618
B. Pete, F. Varga and J. Kovács
Vol. 42
3-(2-Chloroethyl)-7-sulfomethyl-1H-indole-2-carboxylic Acid
Ethyl Ester (1c).
The sulfonate salt (1a-c, 1 mmol) was stirred in
dichloromethane (25 mL) containing dimethylformamide (0.06
mL) and thionyl chloride (1 mL, 14 mmol) at room temperature
until the suspension became almost a clear solution (ca. 4 hours).
In case of 1d chloroform was used at reflux temperature. The
solutions were filtered and the filtrate was evaporated to dryness
to give 3a-d as crystalline solids in almost quantitative yields.
The chloromethylindoles 3a-d decomposed quickly when
exposed to atmospheric moisture.
This compound was obtained as beige crystals, 1.22 g (60%),
1
mp 234-236°; ir (KBr) : 3448, 1684, 1220; H nmr (DMSO-d ):
6
1.32 (t, 3H, J = 7.0 Hz), 3.33 (m, 2H), 3.71 (m, 2H), 4.30 (s, 2H),
4.34 (q, 2H, J = 7.0 Hz), 7.03 (dd, 1H, J = 7.5, 8.2 Hz), 7.17 (d,
13
1H, J = 6.9 Hz), 7.56 (d, 1H, J = 8.2 Hz), 11.17 (s, 1H); C nmr
(DMSO-d ): 12.73, 26.65, 42.89, 53.51, 58.80, 117.41, 117.54,
6
117.77, 118.50, 122.53, 125.86, 126.27, 134.31, 159.97.
Anal. Calcd. for C
Found: C, 48.41 H, 4.58 N, 3.95.
H ClNO S: C, 48.63 H, 4.66 N, 4.05.
3-[2-(Methoxycarbonyl)ethyl]-7-chloromethyl-1H-indole-2-car-
boxylic Acid Ethyl Ester (3a).
14 16 5
1
3-[2-(Dimethylamino)ethyl]-7-sulfomethyl-1H-indole-2-car-
boxylic Acid Ethyl Ester (1d).
This compound was obtained as beige solid, 0.29 g (90%); H
nmr (CDCl ): 1.44 (t, 3H, J = 7.0 Hz), 2.70 (m, 2H), 3.43 (m,
3
2H), 3.66 (s, 3H), 4.46 (q, 2H, J = 7.0 Hz), 4.90 (s, 2H), 7.11 (dd,
This compound was obtained as white crystals, 1.33 g (71%),
1H, J = 7.3, 7.7 Hz), 7.28 (d, 1H, J = 7.2 Hz), 7.73 (d, 1H, J = 8.0
1
mp 282-285°; ir (KBr) : 3448, 1681, 1218; H nmr (D O): 1.41
2
13
Hz), 9.24 (s, 1H); C nmr (CDCl ): 14.46, 20.52, 35.17, 43.66,
3
(t, 3H, J = 7.0 Hz), 2.92 (s, 6H), 3.42 (m, 2H), 3.48 (m, 2H), 4.43
(q, 2H, J = 7.0 Hz), 4.57 (s, 2H), 7.24 (dd, 1H, J = 7.6, 8.1 Hz),
51.68, 61.19, 120.29, 120.81, 121.90, 123.26, 124.20, 126.03,
128.55, 134.38, 162.12, 173.59.
13
7.39 (d, 1H, J = 7.9 Hz), 7.73 (d, 1H, J = 7.7 Hz); C NMR
(DMSO-d ): 15.01, 20.38, 43.14, 55.27, 57.44, 61.62, 117.90,
119.62, 120.12, 121.15, 124.70, 127.94, 128.68, 136.45, 162.23.
3-[3-(Methoxycarbonyl)propyl]-7-chloromethyl-1H-indole-2-
carboxylic Acid Ethyl Ester (3b).
6
Anal. Calcd. for C
Found: C, 54.02 H, 6.19 N, 7.84.
H N O S: C, 54.22 H, 6.26 N, 7.90.
16 22 2 5
This compound was obtained as beige solid, 0.32 g (94%);
1
H nmr (CDCl ): 1.48 (t, 3H, J = 7.0 Hz), 2.06 (m, 2H), 2.41
3
General Procedure for the Esterification of Carboxylic Acids 1a,
1b.
(m, 2H), 3.20 (m, 2H), 3.67 (s, 3H), 4.45 (q, 2H, J = 7.0 Hz),
4.91 (s, 2H), 7.13 (dd, 1H, J = 7.3, 7.9 Hz), 7.26 (d, 1H, J = 7.2
13
Hz), 7.72 (d, 1H, J = 8.1 Hz), 8.98 (s, 1H); C nmr (CDCl ):
3
To methanol (200 mL) cooled to -25 °C was added thionyl
chloride (10 mL) at the same temperature over a period of 0.5
hour and kept for additional 0.5 hour at -25 °C. Indolylmethane-
sulfonic acid 11 or 12 (30 mmol) was added as a solid and the
reaction mixture was allowed to reach room temperature and
stirred for 24 hours. The clear solution was evaporated to dryness
to give 1a or 1b quantitatively.
