Facile water promoted synthesis of 1,2,3-triazolyl dihydropyrimidine-2- thione hybrids - Highly potent antibacterial agents

Article abstract of DOI:10.1016/j.ejmech.2012.10.029

An elegant and efficient synthesis of hitherto novel 1,2,3-triazolyl dihydropyrimidine-2-thione hybrids has been accomplished for the first time in a green solvent viz. water. The hybrid molecules exhibit significant antibacterial activity when screened against four human pathogens viz. Streptococcus pneumonia, Staphylococcus aureus, Pseudomonas aeruginosa and Salmonella typhi. In comparison to the commercially marketed tetracycline, some of them were equally potent and a few more potent.

Full text of DOI:10.1016/j.ejmech.2012.10.029

European Journal of Medicinal Chemistry 58 (2012) 464e469
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Short communication
Facile water promoted synthesis of 1,2,3-triazolyl dihydropyrimidine-2-thione
hybrids e Highly potent antibacterial agents
Nagarajan Sangaraiah a, Sathishkumar Murugan a, Shanmugavelan Poovan a, Ranganathan Raja a,
,
b
b,
*
Ponnuswamy Alagusundaram a , Venkatesan Ramakrishnan , Shanmugaiah Vellasamy
*
a Department of Organic Chemistry, School of Chemistry, Madurai Kamaraj University, Madurai 625021, Tamilnadu, India
b Department of Microbial Technology, School of Biological Sciences, Madurai Kamaraj University, Madurai 625021, Tamilnadu, India
a r t i c l e i n f o
a b s t r a c t
Article history:
An elegant and efficient synthesis of hitherto novel 1,2,3-triazolyl dihydropyrimidine-2-thione hybrids
has been accomplished for the first time in a green solvent viz. water. The hybrid molecules exhibit
significant antibacterial activity when screened against four human pathogens viz. Streptococcus pneu-
monia, Staphylococcus aureus, Pseudomonas aeruginosa and Salmonella typhi. In comparison to the
commercially marketed tetracycline, some of them were equally potent and a few more potent.
Ó 2012 Elsevier Masson SAS. All rights reserved.
Received 28 March 2012
Received in revised form
14 October 2012
Accepted 16 October 2012
Available online 25 October 2012
Keywords:
1,2,3-Triazole
Thione
Water promoted
Tetracycline
Antibacterial
1. Introduction
The heterocycles viz. thiazine [9], imidazole [10], pyrimidine [11],
pyrimidine-2-thione [12,13],1,2,3-triazoles [14,15] and 1,2,4-triazole
Infectious diseases are the world’s leading cause of premature
deaths, killing almost 50,000 people every day [1]. The reason for
this, is mainly attributed to the drug resistance to human patho-
genic bacteria all over the world [2]. In recent years, the multi drug
resistance (MDR) is alarming and the major public health concern
worldwide [3]. Many strains causing infectious diseases that
seemed to be in control are causing deaths each year due to the
absence of an appropriate antibiotic [4].
For instance, Streptococcus pneumonia, Staphylococcus aureus,
Pseudomonas aeruginosa and Salmonella typhi are important path-
ogens causing invasive diseases such as sepsis, meningitis, pneu-
monia [5], nosocomial pneumonia [6], cystic fibrosis, acute
leukemia, organ transplants, and intravenous-drug addiction [7].
Some of these pathogens have been reported to develop resistance
[8] to the well known commercially available drug viz. tetracycline.
In view of this, the current study was undertaken to synthesize and
investigate the antimicrobial activities of a series of 1,2,3-triazolyl
dihydropyrimidine-2-thione hybrids against the above said
human pathogenic bacteria.
[16] have been reported as potential inhibitors of one or more of the
above said pathogens. In view of these bioactivities of the individual
heterocycles, it was envisaged that the synthesis and antibacterial
study of hitherto novel hybrid molecules containing two of the
above said moieties in a single frame is worth the attempt.
