Facile preparation of indolyl-2/3-methylsulfoxides using HF/H 2O2

Article abstract of DOI:10.1080/00397910802517848

A variety of indolyl-2/3-methylsulfides tethered with sensitive functionalities were oxidized to the corresponding sulfoxides using a hitherto unexplored HF/H2O2 system. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910802517848

Synthetic Communications1, 39: 1215–1227, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910802517848
Facile Preparation of
Indolyl-2/3-methylsulfoxides Using HF/H2O2
Ganesan Gobi Rajeshwaran, Neelamegam Ramesh,
and Arasambattu K. Mohanakrishnan
Department of Organic Chemistry, University of Madras,
Guindy Campus, Chennai, India
Abstract: A variety of indolyl-2=3-methylsulfides tethered with sensitive function-
alities were oxidized to the corresponding sulfoxides using a hitherto unexplored
HF=H2O2 system.
Keywords: HF=H2O2, indolyl-2=3-methylsulfide, indolyl-2=3-methylsulfoxide
INTRODUCTION
In general, the preparation of sulfoxides could be easily achieved via the
oxidation of the corresponding sulfide using oxidizing agents.[1] However,
careful quantitative control of the oxidizing reagent is most essential to
prevent the overoxidation of the sulfoxide to the corresponding sulfone.
During the past 25 years, arylmethylsulfoxides and arylmethylsulfones
tethered with functional groups have been exploited as bidentate syn-
thons for the synthesis of naturally occurring aromatic=heteroaromatic
polycycles.[2] The sulfide=sulfoxide=sulfones units attached to the indole
skeleton have been explored as reverse transcriptase[3] as well as tubulin
polymerase[4] inhibitors. Recently, several methods have been developed
for the oxidation of sulfides using H2O2=heteropolyacids,[5] H2O2=
ZrCl2 and H2O2=MoO2Cl2.[7] Very recently, KF=m-3-chloroperbenzoic
[6]
Received June 27, 2008.
Address correspondence to Arasambattu K. Mohanakrishnan, Department of
Organic Chemistry, University of Madras, Guindy Campus, Chennai 600 025,
India. E-mail: mohan_67@hotmail.com
1215

1216
G. G. Rajeshwaran, N. Ramesh, and A. K. Mohanakrishnan
acid (CPBA) has been employed for the preparation of indlolylmethyl sulf-
oxides[8] as well as glycosyl sulfoxides.[9] However, the oxidation of sulfide
with HOF ꢀ CH3CN led to the formation of corresponding sulfones.[10]
RESULTS AND DISCUSSION
In continuation of our work on the synthesis of carbazole alkaloids,[11]
we required different types of indolyl-2=3-methylsulfoxide containing
functional groups such as ester, ketone, and cyanide for annelation
studies.[12] The synthetic utility as well as biological potency of indolyl-
methylsulfoxides prompted us to develop a simple and economically
viable route for the smooth oxidation of indolyl-2=3-methylsulfides into
the corresponding sulfoxides. Accordingly, the oxidation of the sulfide 1a
was planned using 50% H2O2 as an oxidizing agent. Because KF=
m-CPBA has efficiently transformed indolylmethylsulfide into the corre-
sponding sulfoxide,[8] initially the oxidation of the sulfide 1a was
performed using 6 equivalents of KF=H2O2 (1:1) in acetonitrile at room
temperature for 12 h. Contrary to our expectation, the workup of the
reaction led to the isolation of sulfone 3 and sulfoxide 2a in 85% and
10% yields, respectively (Scheme 1).
Using the similar conditions, when the oxidation of sulfide 1a was
performed at room temperature using 6 equivalents HF=H2O2 (1:1) for
1 h, the required sulfoxide 2a could be isolated in the major portion along
with minor amount of sulfone 3 (15% yield). It should be noted that the
oxidation of sulfide 1a using 6 equivalents of H2O2 in the absence of HF
led to the isolation of sulfone 3 as an exclusive product. Encouraged by
this result, we carried out the oxidation of sulfide 1a using varying pro-
portions of 50% H2O2 and 40% aq. HF. Finally, using H2O2 and aq.
HF in the ratio of 4:6 led to the formation of sulfoxide 2a. Thus, the
interaction of 40% aq. HF and 50% H2O2 (4:6) in acetonitrile at room
temperature for 30 min followed by addition of the sulfide 1a led to the
isolation of sulfoxide 2a in 90% yield, (Scheme 2).
Scheme 1. Oxidation of sulfide 1a using KF=H2O2.

