Synthesis of 3-indolylpyrroles via base-mediated cycloaddition of TOSMIC with activated indole-2/3-vinylenes

Article abstract of DOI:10.1080/00397910802406703

A synthesis of various types of 3-indolylpyrroles is reported involving a base-mediated 1,3-dipolar cycloaddition of TOSMIC with activated indole-2/3-vinylenes. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910802406703

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Synthesis of 3-Indolylpyrroles
via Base-Mediated
Cycloaddition of TOSMIC with
Activated Indole-2/3-vinylenes
Ramalingam Balamurugan a , Radhakrishnan
Sureshbabu a , Ganesan Gobi Rajeshwaran a &
Arasambattu K. Mohanakrishnan a
a Department of Organic Chemistry , University of
Madras, Guindy Campus , Chennai, India
Published online: 08 Jan 2009.
To cite this article: Ramalingam Balamurugan , Radhakrishnan Sureshbabu ,
Ganesan Gobi Rajeshwaran & Arasambattu K. Mohanakrishnan (2009) Synthesis
of 3-Indolylpyrroles via Base-Mediated Cycloaddition of TOSMIC with Activated
Indole-2/3-vinylenes, Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic Chemistry, 39:3, 531-543, DOI:
10.1080/00397910802406703
To link to this article: http://dx.doi.org/10.1080/00397910802406703
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Synthetic Communications1, 39: 531–543, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910802406703
Synthesis of 3-Indolylpyrroles via Base-Mediated
Cycloaddition of TOSMIC with Activated
Indole-2/3-vinylenes
Ramalingam Balamurugan, Radhakrishnan Sureshbabu,
Ganesan Gobi Rajeshwaran, and Arasambattu K. Mohanakrishnan
Department of Organic Chemistry, University of Madras, Guindy Campus,
Chennai, India
Abstract: A synthesis of various types of 3-indolylpyrroles is reported involving
a base-mediated 1,3-dipolar cycloaddition of TOSMIC with activated indole-
2=3-vinylenes.
Keywords: Dictyodendrin, 1,3-dipolar cycloaddition, indole-2=3-vinylenes,
indolylpyrroles, indolyl vinyl ester
INTRODUCTION
The tosylmethylisocyanide (TOSMIC) reagent introduced by van Leusen
et al.[1] has found widespread application in organic synthesis. Of these,
the synthesis of five-member heterocycles using TOSMIC is most
explored one. The syntheses of five-member heterocycles include oxa-
zoles,[2] pyrroles,[3] imidazoles,[4] and thiazoles.[5] Among these hetero-
cycles, formation of the pyrrole ring is most important because a large
number of pyrrole unit–based molecules exhibit useful biological
activities. Smith and coworkers have reported[6] a step synthesis of
3-aryl- and 3,4-diaryl(1H)pyrroles involving a base-mediated cycloaddi-
tion of TOSMIC with the electron-deficient mono aryl and diaryl
Received June 7, 2008.
Address correspondence to Arasambattu K. Mohanakrishnan, Department of
Organic Chemistry, University of Madras, Guindy Campus, Chennai 600025,
India. E-mail: mohan_67@hotmail.com
531

532
R. Balamurugan et al.
vinylenes, respectively. Very recently, Misra and coworkers[7] outlined a
regioselective synthesis of 2,3,4-trisubstituted pyrroles involving cycload-
dition of polarized ketene S,S- and N,S-acetals with activated methylene
isocyanides.
RESULTS AND DISCUSSION
In continuation of our work on indole alkaloids using an electrocycliza-
tion strategy,[8] we are interested in the assembly of a tetracyclic core 2
unit of dictyodendrin 1.[9] Retro synthetically, the tetracyclic core unit
2 can be visualized via electrocyclization of 3-indolylpyrroles 3, Scheme 1.
