Microwave-assisted synthesis and antibacterial activity of methyl 1-{2-[4-amino-5-(naphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio]ethyl} -1H-indole-3-carboxylate derivatives

Article abstract of DOI:10.3184/174751913X13716369958329

Twelve new Schiff bases containing a disubstituted 1,2,4-triazole and a monosubstituted indole linked by a thioethyl group were efficiently synthesised via a method employing microwave irradiation. Compared with a conventional method of heating at 100 °C, yields were increased from 46-48 to 82-92% and the reaction times were reduced from 20-25 h to 4-7 min. The structures of these novel hexacyclic Schiff bases were characterised by their spectral data and elemental analysis. Evaluation of their antibacterial activity showed that many of them possess excellent activity against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Bacillus subtilis.

Full text of DOI:10.3184/174751913X13716369958329

JOURNAL OF CHEMICAL RESEARCH 2013
RESEARCH PAPER 413
JULY, 413–416
Microwave-assisted synthesis and antibacterial activity of methyl
1-{2-[4-amino-5-(naphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio]ethyl}-
1H-indole-3-carboxylate derivatives
Yongle Peng, Xingli Liu, Jian Gu and Zhigang Zhao*
College of Chemistry and Environmental Protection Engineering, Southwest University for Nationalities, Chengdu 610041, P. R. China
Twelve new Schiff bases containing a disubstituted 1,2,4-triazole and a monosubstituted indole linked by a thioethyl
group were efficiently synthesised via a method employing microwave irradiation. Compared with a conventional
method of heating at 100 °C, yields were increased from 46–48 to 82–92% and the reaction times were reduced from
20–25 h to 4–7 min. The structures of these novel hexacyclic Schiff bases were characterised by their spectral data
and elemental analysis. Evaluation of their antibacterial activity showed that many of them possess excellent activity
against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Bacillus subtilis.
Keywords: microwave-synthesis, antibacterial activity, Schiff base, indole, 1, 2, 4-triazole
Spectroscopic studies
Antimicrobial agents have been used to treat patients since the
1940s, greatly reducing pain and death from infectious dis-
eases.1 However, these drugs have been used so widely and for
so long that they are no longer so effective.2 During the past
several decades, the number of new antibiotics being brought
to the market has shown a precipitous decline.3 As a result,
developing new antibacterials is quite urgent to keep human
beings healthy. The latest research shows that compounds
containing a Schiff base,4–6 an indole7–9 or a 1,2,4-triazole10–12
possess good antibacterial activity. Building on the achieve-
ments our team have made,13–14 we have designed and synthe-
sised a series of novel Schiff bases containing an indole and a
1,2,4-triazole for the purpose of finding new compounds which
can intensively inhibit the growth of bacteria.
Microwave-synthesis is a well-established technique in green
chemistry and has many advantages compared with traditional
methods, such as faster reaction times, higher yields and is
solvent-free.15–17 It has been applied in many organic syntheses.18
Accordingly, as a further development of our green agenda,19,20
we hoped microwave-synthesis could be used successfully
in the synthesis of our newly designed Schiff bases.
The structures of compounds 7 and 8a–l were characterised by
their IR spectra, 1H NMR spectra, ESI-MS and elemental anal-
yses. In the IR spectra of 7, the absorption band at 3336 cm−1
was assigned to the NH2 group which was absent, as expected,
in the IR spectra of 8a–l. The strong bands at 1596–1575 cm−1
in the IR spectra of 8a–l were attributed to the absorption of
C=N which did not appear in the IR spectrum of 7. The singlet
1
at 4.39 ppm in the H NMR spectra of 7 was assigned to the
1
NH2 group and a similar signal was absent in the H NMR
spectra of 8a–l. The singlet at 7.97–7.64 ppm in 8a–l was
assigned to the ArCHN. The aromatic protons appeared at
8.38–6.43 ppm. The triplet at 4.82 ppm was assigned to the
indole-1-CH2. The singlet at 4.39 ppm was assigned to the
OCH3 group. The triplet at about 3.79 ppm was attributed to
the SCH2 group. Their ESI-MS spectra showed the correct
molecular ion peaks with high intensity. Moreover, their
elemental analyses further confirmed their structures.