Indolyl-2/3-methylsulfoxides
1217
Scheme 2. Preparation of sulfoxide 2a using HF=H2O2.
Further oxidation of the sulfoxide 2a to the corresponding sulfone 3
was not observed under this condition. The applicability of the HF=H2O2
(6:4) system for the sulfoxidation of variety of indolyl-2=3-methylsulfides
was then examined in acetonitrile at room temperature. A ratio of 1:4:6
sulfide=H2O2=HF was found to be the optimum for the smooth transfor-
mation of the sulfides 1a–o into the corresponding sulfoxides 2a–o. The
structures of different types of sulfoxides 2a–o prepared using HF=H2O2
along with their respective yields are presented in Table 1. In all these
cases, the sulfoxides are isolated in good yields (80–92%) without any
trace of sulfones. The indolyl-2-methylsulfoxides 2a–g could be regarded
as bidentate synthons (entries 1–4), and they may be utilized as crucial
intermediates for the synthesis of carbazole derivatives via base-mediated
Michael addition followed by intramolecular cyclization.[12] The isomeric
indolyl-3-methylsulfoxides 2 h and 2i could also be prepared in excellent
yields (entry 5). The HF=H2O2 methodology was also applied to the
synthesis bis- as well as tris-sulfoxides 2l–o (entries 8–10).
In conclusion, we have synthesized several indolylmethylsulfoxides
via sulfoxidation using a combination of 40% aq. HF and 50% H2O2
in acetonitrile with excellent selectivity. The methodology reported herein
is simple, clean, and economically viable for the sulfoxidation of aryl-
methyl as well as hetero-arylmethylsulfides.
EXPERIMENTAL
All melting points were uncorrected. Reagents were purchased from
commercial sources and used as received without purification. Solvents
were dried by standard procedures. Column chromatography was carried
out on silica gel (grade 60, mesh size 230–400, Merck). Infrared (IR) spec-
tra were recorded on a Shimadzu Fourier transform infrared (FT-IR)
8300 instrument. 1H and 13C NMR spectra were recorded in CDCl3 using
tetramethylsilane (TMS) as an internal standard on Jeol GSX 400 and
Bruker-300 spectrometers. Chemical shift values were quoted in parts

1218
G. G. Rajeshwaran, N. Ramesh, and A. K. Mohanakrishnan
Table 1. Preparation of indolylmethylsulfoxides using HF–H2O2
Entry
1
Sulfide
Sulfoxide
Yield (%)a
90
2
89
82
81
3
80
85
4
5
80
85
90
6
85
(Continued )

Indolyl-2/3-methylsulfoxides
1219
Table 1. Continued
Entry
7
Sulfide
Sulfoxide
Yield (%)a
90
8
85
80
9
85
80
10
aIsolated yield after column chromatography.
per million (ppm) and coupling constants were quoted in hertz (Hz).
Chemical shift multiplicities were reported as s ¼ singlet, d ¼ doublet,
t ¼ triplet, q ¼ quartet, m ¼ multiplet, and br ¼ broad. Mass spectra were
recorded on a Jeol DX 303 HF spectrometer. Elemental analysis were
carried out on Vario EL III (CDRI, Lucknow) equipment. The required
sulfides 1a–o were prepared from the corresponding bromomethyl com-
pounds using NaH=HSPh condition in dry tetrahydrofuran (THF).

1220
G. G. Rajeshwaran, N. Ramesh, and A. K. Mohanakrishnan
Representative Procedure for the Preparation of 1-Phenylsulfonyl-2-
phenylsulfinylmethyl-3-acetylindole (2a)
To a solution of 50% H2O2 (0.32 mL, 4.73 mmol) in acetonitrile (5 mL), 40%
aq. HF (0.35 mL, 7.11 mmol) was added and stirred for 30 min at room tem-
perature. To the reaction mixture, a solution of sulfide 2a (0.5 g, 1.18 mmol)
in acetonitrile (5 mL) was added, and stirring was continued for another 2h.
After the sulfide 1a was consumed (monitored by thin-layer chromatogra-
phy, TLC), the reaction mixture was quenched with ice water (15 mL),
extracted with ethyl acetate (2ꢁ 10 mL), and dried (Na2SO4). Removal of
solvent followed by column chromatographic purification (hexane–EA;
7:3) afforded 2a as a colorless solid (0.47g, 90%). Mp: 130–131ꢂC. IR
1
(KBr): 1080 (SO), 1182 (SO2), 1370 (SO2), 1676 (CO) cmꢃ1. H NMR
(CDCl3, 300MHz): d 2.63 (s, 3H, –CH3), 5.03 (d, J ¼ 13.2Hz, 1H, –CH),
5.27 (d, J ¼ 12.9 Hz, 1H, –CH), 7.32–7.42 (m, 2H, Ar-H), 7.44–7.58 (m,
6H, Ar-H), 7.66–7.69 (m, 2H, Ar-H), 7.78–7.81 (m, 1H, Ar-H), 7.86 (d,
J¼ 7.5 Hz, 2H, Ar-H), 8.09–8.12 (m, 1H, Ar-H). 13C NMR (CDCl3, 75
MHz): d 32.21, 55.17, 115.0, 121.08, 124.31, 124.82, 125.86, 126.66,
126.79, 127.01, 129.20, 129.56, 131.41, 134.01, 134.54, 136.30, 138.10,
143.64, 196.40. Anal. calcd. for C23H19NO4S2: C, 63.14; H, 4.38; N, 3.20;
S, 14.66%. Found: C, 63.30; H, 4.09; N, 3.46; S, 14.49%.
Preparation of 1-Phenylsulfonyl-3-cyano-2-phenylsulfinyl
methylindole (2b)
The procedure was similar to that of 2a. Yield: 0.15 g (89%). Mp: 140–
142 ꢂC. IR (KBr): 1083 (SO), 1181 (SO2), 1380 (SO2), 2221 (CN) cmꢃ1
.
1H NMR (500 MHz, CDCl3): d 4.71 (s, 2H), 7.26 (d, J ¼ 7.9 Hz, 1H,
Ar-H), 7.47–7.54 (m, 8H, Ar-H), 7.65 (d, J ¼ 8.4 Hz, 2H, Ar-H), 7.88
(d, J ¼ 8.0 Hz, 2H, Ar # H), 8.07 (d, J ¼ 8.0 Hz, 1H, Ar-H). 13C NMR
(125 MHz, CDCl3): d 57.83, 99.44, 112.83, 114.86, 120.00, 124.21,
125.42, 126.87, 127.20, 129.54, 129.85, 132.02, 135.11, 135.75, 137.52,
137.72, 143.09. Mass (m=z) %: 405 (M # 16, 9%), 231 (35), 154 (39),
141 (28). Anal. calcd. for C22H16N2O3S2: C, 62.84; H, 3.84; N 6.66, S,
15.25%. Found: C, 62.83: H, 3.98; N, 6.51; S, 15.17%.
Preparation of 1-Phenylsulfonyl-2-phenylsulfinylmethyl-3-
bromoindole (2c)
The procedure was similar to that of 2a. Yield: 0.15 g (82%). Mp: 140–
142 ꢂC. IR (KBr): 1080 (SO), 1185 (SO2), 1378 (SO2) cmꢃ1 1H NMR
.