14.50, 24.07, 25.97, 33.69, 43.70, 51.53, 61.05, 120.14,
120.70, 121.96, 124.08, 124.25, 125.92, 128.86, 134.42,
162.28, 174.05.
3-(2-Chloroethyl)-7-chloromethyl-1H-indole-2-carboxylic Acid
Ethyl Ester (3c).
1
This compound was obtained as white solid, 0.28 g (92%); H
3-[2-(Methoxycarbonyl)ethyl]-7-sulfomethyl-1H-indole-2-car-
boxylic Acid Ethyl Ester (1a).
nmr (CDCl ): 1.48 (t, 3H, J = 7.0 Hz), 3.59 (m, 2H), 3.80 (m,
2H), 4.48 (q, 2H, J = 7.0 Hz), 4. 92 (s, 2H), 7.16 (dd, 1H, J = 7.2
3
Hz, 8.1 Hz), 7.29 (d, 1H, J = 7.2 Hz), 7.74 (d, 1H, J = 8.3 Hz),
This compound was obtained as white crystals, 10.20 g (92%),
13
9.18 (s, 1H); C nmr (CDCl ): 14.51, 28.56, 43.63, 44.34,
1
3
mp 188-192°; ir (KBr) : 1726, 1677, 1209; H nmr (D O): 1.52
2
61.41, 120.64, 120.68, 120.88, 121.92, 124.69, 126.21, 128.86,
134.25, 161.90.
(t, 3H, J = 7.0 Hz), 2.75 (m, 2H), 3.37 (m, 2H), 3.68 (s, 3H), 4.50
(q, 2H, J = 7.0 Hz), 4.53 (s, 2H), 7.28 (dd, 1H, J = 7.4, 7.5 Hz),
13
7.44 (d, 1H, J = 7.2 Hz), 7.76 (d, 1H, J = 8.3 Hz); C nmr (D O):
3-[2-(Dimethylamino)ethyl]-7-chloromethyl-1H-indole-2-car-
boxylic Acid Ethyl Ester (3d).
2
13.48, 19.96, 34.66, 52.02, 53.40, 61.65, 115.97, 120.03, 120.29,
122.49, 123.28, 127.41, 128.13, 135.36, 163.07, 175.82.
1
This compound was obtained as white solid, 0.22 g (72%); H
Anal Calcd. for C
H NO S: C, 52.02; H, 5.18; N, 3.79.
16 19 7
nmr (DMSO-d ): δ 1.41 (t, 3H, J = 7.0 Hz), 2.83 (s, 3H), 2.84 (s,
6
Found: C, 51.80; H, 5.21; N, 3.71.
3H), 3.19 (m, 2H), 3.51 (m, 2H), 4.43 (q, 2H, J = 7.0 Hz), 5.22 (s,
3-[3-(Methoxycarbonyl)propyl]-7-sulfomethyl-1H-indole-2-car-
boxylic Acid Ethyl Ester (1b).
2H), 7.15 (dd, 1H, J = 7.5, 7.4 Hz), 7.40 (d, 1H, J = 6.9 Hz), 7.88
13
(d, 1H, J = 8.2 Hz), 11.83 (s, 1H); C nmr (DMSO-d ): δ 14.30,
6
19.75, 41.81, 42.96, 56.26, 60.72, 117.73, 120.13, 121.11,
122.09, 124.59, 126.78, 127.59, 134.37, 161.35.
This compound was obtained as white crystals, 10.80 g (94%),
1
mp 152-154°; ir (KBr) : 1728, 1683, 1203; H nmr (DMSO-d ):
6
1.33 (t, 3H, J = 7.0 Hz), 1.86 (m, 2H), 2.32 (m, 2H), 3.06 (m, 2H),
3.57 (s, 3H), 4.20 (s, 2H), 4.33 (q, 2H, J = 7.0 Hz), 7.01 (dd, 1H,
General Procedure for the Preparation of Methoxymethylindoles
4 and 5.
J = 7.3, 7.5 Hz), 7.14 (d, 1H, J = 7.1 Hz), 7.54 (d, 1H, J = 8.0 Hz),
The sulfonate salt 11 or 12 (1 mmol) was stirred in
dichloromethane (20 mL) containing dimethylformamide (0.06
mL) and thionyl chloride (0.5 mL, 7 mmol) at room temperature
until the suspension became almost a clear solution (ca. 4 hours).
The solution was filtered and evaporated to dryness. The solid
residue was dissolved in methanol (15 mL) and left standing at
room temperature for 1 hour. Methanol was evaporated and the
solid residue was recrystallised from hexane.
13
11.20 (s, 1H); C nmr (DMSO-d +CDCl ): 14.91, 24.08, 26.47,
6
3
33.59, 51.86, 55.69, 60.79, 119.54, 120.33, 123.44, 123.77,
127.92, 128.29, 136.60, 162.32, 173.90.
Anal. Calcd. for C
H NO S: C, 53.25; H, 5.52; N, 3.65.
17 21 7
Found: C, 53.03; H, 5.41; 3.55.
General Procedure for the Reaction of Sulfonic Acids 1a-d with
Thionyl Chloride.