ꢂꢁꢁꢁ
T.A.J. Vijay et al.: Ligand- and catalyst-free intramolecular C-S bond formationꢀ ꢀ3
monitored by TLC analysis. The mixture was then poured into water
and extracted with ethyl acetate. The organic extract was dried over
sodium sulfate and concentrated. The residue of product 1a was crys-
tallized from diethyl ether.
9-benzyl-2-(4-(methylthio)phenyl)thiopyrano[2,3-b]indol-
4(9H)-one [28, 37] (not shown). The suggested SNAr sub-
stitution reaction of the halogen atom by the methylthio
group did not take place with 4-chlorophenyl and 4-bromo-
phenyl substituted indalothiochromen-4-ones 3f,g. The
heterocyclic dithioesters of benzothiophene 2i and thio-
phene 2j underwent the reaction with 1a and 1c, efficiently
furnishing the corresponding indalothiochromen-4-ones
3i, 3j, and 3m in 63%, 56%, and 63% yields, respectively.
6-Bromo substituted indalothiochromen-4-ones 3n and
3o were obtained in the respective yields of 52% and 48%.
The structures of all these products were characterized
and confirmed by spectral analyses.
We propose that the reaction proceeds according to
the mechanism shown in Scheme 2, exemplified by the
particular reaction of 1a with 2a. The carbanion interme-
diate X undergoes a reaction with dithioester 2a to afford
1,3-thioketone Y, which then undergoes keto-enol tau-
tomerization to generate another intermediate product Z.
Finally, an intramolecular addition of mercapto group in Z
followed by elimination of halide ion led to the formation
of the observed product 3a.
A solution of compound 1 (1.0 mmol, 1.0 Eq) in DMF (2 mL) was
added at 0°C to a 60% suspension of NaH in mineral oil (2.5 mmol,
2.5 Eq), and the mixture was stirred for 15 min at room temperature.
Then a solution of dithioester 2 (1.0 mmol, 1.0 Eq) in DMF (2 mL) was
added over a period of 10 min at 0°C, and the mixture was stirred
at room temperature for an additional 7 h. The progress of the reac-
tion was monitored by TLC. The mixture was poured into water and
extracted with ethyl acetate (2ꢀ×ꢀ25 mL). The combined organic layers
were washed with brine (25 mL) and dried over anhydrous sodium
sulfate. The solvent was removed under reduced pressure, and the
crude product was passed through a small plug of silica eluting with
hexane/ethyl acetate (8:2) to afford indalothiochromen-4-ones 3a-o.
Representative products are characterized as follows. Characteriza-
tion of all compounds is given in Supplementary Information.
9-Benzyl-2-phenylthiopyrano[2,3-b]indol-4(9H)-one (3a)ꢁCom-
pound 3a was obtained by the reaction of 1a and 2a in 60% yield
as a pale brown solid; mp 164–166°C; 1H NMR (CDCl3): δ 8.65 (d, J ꢀ=ꢀ
4.8 Hz, 1H), 7.60 (t, J ꢀ=ꢀ 3.6 Hz, 2H), 7.46–7.45 (m, 3H), 7.38–7.36 (m, 3H),
7.29–7.25 (m, 4H), 7.14 (d, J ꢀ=ꢀ 6.4 Hz, 2H), 5.43 (s, 2H); 13C NMR (CDCl3):
δ 178.6, 143.9, 142.9, 137.9, 136.5, 134.6, 130.3, 129.0, 127.2, 127.0, 126.6,
124.7, 122.7, 122.4, 114.2, 108.9, 48.2; IR: 1597, 1481, 1474, 1419, 1334,
−1
+
873, 750, 743, 717, 612 cm ; MS (ESI): m/z ꢀ=ꢀ 368.1 (M ). Anal. Calcd for
C24H17NOS: C, 78.45; H, 4.66; N, 3.81. Found: C, 78.43; H, 4.64; N, 3.79.
9-Benzyl-2-(3,4,5-trimethoxyphenyl)thiopyrano[2,3-b]indol-
4(9H)-one (3e)ꢁCompound 3e was obtained by the reaction of
Experimental details
1
1a and 2e in 76% yield as pale yellow solid; mp 169–171°C; H NMR
All materials were purchased from known commercial sources and
used without further purification. Thin layer chromatography (TLC)
analysis was performed with silica gel 60F254 aluminum sheets
(Merck). Mixtures of hexanes and ethyl acetate in different ratios
were used in TLC analysis. Melting points were determined in open
capillaries and are uncorrected. Infrared (IR) spectra were recorded
on FT-IR spectrometer in KBr pellets. 1H NMR (400 MHz) and 13C NMR
(100 MHz) spectra were collected at NMR Facility, IOE, University of
Mysore.