Biological activity
To evaluate the antimicrobial activity of these novel Schiff
bases, the values of MIC and IC50 were determined via in vitro
biological activity tests. Two Gram-positive bacteria (Staphy-
lococcus aureusATCC6538, Bacillus subtilis ATCC 6633) and
two Gram-negative bacteria (Escherichia coli ATCC 35218,
Pseudomonas aeruginosa ATCC 27853) were used as test
strains.Amoxicillin was used as a positive control and dimethyl
sulfoxide was used as a negative control.
The MIC and IC50 values of these newly synthesised Schiff
bases are shown in Table 2. From Table 2, we can conclude
that compounds 8b, 8c, 8e, 8f, 8h and 8k possess good anti-
bacterial activity to the four test strains. Indeed compounds
8b, 8c, 8e, 8f and 8k showed better inhibition to S. aureus
than did Amoxicillin, as did compounds 8c, 8e, 8f and 8k
towards E. coli and compounds 8f, 8h and 8k towards
P. aeruginosa.
Results and discussion
Synthesis
The synthetic route used is shown in Scheme 1. The trisubsti-
tuted1,2,4-triazole5waspreparedinfourstepsfrom1-naphthoic
acid 1a via compounds 2, 3 and 4 as described previously.21,22
Methyl 1-(2-bromoethyl)-1H-indole-3-carboxylate 6 was pre-
pared by treatment of methyl 1H-indole-3-carboxylate 1b with
1,2-dibromoethane according to a literature method.22 Tricyclic
5 was reacted with bicyclic 6 in the presence of potassium
carbonate to give the pentacyclic amine 7, condensation
of which with a series of araldehydes in acetic acid, either at
100 °C or under microwave irradiation, gave the hexacyclic
imines 8a–l.
According to the antibacterial activity conclusions above,
we can recognise that the aromatic substituents play an impor-
tant role in the antibacterial activity, halogen and nitro groups
effecting enhancement of the antibacterial activity of these
Schiff bases, whereas hydroxy and methoxy did not do so.
Comparison of microwave irradiation and conventional heating
Compared with the traditional heating method, microwave
synthesis showed a lot of advantages such as solvent-free,
shorter reaction times and higher yields, as shown in Table 1.
When compounds 8a–l were synthesised without any solvent
under microwave irradiation, the reaction time was reduced
from 20–25 h to 4–7 min, and the yield was increased from
46–68 to 82–92%.
Experimental
Melting points were measured via a micro-melting point apparatus
and are uncorrected. IR spectra were determined on a 1700 Perkin-
1
Elmer FTIR using KBr disks. H NMR spectra were obtained on
a Varian INOVA 400 MHz spectrometer using TMS as the internal
standard, in DMSO-d6 or CDCl3. Mass spectra were obtained on
Finnigan LCQDECA instrument. Elemental analyses was obtained on
* Correspondent. E-mail: zzg63129@yahoo.com.cn

414 JOURNAL OF CHEMICAL RESEARCH 2013
Scheme 1 Synthetic route for the target compounds.
Table 1 Comparison of microwave irradiation with conven-
tional heating for the efficiency of synthesis of hexacyclic
imines 8a–l by condensation of araldehydes with pentacyclic
amine 7 (Scheme 1)
a Carlo-Erba-1106 autoanalyser. Microwave-assisted reactions were
processed in a microwave reactor (XH-100A, 100-1000 W, Beijing
Xianghu Science and Technology Development Co. Ltd, Beijing,
P. R. China). The sterilisation of equipment and reagents was carried
out in a portable stainless steel pressure steam steriliser (YX280A,
Shanghai Sanshen Medical Instrument Co.,Ltd, Shanghai, P.R. China).
All aseptic operations were performed on a super clean bench
(DL-CJ-1N, Donglian Elactronic & Technology Develepment Co.Ltd,
Beijing, P.R. China). The bacteria were grown in a constant tempera-
ture incubator (ECA-9272, Beijing ECOA Science & Development
Co., Ltd, Beijing, P.R. China). All solvents were purified before use.
