May-Jun 2005
Unusual Tosyl Transfer Solvolysis Reaction
733
MHz (C-13), respectively, in deuteriochloroform. Chemical
shifts are reported in ppm referenced to the residual chloroform
proton signal at 7.26 ppm and C-13 signal at 77.23 ppm unless
otherwise noted. Melting points were taken on a Mel-Temp cap-
illary apparatus and are uncorrected. Analytical thin layer chro-
matrography (tlc) was carried out on J.T. Baker silica gel IB-F
plates (125 µm layer). For purification, radial chromatography
173.1 (s, C=O), 146.1 (s, C-4), 143.1 (s, C-3) and 79.3
(d, C-5) ppm; whereas, 5a shows 173.7 (s, C=O), 147.9
(s, C-4), 133.9 (s, C-3) and 77.5 (d, C-5) ppm. The iso-
meric mono-tosylpyrrolinones show distinctly different
pyrrolinone ring methyl groups in their nmr spectra. In
the C-13 nmr, the exo-methyl of 5a appears at 8.6 ppm,
and the endo-methyl of 5b at 13.1 ppm. In 1 it lies at
13.7 ppm. In the H-nmr, the exo-methyl of 5a appears
at 1.57 ppm, and the endo-methyl of 5b at 2.14 ppm.
The correspondiing methyl resonance in 1 is found at
2.35 ppm. The C-13 and H-nmr data for the ring
methyl resonances of 1 correlate better with the endo-
methyl of 5b.
Final proof of the structure of 1 comes from its X-ray
crystallographic structure (Figure 4). X-ray quality crys-
tals of 1 were grown by slow evaporative diffusion of
hexane into chloroform [8]. In the crystal, both p-toluene-
sulfonyl groups are oriented syn to the pyrrolinone such
that the plane of the pyrrolinone unit is sandwiched
between the p-tolyl planes, leaving the sulfones essentially
eclipsed. The n-butyl group at C(3) has an extended con-
formation. The internal angles of the planar pyrrolinone,
N(1)-C(1)-C(2) = 105.6°, C(1)-C(2)-C(3) = 109.0°, C(2)-
C(3)-C(4) = 110.3°, C(3)-C(4)-N(1) = 101.6° and C(1)-
N(1)-C(4) = 113.4°, are not unusual and are close to those
predicted by molecular mechanics (PCMODEL) [9]:
105.9°, 107.9°, 112.1°, 99.5°, 114.5°, respectively. Other
bond angles, and bond lengths appear to be normal for
toluenesulfonyl and pyrrolinone systems.
was carried out on Merck silica gel PF
with calcium sulfate
254
binder, preparative layer grade. All solvents were reagent grade
obtained from Fisher or Aldrich; deuterated chloroform was from
Cambridge Isotope Laboratories. 3-n-Butyl-4-methyl-2-p-toluene-
sulfonyl-1H-pyrrole (3a) was synthesized according to the litera-
ture procedure [7]. Crystal structure atomic coordinates of 1,
tables of bond lengths, bond angles and torsion angles are avail-
able from the Cambridge Structural Data File (CCDC No.
255164) [8].
4-n-Butyl-3-methyl-5,5-di-p-toluenesulfonyl-3-pyrrolin-2-one
(1).
3-n-Butyl-4-methyl-2-tosylpyrrole 3b [7] (7.0 g, 0.0241 mol)
was dissolved in 200 ml of 10% trifluoroacetic acid-90%
dichloromethane (vol:vol) and stirred for a period of 24 hours to
give an 80:20 mixture of 3a+3b. To the resulting dark blue solu-
tion was added 100 ml of dichloromethane, and the solution was
washed sequentially with 2 x 100 ml of water, 1 x 100 ml of sat-
urated aqueous sodium carbonate solution (using a small amount
of brine solution to break up emulsions), and 1 x 100 ml of brine
solution. The organic solution was then dried over anhydrous
sodium sulfate and removed (rotovap) to give a crude blue oil.
The oil was decolorized by filtering through a short column of
silica, eluting with dichloromethane. The recovered pale yellow
oil was stored at -20 °C for 12 hours; then, it was dissolved in 50
ml of dichloromethane and cooled to -5 °C using an ice-salt bath.
This solution was titrated with 1.06 g (0.02 mol) of bromine in 30
ml of dichloromethane over the course of 20 minutes. The result-
ing solution of 4a+4b was allowed to stir for 20 minutes (at -5
°C) before being quenched with 10% aqueous ammonia, which
was added dropwise over 20 minutes. The aqueous layer was
separated from the organic layer and extracted three times with
50 ml portions of dichloromethane. The combined organic frac-
tions were washed with 2 x 100 ml of saturated aqueous sodium
carbonate, 100 ml of water and 100 ml of brine solution then
dried over anhydrous sodium sulfate. After filtration, the solvent
was evaporated (rotovap). The crude brown oily product
(4a+4b) was taken up in 70 ml of trifluoroacetic acid, then 11.6
ml of water was added dropwise to the stirred solution over about
20 minutes. When all the water had been added, the solution was
allowed to stir for an additional 4 hours before being taken up
into 200 ml of dichloromethane. The solution was washed
sequentially with water (2 x 200 ml), saturated aqueous sodium
carbonate (2 x 200 ml) and brine (100 ml) before being dried over
anhydrous sodium sulfate, filtered and evaporated (rotovap). The
resulting brown oil was crystallized from dichloromethane-n-
hexane to give a solid, which was further purified by radial chro-
matography on silica gel (1:1 hexane-ethyl acetate eluent, or 2%
methanol in dichloromethane) to give 1.0 g (0.002 mol) of 1, in
an overall 18% yield for the three-step reaction from 3a. It had
m.p. 203-206 °C; C-13 and H-nmr shown in Table 1 and an X-ray
crystallographic structure shown in Figure 4.
Figure 4. Thermal ellipsoid representation of 1 including the atomic
numbering scheme. Hydrogen atoms have been omitted for clarity.
Thermal ellipsoids are drawn at 50% probability.
EXPERIMENTAL
Anal. Calcd for C
3.03. Found: C, 59.74; H, 5.70; N, 3.10.
H NO S (461.6): C, 59.84; H, 5.90; N,
Nuclear magnetic resonance (nmr) spectra were obtained on a
GE QE-300 spectrometer operating at 300 MHz (proton) and 75
23 27 5 2
Woydziak, Zachary R.
