H NMR shifts for Hb of thioethers 3 and 7 and thiones 4 and 8.
compounds 3a, 3d, 4a and 4d. In addition, tria-
zole-thioethers 3 and 7 displayed upfield shifts (5.19–3.97
ppm) for proton Hc when compared with the corresponding
thiones 4 and 8 (5.27–4.05 ppm), which was probably re-
lated to the strong electron-donating ability of the thioether
group.
Triazoliums 9–11 showed large downfield shifts for pro-
ton Hb in comparison with triazole-thione 8b, due to the
positive charge on the triazole-thione ring. Meanwhile, the
formation of the second triazolium on the 1,2,4-triazole
moiety also endowed protons Hd and He with larger δ values
than compound 8b (Figure 2). These evidences proved the
structure of bis-triazolium, and the positive charges on ni-
trogen atoms resulted in obvious downfield shifts.
3.4 Antibacterial activity
The antibacterial activity results indicated that all the halo-
benzyl triazole-thiols as well as their derivatives could in-
hibit the growth of the tested bacteria in vitro to some extent.
Particularly, bis-triazole thiones 8a–c and the triazoliums
9–11 showed broader antimicrobial spectrum and potent
antibacterial activities in comparison with other compounds.
Furthermore, the results also showed that incorporation of
the second triazolyl group, which formed compounds 7 and
The 13C NMR spectra of all the compounds were in ac-
cordance with the assigned structures. The conversions of
triazole-thiols 2a and b into thiones 4, 6 and 8 resulted in

Wang QP, et al. Sci China Chem October (2012) Vol.55 No.10
2149
8, gave superior antibacterial efficiency to those of the in-
termediates including triazole-thiol 2 and bromides 5 and 6.
However, most compounds exerted negative efficacy to-
ward MRSA and S. dysenteriae.
kyl and aryl groups were designed and prepared to investi-
gate the effect of the triazolium moiety on antimicrobial
activities. The bioactive results manifested that all the tria-
zoliums exhibited significantly enhanced antibacterial activ-
ities to all the tested strains (MIC = 1–128 μg/mL) than
their precursor 8b, particularly for S. aureus, M. luteus and
E. coli with low inhibitory concentrations in the range of
1–16 μg/mL. It seemed that introduction of electropositive
triazolium should be helpful in improving antibacterial ef-
ficacy. Moreover, alkyl triazolium 9 was more sensitive to
the tested strains than other triazoliums 10–11 especially
toward S. aureus, B. subtilis, E. coli, P. aeruginosa and E.
typhosa with MIC values below 8 μg/mL, which was com-
parable to the reference drugs Chloromycin and Norfloxacin.
Notably, the hexyl triazolium 9a displayed comparable ac-
tivities against all the tested strains to the reference drugs
except for MRSA, particularly toward E. coli (MIC = 1
μg/mL), which was 2- and 4-fold more potent than Chloro-
mycin and Norfloxacin, respectively. Furthermore, it
showed more significant inhibition against P. aeruginosa
than Chloromycin (MIC = 16 μg/mL) at the concentration
of 4 μg/mL, while it was also highly active to S. aureus at
the low concentration of 2 μg/mL. Moreover, the octyl tria-
zolium 9b gave lower anti-P. aeruginosa concentration
(MIC = 8 μg/mL) than Chloromycin (MIC = 16 μg/mL). It
was especially noteworthy that the 2,4-diflorobenzyl de-
Halobenzyl triazole-thiols 2a and b, as shown in Table 3,
exhibited poor activities against all the tested bacterial
strains (MIC = 128–512 μg/mL). No significantly improved
efficiency was obtained for thioethers 3a–f and 5a–f by
introducing alkyl or aryl groups. Interestingly, introduction
of the thione moiety to compounds 4a–f and 6a–f resulted
in increased antibacterial potency to most tested strains in
comparison with compounds 2a and b and the correspond-
ing thioethers 3 and 5. Particularly, 3,4-dichlorobenzyl tria-
zole-thiones 4b–c with halobenzyl substituents exhibited
moderate to good bioactivities (MIC = 32–128 μg/mL) in
inhibiting the growth of all the tested bacteria, while tria-
zole-thiones 6a–f showed moderate activities against
MRSA, S. aureus, P. aeruginosa and E. typhosa at the con-
centration below 128 μg/mL. The results manifested that
thiones were more sensitive to bacteria than the corre-
sponding thioethers, and introduction of different substitu-
ents specially the halobenzyl moieties could attribute to
improved biological activities to some extent.