1-Naphthoic acid 1a and methyl 1H-indole-3-carboxylate 1b were
supplied by Tokyo Chemical Industry Co., Ltd.
a
Compd
Ar
Microwave
method
Conventional tC/tMW
method
Time
/min
Yield
/%
Time
/min
Yield
/%
8a
8b
8c
8d
8e
8f
8g
8h
8i
3-HO-C6H4
4-Br-C6H4
4-NO2-C6H4
4-HO-C6H4
4-F-C6H4
2-Cl-C6H4
2-furyl
5
4
6
5
4
7
5
4
6
6
4
5
86
88
85
87
90
88
88
86
82
85
88
92
1260
1380
1440
1260
1500
1380
1320
1200
1440
1380
1260
1320
57
62
46
54
65
56
60
53
63
58
55
68
252
345
240
252
375
197
264
300
240
230
315
264
Synthesis of intermediate 7
Compound 5 (0.86 g, 3.54 mmoL), compound 6 (1 g, 3.54 mmoL) and
K2CO3 (0.98 g, 7.01 mmoL) were dissolved in DMF (15 mL) in a
50 mL round bottomed flask and stirred at room temperature until
TLC indicated that the reaction was completed. Then DMF was
removed by reduced pressure distillation. The residue was recrystal-
lised in MeOH to give compound 7 as a grey solid (85%), m.p. 171–
173 °C; IR, ν: 3350, 3018, 2970, 1735, 1603, 1433, 1281, 1224, 834,
730 cm−1; 1H NMR (CDCl3) δ 8.19–8.17 (m, 1H, ArH), 8.05–8.03 (d,
J = 8.4 Hz, 1H, ArH), 7.97–7.95 (m, 1H, ArH), 7.92 (s, 1H, ArH),
4-Cl-C6H4
4-CH3O-C6H4
2-HO-C6H4
3-F-C6H4
8j
8k
8l
phenyl
a tC = conventional method time; tMW = microwave method
time.

JOURNAL OF CHEMICAL RESEARCH 2013 415
Table 2 Antibacterial activity of hexacyclic imines 8a–l and a positive control (amoxicillin)
Compd
Inhibitory concentration (µg mL–1)
Gram-positive bacteria
S. aureus B. subtilis
Gram-negative bacteria
E. coli P. aeruginosa
MIC
IC50
MIC
IC50
>64
8.1
6.5
>64
38
3.9
>64
64
>64
>64
MIC
IC50
>64
6.9
3.5
>64
2.3
3.9
23.4
7.9
>64
>64
4
>64
7.3
MIC
IC50
8a
>128
8
>64
>128
16
>128
16
>128
8
>64
4
4.1
>64
5
2.4
>64
2.8
24.1
>64
1.8
>64
2.5
8b
5.2
6.8
>64
8c
8
8
8
8
8d
>128
8
>128
8
>128
4
>128
8
8e
4.2
4.1
29.7
9.1
35.9
8f
8
8
8
4
8g
64
>128
8
32
>128
4
8h
16
16
8i
64
>128
>128
8
>128
8
>128
>128
8
32
>128
4
>128
8
8j
>128
4
>64
8k
3
3.3
>64
2.7
8l
>128
16
>64
>128
16
Amoxicillin
6.4
7.76–7.74 (m, 1H, ArH), 7.69–7.67 (d, J = 6 Hz, 1H, ArH), 7.63–7.32
(m, 4H, ArH), 7.32–7.28 (m, 2H, ArH), 4.78 (t, J = 6.8 Hz, 2H, indole-
CH2), 4.39 (s, 2H, NH2), 3.88 (s, 2H, OCH3), 3.74 (t, J = 6.8 Hz, 2H,
SCH2); ESI–MS (m/z, %): 908.80 [(2M+23)+, 100]. Anal. Calcd for
C24H21N5O2S: C, 64.99; H, 4.77; N, 15.79. Found: C, 65.07; H, 4.75;
N, 15.76%.
2H, SCH2); ESI–MS (m/z, %): 576.98 [(M+1)+, 100]. Anal. Calcd for
C31H24N6O4S: C, 64.57; H, 4.20; N, 14.57. Found: C, 64.60; H, 4.18;
N, 14.55%.