In continuation of our recent work on the environment friendly,
solvent-free synthesis of amides [17e19], thioamides [20], thio-
azolidones [21], spirothiazolidones [22], 1,2,3-triazoles [23], and
synthesis of 1,2,3-triazolyl chalcone [24] in water as solvent, we
herein report an elegant water promoted synthesis of hitherto
novel 1,2,3-triazolyl dihydropyrimidine-2-thione hybrids and
screened their bioactivity against the above mentioned pathogens.
Many of the compounds thus synthesized were found to be equally
potent or more potent than the reference compound viz. tetracy-
cline, the details of which are presented vide infra.
2. Results and discussion
2.1. Chemistry
Owing to the significant features of dihydropyrimidine-2-
thiones, a number of protocols for their synthesis have been devel-
oped. These known methodologies involve the usage of organic
solvents [25,26] which take long reaction time (5e10 h or even
* Corresponding authors. Tel.: þ91 9600868323.
E-mail address: ramradkrish@yahoo.co.in (P. Alagusundaram).
0223-5234/$ e see front matter Ó 2012 Elsevier Masson SAS. All rights reserved.
http://dx.doi.org/10.1016/j.ejmech.2012.10.029

N. Sangaraiah et al. / European Journal of Medicinal Chemistry 58 (2012) 464e469
465
more) [27] or microwave as the energy source [12]. These organic
solvents are hazardous to human health and cause environmental
pollution due to their volatile nature. Hence, organic reactions under
solvent-free conditions and in water medium, being eco-friendly
have attained much importance and are of current interest.
Herein we submit the first report on the synthesis of 1,2,3-
triazolyl dihydropyrimidine-2-thione hybrids in water. It is perti-
nent to note that, the yield of the hybrids in the organic solvent viz.
ethanol and in water medium is comparable, the details of which
are presented in Table 1.
Table 1
Synthesis of 1,2,3-triazolyl dihydropyrimidine-2-thione hybrids (2ael)b in ethanol and water.
S. No
Triazolyl chalcone
R
Product
Ethanol
Water
Yielda (%)
Time (min)
30
Yielda (%)
Time (min)
40
S
HN
N
N
N
NH
1
1a
85
89
CH3
2a
S
HN
N
N
N
NH
H3C
2
3
1b
1c
93
83
30
30
95
85
40
40
O
CH3
O
CH3
2b
S
N
HN
N
N
NH
CH3
CH3
CH3
2c
S
HN
N
N
N
NH
4
5
1d
1e
81
74
30
30
87
81
40
40
Cl
CH3
Cl
2d
S
N
HN
N
N
NH
O2N
CH3
NO2
2e
S
HN
N
N
N
Br
NH
6
7
8
1f
80
76
81
30
30
30
83
80
88
40
40
40
CH3
Br2f
S
HN
N
N
N
Br
NH
1g
1h
Br
CH3
2g
S
HN
N
N
N
NH
Br
CH3
Br
2h
S
HN
N
N
N
NH
9
1i
87
30
91
40
F
CH3
(continued on next page)
F
2i

466
N. Sangaraiah et al. / European Journal of Medicinal Chemistry 58 (2012) 464e469
Table 1 (continued )
S. No
Triazolyl chalcone
R
Product
Ethanol
Water
Yielda (%)
Time (min)
Yielda (%)
Time (min)
S
HN
N
N
N
NH
OCH3
O
O
CH3
CH3
10
1j
86
75
95
30
86
79
93
40
CH3
H3CO
2j
S
HN
N
N
N
NH
Cl
Cl
Cl
11
1k
30
30
40
40
CH3
Cl
2k
S
HN
N
N
N
NH
12
1l
H3C
CH3
CH3
2l
a
Yield of the isolated product.
The synthesized compounds were characterized by NMR (1D & 2D).
b
At the outset,
a
mixture of 1,2,3-triazolyl chalcone (1a,
2.2. Biology
1.0 equiv.), thiourea (1.1 equiv.) and 10% KOH in ethanol was
refluxed (Scheme 1). The reaction was completed in 30 min
affording 1,2,3-triazolyl dihydropyrimidine-2-thione hybrid (2a) in
85% yield. On the other hand, in water, the reaction was completed
in 40 min affording comparable yield (89%) of 2a. The later protocol
avoiding the organic solvent viz. ethanol is greener (Scheme 1).
