Formation of 2-ethynyl-3,4-dihydro-2H-pyrroles in the synthesis of 3H-pyrroles from ketoximes and acetylene in the system KOH - DMSO - hexane

Full text of DOI:10.1134/S1070428015090237

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2015, Vol. 51, No. 9, pp. 1346–1348. © Pleiades Publishing, Ltd., 2015.
Original Russian Text © D.A. Shabalin, E.Yu. Schmidt, M.Yu. Dvorko, N.I. Protsuk, I.A. Ushakov, B.A. Trofimov, 2015, published in Zhurnal Organicheskoi
Khimii, 2015, Vol. 51, No. 9, pp. 1372–1374.
SHORT
COMMUNICATIONS
Formation of 2-Ethynyl-3,4-dihydro-2H-pyrroles in the Synthesis
of 3H-Pyrroles from Ketoximes and Acetylene
in the System KOH–DMSO–Hexane
D. A. Shabalin, E. Yu. Schmidt, M. Yu. Dvorko, N. I. Protsuk,
I. A. Ushakov, and B. A. Trofimov
Favorskii Irkutsk Institute of Chemistry, Siberian Branch, Russian Academy of Sciences,
ul. Favorskogo 1, Irkutsk, 664033 Russia
e-mail: boris_trofimov@irioch.irk.ru
Received April 22, 2015
DOI: 10.1134/S1070428015090237
3
H-Pyrroles constitute a difficultly accessible and
lene with ketone oximes containing only one C–H
bond in the α-position with respect to the oxime group
[2, 3], we studied the reactions of 2-methyl-1-phenyl-
propane-1-one oxime (1a) and cyclohexyl(phenyl)-
methanone oxime (1b) with acetylene under pressure
in the two-phase superbasic system KOH–DMSO–
hexane. Unexpectedly, apart from 3H-pyrroles 2a and
2b, we isolated from the reaction mixtures small
amounts of 2-ethynyl-3,4-dihydro-2H-pyrroles 3a and
3b (Scheme 1).
therefore poorly studied group of nonaromatic pyr-
roles. On the other hand, they exhibit potentially rich
chemistry due to intrinsic tendency to undergo various
rearrangements and addition and cycloaddition reac-
tions [1]. Despite obvious interest attracted by 3H-pyr-
roles and their undoubted promises for organic synthe-
sis as reactive intermediates with unique reactivity, no
somewhat general method for their synthesis has been
developed so far.
While continuing to develop general methodology
Presumably, compounds 3 are formed as a result of
for the synthesis of 3H-pyrroles by reaction of acety-
addition of acetylide ion to the C=N bond (aza-
Scheme 1.
Me
Me
Me
KOH–DMSO–hexane
70°C, 5 min
Me
Me
Ph
Ph
Me + HC CH
+
HC
N
Ph
2a (20%)
N
N
OH
1
a
3a (1%)
KOH–DMSO–hexane
70°C, 5 min
Ph
+
HC CH
+
HC
N
Ph
N
N
Ph
OH
1
b
2b (16%)
3b (2%)
Scheme 2.
R2
R2
R2
R1
R1
R1
HC
C
–OH–
HC
HC
Ph
OH
OH
N
N
N
Ph
Ph
4
3
1
346

