Vol. 29, No. 10 (2017)
Magnesium Catalyzed Dephenylsulfonylation: Synthesis of 5-Ethyl-1H-indole 2233
1
13
phase. H, C NMR spectra were recorded using a Varian
00 MHz instrument and Mass spectra on Agilent LC-MS
instrument.
followed by magnesium turnings (15 g, 617 mmol, 11.75
equiv) under gentle stirring (about 290 rpm). It is observed
that before addition of magnesium, the reaction mass is as
light yellow in colour and then it is changed to pale yellow
colour; once it is added with magnesium to the reaction mass.
Slowly raise the temperature by heating (water bath) to 60-64
°C and maintain it for 3-4 h. While maintaining at reflux
condition the whole reaction mass colour changed to ash in
colour, then after maintaining to 8-9 h under the reflux
condition a sudden frothing was observed in the reaction flask,
it means the reaction gets initiated and this initiation indicates
that the reaction is completed.After completion of the reaction
the reaction mass was cooled to room temperature and filtered
through a 100 mL Buchner funnel packed with Celite 545 bed
(20 g) to remove the excess of magnesium turnings present
in the reaction mass. The resulting filtrate mother liquor was
distilled under reduced pressure at 40 °C. The resulting dark
brown colour viscous liquid material taken in to water (200
mL), then it becomes clear aqueous solution. The resulting
aqueous layer transferred to 500 mL separating funnel and
extracted with ethyl acetate (2 × 100 mL). The combined
organic layers were washed with brine solution (50 mL satu-
rated aqueous sodium chloride solution) and then dried over
anhydrous sodium sulphate (10 g, 7.04 mol). The dried organic
layer was distilled under reduced pressure (40 °C, 18 mm Hg)
to afford the desired product 5-ethyl-1H-indole (7.10 g 98.50
%) as a light brown liquid (Scheme-II). The progress of the
reaction followed by TLC analysis on silica gel with 30 %
EtOAc-hexane as eluent and visualization with UV cabinet,
4
5
-[2-(Phenyl sulfonyl)ethyl]-1H-indole (1) yield (98 %)
was synthesized by Heck-coupling of 5-bromo-indole (10 g,
1 mol) with 1-(vinyl sulfinyl)benzene (6.25 g, 37.1 mol) in
presence of palladium(II)acetate (0.17 g, 0.75 mol), tri-ortho
toloylphosphine (TOTP) (2.5 g, 0.82 mol) and triethylamine
10 g, 9.88 mol) in DMF (105 mL) as solvent. The whole
5
(
reaction mixture was heated to 100-115 °C for 3-4 h. The
reaction mass cooled to 80-85 °C to done the hot filtration.
The resulting filtrate mother liquor was quenched in 100 mL
of water present in 500 mL in Erlenmeyer flask fitted with
mechanical stirrer. The obtained aqueous layer transferred to
00 mL separating funnel and extracted with ethyl acetate (3
75 mL). The combined organics were washed with water
60 mL) and dried over anhydrous sodium sulphate (25 g).
