9054
I.F. Sengul et al. / Tetrahedron 68 (2012) 9050e9055
to afford the macrocycle 8c (0.16 g, 75%) as a yellow solid, mp
>300 ꢀC; nmax (KBr) 3170, 2922, 2856, 1616, 1577, 1488, 1453, 1380,
CH2N), 4.06 (3H, s, linker NMe), 7.14e7.22 (4H, m, indole H), 7.47
(2H, d, J 7.7 Hz, linker H), 7.87e7.90 (4H, m, indole H), 8.33 (2H, s,
CH]N), 8.40 (2H, d, J 7.7 Hz, linker H), 8.54 (2H, s, linker H), 11.77
1284, 1244, 1155, 1125, 1052, 880, 805, 747 cmꢁ1
;
lmax (MeCN)
14,900 cmꢁ1 Mꢁ1), 256 (17,300); 1H NMR (300 MHz,
1.86 (4H, s, CH2), 3.49 (4H, s, CH2N), 3.66 (3H, s, linker
308 nm (
DMSO-d6):
3
(2H, br s, indole NH); 13C NMR (75 MHz, DMSO-d6):
d 23.9, 28.5
d
(CH2), 29.8 (NMe), 61.5 (CH2N), 110.0 (C), 110.5 (CH), 111.5 (CH),
120.8 (CH), 122.3 (CH), 122.5 (CH), 122.6 (C), 122.7 (C), 122.8 (CH),
126.9 (C), 127.2 (CH), 136.6 (C), 141.5 (C), 144.0 (C), 156.8 (CH]N);
HRMS (ESI): [MþH]þ, found 548.2786. C37H34N5 requires 548.2809.
NMe), 7.09e7.21 (4H, m, indole H), 7.48 (2H, d, J 7.7 Hz, linker H),
7.85 (2H, d, J 7.8 Hz, indole H), 7.95 (2H, dd, J 7.8, 1.6 Hz, indole H),
8.24 (2H, d, J 7.7 Hz linker H), 8.50 (2H, s, CH]N), 8.61 (2H, s, linker
H), 11.77 (2H, br s, indole NH); 13C NMR (75 MHz, DMSO-d6):
d 28.0
(CH2), 29.9 (NMe), 61.9 (CH2N), 109.8 (2C), 110.4 (CH), 112.0 (CH),
120.4 (CH), 120.5 (C), 121.3 (CH), 122.3 (C), 122.4 (CH), 122.9 (C),
123.3 (CH), 126.1 (CH), 127.8 (C), 141.3 (C), 156.8 (CH]N); HRMS
(ESI): [MþH]þ, found 520.2496. C35H30N5 requires 520.2501.
4.17. Bis-indole amine macrocycle (10a)
The bis-imine macrocycle 8a (0.100 g, 0.190 mmol) was dis-
solved in absolute ethanol (20 mL). Excess sodium borohydride
(0.030 g, 0.950 mmol) was added and the mixture stirred at room
temperature for 12 h. The reaction was quenched with distilled
water (20 mL), then extracted with ethyl acetate (3ꢂ15 mL). The
combined extracts were dried over sodium sulfate and concen-
trated under reduced pressure before being recrystallised from
dichloromethane/n-hexane to afford compound 10a (0.05 g, 58%) as
a yellow solid, mp >300 ꢀC; nmax (KBr) 3389, 3053, 2926, 2826,
4.14. Bis-indole imine macrocycle (9a)
A
mixture of bis-indole 3,30-dicarbaldehyde 7a (0.300 g,
0.560 mmol) and 1,6-diaminohexane (0.060 g, 0.560 mmol) was
heated at reflux overnight in ethanol (20 mL). The resulting pre-
cipitate was filtered and dried to give compound 9a (0.24 g, 68%) as
a
yellow solid, mp >300 ꢀC (from dichloromethane/hexane).
1633,1557,1451,1343,1196,1126,1008, 817, 750 cmꢁ1
305 nm (
9300 cmꢁ1 Mꢁ1), 242 (11,900); 1H NMR (300 MHz,
DMSO-d6): 1.69 (4H, s, CH2), 2.96 (4H, s, CH2), 3.94 (4H, s, CH2N),
; lmax (MeCN)
Found: C, 71.7; H, 6.1; N, 9.3. C36H32N4O.1.2CH2Cl2 requires C, 71.6;
3
H, 6.2; N, 9.2%; nmax (KBr) 3145, 2972, 2925, 2846, 1627, 1579, 1481,
d
1449, 1380, 1344, 1198, 1121, 1048, 892, 823, 749, 646 cmꢁ1
;
lmax
22,800 cmꢁ1 Mꢁ1), 258 (42,200); 1H NMR
(300 MHz, DMSO-d6): 1.54 (4H, s, 2CH2), 1.80 (4H, s, CH2), 3.63
7.14e7.28 (4H, m, indole H), 7.49 (2H, d, J 7.7 Hz, linker H), 7.70 (2H,
d, J 7.7 Hz, linker H), 7.70e7.90 (2H, br m, amino NH), 7.91e7.98 (4H,
m, indole H), 8.89 (2H, s, linker H), 11.57 (2H, br s, indole NH); 13C
(MeCN) 306 nm (
3
d
(4H, s, CH2N), 7.16e7.30 (4H, m, indole H), 7.52 (2H, d, J 7.7 Hz,
linker H), 7.94 (2H, d, J 8.1 Hz, indole H), 8.05 (2H, d, J 8.1 Hz, indole
H), 8.37 (2H, s, indole CH]N), 8.43 (2H, d, J 7.7 Hz, linker H), 8.56
(2H, s, linker H), 11.97 (2H, br s, indole NH); 13C NMR (75 MHz,
NMR (75 MHz, DMSO-d6): d 26.3, 44.3, 49.0 (CH2), 111.0 (C), 111.6
(CH), 112.5 (CH), 118.7 (CH), 119.3 (CH), 121.4 (CH), 121.8 (CH), 124.5
(C), 128.0 (CH), 128.5 (C), 129.2 (C), 136.0 (C), 136.3 (C), 155.7 (C);
HRMS (ESI): [MþH]þ, found 511.2500. C34H31N4O requires
511.2492.
DMSO-d6):
d 24.2, 28.6 (CH2), 61.5 (CH2N), 110.6 (C), 111.7 (CH),
112.9 (CH), 121.0 (CH), 122.5 (CH), 123.1 (CH), 123.8 (CH), 124.0 (C),
126.8 (C),127.0 (C), 129.0 (CH), 136.7 (C), 142.5 (C), 156.4 (C), 156.6
(CH]N); HRMS (ESI): [MþH]þ, found 535.2475. C36H31N4O re-
quires 535.2492.
4.18. Bis-indole amine macrocycle (10b)
Compound 10b was synthesised according to the method for
compound 10a using bis-imine macrocycle 8b (0.150 g,
0.290 mmol) and excess sodium borohydride (0.050 g, 1.45 mmol)
in absolute ethanol (20 mL) to give compound 10b (0.09 g, 61%) as
a yellow powder, mp >300 ꢀC; nmax (KBr) 3443, 2930, 1630, 1487,
4.15. Bis-indole imine macrocycle (9b)
Bis-indole carbaldehyde 7b (0.300 g, 0.660 mmol), and 1,6-dia-
minohexane (0.070 g, 0.660 mmol) were heated together at reflux
in ethanol (20 mL) overnight. The resulting precipitate was filtered
and dried to yield compound 9b (0.19 g, 55%) as a yellow solid, mp
>300 ꢀC; nmax (KBr) 3339, 2934, 2853, 1632, 1556, 1452, 1393, 1318,
1455, 1364, 1286, 1248, 1155, 1125, 810, 746 cmꢁ1
323 nm (
DMSO-d6):
;
lmax (MeCN)
21,600 cmꢁ1 Mꢁ1), 251 (22,750); 1H NMR (300 MHz,
1.79 (4H, s, CH2), 2.91 (4H, s, CH2), 3.84 (4H, s, CH2N),
3
d
6.98e7.09 (4H, m, indole H), 7.35 (2H, d, J 7.7 Hz, linker H),
7.58e7.75 (2H, br m, amino NH), 7.63 (2H, d, J 7.7 Hz, linker H),
7.67e7.71 (4H, m, indole H), 8.67 (2H, s, linker H), 11.29 (2H, br s,
indole NH), 11.71 (1H, br s, linker NH); 13C NMR (75 MHz, DMSO-
1282, 1245, 821, 748, 609 cmꢁ1
;
lmax (MeCN) 308 nm
10,700 cmꢁ1 Mꢁ1), 256 (14,300); 1H NMR (300 MHz, DMSO-d6):
1.50 (4H, s, CH2), 1.76 (4H, s, CH2), 3.57 (4H, s, CH2N), 7.11e7.23
(
3
d
(4H, m, indole H), 7.46 (2H, d, J 7.7 Hz, linker H), 7.77 (4H, s, indole
H), 8.28 (2H, s, CH]N), 8.37 (2H, d, J 7.7 Hz, linker H), 8.55 (2H, s,
d6): d 26.2, 29.6, 48.9 (CH2), 110.0 (CH), 110.9 (C), 111.2 (CH), 118.5
(CH), 119.0 (CH), 120.8 (CH), 121.3 (CH), 124.4 (C), 126.4 (CH), 128.0
(C), 129.1 (C), 136.0 (C), 136.2 (C), 155.7 (C); HRMS (ESI): [M]þ, found
510.2650. C34H32N5 requires 510.2652.
linker H), 11.87 (2H, br s, indole NH), 11.94 (1H, br s, linker NH); 13
C
NMR (75 MHz, DMSO-d6): d 23.9, 28.5 (CH2), 61.4 (CH2N), 109.8 (C),
111.6 (CH), 112.2 (CH), 120.8 (C), 122.4 (CH), 122.5 (CH), 122.6 (CH),
122.7 (CH), 123.0 (CH), 126.9 (C), 127.1 (C), 136.7 (C), 140.6 (C), 144.3
(C), 156.8 (CH]N); HRMS (ESI): [MþH]þ, found 534.2622. C36H32N5
requires 534.2652.
4.19. Bis-indole amine macrocyle (10c)
Compound 10c was synthesised according to the method for
compound 10a using bis-imine macrocycle 8c (0.120 g,
0.230 mmol) and excess sodium borohydride (0.040 g, 1.15 mmol)
in absolute ethanol (20 mL) to give compound 10c (0.07 g, 65%) as
a yellow powder, mp >300 ꢀC; nmax (KBr) 3405, 2927, 1601, 1487,
4.16. Bis-indole imine macrocycle (9c)
Bis-indole carbaldehyde 7c (0.150 g, 0.320 mmol) and 1,6-dia-
minohexane (0.030 g, 0.320 mmol) were heated together at reflux
in ethanol (20 mL) overnight. The resulting precipitate was filtered
off, dried and recrystallised from dichloromethane/light petroleum
to afford the macrocycle 9c (0.11 g, 63%) as a yellow solid, mp
>300 ꢀC; nmax (KBr) 3365, 3052, 2922, 2847, 1626, 1485, 1452, 1368,
1456, 1346, 1282, 1245, 1158, 1129, 1005, 945, 811, 747 cmꢁ1
;
lmax
20,850 cmꢁ1 Mꢁ1), 306 (20,050), 251 (23,150);
1H NMR (300 MHz, DMSO-d6):
1.70 (4H, s, CH2), 2.81 (4H, s, CH2),
(MeCN) 323 nm (
3
d
3.81 (4H, d, J 5.0, CH2N), 3.93 (3H, s, linker NMe), 6.93e7.01 (4H, m,
indole H), 7.32 (2H, d, J 7.7 Hz, linker H), 7.53 (2H, d, J 7.7 Hz, linker
H), 7.65e7.77 (2H, br m, amino NH), 7.72 (4H, s, indole H), 8.66 (2H,
s, linker H), 11.22 (2H, br s, indole NH); 13C NMR (75 MHz, DMSO-
1339, 1282, 1244, 1156, 1124, 813, 760, 740 cmꢁ1
308 nm (
46,050 cmꢁ1 Mꢁ1), 258 (62,450); 1H NMR (300 MHz,
DMSO-d6):
1.49 (4H, s, 2ꢂCH2), 1.76 (4H, s, CH2), 3.56 (4H, s,
; lmax (MeCN)
3
d
d6): d 26.2, 29.6 (CH2), 44.5 (NMe), 48.8 (CH2), 110.1 (CH), 111.3 (CH),