The broad scope of the greener methodology involving water as
media was established via the synthesis of a library of 1,2,3-triazolyl
dihydropyrimidine-2-thione hybrids (2ael, Scheme 2) in good to
excellent yields (79e95%, Table 1).
2.2.1. Antibacterial activity of compounds against human
pathogens
The cultures ofhumanpathogenicbacteriaS. aureus, S. pneumonia,
P. aeruginosa and S. typhi used in this study were obtained from the
Department of Microbial Technology, School of Biological Sciences,
Madurai Kamaraj University and maintained on Nutrient Agar (NA),
consisting of the following [(g/L) Beef extract 1.0; Yeast extract 2.0;
Peptone 5.0; NaCl 5.0; Agar 15.0; Distilled H2O 1 L; pH 7.2.] in slants or
Petriplates at room temperature (28 ꢀ 2 ꢁC). Originally the above said
S
H2N
NH2
S
N
O
N
N
N
HN
N
N
10% KOH
NH
EtOH, reflux, 30 minutes
or
CH3
CH3
H2O, reflux, 40 minutes
2a
1a
Scheme 1. Optimization for the synthesis of triazolyl dihydropyrimidine-2-thione hybrid (2a).
N
O
N
N
CH3
S
CH3
S
N
O
N
N
N
HN
H2N
NH2
50% NaOH
N
N
NH
O
H2O,
grinding
4-7 minutes
10% KOH, Water
reflux
CH3
CH3
R
1a-l
2a-l
R
R
Scheme 2. Synthesis of 1,2,3-triazolyl dihydropyrimidine-2-thione hybrids.

N. Sangaraiah et al. / European Journal of Medicinal Chemistry 58 (2012) 464e469
467
bacteria were collected from Bose Clinical Laboratory and X-ray
3. Conclusion
(Madurai, Tamilnadu, India) [28]. All strains were identified by stan-
dard biochemical methods [29,30]. The antibacterial activity of the
compounds against humanpathogens was evaluated by the agar well
diffusion method. About 1 mL of inoculums of each test pathogenwas
added to the molten Nutrient Agar (NA) medium and poured into
sterile Petriplates under aseptic conditions. After solidification, a 5-
mm well was made in the center of each plate using a sterile cork
borer. Each compound was dissolved in 10% DMSO [31] to get
An elegant water promoted synthesis of hybrid molecules viz.
triazolyl dihydropyrimidine-2-thiones has been accomplished for
the first time. Many of them exhibited potential antibacterial
activity. Some of them were equally potent to or even of higher
potency than the commercially marketed tetracycline. This study
could be useful as a template for future development through
modification or derivatization to design more potent biologically
active compounds.
different concentrations and filter was sterilized using 0.25
mL filter
paper. Each well received 50 L solution of each compound and the
m
plates were incubated at room temperature. Sterile DMSO (10%) was
used as control. After 48 h, the appearance of inhibition zone around
the well was observed (Table 2).
4. Experimental
All chemicals, reagents and solvents were of commercially high
purity grade purchased from Avra Synthesis Pvt. Ltd. and Merck
Ltd., India. 1H NMR and 13C NMR spectra were recorded in CDCl3
and DMSO-d6 on Bruker Avance 300 MHz spectrometer and the
All the twelve compounds (2ael) exhibited different levels of
inhibitory effects (Table 2) against the tested human pathogenic
bacteria (S. pneumonia, S. aureus, P. aeruginosa and S. typhi).
Compounds with the minimum inhibitory concentration (MIC) in
chemical shifts are reported as
d values in parts per million (ppm)
the range of 8e20
m
g mLꢂ1 are reported as active, MIC in the range
relative to tetramethylsilane, with J values in Hertz. The splitting
patterns in 1H NMR spectra are reported as follows: s ¼ singlet;
d ¼ doublet; br s ¼ broad singlet; br d ¼ broad doublet;
m ¼ multiplet. 13C NMR data are reported with the solvent peak
(CDCl3 ¼ 77.0 MHz) as the internal standard. Elemental analyses
were in agreement with the calculated values i.e. error within
ꢀ0.4%. Electrospray Ionization Mass Spectrometry (ESI-MS) anal-
yses of some representative compounds were recorded in LCQ
Fleet, Thermo Fisher Instruments Limited, US.