A survey of the literature revealed that the base-mediated reaction of
TOSMIC reagent with indole 2=3-aldehydes led to the formation of indo-
lyl oxazoles.[10] Vaquero and coworkers developed[11] a domino process
via interaction of N-carbethoxy-indole-2-carboxaldehydes and TOSMIC
reagent under phase-transfer catalysis (PTC) conditions to synthesize
azolopyrimidines, core tricycles of variolin alkaloids. Pavri and Trudell
reported synthesis of various types of 3-arylpyrroles.[12] In that report,
synthesis of 1-benzyl-3-indolylpyrrole involving a 1,3-dipolar cycloaddi-
tion of methyl-1-benzyl-3-indolylacrylate with TOSMIC was carried
out. Because there is no other report on the synthesis of indolylpyrroles
of type 3, we undertook a systematic study on the synthesis of these com-
pounds. Initial reaction of indole-3-vinyl ester 4a with tosylmethyl isocya-
nide in NaH using dry THF afforded 3-indolylpyrrole 5a in 61% yield
along with a minor amount of starting material 4a. However, when the
reaction was carried out using t-BuOK in dimethylsulfoxide (DMSO),
product 5a was obtained in 70% yield. The product 5a could be isolated
in 75% yield using t-BuOK in dry dimethylformamide (DMF), Scheme 2.
Scheme 1. Retrosynthetic analysis of dictyodendrin.

Synthesis of 3-Indolylpyrroles
533
Scheme 2. Preparation of 3-indolypyrrole 5a.
A list of various vinyl indoles 4a–l employed for base-mediated
1,3-dipolar cycloaddition with TOSMIC reagent and the respective
3-indolylpyrroles 5a–l are summarized in Table 1. The N-phenylsulfo-
nyl-2-methyl-3-vinyl compounds 4a–e underwent a smooth 1,3-dipolar
cycloaddition followed by aromatization to afford respective pyrroles
5a–e in excellent yields (entries 1 and 2). Surprisingly, the 3-vinylester=
ketone compound 4f=4g lacking a 2-methyl substituent afforded corre-
sponding pyrroles 5f=5g in reduced yields (entry 3). The isomeric 2-vinyl
ester=ketone 4h–j also produced respective pyrroles 5h–j in excellent
yields (entry 4). Interaction of TOSMIC reagent with activated
vinyl compound 4k produced pyrrole 5k in 71% yield (entry 5). The 2-
nitro-4,5-dimethoxyphenyl tethered vinyl compound 4l led to the respec-
tive pyrrole 5l in low yield (entry 6). Contrary to earlier reports,[6] all
attempts to form a corresponding pyrrole with electron-deficient aryl
vinylenes 4m even at elevated temperature (TOSMIC=t-BuOK, DMF,
80 ꢀC, 10–12 h) were unsuccessful; the starting material was always
recovered unchanged (Scheme 3).
In summary, the synthesis of various 3-indolylpyrroles 5a–l has been
achieved involving a 1,3-dipolar cycloaddition of TOSMIC reagent with
different types of N-protected indole-2=3-vinylenes. Further studies on
Scheme 3.

534
R. Balamurugan et al.
Table 1. Synthesis of 3-indolylpyrroles using 1,3-dipolar cycloaddition of
TOSMIC
Yield
(%)a
Entry
1
Substrate
Condition
3-Indolylpyrroles
75
77
85
TOSMIC=
t-BuOK
dry DMF, 4–6 H
2
TOSMIC=
t-BuOK
dry DMF, 3 H
75
85
3
TOSMIC=
t-BuOK
dry DMF, 3 H
58
62
74
68
4
TOSMIC=
t-BuOK
dry DMF,
2.5–3 H
83
(Continued )

Synthesis of 3-Indolylpyrroles
535
Table 1. Continued
Yield
(%)a
Entry
5
Substrate
Condition
3-Indolylpyrroles
TOSMIC=
t-BuOK
dry DMF, 3 H
71
6
TOSMIC=
t-BuOK
dry DMF, 4 H
46
aIsolated yield after column chromatography.
conversion of 3-indolylpyrrole into the tetracyclic core skeleton of dictyo-
dendrin involving an electrocyclization strategy are in progress.
