Bromoindole Alkaloids from Laurencia brongniartii
Journal of Natural Products, 2006, Vol. 69, No. 11 1599
powder (114 mg, 96%); mp 176-177 °C (hexane/Et2O); IR (KBr) νmax
2955, 2921, 2851, 1746, 1434, 1340 cm-1; 1H NMR (CDCl3, 400 MHz)
δ 8.38 (1H, s, H-7), 7.72 (1H, s, H-4), 4.11 (3H, s, CH3); 13C NMR
(CDCl3, 100 MHz) δ 150.1 (CO2Me), 134.9 (C-7a), 129.1 (C-3a), 123.6
(C-4), 121.9 (C-6), 120.6 (C-7), 120.3 (C-5), 113.4 (C-2), 104.1 (C-
3), 54.8 (CH3); EIMS m/z 495/493/491/489/487 [M+] (6/25/36/25/6),
449/447/445 (18/29/19), 434/432/430 (26/39/26), 274 (26), 272 (54),
112 (53), 59 (100); FABHRMS m/z 490.7028 (calcd for C10H5NO2-
Br4, 490.7013).
5-Bromoindole (10a): obtained from 3 as a white powder (0.057 g,
75%); mp 91-92 °C (EtOAc/hexane) (lit.10a mp 91 °C); IR (KBr) νmax
3412, 2919, 2850, 1627, 1443, 1411 cm-1; 1H NMR (CDCl3, 400 MHz)
δ 8.13 (1H, br s, N-H), 7.76 (1H, br s, H-4), 7.26 (1H, dd, J ) 8.8,
1.9 Hz, H-6), 7.22 (1H, d, J ) 8.5 Hz, H-7), 7.17 (1H, t, J ) 2.6 Hz,
H-2), 6.48 (1H, t, J ) 2.2 Hz, H-3); 13C NMR (CDCl3, 100 MHz) δ
134.5 (C-7a), 129.8 (C-3a); 125.5 (C-2), 125.0 (C-6), 123.3 (C-4), 113.2
(C-5), 112.6 (C-7), 102.4 (C-3); EIMS m/z 197/195 [M+] (100/96),
116 (87), 89 (34).
3,5-Dibromoindole (10b): obtained from 3 as a white powder (0.005
g, 5%); mp 80-81 °C (EtOAc/hexane); IR (KBr) νmax 2969, 2927,
1450 cm-1; 1H NMR (CDCl3, 400 MHz) δ 8.33 (1H, br s, N-H), 7.72
(1H, d, J ) 1.8 Hz, H-4), 7.32 (1H, dd, J ) 8.8, 1.9 Hz, H-6), 7.24
(1H, d, J ) 8.5 Hz, H-7), 7.22 (1H, d, J ) 2.5 Hz, H-2); 13C NMR
(CDCl3, 100 MHz) δ 134.1 (C-7a), 128.7 (C-3a), 126.3 (C-6), 124.7
(C-2), 122.0 (C-4), 114.1 (C-5), 113.1 (C-7), 91.1 (C-3); EIMS m/z
277/275/273 [M+] (51/100/51), 196/194 (49/50), 115 (54); FABHRMS
m/z 274.8759 (calcd for C8H5NBr2, 274.8768).
General Procedure for the Preparation of 1a and 1b. To a solution
of 7 or 14 (0.1 g, 0.283 mmol) in THF (10 mL) were added NaH (4.2
mmol) and MeI (3.4 mmol), followed by stirring in an ice-cooled bath
for 45 min. The mixture was diluted with EtOAc (100 mL), and the
organic layer was washed with brine (2 × 20 mL), dried over Na2SO4,
and evaporated to dryness in vacuo. The residue was purified by flash
column chromatography eluting with EtOAc/hexane (1:7, v/v).
