A convenient Fischer indole synthesis of 2,3′-biindoles

Article abstract of DOI:10.1016/j.tetlet.2011.03.049

Both symmetrical and unsymmetrical 2,3′-biindoles are efficiently synthesized in good to excellent yields by Fischer indole synthesis. The scope of the method was evaluated by examining substituent effects with para-substituted hydrazines and 3-acylindole

Full text of DOI:10.1016/j.tetlet.2011.03.049

Tetrahedron Letters 52 (2011) 2642–2644
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A convenient Fischer indole synthesis of 2,30-biindoles
⇑
Philip E. Alford, Liangfeng Fu, Joseph K. Kubert, Lingshan Wang, Gordon W. Gribble
Department of Chemistry, Dartmouth College, Hanover, NH 03755, USA
a r t i c l e i n f o
a b s t r a c t
Both symmetrical and unsymmetrical 2,30-biindoles are efficiently synthesized in good to excellent yields
by Fischer indole synthesis. The scope of the method was evaluated by examining substituent effects with
para-substituted hydrazines and 3-acylindoles.
Article history:
Received 25 February 2011
Accepted 9 March 2011
Ó 2011 Elsevier Ltd. All rights reserved.
The Fischer indole synthesis, first described by Emil Fischer in
1883, has prevailed as the flagship indolization method for more
than a century.1 Given our recent interest in the synthesis of bipyr-
roles and biindole natural products, we were surprised to find that
the present method has apparently not been investigated as a gen-
eral approach to 2,30-biindoles.2 Biindole natural products are
ubiquitous and have a strong history of medicinal value.3 The vast
majority of these compounds exhibit a 2,20-linkage, notably the
numerous naturally occurring indolocarbazoles and related deriv-
atives.4 In contrast, 2,30-biindoles, inaccessible from typical bioor-
ganic building blocks, are relatively underrepresented in nature.5
Indirubin (1), isolated from Isatis indigotin, is the biologically ac-
tive component of the traditional Chinese preparation Danggui
Longhui Wan.6 It has been noted that indolocarbazoles bearing a
2,30-biindole are angular equivalents to medicinally active 2,20-
linked structures and members of the remarkably bioactive
[b]-annulated carbazole family.7 Ancorinazole (2), isolated in
2002, is the first naturally occurring indolocarbazole to contain a
2,30-biindole (Fig. 1).8 In supramolecular chemistry progress with
anion sensing molecular devices has celebrated biindoles as some
of the few structures that have found success in this application.9
Few general synthetic methods have been described for 2,30-
biindoles.10 Acid-catalyzed dimerization of indole is a well known
source of the indole dimer 4 which may be dehydrogenated to fur-
nish the parent 2,30-biindole 5 (Scheme 1).11 Though limited to the
preparation of symmetrical biindoles, this method has been widely
used.12 A related method uses 3-bromoindole to produce 5 in one
step.13 While this improved process (Scheme 2) allows the prepa-
ration of asymmetric 2,30-biindoles 8 in good to excellent yields, a
tendency for 3-bromoindole to self-condense and the competitive
production of several types of indole oligomers can result in prob-
lematic reaction conditions.14
reductive cyclization (Scheme 3).15 Unfortunately, this specialized
route relies on the presence of both alkoxy-substituents.
HN
O
HO
NaO3SO
NH
N
H
N
1
2
O
OSO3Na
Figure 1. Biindole natural products.
NH
NH
HCl
Pd/C
PhMe
N
Et2O
N
N
H
H
H
4
5
3
65% overall
Scheme 1. Preparation of 5 via the indole dimer.
R
Br
NH
HCl
+
R
DCM
N
N
H
N
H
H
6
7
8
64-92%
Scheme 2. One-step indole dimerization to asymmetric 8.
O
NO2
OR
OR
SnCl2 • HCl
AcOH
Young et al. described a route to 5,6-dialkoxy-2,30-biindoles 10
via ortho-nitration of a 3-(phenylacetyl)indole 9 followed by
HN
N
H
N
OR
H
RO
9
10
10-54%
⇑
Corresponding author. Tel.: +1 603 646 3118; fax: +1 603 646 3946.