of 22e120
m
g mLꢂ1 are reported as moderate to low inhibition and
those which showed no significant activity are reported as NI (No
Inhibition). The hybrid molecule (2a) with R as the unsubstituted
phenyl ring was a potent inhibitor for all the tested pathogens in
the dosage level (10e19
m
g mLꢂ1) comparable with that of the
reference drug viz. tetracycline (Table 2). Subsequently, various
substituents were introduced in either of the ortho, meta or para
position of the phenyl ring to evaluate their effect on biological
activities. The ortho and meta substituted hybrids (2c, 2g, 2f)
showed moderate to low inhibition irrespective of whether they
are electron releasing or withdrawing. Similar observations could
be recognized in the case of the para substituted compounds with
electron withdrawing groups such as nitro or fluoro or bromo (2e,
2i, 2h) functional groups. However, one of the para substituted
compounds with electron withdrawing chloro function (2d) and
electron releasing substituent viz. methyl group (2l) exhibited high
inhibition against all the tested pathogens. On the other hand,
compound with para substituted electron releasing methoxy
substituent (2b) showed inhibition against P. aeruginosa selectively.
Further, two ortho, para disubstituted compounds with two elec-
tron releasing methoxy substituents (2j) or two electron with-
drawing chloro substituents (2k) showed moderate selective
inhibition against two of the tested pathogens. All the results of the
biological activities are shown in Table 2.
4.1. General procedure for the synthesis of triazolyl dihydropyri-
midine-2-thione (2ael)
A mixture of (E)-1-(1-benzyl-5-methyl-1H-1,2,3-triazol-4-yl)-3-
arylprop-2-en-1-one [24] (1.0 equiv.), thiourea (1.5 equiv.) and 10%
aq. KOH in water or ethanol (10 mL) was refluxed for 30e40 min
and poured onto excess of crushed ice and neutralized with
dilute hydrochloric acid. The precipitated triazolyl dihydropyr-
imidine-2-thione derivatives (2ael) were filtered and recrystallized
from ethanol.
4.1.1. 6-(1-Benzyl-5-methyl-1H-1,2,3-triazol-4-yl)-4-phenyl-3,4-
dihydropyrimidine-2(1H)-thione (2a)
White solid; m.p. 158 ꢁC; Yield: 89%. IR (KBr): v 3411, 3192, 1677,
1552, 1462, 1355, 1181, 834, 729, 700 cmꢂ1 1H NMR (300 MHz,
;
CDCl3):
J ¼ 3.6 Hz, eCH), 5.09 (d, 1H, J ¼ 3.9 Hz, olefinic eCH), 2.2 (s, 3H, e
CH3); 13C NMR (75 MHz, CDCl3):
175.33, 142.42, 137.39, 134.15,
130.47,129.12,128.61,127.11,126.85,126.18, 99.55, 56.80, 52.15, 9.48;
MS (ESI): m/z (%) 362.26 (M þ H); Anal. Calcd. for C20H19N5S: C, 66.46;
H, 5.30; N, 19.37; S, 8.87. Found: C, 66.50; H, 5.28; N, 19.39; S, 8.86.
d 7.12e7.35 (m, 10H, ArH), 5.51 (m, 2H, eCH2), 5.25 (d, 1H,
Table 2
d
In vitro antibacterial activityb of the 1,2,3-triazolyl dihydropyrimidine-2-thione
hybrids (2ael) and tetracycline with MICa g mLꢂ1) values against four human
(m
pathogens.