EXPERIMENTAL
All melting points were uncorrected. Reagents were purchased from com-
mercial 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). IR spectra were
recorded on a Shimadzu Fourier transform infrared (FT-IR) 8300 instru-
1
ment. H and 13C NMR spectra were recorded in CDCl3 using TMS as
an internal standard on a Jeol 400 and Bruker 300 spectrometers, respec-
tively. Chemical shift values were quoted in parts per million, and cou-
pling constants were quoted in hertz. Chemical shift multiplicities were
reported as s ¼ singlet, d ¼ doublet, t ¼ triplet, q ¼ quartet, m ¼ multiplet,
ltiplet, and br ¼ broad. Mass spectra were recorded on a Jeol DX 303 HF
spectrometer. Elemental analyses were carried out on Vario EL III
(CDRI, Lucknow) equipment. The required starting materials 4a–c, 4f,
4g, 4h, and 4j are prepared from the corresponding N-phenylsulfonylin-
dole-3=2-aldehydes following the published procedure.[8c]

536
R. Balamurugan et al.
Preparation of (E)-2-Methyl-3-(2-nitrovinyl)-1H-indole
To a mixture of 2-methyl-1H-indole-3-carbaldehyde (2.5 g, 15.7 mmol),
NH4OAc (1.8 g, 23.5 mmol) and nitro methane (1.4 g, 23.5 mmol) were
added and refluxed for 3 h. The resulting reaction mixture was poured
over crushed ice (200 g), and the solid (2.3 g, 85%) that formed was
1
filtered and dried (CaCl2). Mp: 196 ꢀC. H NMR (CDCl3, 300 MHz): d
2.59 (s, 3H, ꢁCH3), 6.94–7.74 (m, 5H, Ar-H), 8.33 (d, J ¼ 14 Hz, 1H,
ꢁCH ¼), 11.23 (s, 1H, ꢁNH).
Preparation of (E)-tert-Butyl 2-methyl-3-(2-nitrovinyl)-1H-indole-
1-carboxylate 4d
Dimethylaminopyridine (DMAP) (60 mg, 0.49 mmol) was added slowly
to a solution of (E)-2-methyl-3-(2-nitrovinyl)-1H-indole (1 g, 4.9 mmol)
in dry dichloromethane (DCM) (20 mL) and stirred for 0.5 h. Then di-
tert-butyl dicarbonate (1.3 g, 7.42 mmol) in dry DCM (10 mL) was added
and stirred for another 3 h. It was then poured over ice water and
extracted with DCM (2 ꢂ 30 mL). The combined organic extracts were
washed with H2O (2 ꢂ 25 mL) and dried (Na2SO4). Removal of solvent
followed by flash-column chromatographic purification (silica gel; 4%
ethyl acetate in hexane) afforded the compound 4d (1.27 g, 85%). Mp:
116–118 ꢀC. IR (KBr): 1747 (CO2 tBu), 1535 (NO2) cmꢁ1
(CDCl3, 300 MHz): d 1.72 (s, 9H, ꢁ Bu), 2.17 (s, 3H, -CH3), 7.33–7.38
(m, 2H, Ar-H), 7.56–7.81 (m, 2H, Ar-H), 8.14–8.16 (m, 1H, Ar-H),
8.17–8.33 (m, 1H, Ar-H).
.
1H NMR
t
Preparation of (E)-2-Methyl-3-(2-nitrovinyl)-1-(phenylsulfonyl)-
1H-indole 4e
(E)-2-Methyl-3-(2-nitrovinyl)-1H-indole (1 g, 4.9 mmol) in dry THF
(20 mL) was slowly added to a suspension of sodium hydride (356 mg,
7.42 mmol) in dry THF (10 mL) at room temperature under nitrogen
and stirred for 2 h. To the resulting reaction mixture, a solution of ben-
zenesulfonylchloride (1.13 g, 6.43 mmol) in dry THF (10 mL) was added,
and stirring was continued for further 8 h. The solution was poured over
crushed ice (100 g) and then acidified with conc. HCl (1 mL). The solid
formed was filtered and dried. The crude product was recrystallized from
methanol to afford 4e (1.3 g, 77%). Mp: 133 ꢀC. IR (KBr): 1556 (NO2),
1
1367 & 1170 (SO2Ph) cmꢁ1. H NMR (CDCl3, 300 MHz): d 2.62 (s,
3H, ꢁCH3), 6.62 (d, J ¼ 13.4 Hz, 1H, ꢁCH), 7.28–7.51 (m, 6 H, Ar-H),
7.69 (d, J ¼ 7.4 Hz, 2H, ArꢁH), 8.31 (d, J ¼ 8.1 Hz, 2H, Ar-H).