E-mail address: ggribble@dartmouth.edu (G.W. Gribble).
Scheme 3. Reductive-cyclization to 5,6-disubstituted 10.
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.03.049

P. E. Alford et al. / Tetrahedron Letters 52 (2011) 2642–2644
2643
Palladium-catalyzed cross-coupling has also been used to produce
2,30-biindoles.16
HN
HN
HN
HN
HN
H2N
Intrigued by the absence of a general Fischer method, we exam-
ined the indolization of readily available 3-acetylindole 11 and 3-
acetyl-1-(phenylsulfonyl)indole 12.
R1
R1
R1
In the event, acid-catalyzed generation of the desired hydra-
zones was complete by TLC and NMR, and these hydrazones were
used directly in the next step (Scheme 4). Since the neighboring
indole moiety seems to facilitate hydrolysis of the resulting hydra-
zone, anhydrous conditions were necessary. From the protected
hydrazone 14, neat PPA cleanly generated the corresponding 2,30-
biindole 15 in good yield, which was deprotected with aqueous
hydroxide to the parent compound 5, spectroscopically identical
to a sample prepared via indole dimerization (Scheme 1). Direct
conversion of the unprotected hydrazone 13 to the parent 2,30-
biindole was not successful under these conditions.17
To explore the generality of this method, we investigated the ef-
fect of substituents at the para-position of the hydrazine and the a-
position of the starting ketone. Hydrazone formation was per-
formed over molecular sieves and indolizations were conducted
with PPA in toluene in the usual manner to produce 2,30-biindoles
(Table 1).18–33
N
N
N
SO2Ph
SO2Ph
SO2Ph
27
26
Figure 2. Stabilization and tautomerization of hydrazone 26.
It might be noted that the intermediate hydrazone (e.g., 26) can
be considered a vinylogous amidrazone in which the positive
charge resulting from protonation is resonance stabilized by the in-
dole double bond. Although this stabilized species is still capable of
hydrolysis, indolization requires tautomerization to the ene-hydra-
zine 27—a tautomer that lacks the advantage of a delocalized cat-
ion (Fig. 2). We suspect that this effect is amplified in the case of
the unprotected hydrazone 13.
Since many Fischer indole syntheses are known to be rate lim-
iting at tautomerization,1 we suggest that substrates favoring for-
mation of the ene-hydrazine will show improved indolization. An
In each case where para-nitrophenylhydrazine was used, the
resulting hydrazones 23–25 (not shown) resisted indolization.
These stable nitro-substituted hydrazones are deactivated toward
the protonation that precedes both hydrolysis and tautomeriza-
tion, thus allowing them to survive chromatography. The stability
of these compounds highlights the importance of hydrazone tauto-
merization to the corresponding ene-hydrazine for indolization.
a
-phenyl substituent provides a major driving force for this tauto-
merization via conjugative stabilization of the ene-hydrazine—an
effect that results in substantially improved yields. While hydra-
zines with electron-donating substituents were problematic with
the acetyl and propionyl substrates, phenylacetyl-substituted
hydrazines (entries 10 and 11) give excellent results.
In conclusion, a convenient Fischer indole synthesis employing
3-acylindoles and phenylhydrazines affords 2,30-biindoles in good
to excellent yields.
Ph
HN
N
Acknowledgments
O
PhNHNH2
EtOH
PPA
N
This work was supported by the Donors of the Petroleum Re-
search Fund(PRF), administered by the American Chemical Society,
and by Wyeth.
H
PhMe, Δ
N
R
N
R
N
R
11, R = H
12, R = SO2Ph
13, R = H
14, R = SO2Ph
5, R = H (no rxn)
15, R = SO2Ph (62%)
References and notes
Scheme 4. A Fischer indole approach to 2,30-biindole.
1. Robinson, B. The Fischer Indole Synthesis; Wiley: New York, 1982.
2. Fu, L.; Gribble, G. W. Tetrahedron Lett. 2008, 49, 7352–7354; Fu, L.; Gribble, G.
W. Org. Prep. Proced. Int. 2008, 40, 561–566; Fu, L.; Gribble, G. W. Tetrahedron
Lett. 2008, 49, 3545–3548; Gribble, G. W.; Berthel, S. J. Tetrahedron 1992, 48,
8869–8880; Roy, S.; Eastman, A.; Gribble, G. W. Synth. Commun. 2005, 35, 595–
601.
