4520 J . Org. Chem., Vol. 65, No. 15, 2000
Kayaleh et al.
(7.34 mmol), 1.09 g of 4-methoxyphenylacetonitrile (7.41
mmol), and 22.1 mL of LDA (44.2 mmol) was obtained 0.171
g of the 3-aminoindenone (8%). Mp: 184-186 °C. δ H NMR
(DMSO-d6): 3.76 (3H, s); 3.83 (3H, s); 6.94 (2H, d, J ) 8.79
Hz); 7.05 (1H, d, J ) 8.14 Hz); 7.31-7.42 (4H, m); 7.58 (2H,
br). δ 13C NMR (DMSO-d6): 55.0; 55.7; 104.2; 111.7; 113.6;
116.2; 118.0; 125.3; 129.3; 132.9; 141.0; 154.1; 156.0; 159.0;
189.5. MS: M+ ) 281. HRMS: calcd for C17H15NO3 281.1052,
found 281.1057.
(44.0 mmol) there was obtained 0.510 g of the cyclized product
(22%). Mp: 284-287 °C. δ 1H NMR (DMSO-d6): 3.76 (3H, s);
6.97 (2H, d, J ) 8.50 Hz); 7.42-7.51 (2H, m); 7.85-8.02 (5H,
m); 8.82-8.85 (1H, d, J ) 8.36 Hz). MS: M+)301; HRMS:
calcd for C20H15NO2 301.1103, found 301.1099
1
5-Am in o-6-(4-m et h oxyp h en yl)-2-p yr in d in -7-on e (16).
From 1.14 g of ethyl nicotinate (7.35 mmol), 1.08 g of
4-methoxyphenylacetonitrile (7.37 mmol), and 44.3 mL of LDA
(88.6 mmol) was obtained 0.610 g of the cyclized product (33%).
Mp: 263.5-264.5 °C. δ 1H NMR (DMSO-d6): 3.78 (3H, s); 6.99
(2H, d, J ) 8.65 Hz); 7.44 (2H, d, J ) 8.68 Hz); 7.70 (1H, d, J
) 4.63 Hz); 8.11 (2H, br); 8.41 (1H, s); 8.73 (1H, d, J ) 4.70
Hz). δ 13C NMR (DMSO-d6): 55.0; 104.7; 113.6; 113.8; 124.2;
127.9; 129.6; 138.9; 147.0; 154.1; 157.3; 159.0; 189.8. MS: M+
) 252. HRMS: calcd for C15H12N2O2 252.0899, found 252.0902.
5-Am in o-6-(4-m eth oxyp h en yl)-1-p yr in d in e-7-on e (23).
From 1.11 g of ethyl picolinate (7.34 mmol), 1.08 g of 4-meth-
oxyphenylacetonitrile (7.37 mmol), and 22.2 mL of LDA (44.4
mmol) was obtained 1.83 g of the cyclic product (99%). Mp:
3-Am in o-2-(3-m eth oxyp h en yl)-5-m eth oxy-1-in d en on e
(Ta ble 1, En tr y 10). From 1.25 g of methyl 4-methoxyben-
zoate (7.52 mmol), 1.05 g of 3-methoxyphenylacetonitrile (7.13
mmol), and 14.3 mL of LDA (28.6 mmol) there was obtained
0.152 g of the 3-amino-indenone (7.5%). Mp: 250-251 °C. δ
1H NMR (DMSO-d6): 3.78 (3H, s); 3.83 (3H, s); 6.74 (1H, d, J
) 7.77 Hz); 6.83 (1H, d, J ) 2.09 Hz); 7.08 (2H, s); 7.23-7.31
(2H, m); 7.44 (1H, s); 7.84 (2H, br). δ 13C NMR (DMSO-d6):
54.8; 55.8; 103.8; 107.5; 110.5; 112.4; 113.3; 120.3; 120.9; 127.5;
129.1; 134.3; 141.6; 159.8; 160.2; 189.8. MS: M+ ) 281.
HRMS: calcd for C17H15NO3 281.1052, found 281.1041.
