426
S. M. Huber, A. Hennig, F. G. Pu¨hlhofer, and R. Weiss
Vol 46
Phen), 126.2 (CH, Phen), 129.8 (CH, Phen), 130.0 (CH, Phen),
132.0 (C q, Phen), 132.9 (C q, Phen), 134.9 (CH, Phen), 135.6
(C q, Phen),136.2 (C q, Phen), 146.3 (C q, Phen), 158.0 (C q),
160.7 (C q); IR (KBr): 3202, 3025, 2918, 1657, 1602, 1569,
1542, 1511, 1500, 1469, 1449, 1333, 1305, 1248, 1197, 1172,
1101, 1035, 939, 860, 840, 820, 735, 718, 578, 510cmꢀ1; MS
(FABþ): m/z: 340[Mþþ1]; elemental analysis calcd for
C23H21N3: C 81.38, H 6.24, N 12.38; found C 80.86, H 6.24,
N 12.33.
3-(4-Methoxyphenylimino)-5-methoxy-N-(4-methoxyphenyl)-
3H-indol-2-amine 3c. Violet solid; 1H NMR (CDCl3): d ¼
3.57 (s, 3H, CH3), 3.79 (s, 3H, CH3), 3.84 (s, 3H, CH3), 6.54
(d, J ¼ 2.45 Hz, 1H, Phen), 6.76 (dd, J ¼ 8.43, 2.54 Hz, 1H,
Phen), 6.94 (m, 4H, Phen), 7.06 (d, J ¼ 8.95 Hz, 3H, Phen),
7.74 (m, 3H, Phen, NH); 13C NMR (CDCl3): d ¼ 55.5 (CH3),
55.6 (CH3), 112.4 (CH, Phen), 114.4 (CH, Phen), 114.5 (CH,
Phen), 118.1 (CH, Phen), 118.8 (CH, Phen), 120.2 (C q,
Phen), 120.3 (CH, Phen), 121.0 (CH, Phen), 132.0 (C q,
Phen), 141.3 (C q, Phen), 155.2 (C q, Phen), 155.6 (C q,
Phen), 156.1 (C q, Phen), 157.5 (C q, Phen), 158.0 (C q),
159.6 (C q); IR (KBr): 3338, 3000, 2946, 2829, 1632, 1608,
1579, 1542, 1506, 1468, 1435, 1299, 1285, 1238, 1212, 1184,
1172, 1132, 1106, 1038, 1024, 879, 852, 823, 801, 771, 739,
636, 589, 503 cmꢀ1; MS (FABþ): m/z: 388[Mþþ1]; elemental
analysis calcd for C23H21N3O3: C 71.30, H 5.46, N 10.85;
found C 70.68, H 5.45, N 10.57.
20 min. After cooling to RT the solvent was evaporated to
dryness in vacuo. The orange residue was then taken up in
water, filtrated, washed with water and dried under vacuum.
Isatine 4a. Orange solid; 1H NMR (Aceton-d6): d ¼ 7.02
(d, J ¼ 7.92 Hz, 1H, H4), 7.11 (t, J ¼ 7.5 Hz, 1H, H5), 7.52
(d, J ¼ 7.23 Hz, 1H, H7), 7.62 (t, J ¼ 7.71 Hz, 1H, H6),
10.00 (s, 1H, NH); 13C NMR (Aceton-d6): d ¼ 113.3 (C7),
119.3 (C3a), 124.2 (C5), 125.7 (C4), 139.6 (C6), 151.8 (C7a),
160.2 (C2), 185.3 (C3); IR (KBr): 3192, 1730, 1618, 1461,
1332, 1202, 1144, 1096, 947, 771, 661, 638, 480, 456 cmꢀ1
;
MS (FABþ): m/z: 148 [Mþþ1]; elemental analysis calcd for
C8H5NO2 ꢂ 0.25 H2O: C 63.37, H 3.66, N 9.24; found C
63.54, H 3.63, N 8.92.
