March 1998
SYNTHESIS
331
The same reaction was repeated at 110 °C and the results are listed in
the Table.
1
H NMR (400 MHz, CDCl ): d = 3.93 (s, 3 H, CH ), 7.06 (d, J =
3
3
8
6
.8 Hz, 2 H, ArH-3 + ArH-5), 8.71 (d, J = 8.8 Hz, 2 H, ArH-2 + ArH-
).
+
3
-Hydroxybenzonitrile (2b):
MS: m/z (%) = 133 (M , 68), 105 (62), 104 (100), 90 (55), 76 (14), 75
The standard procedure was followed by use of methyl 3-hydroxy- (12), 64 (19), 63 (19).
benzoate (1b; 105 mg, 0.691 mmol, 1.0 equiv), NaN(SiMe ) (1.7 The same reaction was repeated at 185 °C and the results are listed in
3
2
mL, 1.7 mmol, 2.5 equiv), and DMEU (0.50 mL) at 185 °C. The reac- the Table.
tion products were purified by column chromatography (silica gel,
4
0% EtOAc/hexanes) to give pure 2b (69.9 mg, 85%) as a colorless 2-Hydroxy-4-methoxybenzonitrile (2f):14
13a 13b
solid; mp 80–81 °C (MeOH) (lit. mp 79–81 °C); GC tR 12.56 The standard procedure was followed by use ofmethyl 4-methoxysal-
min; TLC R 0.40 (40% EtOAc/hexanes).
icylate (1f; 142 mg, 0.780 mmol, 1.0 equiv), NaN(SiMe ) (2.0 mL,
2.0 mmol, 2.5 equiv), and DMEU (0.50 mL) at 185 °C. The reaction
f
3 2
–1
IR (neat): n = 3307, 2242, 1586, 1481, 1286 cm .
1
H NMR (400 MHz, CDCl ): d = 5.46 (br s, 1 H, OH), 7. 11–7.15 (m, products were purified by column chromatography (silica gel, 40%
3
2
H, ArH-2 + ArH-4), 7.21 (d, J = 8.4 Hz, 1 H, ArH-6), 7.33 (dd, J = EtOAc/hexanes) to give pure 2f (105 mg, 90%) as a colorless solid;
8
.4, 8.4 Hz, 1 H, ArH-5).
mp 111–112 °C (MeOH) (lit.14 mp 111–113 °C); GC tR 11.65 min;
+
MS: m/z (%) = 119 (M , 100), 91 (22), 65 (12), 64 (17), 51 (10).
TLC R 0.36 (50% EtOAc/hexanes).
f
–
1
The same reaction was repeated at 110°C and the results are listed in IR (neat): n = 3219, 2228, 1613, 1514, 1326, 1278, 1213 cm .
the Table.
1
H NMR (400 MHz, CDCl ): d = 3.79 (s, 3 H, CH ), 6.43 (d, J =
3 3
8
.8 Hz, 1 H, ArH-5), 6.52 (s, 1 H, ArH-3), 7.36 (d, J = 8.8 Hz, 1 H,
4
-Hydroxybenzonitrile (2c):
ArH-6).
+
The standard procedure was followed by use of methyl 4-hydroxy- MS: m/z (%) = 149 (M , 100), 134 (9), 106 (67), 92 (13), 91 (38), 79
benzoate (1c; 132 mg, 0.868 mmol, 1.0 equiv), NaN(SiMe ) (2.2 (13), 63 (14), 52 (12), 51 (12).
3
2
mL, 2.2 mmol, 2.5 equiv), and DMEU (0.50 mL) at 185 °C. The re- The same reaction was repeated at 110°C and the results are listed in
action products were purified by column chromatography (silica gel, the Table.
4
0% EtOAc/hexanes) to give pure 2c (96.0 mg, 93%) as a colorless
13a 13b
mp 110–113 °C); GC tR 3,4-Dihydroxybenzonitrile (2g)15 and 4-Hydroxy-3-methoxyben-
zonitrile (2h):
IR (neat): n = 3218, 2229, 1613, 1597, 1514, 1449, 1436, 1379, 1326 The standard procedure was followed by use of methyl 3,4-dimethox-
solid; mp 111–112 °C (MeOH) (lit.
1.43 min; TLC R 0.35 (40% EtOAc/hexanes).
1
f
–1
cm .
ybenzoate (1g; 113 mg, 0.577 mmol, 1.0 equiv), NaN(SiMe )
3 2
1
H NMR (400 MHz, CDCl ): d = 6.30 (br s, 1 H, OH), 6.93 (d, J = 8.8 (2.8 mL, 2.8 mmol, 5.0 equiv), and DMEU (0.50 mL) at 185 °C. The
3
Hz, 2 H, ArH-3 + ArH-5), 7.53 (d, J = 8.8 Hz, 2 H, ArH-2 + ArH-6). reaction products were purified by column chromatography (silica
MS: m/z (%) = 119 (M , 100), 91 (21), 64 (20), 63 (25), 61 (10), 51 gel, 40% EtOAc/hexanes) to give pure 2g (49.1 mg, 63%) as a yellow
+
(
11).
solid and 2h (19.8 mg, 23%) as a yellow solid.
The same reaction was repeated at 110 °C and the results are listed in 2g: mp 155–157 °C (MeOH) (lit.15 mp 153–155 °C); TLC R
0.30
f
the Table. In addition, the standard procedure was followed by use of (50% EtOAc/hexanes).
ethyl 4-hydroxybenzoate (1h; 118 mg, 0.711 mmol, 1.0 equiv), IR (neat): n = 3276, 2228, 1603, 1519, 1444, 1284, 1115 cm .