Indolyl-2/3-methylsulfoxides
1221
(CDCl3, 300 MHz): d 4.59 (d, J ¼ 12.7 Hz, 1H, –CH), 4.76 (d,
J ¼ 12.7 Hz, 1H, –CH), 7.30–7.56 (m, 9H, Ar-H), 7.62 (d, J ¼ 6.8 Hz,
2H, Ar-H), 7.78 (d, J ¼ 7.3 Hz, 2H, Ar-H), 8.12 (d, J ¼ 8.2 Hz, 1H,
Ar-H). 13C NMR (CDCl3, 75 MHz): 57.33, 114.9, 115.49, 120.38,
124.27, 124.76, 126.59, 126.65, 126.78, 126.96, 128.93, 129.17, 129.27,
129.48, 131.44, 134.08, 134.34. Anal. calcd. for C21H16NO3S2Br: C,
53.17; H, 3.40; N, 2.95; S, 13.52%. Found: C, 53.40; H, 3.27; N,
3.21; S, 13.38%.
Preparation of 1-Phenylsulfonyl-3-methyl-2-phenylsulfinyl
methylindole (2d)
The procedure was similar to that of 2a. Yield: 0.58 g (81%). Mp:
141–142 ꢂC. IR (KBr): 1083 (SO), 1172 (SO2), 1387 (SO2) cmꢃ1
.
1H NMR (CDCl3, 300 MHz): d 1.94 (s, 3H, –CH3), 4.48 (d,
J ¼ 13.2 Hz, 1H, –CH), 4.56 (d, J ¼ 13.2 Hz, 1H, –CH), 7.25–7.29
(m, 2H, Ar-H), 7.33–7.40 (m, 4H, Ar-H), 7.45–7.53 (m, 3H, Ar-
H), 7.62–7.64 (m, 2H, Ar-H), 7.72–7.75 (m, 2H, Ar-H), 8.13 (d,
J ¼ 8.0 Hz, 1H, Ar-H).13C NMR (CDCl3, 75 MHz): d 9.04, 57.39,
114.98, 119.48, 123.97, 124.10, 125.63, 125.75, 126.37, 129.11,
129.28, 130.71, 131.20, 133.89, 136.68, 138.38, 143.86. Mass (m=z)
%: 393 (Mþꢃ16, 65), 378 (34). Anal. calcd. for C22H19NO3S2: C,
64.52; H, 4.68; N, 3.42; S, 15.66%. Found: C, 64.68; H, 4.42; N,
3.27; S, 15.49%.
Preparation of Ethyl-1-phenylsulfonyl-2-phenylsulfinylmethylindole-3-
carboxylate (2e)
The procedure was similar to that of 2a. Yield: 0.12 g (80%). Mp: 110–
112 ꢂC. IR (KBr): 1074 (SO), 1180 (SO2), 1368 (SO2), 1728 (CO) cmꢃ1
.
1H NMR (CDCl3, 400 MHz): d 1.40 (t, J ¼ 7.3 Hz, 3H, –CH3), 4.30 (q,
J ¼ 7.2 Hz, 2H, –CH2), 5.13 (d, J ¼ 12.7 Hz, 1H, –CH), 5.43 (d,
J ¼ 12.2 Hz, 1H, –CH), 7.30–7.36 (m, 2H, Ar-H), 7.38–7.48 (m, 2H,
Ar-H), 7.50–7.58 (m, 4H, Ar-H), 7.62 (d, J ¼ 7.8 Hz, 2H, Ar-H),
7.86 (d, J ¼ 8.3 Hz, 2H, Ar-H), 8.07 (d, J ¼ 6.8 Hz, 2H, Ar-H). 13C
NMR (CDCl3, 100 MHz): d 14.22, 55.26, 60.89, 114.55 (2C), 114.60,
122.43, 122.47, 124.29, 124.79, 125.97, 126.76, 128.96, 129.48,
131.27, 134.45, 136.15, 136.20, 138.14, 143.66, 163.99. Mass (m=z)
%: 451 (Mþ, 24), 311 (24). Anal. calcd. for C24H21NO5S2: C, 61.65;
H, 4.53; N, 3.00; S, 13.72%. Found: C, 61.49; H, 4.39; N, 3.24; S,
13.91%.