Table 1
Synthesis of substituted 2,30-biindoles 15–22
3. Hibino, S.; Choshi, T. Nat. Prod. Rev. 2001, 18, 66–87; Sánchez, C.; Méndez, C.;
Salas, J. A. Nat. Prod. Rev. 2006, 23, 1007–1045.
R2
4. Cordell, G. A. The Alkaloids, Chemistry and Biology; Academic Press: Amsterdam,
The Netherlands, 2008. Vol. 65; Gribble, G. W.; Berthel, S. J. Studies in Natural
Products Chemistry, Vol. 12; Elsevier: Amsterdam, The Netherlands, 1993. 365.
5. Ryan, K. S.; Drennan, C. L. Chem. Biol. 2009, 16, 351–364.
6. Hoessel, R.; Leclerc, S.; Endicott, J. A.; Nobel, M. E. M.; Lawrie, A.; Tunnah, P.;
Leost, M.; Damiens, E.; Marie, D.; Marko, D.; Niederberger, E.; Tang, W.;
Eisenbrand, G.; Meijer, L. Nat. Cell Biol. 1999, 1, 60–67; Leclerc, S.; Garnier, M.;
Hoessel, R.; Marko, D.; Bibb, J. A.; Snyder, G. L.; Greengard, P.; Biernat, J.; Wu,
Y.-Z.; Mandelkow, E.-M.; Eisenbrand, G.; Meijer, L. J. Biol. Chem. 2001, 276, 251–
260; Eisenbrand, G.; Hippe, F.; Jakobs, S.; Muehlbeyer, S. J. Cancer Res. Clin.
Oncol. 2004, 130, 627–635.
R1
R1
R2
1.
O
N
NHNH2 • HCl
H
EtOH, AcOH, mol. sieves
2. PPA, PhMe, Δ
N
N
SO2Ph
SO2Ph
Entry
R1
R2
Product
Yielda
7. Bergman, J.; Desarbre, E.; Koch, E. Tetrahedron 1996, 55, 2363–2370; Janosik, T.;
Bergman, J. Tetrahedron 1999, 55, 2371–2380; Tsuchimoto, T.; Matsubayashi,
H.; Kaneko, M.; Nagase, Y.; Miyamura, T.; Shirakawa, E. J. Am. Chem. Soc. 2008,
130, 15823–15835.
8. Meragelman, K. M.; West, L. M.; Northcote, P. T.; Pannel, L. K.; McKee, T. C.;
Boyd, M. R. J. Org. Chem. 2002, 67, 6671–6677.
9. Gale, P. A. Chem. Commun. 2008, 4525–4540.
10. Bocchi, V.; Palla, G. J. Chem. Soc., Chem. Commun. 1983, 1074–1075; Bergman, J.
J. Heterocycl. Chem. 1973, 10, 121–122.
1
2
3
4
5
6
7
8
9
H
H
H
H
F
NO2
H
F
NO2
H
F
NO2
Me
MeO
15
16
23
17
18
24
19
20
25
21
22
62
68
0/78b
83
Me
Me
Me
Ph
Ph
Ph
Ph
Ph
76
0/58b
86
91
0/77b
91
11. Smith, G. F. Adv. Heterocycl. Chem. 1963, 2, 287–309.
10
11
12. Scmitz-Dumont, O.; Nicolojannis, B. Chem. Ber. 1930, 63, 323–328; Wahlström,
N.; Slätt, J.; Stensland, B.; Ertan, A.; Bergman, J.; Janosik, T. J. Org. Chem. 2007,
72, 5886–5889.
13. Bocchi, V.; Palla, G. Tetrahedron 1984, 40, 3251–3256; Bocchi, V.; Palla, G. J.
Chem. Soc., Chem. Commun. 1983, 1074–1075.
92
a
Yields after column chromatography.