Synthesis of 3-Indolylpyrroles
537
Preparation of (E)-Methyl 3-[3-methyl-1-(phenylsulfonyl)-1H-
indol-2-yl]-acrylate 4i
(Carbomethoxymethylene)-triphenylphosphorane (2.68 g, 8.03 mmol)
was added and refluxed for 12 h to a solution of 1-phenylsulfonyl-
3-methylindole-2-aldehyde[8c] (2.0 g, 6.69 mmol) in THF (50 mL). The
solvent was evaporated, and the crude product was purified by column
chromatography to afford compound 4i (1.8 g, 78%). Mp: 190 ꢀC. IR
1
(KBr): 1700 (CO2Me), 1363 & 1172 (SO2Ph) cmꢁ1. H NMR (CDCl3,
300 MHz): d 2.32 (s, 3H, ꢁCH3), 3.89 (s, 3H, ꢁOCH3), 6.14 (d,
J ¼ 16.2 Hz, 1H, ꢁCH ¼), 7.27–7.52 (m, 6H, Ar-H), 7.69 (d, J ¼ 7.5 Hz,
2H, Ar-H), 8.24 (d, J ¼ 7.5 Hz, 2H, Ar-H).
Preparation of (E)-Ethyl 4-[2-methyl-1-(phenylsulfonyl)-
1H-indol-3-yl]-4-oxobut-2-enoate 4k
SeO2 (797 mg, 7.1 mmol) was added to a solution of 1-phenylsulfonyl-2-
methyl-3-acetylindole (1.5 g, 4.7 mmol) in dioxane (40 mL) and refluxed
for 10 h. The resulting reaction mixture was passed over a Celite pad
and washed with DCM (2 ꢂ 15 mL). The combined extracts were washed
with H2O (2 ꢂ 25 mL). Removal of solvent afforded 2-[2-methyl-1-
(phenylsulfonyl)-1H-indol-3-yl]-2-oxoacetaldehyde (1.09 g, 70%), which
was used for a further step. The Wittig reaction of 2-[2-methyl-1-
(phenylsulfonyl)-1H-indol-3-yl]-2-oxoacetaldehyde
similar to that of 4i to afford 4k (0.79 g, 65%). Mp: 97–99 C. IR
was
perꢀformed
(KBr): 1705 (CO2Et), 1648 (CO), 1372 & 1167 (SO2Ph) cmꢁ1 1H
.
NMR (CDCl3, 400 MHz): d 1.30 (t, J ¼ 6.9 Hz, 3H, ꢁCH3), 4.26 (q,
J ¼ 7.2 Hz, 2H, -CH2), 2.82 (s, 3H, -CH3), 6.75 (d, J ¼ 15.9 Hz, 1H,
ꢁCH), 7.29–7.37 (m, 3H, Ar-H), 7.46 (t, J ¼ 8.2 Hz, 1H, Ar-H), 7.56–
7.62 (m, 2H, Ar-H), 7.72 (d, J ¼ 7.6 Hz, 1H, Ar-H), 7.83 (d, J ¼ 7.6 Hz,
2H, Ar-H), 8.25 (d, J ¼ 8.4 Hz, 1H, Ar-H). 13C NMR (CDCl3,
75 MHz): d 14.1, 14.4, 61.3, 114.5, 120.5, 124.6, 125.1, 126.5, 126.7,
129.6, 131.6, 134.4, 136.0, 140.3, 143.1, 165.4, 187.8.
Preparation of (E)-3-(4,5-Dimethoxy-2-nitrophenyl)-1-[2-methyl-
1-(phenylsulfonyl)-1H-indol-3yl]prop-2-en-1-one 4l
The procedure was similar to that of 4i. Yield: 1 g (65%). Mp: 192 ꢀC. IR
1
(KBr): 1664 (CO), 1562 (NO2), 1372 & 1167 (SO2Ph) cmꢁ1. H NMR
(CDCl3, 400 MHz): d 2.85 (s, 3H, ꢁCH3), 3.98 (s, 3H, ꢁOCH3), 3.99
(s, 3H, ꢁOCH3), 6.96–7.02 (m, 2H, ꢁCH), 7.29–7.35 (m, 2H, Ar-H),

538
R. Balamurugan et al.
7.49 (t, J ¼ 7.6 Hz, 2H, Ar-H), 7.57–7.71 (m, 3H, Ar-H), 7.88 (d,
J ¼ 7.2 Hz, 2H, Ar-H), 8.05 (d, J ¼ 15.9 Hz, 1H, Ar-H), 8.26 (d,
J ¼ 8.1 Hz, 1H, Ar-H). 13C NMR (CDCl3, 75 MHz): d 14.6, 56.6, 56.7,
108.0, 110.0, 114.5, 120.4, 120.9, 124.4, 125.1, 125.4, 126.6, 127.4,
129.7, 130.6, 134.4, 136.0, 138.8, 140.9, 141.3, 141.5, 150.1, 153.2,
189.8. MS: m=z, 506 (Mþ). Anal. calcd. for C26H22N2O7S: C, 61.65; H,
4.38; N, 5.53. Found: C, 61.46; H, 4.30; N, 5.80.