Compounds
S. aureus
S. pneumonia
P. aeruginosa
S. typhi
2a
2b
2c
2d
2e
2f
2g
2h
2i
2j
2k
2l
10
NI
37
10
20
22
NI
95
85
NI
43
8
19
40
19
10
20
35
33
44
100
42
25
16
20
NI
12
10
18
9
20
24
NI
100
130
NI
18
NI
4.1.2. 6-(1-Benzyl-5-methyl-1H-1,2,3-triazol-4-yl)-4-(4-metho-
xyphenyl)-3,4-dihydropyrimidine-2(1H)-thione (2b)
25
20
80
90
NI
120
NI
32
NI
White solid; m.p. 198 ꢁC; Yield: 95%; 1H NMR (300 MHz, CDCl3):
d
8.58 (bs, 1H, NH), 7.33e6.90 (m, 9H, ArH), 6.79 (bs, 1H, NH), 5.52
(m, 2H, eCH2), 5.22 (bs, 1H, eCH), 5.07 (bs, 1H, olefinic eCH), 3.79
(s, 3H, eOCH3), 2.22 (s, 3H, eCH3); 13C NMR (75 MHz, CDCl3):
d
175.21, 159.95, 134.65, 134.15, 129.10, 128.54, 128.17, 127.09, 126.11,
140.55, 99.71, 56.31, 55.33, 52.14, 9.45; MS (ESI): m/z (%) 391.42;
Anal. Calcd. for C21H21N5OS: C, 64.43; H, 5.41; N, 17.89; S, 8.19.
Found: C, 64.46; H, 5.40; N, 17.90; S, 8.20.
NI
10
10
NI
13
15
NI
Tetracycline
Control
10
NI
4.1.3. 6-(1-Benzyl-5-methyl-1H-1,2,3-triazol-4-yl)-4-o-tolyl-3,4-
dihydropyrimidine-2(1H)-thione (2c)
NI e No Inhibition.
a
The MIC is defined as the minimum concentration of the compound required to
White solid, m.p. 201 ꢁC; Yield: 85%; 1H NMR (300 MHz, CDCl3):
inhibit 99% of bacterial growth.
b
Values in bold show significant activity compared to tetracycline.
d 8.59 (bs, 1H, NH), 7.41e7.12 (m, 9H, ArH), 6.54 (bs, 1H, NH), 5.54e

468
N. Sangaraiah et al. / European Journal of Medicinal Chemistry 58 (2012) 464e469
5.51 (m, 3H, merged with eCH2 & eCH), 5.07 (bs, 1H, olefinic eCH),
2.39 (s, 3H, eCH3), 2.21 (s, 3H, eCH3); 13C NMR (75 MHz, CDCl3):
3H, eCH3); 13C NMR (75 MHz, CDCl3):
d 9.51, 142.24, 136.01, 133.74,
133.54, 133.43, 133.06, 132.02, 131.07, 120.46, 120.17, 104.86, 59.63,
d
174.80, 140.25, 133.99, 133.81, 130.36, 130.14, 128.52, 127.92,
56.42, 14.04; MS (ESI): m/z (%) 380.27 (M þ H); Anal. Calcd. for
127.51, 127.24, 126.60, 126.34, 126.68, 98.52, 52.86, 51.44, 18.43,
8.89; Anal. Calcd. for C21H21N5S: C, 67.17; H, 5.64; N, 18.65; S, 8.54.
Found: C, 67.20; H, 5.65; N, 18.63; S, 8.52.
C20H18FN5S: C, 63.31; H, 4.78; N, 18.46; S, 8.45. Found: C, 63.35; H,
4.80; N, 18.44; S, 8.43.