8d: White solid (87%), m.p. 198–200 °C (MeOH); IR, ν: 3419,
3058, 2959, 1721, 1688, 1597, 1438, 1293, 1229, 802, 744 738 cm−1;
1H NMR (CDCl3) δ 10.41 (s, 1H, OH), 8.30 (s, 1H, ArH), 8.22 (s, 1H,
ArH), 8.10 (d, J = 8.0 Hz, 1H, ArH), 8.02 (s, 2H, ArH), 7.91 (m, 1H,
ArH), 7.77–7.67 (m, 3H, ArH), 7.64–7.62 (m, 3H, ArH), 7.41 (d,
J = 8.8 Hz, 1H, ArH), 7.28–7.22 (m, 2H, ArH), 6.77 (d, J = 8.4 Hz,
2H, ArH), 4.76–4.72 (t, J = 6.8 Hz, 2H, indole-CH2), 3.79 (s, 3H,
OCH3), 3.74 (t, J = 6.8 Hz, 2H, SCH2); ESI–MS (m/z, %): 547.97
[(M+1)+, 100]. Anal. Calcd for C31H25N5O3S: C, 67.99; H, 4.60; N,
12.79. Found: C, 68.05; H, 4.58; N, 12.75%.
8e: Yellow solid (90%), m.p. 212–214 °C (EtOH); IR, ν: 3054,
2934, 2357, 1697, 1533, 1435, 1395, 1261, 1223, 1160, 775, 749 cm−1;
1H NMR (CDCl3) δ 8.36 (s, 1H, ArH), 8.20 (d, J = 8.0 Hz, 1H, ArH),
8.04 (d, J = 8.0 Hz, 1H, ArH), 7.97 (s, 1H, ArH), 7.94–7.92 (m, 1H,
ArH), 7.89 (d, J = 7.6 Hz, 1H, ArH), 7.76 (d, J = 6.8 Hz, 2H, ArH),
7.64–7.60 (m, 2H, ArH), 7.55–7.53 (m, 2H, ArH), 7.38–7.21 (m, 5H,
ArH), 4.85 (t, J = 6.8 Hz, 2H, indole-CH2), 3.90 (s, 3H, OCH3), 3.80
(t, J = 6.8 Hz, 2H, SCH2); ESI–MS (m/z, %): 1242.41 [(2M+23)+,
100]. Anal. Calcd for C31H24BrN5O2S: C, 60.99; H, 3.96; N, 11.47.
Found: C, 61.05; H, 3.93; N, 11.44%.
8f: Yellow solid (88%), m.p. 160–162 °C (MeOH); IR, ν: 3058,
2942, 2365, 2341, 1697, 1533, 1436, 1395, 1261, 1223, 1160, 775,
749 cm−1; 1H NMR (CDCl3) δ 8.38 (s, 1H, ArH), 8.20 (d, J = 7.6 Hz,
1H, ArH), 8.05 (d, J = 8.0 Hz, 1H, ArH), 7.97 (s, 1H, ArH), 7.95–7.92
(m, 1H, ArH), 7.89 (d, J = 7.6 Hz, 1H, ArH), 7.78–7.74 (m, 2H, ArH),
7.64–7.59 (m, 2H, ArH), 7.55–7.53 (m, 2H, ArH), 7.34–7.28 (m, 3H,
ArH), 7.23–7.18 (m, 2H, ArH), 4.85 (t, J = 6.8 Hz, 2H, indole-CH2),
3.90 (s, 3H, OCH3), 3.80 (t, J = 6.8 Hz, 2H, SCH2); ESI–MS (m/z, %):
1152.53 [(2M+23)+, 100]. Anal. Calcd for C31H24ClN5O2S: C, 65.77;
H, 4.27; N, 12.37. Found: C, 65.81; H, 4.24; N, 12.34%.
8g: Yellow solid (88%), m.p. 212–214 °C (EtOH); IR, ν: 3112,
3054, 2946, 2361, 1698, 1533, 1395, 1224, 1161, 1090, 775, 749 cm−1;
1H NMR (CDCl3) δ 8.20 (d, J = 7.6 Hz, 1H, ArH), 8.02 (d, J = 8.4 Hz,
1H, ArH), 7.96–7.91 (m, 2H, ArH), 7.69 (d, J = 7.2 Hz, 1H, ArH),
7.64 (s, 1H, ArH), 7.61–7.53 (m, 5H, ArH), 7.33–7.28 (m, 3H, ArH),
6.68–6.67 (d, J = 3.2 Hz, 1H, ArH), 6.43 (s, 1H, ArH), 4.83 (t, J =
6.8 Hz, 2H, indole-CH2), 3.90 (s, 3H, OCH3), 3.76 (t, J = 6.8 Hz, 2H,
SCH2); ESI–MS (m/z, %): 1064.75 [(2M+23)+, 100]. Anal. Calcd for
C29H23N5O3S: C, 66.78; H, 4.44; N, 13.43. Found: C, 66.82; H, 4.41;
N, 13.45%.
