Manganese(III) Acetate Mediated Synthesis of 3-arylsulfenylindoles and Evaluation of Their Antibacterial Activity

Article abstract of DOI:10.13005/ojc/340150

The present work reports a simple and efficient method for the sulfenylation of a wide variety of indoles with aryl, benzothiazolethiols using manganese(III) acetate promoted free radical reaction. This method is selective at the C3 position of indoles and offers several advantages such as broad substrate scope, functional group tolerance (bromo, carboxylic acid, methoxy, difluoromethoxy, ester groups) and gives the required products in good to excellent yields. The experimental simplicity makes it a useful and attractive approach for the synthesis of 3-arylsulfenylindoles. The compounds 1-12 are evaluated for the anti-bacterial agents. Most of them exhibited promising activities.

Full text of DOI:10.13005/ojc/340150

ISSN: 0970-020 X
CODEN: OJCHEG
018, Vol. 34, No.(1):
Pg. 457-466
ORIENTAL JOURNAL OF CHEMISTRY
An International Open Free Access, Peer Reviewed Research Journal
2
www.orientjchem.org
Manganese(III) Acetate Mediated Synthesis of
3
-arylsulfenylindoles and Evaluation of Their
Antibacterial Activity
RAVI KUMAR G.M.V.N.A.R. and THANGAMANI ARUMUGAM*
Department of Chemistry, Karpagam University, Karpagam Academy of Higher Education,
Coimbatore- 641021, Tamil Nadu, India.
*
corresponding author: Email: thangabell2003@gmail.com
http://dx.doi.org/10.13005/ojc/340150
(Received: October 25, 2017; Accepted: November 20, 2017)
ABSTRACT
The present work reports a simple and efficient method for the sulfenylation of a wide
variety of indoles with aryl, benzothiazolethiols using manganese(III) acetate promoted free radical
reaction. This method is selective at the C3 position of indoles and offers several advantages
such as broad substrate scope, functional group tolerance (bromo, carboxylic acid, methoxy,
difluoromethoxy, ester groups) and gives the required products in good to excellent yields. The
experimental simplicity makes it a useful and attractive approach for the synthesis of
3-arylsulfenylindoles. The compounds 1-12 are evaluated for the anti-bacterial agents. Most of
them exhibited promising activities.
Keywords: Sulfenylation of indoles, Regioselectivity, Manganese(III) acetate, C-S bond
formation, Antibacterial activity.
4
INTRODUCTION
organic nonlinear optical materials. The following
compounds such as MK-886 (III) is having antitumor
5
Among the most important heterocyclic
units indole nucleus has received major attention
as a key structural building block due to their
medicinal and pharmaceutical applications.
Further 3-thioindole motifs are very common in
activity, L-737,126 (VII) is identified as a potent
anti-HIV agent, the 3-(arylsulfenyl)indole is able
to inhibit human breast cancer cell growth,
vasoconstrictor tinazoline (I) is 4,5-dihydro-2-
(3-indolyl) mercaptoimidazole known as a nasal
6
7
1
2
8
various drugs for the treatment of heart disease,
allergies, these are also utilized in the field of
decongestant and acting as an alpha-adrenergic
3
blocking drug (Figure 1).
This is an
.0 International License (https://creativecommons.org/licenses/by-nc-sa/4.0/ ), which permits unrestricted
NonCommercial use, distribution and reproduction in any medium, provided the original work is properly cited.
Open Access article licensed under a Creative Commons Attribution-NonCommercial-ShareAlike
4

4
58
ARUMUGAM et al., Orient. J. Chem., Vol. 34(1), 457-466 (2018)
It is planned to synthesize analogues of
Recently, various methods are reported for
tinazoline by replacing the imidazole moiety with the 3-arylthiolation of indoles using the various
1
2
benzimidazole because compounds containing sulfenylating agents such as buntesalts,
13
14
15
benzimidazole have numerous biological activities, disulfides, sulfenyl halides, andN-thioarylphthalimides.
9
10
16
for example antitumor and antiparasitic . Although Reagents such as Vanadium oxyacetylacetonate,
1
7
18
19
20
21
compounds containing both indole-benzimidazoles AlCl3 , Selectfluor , NCS , oxone , FeF
,
3
1
1
22
23
are known to show diuretic acitivity but their (bis(trifluoroacetoxy)iodo benzene) , Cu and
2
4
30
complete study is unexplored and hence this work Iodine , and CeCl
have been reported under
3
targets to synthesize compounds containing both different conditions. Particularly substrates
indole-benzimidazoles (or benzothiazole ) through substituted benzimidazolethiol and benzothiazolethiol
C-S bond.
were unexplored in the 3-arylthiolation. Therefore,
the development of a simple, convenient and
general methodology for the sulfenylation of indoles
utilizing a stable and readily available reagent
would extend the scope of this reaction and further
applications of 3-arylsulfenyl indole products.