For the tested bis-triazole thioethers 7a–f, all the com-
pounds displayed good inhibitory efficiency toward bacteri-
al strains when compared with their corresponding bro-
mides 5a–f. Notably, in contrast to 2,4-diflorobenzyl tria-
zole-thioethers 7d–f, the 3,4-dichlorobenzyl ones 7a–c gave
relatively lower MIC values to most tested strains especially
P. aeruginosa (MIC = 16–64 μg/mL). Moreover, triazol-
ylethyl 3,4-dichlorobenzyltriazole-thioether 7a was sensi-
tive to E. typhosa (MIC = 16 μg/mL) and P. aeruginosa
(MIC = 16 μg/mL), which was comparable to the reference
drug Chloromycin, while both compounds 7a and 7f could
inhibit the growth of S. aureus at the moderate concentra-
tion of 32 μg/mL. Compared to mono-triazoles 6a–f and
bis-triazole thioethers 7a–f, the bis-triazole thiones 8a–f
remarkably improved antibacterial properties. Additionally,
the 3,4-dichlorobenzyl triazole-thiones 8a–c displayed wide
and good antibacterial activities particularly against M. lu-
teus and E. coli at the concentrations ranging from 1 to 32
μg/mL, more effective than the 2,4-diflorobenzyl deriva-
tives 8d–f. It is worth noting that compound 8b with the
(CH2)4 linkage exhibited the best bioactivities among all the
thiones to the bacteria (MIC = 1–64 μg/mL), particularly
toward M. luteus with the MIC value of 1 μg/mL, which
was equivalent to the reference drug Norfloxacin and 8-fold
more active than Chloromycin. These results suggested that
introduction of the second triazolyl moiety to the S-triazole
compounds resulted in better antibacterial activities and
broader spectrum. Furthermore, introduction of alkyl link-
ages with different lengths into triazolylalkyl tria-
zole-thiones exhibited obvious effects on antibacterial ac-
tivities.
rived triazolium 10b ex
hibited equipotent inhibitory activity
to Norfloxacin (MIC = 4 μg/mL) against E. coli. Unexpect-
edly, incorporation of coumarin to yield the coumarin de-
rived triazolium 11, which was reported to be of great po-
tential in antimicrobial abilities, did not lead to remarkable
improvements of antibacterial efficacy in comparison with
its corresponding precursor 8b. These facts revealed that the
alkyl triazoliums were specifically favorable for antibacteri-
al efficacy.
Triazoliums, as quaternary ammonium salts with prom-
ising surface activities, have been proved to be favorable for
external uses. Thereby, triazoliums 9a and b with potent
antibacterial efficiencies might be of much potential to be
investigated as external antimicrobial agents.
Overall, the triazole-thione 8b and triazoliums 9–11
showed the most potent activities among all the tested
thio-triazole derivatives against most tested bacteria. More-
over, triazole-thione compounds were more favorable for
antibacterial activities than triazole-thioethers as well as
their precursory triazole-thiols. Meanwhile, the above dis-
cussion indicated that halobenzyl groups especially the
3,4-dichorobenzyl moiety exerted great effects on antibac-
terial activities of the target compounds. Additionally, the
length of the alkyl chain also affected the bioactivities and
the (CH2)4 spacer was found to be the most suitable substit-
uent in this work to enhance antibacterial potency of tria-
zole-thiol derivatives. Finally, incorporation of triazolium
especially the alkyl-substituted ones significantly profited
the antibacterial efficiency in contrast to their precursors.