FORMATION OF 2-ETHYNYL-3,4-DIHYDRO-2H-PYRROLES
1347
Scheme 3.
R2
R2
R2
R2
R1
R1
R1
R1
HC
C
H O
2
HC
HC
–OH–
HC
Ph
N
N
N
N
Ph
Ph
Ph
2
A
3
Scheme 4.
HC CH
K (met.)–THF (dioxane)
Me
H
–
HC
≡
–
C –ArNHC(O)R
R
N
Me
N
Ar
Ar
Ar
N
ArNC(O)R
HC
H
O
Postulated intermediate
Scheme 5.
HC CH
K (met.)–THF (dioxane)
Me
H
–
HC C –ArNH
≡
H C
2
N
Me
N
2
ArNH2
Ar
Ar
Ar
N
–
ArNH
HC
H
Postulated intermediate
Favorskii ethynylation) of hydroxy derivatives 4
The resulting homogeneous solution of potassium
oximate was transferred into a 250-mL Parr 4576A
reactor with an internal stirrer (250 rpm), 40 mL of
hexane was added, the mixture was purged with acety-
lene under pressure to remove air, acetylene was
supplied to a pressure of 10 atm (the pressure did not
exceed 13 atm during the synthesis), the reactor was
heated to 70°C, and heating was immediately turned
off (~5 min at 70°C). The reactor was cooled to room
temperature and emptied, the upper hexane layer was
separated by decanting, and the bottom DMSO layer
was poured into ice water (250 mL), neutralized with
aqueous ammonium chloride (10 wt %, 15 mL), and
extracted with diethyl ether (5×50 mL). The extracts
were combined with the organic phase, washed with
water (3×50 mL), and dried over potassium carbonate.
The drying agent was filtered off, the solvent was
removed, and the residue was subjected to chromatog-
raphy on a 1.6×20-cm column charged with Al O
(
[
intermediates isolated in the synthesis of 3H-pyrroles
4]) or 3H-pyrroles 2. In the first case, the addition is
accompanied by elimination of hydroxide ion
Scheme 2). In the second case, the ethynylation
(
follows the 1,4-addition pattern with subsequent
addition of a proton from the medium to carbanion A
(Scheme 3). Ethynyl derivative 3a was detected in the
reactions of acetylene with both 3H-pyrrole 2a and
hydroxydihydropyrrole 4a, which supports the pro-
posed reaction schemes.
We have found no published examples of direct
base-catalyzed ethynylation of C=N bond, though the
formation of N-(but-3-yn-2-yl)anilines from two
molecules of acetylene and N-aryl amides (Scheme 4)
[
(
5–7] or from aromatic amines and acetylene
Scheme 5) [7, 8] in the presence of metallic potassium
has been postulated to involve addition of acetylide ion
to the C=N bond of intermediate Schiff base.
2
3
using methylene chloride as eluent to isolate 3H-pyr-
role 2a (yield 20%) [2, 10] or 2b (16%) [3]. By
repeated chromatography of the enriched fraction
The formation of 2-ethynyl-3,4-dihydro-2H-pyr-
roles from ketone oximes and acetylene is of funda-
mental importance as the first experimental evidence
of aza-Favorskii reaction [9]. Furthermore, our results
confirm the high reactivity of 3H-pyrroles and
demonstrate for the first time their susceptibility to
nucleophilic attack. In particular, this feature is likely
to be responsible for the poor yields of 3H-pyrroles.
(Al
lated ethynyl derivative 3a or 3b.
-Ethynyl-3,3-dimethyl-2-phenyl-3,4-dihydro-
H-pyrrole (3a). Yield 0.025 g (1%), dark yellow oily
O , 0.8×13-cm; hexane–diethyl ether, 1:3) we iso-
3
2
2
2
–1
material, R 0.21. IR spectrum, ν, cm : 3301, 2964,
f
Reaction of ketone oximes 1a and 1b with acety-
lene in the system KOH–DMSO–hexane (general
procedure). A mixture of 12.5 mmol of oxime 1a or 1b
2934, 2105, 1684, 1620, 1448, 1368, 1253, 973, 750,
702. H NMR spectrum, δ, ppm: 0.48 s (3H, Me),
1.43 s (3H, Me), 2.50 d (1H, 4-H, J = 17.0 Hz), 2.58 s
(1H, ≡CH), 2.77 d (1H, 4-H, J = 17.0 Hz), 7.29–
7.37 m (3H, m-H, p-H), 7.48–7.50 m (2H, o-H), 7.94 s
1
and 0.81 g (12.5 mmol) of KOH·0.5H O in 50 mL of
2
DMSO was stirred for 1 h on heating at 110–115°C.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 51 No. 9 2015

1
348
SHABALIN et al.
1
3
(
2
(
1
1H, 5-H). C NMR spectrum, δ , ppm: 24.7 (Me),
This study was performed under financial support
by the Russian Foundation for Basic Research (project
no. 14-03-00426).
C
3
4
5.3 (Me), 46.2 (C ), 52.1 (C ), 74.7 (C≡CH), 80.4
2
C ), 84.2 (C≡CH); 127.4, 128.0, 129.4, 139.6 (Ph);
5
15
69.9 (C ). N NMR spectrum: δ –39.9 ppm. Mass
N
+
spectrum: m/z 197 [M] .
-Ethynyl-1-phenyl-2-azaspiro[4.5]dec-2-ene
3b). Yield 0.045 g (2%), yellow oily material, R 0.18.
IR spectrum, ν, cm : 3304, 2933, 2855, 2105, 1626,
600, 1491, 1448, 1299, 983, 751, 701. H NMR spec-
trum, δ, ppm: 0.29–0.37 m, 0.81–1.00 m, 1.10–1.31 m,
.41–1.47 m, 1.54–1.66 m, 1.75–1.82 m, and 2.11–
.18 m (10H, CH ); 2.59 s (1H, ≡CH), 2.61 d and
.76 d (1H each, 4-H, J = 17.4 Hz), 7.29–7.37 m (3H,
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2
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 51 No. 9 2015