But
N
O
S
COOH
S
N
Cl
R
H
NH
S
N
N
H
N
(
I) Tinazoline
(II)
COOH
(III)
Cl R =
i
pr (MK-886), OMe
2
F
OMe
S
MeO
MeO
MeO
Although Mn(OAc)3 is a good single-
electron oxidant, selective, mild oxidant and
commercially available. Use of Mn(III)acetate in
C-C bond construction between carbon centered
S
N
SO Ph
CONH
2
MeO
2
S
N
H
H
(
IV)
(VI)
R
2
CO Me
N
H
25
26
radical with olefins and arenes was well
investigated. But its applications are limited mostly
in the field of sulfur-centered free radicals
(
V)
HN
SO
2
Ph
N
SO
2
Ph
CONH
L-737,126
Cl
COOMe
2
N
H
N
27
MeO
2
S
generating from thiols. The main advantage in the
N
H
(IX)
Diuretic Activ, R = Cl, Br
H
(VII)
(VIII)
COX-2 inhibitor
selection of this reagent is its moderate reactivity
thereby is envisioned higher selectivity in the
thioarylation.
Fig.1. Biologically active thioindole derivatives and
indole-benzimidazoles
a
Table 1: Screening of the Optimal Conditions
2
eq. of
H
N
N
HS
Mn(OAc)3
+
S
N
N
Acetic acid
00C, 2h
N
H
H
1a
1b
8
N
1
1H-indole
1
H-benzo[d]imidazole
H
-
2-thiol
2-((1H-indol-3-yl)thio)-
H-benzo[d]imidazole
1
b
Entry Solvent
Temperature (°C) Yield (%)
1
2
3
4
.
.
.
.
DMF
100
80
30
Acetic acid
90
c
H O
2
80
n.r.
n.r.
c
EtOH
80
a
Reaction conditions unless specified otherwise: 1H-Indole (1mmol),
benzothiazole (1mmol) Solvent (10mL), under N2 atmosphere, 2 h.;
b
c
Isolated yield.; n.r. = no reaction.

ARUMUGAM et al., Orient. J. Chem., Vol. 34(1), 457-466 (2018)
459
MATERIAL AND METHODS
Table. 2, entries 10-12). The reaction is tolerant to
bromo substituent on the aromatic ring of indole,
and the corresponding target products were
obtained in good yields (80-84%; Table 2, entries
7-9). Compounds 2a, 3a,5a, 6a,8a, 9a, 11a and
Initially we conducted reaction between
H-indole and 1H-benzoimidazole thiol using
1
Mn(OAc) and tried to optimize the reaction
3
29
conditions (Table 1). In the beginning, this reaction
is conducted under solvent free conditions followed
by preferred solvents such as water and ethanol.
But good results were not observed in the reaction.
Then reaction is examined with toluene, acetonitrile,
12a, are existing as a mixture of tautomers.
Plausible mechanism
2
7c
A plausible mechanism is proposed
involving ligand-exchange pathway for the reaction
of indole with 1H-benzo[d]imidazole-2-thiol (1b)
shown in the scheme-2. The ligand exchange
28
THF, DMF and acetic acid . Among the different
solvents surveyed, better yield was observed with
acetic acid and moderate yield in DMF. Acetic acid
is the solvent of choice, because it has a good
3
between Mn(OAc) and 1H-benzo[d]imidazole-2-
thiol produces the intermediate (IIA), which gets
oxidized to the sulphur centered free radical (IIIA),
and then attacks the electron-rich site of indole i.e.
the 3′-position to yield radical (IVA). Subsequently,
solubility for Mn(OAc) and also giving higher yields
3
in addition to that it degrades rapidly to harmless
substances in the environment.
3
Mn(OAc) oxidizes radical (IVA) to cation (VA) , and
RESULTS AND DISCUSSION
finally loses a proton affording 3-arylthiol product (1).