Yield of recovered hydrazone.
b

2644
P. E. Alford et al. / Tetrahedron Letters 52 (2011) 2642–2644
111.6, 111.5, 111.0, 110.8, 104.2, 104.0, 9.9; HRMS: m/z Calcd for
14. Bocchi, V.; Palla, G. Tetrahedron 1986, 42, 5019–5024.
15. Young, T. E. J. Org. Chem. 1962, 27, 507–510; Young, T. E.; Mizianty, M. F. J. Org.
Chem. 1964, 29, 2030–2031.
16. Liang, Z.; Zhao, J.; Zhang, Y. J. Org. Chem. 2010, 75, 170–171.
17. This transformation has previously been reported as successful, though the
melting point and spectroscopic characteristics of the resulting compound did
not closely match 2,30-biindole Shukri, J.; Al-Azawe, S.; Al-Tai, A. S. J. Indian
Chem. Soc. 1970, 47, 123–124; Al-Azawe, S.; Sarkis, G. Y. J. Chem. Eng. Data
1973, 18, 109–111.
C
23H17N2O2FS: 404.0995. Found: 404.0980.
25. 3-(1-(2-(4-Nitrophenyl)hydrazono)propyl)-1-(phenylsulfonyl)indole (24), 58%:
orange solid, mp 167–168 °C; 1H NMR (500 MHz, CDCl3) d 8.45–8.47 (m,
1H), 8.22–8.24 (d, J = 9.3 Hz, 2H), 8.01–8.03 (m, 1H), 7.98 (br s, 1H), 7.91–
7.93 (m, 2H), 7.81 (s, 1H), 7.55–7.57 (m 1H), 7.45–7.49 (m, 2H), 7.40–7.42
(m, 2H), 7.17–7.19 (d, J = 9.3 Hz, 2H), 2.76 (q, J = 7.8 Hz, 2H), 1.33 (t,
J = 7.8 Hz, 3H); 13C NMR (500 MHz, CDCl3)
d
149.9, 147.2, 138.0, 136.0,
134.4, 129.9, 129.7, 128.1, 127.1, 126.5, 126.0, 125.6, 124.6, 123.9, 121.1,
18. Representative procedure: A solution of phenylhydrazine hydrochloride (75 mg,
0.52 mmol), 3-acetyl-1-(phenylsulfonyl)indole (150 mg, 0.5 mmol), and acetic
acid (3 drops, 0.15 mL) in anhydrous ethanol (2 mL) over molecular sieves (3 Å)
was brought to reflux for 2 h and monitored by TLC. When conversion to 14
was complete, after 8 h, the solvent was removed by rotary evaporation.
Toluene (3 mL) and PPA (1 mL) was added without removing molecular sieves
and the reaction mixture was brought to reflux and monitored by TLC. After
3 h, TLC showed complete conversion. The reaction mixture was neutralized
using sat aq sodium bicarbonate solution, extracted with DCM, washed with
brine, dried over sodium sulfate, and concentrated in vacuo. The resulting
brown oil was purified by column chromatography over silica gel (1:1 hexanes/
DCM) to produce product 15 as a solid (116 mg, 62%).
113.7, 112.3, 20.6, 11.1; HRMS: m/z Calcd for C23H20N4O4S: 448.1205.