Triazoliums 9–11 with various substituents including al-

2150
Wang QP, et al. Sci China Chem October (2012) Vol.55 No.10
Table 3 Antibacterial and antifungal activities for compounds 2–11 expressed as MIC (μg/mL) a,b,c)
Gram-positive bacteria Gram-negative bacteria
Fungi
Compds
S.
aureus
B.
subtilis
M.
luteus
E.
coli
S.
P.
E.
typhosa
C.
albicans
C.
MRSA
dysenteriae
aeruginosa
mycoderma
128
128
256
512
512
256
512
256
128
128
32
2a
2b
3a
3b
3c
3d
3e
3f
128
128
>512
>512
512
>512
>512
256
128
128
128
512
256
128
256
256
512
512
512
>512
128
64
512
512
256
256
256
256
128
128
128
64
128
512
>512
256
256
512
256
256
64
128
128
>512
512
256
>512
512
256
256
64
128
256
512
256
128
512
512
512
256
128
64
256
128
512
256
128
512
256
512
128
64
128
512
>512
>512
512
>512
>512
>512
256
128
32
128
256
512
256
256
512
512
512
256
128
32
256
512
>512
>512
256
256
>512
256
256
64
4a
4b
4c
4d
4e
4f
32
32
32
64
128
256
256
128
512
64
64
128
64
256
512
128
>512
256
512
128
512
512
256
64
256
128
64
256
128
64
512
128
256
256
32
512
64
512
128
128
64
256
128
256
256
128
256
512
256
512
64
128
128
256
512
128
512
>512
64
128
512
64
5a
5b
5c
5d
5e
5f
64
128
128
128
128
128
>512
128
128
512
128
128
256
128
128
128
64
128
256
128
256
>512
128
64
128
512
256
256
>512
64
256
512
256
>512
128
64
256
512
512
>512
128
32
256
64
512
>512
128
64
6a
6b
6c
6d
6e
6f
64
64
128
64
128
128
128
128
128
256
128
256
256
512
64
64
256
256
128
256
256
256
128
256
256
512
64
128
64
64
64
64
64
64
256
64
32
128
64
64
128
64
128
128
32
128
256
256
128
64
64
128
128
128
64
128
512
128
64
128
16
128
16
256
4
7a
7b
7c
7d
7e
7f
128
128
256
256
32
32
256
64
128
128
128
256
512
64
64
2
256
128
256
32
128
256
512
128
16
32
512
512
512
64
128
256
512
16
128
128
32
128
128
64
8a
8b
8c
8d
8e
8f
64
64
64
32
1
32
32
32
32
16
64
64
64
16
32
64
32
64
32
128
64
128
128
64
128
128
128
2
64
64
64
128
128
128
16
128
128
128
4
64
128
64
64
64
128
64
128
64
64
64
64
128
2
64
9a
9b
10a
10b
11
A
32
8
16
1
8
16
32
8
8
16
8
32
8
8
8
32
64
8
64
8
16
128
64
32
64
8
32
16
8
32
16
4
32
16
8
64
32
16
16
16
8
128
4
128
16
32
16
128
–
4
1
4
8
2
8
–
B
4
0.5
–
2
1
4
1
1
4
–
–
C
–
–
–
–
–
–
–
0.5
4
a) Minimal inhibitory concentrations were determined by micro broth dilution method for microdilution plates. b) A = chloromycin, B = norfloxacin, C =
fluconazole. c) MRSA, Methicillin-Resistant Staphylococcus aureus (N315); S. aureus, Staphylococcus aureus (ATCC25923); B. subtilis, Bacillus subtilis;
M. luteus, Micrococcus luteus (ATCC4698); E. coli, Escherichia coli (DH52); S. dysenteriae, Shigella dysenteriae; P. aeruginosa, Pseudomonas aeruginosa;
E. typhosa, Eberthella typhosa; C. albicans, Candida albicans (ATCC76615); C. mycoderma, Candida mycoderma.

Wang QP, et al. Sci China Chem October (2012) Vol.55 No.10
2151
The thiones and triazoliums were promising compounds and
worthy further investigation as potential antibacterial drugs.
particularly to C. albicans. They could be of great potential
as external antimicrobial agents for their satisfactory anti-
bacterial and antifungal properties. These antimicrobial re-
sults demonstrated that some structural factors such as the
alkyl and aryl substituents as well as alkyl spacers could
significantly affect their antimicrobial competence. Fur-
thermore, the prepared triazole-thiones were more suitable
for bioactivities than thioethers. Especially, introduction of
the triazolium moiety would lead to significant improve-
ment of antimicrobial activities.