1222
G. G. Rajeshwaran, N. Ramesh, and A. K. Mohanakrishnan
Preparation of Ethyl-1-phenysulfonyl-5-methoxy-2-
phenylsulfinylmethylindole-3-carboxylate (2f)
The procedure was similar to that of 2a. Yield: 0.3 g (85%). Mp: 93–
94 ꢂC. IR (KBr): 1079 (SO), 1181 (SO2), 1362 (SO2), 1702 (CO) cmꢃ1
.
1H NMR (CDCl3, 300 MHz): d 1.39 (t, J ¼ 7.2 Hz, 3H, –CH3), 3.83 (s,
3H, –CH3), 4.29 (q, J ¼ 7.2 Hz, 2H, –CH2), 5.11 (d, J ¼ 12.3 Hz, 1H, –
CH), 5.39 (d, J ¼ 12.3 Hz, 1H, –CH), 6.97 (dd, J ¼ 2.7 & 9.3 Hz, 1H,
Ar-H), 7.40–7.61 (m, 9H, Ar-H), 7.81 (d, J ¼ 7.2 Hz, 2H, Ar-H), 7.99
(d, J ¼ 9.3 Hz, 1H, Ar-H). 13C NMR (CDCl3, 75 MHz): d 14.21, 55.39,
55.52, 60.87, 104.45, 115.31, 115.49, 124.30, 126.43, 126.64, 128.32,
128.97, 129.13, 130.80, 131.30, 134.43, 136.33, 138.13, 143.62, 157.30,
163.98. Anal. calcd. for C25H23NO6S2: C, 60.35; H, 4.66; N, 2.81%.
Found: C, 60.13; H, 4.65; N, 2.60%.
Preparation of Ethyl-3-[2-(phenylthiomethyl)-1-(phenylsulfonyl)-indol-3-
yl]acrylate (2g)
The procedure was similar to that of 2a. Yield: 0.25 g (80%). Mp: 118 ꢂC.
IR (KBr): 1040 (SO), 1162 (SO2), 1360 (SO2), 1690 (CO) cmꢃ1. 1H NMR
(CDCl3, 300 MHz): d 1.27 (t, J ¼ 7.1 Hz, 3H, –CH3), 4.19 (q, J ¼ 7.2 Hz,
2H, –CH2), 4.54 (d, J ¼ 13.2 Hz, 1H, –CH), 4.70 (d, J ¼ 13.2 Hz, 1H,
–CH), 6.36 (d, J ¼ 15.9 Hz, 1H, –CH), 7.19–7.27 (m, 2H, Ar-H),
7.29–7.33 (m, 6H, Ar-H), 7.34–7.41 (m, 3H, Ar-H), 7.46-7.49 (m, 3H,
Ar-H), 7.70 (d, J ¼ 7.8 Hz, 1H, Ar-H). 13C NMR (CDCl3, 75 MHz): d
14.43, 54.04, 60.15, 111.94, 113.38, 115.30, 120.63, 121.72, 124.10,
125.06, 128.07, 128.28, 129.38, 134.32, 134.58, 136.56, 136.85, 167.50.
Mass (m=z) %: 477 (Mþꢃ16, 46%), 336 (27).
Preparation of Ethyl-1-phenylsulfonyl-3-phenylsulfinylmethylindole-2-
carboxylate (2h)
The procedure was similar to that of 2a. Yield: 0.15 g (85%). Mp: 118–
120 ꢂC. IR (KBr): 1082 (SO), 1190 (SO2), 1370 (SO2), 1720 (CO) cmꢃ1
.
1H-NMR (CDCl3, 300 MHz): d 1.28 (t, J ¼ 7.2 Hz, 3H, –CH3), 4.01–
4.37 (m, 4H, –CH2), 7.04–7.32 (m, 8H, Ar-H), 7.38 (t, J ¼ 7.8 Hz, 2H,
Ar-H), 7.49 (d, J ¼ 7.4 Hz, 1H, Ar-H), 7.84 (d, J ¼ 7.5 Hz, 2H, Ar-H),
7.94 (d, J ¼ 8.3 Hz, 1H, Ar-H). 13C NMR (CDCl3, 75 MHz): d 13.95,
53.64, 62.41, 115.29, 115.42, 117.94, 120.72, 124.10, 124.35, 127.16,
127.35, 128.86, 129.02, 130.82, 131.40, 134.00, 136.75, 137.88, 142.83,
161.11. Anal. calcd. for C24H21NO5S2: C, 61.65; H, 4.53; N, 3.00; S,
13.72%. Found: C, 61.39; H, 4.79; N, 3.25; S, 13.58%.