Representative Procedure for Preparation of 5a
TOSMIC (0.29 g, 1.49 mmol) in dry DMF (2 mL) was added to a suspen-
sion of t-BuOK (0.31 g, 2.76 mmol) in dry DMF (5 mL) at 0 ꢀC. The mix-
ture was stirred for 15 min at the same temperature under a nitrogen
atmosphere and was treated dropwise with a solution of vinyl ester com-
pound 4a (0.5 g, 1.35 mmol) dissolved in dry DMF (4 mL). After the vinyl
ester compound was consumed (monitored by thin-layer chromotogra-
phy, TLC) the reaction mixture was quenched with ice water (10 mL),
extracted with CHCl3 (2 ꢂ 10 mL), and dried (Na2SO4). Removal of sol-
vent followed by column chromatographic purification (hexane–ethylace-
tate (EA); 9:1) afforded 5a as colorless solid (0.41 g, 75%). Mp: 166–
168 ꢀC. IR (KBr): 3242 (N-H), 1672 (CO2Et), 1363 & 1176 (SO2Ph)
1
cmꢁ1. H NMR (CDCl3, 400 MHz): d 0.77 (t, J ¼ 7.1 Hz, 3H, ꢁCH3),
2.41 (s, 3H, ꢁCH3), 3.81–3.91 (m, 2H, ꢁCH2), 6.60 (t, J ¼ 2.4 Hz, 1H,
Ar-H), 7.03–7.16 (m, 3H, Ar-H), 7.35 (t, J ¼ 7.1 Hz, 2H, Ar-H), 7.43–
7.48 (m, 2H, Ar-H), 7.72 (d, J ¼ 7.5 Hz, 2H, Ar-H), 8.05 (d, J ¼ 8.4 Hz,
1H, Ar-H), 10.89 (s, 1H, ꢁNH). 13C NMR (DMSO-d6, 75MHz): d 13.6,
13.7, 58.5, 113.5, 113.6, 114.1, 116.6, 119.5, 120.3, 123.3, 123.7, 125.3,
126.1, 129.7, 131.0, 133.2, 134.2, 135.0, 138.1, 163.7. MS: m=z, 408 (Mþ).
Anal. calcd. for C22H20N2O4S: C, 64.69; H, 4.94; N, 6.86. Found: C,
64.87; H, 4.67; N, 6.53.
Methyl 4-[2-Methyl-1-(phenylsulfonyl)-1H-indol-3-yl]-1H-pyrrole-
3-carboxylate (5b)
The procedure was similar to that of 5a. Yield: 0.41 g (77%). Mp: 228 ꢀC.
1
IR (KBr): 3258 (N-H), 1706 (CO2Me), 1370 & 1172 (SO2Ph) cmꢁ1. H
NMR (CDCl3, 300 MHz): d 2.49 (s, 3 H, ꢁCH3), 3.48 (s, 3H, ꢁOCH3),
(s, 1H, Ar-H), 7.16–7.26 (m, 4H, Ar-H), 7.40–7.58 (m, 3H, Ar-H), 7.81
(d, 2H, Ar-H), 8.17–8.19 (d, J ¼ 8.1 Hz, 1H, Ar-H), 8.60 (s, 1H, ꢁNH).
MS: m=z, 394 (Mþ). Anal. calcd. for C21H18N2O4S: C, 63.94; H, 4.60;
N, 7.10. Found: C, 63.72; H, 4.87; N, 6.91.