3.5 Antifungal activity
The antifungal evaluation revealed that some synthesized
triazole-thioether and triazole-thione derivatives displayed
good activities against the tested fungi C. albicans and C.
mycoderma to some extent. Similar to the antibacterial re-
sults, triazole-thiones 4a–c, 6a–c and 8a–c bearing the
3,4-dichlorobenzyl moiety manifested better antifungal po-
tential than 2,4-difluorobenzyl-substituted triazole-thiones
4d–f, 6d–f and 8d–f and triazole-thioether compounds 3a–f,
5a–f and 7a–f. Especially, the bis-triazole thiones 8a–c and
triazoliums 9–11 gave moderate antifungal abilities with
MIC values below 32 μg/mL to the tested C. albicans. No-
ticeably, both 3,4-dichorobenzyl triazole-thioether 7c and
hexyl triazolium 9a could effectively inhibit the growth of
C. albicans at the concentration of 2 μg/mL. Furthermore,
bis-triazole thioether 7a gave satisfactory anti-C. mycoder-
ma activity at the concentration of 4 μg/mL which was
equivalent to the clinical drug Fluconazole. Moreover, it
was noteworthy that all the triazoliums displayed remarka-
ble bioactivities toward C. albicans with MIC values rang-
ing from 2 to 16 μg/mL, making them potent for further
investigation as potential antifungal agents.
This work was supported by the National Natural Science Foundation of
China (21172181, 81250110089 (The Research Fellowship for Interna-
tional Young Scientists from International (Regional) Cooperation and
Exchange Program)), the key program from Natural Science Foundation of
Chongqing (CSTC2012jjB10026), the Specialized Research Fund for
the Doctoral Program of Higher Education of China (SRFDP
20110182110007) and the Fundamental Research Funds for the Central
Universities (XDJK2011D007, XDJK2012B026).
1
2
3
Zhou CH, Wang Y. Recent researches in triazole compounds as me-
dicinal drugs. Curr Med Chem, 2012, 19: 239–280
Wang Y, Zhou CH. Recent advances in the researches of triazole
compounds as medicinal drugs. Sci Sinca Chim, 2011, 41: 1429–1456
Zhang FF, Gan LL, Zhou CH. Synthesis, antibacterial and antifungal
activities of some carbazole derivatives. Bioorg Med Chem Lett, 2010,
20: 1881–1884
4
5
Gan LL, Fang B, Zhou CH. Synthesis of azole-containing piperazine
derivatives and evaluation of their antibacterial, antifungal and cyto-
toxic activities. Bull Korean Chem Soc, 2010, 31: 3684–3692
Nath M, Sulaxna, Song XQ, Eng G, Kumar A. Synthesis and spectral
studies of organotin(IV) 4-amino-3-alkyl-1,2,4-triazole-5-thionates:
In vitro antimicrobial activity. Spectrochim Acta Part A, 2008, 70:
766–774
4 Conclusions
In summary, a series of new triazole-thiols, thioethers and
thiones as well as some corresponding triazolium deriva-
tives have been successfully synthesized through convenient
and efficient procedures in appreciable yields. All the new
compounds were characterized by 1H NMR, 13C NMR,
FTIR, MS and HRMS spectra. The in vitro antimicrobial
tests revealed that most synthesized compounds showed
moderate to good bioactivities against the selected patho-
genic strains. The 3,4-dichlorobenzyl triazole-thiones ex-
hibited superior antibacterial and antifungal efficacy to oth-
er thioether and thione compounds. Especially, compound
8b with the (CH2)4 spacer gave 8-fold lower inhibitory con-
centration to M. luteus than Chloromycin with the MIC
value of 1 μg/mL, which was equivalent to Norfloxacin.