Indolyl-2/3-methylsulfoxides
1223
Preparation of Ethyl-5-methoxy-1-phenylsulfonyl-3-
phenylsulfinylmethylindole-2-carboxylate (2i)
The procedure was similar to that of 2a. Yield: 0.27 g (90%). Mp: 92–
93 ꢂC. IR (KBr): 1078 (SO), 1187 (SO2), 1373 (SO2), 1720 (CO) cmꢃ1
.
1H NMR (CDCl3, 300 MHz): d 1.37 (t, J ¼ 7.1 Hz, 3H, –CH3), 3.69 (s,
3H, –CH3), 4.23–4.42 (m, 4H, –CH2), 6.52 (d, J ¼ 2.4 Hz, 1H, –CH),
6.97 (dd, J ¼ 2.4 & 6.9 Hz, 1H, –CH), 7.24–7.40 (m, 5H, Ar-H), 7.45
(d, J ¼ 7.2 Hz, 2H, Ar-H), 7.56 (d, J ¼ 7.5 Hz, 1H, Ar-H), 7.83–7.91 (m,
3H, Ar-H). 13C NMR (CDCl3, 75 MHz): d 13.96, 53.72, 55.55, 62.39,
102.11, 116.43, 117.12, 118.20, 124.17, 127.12, 128.97, 130.02, 131.29,
131.37, 131.49, 133.95, 137.53, 143.00, 157.03, 161.10. Anal. calcd. for
C25H23NO6S2: C, 60.35; H, 4.66; N, 2.81; S, 12.89%. Found: C, 60.10;
H, 4.89; N, 3.04; S, 12.66%.
Preparation of 1-Phenylsulfonyl-4-phenylsulfinylmethylindole (2j)
The procedure was similar to that of 2a. Yield: 0.13 g (85%). Mp: 131–
1
132 ꢂC. IR (KBr): 1073 (SO), 1180 (SO2), 1376 (SO2) cmꢃ1. H NMR
(CDCl3, 300 MHz): d 4.14 (d, J ¼ 12.2 Hz, 1H, –CH), 4.34 (d,
J ¼ 12.7 Hz, 1H, –CH), 6.37 (d, J ¼ 3.9 Hz, 1H, Ar-H), 6.90 (d,
J ¼ 7.3 Hz, 1H, Ar-H), 7.15–7.33 (m, 7H, Ar-H), 7.45–7.59 (m, 3H, Ar-
H), 7.86 (d, J ¼ 7.3 Hz, 2H, Ar-H), 7.95 (d, J ¼ 8.3 Hz, 1H, Ar-H). 13C
NMR (CDCl3, 75 MHz): d 61.25, 106.88, 113.56, 122.12, 124.18,
124.61, 125.78, 126.54, 126.80, 128.73, 129.31, 131.11, 131.18, 134.00,
134.66, 138.07, 142.71. Anal. calcd. for C21H17NO3S2: C, 63.77; H,
4.33; N, 3.54; S, 16.22%. Found: C, 63.94; H, 4.51; N, 3.31; S, 16.03%.
Preparation of 1-Phenylsulfonyl-2-methyl-3-(phenylsulfinyl)indole (2k)
The procedure was similar to that of 2a. Yield: 0.15 g (90%). Mp: 136–
1
138oC. IR (KBr): 1373 (SO2), 1183 (SO2), 1093 (SO) cmꢃ1. H NMR
(CDCl3, 300 MHz): d ¼ 2.93 (s, 3H, –CH3), 7.10 (t, J ¼ 7.5 Hz, 1H, Ar-
H), 7.26 (t, 1H, J ¼ 8.4 Hz, Ar-H), 7.41–7.51 (m, 6H, Ar-H), 7.54–7.61
(m, 3H, Ar-H), 7.84 (d, J ¼ 7.5 Hz, 2H, Ar-H), 8.18 (d, 1H, J ¼ 8.4 Hz,
Ar-H). 13C NMR (CDCl3, 75 MHz): d 13.76, 114.49, 120.02, 121.78,
124.3, 124.45, 124.89, 125.32, 126.52, 129.12, 129.67, 130.29, 134.48,
136.52, 138.63, 141.18, 143.26. MS: m=z, 395 (Mþ, 100), 379 (10). Anal.
calcd. for C21H17NO3S2: C, 63.77; H, 4.33; N, 3.54%. Found: C, 63.92; H,
4.54; N, 3.36%.