Synthesis of 3-Indolylpyrroles
539
1-[4-(2-Methyl-1-(phenylsulfonyl)-1H-indol-3-yl)-1H-pyrrol-3-yl]ethanone
(5c)
The procedure was similar to that of 5a. Yield: 0.47 g (85%). Mp: 218–
220 ꢀC. IR (KBr): 3242 (NꢁH), 1635 (CO), 1367 & 1176 (SO2Ph)
1
cmꢁ1. H NMR (DMSO-d6, 300 MHz): d 2.46 (s, 3H, ꢁCH3), 2.69 (s,
3H, -CH3), 6.77 (s, 1H, Ar-H), 7.28–7.56 (m, 7H, Ar-H), 7.81 (d,
J ¼ 6.9 Hz, 2H, Ar-H), 8.18–8.19 (m, 1H, Ar-H), 8.64 (s, 1H, ꢁNH).
MS: m=z, 378 (Mþ). Anal. calcd. for C21H18N2O3S: C, 66.65; H, 4.79;
N, 7.40. Found: C, 66.93; H, 4.54; N, 7.63.
tert-Butyl 2-methyl-3-(4-nitro-1H-pyrrol-3-yl)-1H-indole-1-carboxylate
(5d)
The procedure was similar to that of 5a. Yield: 0.42 g (75%). Mp: 144–
146 ꢀC. IR (KBr): 3280 (NꢁH), 1726 (CO2 tBu), 1465 (NO2), 1369 &
1
t
1157 (SO2Ph) cmꢁ1. H NMR (CDCl3, 400 MHz): d 1.68 (s, 9H, ꢁ Bu),
(s, 3H, ꢁCH3), 6.64 (s, 1H, Ar-H), 7.16–7.23 (m, 3H, Ar-H), 7.74 (s, 1H,
Ar-H), 8.10 (s, 1H, Ar-H), 9.47 (s, 1H, NH). 13C NMR (CDCl3,
100 MHz): d 15.1, 28.2, 83.8, 111.3, 111.7, 115.4, 118.6, 119.9, 121.5,
122.6, 123.5, 129.9, 135.4, 135.6, 135.7, 150.7. MS: m=z, 341 (Mþ). Anal.
calcd. for C18H19N3O4: C, 63.33; H, 5.61; N, 12.31. Found: C, 63.63; H,
5.43; N, 12.02.
2-Methyl-3-(4-nitro-1H-pyrrol-3-yl)-1-(phenylsulfonyl)-1H -indole (5e)
The procedure was similar to that of 5a. Yield: 0.47g (85%). Mp: 117 ꢀC. IR
1
(KBr): 3379 (NꢁH), 1556 (NO2), 1365 & 1176 (SO2Ph) cmꢁ1. H NMR
(CDCl3, 400 MHz): d 2.38 (s, 3H, ꢁCH3), 7.25–7.29 (m, 2H, Ar-H), 7.43–
7.59 (m, 5H, Ar-H), 7.61–7.68 (m, 3H, Ar-H), 7.89 (s, 1H, Ar-H), 11.91
(s, 1H, ꢁNH). MS: m=z, 381 (Mþ). Anal. calcd. for C19H15N3O4S: C,
59.83; H, 3.96; N, 11.02. Found: C, 59.65; H, 4.22; N, 10.87.
Ethyl 4-(1-(Phenylsulfonyl)-1H-indol-3-yl)-1H-pyrrole-3-carboxylate (5f)
The procedure was similar to that of 5a. Yield: 0.32 g (58%). Mp: 196 ꢀC.
1
IR (KBr): 3240 (NꢁH), 1690 (CO2Et), 1367 & 1170 (SO2Ph) cmꢁ1. H
NMR (CDCl3, 300 MHz): d 0.79 (t, J ¼ 7.1 Hz, 3H, ꢁCH3), 3.87–3.91
(m, 2H, ꢁCH2), 6.32 (t, J ¼ 2.4 Hz, 1H, Ar-H), 7.08–7.23 (m, 3H, Ar-
H), 7.45–7.53 (m, 4H, Ar-H), 7.69 (s, 1H, Ar-H), 7.73 (d, J ¼ 7.5 Hz,

540
R. Balamurugan et al.
2H, Ar-H), 8.14 (d, J ¼ 8.2 Hz, 1H, Ar-H), 10.89 (s, 1H, ꢁNH). MS: m=z,
394 (Mþ). Anal. calcd. for C21H18N2O4S: C, 63.94; H, 4.60; N, 7.10.
Found: C, 63.64; H, 4.31; N, 7.42.
