A facile synthesis of 2-[4′-dimethylaminophenyl]-3-aryl-β-carbolinium phenylsulfonates

Article abstract of DOI:10.1016/S0040-4039(02)00488-4

A convenient method for the synthesis of 2-[4′-dimethylaminophenyl]-3-aryl-β-carbolinium phenylsulfonates from the corresponding 2-N′-aryliminomethylene-3-β-arylvinylindoles by thermal oxidative cyclization is reported.

Full text of DOI:10.1016/S0040-4039(02)00488-4

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 3149–3150
A facile synthesis of
2-[4%-dimethylaminophenyl]-3-aryl-b-carbolinium phenylsulfonates
Sathananthan Kannadasan and Panayencheri C. Srinivasan*
Department of Organic Chemistry, University of Madras, Guindy Campus, Chennai 600 025, India
Received 19 December 2001; revised 28 February 2002; accepted 8 March 2002
Abstract—A convenient method for the synthesis of 2-[4%-dimethylaminophenyl]-3-aryl-b-carbolinium phenylsulfonates from the
corresponding 2-N%-aryliminomethylene-3-b-arylvinylindoles by thermal oxidative cyclization is reported. © 2002 Published by
Elsevier Science Ltd.
The synthesis of various substituted b-carbolines con-
tinues to be a goal due to the wide variety of natural
products containing this structural unit. It is known
that 3,4-disubstituted-b-carboline derivatives block ben-
zodiazepam receptors of the central nervous system
(CNS).1 Due to the biological importance of these
compounds there has been much interest in their syn-
thesis through different routes. b-Carboline alkaloids
are usually synthesized from tryptamine derivatives
either through Pictet–Spengler2 or Bischler–Napieralski
reactions.3 To the best of our knowledge there is no
report on the synthesis of 2,3-diaryl-b-carbolines. In
continuation of our studies4 on the synthesis of b-car-
bolines through a non-tryptamine pathway, we report
here a synthesis of 2-[4%-dimethylaminophenyl]-3-aryl-b-
carbolinium phenylsulfonates 5a–c by an oxidative
thermal cyclization of 2-N%-aryliminomethylene-3-b-
arylvinylindoles 4a–c.
2-Methylindole-3-carbaldehyde 1 was converted to the
corresponding1-phenylsulfonyl-3-(b-arylvinyl)-2-bromo-
methylindoles 2a–c by the conventional procedure
(Scheme 1).4c An Arbuzov reaction of 2a–c with triethyl
phosphite afforded the diethyl [1-phenylsulfonyl-3-(b-
arylvinyl)indol-2-yl]methyl phosphonates 3a–c in 85–
91% yields. The structures of these compounds were
1. nBu4NHSO4 / PhSO2Cl
NaOH (50%) / benzene
CHO
CH3
Ar
Br
N
N
2.[Ph3PCH2Ar]Br / NaH / THF
SO2Ph
2a-c
H
1
85-90%
3. NBS / CCl4
NaH / THF
0-5°C 3 h
Ar
(EtO)3P
OEt
OEt
P
180°C
2 h
N
O
N
NMe2
O
PhO2S
3a-c
Ar
Ar
CH3COOH
24 h
N
N
N
H
N
PhO2S
4a-c
NMe2
NMe2
PhSO3
80-86%
5a-c
Scheme 1.
Keywords: b-carbolinium phenylsulfonates; oxidative thermal cyclization.
* Corresponding author. Tel.: 91-44-2351269 ext. 214; fax: 91-44-2352494; e-mail: pancol2000@yahoo.co.in
0040-4039/02/$ - see front matter © 2002 Published by Elsevier Science Ltd.
PII: S0040-4039(02)00488-4

3150
S. Kannadasan, P. C. Srini6asan / Tetrahedron Letters 43 (2002) 3149–3150
Table 1.
Entry
Ar
3
5
Mp (°C)
Yield (%)
Mp (°C)
Yield (%)
a
b
c
2,4-Dichlorophenyl
4-Bromophenyl
2-Bromophenyl
168
150
154
90
85
91
192
185
188
40
45
42
References
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studies.5 An aza Wittig–Horner reaction6 of the phos-
phonate esters 3a–c with 4-nitroso-N,N-dimethylaniline
afforded 2-N%-aryliminomethylene-3-b-arylvinylindoles
4a–c in 80–86% yields. The structures of compounds
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1
4a–c were confirmed by IR and H NMR spectra only.
An oxidative cyclization of compounds 4a–c in boiling
acetic acid gave the corresponding quaternary salts of
b-carboline, namely 2-[4%-dimethylaminophenyl]-3-aryl-
b-carbolinium phenylsulfonates 5a–c in 40–45% yields
(silica gel column EtOAc:MeOH, 95:5). The formation
of b-carbolinium salts probably involves an electrocy-
clization followed by oxidation and hydrolysis of the
N-phenylsulfonyl group. The structures of compounds
5a–c were confirmed by spectral studies,7 elemental
analysis and XRD in the case of 5a (Table 1).5
These compounds may be medicinally interesting in the
light of an observation that quaternary salts of b-carbo-
line derivatives such as fascaplysin, etc. have shown
interesting medicinal properties.8 In conclusion we have
developed a new route for 2,3-diaryl-b-carbolinium
salts via thermal oxidative cyclization of the corre-
sponding imines. Further work on the same line is in
progress.
7. Spectral data for compound 5a: IR: 3423 (NH), 1383 and
1182 cm−1 (SO2).
1H NMR (CDCl3) 300 MHz: l 2.91 (s, 6H, N(CH3 2
6 ) ), 6.46
(d, 2H, J=8.2 Hz, 3% and 5%-H of dimethylaminophenyl
ring), 7.09 (d, 2H, J=8.2 Hz, 2% and 6%-H), 7.25–7.90 (m,
11H, Ar-H), 8.13 (d, 1H, J=7.9 Hz, carboline-8-H), 8.26 (s,
1H, carboline-4-H), 9.49 (s, 1H, carboline-1-H), 13.50 (bs,
1H, NH). 13C NMR (CDCl3) 75 MHz: l 40.03, 111.40,
114.08, 119.13, 121.96, 122.63, 125.96, 126.61, 127.51,
127.97, 129.49, 129.64, 130.23, 131.41, 132.33, 132.53,
132.96, 133.29, 134.38, 135.39, 136.73, 138.71, 145.70,
150.84. Mass (m/z, %): 432 (M+, 41), 434 (M+2, 21), 433
(69), 431 (100), 416 (10), 77 (13).
Acknowledgements
The authors thank CSIR, New Delhi for financial
support and the UGC-SAP to this department from
Government of India for instrument grants.
8. Roll, D. M.; Ireland, C. M.; Lu, H. S. M.; Clardy, J. J. Org.
Chem. 1988, 53, 3276–3278.