1224
G. G. Rajeshwaran, N. Ramesh, and A. K. Mohanakrishnan
Preparation of 1-Phenylsulfonyl-2,3-bis((phenylsulfinyl)methyl)indole (2l)
To a solution of H2O2 50% (0.54 mL, 7.99 mmol) in acetonitrile (10 mL),
40% aq. HF (0.6 mL, 11.97 mmol) was added and stirred for 30 min at
room temperature. To the reaction mixture, a solution of sulfide 1 l
(0.5 g, 0.99 mmol) in acetonitrile (10 mL) was added, and stirring was
continued for another 2 h. After the sulfide 1 l was consumed (monitored
by TLC), the reaction mixture was quenched with ice water (20 mL),
extracted with ethyl acetate (2 ꢁ 15 mL), and dried (Na2SO4). Removal
of solvent followed by column chromatographic purification (hexane–
EA; 3:2) afforded sulfoxide 2 l as a colorless solid. (0.45 g, 85%). Yield:
0.14 g (85%). Mp: 166–168 ꢂC. IR (KBr): 1369 (SO2), 1180 (SO2), 1080
1
(SO) cmꢃ1. H NMR (CDCl3, 300 MHz): d 3.88 (d, 1H, J ¼ 14.1 Hz,
–CH), 4.40–4.49 (m, 1H, –CH), 4.69 (d, J ¼ 14.1 Hz, 2H, –CH), 6.58
(d, J ¼ 7.8 Hz, 1H, Ar-H), 6.90–6.96 (m, 3H, Ar-H), 7.04–7.31 (m, 4H,
Ar-H), 7.45–7.61 (m, 6H, Ar-H), 7.72–7.82 (m, 4H, Ar-H), 8.05 (d,
J ¼ 8.4 Hz, 1H, Ar-H). 13C NMR (CDCl3, 75 MHz): d 51.08, 52.46,
56.49, 57.64, 114.89, 115.19, 118.57, 123.95, 123.99, 125.54, 126.63,
126.67, 128.55, 128.91, 129.18, 129.30, 129.36, 129.43, 129.78, 131.07,
131.26, 131.34, 134.14, 136.08, 137.93, 142.01, 143.00. (1H and 13C
NMR signals are more due to diastereomeric mixture.) Mass (m=z) %:
533 (Mþ, 100), 408 (90), 305 (20). Anal. calcd. for C28H23NO4S3: C,
63.02; H, 4.34; N, 2.62%. Found: C, 63.28; H, 4.52; N, 2.31%.
Preparation of 2,3-Bis((phenylsulfinyl)methyl)benzo[b]thiophene (2m)
The procedure was similar to that of 2a. Yield: 0.15g (80%). Mp: 160–
1
162 ꢂC. IR (KBr): 1082 (SO) cmꢃ1. H NMR (CDCl3, 300 MHz): d 3.93,
(dd, J ¼ 13.8Hz and 3.6 Hz, 1H, Ar-H), 3.99–4.13 (m, 2H, Ar-H), 4.18
(dd, J ¼ 14.1 Hz & 3.6 Hz, 1H, Ar-H), 7.27–7.36 (m, 7H, Ar-H), 7.39–
7.47 (m, 6H, Ar-H), 7.29–7.75 (m, 1H, Ar-H). 13C NMR (CDCl3,
75MHz): d 54.35, 54.74, 56.42, 56.66, 121.75, 122.21, 124.13, 124.48,
124.6, 124.83, 125.01, 125.16, 129.02, 129.17, 131.51, 132.30, 138.64,
138.95, 142.66, 142.84, 143.04. (1H and 13C NMR signals are more due
to diastereomeric mixture.) Mass (m=z) %: 410 (Mþ, 40), 284 (50), 272 (40).
Preparation of 1-Phenylsulfonyl-3,4-dibromo-2,5-
bis((phenylsulfinyl)methyl)pyrrole (2n)
The procedure was similar to that of 2a. Yield: 0.15 g (85%). Brown
1
liquid. IR (KBr): 1382 (SO2), 1175 (SO2), 1085 (SO) cmꢃ1. H NMR