3-Am in o-2-(3,4-d im et h oxyp h en yl)-5-m et h oxy-1-in d e-
n on e (Ta ble 1, En tr y 12). From 1.88 g of methyl 4-meth-
oxybenzoate (11.3 mmol), 2.04 g of 3,4-dimethoxyphenylace-
tonitrile (11.5 mmol), and 34.0 mL of LDA (68.0 mmol) there
was obtained 0.973 g of the 3-aminoindenone (27%). Mp: 270-
272 °C. δ 1H NMR (DMSO-d6): 3.78 (3H, s); 3.81 (3H, s); 3.92
(3H, s); 6.78 (1H, d, J ) 1.80 Hz); 6.82 (2H, s); 7.08 (1H, s);
7.22 (1H, d, J ) 7.85 Hz); 7.39 (1H, s); 7.77 (2H, br). δ 13C
NMR (DMSO-d6): 55.2; 55.6; 103.9; 107.4; 112.0; 120.4; 120.6;
125.7; 127.1; 141.0; 146.5; 148.4; 159.5; 162.3; 188.6. MS: M+
) 311; HRMS: calcd for C18H17NO4 311.1157, found 311.1162.
3-Am in o-2-(4-m eth oxyp h en yl)-4,5,6-tr im eth oxy-1-in d e-
n on e (Ta ble 1, En tr y 13). From 3.40 g of methyl 3,4,5-
trimethoxybenzoate (15.0 mmol), 2.17 g of 4-methoxyphenyl-
acetonitrile (14.7 mmol), and 44.3 mL of LDA (88.6 mmol)
there was obtained 2.36 g of the 3-aminoindenone (45%). Mp:
182-184 °C. δ 1H NMR (DMSO-d6): 3.76 (3H, s); 3.80 (3H, s);
3.88 (3H, s); 3.99 (3H, s); 6.89 (1H, s); 6.95 (2H, d, J ) 8.57
Hz); 7.37 (2H, d, J ) 8.59 Hz). δ 13C NMR (DMSO-d6): 55.0;
56.4; 60.5; 61.4; 101.9; 113.7; 119.6; 125.0; 129.0; 131.4; 143.7;
148.3; 156.7; 157.5; 161.5; 189.1. MS: M+ ) 341. HRMS: calcd
for C19H19NO5 341.1250, found 341.1256.
1
258.5-260 °C. δ H NMR (DMSO-d6): 3.78 (3H, s); 7.00 (2H,
d, J ) 8.23 Hz); 7.35 (1H, t, J ) 12.4 Hz); 7.44 (2H, d, J )
8.22 Hz); 7.99 (1H, d, J ) 7.30 Hz); 8.24 (2H, br); 8.44 (1H, d,
J ) 4.97 Hz). δ 13C NMR (DMSO-d6): 55.1; 104.2; 113.8; 124.4;
125.1; 133.6; 149.6; 154.8; 157.2; 159.6; 188.9. MS: M+ ) 252.
HRMS: calcd for C15H12N2O2 252.0899, found 252.0905.
Tw o-Step Rea ction . (a ) Keto Nitr iles. The requisite
amount of the nitrile was dissolved in THF, and 2 equiv of
NaH was added to the solution, followed by 1 equiv of the
aromatic ester. The mixture was then brought to reflux. After
the reaction was complete as judged by TLC, it was cooled and
brought to ice temperature. Water was added, and the bulk of
THF was removed under reduced pressure. The aqueous layer
was washed with dichloromethane and then acidified with 1
M HCl to give a precipitate. This was extracted with dichlo-
romethane, and the extracts were washed with saturated
sodium bicarbonate and then with water. The organic layer
was dried with magnesium sulfate, filtered, and concentrated
under reduced pressure to give an oil. The latter (keto-nitrile)
was either used as such for the next step or triturated with
hexane/ethyl acetate to yield the solid product. (b) Cycliza -
tion of Keto Nitr iles. The requisite amount of keto nitrile
was added to 4 equiv of LDA at -10 °C. The reaction was left
to stir overnight. After it was complete, it was worked up the
same way as per the one-stage reaction.
3-Am in o-2-m eth yl-1-in d en on e (Ta ble 2, En tr y 1). From
1.05 g of ethyl benzoate (7.00 mmol), 0.380 g of propionitrile
(6.91 mmol), and 21.0 mL of LDA (42.0 mmol) there was
obtained 0.910 g of the 3-aminoindenone (83%). Mp: 222-223
°C. δ 1H NMR (DMSO-d6): 1.56 (3H, s); 7.14 (1H, d, J ) 6.92
Hz); 7.21-7.33 (2H, m); 7.43 (1H, d, J ) 4.38 Hz); 7.53 (2H,
br). δ 13C NMR (DMSO-d6): 6.0; 99.2; 117.5; 129.3; 130.3;
135.8; 138.8; 162.5; 191.4. MS: M+ ) 159. HRMS: calcd for
3-Am in o-2-(4-m eth oxyp h en yl)-5-m eth oxy-1-in d en on e
(Ta ble 1, En tr y 1). From 6.14 g of methyl 4-methoxybenzoate
(36.9 mmol), 5.42 g of 4-methoxyphenylacetonitrile (36.8
mmol), and 2.98 g of NaH (74.5 mmol), 7.60 g of the keto
nitrile11 was obtained (74%). Second step: From 7.60 g of the
keto nitrile (27.0 mmol) and 61.0 mL of LDA (122.0 mmol) was
obtained 6.10 g of the 3-aminoindenone (80%). Overall yield:
59%.