Synthesis of compounds 8a–l; conventional method
Compound 7 (66.4 mg, 0.15 mmoL) and an aromatic aldehyde
(0.15 mmoL) were dissolved in acetic acid (2 mL) in a 10 mL round
bottom flask and stirred and heated to 100 °C. The reaction was
monitored by TLC to ensure that it was completed. Then the solvent
was removed by reduced pressure distillation. The residue was recrys-
tallised in MeOH or EtOH to give compounds 8ª–l (46–68%) as solids
of various colours.
Synthesis of compounds 8a–l; microwave method
Compound 7 (66.4 mg, 0.15 mmoL), an aromatic aldehyde (0.15 mmoL)
and two drops of acetic acid (catalyst) were mixed thoroughly by
grinding in a porcelain mortar. The mixture was added into a spe-
cialised vessel which was placed in a microwave oven and irradiated
at 300 W for 4–7 min. The reaction was monitored by TLC until it was
completed. The mixture was recrystallised in MeOH or EtOH to
obtain the pure products 8a–l (82–92%) as solids of various colours.
The physical and spectra data of the compounds 8a–l are as follows.
8a: White solid (86%), m.p. 182–184 °C (MeOH); IR, ν: 3560,
3053, 2946, 2830, 2720, 1688, 1574, 1539, 1438, 1399, 1290, 1271,
770, 746 cm−1; 1H NMR (DMSO-d6) δ 9.78 (s, 1H, OH), 8.38 (s, 1H,
ArH), 8.23 (s, 1H, ArH), 8.13 (d, J = 7.6 Hz, 1H, ArH), 8.03 (d, J =
7.2 Hz, 2H, ArH), 7.87 (s, 1H, ArH), 7.74 (t, J = 6.4 Hz, 2H, ArH),
7.66 (t, J = 8.0 Hz, 1H, ArH),7.60–7.58 (m, 2H, ArH), 7.29–7.19
(m, 3H, ArH), 6.94 (t, J = 8.0 Hz, 3H, ArH), 4.77 (t, J = 6.8 Hz,
2H, indole–CH2), 3.79 (s, 3H, OCH3), 3.76 (t, J = 6.8 Hz, 2H, SCH2);
ESI–MS (m/z, %): 547.89 [(M+1)+, 100].Anal. Calcd for C31H25N5O3S:
C, 67.99; H, 4.60; N, 12.79. Found: C, 68.06; H, 4.58; N, 12.76%.
8b: White solid (88%), m.p. 126–128 °C (MeOH); IR, ν: 3052,
2945, 2361, 2354, 1698, 1587, 1532, 1464, 1436, 1395, 1280, 1222,
1160, 774, 748 cm−1; 1H NMR (CDCl3) δ 8.20 (t, J = 6.8 Hz, 1H, ArH),
8.03 (d, J = 8.4 Hz, 1H, ArH), 7.95 (s, 1H, ArH), 7.93–7.89 (m, 2H,
ArH), 7.79 (s, 1H, ArH), 7.70 (d, J = 6.8 Hz, 1H, ArH), 7.59–7.53 (m,
4H, ArH), 7.45 (d, J = 8.0 Hz, 2H, ArH), 7.33–7.28 (m, 2H, ArH),
7.25 (d, J = 8.8 Hz, 2H, ArH), 4.83 (t, J = 6.8 Hz, 2H, indole-CH2),
3.90 (s, 3H, OCH3), 3.79–3.75 (t, J = 6.8 Hz, 2H, SCH2); ESI–MS
(m/z, %): 611.96 [(M+1)+, 100]. Anal. Calcd for C31H24BrN5O2S: C,
60.99; H, 3.96; N, 11.47. Found: C, 61.06; H, 3.94; N, 11.45%.