(DMSO-d6): δ 8.43 (d, J ꢀ=ꢀ 7.7 Hz, 1H), 7.76 (d, J ꢀ=ꢀ 8.1 Hz, 1H), 7.42 (t, J ꢀ=ꢀ
7. 2 Hz, 1H), 7.44–7.23 (m, 7H), 7.02 (s, 2H), 5.73 (s, 2H), 3.89 (s, 6H), 3.73
(s, 3H); 13C NMR (DMSO-d6): δ 177.8, 153.8, 144.1, 142.7, 138.1, 136.0,
131.8, 129.3, 128.4, 127. 5, 126.2, 125.0, 124.4, 122.6, 121.8, 110.7, 105.1,
60.6, 56.6, 48.0; IR: 1599, 1505, 1479, 1420, 1332, 1249, 1126, 1008, 829,
−1
+
758, 667 cm ; MS (ESI): m/z ꢀ=ꢀ 458.7 (M ). Anal. Calcd for C24H16ClNOS:
C, 70.88; H, 5.07; N, 3.06. Found: C, 70.85; H, 5.05; N, 3.05.
9-Benzyl-2-(4-fluorophenyl)thiopyrano[2,3-b]indol-4(9H)-
one (3h)ꢁCompound 3h was obtained by the reaction of 1a and 2h in
53% yield as creamy solid; mp 155–157°C; 1H NMR (CDCl3): δ 8.59 (d,
J ꢀ=ꢀ 4.8 Hz, 1H), 7.61–7.57 (m, 2H), 7.42–7.25 (m, 7H), 7.20–7.13 (m, 4H),
5.47 (s, 2H); 13C NMR (CDCl3): δ 165.3, 162.8, 138.0, 134.3, 132.3, 129.2,
128.3, 126.1, 125.1, 124.3, 122.7, 116.4, 109.0, 48.4; IR: 1607, 1486, 1452,
One-pot synthesis of indalothiochromen-4-ones 3a-o
A solution of N,N-dimethylformamide (DMF, 10.5 mL, 3 Eq) in dichlo-
romethane (20 mL) was treated dropwise at 0°C with a solution of
phosphorus oxychloride (11 mL, 3 Eq) in dichloromethane (20 mL).
The mixture was stirred for 15 min, then treated slowly with a solu-
tion of 2-oxindole (A, 5 g, 1 Eq) in chloroform (20 mL), and stirred
under reflux for 5 h. Afer the addition of crushed ice and stirring for
an additional 20 min, the separation of two layers was observed. The
aqueous layer was adjusted to pH 7 with sodium acetate. The mixture
was lef at room temperature overnight, and then the resultant pre-
cipitate of product B was collected by filtration, washed with water,
and dried [35].
−1
+
1230, 1162, 1107, 1334, 833, 746, 559 cm ; MS (ESI): m/z ꢀ=ꢀ 386.6 (M ).
Anal. Calcd for C24H16ClNOS: C, 74.78; H, 4.18; N, 3.63. Found: C, 74.76;
H, 4.16; N, 3.62.
2-(Benzo[b]thiophen-3-yl)-9-benzylthiopyrano[2,3-b]indol-
4(9H)-one (3j)ꢁCompound 3j was obtained by the reaction of 1a and
2j in 56% yield as amber solid; mp 145–149°C; 1H NMR (CDCl3): δ 8.47
(d, J ꢀ=ꢀ 7.2 Hz, 1H), 8.01 (d, J ꢀ=ꢀ 8.0 Hz, 2H), 7.85–7.75 (m, 4H), 7.42–7.31
(m, 5H), 7.25–7.18 (m, 2H), 7.12 (d, J ꢀ=ꢀ 7.6 Hz, 1H), 5.51 (s, 2H); 13C NMR
(CDCl3): δ 182.1, 147.8, 141.1, 137.5, 135.9, 132.1, 129.3, 128.8, 128.6, 127.6,
126.6, 125.1, 124.6, 122.5, 122.2, 121.4, 119.8, 112.5, 110.9, 109.9, 60.7; IR:
Next, a mixture of compound B (2.5 g) and potassium hydroxide
(1.25 g, 1.5 Eq) in dry DMF (10 mL) was stirred for 10 min before treat-
ment with benzyl bromide (1.4 mL, 1.1 Eq). The mixture was stirred
at room temperature until substrate B was completely consumed, as
−1
1586, 1480, 1424, 1419, 1266, 1117, 755, 752, 733, 401 cm ; MS (ESI):
+
m/z ꢀ=ꢀ 423.8 (M ). Anal. Calcd for C26H17NOS2: C, 73.73; H, 4.05; N, 3.31.
Found: C, 73.72; H, 4.03; N, 3.30.
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