3-Am in o-2-(4-m eth oxyph en yl)-1-in den on e (Table 1, En -
tr y 2). From 1.06 g of methyl benzoate (7.78 mmol), 1.11 g of
4-methoxyphenylacetonitrile (7.54 mmol), and 0.790 g of NaH
(19.8 mmol) there was obtained 1.35 g of the keto nitrile11
(64%). Second step: From 0.700 g of the keto nitrile (2.79
mmol) and 6.00 mL of LDA (12.0 mmol) was obtained 0.610 g
of the 3-aminoindenone (87%). Overall yield: 55.5%.
3-Am in o-2-(2-m eth oxyp h en yl)-5-m eth oxy-1-in d en on e
(Ta ble 1, En tr y 3). From 5.64 g of methyl 4-methoxybenzoate
(33.9 mmol), 5.00 g of 2-methoxyphenylacetonitrile (34.0
mmol), and 2.76 g of NaH (69.0 mmol) there was obtained 8.10
g of the keto nitrile12 (85%). Second step: From 7.64 g of the
keto nitrile (27.2 mmol) and 54.4 mL of LDA (108.8 mmol) was
obtained 6.08 g of the 3-amino-indenone (80%). Overall yield:
69%.
C
10H9NO 159.0684, found 159.0689.
3-Am in o-2-eth yl-5-m eth oxy-1-in d en on e (Ta ble 2, En tr y
2). From 1.93 g of methyl 4-methoxybenzoate (11.6 mmol),
0.790 g of butyronitrile (11.5 mmol), and 34.5 mL of LDA (69.0
mmol) there was obtained 1.05 g of the 3-aminoindenone
1
(49%). Mp: 205-207 °C. δ H NMR (DMSO-d6): 0.93 (3H, t,
J ) 14.8 Hz); 2.13 (2H, quadruplet; J ) 17.2 Hz); 3.77 (3H, s);
6.68 (1H, dd, J ) 9.87 Hz; J ) 5.72 Hz); 7.07 (1H, d, J ) 3.80
Hz); 7.15 (1H, s); 7.42 (2H, br). δ 13C NMR (DMSO-d6): 15.6;
16.0; 55.5; 106.3; 109.0; 110.6; 119.8; 127.7; 141.4; 160.0; 161.9;
191.1. MS: M+ ) 203; HRMS: calcd for C12H13NO2 203.0946,
found 203.0943.
3-Am in o-2-th iop h en yl-5-1-in d en on e (Ta ble 2, En tr y 3).
From 1.06 g of phenylthioacetonitrile (7.11 mmol), 1.07 g of
ethyl benzoate (7.13 mmol), and 14.3 mL of LDA (28.6 mmol)
there was obtained 0.300 g of the 3-aminoindenone (17%).
1
Mp: 190-191 °C. δ H NMR (DMSO-d6): 7.07 (3H, dd, J )
9.00 Hz; J ) 6.30 Hz); 7.22 (2H, t, J ) 15.3 Hz); 7.40 (1H, m);
7.48-7.51 (2H, m); 7.78 (1H, dd, J ) 8.40 Hz; J ) 4.80 Hz). δ
13C NMR (DMSO-d6): 88.3; 119.8; 120.0; 124.6; 125.0; 128.8;
131.3; 131.4; 135.7; 136.7; 138.6; 169.8; 189.0. MS: M+ ) 253.
HRMS: calcd for C15H11NOS 253.0561, found 253.0563.
3-Am in o-2-(4-m eth oxyp h en yl)-1-[ben z][e]-1-in d en on e
(12). From 1.50 g of 1-ethylnaphthoate (7.50 mmol), 1.08 g of
4-methoxyphenylacetonitrile (7.37 mmol), and 22.0 mL of LDA
3-Am in o-2-(2-m eth oxyph en yl)-1-in den on e (Table 1, En -
tr y 4). From 5.40 g of methyl benzoate (39.7 mmol), 5.88 g of
2-methoxyphenylacetonitrile (38.7 mmol), and 3.22 g of NaH
(11) Cook, C. E.; Corley, R. C.; Wall, M. E. J . Org. Chem. 1965, 30,
4114.
(12) Chatterjea, J . N. J . Ind. Chem. Soc. 1970, 47, 4261.