8c: Yellow solid (85%), m.p. 148–150 °C (EtOH); IR, ν: 3110,
8h: Yellow solid (86%); m.p. 152–154 °C (MeOH); IR, ν: 3050,
1
2938, 1697, 1588, 1395, 1223, 1161, 1090, 775, 749 cm−1; H NMR
(CDCl3) δ 8.20–8.18 (m, 1H, ArH), 8.03 (d, J = 8.4 Hz, 1H, ArH), 7.96
(s, 1H, ArH), 7.93–7.90 (m, 2H, ArH), 7.81 (s, 1H, ArH), 7.71–7.69
(d, J = 6.8 Hz, 1H, ArH), 7.60–7.57 (m, 2H, ArH), 7.55–7.53 (m, 3H,
ArH), 7.33–7.28 (m, 5H, ArH), 4.84 (t, J = 6.8 Hz, 2H, indole-CH2),
3.90 (s, 3H, OCH3), 3.79 (t, J = 6.8 Hz, 2H, SCH2); ESI–MS (m/z, %):
565.90 [(M+1)+, 100]. Anal. Calcd for C31H24ClN5O2S: C, 65.77; H,
4.27; N, 12.37. Found: C, 65.82; H, 4.25; N, 12.35%.
1
3050, 2948, 1694, 1523, 1346, 1226, 1162, 846, 777, 744 cm−1; H
NMR (CDCl3) δ 8.19 (d, J = 6.8 Hz, 1H, ArH), 8.15 (d, J = 8.8 Hz, 2H,
ArH), 8.07 (d, J = 8.4 Hz, 1H, ArH), 7.95 (d, J = 8.0 Hz, 1H, ArH),
7.87 (s, 1H, ArH), 7.83 (t, J = 5.6 Hz, 2H, ArH), 7.73 (d, J = 6.8 Hz,
1H, ArH), 7.62–7.49 (m, 6H, ArH), 7.31–7.27 (m, 2H, ArH), 4.84 (t,
J = 6.8 Hz, 2H, indole-CH2), 3.89 (s, 3H, OCH3), 3.82 (t, J = 6.8 Hz,

416 JOURNAL OF CHEMICAL RESEARCH 2013
8i: White solid (82%), m.p. 117–119 °C (EtOH); IR, ν: 3054, 2942,
1698, 1597, 1258, 1166, 1089, 775, 749 cm−1; 1H NMR (CDCl3)
δ 8.21 (d, J = 6.8 Hz, 1H, ArH), 8.02–7.96 (m, 3H, ArH), 7.91 (t, J =
6.8 Hz, 1H, ArH), 7.81 (s, 1H, ArH), 7.71 (d, J = 7.2 Hz, 1H, ArH),
7.61–7.53 (m, 4H, ArH), 7.38 (d, J = 8.8 Hz, 2H, ArH), 7.33–7.28 (m,
2H, ArH), 6.82 (d, J = 8.8 Hz, 2H, ArH), 4.84 (t, J = 6.8 Hz, 2H,
indole-CH2), 3.90 (s, 3H, COOCH3), 3.79 (s, 3H, ArOCH3), 3.77 (t,
J = 6.8 Hz, 2H, SCH2); ESI–MS (m/z, %): 561.98 [(M+1)+, 100].
Anal. Calcd for C32H27N5O3S: C, 68.43; H, 4.85; N, 12.47. Found: C,
68.49; H, 4.82; N, 12.45%.
of the test compounds dissolved in DMSO were prepared to final con-
centrations of 640, 320, 160, 80, 40, 20, 10, 5 µg mL−1. Bacteria fluids
of 0.5 McFarland standards were painted on bouillon medium and
then filter papers (diameter of 6 mm) saturated with compound dilu-
tions above were placed on top of the growing bacteria. The diameter
of the inhibition zone was obtained after incubation at 37 °C for 16 h.
We are grateful for financial support from the Science and
TechnologyDepartmentofSichuanProvince(No.2012JY0028)
and the Postgraduate Degree Construction Project of South-
west University for Nationalities (No. 2013XWD-S0703).