The optimized condition for regeo
selective sulfenylation reaction of indoles consists
EXPERIMENTAL
of using Indole (1.0equiv.), thiol (1.0 equiv.), reagent
Chemistry
°
(2 equiv.) in acetic acid at 80 C for 2 h (Table-1,
Melting points were determined in open
capillaries and are uncorrected. IR spectra
entry 2).With this optimized reaction condition, the
scope of the reaction is extended by taking into
account various thiols with indole derivatives. As
shown in the Table. 2, unsubstituted indole with
thiol yielded with the required products (85- 90%,
entries 1-3), indoles with electron-donating methyl
group (88-92%; Table entries 4,5,6,13 & 14)
resulted higher yields in comparison to those
having electron-withdrawing groups(72-76%;
(
KBr) were recorded on a Jasco, FT/IR–4100
spectrophotometer. Mass spectras were recorded
1
13
on Shimadzu, LC-2010EV. H NMR and C NMR
spectra were recorded on JEOL 400MHz and
Brukar Avance 300 MHz spectrometer. TMS was
used as internal reference. All the analysis data
obtained at Sapala Organics Private Limited,
Hyderabad.
N
N
N
Mn(OAc)
Ligand
3
S
HS
S
+
N
H
(
III)Mn
N
H
-
Mn(II)
N
H
N
H
exchange
1b
(IIA)
1a
(
IIIA)
H
N
H
N
H
N
S
S
S
N
-H+
N
N
+
N
H
N
N
H
H
1
Mn(II)
Mn(III)
(VA)
(
IVA)
Scheme-2: Mechanism involved in the arythiolation of Indoles

4
60
ARUMUGAM et al., Orient. J. Chem., Vol. 34(1), 457-466 (2018)
Table. 2: Reaction of various indoles with different thiols using Mn(OAc)3

ARUMUGAM et al., Orient. J. Chem., Vol. 34(1), 457-466 (2018)
461
MATERIALS AND METHODS
(400MHz, DMSO-d ,25°C) δ 6.90-6.93 (m, 1H), 7.05-
6
7
.36(m , 4H), 7.45 -7.52 (d, J = 7.8 Hz, 4H), 7.91 (1
Manganese(III) acetate mono hydrate
13
H, d, J = 2.3 Hz), 11.82 (br s, 1H); C NMR (100
used for these reactions was purchased from Aldrich
MHz, DMSO-d ) δ 95.2, 112.3, 113.6, 116.8, 118.0,
6
&
Company. All the other solvents and raw materials
1
3
20.3, 122.2, 128.7, 133.2, 136.6, 145.7, 202.3; IR:
411cm (N-H); ESI-mass: m/z 332 [M +1 peak].
were purchased from common suppliers. Reactions
were monitored by thin-layer chromatography (TLC)
on silica gel plates (60A°; Aldrich & Company),
visualized under 254 nm ultraviolet Light. Column
chromatography separations were performed using
silica gel (70–230 mesh) obtained from the Aldrich
Company. The solvents used for elution varied
depending on the compound and included either
one or a combination of hexane and ethylacetate.
All reactions were conducted under a nitrogen
atmosphere unless otherwise noted.
-1
. +
Mol. Formula: C H F N OS
16
11
2
3
2
-(1H-indol-3-ylthio)-6-methoxy-1H-benzo[d]
imidazole & 2-(1H-indol-3-ylthio)-5-methoxy-1H-
benzo[d]imidazole (compound 3 as tautomeric
mixture of 3a and 3a’)
0
0
8
5% Yield; m.p. 219-221 C C; R= 0.77
f
1
(
Hexane: Ethyl acetate, 60:40, v/v); H NMR (400
MHz, DMSO-d , 25°C) δ ppm 3.71 (s, 3H), 6.68 (dd,
6
J= 8.6, 2.3 Hz, 1H), 6.86 (br s, 1H), 7.07 - 7.11(m,
1H), 7.15 - 7.29 (m, 2H), 7.47 (br d, J = 7.82 Hz, 1H),
7.51 (d, J = 7.83 Hz, 1H), 7.87 (d, J = 2.35 Hz, 1H),
Typical experimental procedure for the synthesis
of Compounds 1-14.