1-[4-(1-(Phenylsulfonyl)-1H-indol-3-yl)-1H-pyrrol-3-yl]ethanone (5g)
The procedure was similar to that of 5a. Yield: 0.34g (62%). mp: 240 ꢀC. IR
1
(KBr): 3224 (NꢁH), 1631 (CO), 1367 & 1174 (SO2Ph) cmꢁ1. H NMR
(DMSO-d6, 300 MHz): d 2.36 (s, 3H, ꢁCH3), 7.21–7.27 (m, 2H, Ar-H),
7.34 (t, J ¼ 7.5 Hz, 1H, Ar-H), 7.57 (t, J ¼ 8.1 Hz, 3H, Ar-H), 7.63–7.66
(m, 1H, Ar-H), 7.82 (s, 1H, Ar-H), 7.94–8.04 (m, 4H, Ar-H), 11.73 (s,
1H, ꢁNH). 13C NMR (DMSO-d6, 75 MHz): d 28.1, 113.0, 113.3, 116.9,
120.5, 121.0, 122.3, 123.4, 124.4, 124.6, 126.5, 127.9, 129.7, 130.3, 134.1,
134.4, 137.0, 192.8. MS: m=z, 364 (Mþ). Anal. calcd. for C20H16N2O3S:
C, 65.92; H, 4.43; N, 7.69. Found: C, 65.71; H, 4.21; N, 7.47.
1-[4-(3-Methyl-1-(phenylsulfonyl)-1H-indol-2-yl)-1H-pyrrol-3-yl]ethanone
(5h)
The procedure was similar to that of 5a. Yield: 0.41 g (74%). Mp: 224–
226 ꢀC. IR (KBr): 3352 (NꢁH), 1664 (CO), 1363 & 1166 (SO2Ph)
1
cmꢁ1. H NMR (DMSO-d6, 300 MHz): d 1.93 (s, 3H, ꢁCH3), 2.18 (s,
3H, ꢁCH3), 6.82 (s, 1H, Ar-H), 7.26–7.34 (m, 2H, Ar-H), 7.43–7.48
(m, 5H, Ar-H), 7.55–7.57 (m, 1H, Ar-H), 7.70 (s, 1H, Ar-H), 8.06 (d,
J ¼ 7.8 Hz, 1H, Ar-H), 11.65 (s, 1H, ꢁNH). 13C NMR (DMSO-d6,
75 MHz): d 9.2, 28.9, 111.4, 114.4, 117.9, 118.9, 122.6, 123.2, 124.2,
125.3, 125.7, 126.1, 129.1, 130.7, 131.2, 133.7, 135.7, 138.2, 191.7. MS:
m=z, 378 (Mþ). Anal. calcd. for C21H18N2O3S: C, 66.65; H, 4.79; N,
7.40. Found: C, 66.27; H, 4.92; N, 7.69.
Methyl 4-[3-Methyl-1-(phenylsulfonyl)-1H-indol-2-yl]-1H-pyrrole-
3-carboxylate (5i)
The procedure was similar to that of 5a. Yield: 0.37 g (68%). Mp: 218–
220 ꢀC. IR (KBr): 3264 (N-H), 1672 (CO2Me), 1360 & 1180 (SO2Ph)
1
cmꢁ1. H NMR (DMSO-d6, 300 MHz): d 1.95 (s, 3H, ꢁOCH3), 2.50 (s,
3H, ꢁCH3), 6.87 (t, J ¼ 2.1 Hz, 1H, Ar-H), 7.24–7.60 (m, 9H, Ar-H),
8.08 (d, J ¼ 8.1 Hz, 1H, Ar-H), 11.65 (s, 1H, ꢁNH). MS: m=z, 394
(Mþ). Anal. calcd. for C21H18N2O4S: C, 63.94; H, 4.60; N, 7.10. Found:
C, 63.72; H, 4.82; N, 7.39.

Synthesis of 3-Indolylpyrroles
541
1-[4-(1-(Phenylsulfonyl)-3-(phenylthio)-1H-indol-2-yl)-1H-pyrrol-
3-yl]ethanone (5j)
The procedure was similar to that of 5a. Yield: 0.45 g (83%). Mp: 190ꢀC.
