1384
R. S. Kumar and P. T. Perumal
Vol 43
soluble, the yield dropped substantially due to polymer-
izations of starting material in the acidic medium.
However in water because of heterogeneity of the reaction
mixture such polymerization does not take place and the
desired reaction proceeds smoothly giving the Michael
adduct in good to excellent yeilds.
Table 1
Time(h) Yeild(%)a
S.No
1
Michael adduct
Ph
Indole
Olefin
NO2
NO2
65
76
1.0
2.0
Ph
N
H
N
H
Ph
NO2
NO2
NO2
Scheme 1
NO2
2
N
Ph
N
R3
R4
R3
EWG
Ph
KHSO4
EWG
94
1.5
+
R4
RT, H2O
R2
N
NO2
R2
N
Ph
R1
3
4
5
6
N
R1
H
N
1
H
Ph
2 a - j
R1 = H, Me
R4 = Ph,H,
MeO
2.5
75
60
MeO
NO2
NO2
R
R
2 = H, Me
3 = Br, OMe
EWG = NO2, COR
Ph
Ph
N
H
N
H
Ph
NO2
Br
Br
In summary we have developed
a simple and
10.0
environmental friendly protocol for the Michael addition
of indoles using water as solvent. This protocol eliminates
the use of hazardous organic solvents and is operationally
simple since the product can be easily isolated by a simple
phase separation and the aqueous solution containing the
catalyst can be reused.
N
N
H
H
O
O
3.0
3.0
85
90
N
H
N
H
O
O
7
N
H
N
H
EXPERIMENTAL
O
MeO
O
MeO
3.0
24
96
Representative Experimental Procedure.
8
9
N
H
N
To 0.260 g (1.74 mmol) of ꢀ-nitrostyrene in water (10
mL) was added KHSO4 0.07 g (30 mol%) and the mixture
stirred for 5 min and then 2-methylindole 0.256 g (1.74
mmol) was added and the stirring was continued and the
progress of the reaction was monitored by TLC. After
completion of the reaction, reaction mixture was extracted
with ethyl acetate (3x10mL) and ethylacetate was dried over
anhydrous sodium sulphate, filtered and concentrated under
reduced pressure and the residue was column chromato-
graphed over silica gel using ethylacetate / pet-ether
(9.5/0.5) as eluent to get the pure product 0.45g (94%) yield.
H
O
O
50b
N
H
N
H
O
O
10
80b
N
H
24
N
H
a.Isolated yields after coloumn chromatography; b 20mol % of catalyst
is used.
Spectral Data for Selected Compounds.
1
(2a): Viscous oil; IR 3400, 3050, 1550, 1373 cm-1; H NMR
32.9, 41.6, 77.4, 109.6, 112.8, 119.1, 119.6, 122.3, 126.5, 126.6,
127.6 127.8, 129.0, 137.3, 139.4
(2f): Pale orange solid m.p. 71– 73˚C; IR 3014, 2880, 1695
(500MHz, CDCl3): ꢁ 8.08 (brs, NH, 1H), 7.46(d, J = 8.05 Hz,
1H,), 7.34-7.31(m, 5H), 7.28-7.27(m, 1H), 7.21( t, J = 8.05 Hz,
1H), 7.09(t, J = 8.0Hz, 1H,), 6.98(d, J = 2.25Hz, 1H,), 5.19(t, J
F= 8.0Hz, 1H,), 5.01(dd, J = 7.45, 12.6Hz, 1H,), 4.94(dd, J =
8.05, 12.6Hz, 1H,). 13C NMR (125MHz, CDCl3): ꢁ 41.7, 77.4,
111.5, 114.4, 119.0, 120.0, 121.7, 122.7, 126.2, 127.6, 127.8
129.0, 136.5, 139.3.
1
1412 cm-1; H NMR (500MHz, CDCl3): ꢁ 8.12(brs, NH, 1H),
7.60(d, J = 8.4Hz, 1H), 7.34(d, J = 8.4 Hz, 1H), 7.23-7.13(m, 2H),
6.95(brs, 1H,), 3.07(t, J = 7.65 Hz, 2H), 2.85 (t, J = 7.65 Hz, 2H),
2.15 (s, 3H). 13CNMR (125MHz,CDCl3): ꢁ 209.2, 136.4, 127.2,
122.1, 121.6, 119.3 118.7,115.1, 111.3, 44.2, 30.1,19.4.
1
(2j): Viscous oil; IR 3380,2860,1704,1473 cm-1; H NMR
(2b): Colourless solid, m.p 72 °C; IR 3058, 2918,1551,1469
1
cm-1; H NMR (500MHz, CDCl3): ꢁ 7.48(d, J = 8.0Hz, 1H,),
(500MHz, CDCl3): ꢁ 7.89(brs, NH, 1H), 7.59(d, J = 7.65Hz,
1H), 7.25(d, J = 7.60Hz, 1H), 7.12-7.06(m, 2H), 3.44(t, J =
12.2Hz, 1H), 3.15(t, J = 12.2Hz, 1H), 2.66-2.64(m, 3H), 2.35(s,
3H), 2.18-2.04 (m, 4H,).13C NMR (125MHz, CDCl3): ꢁ 214.7,
7.37-7.25(m, 7H), 7.09(d, J = 8.0Hz, 1H), 6.87(s, 1H), 5.20(d, J
= 8.05, 1H), 5.05(dd, J = 8.05, 12.6Hz, 1H), 4.94(dd, J =
8.55,12.6Hz,1H,), 3.74(s, 3H). 13C NMR (125MHz, CDCl3): ꢁ