Manganese triacetate (2 mmol) is added
portion wise to a pre dissolved solution of Indole
13
11.78 (br s, 2H); C NMR(100 MHz, DMSO-d ) δ
6
ppm 55.3, 96.1, 110.3, 112.2, 118.1, 120.1, 122.1,
(1mmol) and benzimidazolethiol (1mmol) in acetic
-1
1
28.8, 132.8, 136.6, 155.1; IR: 3363 cm (N-H);
acid (10mL) at room temperature under Nitrogen
. +
ESI-Mass: m/z 296[M +1 peak]; Mol. Formula:
C H N OS
°
atmosphere. The reaction mixture is stirred at 80 C
1
6
13
3
for 2 hours. After completion of reaction, as
monitored by T.L.C analysis, the reaction mixture
was quenched by the addition of water 20 ml. The
organic compounds are extracted with ethyl acetate
2
-(7-methyl-1H-indol-3-ylthio)-1H-benzo [d]
imidazole (compound 4)
0
8
3% yield; m.p. 183 C; Rf= 0.49 (Hexane:
(
3x20ml). The combined layers are dried over
1
Ethyl acetate, 70:30, v/v); H NMR(300 MHz, DMSO-
anh.Na SO . The required product is purified by
2
4
d6, 27°C) δ ppm 2.55 (3 H, s), 6.98−7.06 (4 H, m),
column chromatography, eluted with 8% methanol
in DCM to get the product. The product is confirmed
7
.22 - 7.29 (2 H, m), 7.40−7.43 (1 H, m), 7.90 (1 H,
1
d, J=2.7 Hz), 11.77 (1H, s), - 11.83 (1 H, s); H NMR
1
13
by H, C, NMR, IR and mass.
(
7
300 MHz, CDCl3, 27°C) δ ppm 2.56 (3 H, s),
.03 −7.19 (6 H, m), 7.47 - 7.52 (2 H, m), 8.38 (1 H,
2
-(1H-indol-3-ylthio)-1H-benzo[d]imidazole
1
3
bs); C NMR (500 MHz, DMSO-d ) δ ppm 97.5,
(
Compound 1):
6
°
115.5, 118.0, 118.0, 121.5, 121.9, 123.0, 123.9,
9
0% Yield; m.p. 221 C; R = 0.750
f
1
126.1, 127.7, 133.5, 154.0, 171.4; ESI-Mass: m/z
(
hexane:ethyl acetate, 60:40, v/v); H NMR (400
.+
MHz, DMSO-d , 25°C) δ ppm 8.32 - 8.43 (3 H, m),
280 [M +1 peak]; Mol. Formula: C H N S
16 13 3
6
8
.52 (1 H, t, J=7.44 Hz), 8.66 (2 H, br s), 8.79 (1 H,
2
-(7-methyl-1H-indol-3-ylthio)-6-methoxy-1H-
d, J=8.1 Hz), 8.83 - 8.86 (1 H, m), 9.21 (1 H, d, J=3.1
13
Hz), 13.13 (2 H, br s); C NMR (101 MHz, DMSO-
benzo[d]imidazole & 2-(7-methyl-1H-indol-3-
ylthio)-5-methoxy-1H-benzo[d]imidazole(compound
5 as tautomeric mixture of 5a and 5a’)
d ) δ ppm 95.6, 112.3, 118.1, 120.2, 121.2, 121.2,
6
-
1
1
22.1, 128.8, 133.0, 136.6, 150.9; IR: 3381 cm (N-
H); ESI-mass: m/z 266[M +1 peak]; Mol.
Formula:C H N S;
.
+
0
Yield 90% ; m.p. 183 C; Rf= 0.6 (hexane:
1
ethyl acetate, 70:30, v/v); H NMR (400 MHz, DMSO-
1
5
11
3
d6, 25°C) δ ppm 2.45 (6 H, s), 3.30(6 H, s), 3.66(6 H,
s), 3.77(6 H, s), 6.45(1 H, d, J=2 Hz), 6.57(1 H, d,
J=2 Hz), 6.57(1 H, d, J=2 Hz), 6.74-6.79 (2H,
m),6.83-6.87 (2H, m), 6.97-7.01 (5H, m), 7.16 (1H,
2
-(1H-indol-3-ylthio)-6-(difluoromethoxy)-1H-
benzo[d]imidazole & 2-(1H-indol-3-ylthio)-5-
difluoromethoxy)-1H-benzo[d]imidazole(Compound
(
2
13
as tautomeric mixture of 2a and 2a’):
d, J=8.8Hz), 7.42-7.47 (2H, m); C NMR (101 MHz,
0
0
Yield 88%; m.p. 209-211 C C; R = 0.77
DMSO-d ) δ ppm 16.7, 55.6, 55.6, 94.7, 94.7, 99.5,
f
6
1
(
hexane: ethyl acetate, 60:40, v/v); H NMR
99.7, 109.9, 110.2, 110.3, 110.9, 118.0, 118.1,

4
62
ARUMUGAM et al., Orient. J. Chem., Vol. 34(1), 457-466 (2018)
1
1
1
19.6, 120.8, 120.9, 122.5, 122.5, 124.9, 126.4, 2-(5-bromo-1H-indol-3-ylthio)-5-methoxy-1H-
26.4, 128.2, 128.4, 128.5, 131.6, 134.0, 134.1, benzo[d]imidazole & 2-(5-bromo-1H-indol-3-
-1
35.1, 156.1, 156.6, 170.1; IR: 3410 cm (N-H); ESI- ylthio)-6-methoxy-1H-benzo[d]imidazole
.
