Mendeleev
Communications
Mendeleev Commun., 2014, 24, 368–369
2-(2-Ethynyl-1-aziranyl)-3,4-dihydro-2H-pyrrole:
a one-pot assembly from isopropyl phenyl ketoxime
and acetylene during the synthesis of 3H-pyrrole
Dmitrii A. Shabalin, Tatyana E. Glotova, Igor A. Ushakov, Marina Yu. Dvorko, Alexander V. Vashchenko,
Vladimir I. Smirnov, Elena Yu. Schmidt, Al’bina I. Mikhaleva and Boris A. Trofimov*
A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences, 664033 Irkutsk,
Russian Federation. Fax: +7 3952 419 346; e-mail: boris_trofimov@irioch.irk.ru
DOI: 10.1016/j.mencom.2014.11.020
Reaction between isopropyl phenyl ketoxime and acetylene in the KOH–DMSO–n-hexane system (70°C, ~5 min), along with known
3,3-dimethyl-2-phenyl-3H-pyrrole (51% yield) and 4,4-dimethyl-5-phenyl-1-vinyl-2-pyrrolidinone (7% yield), affords also unexpected
2-(2-ethynyl-3,3-dimethyl-2-phenyl-1-aziranyl)-4,4-dimethyl-5-phenyl-3,4-dihydro-2H-pyrrole (4% yield).
The most straightforward route to 3H-pyrroles by reaction
between acetylene and ketoximes having just one a-hydrogen
atom1,2 still remains unoptimized. One means to improve moderate
yields (~50%) of the target products seems in studying the inter-
mediates and minor products of the reaction, which can shed light
on the mechanism and hence provide better control of the process.
The following intermediates and minor products have been isolated
and identified: O-vinyloximes,3 2-hydroxypyrrolines,4 pyrrolines,5
and 4,4-dimethyl-5-phenyl-1-vinyl-2-pyrrolidinone,6 most of them
supporting the common mechanism7 of the reaction course.
Here we report that during the further scrutinized work-up of
the reaction mixture obtained from isopropyl phenyl ketoxime 1
and acetylene in the KOH–DMSO–n-hexane system (70°C) we
isolated and characterized (X-ray, 1H, 13C, 15N NMR, IR, MS) the
absolutely unexpected minor product, 2-(2-ethynyl-3,3-dimethyl-
2-phenyl-1-aziranyl)-4,4-dimethyl-5-phenyl-3,4-dihydro-2H-
pyrrole 2 apart from the regular 3,3-dimethyl-2-phenyl-3H-pyrrole
31 and the aforementioned 4,4-dimethyl-5-phenyl-1-vinyl-2-pyr-
rolidinone 46 (Scheme 1).†
Although molecule 2 contains two asymmetric carbon atoms,
only one diastereomer is formed: the NMR spectra manifest only
one set of signals.
The structure of compound 2 unambiguously follows from
single-crystal X-ray diffraction analysis (Figure 1)‡ and 1H, 13
C
The reaction between isopropyl phenyl ketoxime 1 and acetylene in the
KOH–DMSO–n-hexane system. A 0.3 dm3 Parr reactor equipped with
a magnetic stirrer (250 rpm) was charged with hexane (40 ml) and a
potassium oximate solution in DMSO prepared by heating of a mixture
of isopropyl phenyl ketoxime 1 (2.04 g, 12.5 mmol) and KOH∙0.5H2O
(0.81 g, 12.5 mmol) in DMSO (50 ml) at 110–115°C for 1 h. The reactor
was fed with acetylene and then decompressed to atmospheric pressure to
remove air. The reactor was fed again with acetylene (initial pressure was
10 atm) and heated up to 70°C and then heating was immediately ceased
that took overall 20 min (about 5 min at 70°C). After cooling, the reaction
mixture was discharged and the hexane layer was separated. The DMSO
solution was poured into ice water (250 ml), neutralized with NH4Cl, and
extracted with diethyl ether (5×50 ml). The organic layers were combined,
washed with H2O (3×50 ml) and dried over MgSO4 overnight.After distilling
off the solvents, the residue (2.14 g, brown oil) was chromatographed on
the column (1.9×30 cm, CH2Cl2 as eluent) to afford the fractions with
Rf = 0.45–0.70 and 0.20–0.45.