Found: 448.1220
26. 3-Phenyl-10-(phenylsulfonyl)-2,30-biindole (19), 86%: white solid; mp 201–
202 °C; 1H NMR (500 MHz, CDCl3) d 8.31 (br s, 1H), 8.03–8.04 (d, J = 8.3 Hz,
1H), 7.81–7.83 (m, 2H), 7.75–7.77 (d, J = 7.8 Hz, 1H), 7.57–7.60 (m, 2H), 7.56 (s,
1H), 7.45–7.48 (m, 2H), 7.37–7.40 (m, 3H), 7.25–7.36 (m, 5H), 7.16-7.21 (m,
2H); 13C NMR (500 MHz, CDCl3) d 138.1, 136.3, 135.3, 135.0, 134.2, 129.9,
129.6, 129.5, 128.7, 128.3, 127.1, 126.7, 126.6, 125.5, 125.4, 124.0, 123.1, 121.1,
120.8, 119.9, 116.9, 115.5, 114.0, 111.2; HRMS: m/z Calcd for C28H20N2O2S:
448.1246. Found 448.1237
27. 5-Fluoro-3-phenyl-10-(phenylsulfonyl)-2,30-biindole (20), 91%: white–yellow
solid, 195–196 °C; 1H NMR (500 MHz, CDCl3) d 8.33 (br s, 1H), 8.02–8.04 (d,
J = 8.3 Hz, 1H), 7.80–7.81 (d, J = 8.8 Hz, 2H), 7.57–7.60 (m, 1H), 7.56 (s, 1H),
7.45–7.48 (m, 2H), 7.26–7.40 (m, 10H), 7.15–7.18 (m, 1H), 7.00–7.04 (m, 1H)
13C NMR (500 MHz, CDCl3) d 159.7, 157.9, 138.1, 135.3, 134.6, 134.3, 132.8,
129.7, 129.6, 129.2, 128.9, 128.5, 127.1, 126.8, 125.6, 125.5, 124.1, 121.0, 115.2,
114.0, 111.9, 111.6, 111.3, 104.9, 104.7; HRMS: m/z Calcd for C28H19N2O2SF:
466.1151. Found 466.1145.
19. 3-(Phenylacetyl)-1-(phenylsulfonyl)indole: white solid; mp 104–105 °C; 1H NMR
(500 MHz, CDCl3) d 8.34 (d, J = 7.0 Hz, 1H), 8.25 (s, 1H), 7.93 (d, J = 8.0 Hz, 1H),
7.86 (d, J = 6.6 Hz, 2H), 7.57–7.61 (m, 1H), 7.45–7.49 (m, 2H), 7.29–7.39 (m,
7H), 4.21 (s, 2H); 13C NMR, (500 MHz, CDCl3) d 193.6, 137.6, 125.1, 134.9,
134.8, 132.6, 129.9, 129.6, 129.0, 128.1, 127.3, 127.3, 1276.2, 125.3, 123.5,
121.1, 113.3, 47.6; HRMS: m/z Calcd for
C22H16O2N2S: 375.0929. Found:
375.0919.
28. 5-Methoxy-3-phenyl-10-(phenylsulfonyl)-2,30-biindole (22), 92%: white solid, mp
20. 10-(Phenylsulfonyl)-2,30-biindole (15), 62%: yellow solid; mp 165–166 °C; 1H
NMR (500 MHz, CDCl3) d 8.34 (br s, 1H), 8.09 (m, 1H), 7.94–7.97 (m, 3H), 7.86
(m, 1H), 7.67 (m, 1H), 7.54–7.58 (m, 1H), 7.35–7.48 (m, 5H), 7.22–7.26 (m, 1H),
7.15–7.19 (m, 1H), 6.88 (m, 1H); 13C NMR (500 MHz, CDCl3) d 138.1, 136.5,
135.7, 134.4, 130.5, 129.7, 129.2, 128.8, 127.1, 125.8, 124.3, 122.9, 122.3, 121.1,
120.8, 120.6, 116.4, 114.1, 111.1, 102.1; MS (EI): m/z (%) 372 ([M+]), 316, 292,
276, 248, 231 (100), 204, 176, 141, 129, 107, 77; HRMS: m/z Calcd for
176–179 °C; 1H NMR (500 MHz, CDCl3)
d 8.26 (br s, 1H), 8.01–8.03 (d,
J = 8.3 Hz, 1H), 7.78–7.82 (m, 2H), 7.54–7.57 (m, 1H), 7.52 (s, 1H), 7.26–7.47
(m, 9H), 7.15–7.19 (m, 2H), 6.92–6.96 (d, 1H), 3.84 (s, 3H); 13C NMR (500 MHz,
CDCl3) d 155.1, 138.1, 135.3, 135.2, 134.2, 131.5, 129.9, 129.6, 129.4, 128.8,
128.8, 127.5, 127.1, 126.5, 125.5, 125.3, 124.0, 121.1, 116.7, 115.6, 114.0, 113.4,
112.1, 101.3, 56.2; HRMS: m/z Calcd for
C29H22N2O3S: 478.1351. Found:
478.1359.