+
mass: m/z 310 [M +1 peak]; Mol. Formula: (compound 9 as tautomeric mixture of 9a and
C H N OS
9a’)
1
7
15
3
0
Yield 80% , m.p. 190 C, Rf Value 0.47 (in
1
2-(7-methyl-1H-indol-3-ylthio)-6-(difluoromethoxy)- 10% methanol in DCM), H NMR (400 MHz, DMSO-
1Hbenzo[d]imidazole & 2-(7-methyl-1H-indol-3- d6, 25°C) δ ppm 3.70(3H, s), 6.69(1H, dd, J= 8.8Hz,
ylthio)-5-(difluoromethoxy)-1H-benzo[d]imidazole J=2.4Hz), 6.86 (1H, bs), 7.23(1H, d, J=7.2 Hz),
(
compound 6 as tautomeric mixture of 6a and 6a’) 7.3(1H, dd, J=8.4, J=3.2 Hz), 7.47(1H, d, J=7.2 Hz),
0
Yield 89%, m.p. 110 C, R= 0.77 (hexane: 7.57 (1H, s), 7.91 (1H, d, J=2.8Hz), 11.82 (1H, s),
f
1
13
ethyl acetate, 60:40, v/v); H NMR (400 MHz, DMSO- 11.95(1H, s); C NMR (101 MHz, DMSO-d ) δ ppm
6
5
5.3, 95.2, 96.0, 106.0, 110.4, 112.9, 114.4, 120.2,
d6, 25°C) δ ppm 2.53 - 2.54 (4 H, m), 6.89 - 6.93 (2 H,
-
1
124.7, 130.7, 134.4, 135.3, 155.1; IR: 3389 cm (N-
m), 6.98 - 7.04 (3 H, m), 7.10 (2 H, s), 7.90 (1 H, d,
+
13
H); ESI mass: m/z 373[M. +1 peak]; Mol. Formula:
C H BrN OS
J=3.1 Hz), 11.67 - 12.07 (2 H, m) C NMR (101
1
6
12
3
MHz, DMSO-d ) δ ppm 16.5, 58.2, 95.5, 113.6, 114.3,
6
1
1
15.6, 116.8, 120.5, 121.6, 122.7, 128.5, 132.9,
methyl 3-(1H-benzo[d]imidazol-2-ylthio)-1H-
indole-4-carboxylate (compound 10)
-
1
36.1, 145.7, 152.7; IR: 3402 cm (N-H); ESI mass:
m/z 346 [M.++1 peak]; Mol. Formula: C H F N OS
17
13
2
3
0
Yield 76%, m.p. 240 C, Rf Value 0.54(in
1
1
0% methanol in DCM); H NMR (400 MHz, DMSO-
2
-(5-bromo-1H-indol-3-ylthio)-1H-benzo[d]
d6) δ ppm 1.07 - 1.27 (m, 1 H), 3.67-3.95 (m, 4 H),
.01 - 7.13 (m, 2 H), 7.23 - 7.34 (m, 1 H), 7.40 - 7.50
m, 1 H), 7.63 (d, J=8.6Hz, 1H), 7.84 (dd, J=8.6, 1.5
imidazole (compound 7)
7
0
Yield 84% , m.p. 268-270 C, Rf Value 0.86
(
1
(10% methanol in DCM); H NMR (400 MHz, DMSO-
Hz, 1H), 8.04 - 8.16 (m, 2H), 11.97 (s, 1H), 12.19 (br
d6, 25°C) δ ppm 7.06 -7.08 (2 H, m), 7.30 - 7.35 (3 H,
13
s, 1H); C NMR (101 MHz, DMSO-d ) δ ppm 51.7,
6
m), 7.47 – 7.49 (1 H, d , J=8.4), 7.57 (1H, d, J=1.6),
9
1
1
7.4, 110.5, 112.5, 117.4, 120.4, 121.1, 121.5,
13
7.93 (1H, d, J=2.8), 11.99 (2H, bs); C NMR (101
21.7, 123.1, 128.5, 135.2, 139.3, 143.9, 150.4,
MHz, DMSO-d ) δ ppm 95.2, 113.0, 113.7, 116.8,
6
-1
66.8; IR: 1688 cm (ester, C=O stretching), 1618
114.5, 120.2, 124.8, 130.7, 134.8, 135.4, 145.8; IR:
.