4.1.10. 6-(1-Benzyl-5-methyl-1H-1,2,3-triazol-4-yl)-4-(2,4-dimeth-
oxyphenyl)-3,4-dihydropyrimidine-2(1H)-thione (2j)
4.1.4. 6-(1-Benzyl-5-methyl-1H-1,2,3-triazol-4-yl)-4-(4-chloro-
phenyl)-3,4-dihydropyrimidine-2(1H)-thione (2d)
White solid; m.p. 179 ꢁC; Yield: 86%; 1H NMR (300 MHz, CDCl3):
White solid; m.p. 189 ꢁC; Yield: 87%; IR (KBr): v 3302, 3220,
d 8.57 (bs, 1H, NH), 7.33e6.84 (m, 8H, ArH), 6.80 (bs, 1H, NH), 5.50
1563, 1506, 1470, 1250, 1179, 1031, 826, 734 cmꢂ1
;
1H NMR
(m, 2H, eCH2), 5.21 (bs, 1H, eCH), 5.05 (bs, 1H, olefinic eCH), 3.85
(300 MHz, DMSO-d6):
d 9.21 (bs, 1H, NH), 9.03 (bs, 1H, NH), 7.17e
(bs, 6H, eOCH3), 2.21 (s, 3H, eCH3); 13C NMR (75 MHz, CDCl3):
7.40 (m, 9H, ArH), 5.58 (m, 2H, eCH2), 5.28 (bs, 1H, eCH), 5.17 (bs,
d 175.25, 149.77, 149.52, 137.41, 135.01, 134.11, 130.37, 129.11, 128.56,
1H, olefinic eCH), 2.26 (s, 3H, eCH3); 13C NMR (75 MHz, DMSO-
127.10, 126.18, 119.29, 111.59, 110.17, 99.61, 56.67, 56.10, 56.01, 52.15,
9.47; Anal. Calcd. for C22H23N5O2S: C, 62.69; H, 5.50; N, 16.61; S,
7.61. Found: C, 62.72; H, 5.51; N, 16.63; S, 7.59.
d6):
d 172.97, 140.70, 135.59, 133.32, 130.83, 129.67, 126.97, 126.84,
126.48, 126.20, 125.82, 125.43, 124.55, 98.57, 52.50, 49.30, 7.09; MS
(ESI): m/z (%) 396.17 (M þ H); Anal. Calcd. for C20H18ClN5S: C,
60.67; H, 4.58; N, 17.69; S, 8.10. Found: C, 60.68; H, 4.557; N, 17.68;
S, 8.11.
4.1.11. 6-(1-Benzyl-5-methyl-1H-1,2,3-triazol-4-yl)-4-(2,4-dichlo-
rophenyl)-3,4-dihydropyrimidine-2(1H)-thione (2k)
White solid; m.p. 205 ꢁC; Yield: 79%; 1H NMR (300 MHz, DMSO-
d6):
5.42 (bs,1H, eCH), 5.24 (bs,1H, olefinic eCH), 2.12 (s, 3H, eCH3); 13
NMR (75 MHz, DMSO-d6): 173.74, 137.62, 133.08, 131.35, 129.58,
d 9.12 (bs, 2H, NH), 7.42e7.09 (m, 8H, ArH), 5.50 (m, 2H, eCH2),
4.1.5. 6-(1-Benzyl-5-methyl-1H-1,2,3-triazol-4-yl)-4-(4-nitro-
phenyl)-3,4-dihydropyrimidine-2(1H)-thione (2e)
C
White solid; m.p. 195 ꢁC; Yield: 81%; 1H NMR (300 MHz, DMSO-
d
129.41, 127.59, 127.17, 126.83, 126.08, 126.03, 125.27, 124.99, 96.33,
76.36, 50.32, 49.21, 6.93; Anal. Calcd. for C20H17Cl2N5S: C, 55.82; H,
3.98; N, 16.27; S, 7.45. Found: C, 55.86; H, 3.96; N, 16.25; S, 7.46.
d6):
5.19 (bs, 1H, olefinic eCH), 2.29 (s, 3H, eCH3); 13C NMR (75 MHz,
DMSO-d6): 182.46, 149.75, 139.77, 137.72, 131.35, 130.36, 128.39,
d 7.51e7.16 (m, 9H, ArH), 5.53 (m, 2H, eCH2), 5.23 (bs, 1H, eCH),
d
127.98, 127.70, 126.36, 125.37, 122.23, 98.63, 55.73, 52.24, 8.90;
Anal. Calcd. for C20H18N6O2S: C, 59.10; H, 4.46; N, 20.68; S, 7.89.
Found: C, 59.14; H, 4.47; N, 20.67; S, 7.88.
