Synthesis of macrocyclic systems derived from di-(2-indolyl)heteroarenes

Article abstract of DOI:10.1016/j.tet.2012.08.063

A number of new 3,6-di-(2-indolyl)-dibenzofuran and carbazole derivatives have been prepared from dibenzofuran and carbazole linkers via the Fischer indole synthesis. The bis-indoles were successfully formylated at C3 and the resulting dicarbaldehydes wer

Full text of DOI:10.1016/j.tet.2012.08.063

Tetrahedron 68 (2012) 9050e9055
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journal homepage: www.elsevier.com/locate/tet
Synthesis of macrocyclic systems derived from di-(2-indolyl)heteroarenes
*
Ibrahim F. Sengul, Kasey Wood, Naresh Kumar, David StC. Black
School of Chemistry, The University of New South Wales, UNSW Sydney, NSW 2052, Australia
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 17 May 2012
Received in revised form 3 August 2012
Accepted 20 August 2012
Available online 27 August 2012
A number of new 3,6-di-(2-indolyl)-dibenzofuran and carbazole derivatives have been prepared from
dibenzofuran and carbazole linkers via the Fischer indole synthesis. The bis-indoles were successfully
formylated at C3 and the resulting dicarbaldehydes were combined with diamines to generate indole
based imine macrocyclic systems.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Bis-indoles
Macrocycles
Fischer indole synthesis
Imines
Schiff bases
1. Introduction
potential as novel fluorescent probes,12 optoelectronic materials13
and semiconductors.14
Bis-indole alkaloids are interesting heterocyclic compounds
because many examples have been isolated from natural sources
and display a wide range of pharmacological activity.1 In particular,
a common structural motif amongst these bis-indoles is the con-
nection of the two indole rings via a five- or six-membered aryl or
heteroaryl ring. Examples include the nortopsentins AeC, which
show cytotoxicity and antifungal activity2 and dragmacidin D,
which is an inhibitor of serine/threonine protein phosphatases.3
In general, bis-3-indoles are perhaps the most prolific of this
class, but bis-2-indoles have also attracted recent attention because
of their use as tubulin polymerisation inhibitors,4 antibacterial
agents,5 CDK inhibitors and cytotoxic agents,6 as well as organic
semiconductors7 and light emitting compounds.8
Macrocyclic bis-indole systems are also of interest for pharma-
ceutical purposes and as receptors and chemosensors. For instance,
bis(indolyl)maleimides 1 have been the focus of extensive de-
velopment as protein kinase C inhibitors9 and the macrocyclic
tetraindole 2 is reported to strongly bind a range of anions10 (Fig. 1).
In our current study, we were interested in the synthesis of bis-
2-indolyls linked by structurally rigid carbazole or dibenzofuran
ring systems as precursors to novel macrocycles. In addition, 3,6-
diaryl or heteroaryl dibenzofurans and carbazoles have been as-
sociated with cytotoxic and antiplatelet activity,11 and show
Further, since indoles can be readily formylated, subsequent
imine formation by reaction with amines is an effective strategy for
the preparation of a diverse range of novel macrocyclic structures.
Imines also show varied pharmacological effects, for example, in-
dole-3-carbaldimines show antimicrobial activity,15 and also can
facilitate metal complexation.16 It was thereforeanticipated that this
methodology of imine formation could be readily extended to our
targeted 3,6-bis-(2-indolyl)-dibenzofuran and carbazole systems.
H
N
tBu
tBu
O
O
N
N
H
N
H
N
H
N
H
N
F
O
tBu
tBu
R
1
2
Fig. 1. Macrocyclic bis-indole systems.
2. Results and discussion
The synthesis of a new range of macrocyclic systems derived
from 3,6-bis-(2-indolyl)-dibenzofuran and related carbazoles was
approached via the Fischer indole synthesis.
* Corresponding author. Tel.: þ61 2 9385 4698; fax: þ61 2 9385 6141; e-mail
addresses: n.kumar@unsw.edu.au (N. Kumar), d.black@unsw.edu.au (D.StC. Black).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.08.063

I.F. Sengul et al. / Tetrahedron 68 (2012) 9050e9055
9051
Dibenzofuran (3a), carbazole (3b) and N-methylcarbazole (3c)
were acetylated under FriedeleCrafts conditions by heating at
50 ꢀC with 2 equiv of acetyl chloride and aluminium trichloride in
carbon disulfide.17e19 The resulting dibenzofuran 4a, carbazole 4b
and N-methylcarbazole 4c were obtained in 90%, 85% and 83%
yields, respectively. The aromatic ketones 4aec were subsequently
reacted at reflux for 2 h in ethanol and glacial acetic acid with
2 equiv of phenylhydrazine to give phenylhydrazones 5aec in
70e80% yield (Scheme 1). Acid-catalysed cyclisation at 110 ꢀC using
methanesulfonic acid then gave the targeted 3,6-bis-(2-indolyl)-
dibenzofuran 6a and carbazoles 6b,c in 67e75% yield. The 1H NMR
spectrum of dibenzofuran 6a was characteristic for these bis-2-
Heating bis-indole dicarbaldehyde 7a at reflux with 1,2-
diaminoethane in absolute ethanol for 12 h led only to recovery
of the starting material. In a similar fashion, no reaction was ob-
served upon heating with 1,2-diaminobenzene. This suggested that
the rigidity of the dibenzofuran moiety necessitates the use of
longer, more flexible linkers in order to produce the desired
macrocycles.
Accordingly, treatment of bis-indole dicarbaldehyde 7a with
1,4-diaminobutane at reflux for 12 h afforded the bisindolo-
macrocyclic imine 8a in 73% yield. The 1H NMR spectrum showed
the new imine resonance at
d 8.68 and the methylene protons at
d
1.86 and 3.76. Mass spectrometry also confirmed that the 18-
indoles, showing the indole H3 proton at
noid protons as doublets at 7.42 and 7.83 and a multiplet at
The dibenzofuran protons were present as doublets at 7.55 and
8.65 and a doublet of doublets at 8.05 and the NH groups
appeared as a broad singlet at 11.66. Mass spectrometry provided
d
6.96 and the benze-
membered macrocycle was formed in preference to a dimeric or
other higher order system, showing a molecular ion at 506. The
related analogues 8b and 8c were similarly prepared in good yields
of 67% and 75%, respectively, upon reaction with 1,4-
diaminobutane.
d
d
7.13.
d
d
d
further structural confirmation, with the anticipated molecular
ions present at 398, 397, 411 for bis-2-indoles 6a, 6b and 6c,
respectively.
The diamine linker was subsequently increased by a further two
methylene units. Heating bis-indole dicarbaldehydes 7aec with
1,6-diaminohexane overnight successfully afforded macrocyclic
imines 9aec in 55e68%. Mass spectrometry analysis confirmed
that the 20-membered macrocyclic imines were produced, dis-
playing molecular ions at m/z 534, 533 and 547, respectively. Once
again the formation of any higher order macrocycles was not
evident.
Reduction of the macrocyclic imines 8aec and 9aec to give the
related amine analogues 10aec and 11aec, respectively, was ach-
ieved in moderate yields of 56e65% by treatment with sodium
borohydride in ethanol at room temperature for 6 h. The resulting
diaza macrocycles 10aec and 11aec would be expected to show
Formylationof the C3 indole positions was readilyachieved using
VilsmeiereHaack conditions at 0 ꢀC and in the presence of an excess
of phosphoryl chloride. The resulting bis-indole dicarbaldehydes
7aec were obtained in 85e90% yield as yellow solids. Reaction at C3
was confirmed by 1H NMR spectroscopy, in which the characteristic
H3 protons of the precursors were absent and the new CHO protons
appeared as sharp singlets at
displayed the expected carbonyl resonance at
d
10.1. The 13C NMR spectra similarly
186.0.
d
Schiff base condensation of the bis-indole dicarbaldehydes 7aec
with a range of primary diamines was subsequently investigated.
Scheme 1. Reagents and conditions: (a) AlCl3, CH3COCl, CS2, 50 ꢀC, 6 h, (83e90%); (b) NH2NHPh, EtOH, HOAc, reflux, 3 h, (70e80%); (c) methanesulfonic acid, 110 ꢀC, 1.5 h,
(67e75%); (d) POCl3, DMF, 0 ꢀC, overnight, (85e90%); (e) diamine, EtOH, reflux, 12 h, (55e75%); (f) NaBH4, EtOH, rt, 6 h, (56e65%).

9052
I.F. Sengul et al. / Tetrahedron 68 (2012) 9050e9055
greater structural flexibility than their imine precursors. The 1H
NMR spectrum of compound 10b was characteristic for these diaza
macrocycles and showed the appearance of the amine signal at
nmax (KBr) 3380, 3048, 1598, 1493, 1423, 1368, 1329, 1297, 1245,
1131, 1070, 1021, 877, 746 cmꢁ1
lmax (MeCN) 340 nm
46,100 cmꢁ1 Mꢁ1), 248 (33,800); 1H NMR (300 MHz, DMSO-d6):
2.42 (6H, s, Me), 6.79 (2H, t, J 6.7 Hz, aryl H), 7.20e7.30 (10H, m,
;
(
3
d
3.94 along with the absence of the imine resonance at
d
8.62.
d
aryl H and NH), 7.45 (2H, d, J 8.1 Hz, linker H), 8.02 (2H, dd, J 8.1,
1.6 Hz, linker H) 8.54 (2H, d, J 1.6 Hz, linker H), 11.39 (1H, br s,
3. Conclusions
carbazole NH); 13C NMR (75 MHz, DMSO-d6):
d 13.7 (Me), 111.4
Bis-2-indolyl-arenes 6aec, linked by heterocyclic dibenzofuran
or carbazole moieties, were successfully prepared through appli-
cation of the Fischer indole synthetic method. The macrocyclic
imines 8aec and 9aec were subsequently derived from these bis-
2-indoles through a sequence of formylation and reaction with 1,4-
diaminobutane and 1,4-diaminohexane. The successful formation
of macrocyclic compounds was found to be dependent upon the
length and flexibility of the diamine linker. The related amine
macrocycles 10aec and 11aec were also prepared through sodium
borohydride reduction of the imines 8aec and 9aec, respectively.
(CH), 113.1 (CH), 117.9 (CH), 118.8 (CH), 122.9 (C), 123.8 (CH), 129.2
(CH), 130.9 (C), 140.1 (C), 142.5 (imine C), 146.8 (C); HRMS (ESI):
[MþH]þ, found 432.2167. C28H26N5 requires 432.2183.
4.4. 9-Methyl-3,6-bis((E)-1-(2-phenylhydrazono)ethyl)-9H-
carbazole (5c)
Compound 5c was synthesised according to the method for
compound 5a using 9-methyl-3,6-diacetylcarbazole (4c)17 (2.00 g,
7.50 mmol) and phenylhydrazine (1.62 g, 15.0 mmol) in ethanol
(30 mL). The resulting precipitate was collected to give compound
5c (2.62 g, 78%) as yellow crystals, mp 210e212 ꢀC; nmax (KBr) 3417,
3336, 3047, 2925, 1600, 1492, 1373, 1331, 1297, 1246, 1134, 806, 751,
4. Experimental
4.1. General
690 cmꢁ1
;
lmax (MeCN) 344 nm (
3
69,250 cmꢁ1 Mꢁ1), 251 (59,100);
1H NMR (300 MHz, DMSO-d6):
d
2.40 (6H, s, Me), 3.89 (3H, s, NMe),
All reagents and solvents were obtained from commercial
sources and appropriately purified, if necessary. Melting points
were measured using a Mel-Temp melting point apparatus and are
uncorrected. Microanalyses were performed on a Carlo Erba Ele-
mental Analyser EA 1108 at the Campbell Microanalytical Labora-
tory, University of Otago, New Zealand. 1H and 13C NMR spectra
were obtained on Bruker DPX300 (300 MHz) and Bruker DPX600
(600 MHz) spectrometers. Mass spectra were recorded on either
a Bruker FT-ICR MS (EI) or a Micromass ZQ2000 (ESI). Infrared
spectra were recorded with a Thermo Nicolet 370 FTIR Spectrom-
eter using KBr discs. Column chromatography was carried out using
Merck 230e400 mesh ASTM silica gel, whilst preparative thin layer
chromatography was performed using Merck silica gel 7730
6.79 (2H, t, J 6.6 Hz, aryl H), 7.12e7.22 (10H, m, aryl H and NH), 7.52
(2H, d, J 8.1 Hz, linker H), 8.03 (2H, dd, J 8.1, 1.6 Hz, linker H), 8.50
(2H, d, J 1.6 Hz, linker H); 13C NMR (75 MHz, DMSO-d6):
d 13.8 (Me),
29.6 (NMe), 109.5 (CH), 113.1 (CH), 117.9 (CH), 118.8 (CH), 122.4 (C),
123.8 (CH), 129.2 (CH), 131.1 (C), 141.0 (C), 142.4 (imine C), 146.8 (C);
HRMS (ESI): [MþH]þ, found 446.2296. C29H28N5 requires 446.2339.
4.5. 2,8-Di(1H-indol-2-yl)dibenzo[b,d]furan (6a)
A mixture of compound 5a (2.00 g, 5.02 mmol) and meth-
anesulfonic acid (10 mL) was stirred at 110 ꢀC for 1 h. Ice water
(150 mL) was added and the mixture was stirred for a further
30 min. The precipitate was filtered, washed with water and
recrystallised from 95% ethanol to yield compound 6a (1.38 g, 75%)
as a yellow solid, mp 214e216 ꢀC; nmax (KBr) 3407, 3047, 1600, 1477,
60GF254
.
4.2. 2,8-Bis((E)-1-(2-phenylhydrazono)ethyl)dibenzo[b,d]furan
(5a)
1448, 1425, 1347, 1298, 1275, 1199, 1022, 875, 791, 751, 738 cmꢁ1
lmax (MeCN) 318 nm (
105,500 cmꢁ1 Mꢁ1), 244 (112,500), 205
(111,500); 1H NMR (300 MHz, DMSO-d6):
6.96 (2H, d, J 1.5 Hz,
;
3
d
A
mixture of 3,6-diacetyldibenzofuran (4a)20 (1.00 g,
indole H), 7.01e7.13 (4H, m, indole H), 7.42 (2H, d, J 8.1 Hz, indole
H), 7.55 (2H, d, J 7.7 Hz, linker H), 7.83 (2H, d, J 8.1 Hz, indole H), 8.05
(2H, dd, J 7.7, 1.6 Hz linker H), 8.65 (2H, d, J 1.6 Hz, linker H), 11.66
3.96 mmol), phenylhydrazine (0.850 g, 7.93 mmol) and a few drops
of glacial acetic acid in ethanol (30 mL) was heated at reflux for 2 h.
The resulting precipitate was filtered and washed with 2 M aq HCl,
then cold 95% ethanol (20 mL) before being recrystallised from
ethanol to yield compound 5a (1.37 g, 80%) as yellow crystals, mp
190e192 ꢀC; nmax (KBr) 3408, 3058, 2926, 1677, 1633, 1598, 1497,
(2H, br s, indole NH); 13C NMR (75 MHz, DMSO-d6):
d 99.0 (CH),
111.7 (CH), 112.7 (CH), 118.0 (CH), 119.8 (CH), 120.3 (CH), 121.9 (CH),
124.5 (C), 125.7 (CH), 128.4 (C), 129.2 (C), 137.6 (C), 138.2 (C), 155.8
(C); HRMS (ESI): [MþH]þ, found 399.1462. C28H19N2O requires
399.1492.
1424, 1359, 1251, 1198, 1022, 818, 752, 693 cmꢁ1
331 nm (
69,550 cmꢁ1 Mꢁ1), 235 (71,400); 1H NMR (300 MHz,
CDCl3): 2.39 (6H, s, Me), 6.88 (2H, t, J 6.7 Hz, aryl H), 7.22e7.36
; lmax (MeCN)
3
d
4.6. 3,6-Di(1H-indol-2-yl)-9H-carbazole (6b)
(10H, m, aryl H, NH), 7.57 (2H, d, J 9.0 Hz, linker H), 7.97 (2H, dd, J
8.1, 1.6 Hz, linker H), 8.33 (2H, d, J 1.6 Hz, linker H); 13C NMR
(75 MHz, CDCl3): d 12.7 (Me),111.5 (CH),113.3 (CH),118.0 (CH),118.8
Compound 6b was synthesised according to the method for
compound 6a using phenylhydrazone 5b (1.40 g, 3.52 mmol) and
methanesulfonic acid (15 mL). Recrystallisation of the resulting
precipitate from 95% ethanol gave compound 6b (0.83 g, 67%) as
a yellow powder, mp >300 ꢀC. Found C, 79.7; H, 4.8; N, 9.7.
(C), 120.3 (CH), 124.2 (C), 125.4 (CH), 129.2 (CH), 131.7 (C), 145.1
(imine C), 156.7 (C); HRMS (ESI): [MþH]þ, found 433.1991.
C
28H25N4O requires 433.2023.
C
28H19N3$1.5H2O requires C, 79.9; H, 5.1; N, 9.9%; nmax (KBr) 3403,
3049, 1604, 1481, 1450, 1441, 1404, 1346, 1281, 1236, 1134, 787, 749,
590 cmꢁ1 72,750 cmꢁ1 Mꢁ1), 250 (59,350),
lmax (MeOH) 330 nm (
205 (71,300); 1H NMR (300 MHz, DMSO-d6):
6.88 (2H, d, J 1.5 Hz,
4.3. 3,6-Bis((E)-1-(2-phenylhydrazono)ethyl)-9H-carbazole
(5b)
;
3
d
Compound 5b was synthesised according to the method for
compound 5a using 3,6-diacetylcarbazole (4b)17e19 (1.00 g,
3.96 mmol) and phenylhydrazine (0.89 g, 7.93 mmol) in ethanol
(30 mL). The resulting precipitate was collected to give compound
5b (1.19 g, 70%) as yellow crystals, mp 230e232 ꢀC. Found C, 76.2; H,
5.9; N, 14.9. C28H25N5$0.6C2H5OH requires C, 76.3; H, 6.2; N, 15.2;
indole H), 6.99e7.11 (4H, m, indole H), 7.44 (2H, d, J 8.1 Hz, indole
H), 7.55 (2H, d, J 7.7 Hz, linker H), 7.61 (2H, d, J 8.1 Hz, indole H), 7.92
(2H, dd, J 7.7, 1.6 Hz, linker H), 8.68 (2H, d, J 1.6 Hz, linker H), 11.48
(1H, br s, linker NH), 11.55 (2H, br s, indole NH); 13C NMR (75 MHz,
DMSO-d6):
d 97.6 (CH), 111.5 (CH), 112.0 (CH), 117.3 (CH), 119.6 (CH),
120.0 (CH), 121.3 (CH), 123.3 (C), 123.9 (C), 124.1 (CH), 129.4 (C),

I.F. Sengul et al. / Tetrahedron 68 (2012) 9050e9055
9053
137.4 (C), 139.6 (C), 140.1 (C); HRMS (ESI): [MþH]þ, found 398.1616.
4.10. 2,20-(9-Methyl-9H-carbazole-3,6-diyl)bis(1H-indole-3-
carbaldehyde) (7c)
C
28H20N3 requires 398.1652.
Compound 7c was synthesised according to the method for
compound 7a using phosphoryl chloride (1.00 mL, 10.71 mmol) in
dimethylformamide (5.0 mL) and 2-indolyl carbazole 6c (1.00 g,
2.14 mmol) in dimethylformamide (5.0 mL) to give the bis-indole-3-
carbaldehyde 7c (1.05 g, 90%) as a yellow solid, mp 240e242 ꢀC;
nmax (KBr) 3410, 2930,1662, 1488, 1452, 1370,1283,1248, 1147,1153,
4.7. 3,6-Di(1H-indol-2-yl)-9-methyl-9H-carbazole (6c)
The 9-methyl-9H-carbazole 6c was synthesised according to the
method for compound 6a using phenylhydrazone 5c (2.20 g,
5.35 mmol) and methanesulfonic acid (15 mL). Recrystallisation of
the resulting precipitate from 95% ethanol gave compound 6c
(1.48 g, 73%) as a yellow powder, mp >300 ꢀC; nmax (KBr) 3406,
3048, 1626, 1598, 1486, 1453, 1426, 1350, 1295, 1255, 1155, 787,
811, 748 cmꢁ1
;
lmax (MeCN) 307 nm (
3
33,450 cmꢁ1 Mꢁ1), 255
4.05 (3H, s, NMe),
(48,400); 1H NMR (300 MHz, DMSO-d6):
d
751 cmꢁ1
;
lmax (MeCN) 331 nm (
3
38,400 cmꢁ1 Mꢁ1), 311 (39,500),
3.96
7.24e7.30 (4H, m, indole H), 7.55 (2H, d, J 7.2 Hz, linker H),
7.86e7.97 (4H, m, indole H), 8.25 (2H, dd, J 7.2, 1.2 Hz, indole H),
8.83 (2H, d, J 1.2 Hz, linker H), 10.08 (2H, s, CHO), 12.55 (2H, br s,
252 (40,200), 203 (49,450); 1H NMR (300 MHz, DMSO-d6):
d
(3H, s, NMe), 6.92 (2H, d, J 1.5 Hz, indole H), 7.00e7.11 (4H, m, in-
dole H), 7.44 (2H, d, J 8.1 Hz, indole H), 7.56 (2H, d, J 7.7 Hz, linker H),
7.73 (2H, d, J 8.1 Hz, indole H), 8.02 (2H, dd, J 7.7, 1.6 Hz, linker H),
8.71 (2H, d, J 1.8 Hz, linker H), 11.58 (2H, br s, indole NH); 13C NMR
indole NH); 13C NMR (75 MHz, DMSO-d6):
d 29.9 (NMe), 110.6 (CH),
112.2 (CH), 113.5 (C), 121.3 (CH), 122.7 (CH), 123.3 (CH), 123.8 (CH),
124.2 (C), 126.4 (C), 128.3 (CH), 136.4 (C), 142.2 (C), 150.9 (C), 162.7
(C), 186.3 (CHO); HRMS (ESI): [MþNa]þ, found 490.1492.
(75 MHz, DMSO-d6): d 29.6 (NMe), 97.7 (CH), 110.2 (CH), 111.4 (CH),
C31H21N3NaO2 requires 490.1526.
117.3 (CH), 119.6 (CH), 120.0 (CH), 121.3 (CH), 122.8 (C), 124.0 (CH),
124.1 (C), 129.4 (C), 137.4 (C), 139.4 (C), 141.0 (C); HRMS (ESI):
[MþH]þ , found 412.1777. C29H22N3 requires 412.1808.
4.11. Bis-indole imine macrocycle (8a)
mixture of bis-indole 3,30-dicarbaldehyde 7a (0.400 g,
A
4.8. 2,20-(Dibenzo[b,d]furan-2,8-diyl)bis(1H-indole-3-
carbaldehyde) (7a)
0.88 mmol) and 1,4-diaminobutane (0.070 g, 0.880 mmol) was
heated at reflux overnight in ethanol (20 mL). The resulting pre-
cipitate was filtered and dried to give compound 8a (0.32 g, 73%) as
a yellow solid, mp >300 ꢀC; nmax (KBr) 3625, 3172, 2923, 2858,
1632, 1577, 1483, 1449, 1379, 1245, 1190, 1123, 1024, 822, 747,
Dimethylformamide (5 mL) and phosphoryl chloride (1.10 mL,
11.0 mmol) were stirred in an ice bath for 20 min. A cooled solution
of 2-indolyl dibenzofuran 6a (1.00 g, 2.22 mmol) in dry dime-
thylformamide (5 mL) was then added dropwise and the resulting
solution stirred overnight. The reaction was then quenched with
water and the mixture basified to high pH with 5 M aq sodium
hydroxide. The mixture was stirred at ambient temperature for
30 min before the resulting precipitate was filtered, washed with
water and dried to give the bis-indole-3-carbaldehyde 7a (1.02 g,
90%) as a yellow solid, mp 258e260 ꢀC; nmax (KBr) 3415, 1633, 1583,
748 cmꢁ1
1H NMR (300 MHz, DMSO-d6):
;
lmax (MeCN) 307 nm (
3
44,400 cmꢁ1 Mꢁ1), 256 (78,350);
1.87 (4H, s, CH2), 3.67 (4H, s,
d
CH2N), 7.13e7.26 (4H, m, indole H), 7.51 (2H, d, J 8.1 Hz, linker H),
7.98 (4H, s, indole H), 8.21 (2H, d, J 8.1 Hz, linker H), 8.62 (2H, s,
CH]N), 8.67 (2H, s, linker H), 11.57 (2H, br s, indole NH); 13C NMR
(75 MHz, DMSO-d6): d 28.1 (CH2), 61.8 (CH2N), 110.7 (C), 111.9 (CH),
112.4 (C), 112.6 (CH), 120.8 (CH), 121.4 (CH), 122.2 (C), 123.0 (C),
123.9 (CH), 124.1 (CH), 126.8 (C), 127.6 (C), 127.7 (CH), 141.3, (C),
156.3 (CH]N); HRMS (ESI): [MþH]þ, found 507.2176. C34H27N4O
requires 507.2179.
1452, 1374, 1203, 1101, 743, 699, 548 cmꢁ1
22,550 cmꢁ1 Mꢁ1), 255 (43,400), 228 (27,400); 1H NMR (300 MHz,
DMSO-d6): 7.24e7.34 (4H, m, indole H), 7.54 (2H, d, J 7.2 Hz, linker
;
lmax (MeCN) 308 nm (
3
d
H), 8.02 (4H, br s, indole H), 8.22 (2H, d, J 7.2 Hz, linker H), 8.82 (2H,
4.12. Bis-indole imine macrocycle (8b)
br s, linker H), 10.08 (2H, s, CHO), 12.55 (2H, br s, indole NH); 13C
NMR (75 MHz, DMSO-d6):
d 112.4 (CH), 112.9 (CH), 113.9 (C), 121.4
Bis-indole carbaldehyde 7b (0.200 g, 0.44 mmol), and 1,4-dia-
minobutane (0.030 g, 0.44 mmol) were heated together at reflux in
ethanol (20 mL) overnight. The resulting precipitate was filtered off
and dried to give compound 8b (0.14 g, 67%) as a yellow solid, mp
>300 ꢀC (from dichloromethane/hexane). Found C, 65.3; H, 4.9; N,
10.4. C34H27N5$1.8CH2Cl2 requires C, 65.3; H, 4,6; N, 10.3%; nmax
(KBr) 3395, 3230, 2925, 2849, 1625, 1578, 1452, 1377, 1339, 1283,
(CH), 122.8 (CH), 124.1 (CH), 124.2 (CH), 124.3 (C), 125.7 (C), 126.2
(C), 130.2 (CH), 136.4 (C), 149.4 (C), 157.1 (C), 186.2 (CHO); HRMS
(ESI): [MꢁH]þ, found 453.1234. C30H17N2O3 requires 453.1245.
4.9. 2,20-(9H-Carbazole-3,6-diyl)bis(1H-indole-3-
carbaldehyde) (7b)
1242, 745 cmꢁ1
(52,300); 1H NMR (300 MHz, DMSO-d6):
;
lmax (MeCN) 308 nm (
3
41,250 cmꢁ1 Mꢁ1), 256
1.87 (4H, s, CH2), 3.68
Compound 7b was synthesised according to the method for
compound 7a using phosphoryl chloride (1.10 mL, 11.0 mmol) in
dimethylformamide (5 mL) and compound 13 (1.00 g, 2.20 mmol)
in dimethylformamide (5.00 mL) to give the bis-indole-3-
carbaldehyde 7b (0.96 g, 85%) as a yellow solid, mp 254e256 ꢀC.
Found: C, 74.9; H, 4.7; N, 8.8. C30H19N3O2$1.5H2O requires C, 74.9; H,
4.6; N, 8.7%; nmax (KBr) 3237, 1628, 1581, 1453, 1372, 1245, 1135, 747,
d
(4H, s, CH2N), 7.11e7.24 (4H, m, indole H), 7.49 (2H, d, J 7.7 Hz, linker
H), 7.85 (2H, s, indole H), 7.88 (2H, dd, J 8.1, 1.4 Hz, indole H), 8.26
(2H, d, J 7.7 Hz linker H), 8.47 (2H, s, CH]N), 8.63 (2H, s, linker H),
11.87 (2H, br s, indole NH), 11.94 (1H, br s, linker NH); 13C NMR
(75 MHz, DMSO-d6): d 27.9 (CH2), 61.9 (CH2N), 109.9 (C), 111.6 (CH),
112.2 (CH), 120.7 (CH), 121.4 (CH), 122.2 (C), 122.6 (CH), 122.8 (C),
123.4 (CH), 125.9 (CH), 127.5 (C), 136.5 (C), 140.5 (C), 143.1 (C), 156.7
(CH]N); HRMS (ESI): [MþH]þ, found 506.2322. C34H28N5 requires
506.2339.
629 cmꢁ1
;
lmax (MeCN) 310 nm (
3
49,900 cmꢁ1 Mꢁ1), 255 (71,100),
7.22e7.27 (4H, m,
200 (69,450); 1H NMR (300 MHz, DMSO-d6):
d
indole H), 7.52 (2H, d, J 7.2 Hz, linker H), 7.78 (2H, d, J 8.1 Hz, indole
H), 7.87 (2H, dd, J 8.1, 1.2 Hz, indole H), 8.23 (2H, dd, J 7.2, 1.2 Hz,
linker H), 8.78 (2H, d, J 1.2 Hz, linker H), 10.07 (2H, s, CHO), 11.53
(1H, br s, linker NH), 11.68 (2H, br s, indole NH); 13C NMR (75 MHz,
4.13. Bis-indole imine macrocycle (8c)
DMSO-d6):
d
112.2 (2CH), 113.4 (C), 121.2 (C), 121.3(CH), 122.6 (CH),
Bis-indole carbaldehyde 7c (0.200 g, 0.42 mmol) and 1,4-
diaminobutane (0.040 g, 0.420 mmol) were heated together at
reflux in ethanol (20 mL) overnight. The resulting precipitate was
filtered and recrystallised from dichloromethane/light petroleum
123.1 (C), 123.3 (CH), 123.8 (CH), 126.4 (C), 128.2 (CH), 136.4 (C),
141.4 (C), 151.1 (aryl C), 186.3 (CHO); HRMS (ESI): [MþH]þ, found
454.1517. C30H20N3O2 requires 454.1556.

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),

I.F. Sengul et al. / Tetrahedron 68 (2012) 9050e9055
9055
118.5 (CH), 119.1 (CH), 120.8 (CH), 121.3 (CH), 122.8 (C), 124.2 (C),
126.5 (C), 126.6 (CH), 129.4 (C), 136.1 (C), 137.2 (C), 141.0 (C); HRMS
(ESI): [MþH]þ, found 524.2798. C35H34N5 requires 524.2809.
1.55 mmol) in absolute ethanol (20 mL) to give compound 11c
(0.1 g, 62%) as a yellow powder, mp 290e292 ꢀC; nmax (KBr) 3410,
3051, 2929, 1604, 1488, 1456, 1360, 1285, 1246, 1152, 1022, 810,
746 cmꢁ1
;
lmax (MeCN) 312 nm
(
3
13,650 cmꢁ1 Mꢁ1), 250
1.27 (4H, s, CH2), 1.54
4.20. Bis-indole amine macrocycle (11a)
(14,650); 1H NMR (300 MHz, DMSO-d6):
d
(4H, s, CH2), 2.77 (4H, s, CH2), 4.00 (3H, s, linker NMe), 4.10 (4H, s,
CH2), 7.04e7.17 (4H, m, indole H), 7.45 (2H, d, J 7.7 Hz, linker H),
7.50e7.90 (2H, br m, amino NH), 7.72e7.86 (6H, m, linker H, in-
dole H), 8.84 (2H, s, linker H), 11.52 (2H, br s, indole NH); 13C
Compound 11a was synthesised according to the method for
compound 10a using bis-imine macrocycle 9a (0.140 g,
0.260 mmol) and excess sodium borohydride (0.050 g, 1.30 mmol)
in absolute ethanol (20 mL) to give compound 11a (0.08 g, 58%) as
a yellow powder, mp >300 ꢀC; nmax (KBr) 3422, 2925, 2850, 1633,
NMR (75 MHz, DMSO-d6):
d 26.4 (CH2), 28.0 (CH2), 29.7 (NMe),
44.3 (CH2), 49.2 (CH2) 110.1 (CH), 111.5 (CH), 119.2 (2C), 119.3
(2CH), 121.0 (C), 121.6 (2CH), 122.6 (C), 127.0 (C), 127.2 (CH), 136.1
(C), 141.0 (C); HRMS (ESI): [MþH]þ, found 552.3117. C37H38N5
requires 552.3122.
1483, 1450, 1341, 1273, 1200, 1124, 821, 743, 610 cmꢁ1
305 nm (
DMSO-d6):
;
lmax (MeCN)
44,000 cmꢁ1 Mꢁ1), 240 (61,200); 1H NMR (300 MHz,
1.39 (4H, s, CH2), 2.10 (4H, s, CH2), 2.72 (4H, s, CH2),
3
d
3.90 (4H, s, CH2), 7.05e7.17 (4H, m, indole H), 7.43 (2H, d, J 7.7 Hz,
linker H), 7.70e7.90 (2H, br m, amino NH), 7.72 (2H, d, J 7.7 Hz,
linker H), 7.86 (2H, d, J 8.1 Hz indole H), 7.94 (2H, d, J 8.1 Hz, indole
H), 8.66 (2H, s, linker H), 11.33 (2H, br s, indole NH); 13C NMR
Acknowledgements
We thank the University of New South Wales and the Australian
Research Council for their financial support.
(75 MHz, DMSO-d6): d 26.3, 29.0, 44.3, 49.2 (CH2), 111.4 (2CH), 112.4
(CH), 119.2 (2CH), 121.8 (CH), 124.1(C), 128.6 (CH), 128.7 (2C), 129.4
(C), 136.2 (2C), 155.8 (C); HRMS (ESI): [MþH]þ, found 539.2787.
References and notes
C
36H35N4O requires 539.2805.
1. Kumar, D.; Kumar, N. M.; Chang, K. H.; Gupta, R.; Shah, K. Bioorg. Med. Chem.
Lett. 2011, 77, 182e188.
4.21. Bis-indole amine macrocycle (11b)
2. Gu, X. H.; Wan, X. Z.; Jiang, B. Bioorg. Med. Chem. Lett. 1999, 9, 569e572.
3. Garg, N. K.; Sarpong, R.; Stoltz, B. M. J. Am. Chem. Soc. 2002, 124, 13179e13184.
4. Dalton, J.; Miller, D.; Ahn, S.; Duke, C., III; Hwang, D. J.; Yang, J. U.S. Patent
US0,142,832 A1, 2009.
Compound 11b was synthesised according to the method for
compound 10a using bis-imine macrocycle 9b (0.170 g,
0.310 mmol) and excess sodium borohydride (0.050 g, 1.55 mmol)
in absolute ethanol (20 mL) to give compound 11b (0.09 g, 56%) as
a yellow powder, mp >300 ꢀC; nmax (KBr) 3420, 2926, 2852, 1631,
5. Jacobs, M. R.; Bajaksouzian, S.; Good, C. E.; Butler, M. M.; Williams, J. D.; Peet, N.
P.; Bowlin, T. L.; Endimiani, A.; Bonomo, R. A. Diagn. Microbiol. Infect. Dis. 2011,
69, 114e116.
ꢀ
6. Jacquemard, U.; Dias, N.; Lansiaux, A.; Bailly, C.; Loge, C.; Robert, J. M.; Lozach,
1487, 1455, 1363, 1284, 1246, 1153, 1125, 809 cmꢁ1
318 nm (
DMSO-d6):
;
lmax (MeCN)
30,550 cmꢁ1 Mꢁ1), 250 (33,750); 1H NMR (300 MHz,
1.20 (4H, s, CH2), 2.27 (4H, s, CH2), 3.67 (4H, s, CH2),
O.; Meijer, L.; Merour, J. Y.; Routier, S. Bioorg. Med. Chem. 2008, 16,
4932e4953.
7. Yoshikawa, E.; Miyata, Y.; Yanagawa, M. JPN Patent JP 015829 A, 2010.
8. Sugimoto, K.; Tominaga, T. PCT Patent WO084852 A1, 2010.
9. Goekjian, P. G.; Wu, G. Z.; Chen, S.; Zhou, L.; Jirousek, M. R.; Gillig, J. R.; Ballas, L.
M.; Dixon, J. T. J. Org. Chem. 1999, 64, 4238e4246.
10. Chang, K. J.; Moon, D.; Lah, M. S.; Jeong, K. S. Angew. Chem., Int. Ed. 2005, 117,
8140e8143.
11. Wang, T. C.; Chen, I. Helv. Chim. Acta 2004, 87, 983e990.
12. Mahapatra, A. K.; Roy, J.; Sahoo, P. Tetrahedron Lett. 2011, 52, 2965e2968.
13. Koyuncu, F. B.; Sefer, E.; Koyuncu, S.; Ozdemir, E. Macromolecules 2011, 44,
8407e8414.
14. Tacca, A.; Po, R.; Caldararo, M.; Chiaberge, S.; Gila, L.; Longo, L.; Mussini, P. R.;
Pellegrino, A.; Perin, N.; Salvalaggio, M. Electrochim. Acta 2011, 56,
6638e6653.
15. Sari, N.; Arslan, S.; Logoglu, E.; Akiyan. Gazi Univ. J. Sci. 2010, 16, 283e288.
16. Osowole, A. E-J. Chem. 2008, 5, 130e135.
3
d
3.77 (4H, s, CH2), 6.77e6.90 (4H, m, indole H), 7.18 (2H, d, J 7.7 Hz,
linker H), 7.40e7.60 (2H, br m, amino NH), 7.43 (2H, d, J 7.7 Hz,
linker H), 7.51 (2H, d, J 8.1 Hz, indole H), 7.58 (2H, d, J 8.1 Hz, indole
H), 8.44 (2H, s, linker H), 11.04 (2H, br s, indole NH), 11.10 (1H, br s,
linker NH); 13C NMR (75 MHz, DMSO-d6):
d 26.4, 29.2, 44.4, 49.1
(CH2), 109.9 (CH), 110.6 (C), 111.3 (CH), 119.0 (2CH), 120.0 (C), 121.1
(CH), 121.3 (CH), 124.3 (C), 127.0 (CH), 129.6 (C), 136.1 (C), 137.5 (C),
140.9 (C); HRMS (ESI): [MþH]þ, found 538.2930. C36H36N5 requires
538.2965.
4.22. Bis-indole amine macrocycle (11c)
17. Plant, S. G. P.; Rogers, K. M.; Williams, S. B. C. J. Chem. Soc. 1935, 741e744.
18. Dreher, S. D.; Weix, D. J.; Katz, T. J. J. Org. Chem. 1999, 64, 3671e3678.
ꢀ
ꢀ
ꢀ
19. Velasco, D.; Castellanos, S.; Lopez, M.; Lopez-Calahorra, F.; Brillas, E.; Julia, L. J.
Compound 11c was synthesised according to the method for
compound 10a using bis-imine macrocycle 9c (0.170 g,
0.310 mmol) and excess sodium borohydride (0.060 g,
Org. Chem. 2007, 72, 7523e7532.
20. Bruce, M. J.; McLean, G. A.; Royles, B. L. J.; Smith, D. M.; Standring, P. N. J. Chem.
Soc., Perkin Trans. 1 1995, 1789e1795.