First example of the synthesis of pyrrolecarbaldehyde with electron-deficient acetylene substituents

Full text of DOI:10.1134/S1070428013080265

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2013, Vol. 49, No. 8, pp. 1241−1243. © Pleiades Publishing, Ltd., 2013.
Original English Text © L.N. Sobenina, M.V. Markova, D.N. Tomilin, E.V. Tret’yakov, V.I. Ovcharenko, A.I. Mikhaleva, B.A. Trofimov, 2013, published in Zhurnal
Organicheskoi Khimii, 2013, Vol. 49, No. 8, pp. 1255−1256.
SHORT
COMMUNICATIONS
First Example of the Synthesis of Pyrrolecarbaldehyde
with Electron-Deficient Acetylene Substituents
L. N. Sobeninaa, M. V. Markovaa, D. N. Tomilina, E. V. Tret’yakovb,
V. I. Ovcharenkob, A. I. Mikhalevaa, and B. A. Trofimova
aFawodrsky Irkutsk Institute of Chemistry, Siberian Branch, Russian Academy of Sciences,
Irkutsk, 664033 Russia
e-mail: boris_trofimov@irioch.irk.ru
bInstitute “International Tomographic Center,” Siberian Branch, Russian Academy of Sciences, Novosibirsk, Russia
Received February 28, 2013
DOI: 10.1134/S1070428013080265
Pyrrolecarbaldehydes with acetylene substituents are
widely applied to organic syntesis although the systematic
research in this field has been started only a little earlier
than a decade ago. Now the ethynyl pyrrolecarbaldehydes
are used for the preparation of polyfunctional derivatives
of pyrrole and indole of definite structure and properties
[1–6]. They also play a key role in designing macrocycles
whose natural analogs possess special kinds of biological
action [7–12].
of low efficiency with activated acetylenes [14]. Yet such
ethynylpyrrolecarbaldehydes would provide new oppor-
tunities to the targeted organic synthesis, in particular, for
the preparation of polyfunctional stable organic radicals
and polyradicals [15–17].
In this communication we describe for the first time a
simple convenient protocol of the synthesis of such com-
pounds by an example of the preparation of the first speci-
men of pyrrolecarbaldehydes with the electron-deficient
acetylene substituent. It includes the acetal protection of
the aldehyde group of the pyrrole-2-carbaldehyde by the
reaction with 2,2-dimethylpropanediol in the presence
of p-toluenesulfonic acid, introducing benzoylethynyl
group into the pyrrole ring of acetal I by “palladiumless”
cross-coupling with 3-bromo-1-phenyl-2-propyn-1-one
on alumina, and the removal of the acetal protection in
ethynylpyrrole II by the mild acid-catalyzed hydrolysis
Now the ethynylpyrrolecarbaldehydes are obtained
as a rule by criss-coupling of difficultly available and
unstable halopyrrolecarbaldehydes with terminal acety-
lenes [4–12] or their organometallic derivatives [13] in the
presence of palladium catalysts (Sonogashira reaction).
However the ethynylpyrrolecarbaldehydes containing in
the acetylene substituent electron-acceptor functions are
not known up till now since the Sonogashira reaction is
Me
Me
OH
OH
O
O
TsOH
C6H6
Me
N
H
N
H
O
Me
I
O
Br
O
O
HCl
Me
O
O
Ph
Al2O3, 20_25oC, 6 h
N
N
H
O
H
Me
Ph
Ph
III
II
1241