2,3,6-Tribromo-1-methylindole (1a): obtained from 14 as a pale
brown powder (0.099 g, 95%); mp 90-91 °C (EtOAc/hexane) (lit.2a
mp 90.5-91 °C); IR (film) νmax 2937, 1607, 1561, 1497, 1461, 1416,
1331, 1221 cm-1; 1H NMR (CDCl3, 400 MHz) δ 7.40 (1H, d, J ) 1.5
Hz, H-7), 7.31 (1H, d, J ) 8.4 Hz, H-4), 7.24 (1H, d, J ) 8.4, 1.8 Hz,
H-5), 3.70 (3H, s, CH3); 13C NMR (CDCl3, 100 MHz) δ 136.9 (C-7a),
125.9 (C-3a), 124.2 (C-5), 120.2 (C-4), 116.8 (C-5), 115.7 (C-2), 112.7
(C-7), 93.1 (C-3), 32.6 (CH3); EIMS m/z 371/369/367/365 [M+] (38/
99/100/34), 356/354/352/350 (6/18/19/7), 290/288/286 (6/13/7), 249/
247/245 (5/10/5, 194/192 (17/18), 128 (24), 87 (21); FABHRMS m/z
366.8018 (calcd for C9H6NBr3, 366.8030).
General Procedure for the Preparation of 1c, 7, and 14. To a
stirred solution of the appropriate indole 6 (0.1 g, 0.243 mmol), 8 (0.1
g, 0.204 mmol), or 13 (0.1 g, 0.204 mmol) in MeOH (20 mL) was
added NaH (2 molar equiv), and the mixture was heated under
reflux for 2 h. After cooling to room temperature the MeOH was
evaporated under reduced pressure and the residue was dissolved in
EtOAc (50 mL). The organic phase was washed with a saturated
solution of NH4Cl (2 × 20 mL) and brine (2 × 20 mL), dried over
Na2SO4, filtered, and evaporated to dryness in vacuo. The residue was
purified by flash column chromatography eluting with EtOAc/hexane
(1:7, v/v).
2,3,5,6-Tetrabromoindole (1c): obtained from 8 as a pale brown
powder (0.08 g, 91%); mp 153-154 °C (EtOAc/hexane); IR (KBr)
1
νmax 3380, 2924, 2854, 1436 cm-1; H NMR (CDCl3, 400 MHz) δ
8.34 (1H, br s, N-H), 7.73 (1H, s, H-4), 7.57 (1H, s, H-7); 13C NMR
(CDCl3, 100 MHz) δ 135.1 (C-7a), 128.4 (C-3a), 123.4 (C-4), 119.2
(C-6), 117.1 (C-5), 115.6 (C-7), 112.4 (C-2), 93.9 (C-3); EIMS m/z
437/435/433/431/429 [M+] (16/64/100/64/17), 356/354/352/350 (15/
38/38/13), 275/273/271 (23/41/22), 137 (34), 86 (43); FABHRMS m/z
432.6965 (calcd for C8H3NBr4, 432.6958).
2,3,5-Tribromoindole (7): obtained from 6 as a pale brown powder
(0.077 g, 90%); mp 150-151 °C (EtOAc/hexane); IR (KBr) νmax 2918,
1
2850, 1635, 1456, 1434, 1325 cm-1; H NMR (CDCl3, 400 MHz) δ
8.34 (1H, br s, N-H), 7.61 (1H, d, J ) 1.1 Hz, H-4), 7.29 (1H, dd, J
) 8.8, 1.8 Hz, H-6), 7.13 (1H, d, J ) 8.8 Hz, H-7); 13C NMR (CDCl3,
100 MHz) δ 134.4 (C-7a), 129.2(C-3a), 126.6 (C-6), 121.6 (C-4), 114.7
(C-5), 112.3 (C-7), 111.4 (C-2), 93.8 (C-3); EIMS m/z 357/355/353/
351 [M+] (33/100/99/35), 276/274/272 (27/55/27), 249/247/245 (7/13/
7), 195/193 (19/19), 114 (37); FABHRMS m/z 354.7860 (calcd for
C8H4NBr3, 354.7853).