C
22H16O2N2S: 372.0933. Found: 372.0931.
29. 3-(1-(2-(4-Nitrophenyl)hydrazono)-2-phenylethyl)-1-(phenylsulfonyl)indole (25),
77%: bright orange solid, mp 198–200 °C; 1H NMR (500 MHz, CDCl3) d 8.50–
8.54 (m, 1H), 8.15–8.18 (d, J = 2H), 8.00–8.05 (m, 1H), 7.98 (s, 1H), 7.81–7.86
(m, 3H), 7.32–7.58 (m, 10H), 7.01–7.06 (d, J = 2H), 4.17 (s, 2H); 13C NMR
(500 MHz, CDCl3) d 149.7, 143.9, 140.8, 137.9, 136.0, 134.5, 134.4, 129.9, 129.8,
129.7, 128.1, 127.9, 127.1, 126.4, 126.4, 126.0, 124.7, 123.9, 122.4, 113.8, 112.4,
34.3; HRMS: m/z Calcd for C28H22N4O4S: 510.1362. Found: 510.1373.
30. 5-Methyl-3-phenyl-10-(phenylsulfonyl)-2,30-biindole (21), 91%: white solid, mp
135–136 °C; 1H NMR (500 MHz, CDCl3) d 8.21 (br s, 1H), 8.03 (d, J = 8.3 Hz, 1H),
7.81 (d, J = 8.3 Hz, 2H), 7.53–7.59 (m, 3H), 7.44–7.47 (m, 2H), 7.28–7.40 (m,
8H), 7.15–7.18 (m, 1H), 7.1–7.12 (m, 1H), 2.47 (s, 3H); 13C NMR (500 MHz,
CDCl3) d 138.1, 135.3, 135.2, 134.7, 134.2, 130.2, 130.0, 129.6, 128.7, 128.6,
127.1, 126.8, 126.5, 125.5, 125.3, 124.7, 124.0, 121.1, 119.4, 115.7, 114.0, 110.9,
21.8.
21. 5-Fluoro-10-(phenylsulfonyl)-2,30-biindole (16), 68%: yellow solid, mp 190–
192 °C; 1H NMR (500 MHz, CDCl3) d 8.37 (br s, 1H), 8.08 (m, 1H), 7.91–7.97
(m, 3H), 7.87 (s, 1H), 7.54–7.59 (m, 1H), 7.28–7.49 (m, 6H), 6.95–7.00 (m, 1H),
6.83 (m, 1H); 13C NMR (500 MHz, CDCl3) d 160.0, 156.9, 138.1, 135.6, 134.4,
132.3, 129.7, 128.7, 127.1, 125.8, 124.3, 122.5, 116.1, 114.1, 111.5, 111.2, 110.9,
109.1, 105.7, 102.1; MS (EI): m/z (%) 390 ([M+]), 365, 325, 316, 289, 276, 249
(100), 236, 222, 191, 177, 149, 125, 111, 97, 71. HRMS: m/z Calcd for
C
22H15O2N2SF: 390.0838. Found: 390.0837.
22. 3-(1-(2-(4-Nitrophenyl)hydrazono)ethyl)-1-(phenylsulfonyl)indole (23), 78%:
yellow solid; 1H NMR (500 MHz, CDCl3) d 8.45–8.48 (m, 1H), 8.23 (m, 2H),
8.00–8.03 (m, 1H), 7.91–7.94 (m, 2H), 7.88 (br s, 1H), 7.81 (s, 1H), 7.56–7.60
(m, 1H), 7.46–7.50 (m, 2H), 7.40–7.43 (m, 2H), 7.17–7.20, (m, 2H), 2.36 (s, 3H);
13C NMR (500 MHz, CDCl3) d 171.5, 149.9, 142.1, 140.7, 138.1, 135.9, 134.4,
129.7, 127.1, 126.5, 126.0, 124.6, 123.9, 122.3, 113.6, 112.3, 13.6; MS (EI): m/z
(%) 434 ([M+]), 404, 293 (100), 278, 247, 232, 206, 117, 156, 143, 115, 103, 77;
HRMS: m/z Calcd for C22H18O4N4S: 434.1049. Found: 434.1049.