SOBENINA et al.
1242
in aqueous acetone. The key stage, the cross coupling of
acetal I with 3-bromo-1-phenyl-2-propyn-1-one, pro-
ceeds without compounds of transition metals, bases, and
solvent at room temperature.
ether was added, the solution obtained was twice washed
with brine and 5% solution of NaHCO3, and dried with
K2CO3. The residue after removing ether (0.59 g) was
purified by column chromatography on Al2O3 (eluents
hexane, then hexane–ethyl ether, 3 : 1, 1 : 1, 1 : 3,. Yield
0.24 g (42%) yellow crystals, mp 195–199°С. IR spec-
trum, ν, cm-1: 3230 (NH), 2194 (C≡C), 1662 (НCO),
1630 (COPh). 1H NMR spectrum (acetone-d6), δ, ppm:
6.97 d.d (1H, H3, J 2.9, 3.4 Hz), 7.11 d.d (1H, H4, J 2.7,
3.4 Hz), 7.58 m (2Н, Hm), 7.72 m (1Н, Hп), 8.23 m (2Н,
Ho), 9.67 s (1H, HCO), 12.07 br.s (1Н, NH). 13С NMR
spectrum, δ, ppm: 85.1 (С≡), 91.5 (≡С), 120.4 (C5), 121.9
(C4), 129.7 (Cm), 130.07 (Сo, C3), 135.2 (Сп), 136.7
(С2), 137.6 (Cи), 177.3 (PhC=O), 180.4 (НС=О). Found,
%: С 75.36; H 4.09; N 6.29. C14H9NO2. Calculated, %:
C 75.33; H 4.06; N 6.27.
The efficiency of this new reaction of “palladium-
less” cross-coupling is already confirmed by numerous
syntheses of ethynylpyrroles and indoles [18–21]. Taking
this into account further systematic development and
optimization of all three stages of the suggested proto-
col may provide a general approach to the synthesis of
pyrrolecarbaldehydes with electron-deficient acetylene
substituents.
1Н and 13С NMR spectra were registered on a spec-
trometer Bruker DPX-400 [400 (1Н), 100.6 МHz (13С)].
IR spectra were recorded on a spectrophotometer Bruker
IFS25 from pellets with KBr.
2-(5,5-Dimethyl-1,3-dioxan-2-yl)pyrrole (I) was ob-
tained by procedure [22].
ACKNOWLEDGMENTS
3-[5-(5,5-Dimethyl-1,3-dioxan-2-yl)pyrrole-2-yl]-
1-phenyl-2-propyn-1-one (II). In a porcelain mortar
were thoroughly ground for 5 min 0.33 g (1.821 mmol)
of 2-(5,5-dimethyl-1,3-dioxan-2-yl)pyrrole (I) and 0.38 g
of (1.821 mmol) 3-bromo-1-phenyl-2-propyn-1-one with
7 g (10-fold excess with respect to the reagents mass) of
alumina, and the mixture was left standing with alumina
at room temperature for 6. Then the reaction mixture was
applied to a column packed with Al2O3 and by elution
first with hexane, then with hexane–ethyl ether, 3 : 1, 1 :
1, 1 : 3, we isolated first unreacted 3-bromo-1-phenyl-2-
propyn-1-one, then ethynylpyrrole II. Yield 0.24 g (43%),
lustrous gray-green needle crystals, mp 141–143°С. IR
spectrum, ν, cm–1: 3314 (NH), 2174 (C≡C), 1625 (CO).
1H NMR spectrum (CDCl3), δ, ppm: 0.84 s (3H, Me),
1.24 s (3H, Me), 3.64, 3.76 d.d (4H, 2CH2, J 11.2 Hz),
5.51 s (1Н, OCHO), 6.30 d.d (1H, H4, J 2.9, 3.4 Hz),
6.83 d.d (1H, H3, J 2.7, 3.4 Hz), 7.53 m (2Н, Hm), 7.61 m
(1Н, Hп), 8.18 m (2Н, Ho), 9.10 br.s (1Н, NH). 13С NMR
spectrum, δ, ppm: 21.9 (Me), 23.1 (Me), 30.4 (Me2CH),
77.5 (CH2O), 88.0 (С≡), 91.9 (≡C), 96.0 (OCHO), 108.4
(C4), 109.8 (C2), 120.9 (C3), 128.6 (Cm), 129.4 (Сo),
133.9 (Сп), 134.5 (С5), 136.8 (Cи), 177.6 (С=О). Found,
%: С 73.48; H 6.16; N 4.51. C19H19NO3. Calculated, %:
C 73.77; H 6.19; N 4.53.
The study was carried out under the financial support
of the Russian Foundation for Basic Research (grant
no.13-03-91150 GFEN-а) and of the Presidium of the
Russian Academy of Sciences (project no. 28).
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