Letters to the editor: Features of the base-catalyzed reaction of 1-vinyl-4,5-dihydro-1h-benzo[g]indole-2-carbaldehyde with phenylacetylene

Full text of DOI:10.1007/s10593-012-1061-8

Chemistry of Heterocyclic Compounds, Vol. 48, No. 5, August, 2012 (Russian Original Vol. 48, No. 5, May, 2012)
LETTERS TO THE EDITOR
FEATURES OF THE BASE-CATALYZED REACTION OF 1-VINYL-
4,5-DIHYDRO-1H-BENZO[g]INDOLE-2-CARBALDEHYDE WITH
PHENYLACETYLENE
E. Yu. Schmidt1, I. A. Bidusenko1, N. I. Protsuk1, I. A. Ushakov1,
A. V. Ivanov1, A. I. Mikhaleva1, and B. A. Trofimov1*
Keywords: acetylene, pyrrolecarbaldehyde, prototropic rearrangement, superbase.
The current chemistry of pyrrolecarbaldehydes is one of the fundamental areas of fine organic synthesis.
Pyrrolecarbaldehydes are used as building blocks in the preparation of porphyrins [1, 2], ligands for metal
complexes [3, 4], medications [5], and precursors of optoelectronic materials [6-8]. Transformations of
pyrrolecarbaldehydes give carbolines [9], cyanopyrroles [10], and divinylpyrroles [11]. The high synthetic
potential of a carbonyl group in combination with the biological importance of pyrroles ensures a steady interest
in this class of compounds.
There has recently been developed a preparative method for the preparation of 1-vinylpyrrole-
2-carbaldehydes by the formylation of 1-vinylpyrroles [12, 13], which are readily obtained from ketones (via
ketoximes) and acetylene [14, 15].
It is known that aldehydes react with acetylenes in the presence of a base, giving secondary acetylenic
alcohols (the Favorsky reaction) [16, 17]. However, examples of pyrrolecarbaldehyde ethynylation using
acetylenes have not been reported in the literature. The use of 1-vinylpyrrole-2-carbaldehydes as starting
material in the synthesis of acetylenic alcohols could even further broaden their synthetic potential, thanks to the
combination of ethynylcarbinol and vinylpyrrole fragments in a single molecule.
Continuing our studies in this area, we have found that 1-vinyl-4,5-dihydro-1H-benzo[g]indole-2-carb-
aldehyde (1) reacts with phenylacetylene (2) in a suspension of KOH–DMSO (20ºC, 1.5 h), forming the
E-configured ,-ethylenic ketone 5 in a non-optimized yield of 24%, rather than the expected acetylenic alcohol 3.
It should be noted that the ketone 5 was obtained exclusively as the E-isomer. The analogous
Z-configured product could not be identified by NMR spectroscopy or by GLC, even in the reaction mixture.
The formation of ketone 5 evidently begins with a nucleophilic addition of phenylacetylene 2 to the
carbonyl group of the pyrrolecarbaldehyde 1, to give the secondary acetylenic alcohol 3, which prototropically
rearranges via the allenic alcohol 4 into the ,-ethylenic ketone 5.
_____
*To whom correspondence should be addressed, e-mail: boris_trofimov@irioch.irk.ru.
1
A. E. Favorsky Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences, 1 Favorsky St.,
Irkutsk 664033, Russia.
_____________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 883-885, May, 2012. Original
article submitted December 22, 2011; revision submitted May 2, 2012.
822
0009-3122/12/4805-0822©2012 Springer Science+Business Media, Inc.

HC
KОН
DMSO
OH
N
O
+
N
20°C
1.5 h
CH2
CH2
1
2
3
5
4
3a
6
8
5a
3
7
9a 9b
O
2
N
OH
9
N
α
α'
β'
βCH2
CH2
4
5
There are examples in the literature of the base-catalyzed isomerization of aromatic series propargyl
alcohols (including those formed in situ [18-19]), to give ,-unsaturated ketones [20-24]. However, this
reaction has not been previously reported in the chemistry of pyrrole.
The discovered reaction can evidently be used as the basis for developing a preparatively acceptable and
stereoselective method for currently unknown 1-vinylpyrrolyl(indolyl)styryl ketones, which are promising
building blocks in the design of novel pyrrole and indole derivatives. Such a synthesis broadens preparative
possibilities for making available 1-vinylpyrrole-2-carbaldehydes, and also adds to the chemistry of pyrrole and
acetylene.
1
13
IR spectra were recorded on a Bruker Vertex 70 spectrometer. H and C NMR spectra were recorded
on a Bruker DPX-400 spectrometer (400 and 100 MHz respectively) using CDCl3 with HMDS as internal
standard at  0.05 ppm. Assignment of the signals was achieved using the COSY, NOESY, HSQC and HMBC
2D NMR methods. Elemental analysis was performed on a Flash EA 1112 instrument. The melting point was
determined on a Micro-Hot-Stage PolyTherm A instrument.
(E)-1-(1-Vinyl-4,5-dihydro-1H-benzo[g]indol-2-yl)-3-phenylprop-2-en-1-one (5). The pyrrolecarb-
aldehyde 1 (0.22 g, 0.99 mmol), phenylacetylene (2) (0.10 g, 0.99 mmol) and KOH·0.5H2O (0.06 g, 0.92 mmol)
were stirred in DMSO (10 ml) for 1.5 h at room temperature. The reaction mixture was diluted with water (20
ml), neutralized with NH4Cl and extracted with ether (75 ml). The ether extract was washed with water (35
ml) and dried over MgSO4 (about 12 h). Evaporation of the ether gave a brown, resinous mass (0.30 g) which
was chromatographed on a column (basic alumina, pH 8.25, eluent hexane–diethyl ether, 10:1) to yield the pure
ketone 5. Yield 0.08 g (24%). Orange crystals; mp 38-40ºC. IR spectrum, , cm-1: 3435, 3105, 3080, 3057,
2929, 2895, 2849, 1646, 1590, 1539, 1495, 1465, 1428, 1356, 1301, 1199, 1172, 1152, 1128, 1109, 1068, 994,
1
974, 901, 764, 742, 684, 573. H NMR spectrum, , ppm (J, Hz): 7.75-7.77 (1Н, m, H-9); 7.74 (1H, dd,
3J = 15.7, 3J = 8.1, -CH); 7.73 (1Н, d, 3J = 15.8, '-CH); 7.58-7.61 (2H, m, H-2,6 Ph); 7.36-7.39 (2H, m, H-3,5
Ph); 7.37 (1Н, d, 3J = 15.8, '-CH); 7.25-7.26 (1H, m, H-6); 7.16-7.18 (1Н, m, Н-7); 7.13-7.14 (2Н, m, Н-4 Ph,
Н-8); 7.03 (1Н, s, Н-3); 5.28 (1H, d, 3J = 8.1) and 5.15 (1H, d, 3J = 15.7, -СН2); 2.91 (2H, t, 3J = 7.7, 4-СН2);
2.67 (2H, t, 3J = 7.7, 5-СН2). 13C NMR spectrum, , ppm: 176.8 (C=О); 141.6 (C-'); 138.3 (C-9a); 136.6 (C-2);
135.4 (C-i); 134.6 (C-9b); 134.4 (C-); 130.0 (C-p); 128.9 (C-m); 128.6 (C-6); 128.3 (C-o); 128.1 (C-5a); 127.2
(C-8); 126.1 (C-7); 124.7 (C-3a); 124.5 (C-9); 123.9 (C-'); 118.0 (C-3); 113.5 (C-); 30.7 (C-5); 22.1 (C-4).
Found, %: C 85.19; H 6.05; N 4.08. C23H19NO. Calculated, %: C 84.89; H 5.89; N 4.30.
823