Indolyl-2/3-methylsulfoxides
1225
(CDCl3, 300 MHz): d 4.10–4.58 (m, 4H, –CH2), 7.21–7.34 (m, 3H, Ar-H)
7.47–7.83 (m, 12H, Ar-H). 13C NMR (CDCl3, 75 MHz): d 57.03, 57.51,
60.41, 124.52, 124.34, 125.74, 126.32, 126.4, 127.18, 127.56, 129.06,
129.39, 130.21, 130.24, 131.74, 142.83. (1H and 13C NMR signals are
more due to diastereomeric mixture.) Anal. calcd. for C24H19Br2NO4S3:
C, 44.94; H, 2.99; N, 2.18%. Found: C, 44.70; H, 2.78; N, 2.42%.
Preparation of 1,3,5-Trimethyl-2,4,6-tris((phenylsulfinyl)methyl)benzene (2o)
To a solution of 50% H2O2 (0.35mL, 4.93 mmol) in acetonitrile (5 mL),
40% aq. HF (0.37 mL, 7.4 mmol) was added and stirred for 30min at room
temperature. To the reaction mixture, a solution of sulfide (0.2 g, 0.4 mmol)
in acetonitrile (5 mL) was added, and stirring was continued for another 2 h.
After the sulfide compound (2o) was consumed (monitored by TLC), the
reaction mixture was quenched with ice water (15 mL), extracted with ethyl
acetate (2 ꢀ 10mL), and dried (Na2SO4). Removal of solvent, followed by
column chromatographic purification (hexane–EA; 1:1) afforded (2o) as a
colorless solid. Yield: 0.25g (80%). Mp: 190 ꢁC. IR (KBr): 1082 (SO)
1
cmꢂ1. H NMR (CDCl3, 300 MHz): d 1.74–2.16 (m, 9H, –CH3), 3.99–
4.13 (m, 3H, –CH2), 4.34–4.45 (m, 3H, –CH2), 7.48–7.52 (m, 15H, Ar-H),
13C NMR (CDCl3, 75MHz): 17.62, 17.81, 59.53, 59.65, 123.96, 124.55,
126.86, 126.99, 129.22, 131.33, 131.39, 131.47, 139.15, 139.32, 143.36,
143.51. (1H and 13C NMR signals are more due to diastereomeric mixture.)
Mass (m=z) %: 534 (Mþ, 60%), 408 (20), 282 (10).
1-Phenylsulfonyl(2-((phenylsulfonyl)methyl)-indol-3-yl)ethanone (3)
Colorless solid. Yield: 0.07 g (10%). Mp: 190 ꢁC. IR (KBr): 1385 (SO2),
1
1173 (SO2) cmꢂ1. H NMR (CDCl3, 300 MHz): 2.62 (s, 3H, –CH3),
5.70 (s, 2H, –CH2), 7.34–7.37 (m, 2H, Ar-H), 7.39–7.45 (m, 2H, Ar-H),
7.50–7.55 (m, 3H, Ar-H), 7.64–7.69 (m, 1H, Ar-H), 7.75–7.76 (m, 1H,
Ar-H), 7.80–7.84 (m, 4H, Ar-H), 7.98–8.02 (m, 1H, Ar-H). 13C NMR
(CDCl3, 75 MHz): 31.80, 52.42, 115.28, 120.95, 124.77, 125.99, 126.43,
126.85, 128.70, 129.12, 129.41, 130.51, 133.95, 134.42, 136.52, 138.04,
138.93, 196.57.
ACKNOWLEDGMENTS
We thank Council of Scientific and Industrial Research (CSIR), New
Delhi (01-(2071)/06/EMR-II)) for the financial support. Authors thank