31. 2,30-Biindole (5): white solid, mp 197–198 °C (Lit.13 mp 204–205 °C); 1H
NMR (500 MHz, CDCl3) d 9.08 (br s, 1H), 8.86 (br s, 1H), 7.99 (m, Hz), 7.58
(m, 1H), 7.46 (m, 1H), 7.33 (m, 1H), 7.17–7.23 (m, 2H), 7.04–7.14 (m, 2H),
6.75 (m, 1H).
23. 3-Methyl-10-(phenylsulfonyl)-2,30-biindole (17), 83%: yellow–white solid, 85–
87 °C; 1H NMR (500 MHz, CDCl3) d 8.05 (br s, 1H), 7.99–8.01 (m, 1H), 7.84–7.87
(m, 2H), 7.63 (s, 1H), 7.57–7.60 (m, 1H), 7.52–7.55 (m, 1H), 7.43–7,47 (m, 1H),
7.33–7.37 (m, 2H), 7.27–7.30 (m, 2H), 7.19–7.23 (m, 1H), 7.11–7.15 (m, 1H),
7.06–7.10 (m, 1H), 2.29 (s, 3H); 13C NMR (500 MHz, CDCl3) d 138.2, 136.4,
135.3, 134.4, 129.9, 129.7, 129.6, 127.1, 126.7, 125.6, 124.6, 124.2, 122.7, 121.1,
119.9, 119.2, 115.9, 114.2, 111.1, 110.4, 10.0.
32. 3-(1-(2-Phenylhydrazono)ethyl)indole (13): brown oil, 1H NMR (500 MHz,
CDCl3) d 7.94 (br s, 1H), 7.69 (m, 2H), 7.43–7.47 (m, 1H), 7.11–7.19 (m, 2H),
6.78–6.83 (m, 2H), 2.33 (s, 3H); 13C NMR (500 MHz, CDCl3) d 149.8, 145.0,
140.2, 131.4, 129.7, 129.0, 126.7, 126.4, 120.0, 118.9, 118.6, 118.3, 115.5,
12.8; MS (EI): m/z (%) 249 ([M+], 100), 233, 207, 180, 157, 132, 104, 91, 77;
HRMS: m/z Calcd for C16H15N3: 249.1266. Found: 249.1268.
24. 5-Fluoro-3-methyl-10-(phenylsulfonyl)-2,30-biindole (18), 76%: yellow solid, mp
78–79 °C; 1H NMR (500 MHz, CDCl3) d 8.09–8.11 (d, J = 8.3 Hz, 1H), 8.06 (br s,
1H), 7.95–7.97 (d, J = 8.7 Hz, 2H), 7.73 (s, 1H), 7.68–7.69 (d, J = 8.5 Hz, 1H),
7.56–7.59 (m, 1H), 7.47–7.50 (m, 2H), 7.28–7.43 (m, 1H), 7.24–7.26 (m, 3H),
6.95–6.99 (m, 1H), 2.35 (s, 3H); 13C NMR (500 MHz, CDCl3) d 159.1, 138.2,
135.3, 134.4, 132.8, 129.7, 128.5, 127.1, 125.7, 124.7, 124.2, 120.9, 115.4, 114.2,
33. 3-(1-(2-Phenylhydrazono)ethyl)-1-(phenylsulfonyl)indole (14): brown oil, 1H
NMR (500 MHz, CDCl3) d 8.58–8.60 (m, 1H), 8.02–8.03 (m, 1H), 7.91–7.92 (d,
J = 7.5 Hz, 2H), 7.72 (s, 1H), 7.50–7.53, (m, 1H), 7.38–7.44 (m, 7H), 7.32–7.35
(m, 2H), 7.19–7.20 (m, 1H) 2.25 (s, 3H); 13C NMR (500 MHz, CDCl3) d 145.3,
138.1, 138.1, 136.0, 134.6, 129.6, 129.6, 128.4, 127.0, 125.7, 124.6, 124.4, 124.4,
123.3, 120.5, 113.5, 113.4, 13.3.