8j: White solid (85%), m.p. 190–192 °C (MeOH); IR, ν: 3390,
3052, 2944, 2360, 2342, 1698, 1603, 1533, 1463, 1396, 1262, 1224,
1
1158, 1090, 776, 749 cm−1; H NMR (CDCl3) δ 9.85 (s, 1H, OH),
8.20–8.19 (d, J = 7.2 Hz, 1H, ArH), 8.04 (d, J = 8.4 Hz, 1H, ArH),
7.97 (s, 1H, ArH), 7.94 (d, J = 8.0 Hz, 3H, ArH), 7.69 (d, J = 7.2 Hz,
1H, ArH), 7.60 (t, J = 7.6 Hz, 4H, ArH), 7.36–7.28 (m, 3H, ArH), 6.92
(d, J = 8.4 Hz, 1H, ArH), 6.81–6.73 (m, 2H, ArH), 4.85 (t, J = 6.8 Hz,
2H, indole-CH2), 3.89 (s, 3H, OCH3), 3.81 (t, J = 6.8 Hz, 2H, SCH2);
ESI–MS (m/z, %): 1116.32 [(2M+23)+, 100]. Anal. Calcd for
C31H25N5O3S: C, 67.99; H, 4.60; N, 12.79. Found: C, 68.05; H, 4.57;
N, 12.75%.
8k: Yellow solid (88%), m.p. 149–151 °C (EtOH); IR, ν: 3054,
2946, 2361, 2344, 1697, 1533, 1448, 1396, 1380, 1261, 1224, 1161,
1090, 776, 749 cm−1; 1H NMR (CDCl3) δ 8.20 (t, J = 7.2 Hz, 1H, ArH),
8.04 (d, J = 8.4 Hz, 1H, ArH), 7.96 (s, 1H, ArH), 7.94–7.89 (m, 2H,
ArH), 7.82 (s, 1H, ArH), 7.72 (d, J = 6.8 Hz, 1H, ArH), 7.60–7.54 (m,
4H, ArH), 7.33–7.28 (m, 3H, ArH), 7.19 (d, J = 9.6 Hz, 1H, ArH),
7.14–7.10 (m, 1H, ArH), 7.07 (d, J = 7.6 Hz, 1H, ArH), 4.84 (t, J =
6.8 Hz, 2H, indole-CH2), 3.90 (s, 3H, OCH3), 3.80 (t, J = 6.8 Hz, 2H,
SCH2); ESI–MS (m/z, %): 1120.56 [(2M+23)+, 100]. Anal. Calcd for
C31H24FN5O2S: C, 67.74; H, 4.40; N, 12.74. Found: C, 67.80; H, 4.37;
N, 12.70%.
8l: Pale solid (92%), m.p. 94–96 °C (EtOH); IR, ν: 3053, 2945,
2361, 2328, 1698, 1533, 1396, 1374, 1261, 1224, 1161, 1090, 776,
750 cm−1; 1H NMR (CDCl3) δ 8.20 (t, J = 6.4 Hz, 1H, ArH), 8.02 (d,
J = 8.4 Hz, 1H, ArH), 7.96 (s, 2H, ArH), 7.93–7.90 (m, 1H, ArH), 7.88
(s, 1H, ArH), 7.71 (d, J = 7.2 Hz, 1H, ArH), 7.61–7.53 (m, 4H, ArH),
7.45–7.39 (m, 3H, ArH), 7.33–7.28 (m, 4H, ArH), 4.84 (t, J = 6.8 Hz,
2H, indole-CH2), 3.89 (s, 3H, OCH3), 3.78 (t, J = 6.8 Hz, 2H, SCH2);
ESI–MS (m/z, %): 530.01 [(M+1)+, 100].Anal. Calcd for C31H25N5O2S:
C, 70.04; H, 4.74; N, 13.17. Found: C, 70.09; H, 4.71; N, 13.14%.
Antibacterial activity test for the MIC values (in vitro): The MIC
was evaluated by the double dilution method in tubes employing
standard inoculums of 105 CFU mL−1. Successive dilutions of the
test compounds dissolved in DMSO (1 mL) were prepared to final
concentrations of 256, 128, 64, 32, 16, 8, 4, 2, 1, 0.5, 0.25 µg mL−1.
Bacterial fluid of 0.5 McFarland standards (1 mL) was added into
each test solution. The MIC values were visually determined by inhi-
bition of the visible bacterial growth after incubation for 16 h at
37 °C.
Received 13 March 2013; accepted 14 May 2013
Paper 1301834 doi: 10.3184/174751913X13716369958329
Published online: 18 July 2013
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