–
1
1
NaN(SiMe ) (1.8 mL, 1.8 mmol, 2.5 equiv), and DMEU (0.50 mL)
H NMR (400 MHz, CDCl ): d = 6.89 (d, J = 8.8 Hz, 1 H, ArH-5),
3
3
2
at 185 °C. The reaction products were purified by column chromatog- 7.05 (d, J = 8.8 Hz, 1 H, ArH-6), 7.13 (s, 1 H, ArH-2).
+
raphy (silica gel, 40% EtOAc/hexanes) to give pure 2c (73.6 mg, MS: m/z (%) = 135 (M , 100), 117 (12), 106 (11), 89 (38), 79 (10), 62
8
7%) as a colorless solid.
Furthermore, the same reaction was repeated at 110°C and the results 2h: mp 87–88 °C (MeOH) (lit.1 mp 85–87 °C); GC t
TLC R 0.45 (50% EtOAc/hexanes).
(28), 52 (25), 51 (22).
3b
11.67 min;
R
are listed in the Table.
f
–
1
IR (neat): n = 3364, 2955, 2225, 1599, 1515, 1458, 1423, 1271 cm .
1
H NMR (400 MHz, CDCl ): d = 3.93 (s, 3 H, CH ), 6.98 (d, J = 8.0
3
3
2
-Methoxybenzonitrile (2d):
Hz, 1 H, ArH-5), 7.09 (s, 1 H, ArH-2), 7.23 (d, J = 8.0 Hz, 1 H, ArH-
The standard procedure was followed by use of methyl 2-methoxy-
benzoate (1d; 116 mg, 0.699 mmol, 1.0 equiv), NaN(SiMe3)2
6
).
MS: m/z (%) = 149 (M , 91), 134 (100), 106 (80), 77 (8), 63 (9), 51
16).
+
(1.7 mL, 1.7 mmol, 2.5 equiv), and DMEU (0.50 mL) at 110°C. The
(
reaction products were purified by column chromatography (silica
gel, 40% EtOAc/hexanes) to give pure 2a (49.9 mg, 60%) as a color-
less solid and 2d (20.5 mg, 22%) as a colorless liquid.1
-Hydroxy-4-methoxybenzonitrile (2i):16
3
3b
The standard procedure was followed by use of methyl 3,4-dimeth-
oxybenzoate (1g; 102 mg, 0.520 mmol, 1.0 equiv), NaN(SiMe3)2
2
d: GC t 9.96 min; TLC R 0.43 (40% EtOAc/hexanes).
R f
IR (neat): n – 3080, 3015, 2975, 2949, 2843, 2228, 1599, 1580, 1494,
(2.6 mL, 2.6 mmol, 5.0 equiv), and DMEU (0.50 mL) at 110 °C. The
–1
1
465, 1437 cm .
reaction products were purified by column chromatography (silica
1
H NMR (400 MHz, CDCl ): d = 3.94 (s, 3 H, OCH ). 6.97–7.03 (m,
3
3
gel, 50% EtOAc/hexanes) to give pure 2h (42.7 mg, 55%) as a yellow
2
H, ArH-3 + ArH-5), 7.53–7.57 (m, 2 H, ArH-4 + ArH-6).
13a
solid and 2i (13.9 mg, 18%) as a yellow solid.
+
MS: m/z (%) = 133 (M , 100), 105 (62), 104 (100), 90 (49),76 (15),
5 (14), 63 (24).
16
2
i: mp 129–130°C (MeOH) (lit. mp 130–132°C); GC t 12.03 min;
R
7
TLC R 0.42 (50% EtOAc/hexanes).
f
The same reaction was repeated at 185 °C and the results are listed in
the Table.
IR (neat): n = 3385, 3078, 3027, 2984, 2950, 2227, 1732, 1605, 1591,
–1
1
515, 1458, 1447, 1421, 1378 cm .
1
H NMR (CDCl , 400 MHz): d = 3.97 (s, 3 H, CH ), 5.74 (bs, 1 H,
OH), 6.89 (d, J = 8.8 Hz, 1 H, ArH-5), 7. 17 (s, 1 H, ArH-2), 7.19 (d,
3
3
4
-Methoxybenzonitrile (2e):
The standard procedure was followed by use of methyl 4-methoxy- J = 8.8 Hz, 1 H, ArH-6).
+
benzoate (1e; 134 mg, 0.807 mmol, 1.0 equiv), NaN(SiMe ) (2.0 MS: m/z (%) = 149 (M , 100), 134 (10), 119 (23), 107 (17), 106 (73),
3
2
mL, 2.0 mmol, 2.5 equiv), and DMEU (0.50 mL) at 110 °C. The reac- 92 (16), 91 (44), 78 (14), 77 (10), 63 (16), 51 (10).
tion products were purified by column chromatography (silica gel,
4
0% EtOAc/hexanes) to give pure 2c (56.6 mg, 59%) as a colorless 3-Cyanoindole (4):
13a
solid and 2e (27.9 mg, 26%) as a yellow solid.
The standard procedure was followed by use of methyl indole-3-
e: mp 56–57 °C (MeOH) (lit.1 mp 57–59 °C); GC t 7.85 min; TLC carboxylate (3; 115 mg, 0.657 mmol, 1.0 equiv), NaN(SiMe
) (1.6 mL,
R
3 2
3b
2
Rf 0.41 (4O% EtOAc/hexanes).
IR (neat): n – 2949, 2724, 2580, 2231, 1604, 1591, 1503, 1455 cm
1.6 mmol, 2.5 equiv), and DMEU (0.50 mL) at 185 °C. The reaction
products were purified by column chromatography (silica gel, 40%
–1.