1
5-Methylisatine 4b. Orange/red solid; H NMR (Aceton-d6):
d ¼ 2.29 (s, 3H, CH3), 6.89 (d, J ¼ 7.98 Hz, 1H, H7), 7.31 (s,
1H, H4), 7.41 (d, J ¼ 8.01 Hz, 1H, H6), 9.87 (s, 1H, NH);
13C NMR (Aceton-d6): d ¼ 20.4 (CH3), 113.2 (C7), 119.3
(C3a), 125.8 (C4), 133.9 (C5), 140.0 (C6), 149.7 (C7a), 160.4
(C2), 185.5 (C3); IR (KBr): 3286, 1743, 1626, 1491, 1438, 1399,
1304, 1195, 1127, 825, 738, 659, 552, 456 cmꢀ1; MS (FABþ):
m/z 161[Mþ]; elemental analysis calcd for C9H7NO2: C 67.08, H
4.38, N 8.69; found C 67.00, H 4.22, N 8.77.
1
5-Methoxyisatine 4c. Orange solid; H NMR (DMSO-d6): d
¼ 3.73 (s, 3H, OCH3), 6.83 (d, J ¼ 8.52 Hz, 1H, H7), 7.05 (d,
J ¼ 2.63 Hz, 1H, H4), 7.17 (dd, J ¼ 8.52, 2.72 Hz, 1H, H6),
10.83 (s, 1H, NH); 13C NMR (DMSO-d6): d ¼ 55.7 (OCH3),
108.7 (C4), 113.3 (C6), 118.0 (C3a), 124.8 (C7), 144.6 (C7a),
155.3 (C5), 159.5 (C2), 184.6 (C3); IR (KBr): 3156, 3101,
1748, 1732, 1637, 1607, 1492, 1446, 1408, 1309, 1284, 1265,
1242, 1201, 1154, 1035, 982, 903, 825, 773, 740, 703, 657,
603, 459 cmꢀ1; MS (FABþ): m/z 178 [MþþH]; elemental
analysis calcd for C9H7NO3: C 61.02, H 3.98, N 7.90; found C
60.38, H 4.06, N 7.80.
3-(3-Bromophenylimino)-6-bromo-N-(3-bromophenyl)-3H-
1
indol-2-amine 3d. Red solid; H NMR (CDCl3): d ¼ 6.51 (d,
J ¼ 8.24 Hz, 1H, Phen), 6.83 (dd, J ¼ 8.24, 1.65 Hz, 1H,
Phen), 6.96 (m, 1H, Phen), 7.22 (m, 4H, Phen), 7.41 (m, 1H,
Phen), 7.68 (m, 1H, Phen), 8.06 (s, 1H, NH); 13C NMR
(CDCl3): d ¼ 117.4 (CH, Phen), 117.7 (C q, Phen), 117.9
(CH, Phen), 121.8 (CH, Phen), 122.2 (CH, Phen), 122.7 (CH,
Phen), 122.9 (C q, Phen), 123.1 (C q, Phen), 126.0 (CH,
Phen), 126.3 (CH, Phen), 126.9 (CH, Phen), 128.8 (CH, Phen),
129.6 (C q, Phen), 130.5 (CH, Phen), 130.5 (C q, Phen), 130.8
(CH, Phen), 139.3 (C q, Phen), 149.5 (C q, Phen), 157.9 (C q),
159.3 (C q); IR (KBr): 3316, 1672, 1625, 1594, 1564, 1543,
1478, 1466, 1439, 1409, 1308, 1262, 1229, 1187, 1088, 1051,
1022, 994, 921, 872, 853, 808, 767, 738, 677, 657, 596, 424
cmꢀ1; MS (FABþ): m/z: 532[Mþ-2], 534[Mþ], 536[Mþþ2];
elemental analysis calcd for C23H21Br3N3: C 44.98, H 2.26, N
7.87; found C 44.30, H 2.77, N 7.48.