The obtained yellow colour solid compound of 5-[(E)-2-
phenyl sulfonyl)vinyl]-1H-indole (6.5 g, 22.9 mol) after
concentration of the dried organic layer was directly taken for
olefin reduction in Parr apparatus with (8 g, 9.3 mol, 50 %
wet w/w) Raney-Nickel in methanol (100 mL). The catalytic
hydrogenation performed under hydrogen pressure (H
5 PSI) for 6-7 h under room temperature, after completion
5
×
(
(
2
, 70-
7
of the reaction by TLC analysis on silica gel with 40 % EtOAc-
hexane). The excess Raney-nickel removed by passing through
Celite 545 bed of Buchner flask (100 mL) filtration and
concentrated the filtrate mother liquor under reduced pressure
to afford the desired product 5-(2-(phenyl sulfonyl)ethyl)-1H-
indole [7] (1) (Scheme-I) (5.57 g, yield 85.2 %) as off-white
the product (2) spot has at R
(1) has R = 0.35 (blue) in the TLC plate. The chemical structure
obtained product was confirmed by its spectral analysis of H,
f
= 0.80 (blue) and starting material
powder after isolating in MTBE solvent (15 mL) and it has
the following spectral properties: H NMR (400 MHz, CDCl
f
1
1
3
)
13
1
δ: 2.91 (t, J = 2.7 Hz, 2H), 3.62 (t, J = 2.9 Hz, 2H), 6.30 (bs,
H), 6.89 (d, J = 8.3 Hz, 1H), 7.31 (m, 1H), 7.65 (t, J = 7.7
Hz, 1H), 7.74 (t, J = 7.3 1H), 7.96 (d, J = 5.3Hz, 1H), 10.96
C NMR, FT-IR, mass. H NMR (400 MHz, CDCl ) δ: 1.31
3
1
(t, J = 7.2 Hz, 3H), 2.75-2.80 (q, J = 7.2 Hz, 2H), 6.52 (m,
1H), 7.07 (d, J = 7.2 Hz, 1H), 7.17 (t, J = 7.2 Hz, 1H), 7.32
1
3
13
(
s, 1H). C NMR (100 MHz, CDCl3) δ: 28.34, 56.31, 100.67,
(d, J = 7.2 Hz, 1H), 7.49 (s, 1H), 8.04 (s, 1H). C NMR (100
1
1
2
11.31, 119.35, 121.54, 125.52, 127.67, 127.76, 129.33,
MHz, CDCl ) δ: 16.45, 28.92, 102.14, 110.70, 119.02, 122.53,
3
-1
-1
33.68, 134.71, 139.01. FT-IR (neat, cm ): 3179, 2924, 2855,
727, 1462, 1377, 721. Elemental analysis calculated for
11N: C, 82.72; H, 7.64; N, 9.65. MS calculated for [M-H]
85.36, found 284.00. The purity was determined to be 99.2
by HPLC chromatography.
Synthesis of 5-ethyl-1H-indole (2): A 250 mL clean and
124.20, 127.99, 134.18, 135.68. FT-IR (neat, cm ): 3179, 2924,
2855, 2727, 1462, 1377, 721. Elemental analysis calculated
+
C
10
H
for C10H11N: C, 82.72; H, 7.64; N, 9.65. MS calculated for
+
2
%
[M+H] 145.09, found 146.2. The purity was determined to
be 98.57 % by GC chromatography and as well as quantitative
NMR calculation.
flame dried three necked round bottomed flask, the center neck
was equipped with mechanical stirrer. The other two side necks
of were fitted with 5 cm glass thermo-pocket and water conden-
ser with nitrogen gas in-let tube to maintain inert atmosphere.
The flask allowed to cool to room temperature, then added 5-
O
S
Mg
O
N
N
H
-indole
Methanol
1
2
H
5
-(2-(Phenylsulfonyl)ethyl)-1
H
5-Ethyl-1
H
-indole
[
2-(phenyl sulfonyl)ethyl]-1H-indole (1) (15 g, 52.5 mmol,
.00 equiv), anhydrous methanol (450 mL, 30 vol) and addition
Scheme-II: Synthesis of 5-Ethyl-1H-indole from compound 1
1
O
S
O
Heck coupling
Pd(OAC)2
Raney-Nickel
Methanol
Br
O
S
S
O
O
N
H
TEA/DMF
TOTP
O
N
N
1
H
H
-indole
5
-(2-(phenylsulfonyl)ethyl)-1
H
5-Bromo-1
H
-indole
1-(Vinylsulfonyl)benzene
5-((E)-2-(phenylsulfonyl)vinyl)-1H-indole
Scheme-I: Synthesis of 5-(2-(phenyl sulfonyl)ethyl)-1H-indole