By the repeated chromatography (1.8×20 cm, hexane–diethyl ether,
9:1) of the first fraction, 2-(2-ethynyl-3,3-dimethyl-2-phenyl-1-aziranyl)-
4,4-dimethyl-5-phenyl-3,4-dihydro-2H-pyrrole 2 (0.09 g, 4%, Rf = 0.62)
and 3,3-dimethyl-2-phenyl-3H-pyrrole 3 (1.09 g, 51%, Rf = 0.49) were
isolated.
From the second fraction, 0.19 g (7%, Rf = 0.42) of 4,4-dimethyl-
5-phenyl-1-vinyl-2-pyrrolidinone 4 was isolated by the repeated column
chromatography (1.2×20 cm, hexane–diethyl ether, 3:1).
Me
KOH–DMSO–n-hexane
Ph
HC CH
+
70 °C, 5 min
Me
NOH
1
Me
Me
N
Me
N
Me
Me
Me
3
4
Me
Me
+
2
+
5
3'
1
Ph
O
Ph
Ph
N
2'
N
1'
Physical-chemical characteristics of the isolated compounds corre-
sponded to the literature data: compound 3,1 compound 4.6
Ph
2-(2-Ethynyl-3,3-dimethyl-2-phenyl-1-aziranyl)-4,4-dimethyl-5-phenyl-
3,4-dihydro-2H-pyrrole 2: colourless crystals, mp 118–120°C (hexane).
IR (KBr, n/cm–1): 3229, 2962, 2929, 2106, 1628, 1601, 1492, 1449, 1339,
2 (4%)
3 (51%)
Scheme 1
The IR spectra were recorded on a Bruker IFS25 spectrophotometer as
4 (7%)
1
1147, 765, 697. H NMR (CDCl3) d: 1.00 (s, 3H, C3'Me), 1.42 (s, 3H,
C4Me), 1.50 (s, 3H, C4Me), 1.75 (s, 3H, C3'Me), 2.09 (dd, 1H, CH2,
†
KBr pellets or thin films. Mass spectra were measured on anAgilent 5975C
spectrometer. Sample introduction was carried out through an Agilent
6890N gas chromatograph: the column was an HP-5MS (0.25 mm × 30 m ×
× 0.25 mm); carrier gas – helium, constant flow. NMR spectra were recorded
on Bruker DPX-400 and AV-400 spectrometers (400.1 MHz for 1H,
100.6 MHz for 13C, and 40.5 MHz for 15N) in CDCl3 using HMDSO as
internal standard. Basic aluminum oxide was used for column chromato-
graphy, and Silufol plates for TLC (eluent, hexane–diethyl ether, 1:1).
Visualization was made with iodine vapor.
3J 7.1 Hz, 2J 12.5 Hz), 2.31 (dd, 1H, CH2, 3J 6.4 Hz, 2J 12.5 Hz), 2.47 (s,
3
3
1H, ºCH), 4.84 (dd, 1H, CH, J 6.4 Hz, J 7.1 Hz), 7.26 (m, 1H, p-H,
C2'Ph), 7.34 (m, 2H, m-H, C2'Ph), 7.40 (m, 3H, p-H, m-H, C5Ph), 7.58
(m, 2H, o-H, C2' Ph), 7.80 (m, 2H, o-H, C5Ph). 13C NMR (CDCl3) d: 16.6
(C3'Me), 23.4 (C3'Me), 26.8 (C4Me), 27.6 (C4Me), 45.8 (C2'), 48.7 (C3),
49.6 (C3'), 50.5 (C4), 73.2 (CºCH), 82.6 (C2), 82.7 (CºCH), 127.2 (p-C,
C2' Ph), 128.0 (o-C, m-C, C2' Ph), 128.2 (m-C, C5Ph), 128.3 (o-C, C5Ph),
129.6 (p-C, C5Ph), 134.9 (i-C, C5Ph), 139.5 (i-C, C2'Ph), 181.2 (C=N).
15N NMR (CDCl3) d: –309.2 (N1'), –50.0 (N1). MS (EI), m/z: 342 [M]+.
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