Moreover, triazoliums, especially the alkyl substituted ones,
displayed the best antimicrobial activities among all the
tested compounds against all the bacteria. Particularly, the
hexyl triazolium 9a showed comparable bioactivities
against S. aureus (MIC = 2 μg/mL), E. coli (MIC = 1 μg/mL)
and P. aeruginosa (MIC = 4 μg/mL) to the reference drugs
Chloromycin and Norfloxacin. Equally important, the octyl
triazolium 9b exhibited equivalent or even better inhibitory
potency toward E. typhosa and P. aeruginosa than the ref-
erence drug Chloromycin at the concentration of 8 μg/mL.
In addition, the triazoliums were also sensitive to fungi,
6
7
Wei QL, Zhang SS, Gao J, Li WH, Xu LZ, Yu ZG. Synthesis and
QSAR studies of novel triazole compounds containing thioamide as
potential antifungal agents. Bioorg Med Chem, 2006, 14: 7146–7153
Jadhav GR, Shaikh MU, Kale RP, Shiradkar MR, Gill CH. SAR
study of clubbed[1,2,4]-triazolyl with fluorobenzimidazoles as anti-
microbial and antituberculosis agents. Eur J Med Chem, 2009, 44:
2930–2935
Patel NB, Khan IH, Rajani SD. Pharmacological evaluation and
characterizations of newly synthesized 1,2,4-triazoles. Eur J Med
Chem, 2010, 45: 4293–4299
8
9
He R, Chen YF, Chen YH, Ougolkov AV, Zhang JS, Savoy DN, Bil-
ladeau DD, Kozikowski AP. Synthesis and biological evaluation of
triazol-4-ylphenyl-bearing histone deacetylase inhibitors as anti-
cancer agents. J Med Chem, 2010, 53: 1347–1356
10 Lee J, Kim SJ, Choi H, Kim YH, Lim IT, Yang H, Lee CS, Kang HR,
Ahn SK, Moon SK, Kim DH, Lee S, Choi NS, Lee KJ. Identification
of CKD-516: A potent tubulin polymerization inhibitor with marked
antitumor activity against murine and human solid tumors. J Med
Chem, 2010, 53: 6337–6354
11 Al-Omar MA, Al-Abdullah ES, Shehata IA, Habib EE, Ibrahim TM,
El-Emam AA. Synthesis, antimicrobial, and anti-inflammatory
activities of novel 5-(1-adamantyl)-4-arylideneamino-3-mercapto-
1,2,4-triazoles and related derivatives. Molecules, 2010, 15:
2526–2550
12 Deng XQ, Wei CX, Li FN, Sun ZG, Quan ZS. Design and synthesis
of 10-alkoxy-5,6-dihydro-triazolo[4,3-d]benzo[f][1,4] oxazepine de-
rivatives with anticonvulsant activity. Eur J Med Chem, 2010, 45:
3080–3086
13 Fang B, Zhou CH, Rao XC. Synthesis and biological activities of

2152
Wang QP, et al. Sci China Chem October (2012) Vol.55 No.10
novel amine-derived bis-azoles as potential antibacterial and antifun-
gal agents. Eur J Med Chem, 2010, 45: 4388–4398
adiazoles bearing 4-methylthiobenzyl moiety. Eur J Med Chem, 2009,
44: 551–557
29 Mallikarjuna BP, Sastry BS, Kumar GVS, Rajendraprasad Y, Chan-
drashekar SM, Sathisha K. Synthesis of new 4-isopropylthiazole hy-
drazide analogs and some derived clubbed triazole, oxadiazole ring
systems-a novel class of potential antibacterial, antifungal and an-
titubercular agents. Eur J Med Chem, 2009, 44: 4739–4746
30 Bonanomi G, Braggio S, Capelli AM, Checchia A, Fabio RD, Mar-
chioro C, Tarsi L, Tedesco G, Terreni S, Worby A, Heibreder C,
Micheli F. Triazolyl azabicyclo[3.1.0]hexanes: a class of potent and
selective dopamine D3 receptor antagonists. ChemMedChem, 2010, 5:
705–715
31 Kucukguzel I, Kucukguzel SG, Rollasa S, Kiraz M. Some
3-thioxo/alkylthio-1,2,4-triazoles with a substituted thiourea moiety
as possible antimycobacterials. Bioorg Med Chem Lett, 2001, 11:
1703–1707
32 Bayrak H, Demirbas A, Karaoglu SA, Demirbas N. Synthesis of
some new 1,2,4-triazoles, their Mannich and Schiff bases and evalua-
tion of their antimicrobial activities. Eur J Med Chem, 2009, 44:
1057–1066
33 Bhatia MS, Zarekar BE, Choudhari PB, Ingale KB, Bhatia NM.
Combinatorial approach: identification of potential antifungals from
triazole minilibraries. Med Chem Res, 2011, 20: 116–120.
34 Kalhor M, Mobinikhaledi A, Dadras A, Tohidpour M. Synthesis and
antimicrobial activity of some novel substituted 1,2,4-triazoles bear-
ing 1,3,4-oxadiazoles or pyrazoles. J Heterocycl Chem, 2011, 48:
1366–1370
35 Almajan GL, Barbuceanu S, Almajan E, Draghici C, Saramet G.
Synthesis, characterization and antibacterial activity of some triazole
Mannich bases carrying diphenylsulfone moieties. Eur J Med Chem,
2009, 44: 3083–3089
36 Deprez-Poulain RF, Charton J, Leroux V, Deprez BP. Convenient
synthesis of 4H-1,2,4-triazole-3-thiols using di-2-pyridylthiono-car-
bonate. Tetrahedron Lett, 2007, 48: 8157–8162
37 Mavrova AT, Wesselinova D, Tsenov YA, Denkova P. Synthesis,
cytotoxicity and effects of some 1,2,4-triazole and 1,3,4-thiadiazole
derivatives on immunocompetent cells. Eur J Med Chem, 2009, 44:
63–69
38 Tamilselvi A, Mugesh G. Interaction of heterocyclic thiols/thiones
eliminated from cephalosporins with iodine and its biological impli-
cations. Bioorg Med Chem Lett, 2010, 20: 3692–3697
39 Li ZZ, Gu Z, Yin K, Zhang R, Deng Q, Xiang JN. Synthesis of sub-
stituted-phenyl-1,2,4-triazol-3-thione analogues with modified
D-glucopyranosyl residues and their antiproliferative activities. Eur J
Med Chem, 2009, 44: 4716–4720
40 Wang XL, Wan K, Zhou CH. Synthesis of novel sulfanilamide-
derived 1,2,3-triazoles and their evaluation for antibacterial and anti-
fungal activities. Eur J Med Chem, 2010, 45: 4631–4639
41 Wei JJ, Jin L, Wan K, Zhou CH. Synthesis of novel
D-glucose-derived benzyl and alkyl 1,2,3-triazoles as potential anti-
fungal and antibacterial agents. Bull Korean Chem Soc, 2011, 32:
229–238
42 Ezabadi IR, Camoutsis C, Zoumpoulakis P, Geronikaki A, Soković
M, Glamočilijad J, Ćirić A. Sulfonamide-1,2,4-triazole derivatives as
antifungal and antibacterial agents: Synthesis, biological evaluation,
lipophilicity, and conformational studies. Bioorg Med Chem, 2008,
16: 1150–1161
14 Acetti D, Brenna E, Fuganti C, Gatti FG, Serra S. Enzyme-catalysed
approach to the preparation of triazole antifungals: synthesis of
(–)-genaconazole. Tetrahedron: Asymmetry, 2009, 20: 2413–2420
15 Genin MJ, Allwine DA, Anderson DJ, Barbachyn MR, Emmert DE,
Garmon SA, Graber DR, Grega KC, Hester JB, Hutchinson DK,
Morris J, Reischer RJ, Ford CW, Zurenko GE, Hamel JC, Schaadt
RD, Stapert D, Yagi BH. Substituent effects on the antibacterial ac-
tivity of nitrogen carbon-linked (azolylphenyl)oxazolidinones with
expanded activity against the fastidious gram-negative organisms
Haemophilus influenzae and Moraxella catarrhalis. J Med Chem,
2000, 43: 953–970
16 Bhandari K, Srinivas N, Shiva KGB, Shukla PK. Tetrahydronaphthyl
azole oxime ethers: The conformationally rigid analogues of oxicon-
azole as antibacterials. Eur J Med Chem, 2009, 44: 437–447
17 Eswaran S, Adhikari AV, Shetty NS. Synthesis and antimicrobial ac-
tivities of novel quinoline derivatives carrying 1,2,4-triazole moiety.
