mol). The mixture was stirred for 2 h, and then 1 M HCl was
added slowly. Ethanol was evaporated; the resulting oil was
taken into dichloromethane and washed with water. The organic
layer was dried over Na2SO4, and then evaporated to give 410a
in quantitative yield (5.02 g). Without further purification, this
was dissolved in toluene (150 mL), and benzotriazole (3.57 g,
0.03 mol) was added followed by a catalytic amount of p-TSA,
(250 mg, 0.0015 mol). The mixture was refluxed under Dean-
Stark apparatus for 10 h. Then the mixture was washed with
10% Na2CO3 solution (100 mL) and water (100 mL) and dried
over Na2SO4. Evaporation of the solvent afforded an oil, which
is a mixture of 5b and 5a (70/30); the two isomers were separated
on silica gel chromatography (hexane/ethyl acetate:3/1), and the
minor isomer 5a was converted to 5b by heating neat at 200 °C
SCHEME 3
1
for 1 h. White microcrystals (70%): mp 95 °C; H NMR δ 2.06
(d, J ) 7 Hz, 3H), 6.04 (q, J ) 7.0 Hz, 1H), 6.37 (br, 1H), 7.15 (t,
J ) 2.7 Hz, 1H), 7.29 (s, 1H), 7.34-7.42 (m, 2H), 7.49-7.55 (m,
2H), 7.60-7.65 (m, 1H), 7.88-7.90 (m, 4H); 13C NMR δ 21.0,
59.7, 112.6, 118.0, 118.1, 121.3, 126.2, 126.9, 128.4, 129.4, 134.0,
138.6, 144.1. Anal. Calcd for C18H16O2N4S: C, 61.35; H, 4.58;
N, 15.90. Found: C, 61.53; H, 4.56; N, 15.79.
Gen er a l P r oced u r e for th e P r ep a r a tion of In d oles 1a -
f. To a solution of 2-1-[1-(phenylsulfonyl)-1H-pyrrol-3-yl]ethyl-
2H-1,2,3-benzotriazole (5b) (2 mmol) in THF (30 mL) at -78
°C was added n-butyllithium (1.58 M in cyclohexane, 1.43 mL,
2.2 mmol). The solution, which turned brown, was stirred for
10 min followed by the addition of appropriate chalcone (2.2
mmol) in one portion. The solution was kept at -78 °C for an
hour, then the temperature was allowed to rise to room tem-
perature and the mixture was stirred overnight. Saturated NH4-
Cl solution (10 mL) was added and the organic layer was
extracted with ethyl acetate. The combined ethyl acetate layer
was washed with water and concentrated. The residue was
refluxed with 50 mL of 10% H2SO4 2-propanol solution. After
24 h, the solution was cooled and neutralized with Na2CO3
solution. The organic phase was extracted with ethyl acetate
and the combined organic layer was washed with water and
brine, dried over Na2SO4, and concentrated under vacuum and
the oil was purified by column chromatography over silica gel
(hexane/ethyl acetate 4/1) to give the pure product.
substituted chalcones 9b-f also reacted similarly and the
respective indoles 1b-f were isolated in yields of 40 to
65%.
The reactions proceeded through the selective 1,4-
addition of 6 to the enones. We expected that the
interconvertible mixture of 7 and 8 thus formed would
spontaneously cyclize, followed by aromatization to the
indole. However, mild acid treatment was required to
facilitate the cyclization. In the case of 1b, intermediate
7b was isolated. In the case of 1d , 8d was isolated. For
the other indoles prepared, the intermediate addition
products were subjected to acid treatment without isola-
tion. Attempts to generalize this methology with use of
R,â-unsaturated esters failed.
In conclusion we have described a novel route to
substituted indoles proceeding under mild conditions. The
procedure utilizes three characteristics of benzotriazole
chemistry: its easy introduction (4 to 5), its ability to
stabilize an adjacent negative charge (5 to 6), and its
ability to act as a leaving group (7 to 8).
4-Meth yl-5,7-d iph en yl-1-(p h en ylsu lfon yl)-1H-in d ole (1a ).
1
Yellow prisms (60%): mp 153 °C; H NMR δ 2.52 (s, 3H), 6.93
(d, J ) 4.0 Hz, 1H), 7.08 (s, 1H), 7.20-7.70 (m, 15H), 7,87 (d, J
) 4.5 Hz, 1H); 13C NMR δ 16.3, 108.6, 126.4, 126.7, 126.8, 126.8,
127.3, 127.9, 128.0, 128.7, 129.5, 129.7, 130.2, 130.8, 132.1, 133.1,
133.4, 137.0, 138.3, 140.5, 141.0. Anal. Calcd for C27H21NO2S:
C, 76.57; H, 5.00; N, 3.31. Found: C, 76.78; H, 5.12; N, 3.15.