4.1.12. 6-(1-Benzyl-5-methyl-1H-1,2,3-triazol-4-yl)-4-p-tolyl-3,4-
dihydropyrimidine-2(1H)-thione (2l)
White solid; m.p. 168 ꢁC; Yield: 93%. 1H NMR (300 MHz, CDCl3):
d
8.57 (bs, 1H, NH), 7.31e7.14 (m, 9H, ArH), 6.92 (bs, 1H, NH), 5.51
4.1.6. 6-(1-Benzyl-5-methyl-1H-1,2,3-triazol-4-yl)-4-(3-bromo-
phenyl)-3,4-dihydropyrimidine-2(1H)-thione (2f)
(m, 2H, eCH2), 5.22 (bs, 1H, eCH), 5.07 (bs, 1H, olefinic eCH), 2.32
(s, 3H, eCH3), 2.23 (s, 3H, eCH3); 13C NMR (75 MHz, CDCl3):
White solid, m.p. 185 ꢁC; Yield: 83%; 1H NMR (300 MHz, CDCl3):
d
175.25, 139.53, 138.52, 137.42, 134.16, 130.38, 129.78, 129.90,
d
7.61e6.98 (m, 9H, ArH), 5.55 (m, 2H, eCH2), 5.20 (bs, 1H, eCH);
5.18 (bs, 1H, olefinic eCH), 2.27 (s, 3H, eCH3); 13C NMR (75 MHz,
CDCl3): 175.35, 144.81, 134.03, 131.55, 130.65, 130.50, 129.84,
128.54, 127.08, 126.78, 126.07, 99.69, 56.55, 52.13, 21.04, 9.47; MS
(ESI): m/z (%) 376.30 (M þ H); Anal. Calcd. for C21H21N5S, 67.17; H,
5.64; N, 18.65; S, 8.54. Found: C, 67.21; H, 5.62; N, 18.63; S, 8.53.
d
129.05, 128.50, 127.03, 126.53, 125.42, 98.58, 56.06, 52.07, 9.43;
Anal. Calcd. for C20H18BrN5S: C, 54.55; H, 4.12; N, 15.90; S, 7.28.
Found: C, 54.58; H, 4.11; N, 15.91; S, 7.27.
Acknowledgments
The authors wish to acknowledge IRHPA, DST for providing
300 MHz NMR instrument for recording the NMR spectra, DST-
PURSE, UGC (BSR)-Meritorious Scheme for giving financial
support and Department of Microbial Technology, School of Bio-
logical sciences, Madurai Kamaraj University for providing the
cultures of human pathogens used in this study.
4.1.7. 6-(1-Benzyl-5-methyl-1H-1,2,3-triazol-4-yl)-4-(2-bromo-
phenyl)-3,4-dihydropyrimidine-2(1H)-thione (2g)
White solid; m.p. 179 ꢁC; Yield: 83%; 1H NMR (300 MHz, CDCl3):
7.56e7.16 (m, 9H, ArH), 5.69 (bs, 1H, eCH), 5.58 (m, 2H, eCH2), 5.28
(bs, 1H, olefinic eCH), 2.25 (s, 3H, eCH3); 13C NMR (75 MHz, CDCl3):
d
175.92, 40.79, 137.26, 134.11, 133.12, 130.56, 129.87, 129.10, 128.93,
128.60, 128.55, 127.12, 126.96, 121.38, 97.54, 55.50, 52.15, 9.49; Anal.
Calcd. for C20H18BrN5S: C, 54.55; H, 4.12; 15; N, 15.90; S, 7.28.
Found: C, 54.57; H, 4.13; N, 15.91; S, 7.26.
Appendix A. Supplementary data
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.ejmech.2012.10.029.
4.1.8. 6-(1-Benzyl-5-methyl-1H-1,2,3-triazol-4-yl)-4-(4-bromo-
phenyl)-3,4-dihydropyrimidine-2(1H)-thione (2h)
White solid; m.p. 185 ꢁC; Yield: 88%; 1H NMR (300 MHz, CDCl3):
References
d
8.68 (bs, 1H, NH), 8.62 (bs, 1H, NH), 7.51e7.16 (m, 9H, ArH), 5.53
(m, 2H, eCH2), 5.19 (bs, 1H, eCH), 5.14 (bs, 1H, olefinic eCH), 2.25 (s,
3H, eCH3); 13C NMR (75 MHz, CDCl3):
174.41, 141.71, 136.72,
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