2,3,5-Tribromo-1-methylindole (1b): obtained from 7 as white
crystals (0.098 g, 95%); mp 121-122 °C (EtOAc/hexane) (lit.2a mp
120-122 °C); IR (KBr) νmax 2921, 2851, 1631, 1463, 1420, 1362 cm-1
;
1H NMR (CDCl3, 400 MHz) δ 7.62 (1H, d, J ) 1.8 Hz, H-4), 7.30
(1H, dd, J ) 8.7, 1.8 Hz, H-6), 7.12 (1H, d, J ) 8.8 Hz, H-7), 3.75
(3H, s, CH3); 13C NMR (CDCl3, 100 MHz) δ 135.2 (C-7a), 128.6 (C-
3a), 126.0 (C-6), 121.6 (C-4), 116.5 (C-2), 114.4 (C-5), 111.3 (C-7),
92.2 (C-3), 32.7 (CH3); EIMS m/z 371/369/367/365 [M+] (34/100/95/
34), 356/354/352/350 (3/9/9/3), 290/288/286 (6/14/7), 289/287/285 (6/
9/4), 249/247/245 (4/8/4, 209/207 (15/16), 194/192 (14/16); FABHRMS
m/z 366.8035 (calcd for C9H6NBr3, 366.8030).
2,3,6-Tribromoindole (14): obtained from 13 as a pale brown
powder (0.080 g, 94%); mp 74-75 °C (EtOAc/hexane); IR (film) νmax
1
3408, 1719, 1612, 1442, 1221 cm-1; H NMR (CDCl3, 400 MHz) δ
8.30 (1H, br s, N-H), 7.44 (1H, d, J ) 1.1 Hz, H-7), 7.34 (1H, d, J
) 8.4 Hz, H-4), 7.29 (1H, dd, J ) 8.4, 1.4 Hz, H-5); 13C NMR (CDCl3,
100 MHz) δ 136.3 (C-7a), 126.7 (C-3a), 124.8 (C-5), 120.3 (C-4), 117.3
(C-6), 113.8 (C-7), 110.8 (C-2), 94.9 (C-3); EIMS m/z 351/353/355/
357 [M+] (19/57/56/18), 272/274/276 (18/35/17), 97 (27), 71 (74), 57
(100); FABHRMS m/z 354.7853 (calcd for C8H4NBr3, 354.7853).
Acknowledgment. This research was supported in part by CONA-
CYT (Mexico) grant 2002-C01-40641/A-1. We thank QFB A. Her-
na´ndez (CINVESTAV-IPN) for X-ray analysis support.
5-Bromoindoline (9). To a stirred solution of 3 (0.1 g, 0.39 mmol)
in MeOH (20 mL) was added a 20% aqueous solution of NaOH (10
mL), and the mixture was heated under reflux for 2 h. The MeOH was
evaporated in vacuo, and the residue was diluted with EtOAc (100
mL). The organic phase was washed with brine (2 × 20 mL), dried
over Na2SO4, filtered, and evaporated to dryness in vacuo. The residue
was purified by flash column chromatography eluting with EtOAc/
hexane (1:7, v/v) to give 910b as a pale brown powder (0.07 g, 91%);
mp 39-40 °C (EtOAc/hexane) (lit.10c mp 36-40 °C); IR (film) νmax
3386, 2933, 2856, 1604, 1486, 1471, 1248 cm-1; 1H NMR and MS in
agreement with published values; 13C NMR (CDCl3, 100 MHz) δ 150.8
(C-7a), 131.9 (C-3a), 129.9 (C-6), 127.7 (C-4), 110.7 (C-7), 110.2 (C-
5), 48.0 (C-2), 29.8 (C-3).
Procedure for the Preparation of 10a and 10b. To a stirred
solution of 3 (0.1 g, 0.39 mmol) in CCl4 (20 mL) was added Br2 (20
µL, 0.39 mmol) in CCl4 (10 mL) over 1 h, and stirring at room
temperature continued for another 1 h. The reaction mixture was worked
up as usual to give a pale yellow solid, which was dissolved in MeOH
(20 mL), NaH (2 molar equiv) was added, and the mixture was heated
under reflux for 2 h. After cooling to room temperature the MeOH
was evaporated under reduced pressure, and the residue was dissolved
in EtOAc (50 mL). The organic phase was washed with a saturated
solution of NH4Cl (2 × 20 mL) and brine (2 × 20 mL), dried over
Na2SO4, filtered, and evaporated to dryness in vacuo. The residue was
purified by flash column chromatography eluting with EtOAc/hexane
(1:7, v/v).
Supporting Information Available: Heteronuclear long-range
coupling constants for 1c and 8 (Table S1) and X-ray data for compound
3 (Tables S2 and S3). This material is available free of charge via the
References and Notes
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