Eur J Med Chem, 2009, 44: 4637–4647
18 Shi Y, Zhou CH, Zhou XD, Geng RX, Ji QG. Synthesis and antimi-
crobial evaluation of coumarin-based benzotriazoles and their syner-
gistic effects with chlromycin and fluconazole. Acta Pharmac Sin,
2011, 46: 798–810
19 Borate HB, Maujan SR, Sawargave SP, Chandavarkar MA, Vaiude
SR, Joshi VA, Wakharkar RD, Iyer R, Kelkar RG, Chavan SP, Kunte
SS. Fluconazole analogues containing 2H-1,4-benzothiazin-3(4H)-
one or 2H-1,4-benzoxazin-3(4H)-one moieties, a novel class of an-
ti-Candida agents. Bioorg Med Chem Lett, 2010, 20: 722–725
20 Kumarasamy KK, Toleman MA, Walsh TR, Bagaria J, Butt F,
Balakrishnan R, Chaudhary U, Doumith M, Giske CG, Irfan S,
Krishnan P, Kumar AV, Maharjan S, Mushtaq S, Noorie T, Paterson
DL, Pearson A, Perry C, Pike R, Rao B, Ray U, Sarma JB, Sharma M,
Sheridan E, Thirunarayan MA, Turton J, Upadhyay S, Warner M,
Welfare W, Livermore DM, Woodford N. Emergence of a new
antibiotic resistance mechanism in India, Pakistan, and the UK: A
molecular, biological, and epidemiological study. Lancet Infect Dis,
2010, 10: 597–602
21 Bielaszewska M, Mellmann A, Zhang WL, Köck R, Fruth A,
Bauwens A, Peters G, Karch H. Characterisation of the Escherichia
coli strain associated with an outbreak of haemolytic uraemic
syndrome in Germany, 2011: A microbiological study. Lancet Infect
Dis, 2011, 11: 671–676
22 Dan ZG, Zhang J, Yu SC, Hu HG, Chai XY, Sun QY, Wu QY. De-
sign and synthesis of novel triazole antifungal derivatives based on
the active site of fungal lanosterol 14a-demethylase (CYP51). Chi-
nese Chem Lett, 2009, 20: 935–938
23 Güzeldemirci NU, Küçükbasmacı Ö. Synthesis and antimicrobial ac-
tivity evaluation of new 1,2,4-triazoles and 1,3,4-thiadiazoles bearing
imidazo[2,1-b]thiazole moiety. Eur J Med Chem, 2010, 45: 63–68
24 Soni B, Ranawat MS, Sharma R, Bhandari A, Sharma S. Synthesis
and evaluation of some new benzothiazole derivatives as potential
antimicrobial agents. Eur J Med Chem, 2010, 45: 2938–2942
25 Marino JP, Fisher PW, Hofmann GA, Kirkpatrick RB, Janson CA,
Johnson RK, Ma C, Mattern M, Meek TD, Ryan MD, Schulz C,
Smith WW, Tew DG, Tomazek TA, Veber DF, Xiong WC,
Yamamoto Y, Yamashita K, Yang G, Thompson SK. Highly potent
inhibitors of methionine aminopeptidase-2 based on a 1.2.4-triazole
pharmacophore. J Med Chem, 2007, 50: 3777–3785
26 Wan K, Zhou CH. Synthesis of novel halobenzyloxy and alkoxy
1,2,4-triazoles and evaluation for their antifungal and antibacterial
activities. Bull Korean Chem Soc, 2010, 31: 2003–2010
27 Kumar GVS, Rajendraprasad Y, Mallikarjuna BP, Chandrashekar