1
6-Bromoisatine 4d. Yellow/orange solid; H NMR (DMSO-
d6): d ¼ 7.07 (d, J ¼ 1.47 Hz, 1H, H7), 7.25 (dd, J ¼ 7.99,
1.57 Hz, 1H, H5), 7.43 (d, J ¼ 7.97 Hz, 1H, H4), 11.16 (s,
1H, NH); 13C NMR (DMSO-d6): d ¼ 114.9 (C7), 117.0 (C3a),
125.6 (C5), 126.2 (C3), 131.6 (C6), 151.5 (C7a), 159.3 (C2),
183.2 (C3); IR (KBr): 3172, 1744, 1716, 1609, 1443, 1327,
1262, 1246, 1206, 1100, 1053, 953, 907, 892, 789, 742, 663,
589, 511, 471 cmꢀ1; MS-EI: m/z 224 [Mþ, 79Br], 226 [Mþ,
81Br]; elemental analysis calcd for C8H4NO2Br: C 42.51, H
1.78, N 6.20; found C 41.80, H 2.15, N 5.78.
1
3-(4-Fluorophenylimino)-5-fluoro-N-(4-fluorophenyl)-3H-
1
indol-2-amine 3e. Red solid; H NMR (CDCl3): d ¼ 6.44 (m,
5-Fluoroisatine 4e. Orange/red solid; H NMR (DMSO-d6):
d ¼ 6.89 (dd, J ¼ 8.8, 3.85, 1H, H7), 7.35 (dd, J ¼ 7.14, 2.74
Hz, 1H, H4), 7.42 (m, 1H, H6), 11.03 (s, 1H, NH); 13C NMR
(DMSO-d6): d ¼ 111.30, 111.53 (C4), 113.46, 113.53 (C7),
118.47, 118.54 (C3a), 124.47, 124.71 (C6), 146.8 (C7a), 156.9
(C2), 159.35, 159.53 (C5), 183.9 (C3); 19F NMR (DMSO-d6):
d ¼ 121.0 (m, C5F); IR (KBr): 3213, 1738, 1619, 1489, 1389,
1290, 1262, 1141, 1105, 912, 890, 847, 792, 739, 655, 604,
459 cmꢀ1; MS (FABþ): m/z 166 [Mþþ1]; elemental analysis
calcd for C8H4NO2F ꢂ 0.5 H2O: C 55.18, H 2.89, N 8.04;
found C 54.29, H 3.09, N 7.29.
General procedure for the preparation of 4f,g. A solution
of 0.92 mL (12 mmol) DMF in 25 mL THF was cooled to
0ꢁC and under inert gas conditions 1.03 mL (12 mmol) oxalyl
chloride were added. After stirring for 2 h at room tempera-
ture, the suspension was again cooled to 0ꢁC and a solution of
2.1 mL (12 mmol) Hu¨nig’s base (NEtiPr2) was added drop-
wise. After stirring for 1 h at 0ꢁC and 2 h at room
1H, Phen), 6.83 (m, 2H, Phen), 7.01 (m, 5H, Phen), 7.15 (m,
2H, Phen), 7.78 (m, 2H, Phen); 13C NMR (CDCl3): d ¼ 112.6,
112.9 (CH, Phen), 115.5, 115.7 (C q, Phen), 115.8, 116.0 (CH,
Phen), 116.2, 116.2 (C q, Phen), 116.3, 116.6 (CH, Phen),
119.4 (C q, Phen), 119.6, 119.7 (C q, Phen), 120.5 (CH,
Phen), 120.6 (CH, Phen), 120.6 (CH, Phen), 120.7 (CH, Phen),
143.9 (C q), 157.3, 157.7 (C q, Phen), 159.7, 160.1 (C q,
Phen), 162.1 (C q); IR (KBr): 3199, 1656, 1629, 1578, 1544,
1500, 1460, 1302, 1270, 1232, 1206, 1184, 1153, 1124, 890,
847, 826, 741, 581, 516, 498, 464 cmꢀ1; MS (FABþ): m/z:
352[Mþþ1]; elemental analysis calcd for C23H21F3N3x0.5
H2O: C 66.66, H 3.64, N 11.66; found C 65.58, H 3.59, N
11.53.
General procedure for the preparation of 4a–e. A solu-
tion of 2.3 mmol of the isatin derivatives 3a–e, 30 mL glacial
acetic acid, 4 mL conc. HCl and 4 mL H2O was refluxed for
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet