Synthesis, complexation studies and biological applications of some novel stilbenophanes, indolophanes and bisindolostilbenophanes via McMurry coupling

Article abstract of DOI:10.1016/j.tet.2006.09.078

Various types of stilbenophanes, indolophanes and bisindolostilbenophanes were synthesized by intra-, inter- and tandem intra-, intermolecular McMurry coupling. Some of the indolophanes and bisindolostilbenophanes exhibited significant activity against th

Full text of DOI:10.1016/j.tet.2006.09.078

Tetrahedron 62 (2006) 12041–12050
Synthesis, complexation studies and biological applications of
some novel stilbenophanes, indolophanes and
bisindolostilbenophanes via McMurry coupling
a
b
b
Perumal Rajakumar,a, Merikapudi Gayatri Swaroop, S. Jayavelu and K. Murugesan
*
aDepartment of Organic Chemistry, University of Madras, Guindy Campus, Chennai 600 025, Tamil Nadu, India
bCentre for Advanced Studies in Botany, University of Madras, Guindy Campus, Chennai 600 025, Tamil Nadu, India
Received 13 June 2006; revised 6 September 2006; accepted 21 September 2006
Available online 27 October 2006
Abstract—Various types of stilbenophanes, indolophanes and bisindolostilbenophanes were synthesized by intra-, inter- and tandem intra-,
intermolecular McMurry coupling. Some of the indolophanes and bisindolostilbenophanes exhibited significant activity against the growth of
various bacteria. Complexation of some of the cyclophanes with TCNQ has also been studied.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
used to synthesize symmetrical and unsymmetrical pyridi-
nophanes.11
The synthesis of [2,2]paracyclophane1 by Cram and
Steinberg was a revolutionary breakthrough in the field of
cyclophane chemistry. In the synthesis of cyclophanes, the
ring-closing step is often crucial2 and various reagents and
reaction conditions have been developed for this purpose.
Many reagents containing transition metals were used for
the ring-closing step in cyclophane synthesis. Samarium-
catalyzed intramolecular pinacol coupling has been used in
the synthesis of planar and chiral paracyclophanes.3 Macro-
cyclic pyridinophanes4 from a,u-diynes were synthesized
by cobalt-mediated [2+2+2] cycloaddition. Biaryl type
cyclophanes5 were synthesized from [2,5]metacyclophane-
bromides and triflates by Suzuki coupling. Electro-active tris-
(tetrathiafulvaleno)dodecadehydro[18]annulenes6 with ester
substituents were synthesized by palladium-mediated cyclo-
trimerization of 4,5-diethynyl-tetrathiafulvalenes. Recently,
ruthenium-catalyzed ring-closing metathesis proved to be
a straightforward method to synthesize allenic cyclophanes.7
Use oflow valenttitanium forthesynthesisof supramolecular
structures has gained great impetus during recent times. An
intramolecular McMurry coupling reaction was used as a
key step in the enantiospecific synthesis of (+)-ipalbidine.12
Molecular clocks13 and artificial molecular devices such
as light-driven molecular motors14 were synthesized by
the application of McMurry coupling. Symmetrical and
unsymmetrical stilbenes15 and highly distorted cone calyx-
[4]arenes16 and porphyrin derivatives17 from tetrapyrrole-
dialdehyde have also been synthesized using intramolecular
McMurry coupling. Stilbenophanes are an interesting class
of compounds and are synthesized by inter-18 and intra-
molecular19 McMurry coupling technique.
The synthesis of biologically active cyclophanes20 has at-
tracted supramolecular chemists in recent times. The indole
moiety is present in a number of natural products21 and
known to be a bioactive nucleus.22 Cyclophanes with an
indole moiety, which are also called indolophanes23 have
received attention during recent times due to their applica-
tions in various fields. The synthesis of stilbene based indo-
lophanes, bisindolostilbenophanes,24 were reported recently
from this laboratory by using McMurry coupling. We wish to
report herein the synthesis and host–guest complexation
studies of various types of stilbenophanes 4a–4d and indolo-
phanes 6a–6c, 6d–6f, 8a–8d and 11a-11b with TCNQ. We
also wish to report the antimicrobial properties of various
indolophanes towards three important types of pathogenic
bacteria viz. Salmonella typhi, Serratia marcensis and
Streptococcus pneumoniae.
Microwave technology has been used for the synthesis of
cationic cyclophanes.8 The synthesis of thiacyclophanes
by a one-pot reaction, utilizing a suitable dibromide and
methanedithiolate generated from the double reduction of
CS2 with NaBH4 has also been reported from this labora-
tory.9 Recently, indolophanes and cylindrical indolophanes
were synthesized by tandem alkylation methodology
using NaH.10 Ring-closing metathesis has been successfully
* Corresponding author. Tel.: +91 44 22351269; fax: +91 44 22300488;
e-mail: perumalrajakumar@hotmail.com
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.09.078

12042
P. Rajakumar et al. / Tetrahedron 62 (2006) 12041–12050
2. Results and discussion
2.1. Stilbenophanes with m-terphenyl moiety
m-Terphenyldibromide 2a25 obtained by the radical bromi-
nation of m-terphenyl 1a was oxidized with tetrabutylammo-
nium dichromate TBADC in CHCl3 to give dialdehyde 3a in
69% yield. Addition of 1 equiv of the dialdehyde to a
solution of 20 equiv of TiCl4 and 40 equiv of Zn in THF,
followed by refluxing for 6 h resulted in the formation of
stilbenophane 4a (Scheme 1). Stilbenophanes 4b and 4c
were synthesized by using similar methodology from the
corresponding dialdehydes 3b and 3c. Reaction of p-tolyl-
magnesiumbromidewith 2,4,6-tribromoiodobenzene in THF
gave m-terphenyl 1d in 78% yield. m-Terphenyl 1d25 on
NBS bromination afforded the corresponding dibromide
2d. Treatment of dibromide 2d with TBADC in CHCl3 gave
dialdehyde 3d in 69% yield. Dialdehyde 3d underwent inter-
molecular McMurry coupling to give the stilbenophane 4d.
Figure 1. ORTEP diagram for the indolophane 6b.
were treated with indole-3-aldehyde to give dialdehydes
5b and 5c in 72 and 74% yields, respectively. Dialdehydes
5b and 5c underwent intramolecular McMurry coupling to
give indolophanes 6b and 6c. The structures of indolophanes
6b26 and 6c27 were thoroughly characterized by spectral and
analytical data and further confirmed by single crystal X-ray
analysis. The ORTEP diagrams of the cyclophanes 6b and 6c
are shown in Figs. 1 and 2, respectively. However, the di-
aldehydes 5d–5f with spacer units such as p-xylyl, 2,5-
dimethoxy-p-xylyl and 4,40-bis(methylene)-1,10-biphenyl
underwent intermolecular McMurry coupling to yield the
indolophanes 6d–6f (Scheme 2). From the above observa-
tion it is clear that dialdehydes 5a–5f underwent coupling
either intramolecularly or intermolecularly depending upon
the spacer unit.
Br
Br
Y
Y
i
X
X
1a X=H, Y=H
1b X=H, Y=Br
1c X=H, Y=COOMe
1d X=Br, Y=H
X
2a X=H, Y=H
2b X=H, Y=Br
2c X=H, Y=COOMe
2d X=Br, Y=H
ii
OHC
CHO
Y
Y
Y
iii
2.3. Synthesis of indolophanes with m-terphenyl spacer
unit
X
3a X=H, Y=H
3b X=H, Y=Br
3c X=H, Y=COOMe
3d X=Br, Y=H
X
The McMurry coupling was next used for the synthesis of
indolophanes with a m-terphenyl spacer. Dibromide 2a on
N-alkylation with indole-3-aldehyde in 25% NaOH in
CH3CN afforded dialdehyde 7a. The 1H and 13C NMR
4a X=H, Y=H
4b X=H, Y=Br
4c X=H, Y=COOMe
4d X=Br, Y=H
Scheme 1. Reagents and conditions: (i) NBS (2.1 equiv), benzoyl peroxide,
CCl4, reflux, 40 h, 80% (2a), 80% (2b), 78% (2c), 80% (2d); (ii) TBADC,
CHCl3, reflux, 6 h, 69% (3a), 67% (3b), 60% (3c), 69% (3d); (iii) TiCl4
(20 equiv), Zn (40 equiv), pyridine, THF, reflux, 6 h, 24% (4a), 18% (4b),
25% (4c), 24% (4d).
2.2. Synthesis of indolophanes with a smaller cavity
The synthetic utility of McMurry coupling has been investi-
gated for the synthesis of indolophanes, another rare class of
cyclophanes. o-Xylyl dibromide was reacted with indole-3-
aldehyde in CH3CN and 25% NaOH for 2 days to give pre-
indolophane dialdehyde 5a in 70% yield. Formation of 5a
1
was confirmed by H NMR, 13C NMR, mass spectral data
and elemental analysis. When 1 equiv of dialdehyde 5a
was treated with 20 equiv of TiCl4 and 40 equiv of Zn in
THF under reflux, indolophane 6a was obtained in 19% yield
through intramolecular McMurry coupling. The structure of
1
indolophane 6a was further confirmed by H NMR, 13C
NMR, FABMS spectral data and elemental analysis. Simi-
larly m-xylyl dibromide and 2,6-bis(bromomethyl)pyridine
Figure 2. ORTEP diagram for the indolophane 6c.

P. Rajakumar et al. / Tetrahedron 62 (2006) 12041–12050
12043
aromatic protons. In the 13C NMR spectrum, the NCH2 car-
bons appeared at d 54.8 and aldehydic carbons appeared
at d 184.8. Dialdehyde 7a on treatment with low valent
titanium under the conditions described earlier afforded
R
H
N
N
N
ii
i
CHO
CHO
CHO
1
indolophane 8a in 8% yield. In the H NMR spectrum,
5a R= o-xylyl
5b R= m-xylyl
two singlets were observed for indolophane 8a at d 5.23
and 6.86 for NCH2 and olefinic protons, in addition to aro-
matic protons. In the 13C NMR spectrum, cyclophane 8a
showed 13 signals and the structure was further confirmed
byFABMSspectrum andelementalanalysis. Similarmethod-
ology was used to synthesize the indolophanes 8b–8d with
a m-terphenyl spacer unit (Scheme 3).
5c R= 2,6-dimethylpyridine
5d R= p-xylyl
5e R= 2,5-dimethoxy-p-xylyl
5f R= 4,4'-bis(methylene)-1,1'-biphenyl
R
R
N
N
N
N
or
2.4. Synthesis of bisindolostilbenophanes by using
tandem intra- and intermolecular McMurry coupling
6a R= o-xylyl
6b R= m-xylyl
Encouraged by the versatility of the McMurry coupling tech-
nique for the synthesis of stilbenophanes and indolophanes
with various spacer units, the technique was further extended
for the synthesis of cylindrical cyclophanes, which are a
very rare class of cyclophanes. 1,3,5-Trimethyl-tris(bromo-
methyl)benzene28 was N-alkylated by using indole-3-alde-
hyde to give the trialdehyde 10a (Scheme 4). The
trialdehyde 10a on treatment with low valent titanium under-
went both intra- and intermolecular McMurry coupling to
afford only the bisindolostilbenophane 11a in 24% yield
and not the cylindrical cyclophane. The structure was further
confirmed by 1H NMR,24b 13C NMR,24b FABMS spectra and
elemental analysis. By similar methodology, 1,3,5-tris(bro-
momethyl)benzene was N-alkylated with indole-3-aldehyde
to give trialdehyde 10b in 78% yield. Trialdehyde 10b also
N
N
6c R= 2,6-dimethylpyridine
R
6d R= p-xylyl
6e R= 2,5-dimethoxy-p-xylyl
6f R= 4,4'-bis(methylene)-1,1'-biphenyl
Scheme 2. Reagents and conditions: (i) o,m,2,6-dimethylpyridine, p-2,5-di-
methoxy-p-xylyl, 4,40-bis(bromomethyl)-1,10-biphenyl dibromide, CH3CN,
25% NaOH, 48 h, 70% (5a), 72% (5b), 74% (5c), 74% (5d), 66% (5e), 68%
(5f); (ii)TiCl4 (20 equiv), Zn (40 equiv), THF, pyridine, reflux overnight,
19% (6a), 24% (6b), 36% (6c), 20% (6d), 23% (6e), 18% (6f).
spectra are in accordance with the proposed structure. In
the H NMR spectrum, the NCH2 and aldehydic protons
appeared as a singlet at d 5.40 and 10.01 in addition to
1
CHO
N
CHO
H
N
i
N
CHO
Y
X
N
CHO
Br
H
N
X
X
X
X
i
+
7a X=H, Y=H
7b X=H, Y=Br
7c X=H, Y=I
7d X=Br, Y=H
CHO
N
X
N
Br
X
Br
X
Y
9a X=CH3
9b X=H
CHO
CHO
10a X=CH3
10b X=H
N
N
N
N
N
X
N
X
X
ii
H
N
N
ii
H
X
X
Y
X
X
N
N
8a X=H, Y=H
8b X=H, Y=Br
8c X=H, Y=I
8d X=Br, Y=H
11a X=CH3
11b X=H
Scheme 3. Reagents and conditions: (i) 2a/2b/2c/2d, CH3CN, 25% NaOH,
48 h, 78% (7a), 76% (7b), 77% (7c), 70% (7d); (ii) TiCl4 (20 equiv), Zn
(40 equiv), THF, pyridine, reflux overnight, 8% (8a), 6% (8b), 5% (8c), 8%(8d).
Scheme 4. Reagents and conditions: (i) CH3CN, 25% NaOH, rt, 48 h, 80%
(10a), 78% (10b); (ii) TiCl4 (30 equiv), Zn (60 equiv), THF, pyridine, reflux
overnight, 24% (11a), 22% (11b).

12044
P. Rajakumar et al. / Tetrahedron 62 (2006) 12041–12050
CHO
O
Br
X
X
OH
X
X
i
ii
+
uncharacterisable product
3
O
X
O
Br
X
Br
CHO
9a X=CH3
9b X=H
CHO
CHO
12a X=CH3
12b X=H
Scheme 5. Reagents and conditions: (i) DMF, K2CO3, 80 ꢀC, 48 h, 65% (12a), 67% (12b); (ii) TiCl4 (30 equiv), Zn (60 equiv), THF, pyridine, reflux, overnight.
underwent cyclization intra- and intermolecularly with low
valent titanium in tandem nature to give bisindolostilbeno-
phane 11b in 22% yield. Tandem intra- and intermolecular
McMurry coupling technique for the synthesis of bisindolos-
tilbenophanes 11a and 11b is the first of its kind in the
literature.
(30 equiv) and Zn (60 equiv) in THF under reflux gave un-
characterizable products (Scheme 5). This may be due to
the non-rigidity of the trialdehyde due to the ether linkage,
which can give some flexibility and hence could lead to
polymerization. It is noteworthy to mention that trialdehydes
10a and 10b could undergo both intra- and intermolecular
McMurry coupling to give cyclophanes 11a and 11b,
whereas trialdehydes 12a and 12b gave only uncharacteriz-
able products.
2.5. Synthesis of dioxastilbenophanes
McMurry coupling has been successfully used in the synthe-
sis of dioxastilbenophanes.29 Encouraged by such earlier re-
ports from our laboratory, we focused our attention on the
synthesis of cyclophanes from trialdehydes 12a and 12b.
O-Alkylation of 1,3,5-trimethyl-tris(bromomethyl)benzene
with p-hydroxybenzaldehyde afforded the trialdehyde 12a
in 65% yield. Similarly, O-alkylation of 1,3,5-tris(bromo-
methyl)benzene with p-hydroxybenzaldehyde afforded
trialdehyde 12b.30 12a (1 equiv) was treated with TiCl4
2.6. Attempted synthesis of cylindrical stilbenophanes
Intermolecular McMurry coupling of dialdehydes 3a–3d to
give stilbenophanes 4a–4d prompted us to explore this
technique for the synthesis of cylindrical stilbenophane 15.
Tribromide 1331 on oxidation with TBADC in CHCl3
afforded trialdehyde 14 in 69% yield. The structure of
trialdehyde 14 was confirmed by 1H NMR, 13C NMR spectra
and elemental analysis. Trialdehyde 14 on treatment with
TiCl4 and Zn under refluxing conditions afforded uncharac-
terizable products (Scheme 6).
Br
Br
OHC
CHO
i
3. Antibacterial studies of the indolophanes
S. No. Indolophanes Concentration
(mg/mL)
Zone of inhibitiona (mm)
Salmonella Serratia Streptococcus
Br
CHO
typhi
marcescens pneumoniae
13
14
1
2
3
4
5
6b
25
50
75
4.4
6.2
9.6
6.0
8.4
10.4
5.0
6.5
9.7
ii
6c
25
50
75
5.2
8.2
11.2
5.6
8.2
10.6
5.2
6.2
8.8
8a
25
50
75
4.9
7.8
10.9
5.3
7.8
10.3
4.9
5.8
8.5
8d
25
50
75
5.0
8.0
11.1
5.4
8.0
10.4
5.1
6.0
8.7
11a
11b
25
50
75
5.0
9.2
12.0
5.4
8.8
10.2
5.8
7.0
10.2
6
25
50
75
5.2
8.2
11.2
5.6
8.2
10.6
5.2
6.2
8.8
15
Scheme 6. Reagents and conditions: (i) TBADC, CHCl3, reflux, 6 h, 69%;
(ii) TiCl4 (30 equiv), Zn (60 equiv), pyridine, THF, reflux, overnight.
a
Values of zone of inhibition are the mean of six replicates.

P. Rajakumar et al. / Tetrahedron 62 (2006) 12041–12050
12045
Bacterial cultures such as S. typhi, S. marcensis and S. pneu-
moniae were obtained from Madras Medical College, Chen-
nai, India. All the cultures were maintained on nutrient agar
medium. The activity was tested by disc diffusion method.32
of cyclophane]/absorbance versus 1/concentration of guest
was linear (Fig. 3). From the slope and the intercept values
Ka (Ka¼interceptꢁslopeꢂ1) and 3 (3¼interceptꢂ1) were
evaluated. The plots were linear and suggest that the pre-
dominant species in the solution was 1:1 complex. Ka and
3 values of CT complexes formed from 6a–6c, 11a and
11b are shown in Table 2.
3.1. Methodology
Each of the bacterium was inoculated in 50 mL of nutrient
broth individually and was incubated in an environ shaker
for 10 h at 150 rpm. About 150 mL of each of the broth cul-
ture was amended with 125 mL of molten nutrient agar
medium and was plated. Indolophanes 6b, 6c, 8a, 8d, 11a
and 11b each at 25, 50 and 75 mg/mL were prepared in
CHCl3 and were loaded onto filter paper disc. The discs
were then dried and placed on each of the bacterium
amended medium. The assay plates were incubated at
35 ꢀC for 48 h. The zone of inhibition was measured, which
was expressed in millimetre.
0.000025
0.00002
0.000015
0.00001
0.000005
0
y = 9E-11x + 7E-07
R2 = 0.9997
250000
0
50000
100000
150000
200000
3.2. Results
1/[X]
While screening on nutrient agar medium, all the six indolo-
phanes 6b, 6c, 8a, 8d, 11a and 11b at all the concentrations
produced noteworthy inhibition against S. typhi, S. marcensis
and S. pneumoniae. However, 6c, 8a, 8d, 11a and 11b in-
hibited S. typhi significantly followed by Serratia marcensis
when compared with S. pneumoniae. On the contrary, 6b in-
hibited effectively Serratia marcensis than the others.
Figure 3. Plot between 1/[X] and [Y]/A for compound 6b.
Table 2. Complexation of TCNQ with cyclophanes 6a–6c, 11a and 11b
Cyclophane
Ka
3
6a
6b
6c
11a
11b
1ꢁ103
2ꢁ108
2ꢁ107
7.14ꢁ102
7.936ꢁ103
2.5ꢁ104
1.4ꢁ106
2ꢁ105
2.00ꢁ103
1.66ꢁ105
4. Complexation studies
Cyclophanes 6a–6c, 11a and 11b exhibited charge transfer
complexes with TCNQ among all the cyclophanes reported
in this paper. Complexation studies of 6a–6c, 11a and 11b
with TCNE and PQT were not successful. Cyclophanes
6a–6c, 11a and 11b show UV–vis absorption maxima at
241.3, 234, 274, 232 and 230 nm, respectively. However,
the acceptor TCNQ shows absorption maxima at 274 nm.
Cyclophanes 6a–6c, 11a and 11b form a charge transfer
complex with TCNQ as evidenced by the appearance of ab-
sorption maxima at 395, 398, 396, 398 and 397, respectively.
The studies were carried out as outlined below.
Cyclophane 6c complexes with TCNQ more strongly than
6b, which is followed by 6a. In the case of 11a and 11b,
the former one complexes more effectively than the latter.
5. Conclusion
Various types of stilbenophanes, indolophanes and bisindo-
lostilbenophanes were obtained by intra-, inter-, tandem
intra- and intermolecular McMurry coupling. Some of
the indolophanes exhibited noteworthy inhibition against
S. typhi, S. marcescens and S. pneumoniae. Charge transfer
studies were carried out with some indolophanes and TCNQ.
In a typical experiment, 3 mL aliquot of a standard stock so-
lution of the cyclophane in 1:1 mixture of CHCl3/CH3CN
was placed in a quartz cuvette. A known amount of the elec-
tron deficient guest molecule was added in incremental
amounts and changes in absorbance of the CT bands were
recorded. Table 1 shows the CT complexation studies of
6b with various concentrations of TCNQ. A plot of [concn
6. Experimental
6.1. General
All melting points are uncorrected. 1H and 13C NMR spectra
were recorded in CDCl3 using TMS as an internal standard on
a JEOL 400 and JEOL 500 spectrometers at 500, 400, 125 and
100 MHz, respectively. Mass spectra were recorded on a
JEOL DX 303 HF spectrometer and FAB mass spectra were
recorded on a JEOL SX 102/DA-6000 mass spectrometer.
Table 1. Benesi–Hildebrand treatment data of the CT complex formed
between the cyclophane 6b and TCNQ lmax¼398 nm. Concentration of
cyclophane 6b¼10ꢂ5 M
Concentration of
guest, [X] (M)
Absorbance
(A)
[Y]/A (M)
1/[X] (Mꢂ1
)
4.9ꢁ10ꢂ6
9.8ꢁ10ꢂ6
14.7ꢁ10ꢂ6
19.6ꢁ10ꢂ6
24.5ꢁ10ꢂ6
0.500
0.978
1.424
1.811
2.088
0.00002
204,081
102,040
68,027
51,020
40,816
0.0000102
0.000007
0.0000055
0.0000047
6.2. Procedure A for NBS bromination
Freshly recrystallized N-bromosuccinimide (NBS)
(92 mmol/135 mmol) was added in 5–6 equal portions at
Ka¼7.14ꢁ102 Mꢂ1, 3¼2ꢁ107 Mꢂ1 cmꢂ1, SD¼99.97 (%).

12046
P. Rajakumar et al. / Tetrahedron 62 (2006) 12041–12050
6 h apart to a solution of methyl aryl compound (44 mmol)
in CCl4 (350 mL) heated at reflux; each addition was
immediately followed by adding a few milligrams of benzoyl
peroxide. After 40 h of total reaction time at reflux the
mixture was cooled and the precipitated succinimide was
removed by filtration. The solvent was removed and the
residue was chromatographed (SiO2) from hexane/CHCl3
and then recrystallized.
removed under reduced pressure and the aqueous solution
was extracted several times with CH2Cl2. Combined organic
layers were washed with water and brine and dried over an-
hydrous Na2SO4. The residue obtained after solvent removal
was chromatographed in hexane to give 1d as a white solid in
78% (15 g); mp 126–130 ꢀC; [found: C, 71.25; H, 5.10.
C20H17Br requires C, 71.23; H, 5.08%]; dH (500 MHz,
CDCl3) 7.67–7.66 (m, 3H, Ph); 7.51–7.49 (m, 4H, Ph);
7.27–7.25 (m, 4H, Ph); 2.41 (s, 6H, CH3); dC (125 MHz,
CDCl3) 143.6, 138.0, 137.0, 129.7, 128.5, 127.1, 124.5,
123.3, 21.3; m/z (EI) 337 (M+), 339 (M++2).
6.3. General procedure B for oxidation of dibromide
to dialdehyde
Tetrabutylammonium dichromate (TBADC) was prepared
by stirring a heterogeneous mixture of tetrabutylammonium
hydrogen sulfate (100 mmol) in CH2Cl2 (100 mL) and
K2CrO4 (250 mmol) in water (100 mL) at room temperature
for 2 h. The reagent was obtained from the organic layer as
orange coloured pasty mass. The dibromide was dissolved in
CHCl3, mixed with TBADC (1.32 equiv) and refluxed for
6 h. CHCl3 was removed under reduced pressure and the
resulting pasty mass was mixed with column silica gel and
chromatographed. Elution with a mixture of CHCl3/hexane
(2:3) gave the respective dialdehyde.
6.5.2. Compound 2d. Following the general procedure A,
dibromide 2d was obtained as a light yellow colour solid
in 80% yield; mp 148–151 ꢀC; [found: C, 48.51; H, 3.02.
C20H15Br3 requires C, 48.52; H, 3.05%]; dH (500 MHz,
CDCl3) 7.70–7.65 (m, 3H, Ph); 7.58–7.55 (m, 4H, Ph);
7.49–7.47 (m, 4H, Ph); 4.54 (s, 4H, CH2); dC (125 MHz,
CDCl3) 143.0, 139.8, 137.8, 129.8, 129.2, 127.7, 127.5,
124.8, 33.1; m/z (EI) 495 (M+), 497 (M++2), 499 (M++4).
6.5.3. Compound 3a. Following the general procedure B,
dialdehyde 3a was obtained as a white solid in 69% yield;
mp 204–208 ꢀC; [found: C, 83.92; H, 4.95. C20H14O2 re-
quires C, 83.90; H, 4.93%]; IR (KBr) nmax: 1686 cmꢂ1; dH
(500 MHz, CDCl3) 10.08 (s, 2H, CHO); 7.99 (d, 4H,
J 8.6 Hz, Ph); 7.87 (s, 1H, Ph); 7.81 (d, 4H, J 8.0 Hz, Ph);
7.69–7.67 (m, 2H, Ph); 7.62–7.60 (m, 1H, Ph); dC
(125 MHz, CDCl3) 191.9, 146.7, 140.6, 135.4, 130.4,
129.7, 127.8, 127.4, 126.5; m/z (EI) 286 (M+).
6.4. General procedure C for N-alkylation
To a solution of indole-3-aldehyde (7.5 mmol) in CH3CN
(50 mL), NaOH (25%) solution was added and stirred for
10 min. The bromide (15.9 mmol/22.5 mmol) in acetonitrile
(20 mL) was added at once and stirred at room temperature
for 48 h. After completion of the reaction CH3CN was re-
moved under reduced pressure and the reaction mixture
was extracted with CH2Cl2 (300 mL), washed with water,
brine and dried over anhydrous Na2SO4. The solvent was
removed under reduced pressure and the residue was chro-
matographed using hexane and ethyl acetate (3:2) as eluent.
6.5.4. Compound 3b. Following the general procedure B,
dialdehyde 3b was obtained as a light yellow colour solid
in 67% yield; mp 215–217 ꢀC; [found: C, 65.75; H, 3.56.
C20H13BrO2 requires C, 65.77; H, 3.59%]; IR (KBr) nmax
:
1696 cmꢂ1; dH (500 MHz, CDCl3) 10.06 (s, 2H, CHO);
7.95–7.91 (m, 4H, Ph); 7.85–7.81 (m, 7H, Ph); dC
(125 MHz, CDCl3) 191.6, 145.0, 143.1, 137.9, 132.6,
130.2, 129.8, 127.3, 124.9; m/z (EI) 365 (M+), 367 (M++2).
6.5. General procedure D for McMurry coupling
A solution of zero valent titanium prepared from TiCl4
(20 equiv/30 equiv) with zinc (40 equiv/60 equiv) in dry
THF (75 mL) under a nitrogen atmosphere at 0 ꢀC was
allowed to attain room temperature after 0.5 h and then re-
fluxed for 1 h. Aldehyde was added in one lot to the freshly
prepared low valent titanium. After the addition, the reaction
mixture was refluxed overnight. The reaction mixture was
cooled and then quenched with saturated K2CO3 solution.
The precipitated inorganic material was removed by filtra-
tion. The precipitate was thoroughly washed with THF for
several times and the combined THF extract was removed
under reduced pressure. The residue was then dissolved in
water and extracted in CHCl3 (200 mL), washed with water
(2ꢁ200 mL), brine (100 mL) and dried over Na2SO4. Crude
product, obtained after evaporation of CHCl3, was purified
by column chromatography.
6.5.5. Compound 3c. Following the general procedure B, di-
aldehyde 3c was obtained as a light yellow colour solid in
60% yield; mp 209–211 ꢀC; [found: C, 76.70: H, 4.73.
C22H16O4 requires C, 76.73; H, 4.68%]; IR (KBr) nmax
:
1699, 1720 cmꢂ1; dH (500 MHz, CDCl3) 10.06 (s, 2H,
CHO); 7.93 (d, 4H, J 8.0 Hz, Ph); 7.61–7.55 (m, 3H, Ph);
7.45–7.44 (m, 4H, Ph); 3.37 (s, 3H, COOCH3); dC
(125 MHz, CDCl3) 192.0, 169.2, 146.5, 139.6, 135.6,
132.6, 130.0, 129.9, 129.2, 52.2, 30.5; m/z (EI) 345 (M+).
6.5.6. Compound 3d. Following the general procedure B,
dialdehyde 3b was obtained as a light yellow colour solid
in 69% yield; mp 223–226 ꢀC; [found: C, 65.79; H, 3.61.
C20H13BrO2 requires C, 65.77; H, 3.59%]; IR (KBr) nmax
:
1703 cmꢂ1; dH (500 MHz, CDCl3) 10.07 (s, 2H, CHO);
7.99 (s, 2H, Ph); 7.97 (s, 2H, Ph); 7.79–7.75 (m, 7H, Ph);
dC (125 MHz, CDCl3) 191.7, 145.2, 142.5, 135.9, 130.5,
130.2, 127.9, 125.2, 123.8; m/z (EI) 365 (M+), 367 (M++2).
6.5.1. Compound 1d. To a stirred solution of p-tolylmagne-
siumbromide (prepared from 31.1 g, 18.1 mmol of p-bromo-
toluene and 4.41 g, 18.1 mmol of Mg in 40 mL of THF)
under N2 atmosphere was added dropwise 2,4,6-tribromo-
benzene in THF (150 mL) (5.6 mmol) over 1 h at reflux.
Stirring was continued for 6 h, after which the reaction was
quenched with cold, dilute HCl (40 mL). Then THF was
6.5.7. Compound 4a. Following the general procedure D,
stilbenophane 4a was obtained as a light yellow colour
solid in 24% yield; mp >300 ꢀC; [found: C, 94.42; H,
5.53. C40H28 requires C, 94.45; H, 5.55%]; dH (400 MHz,

P. Rajakumar et al. / Tetrahedron 62 (2006) 12041–12050
12047
CDCl3) 7.50–7.42 (m, 8H, Ph); 7.36 (d, 8H, J 8.2 Hz, Ph);
7.06 (d, 8H, J 8.2 Hz, Ph); 6.74 (s, 4H, CH]CH); dC
(100.4 MHz, CDCl3) 141.6, 140.2, 136.6, 131.0, 129.8,
129.2, 126.9, 125.0, 124.9; m/z (FABMS) 508 (M+).
2H, CHO); 8.32 (d, 2H, J 7.7 Hz, Ar); 7.79 (s, 2H, Ar);
7.54 (m, 1H, Ar); 7.33–7.30 (m, 2H, Ar); 7.28–7.25 (m,
4H, Ar); 6.89 (d, 2H, J 7.7 Hz, Ar); 5.44 (s, 4H, NCH2); dC
(125 MHz, CDCl3) 184.8, 155.8, 138.9, 138.7, 137.4,
124.4, 123.3, 122.3, 120.7, 110.4, 52.5; m/z (EI) 393 (M+).
6.5.8. Compound 4b. Following the general procedure D,
stilbenophane 4b was obtained as a light yellow colour solid
in 18% yield; mp >300 ꢀC; [found: C, 72.08; H, 3.97.
C40H26Br2 requires C, 72.04; H, 3.93%]; dH (400 MHz,
CDCl3) 7.42–7.32 (m, 6H, Ph); 7.25 (d, 8H, J 8.3 Hz, Ph);
6.91 (d, 8H, J 8.3 Hz, Ph); 6.78 (s, 4H, CH]CH); dC
(100.4 MHz, CDCl3) 142.7, 139.6, 135.5, 130.7, 128.9,
128.1, 127.1, 125.2, 124.7; m/z (FABMS) 666 (M+), 668
(M++2), 670 (M++4).
6.5.14. Compound 5d. Following the general procedure C,
dialdehyde 5d was obtained as a light brown colour solid in
74% yield; mp 187–190 ꢀC; [found: C, 79.58; H, 5.16; N,
7.11. C26H20N2O2 requires C, 79.57; H, 5.14; N, 7.14%];
IR (KBr) nmax: 1657 cmꢂ1; dH (500 MHz, CDCl3) 10.00
(s, 2H, CHO); 8.33 (m, 2H, Ar); 7.74 (s, 2H, Ar); 7.52 (d,
4H, J 8.4 Hz, Ar); 7.35–7.30 (m, 2H, Ar); 7.25–7.22 (m,
4H, Ar); 5.39 (s, 4H, NCH2); dC (125 MHz, CDCl3) 184.8,
140.5, 138.6, 137.5, 134.7, 127.8, 125.6, 124.3, 123.3,
122.3, 118.7, 110.5, 50.7; m/z (EI) 392 (M+).
6.5.9. Compound 4c. Following the general procedure D,
stilbenophane 4c was obtained as a light yellow colour solid
in 25% yield; mp >300 ꢀC; [found: C, 84.62; H, 5.20.
C44H32O4 requires C, 84.59; H, 5.16%]; dH (400 MHz,
CDCl3) 7.48–7.41 (m, 6H, Ph); 7.36 (d, 8H, J 7.8 Hz, Ph);
7.22 (d, 8H, J 7.8 Hz, Ph); 6.86 (s, 4H, CH]CH); 3.37 (s,
6H, COOCH3); dC (100.4 MHz, CDCl3) 205.5, 140.5,
139.7, 138.1, 130.4, 129.4, 127.2, 127.0, 126.4, 125.7,
51.5; m/z (FABMS) 624 (M+).
6.5.15. Compound 5e. Following the general procedure C,
dialdehyde 5e was obtained as a light brown colour solid
in 66% yield; mp 196–200 ꢀC; [found: C, 74.30; H, 5.37;
N, 6.21. C28H24N2O4 requires C, 74.32; H, 5.35; N,
6.19%]; IR (KBr) nmax: 1647 cmꢂ1; dH (500 MHz, CDCl3)
9.98 (s, 2H, CHO); 8.31–8.28 (m, 2H, Ar); 7.72 (s, 2H,
Ar); 7.39–7.38 (m, 2H, Ar); 7.31–7.30 (m, 2H, Ar); 7.25
(s, 2H, Ar); 6.51 (s, 2H); 5.30 (s, 4H, NCH2); 3.64 (s, 6H,
OCH3); dC (125 MHz, CDCl3) 184.8, 151.2, 138.8, 137.6,
125.5, 124.5, 124.2, 123.1, 122.2, 118.4, 111.8, 110.4,
56.1, 46.0; m/z (EI) 452 (M+).
6.5.10. Compound 4d. Following the general procedure D,
stilbenophane 4d was obtained as a light yellow colour solid
in 24% yield; mp >300 ꢀC; [found: C, 72.02; H, 3.91.
C40H26Br2 requires C, 72.04; H, 3.93%]; dH (400 MHz,
CDCl3) 7.64–7.42 (m, 6H, Ph); 7.31 (d, 8H, J 8.3 Hz, Ph);
7.04 (d, 8H, J 7.8 Hz, Ph); 6.74 (s, 4H, CH]CH); dC
(100.4 MHz, CDCl3) 143.9, 139.0, 133.4, 128.7, 127.0,
126.6, 126.0, 123.6, 123.3; m/z (FABMS) 666 (M+), 668
(M++2), 670 (M++4).
6.5.16. Compound 5f. Following the general procedure C,
dialdehyde 5f was obtained as a light brown colour solid
in 68% yield; mp 136–140 ꢀC; [found: C, 82.05; H, 5.19;
N, 5.99. C32H24N2O2 requires C, 82.03; H, 5.16; N,
5.98%]; IR (KBr) nmax: 1651 cmꢂ1; dH (500 MHz, CDCl3)
10.01 (s, 2H, CHO); 8.34–8.32 (m, 2H, Ar); 7.74 (s, 4H,
Ar); 7.54–7.51 (m, 2H, Ar); 7.35–7.30 (m, 4H, Ar); 7.25–
7.20 (m, 6H, Ar); 5.39 (s, 4H, NCH2); dC (125 MHz,
CDCl3) 184.7, 140.5, 138.5, 137.5, 134.8, 127.8, 125.6,
124.3, 123.2, 122.3, 118.7, 110.5, 50.7; m/z (EI) 468 (M+).
6.5.11. Compound 5a. Following the general procedure C,
dialdehyde 5a was obtained as a light brown colour solid
in 70% yield; mp 156–158 ꢀC; [found: C, 79.59; H, 5.11;
N, 7.18. C26H20N2O2 requires C, 79.57; H, 5.14; N,
7.14%]; IR (KBr) nmax: 1647 cmꢂ1; dH (500 MHz, CDCl3)
9.90 (s, 2H, CHO); 8.05 (d, 2H, J 8.1 Hz, Ar); 7.42 (s, 2H,
Ar); 7.41–7.40 (m, 2H, Ar); 7.27–7.24 (m, 4H, Ar); 7.16–
7.11 (m, 4H, Ar); 5.24 (s, 4H, NCH2); dC (125 MHz,
CDCl3) 184.8, 137.5, 137.4, 133.2, 129.9, 129.8, 125.5,
124.6, 123.6, 122.4, 118.9, 110.0, 48.4; m/z (EI) 392 (M+).
6.5.17. Compound 6a. Following the general procedure D,
indolophane 6a was obtained as a light yellow colour solid in
19% yield; mp 126 ꢀC; [found: C, 86.61, H, 5.63; N, 7.79.
C26H20N2 requires C, 86.64; H, 5.59; N, 7.77%]; dH
(400 MHz, CDCl3) 8.17 (d, 2H, J 7.4 Hz, Ar); 7.79 (d, 2H,
J 8.6 Hz, Ar); 7.64 (t, 2H, J 7.5 Hz, Ar); 7.46 (d, 4H,
J 8.6 Hz, Ar); 7.29 (t, 2H, J 7.5 Hz, Ar); 6.72 (s,
2H, CH]CH); 6.30 (s, 2H, Ar); 5.80 (s, 4H, NCH2); dC
(100.4 MHz, CDCl3) 153.9, 136.4, 130.3, 129.5, 128.9,
125.1, 124.2, 120.0, 119.4, 112.0, 108.5, 46.2; m/z (FABMS)
360 (M+).
6.5.12. Compound 5b. Following the general procedure, C
dialdehyde 5b was obtained as a light brown colour solid
in 72% yield; mp 130–132 ꢀC; [found: C, 79.55; H, 5.12;
N, 7.19. C26H20N2O2 requires C, 79.57; H, 5.14; N,
7.14%]; IR (KBr) nmax: 1631 cmꢂ1; dH (500 MHz, CDCl3)
9.97 (s, 2H, CHO); 8.31 (d, 2H, J 7.5 Hz, Ar); 7.65 (s, 2H,
Ar); 7.33–7.31 (m, 4H, Ar); 7.29–7.25 (m, 4H, Ar); 7.20–
7.18 (m, 1H, Ar); 6.89 (s, 1H, Ar); 5.27 (s, 4H, NCH2); dC
(125 MHz, CDCl3) 184.7, 138.3, 137.3, 136.7, 130.1,
127.1, 125.6, 124.4, 123.3, 122.3, 118.7, 110.3, 50.7; m/z
(EI) 392 (M+).
6.5.18. Compound 6b. Following the general procedure D,
indolophane 6b was obtained as a light yellow colour solid in
24% yield; mp 297 ꢀC; [found: C, 86.68; H, 5.61; N, 7.77.
C26H20N2 requires C, 86.64; H, 5.59; N, 7.77%]; dH
(400 MHz, CDCl3) 7.59 (d, 2H, J 7.3 Hz, Ar); 7.23 (d,
2H, J 7.8 Hz, Ar); 7.18–7.14 (m, 3H, Ar); 7.12 (d, 2H,
J 7.8 Hz, Ar); 7.07 (d, 2H, J 7.3 Hz); 6.79 (s, 2H,
CH]CH); 6.49 (s, 2H, Ar); 6.09 (s, 1H); 4.98 (s,
4H, NCH2); dC (100.4 MHz, CDCl3) 139.0, 138.0, 128.5,
128.1, 126.1, 125.0, 122.2, 120.1, 119.7, 114.2, 110.1,
49.6; m/z (FABMS) 360 (M+).
6.5.13. Compound 5c. Following the general procedure C,
dialdehyde 5c was obtained as a light brown colour solid in
74% yield; mp 178–182 ꢀC; [found: C, 76.34; H, 4.89; N,
10.65. C25H19N3O2 requires C, 76.32; H, 4.87; N, 10.68%];
IR (KBr) nmax: 1652 cmꢂ1; dH (500 MHz, CDCl3) 10.01 (s,

12048
P. Rajakumar et al. / Tetrahedron 62 (2006) 12041–12050
6.5.19. Compound 6c. Following the general procedure D,
indolophane 6c was obtained as a light yellow colour solid
in 36% yield; mp 228–232 ꢀC; [found: C, 83.09; H, 5.32;
N, 11.64. C25H19N3 requires C, 83.08; H, 5.30; N,
11.63%]; dH (500 MHz, CDCl3) 7.72 (d, 2H, J 7.7 Hz,
Ar); 7.54 (t, 1H, J 7.6 Hz, Ar); 7.31–7.29 (m, 2H, Ar);
7.19 (m, 1H, Ar); 7.17–7.13 (m, 4H, Ar); 7.11 (s, 1H, Ar);
6.86 (s, 2H, Ar); 6.82 (s, 2H, CH]CH); 5.17 (s, 4H,
NCH2); dC (125 MHz, CDCl3) 155.2, 136.9, 136.6, 131.2,
128.9, 122.9, 121.1, 120.2, 119.4, 119.0, 111.7, 108.9,
49.8; m/z (FABMS) 361 (M+).
Ar); 7.39–7.37 (m, 6H, Ar); 7.33–7.31 (m, 6H, Ar); 7.25–
7.21 (m, 5H, Ar); 5.54 (s, 4H, NCH2); dC (125 MHz,
CDCl3) 184.9, 143.1, 138.8, 137.6, 130.5, 130.4, 130.3,
126.9, 126.8, 125.6, 118.7, 110.6, 110.5, 50.7; m/z (EI)
623 (M+), 625 (M++2).
6.5.25. Compound 7c. Following the general procedure C,
dialdehyde 7c was obtained as a brown colour solid in
77% yield; mp 128–132 ꢀC; [found: C, 68.09; H, 4.09; N,
4.20. C38H27N2O2I requires C, 68.07; H, 4.06; N, 4.18%];
IR (KBr) nmax: 1652 cmꢂ1; dH (500 MHz, CDCl3) 10.02
(s, 2H, CHO); 8.34–8.33 (m, 2H, Ar); 7.77 (s, 2H, Ar);
7.41–7.36 (m, 5H, Ar); 7.35–7.30 (m, 6H, Ar); 7.25–7.20
(m, 6H, Ar); 5.36 (s, 4H, NCH2); dC (125 MHz, CDCl3)
184.8, 143.1, 142.0, 138.7, 137.6, 134.9, 130.4, 130.3,
130.8, 130.2, 126.9, 126.8, 125.6, 118.7, 97.6, 94.8, 50.7;
m/z (EI) 670 (M+).
6.5.20. Compound 6d. Following the general procedure D,
indolophane 6d was obtained as a light yellow colour solid in
20% yield; mp 135 ꢀC; [found: C, 86.68; H, 5.61; N, 7.76.
C52H40N4 requires C, 86.64; H, 5.59; N, 7.77%]; dH
(400 MHz, CDCl3) 7.50 (d, 8H, J 7.8 Hz, Ar); 7.14 (d,
8H, J 8.3 Hz, Ar); 7.03 (d, 4H, J 7.8 Hz, Ar); 7.07 (d, 4H,
J 7.8 Hz); 6.94 (s, 4H, Ar); 6.77 (s, 4H, CH]CH); 5.13 (s,
8H, NCH2); dC (125 MHz, CDCl3) 140.0, 137.1, 136.7,
129.0, 127.4, 127.3, 125.9, 121.7, 119.2, 118.9, 111.1,
109.5, 49.6; m/z (FABMS) 720 (M+).
6.5.26. Compound 7d. Following the general procedure C,
dialdehyde 7d was obtained as a brown colour solid in 70%
yield; mp 218–222 ꢀC; [found: C, 73.22; H, 4.33; N, 4.53.
C38H27N2O2Br requires C, 73.20; H, 4.36; N, 4.49%]; IR
(KBr) nmax: 1646 cmꢂ1; dH (500 MHz, CDCl3) 10.01 (s,
2H, CHO); 8.33–8.30 (m, 2H, Ar); 7.75 (s, 4H, Ar); 7.65
(s, 2H, Ar); 7.54 (d, 4H, J 8.0 Hz); 7.35–7.30 (m, 4H, Ar);
7.26–7.24 (m, 5H, Ar); 5.40 (s, 4H, NCH2); dC (125 MHz,
CDCl3) 185.3, 142.1, 141.9, 139.6, 137.7, 135.4, 131.4,
131.1, 130.9, 130.6, 128.9, 128.6, 127.9, 125.9, 119.8,
110.9, 50.9; m/z (EI) 623 (M+), 625 (M++2).
6.5.21. Compound 6e. Following the general procedure D,
indolophane 6e was obtained as a light yellow colour solid
in 23% yield; mp 134 ꢀC; [found: C, 79.94; H, 5.77; N,
6.68. C56H48N4O4 requires C, 79.98; H, 5.75; N, 6.66%];
dH (400 MHz, CDCl3) 7.48 (d, 4H, J 7.8 Hz, Ar); 7.21 (d,
4H, J 8.3 Hz, Ar); 7.09 (m, 8H, Ar); 7.02 (t, 4H, J 7.3 Hz,
Ar); 6.80 (s, 4H, CH]CH); 6.24 (s, 4H, Ar); 5.11 (s, 8H,
NCH2); 3.49 (s, 12H, OCH3); dC (100.4 MHz, CDCl3)
150.8, 136.8, 128.8, 126.0, 125.9, 121.5, 118.9, 118.6,
111.1, 110.6, 109.5, 55.9, 55.8, 44.5; m/z (FABMS) 840 (M+).
6.5.27. Compound 8a. Following the general procedure D,
indolophane 8a was obtained as a light yellow colour solid in
8% yield; mp 224–229 ꢀC; [found: C, 89.01; H, 5.53; N,
5.46. C76H56N4 requires C, 89.03; H, 5.51; N, 5.46%]; dH
(500 MHz, CDCl3) 7.60 (s, 2H, Ar); 7.53–7.52 (m, 4H,
Ar); 7.46–7.42 (m, 12H, Ar); 7.22–7.20 (m, 6H, Ar); 7.18–
7.13 (m, 12H, Ar); 7.12–7.04 (m, 8H); 6.86 (s, 4H,
CH]CH); 5.23 (s, 8H, NCH2); dC (125 MHz, CDCl3)
140.4, 129.0, 127.6, 127.4, 126.2, 126.0, 125.9, 121.8,
119.2, 118.9, 110.1, 109.5, 49.6; m/z (FABMS) 1025.
6.5.22. Compound 6f. Following the general procedure D,
indolophane 6f was obtained as a light yellow colour solid
in 18% yield; mp 137 ꢀC; [found: C, 88.06; H, 5.55; N,
6.43. C64H48N4 requires C, 88.04; H, 5.54; N, 6.42%]; dH
(400 MHz, CDCl3) 7.52 (d, 8H, J 7.3 Hz, Ar); 7.38 (d, 8H,
J 8.3 Hz, Ar); 7.18–7.07 (m, 20H, Ar); 6.84 (s, 4H,
CH]CH); 5.20 (s, 8H, NCH2); dC (100.4 MHz, CDCl3)
137.0, 136.7, 129.0, 127.3, 127.2, 125.8, 121.7, 119.1,
118.8, 110.5, 109.4, 49.5; m/z (FABMS) 872 (M+).
6.5.28. Compound 8b. Following the general procedure D,
indolophane 8b was obtained as a light yellow colour solid in
6% yield; mp 231–233 ꢀC; [found: C, 77.20; H, 4.58; N,
4.78. C76H54Br2N4 requires C, 77.16; H, 4.60; N, 4.74%];
dH (500 MHz, CDCl3) 7.64–7.52 (m, 6H, Ar); 7.47–7.27
(m, 8H, Ar); 7.25–7.22 (m, 12H, Ar); 7.19–7.15 (m, 8H,
Ar); 7.10–7.08 (m, 8H, Ar); 6.88 (s, 4H, CH]CH); 5.25
(s, 8H, NCH2); dC (125 MHz, CDCl3) 131.1, 130.5, 128.8,
127.6, 126.9, 126.5, 126.2, 122.8, 121.7, 119.9, 118.9,
114.1, 110.5, 50.2; m/z (FABMS) 1180 (M+), 1182
(M++2), 1184 (M++4).
6.5.23. Compound 7a. Following the general procedure C,
dialdehyde 7a was obtained as a light brown colour solid
in 78% yield; mp 218–220 ꢀC; [found: C, 83.84; H, 5.16;
N, 5.16. C38H28N2O2 requires C, 83.80; H, 5.18; N,
5.14%]; IR (KBr) nmax: 1650 cmꢂ1; dH (500 MHz, CDCl3)
10.01 (s, 2H, CHO); 8.34–8.32 (m, 2H, Ar); 7.75 (s, 2H,
Ar); 7.59 (d, 4H, J 8.6 Hz, Ar); 7.54–7.49 (m, 4H, Ar);
7.37–7.34 (m, 2H, Ar); 7.33–7.30 (m, 4H, Ar); 7.26–7.25
(m, 4H, Ar); 5.40 (s, 4H, NCH2); dC (125 MHz, CDCl3)
184.8, 141.3, 141.0, 137.5, 134.6, 128.0, 127.8, 126.5,
126.0, 125.6, 124.3, 123.3, 122.3, 118.6, 110.5, 50.8; m/z
(EI) 545 (M+).
6.5.29. Compound 8c. Following the general procedure D,
indolophane 8c was obtained as a light yellow colour solid
in 5% yield; mp 218–220 ꢀC; [found: C, 71.50; H, 4.28; N,
4.36. C76H54I2N4 requires C, 71.48; H, 4.26; N, 4.39%];
dH (500 MHz, CDCl3) 7.53–7.48 (m, 6H, Ar); 7.35–7.27
(m, 8H, Ar); 7.22–7.18 (m, 12H, Ar); 7.16–7.14 (m, 8H,
Ar); 7.12–7.11 (m, 8H, Ar); 6.94 (s, 4H, CH]CH); 5.29
(s, 8H, NCH2); dC (125 MHz, CDCl3) 130.3, 129.9, 127.7,
127.3, 126.9, 126.4, 126.0, 121.7, 120.9, 119.1, 118.9,
111.1, 109.5, 49.6; m/z (FABMS) 1276.
6.5.24. Compound 7b. Following the general procedure C,
dialdehyde 7b was obtained as a light brown colour solid
in 76% yield; mp 132–134 ꢀC; [found: C, 73.24; H, 4.39;
N, 4.51. C38H27N2O2Br requires C, 73.20; H, 4.36; N,
4.49%]; IR (KBr) nmax: 1651 cmꢂ1; dH (500 MHz, CDCl3)
9.99 (s, 2H, CHO); 8.35–8.33 (m, 2H, Ar); 7.76 (s, 2H,

P. Rajakumar et al. / Tetrahedron 62 (2006) 12041–12050
12049
6.5.30. Compound 8d. Following the general procedure D,
indolophane 8d was obtained as a light yellow colour solid in
8% yield; mp 215–217 ꢀC; [found: C, 77.18; H, 4.57; N,
4.76. C76H54Br2N4 requires C, 77.16; H, 4.60; N, 4.74%];
dH (500 MHz, CDCl3) 7.44–7.36 (m, 6H, Ar); 7.34–7.27
(m, 8H, Ar); 7.21-7.13 (m, 12H, Ar); 7.11–7.05 (m, 8H,
Ar); 7.01–6.97 (m, 8H, Ar); 6.87 (s, 4H, CH]CH); 5.24
(s, 8H, NCH2); dC (125 MHz, CDCl3) 131.9, 131.1, 129.3,
128.7, 127.9, 127.4, 127.1, 126.8, 123.4, 122.7, 121.2,
120.6, 119.8, 117.8, 111.2, 50.4; m/z (FABMS) 1180 (M+),
1182 (M++2), 1184 (M++4).
6.5.35. Compound 12a. A mixture of p-hydroxybenzalde-
hyde (2 mmol) and tribromide 9a (7.7 mmol) and K2CO3
(3.46 g) in anhydrous DMF (30 mL) were stirred under
nitrogen for 48 h at 60 ꢀC. The reaction mixture was poured
into water (1 L) and stirred. The resulting precipitate was
filtered, washed with water (3ꢁ150 mL) and dissolved in
CH2Cl2 (350 mL). The organic layer was washed with
NaOH solution (5% w/v, 2ꢁ100 mL), dried (Na2SO4) and
evaporated to give a residue, which was chromatographed
(SiO2) using hexane/CHCl3 (1:2) to give the trialdehyde
12a in 65% yield; mp 140–142 ꢀC [found: C, 75.81; H,
5.81. C33H30O6 requires C, 75.84; H, 5.79%]; IR (KBr)
nmax: 1680 cmꢂ1; dH (500 MHz, CDCl3) 9.90 (s, 3H,
CHO); 7.88 (d, 6H, J 8.4 Hz, Ph); 7.13 (d, 6H, J 8.4 Hz,
Ph); 5.21 (s, 6H, PhCH2); 2.45 (s, 9H, CH3); dC
(125 MHz, CDCl3) 190.9, 164.0, 139.8, 132.2, 131.4,
130.4, 114.9, 65.3, 16.2; m/z (EI) 522 (M+).
6.5.31. Compound 10a. Following the general procedure C,
trialdehyde 10a was obtained as a light brown colour solid in
80% yield; mp 199–201 ꢀC; [found: C, 79.14; H, 5.63, 6.99.
C39H33N3O3 requires C, 79.16; H, 5.62; N, 7.10]; IR (KBr)
nmax: 1649 cmꢂ1; dH (500 MHz, CDCl3) 9.89 (s, 3H, CHO);
8.28 (d, 3H, J 7.5 Hz, Ar); 7.51 (d, 3H, J 8.0 Hz, Ar); 7.41–
7.34 (m, 6H, Ar); 7.27 (s, 3H, Ar); 5.43 (s, 6H, NCH2); 2.28
(s, 9H, CH3); dC (125 MHz, CDCl3) 184.6, 140.5, 137.4,
135.2, 130.9, 125.9, 124.5, 123.7, 122.1, 118.6, 109.9,
45.5, 16.6; m/z (EI) 591 (M+).
6.5.36. Compound 12b. Following the procedure as men-
tioned for compound 12a trialdehyde 12b was obtained in
67% yield; mp 141–143 ꢀC [found: C, 75.01; H, 5.01.
C30H24O6 requires C, 74.99; H, 5.03]; IR (KBr) nmax
:
1682 cmꢂ1; dH (500 MHz, CDCl3) 9.88 (s, 3H, CHO);
7.83 (d, 6H, J 8.4 Hz, Ph); 7.49 (s, 3H, Ph); 7.06 (d, 6H,
J 8.4 Hz, Ph); 5.18 (s, 6H, PhCH2); dC (125 MHz, CDCl3)
190.9, 163.5, 137.4, 132.1, 130.4, 126.3, 115.2, 69.81; m/z
(EI) 480 (M+).
6.5.32. Compound 10b. Following the general procedure
C, trialdehyde 10b was obtained as a brown colour solid
in 78% yield; mp 174–178 ꢀC; [found: C, 78.65; H, 4.96;
N, 7.66. C36H27N3O3 requires C, 78.67; H, 4.95; N,
7.65%]; IR (KBr) nmax
: ; dH (500 MHz,
1653 cmꢂ1
CDCl3) 9.90 (s, 3H, CHO); 8.28 (d, 3H, J 8.0 Hz, Ar);
7.55 (s, 3H, Ar); 7.30–7.28 (m, 3H, Ar); 7.21–7.18 (m,
3H, Ar); 7.04 (d, 3H, J 8.6 Hz, Ar); 6.80 (s, 3H, Ar);
5.22 (s, 6H, NCH2); dC (125 MHz, CDCl3) 184.6, 138.0,
137.1, 125.5, 125.2, 124.4, 123.3, 122.4, 118.8, 110.2,
50.4; m/z (EI) 549 (M+).
6.5.37. Compound 14. Following the general procedure B,
trialdehyde 14 was obtained as a white colour solid in 69%
yield; mp 230–234 ꢀC; [found: C, 83.04; H, 4.64.
C27H18O3 requires C, 83.06; H, 4.65%]; IR (KBr) nmax
:
1691 cmꢂ1; dH (500 MHz, CDCl3) 10.09 (s, 3H, CHO);
8.02 (d, 6H, J 8.4 Hz, Ph); 7.90 (s, 3H, J 8.4 Hz, Ph); 7.86
(d, 6H, J 7.7 Hz, Ph); dC (125 MHz, CDCl3) 191.9, 146.4,
141.7, 135.8, 130.5, 128.1, 126.6; m/z (EI) 390 (M+).
6.5.33. Compound 11a. Following the general procedure D,
indolophane 11a was obtained as a light yellow colour solid
in 24% yield; mp 222–226 ꢀC; [found: C, 86.11; H, 6.05; N,
7.68. C78H66N6 requires C, 86.15; H, 6.12; N, 7.73%]; dH
(500 MHz, CDCl3) 7.62 (d, 2H, J 7.5 Hz, Ar); 7.53 (d,
4H, J 8.0 Hz, Ar); 7.47 (d, 2H, J 8.0 Hz, Ar); 7.38 (d, 4H,
J 8.1 Hz, Ar); 7.29 (t, 2H, J 8.0 Hz, Ar); 7.25 (s, 2H, Ar);
7.20–7.17 (m, 6H, Ar); 7.08 (t, 4H, J 7.5 Hz, Ar); 6.87 (s,
4H, Ar); 6.42 (s, 4H, CH]CH); 6.35 (s, 2H, CH]CH);
5.50 (d, 4H, J 14.3 Hz, NCH2); 5.35 (s, 4H, NCH2); 5.23
(d, 4H, J 14.3 Hz, NCH2); 2.48 (s, 12H, CH3); 2.26 (s, 6H,
CH3); dC (125 MHz, CDCl3) 141.2, 137.4, 137.2, 136.7,
135.1, 130.8, 129.2, 128.0, 127.5, 127.4, 123.0, 121.7,
119.8, 119.7, 119.3, 119.1, 111.9, 110.8, 109.0, 108.9,
44.7, 44.6, 16.7, 16.2; m/z (FABMS) 1087 (M+).
Acknowledgements
The authors thank CSIR, New Delhi for financial assistance.
M.G.S. thanks University of Madras for providing URF,
SAIF, Lucknow and Chennai for providing FABMS.
References and notes
1. Cram, D. J.; Steinberg, H. J. Am. Chem. Soc. 1951, 73, 5691–
5704.
2. (a) Yamato, T.; Hideshima, C.; Nagano, Y.; Tashiro, M.
J. Chem. Res., Synop. 1996, 266–267; (b) Losensky, H. W.;
€
6.5.34. Compound 11b. Following the general procedure D,
indolophane 11b was obtained as a light yellow colour solid
in 22% yield; mp 282–289 ꢀC; [found: C, 86.12; H, 5.37; N,
8.34. C72H54N6 requires C, 86.20; H, 5.43; N, 8.38%]; dH
(500 MHz, CDCl3) 7.67 (d, 4H, J 7.5 Hz, Ar); 7.61 (d, 2H,
J 7.5 Hz); 7.25–7.11 (m, 20H, Ar); 6.85 (s, 6H, Ar); 6.81
(s, 4H, Ar); 6.50 (s, 4H, CH]CH); 6.01 (s, 2H,
CH]CH); 5.17 (s, 4H, NCH2); 4.95 (s, 8H, NCH2); dC
(125 MHz, CDCl3) 139.3, 137.8, 137.5, 136.7, 129.5,
129.0, 128.2, 128.1, 125.2, 125.1, 124.7, 124.2, 121.9,
119.8, 119.4, 119.2, 119.0, 113.8, 111.2, 109.8, 109.5,
49.5, 49.0; m/z (FABMS) 1002 (M+).
Selthanan, H.; Ehlen, A.; Vogtle, F.; Bargon, J. Angew.
Chem. 1988, 100, 1225–1227; (c) Larkins, H. L.; Hamilton,
A. D. Tetrahedron Lett. 1986, 27, 2721–2724; (d) M€uller, E.;
Roscheisen, G. Chem. Ber. 1957, 90, 543–553; (e) Elix, J. A.;
Sargent, M. V. J. Am. Chem. Soc. 1968, 90, 1631–1634; (f)
Vinod, T. K.; Hart, H. Tetrahedron Lett. 1988, 29, 885–888;
(g) Kang, H. C.; Hanson, A. W.; Eaton, B.; Boekelheide, V.
J. Am. Chem. Soc. 1985, 107, 1979–1985; (h) Chastrette, M.;
Chastrette, F. J. Chem. Soc., Chem. Commun. 1973, 534–535;
€
€
(i) Vogel, E.; Kocher, S.; Lex, J. Angew. Chem., Int. Ed.
Engl. 1986, 25, 257–259; (j) Rubin, Y.; Parker, T. C.; Khan,
S. I.; Holliman, C. L.; McElvany, W. J. Am. Chem. Soc.

12050
P. Rajakumar et al. / Tetrahedron 62 (2006) 12041–12050
1996, 118, 5308–5309; (k) Camacho, D. H.; Salo, E. V.; Guan,
19. (a) Tanner, D.; Wennerstrom, O.; Norinder, U. Tetrahedron
1986, 42, 4499–4502; (b) Kasahara, A.; Izumi, T. Chem.
Lett. 1978, 21–22; (c) Kasahara, A.; Izumi, T.; Shimizu, I.
Chem. Lett. 1979, 1119–1122; (d) Eisch, J. J.; Kaska, D. D.;
Peterson, C. J. J. Org. Chem. 1966, 31, 453–456; (e) Ben, I.;
Castedo, L.; Saa, J. M.; Seijas, J. A.; Suau, R.; Tojo, G.
J. Org. Chem. 1985, 50, 2236–2240; (f) Muller, K.;
Meier, H.; Bouas-Laurent, H.; Desvergne, J. P. J. Org. Chem.
1996, 61, 5474–5480; (g) Meier, H.; Fetten, M. Tetrahedron
Lett. 2000, 41, 1535–1538; (h) Misumi, S.; Otsubo, T. Acc.
Chem. Res. 1978, 11, 251–256; (i) Kasahara, A.; Izumi, T.;
Shimizu, I.; Satou, M.; Katou, T. Bull. Chem. Soc. Jpn. 1982,
55, 2434–2440.
Z. Org. Lett. 2004, 6, 865–868; (l) Smith, B. B.; Hill, D. E.;
Crop, T. A.; Walsh, R. D.; Cartrette, D.; Hipps, S.; Shachter,
A. M.; Pennington, W. T.; Kwochka, W. R. J. Org. Chem.
2002, 67, 5333–5337; (m) Heuft, M.; Collins, S. K.; Fallis,
A. G. Org. Lett. 2003, 11, 1911–1914; (n) Smith, A. B., III;
Adams, C. M.; Kozmin, A.; Paone, D. V. J. Am. Chem. Soc.
2001, 123, 5925–5937.
3. Ueda, T.; Kanomata, N.; Machida, H. Org. Lett. 2005, 7, 2365–
2368.
4. Bonaga, V. R. L.; Zhang, H.-C.; Moretto, A. F.; Ye, H.;
Gauthier, D. A.; Li, J.; Leo, C. G.; Maryanoff, B. E. J. Am.
Chem. Soc. 2005, 127, 3473–3485.
5. Yukihiro, O.; Masanori, Y.; Jun, N. Synlett 2005, 352–354.
6. Enozawa, H.; Hasegawa, M.; Takamatsu, D.; Fukui, K.-I.;
Iyoda, M. Org. Lett. 2006, 8, 1917–1920.
7. Christian, E. J.; Norbert, K. Eur. J. Org. Chem. 2005, 11, 2322–
2329.
8. Rajakumar, P.; Murali, V. Chem. Commun. 2001, 2710–2711.
9. Rajakumar, P.; Dhanasekaran, M.; Selvam, S.; Aravindan,
P. G.; Velmurugan, D. J. Org. Chem. 2005, 70, 3267–3270.
10. Rajakumar, P.; Gayatri Swaroop, M. Tetrahedron Lett. 2006,
47, 3019–3022.
20. Wipf, P.; Furegati, M. Org. Lett. 2006, 8, 1901–1904.
21. Yu, J.; Wang, T.; Liu, X.; Deschamps, J.; Anderson, J. F.; Liao,
X.; Cook, J. M. J. Org. Chem. 2003, 68, 7565–7581.
22. Nussbaum, F. V. Angew. Chem., Int. Ed. 2003, 42, 3068–3071.
23. (a) Bodwell, G. J.; Li, J.; Miller, D. O. Tetrahedron 1999, 55,
12939–12956; (b) Ortner, B.; Waibel, R.; Gmeiner, P. Angew.
Chem., Int. Ed. 2001, 40, 1283–1285; (c) Bodwell, G. J.; Li,
J. Org. Lett. 2002, 4, 127–130; (d) Black, D. StC.; Craig,
D. C.; Rezaie, R. Chem. Commun. 2002, 810–811; (e) Gibe,
R.; Green, J. R.; Davidson, G. Org. Lett. 2003, 5, 1003–1005.
24. Part of the synthesis described in this paper has been published
as two separate short communications, see: (a) Rajakumar, P.;
Gayatri Swaroop, M. Tetrahedron Lett. 2004, 45, 6165–6167;
(b) Rajakumar, P.; Gayatri Swaroop, M. Tetrahedron Lett.
2005, 46, 8543–8546.
25. Hart, H.; Rajakumar, P. Tetrahedron 1995, 51, 1313–1336.
26. Senthil Kumar, G.; Chinnakali, K.; Gayatri Swaroop, M.;
Rajakumar, P.; Fun, H.-K. Acta Crystallogr., Sect. E 2006, 62,
1809–1811.
27. Senthil Kumar, G.; Chinnakali, K.; Gayatri Swaroop, M.;
Rajakumar, P.; Fun, H.-K. Acta Crystallogr., Sect. E 2006,
62, 2608–2610.
11. Branowska, D.; Rykowski, A. Tetrahedron 2005, 61, 10713–
10718.
12. Toshio, H.; Hidenori, N.; Hiromasa, N.; Hirotake, M.
Tetrahedron Lett. 2003, 44, 3035–3038.
ꢀ
´
´
´
13. Garcia Martınez, A.; Osıo Barcina, J.; de Fresno Cerezo, A.;
del Rosario Torres Salvador, M. Chem.—Eur. J. 2003, 9,
1157–1165.
14. Ter Wiel, M. K. J.; Van Delden, R. A.; Meetsma, A.; Feringa,
B. L. J. Am. Chem. Soc. 2003, 125, 15076–15086.
15. Mayekar, N. V.; Chattopadhyay, S.; Nayak, S. K. Synthesis
2003, 2041–2046.
16. Arduini, A.; Fami, S.; Pochini, A.; Sicuri, A.; Ungaro, R.
Tetrahedron 1995, 51, 7951–7958.
17. Aukauloo, M. A.; Guilard, R. New J. Chem. 1994, 18, 1205–
1207.
18. (a) Tanner, D.; Weennerstrom, O. Tetrahedron Lett. 1981, 22,
2313–2316; (b) Vogel, E.; Sicken, M.; Rohrig, P.; Schmickler,
H.; Lex, J.; Ermer, O. Angew. Chem., Int. Ed. Engl. 1988, 27,
411–414.
ˇˇ
ˇ
28. Jirı, Z.; Magdalena, P.; Petr, H.; Milos, T. Synthesis 1994, 1132.
29. Rajakumar, P.; Murali, V. Tetrahedron 2004, 60, 2351–2360.
30. Rajakumar, P.; Srisailas, M. Tetrahedron Lett. 2002, 43, 1909–
1913.
€
31. Sendoff, N.; Kibener, W.; Vogtle, F.; Franken, S.; Puff, H.
Chem. Ber. 1988, 121, 2179–2185.
32. Nair, R.; Kalariya, T.; Chanda, S. Turk. J. Biol. 2005, 29, 41–47.