SM, Kistayya C. Synthesis of some novel 2-substituted-5-[iso-
propylthiazole] clubbed 1,2,4-triazole and 1,3,4-oxadiazoles as po-
tential antimicrobial and antitubercular agents. Eur J Med Chem,
2010, 45: 2063–2074
43 Luo Y, Lu YH, Gan LL, Zhou CH, Wu J, Geng RX, Zhang YY.
Synthesis, antibacterial and antifungal activities of novel 1,2,4-tria-
zolium derivatives. Arch Pharm, 2009, 342: 386–393
44 Sztanke K, Pasternak K, Sidor-Wójtowicz A, Truchlińskac J,
Jóźwiakd K. Synthesis of imidazoline and imidazo[2,1-c][1,2,4] tria-
zole aryl derivatives containing the methylthio group as possible an-
tibacterial agents. Bioorg Med Chem, 2006, 14: 3635–3642
45 Gülerman NN, Doğan HN, Rollas S, Johansson C, Çelik C. Synthesis
and structure elucidation of some new thioether derivatives of
1,2,4-triazoline-3-thiones and their antimicrobial activities. Il
Farmaco, 2001, 56: 953–958
28 Prasad DJ, Ashok M, Karegoudar P, Poojary B, Holla BS, Kumari
NS. Synthesis and antimicrobial activities of some new triazolothi-

Wang QP, et al. Sci China Chem October (2012) Vol.55 No.10
2153
46 Demirbas A, Sahin D, Demirbas N, Karaoglu SA. Synthesis of some
new 1,3,4-thiadiazol-2-ylmethyl-1,2,4-triazole derivatives and inves-
tigation of their antimicrobial activities. Eur J Med Chem, 2009, 44:
2896–2903
47 Zhang YY, Zhou CH. Synthesis and activities of naphthalimide az-
oles as a new type of antibacterial and antifungal agents. Bioorg Med
Chem Lett, 2011, 21: 4349–4352
rin triazole derivatives as potential antimicrobial agents. Bioorg Med
Chem Lett, 2011, 21: 956–960
51 Kadi AA, El-Brollosy NR, Al-Deeb OA, Habib EE, Ibrahim TM,
El-Emam AA. Synthesis, antimicrobial, and anti-inflammatory
activities of novel 2-(1-adamantyl)-5-substituted-1,3,4-oxadiazoles
and 2-(1-adamantylamino)-5-substituted-1,3,4-thiadiazoles. Eur
Med Chem, 2007, 42: 235–242
J
48 Moulin A, Bibian M, Blayo A, Habnouni SE, Martinez J, Fehrentz J.
Synthesis of 3,4,5-trisubstituted-1,2,4-triazoles. Chem Rev, 2010, 110:
1809–1827
52 Özbek N, Katırcıoglu H, Karacan N, Baykal T. Synthesis, character-
ization and antimicrobialactivity of new aliphatic sulfonamide.
Bioorg Med Chem, 2007, 15: 5105–5109
49 Zhang YY, Mi JL, Zhou CH, Zhou XD. Synthesis of novel flucona-
zoliums and their evaluation for antibacterial and antifungal activities.
Eur J Med Chem, 2011, 46: 4391–4402
53 Davari MD, Bahrami H, Haghighi ZZ, Zahedi M. Quantum chemical
investigation of intramolecular thione-thiol tautomerism of
1,2,4-triazole-3-thione and its disubstituted derivatives. J Mol Model,
2010, 16: 841–855
50 Shi Y, Zhou CH. Synthesis and evaluation for a class of new couma-