7-(4-Meth oxyph en yl)-4-m eth yl-5-(4-m eth ylph en yl)-1-(ph e-
n ylsu lfon yl)-1H-in d ole (1b). Pale yellow prisms (63%): mp
Exp er im en ta l Section
1
153 °C; H NMR δ 2.43 (s, 3H), 2.49 (s, 3H), 3.90 (s, 3H), 6.77
Melting points were determined on a Bristoline hot-stage
microscope and are uncorrected. 1H (300 MHz) and 13C (75 MHz)
NMR spectra were recorded on a 300-MHz NMR spectrometer
in chloroform-d solution. Column chromatography was per-
formed on silica gel. THF was distilled from sodium-benzophe-
none ketal prior to use. All the reactions were performed under
a nitrogen atmosphere and in flame-dried glasswares.
P r ep a r a tion of 1-(1-(P h en ylsu lfon yl)-1H-p yr r ol-3-yl))-
eth a n on e (3).10b To a suspension of anhydrous AlCl3 (4 g, 0.03
mol) in 40 mL of 1,2-dichloroethane at room temperature was
added slowly acetyl chloride (1.57 g 0.02 mol). The resulting
(d, J ) 8.5 Hz, 2H), 6.89 (d, J ) 3.5 Hz, 1H), 7.00 (s, 1H), 7.13
(d, J ) 8.7 Hz, 2H), 7.21-7.44 (m, 8H), 7.44-7.59 (m, 1H), 7.84
(d, J ) 4.0 Hz, 1H); 13C NMR δ 16.3, 21.1, 55.2, 108.5 112.7,
126.4, 126.6, 127.5, 128.7, 129.5, 130.2, 130.9, 131.0, 132.4, 132.8,
133.0, 133.3, 136.4, 137.0, 138.1, 138.5, 158.6. Anal. Calcd for
C29H25NO3S: C, 74.49; H, 5.39; N, 3.00. Found: C, 74.36; H,
5.43; N, 2.84.
5-(4-Ch lor oph en yl)-7-(4-m eth oxyph en yl)-4-m eth yl-1-(ph e-
n ylsu lfon yl)-1H-in d ole (1c). Gray needles (62%): mp 157 °C
1H NMR δ 2.41 (s, 3H), 3.84 (s, 3H), 6.71 (d, J ) 8.5 Hz, 2H),
6.84 (d, J ) 4.0 Hz, 1H), 6.90 (s, 1H), 7.05 (d, J ) 8.5 Hz, 2H),
7.20-7.39 (m, 8H), 7.43-7.55 (m, 1H), 7.80 (d, J ) 4 Hz, 1H);
13C NMR δ 16.2, 55.2, 108.2, 112.7, 126.4, 126.6, 127.6, 128.2,
128.7, 130.4, 130.7, 130.9, 130.9, 132.6, 132.6, 132.8, 133.1, 133.9,
135.7, 138.6, 139.5, 158.7. Anal. Calcd for C28H22ClNO3S: C,
68.91; H, 4.54; N, 2.87. Found: C, 68.72; H, 4.45; N, 2.71.
4,7-Dim eth yl-5-ph en yl-1-(ph en ylsu lfon yl)-1H-in dole (1d).
solution was stirred for 20 min, then
a solution of 1-H-
phenylsulfonyl-pyrrole (2 g, 0.01 mol) in 15 mL of 1,2-dichloro-
ethane was added slowly and the mixture was stirred at room
temperature for 3 h. The reaction mixture was poured into ice
and water, and the product was extracted with dichloromethane.
After concentration the solid obtained was recrystallized from
diethyl ether. White needles (92%): mp 97 °C (lit.10b mp 97-99
°C); 1H NMR δ 2.41 (s, 3H), 6.67 (dd, J ) 1.5, 3.5 Hz, 1H), 7.19
(dd, J ) 2.5, 3.5 Hz, 1H), 7.42-7.72 (m, 3H), 7.76 (dd, J ) 2.5,
3.5 Hz, 1H), 7.95-7.99 (m, 2H); 13C NMR δ 27.3, 112.5,
121.7;124.6, 127.2, 129.8, 134,6, 139.2, 196.2.
1
Yellow prisms (43%): mp 102 °C; H NMR δ 2.46 (s, 3H), 2.57
(s, 3H), 6.87 (d, J ) 4 Hz, 1H), 7.02 (s, 1H), 7.36-7.65 (m, 9H),
7,79 (d, J ) 8.0 Hz, 2H), 7.93 (d, J ) 4 Hz, 1H); 13C NMR δ
16.1, 21.5, 107.5, 121.6, 125.4, 126.4, 126.7, 128.1, 129.4, 129.6,
129.6, 130.4, 133.1, 133.6, 133.6, 137.1, 140.2, 141.4. Anal. Calcd
for C22H19NO2S: C, 73.10; H, 5.30; N, 3.87. Found: C, 73.32; H,
5.21; N, 3.64.
P r ep a r a t ion of 1-[1-(P h en ylsu lfon yl)-1H-p yr r ol-3-yl]-
eth yl-2H-1,2,3-ben zotr ia zole (5b). To a solution of 5 g (0.020
mol) of 3 in 200 mL of ethanol was added NaBH4 (0.76 g 0.02
J . Org. Chem, Vol. 68, No. 14, 2003 5729