+
(
ester, C=O asym. Str.);ESI Mass: m/z 324 [M +1
-
1
. +
3
392cm (N-H); ESI-mass: m/z 344 [M +1 peak];
peak]; Mol. Formula: C H N O S
17
13
3
2
Mol. Formula: C H BrN S
15
10
3
methyl 3-(5-methoxy-1H-benzo[d]imidazol-2-
ylthio)-1H-indole-4-carboxylate & methyl 3-(6-
methoxy-1H-benzo[d]imidazol-2-ylthio)-1H-
indole-4-carboxylate (compound 11 as
2
-(5-bromo-1H-indol-3-ylthio)-5-(difluoromethoxy)-
H-benzo[d]imidazole & 2-(5-bromo-1H-indol-3-
1
ylthio)-6-(difluoromethoxy)-1H-benzo[d]
imidazole (compound 8 as tautomeric mixture of
tautomeric mixture of 11a and 11a’)
8a and 8a’)
0
7
6% Yield, m.p. 220 C, Rf Value 0.60(in
0
Yield 81% , m.p. 240 C, Rf =0.51 (in 10%
1
1
0% methanol in DCM); H NMR (400 MHz, DMSO-
1
methanol in DCM); H NMR (400 MHz, DMSO-d ) δ
6
d6, 25°C) δ ppm 1.15 - 1.35 (1 H, m), 3.29 (1 H, br s),
ppm 6.97(1 H, dt, J=5.8, 2.5 Hz), 7.16 (1 H, s), 7.22(1 3.36 (3 H, br s), 3.70 - 3.90 (7 H, m), 6.71 (1 H, d,
H, br s), 7.30 - 7.48(3 H, m), 7.55(1 H, d, J=8.6 Hz), J=8.8Hz), 6.87 (1 H, br s), 7.24 (1 H, br d, J=8.6 Hz),
7
-
.63(1 H, d, J=1.5Hz), 8.02(1 H, d, J=2.3Hz), 11.96 7.62 (1 H, d, J=8.6Hz), 7.84 (1 H, dd, J=8.6, 1.5Hz),
1
12.21(2 H, m); H NMR (400 MHz, CD OD) δ ppm 8.04 (1 H, d, J=2.3Hz), 8.16 (1H, s), 12.17 (1H, br s);
3
13
6.69(1H, t, 74.4 Hz), 6.91 (1H, d, J=8.8Hz), 6.93 (5H
C NMR (101 MHz, DMSO-d ) δ ppm 51.7, 55.3,
6
13
,
d , J= 8.8) C NMR (101 MHz, DMSO-d ) δ ppm 97.8, 110.4, 112.4, 120.4, 121.7, 123.0, 128.5,
6
-1
95.6, 112.9, 114.4, 120.2, 121.3, 124.7, 130.8, 134.6, 135.0, 139.3, 155.2, 166.8;IR:1685 cm (ester, C=O
-1
135.3, 150.38; IR: 3398 cm (N-H); ESI-mass: m/z 411 symm. str.), 1619 (ester, C=O asym. Str.) ESI mass:
+
. +
[M. +1 peak]; Mol. Formula: C H BrF N OS
m/z 354 [M +1 peak]; Mol. Formula: C H N O S
18 15 3 3
16
10
2
3

ARUMUGAM et al., Orient. J. Chem., Vol. 34(1), 457-466 (2018)
463
Table.3: Anti-bacterial activity (Cup-plate Method)
Conc
of test
Zone of inhibition in mm (mean ± SD)
Compound
sample
n=3
(
µg/mL)
S.A.
P.A.
B.S.