REFERENCES
1.
2.
3.
4.
5.
H. Furuta, H. Maeda, T. Furuta, and A. Osuka, Org. Lett., 2, 187 (2000).
A. Wiehe, C. Ryppa, and M. O. Senge, Org. Lett., 4, 3807 (2002).
L.-Y. Yang, Q.-Q. Chen, G.-Q. Yang, and J.-S. Ma, Tetrahedron, 59, 10037 (2003).
L. Yang, Y. Zhang, Q. Chen, and J.-S. Ma, Monatsch. Chem., 135, 223 (2004).
J. Т. Hunt, Т. Mitt, R. Borzilleri, J. Gullo-Brown, J. Fargnolli, В. Fink, W.-C. Han, S. Mortillo, G. Vite,
В. Wautlet, Т. Wong, C. Yu, X. Zheng, and R. J. Bhide, J. Med. Chem., 47, 4054 (2004).
W. G. O'Neal, W. P. Roberts, I. Ghosh, H. Wang, and P. A. Jacobi, J. Org. Chem., 71, 3472 (2006).
D. Gerlach, E. Brendler, T. Heine, and J. Wagler, Organometallics, 26, 234 (2007).
J.-P. Tremblay-Morin, S. Faure, D. Samar, C. Stern, R. Guilard, and P. D. Harvey, Inorg. Chem., 44,
2836 (2005).
6.
7.
8.
9.
10.
11.
12.
H. Zhang and R. C. Larock, J. Org. Chem., 67, 7048 (2002).
P. A. Pavlov, Zh. Org. Khim., 37, 1376 (2001).
R. Settambolo, M. Marani, and A. Caiazzo, J. Org. Chem., 63, 10022 (1998).
A. I. Mikhaleva, A. B. Zaitsev, A. V. Ivanov, E. Yu. Schmidt, A. M. Vasil'tsov, and B. A. Trofimov,
Tetrahedron Lett., 47, 3693 (2006).
13.
A. I. Mikhaleva, A. V. Ivanov, E. V. Skital'tseva, I. A. Ushakov, A. M. Vasil'tsov, and B. A. Trofimov,
Synthesis, 587 (2009).
14.
15.
B. A. Trofimov and A. I. Mikhaleva, N-Vinylpyrroles [in Russian], Nauka, Novosibirsk (1984).
B. A. Trofimov, A. I. Mikhaleva, E. Yu. Schmidt, and L. N. Sobenina, Adv. Heterocycl. Chem., 99, 209
(2010).
16.
17.
18.
A. E. Favorsky and M. P. Skosarevskii, Zh. Russ. Phys. Khim. Obshch., 32, 652 (1900).
B. A. Trofimov, Curr. Org. Chem., 6, 1121 (2002).
T. Ishiwaka, T. Mizuta, K. Hagiwara, T. Aikawa, T. Kudo, and S. Saito, J. Org. Chem., 68, 3702
(2003).
19.
20.
21.
22.
23.
24.
M. Sun, Q. Shi, G. Huang, Y. Liang, and Y. Ma, Synthesis, 2482 (2005).
K. Tanaka and T. Shoji, Org. Lett., 7, 3561 (2005).
J. P. Sonye and K. Koide, Synth. Commun., 36, 599 (2006).
K. Tanaka, T. Shoji, and M. Hirano, Eur. J. Org. Chem., 2687 (2007).
J. P. Sonye and K. Koide, J. Org. Chem., 72, 1846 (2007).
Y. Watanabe and T. Yamazaki, J. Org. Chem., 76, 1957 (2011).
824