1226
G. G. Rajeshwaran, N. Ramesh, and A. K. Mohanakrishnan
Department of Science and Technology-Fund for Improvement of
Science and Technology (DST-FIST) for 300 MHz NMR facility.
REFERENCES
1. (a) Sato, K.; Hyodo, M.; Aoki, M.; Zheng, X.-Q.; Noyorip, R. Oxidation of
sulfides to sulfoxides and sulfones with 30% hydrogen peroxide under organic
solvent- and halogen-free conditions. Tetrahedron 2001, 57, 2469–2476; (b)
ꢀ
´
Fraile, J. M.; Garcıa, J. I.; Lazaro, B.; Mayoral, J. A. A mild, efficient,
and selective oxidation of sulfides to sulfoxides. Chem. Commun. 1998,
1807–1808; (c) Greenhalgh, R. P. Selective oxidation of phenyl sulphides to
sulphoxides or sulphones using oxone and wet alumina. Synlett 1992, 235–
236; (d) Shukla, V. G.; Salgaonkar, P. D.; Akamanchi, K. G. A mild, chemo-
selective oxidation of sulfides to sulfoxides using o-iodoxybenzoic acid and
tetraethylammonium bromide as a catalyst. J. Org. Chem. 2003, 68, 5422–
5425; (e) Hajipour, A. R.; Ruoho, A. E. Benzyltriphenylphosphoniumchlor-
ochromate (BTPPCC): An efficient and novel reagent for oxidation of sulfide
to the corresponding sulfoxides under non-aqueous conditions. Sulfur Lett.
2003, 26, 83–87; (f) Kowalski, P.; Mitka, K.; Ossowska, K.; Kolarska, Z. Oxi-
dation of sulfides to sulfoxides. Part 1: Oxidation using halogen derivatives.
Tetrahedron 2005, 61, 1933–1953.
2. (a) Hauser, F. M.; Chakrapani, S.; Ellenberger, W. P. Total synthesis of
(ꢄ)-7-con-O-methylnogarol. J. Org. Chem. 1991, 56, 5248–5250; (b) Hauser,
F. M.; Gauuan, P. J. F. Total synthesis of (ꢄ)-biphyscion. Org. Lett. 1999, 1,
671–672; (c) Hauser, F. M.; Yin, H. A new route to benzo[4,5]cyclohepta[1,2-
b]naphthalenes: Synthesis of radermachol. Org. Lett. 2000, 2, 1045–1047; (d)
Hauser, F. M.; Dorsch, W. A.; Mal, D. Total synthesis of (ꢄ)-O-methyl PD
116740. Org. Lett. 2002, 4, 2237–2239; (e) Hauser, F. M.; Liao, H.; Sun, Y.
Regiospecific synthesis of
a benanomicinone=pradimicinone analogue.
Org. Lett. 2002, 4, 2241–2243; (f) Hauser, F. M.; Dorsch, W. A. A new
regiospecific preparation of xanthones. Org. Lett. 2003, 5, 3753–3754.
3. (a) Williams, T. M.; Ciccarone, T. M.; MacTough, S. C.; Rooney, C. S.;
Balani, S. K.; Condra, J. H.; Emini, E. A.; Goldman, M. E.; Greenlee, W.
J.; Kauffman, L. R.; O’Brien, J. A.; Sardana, V.; Schleif, W. A.; Theoharides,
A. D.; Anderson, P. S. 5-Chloro-3-(phenylsulfonyl)indole-2-carboxamide: A
novel, non-nucleoside inhibitor of HIV-1 reverse transcriptase. J. Med. Chem.
1993, 36, 1291–1294; (b) Silvestri, R.; De Martino, G.; La Regina, G.; Artico,
M.; Massa, S.; Vargiu, L.; Mura, M.; Loi, A. G.; Marceddu, T.; La Colla, P.
Novel indolyl aryl sulfones active against HIV-1 carrying NNRTI resistance
mutations: Synthesis and SAR studies. J. Med. Chem. 2003, 46, 2482–2493.
4. (a) La Regina, G.; Edler, M. C.; Brancale, A.; Kandil, S.; Coluccia, A.;
´
Piscitelli, F.; Hamel, E.; De Martino, G.; Matesanz, R.; Dıaz, J. F.; Scovassi,
A. I.; Prosperi, E.; Lavecchia, A.; Novellino, E.; Artico, M.; Silvestri, R.
Arylthioindole inhibitors of tubulin polymerization, 3: Biological evaluation,
structure–activity relationships and molecular modeling studies. J. Med.

Indolyl-2/3-methylsulfoxides
1227
Chem. 2007, 50, 2865–2874; (b) La Regina, G.; Coluccia, A.; Piscitelli, F.;
Bergamini, A.; Sinistro, A.; Cavazza, A.; Maga, G.; Samuele, A.; Zanoli,
S.; Novellino, E.; Artico, M.; Silvestri, R. Indolyl aryl sulfones as HIV-1
non-nucleoside reverse transcriptase inhibitors: Role of two halogen atoms
at the indole ring in developing new analogues with improved antiviral activ-
ity. J. Med. Chem. 2007, 50, 5034–5038.
ꢀ
5. Romanelli, G. P.; Vazquez, G. P.; Tundo, P. New heteropolyacids as cata-
lysts for the selective oxidation of sulfides to sulfoxides with hydrogen perox-
ide. Synlett 2005, 75–78.
6. Bahrami, K. Selective oxidation of sulfides to sulfoxides and sulfones
using hydrogen peroxide (H2O2) in the presence of zirconium tetrachloride.
Tetrahedron Lett. 2006, 47, 2009–2012.
7. Jeyakumar, K.; Chand, D. K. Selective oxidation of sulfides to sulfoxides
and sulfones at room temperature using H2O2 and a Mo(VI) salt as catalyst.
Tetrahedron Lett. 2006, 47, 4573–4576.
8. Mohanakrishnan, A. K.; Ramesh, N. An efficient preparation of 1-phenyl-
sulfonylindolyl methylsulfoxides using KF=m-CPBA. Tetrahedron Lett.
2005, 46, 4231–4233.
9. Agnihotri, G.; Misra, A. K. Fast and selective oxidation of thioglycosides
to glycosyl sulfoxides using KF=m-CPBA. Tetrahedron Lett. 2005, 46,
8113–8116.
10. Rozen, S.; Bareket, Y. Oxidation of sulfur containing compounds with
HOF ꢀ CH3CN. J. Org. Chem. 1997, 62, 1457–1462.
11. (a) Mohanakrishnan, A. K.; Srinivasan, P. C. A versatile construction of the
8H-quino[4,3-b]carbazole ring system as a potential DNA binder. J. Org.
Chem. 1993, 60, 1939–1946; (b) Mohanakrishnan, A. K.; Balamurugan, R.
A novel synthesis of N-protected carbazoles involving electrocyclization of
in situ generated enamines. Tetrahedron Lett. 2005, 46, 4045–4048.
12. Mohanakrishnan, A. K.; Srinivasan, P. C. One pot synthesis of 4-hydroxy-3-
substituted carbazoles via sulfoxide stabilised carbanion. Tetrahedron Lett.
1993, 34, 1343–1346.