IR (KBr): 3280 (N-H), 1643 (CO), 1373 & 1176 (SO2Ph) cmꢁ1. 1H NMR
(CDCl3, 300 MHz): d 2.31 (s, 3H, ꢁCH3), 6.90 (s, 1H, Ar-H), 7.00–7.05
(m, 3H, Ar-H), 7.06–7.12 (m, 3H, Ar-H), 7.22 (t, J ¼ 7.5 Hz, 3H, Ar-H),
7.29 (t, J ¼ 7.2 Hz, 1H, Ar-H), 7.42–7.51 (m, 3H, Ar-H), 7.68 (s, 1H, Ar-
H), 7.73 (s, 1H, Ar-H), 12.26 (s, 1H, -NH). MS: m=z, 472 (Mþ). Anal.
calcd. for C26H20N2O3S2: C, 66.08; H, 4.27; N, 5.93. Found: C, 66.34;
H, 4.51; N, 5.70.
Ethyl 4-[2-Methyl-1-(phenylsulfonyl)-1H-indole-3-carbonyl]-1H-pyrrole-3-
carboxylate (5k)
The procedure was similar to that of 5a. Yield: 0.39 g (71%). Mp: 110 ꢀC.
IR (KBr): 3388 (NꢁH), 1716 (CO2Et), 1643 (CO), 1373 & 1176 (SO2Ph)
1
cmꢁ1. H NMR (CDCl3, 400 MHz): d 1.00 (t, J ¼ 7.1 Hz, 3H, ꢁCH3),
2.33 (s, 3 H, ꢁCH3), 3.76 (q, J ¼ 7.2 Hz, 2H, ꢁCH2), 6.82 (t, J ¼ 2.1 Hz,
Hz, 1H, Ar-H), 6.95–7.21 (m, 5H, Ar-H), 7.27–7.41 (m, 3H, Ar-H), 7.83
(d, J ¼ 7.6 Hz,1H, Ar-H), 8.21 (d, J ¼ 8.2 Hz, 1H, Ar-H), 8.68 (s, 1H,
ꢁNH). MS: m=z 436 (Mþ). Anal. calcd. for C23H20N2O5S: C, 63.29;
H, 4.62; N, 6.42. Found: C, 63.04; H, 4.38; N, 6.61.
[4-(4,5-Dimethoxy-2-nitrophenyl)-1H-pyrrol-3-yl)(2-methyl-
1-(phenylsulfonyl)-1H-indol-3-yl]methanone (5l)
The procedure was similar to that of 5a. Yield: 0.24 g (46%). Mp:
217 ꢀC. IR (KBr): 3390 (N-H), 1623 (CO), 1517 (NO2), 1375 & 1182
(SO2Ph) cmꢁ1
.
1H NMR (CDCl3, 300 MHz): d 2.63 (s, 3H, ꢁCH3),
3.93 (s, 3H, ꢁOCH3), 3.96 (s, 3H, ꢁOCH3), 6.79 (s, 1H, Ar-H), 6.85
(t, J ¼ 2.1 Hz, 1H, Ar-H), 7.11 (t, J ¼ 2.1 Hz, 1H, Ar-H), 7.15–7.20
(m, 1H, Ar-H), 7.46 (t, J ¼ 8.1 Hz, 3H, Ar-H), 7.52–7.59 (m, 2H, Ar-
H), 7.66 (s, 1H, Ar-H), 7.80–7.83 (d, J ¼ 7.5 Hz, 2H, Ar-H), 8.18 (d,
J ¼ 8.4 Hz, 1H, Ar-H), 8.63 (s, 1H, -NH). 13C NMR (CDCl3,
75 MHz): d 14.2, 56.2, 56.3, 108.1, 114.0, 114.4, 118.8, 120.7, 121.9,
122.7, 123.7, 124.5, 124.6, 124.7, 126.5, 127.4, 128.4, 129.4, 134.0,
135.7, 138.7, 139.0, 141.3, 147.7, 152.2, 186.5. MS: m=z, 545 (Mþ).
Anal. calcd. for C28H23N3O7S: C, 61.64; H, 4.25; N, 7.70. Found: C,
61.87; H, 4.03; N, 7.99.

542
R. Balamurugan et al.
ACKNOWLEDGMENTS
We thank CSIR, New Delhi [01(2071)=06=EMR-II], for the financial
support. Authors thank DST-FIST for use of the 300-MHz NMR facility.
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