S. typhi
E. coli
2
3
1
4
8
7
9
5
6
800
18 ± 0.2
15 ± 0.1
11 ± 0.1
26 ± 0.2
24 ± 0.1
17 ± 0.1
26 ± 0.1
22 ± 0.2
18 ± 0.1
18 ± 0.3
13 ± 0.2
-
26 ± 0.2
24 ± 0.3
20 ± 0.1
22 ± 0.2
17 ± 0.3
11 ± 0.1
24 ± 0.2
22 ± 0.3
15 ± 0.1
13 ± 0.2
12 ± 0.3
-
24 ± 0.2
20 ± 0.2
19 ± 0.1
14 ± 0.2
13 ± 0.1
-
24 ± 0.1
18 ± 0.3
12 ± 0.2
24 ± 0.1
22 ± 0.3
16 ± 0.2
36 ± 0.2
20 ± 0.1
20 ± 0.3
19 ± 0.1
14 ± 0.1
12 ± 0.1
11 ± 0.2
22 ± 0.2
20 ± 0.1
18 ± 0.2
20± 0.1
18 ± 0.2
14± 0.1
23 ± 0.1
21 ± 0.3
20 ± 0.2
16 ± 0.1
15 ± 0.3
15 ± 0.2
26 ± 0.1
22 ± 0.3
18 ± 0.2
22 ± 0.1
20 ± 0.3
17 ± 0.2
23 ± 0.1
22 ± 0.3
20 ± 0.2
26 ± 0.1
18 ± 0.1
13 ± 0.2
26 ± 0.1
23 ± 0.1
19 ± 0.2
25 ± 0.1
20 ± 0.1
18 ± 0.2
36 ± 0.2
24 ± 0.1
20 ± 0.1
19 ± 0.1
18 ± 0.2
14 ± 0.1
-
18 ± 0.2
15 ± 0.1
14 ± 0.2
14 ± 0.1
13 ± 0.2
11 ± 0.1
27 ± 0.2
22 ± 0.2
18 ± 0.1
13 ± 0.2
11 ± 0.3
-
22 ± 0.3
19 ± 0.2
12 ± 0.2
12 ± 0.3
-
28 ± 0.1
26 ± 0.2
23 ± 0.1
20 ± 0.2
20 ± 0.1
17 ± 0.1
29 ± 0.1
27 ± 0.3
22 ± 0.1
28 ± 0.2
26 ± 0.1
22 ± 0.2
28 ± 0.2
22 ± 0.1
16 ± 0.1
16 ± 0.1
14 ± 0.3
13 ± 0.2
24 ± 0.3
22 ± 0.2
-
17 ± 0.1
13 ± 0.3
11 ± 0.2
28 ± 0.1
25 ± 0.1
18 ± 0.2
30 ± 0.1
29 ± 0.2
22 ± 0.2
28 ± 0.1
22 ± 0.3
19 ± 0.1
29 ± 0.1
24 ± 0.3
24 ± 0.1
31 ± 0.2
4
2
00
00
800
4
2
00
00
800
22 ± 0.2
20 ± 0.1
20 ± 0.2
22 ± 0.2
18 ± 0.1
15 ± 0.1
20 ± 0.1
20 ± 0.3
18 ± 0.2
20 ± 0.1
19 ± 0.3
13 ± 0.2
16 ± 0.1
15 ± 0.3
12 ± 0.2
26 ± 0.1
22 ± 0.1
18 ± 0.2
24 ± 0.1
18 ± 0.3
13 ± 0.2
28 ± 0.1
16 ± 0.1
11 ± 0.2
27 ± 0.2
23 ± 0.1
19 ± 0.2
23 ± 0.2
20 ± 0.1
17 ± 0.2
34 ± 0.1
4
2
00
00
800
4
2
00
00
800
4
2
00
00
800
4
2
00
00
-
800
20 ± 0.3
19 ± 0.2
19 ± 0.1
13 ± 0.3
11 ± 0.2
-
19 ± 0.1
15 ± 0.2
11 ± 0.2
19 ± 0.3
12 ± 0.1
-
24 ± 0.1
18 ± 0.1
13 ± 0.2
18 ± 0.1
16 ± 0.1
15 ± 0.2
32 ± 0.2
4
2
00
00
800
4
2
00
00
800
4
2
00
00
1
1
1
0
1
2
800
4
2
00
00
800
4
2
00
00
800
4
2
00
00
Standard
Amoxicillin)
1mg/ml
(
S.A.- Staphylococcus aureus; P.A. - pseudomonas aeruginosa;
B.S. - Bacillus subtilius; S.T. - Salmonella typhi; E Coli- Escherichia coli
Note: Bore size: 8 mm; Standard: Amoxcillin; Control: DMF (Dimethyl Formamide)

4
64
ARUMUGAM et al., Orient. J. Chem., Vol. 34(1), 457-466 (2018)
methyl3-(5-(difluoromethoxy)-1H- Anti-bacterial activity
benzo[d]imidazol-2-ylthio)-1H-indole-4-
The newly synthesized compounds 1 to
carboxylate & methyl 3-(6-(difluoromethoxy)-1H- 12 are screened for antibacterial activity against
benzo[d]imidazol-2-ylthio)-1H-indole-4-
carboxylate (compound 12 as tautomeric mixture
of 12a and 12a’)
gram-positive bacterium (B. subtilis and S. aureus)
and Gram-negative bacteria (P. aeruginosa, E. coli
and S. typhi). Dimethyl formamide is used as solvent
control. The bacterial culture was inoculated on
nutrient agar (Merck & Co.) (20 mL) and poured
into sterilized Petri dishes (99 mm). Media plates
were inoculated with liquid cultures homogeneously
by spread plate method. All the test compounds
were dissolved in dimethyl formamide(DMF) to get
0
Yield 72% , m.p. 205-207 C, Rf Value
1
0
.45(in 10% methanol in DCM); H NMR (400 MHz,
DMSO-d , 25°C) δ ppm 3.74 (1 H, s), 3.78 - 3.86 (3
6
H, m), 6.93 (1H, br d, J=6.2Hz), 7.11 (1H, s), 7.17
(
1H, br s), 7.24 - 7.44 (1H, m), 7.64 (1H, br d,
J=8.6Hz), 7.85 (1H, br d, J=7.8Hz), 8.04 - 8.11 (1H,
13
m), 8.11 - 8.17 (1 H, m), 11.99 - 12.27 (2 H, m);
C
NMR (101 MHz, DMSO-d ) δ ppm 51.5, 51.7, 97.0, different concentration of 100 µL and loaded into
6
1
1
1
12.5, 113.7, 120.3, 121.8, 123.1, 124.8, 128.5, the wells of agar plates directly. Plates inoculated
-
1
o
35.3, 139.3, 145.8, 166.8; IR: 3312 cm (N-H), with the bacteria were incubated at 37 C for
698 (ester, C=O symm. Str.), 1619 (ester, C=O
24 hours. All determinations were done in triplicates.
.
+
asymm. Str.); ESI mass: m/z 390 [M +1 peak]; Mol.
Formula: C H F N O S
Amoxicillin (1mg/mL) were used as standard drugs
for antibacterial.
18
13
2
3
3
2
-(7-methyl-1H-indol-3-ylthio)benzo[d]thiazole
The results for antibacterial activities
depicted in Table 3. It reveals most of the
compounds (1, 2, 4, 6, 8, 10, 11, and 12) showing
good anti-bacterial activity against E.coli.
Incorporation of the ester group in the fourth position
of the indole nucleus is favorable to anti-bacterial
activity. Whereas the incorporation of Bromo or
(Compound 13)
0
Yield 92% , m.p. 210 C, Rf Value 0.80
1
(
10% methanol in DCM) H NMR (300 MHz, DMSO-
d6, 27°C) δ ppm 2.54 (3 H, s), 7.03 (2 H, m), 7.22-
7
.28 (1H, m), 7.35-7.43 (2H, m), 7.8 (2H, d, J=
1
8.7Hz), 12.04 (1H, bs); H NMR (300 MHz, CD OD-
3
d6, 27°C) δ ppm 2.58 (3 H, s), 7.06 −7.11 (2 H, m),
7
.23-7.28 (1H, t, J=7.2Hz), 7.39-7.44 (2H, m), 7.65- Methyl group on the indole nucleus is unfavorable
13
7
.68 (1H,d, J=8.1Hz), 7.75 -7.78 (2H, m); C NMR to anti-bacterial activity.
(
500 MHz, DMSO-d , 27 °C) 16.5, 97.5, 115.5,
6
1
1
21.02, 121.0, 121.5, 121.9, 123.0, 123.9, 126.1,
CONCLUSION
-
1
27.7, 133.5, 154.0, 173.4; ; IR: 3418 cm (N-H);
.
+
ESI mass: m/z 297 [M +1 peak]; Mol. Formula:
C H N S
A simple, convenient and inventive
protocol for the sulfenylation of indoles using
1
6
12
2
2
Mn(OAc) reagent was developed. This method
3
2
(
-(7-methyl-1H-indol-3-ylthio)benzoic acid offers several advantages such as broad substrate
compound 14)
scope, high yields and regioselectivity. The
0
Yield 88% , m.p.143 C, Rf Value 0.61(10% experimental simplicity makes it a valuable and
1
methanol in DCM); H NMR (300 MHz, CD3OD, 27 elegant strategy for the synthesis of 3-sulfenyl
°
C) δ ppm 2.58 (3H, s), 7.73 −7.76 (1H, dd, J=0.9Hz, indoles.
J=6Hz), 6.92-6.98 (2H, m), 7.04 (1H,t, J=6.3), 7.10
(
1H, t, J=5.7), 7.98 (1H, d, J=5.7), 7.48 (1H, m), 7.96
ACKNOWLEDGMENTS
We are thankful to the Management of
Karpagam University to carry out my ours
(1H, dd, J=6, J=1.2), 11.09 (1H, bs) ESI mass: m/z
.
+
2
84[M +1 peak]; Mol. Formula: C H NO S
16 13 2
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