1
306
Can. J. Chem. Vol. 80, 2002
1
-Methyl-5-(1H-pyrrol-2-ylmethylene)-imidazolidine-2,4-
122.2 (C6), 115.1 (C5), 113.5 (C3>), 111.9 (C4>). 7, 8:
ESI+-MS: 195.0 ([M + H] ).
+
dione: E-isomer (1) and Z-isomer (2)
Obtained as a 93:7 E–Z mixture, with 65% overall yield
after purification of the crude product using hexane–acetone
Analytical HPLC
1
(
6:1). 1: H NMR (DMSO): 11.99 (s, 1H, NH1>), 11.45 (s,
The chromatographic system consisted of an HP 1100 liq-
uid chromatograph (Hewlett-Packard, Germany) coupled in
series with an HP photodiode array detector (PAD), an evap-
oration light scattering detector (Polymer Labs, U.K), and an
HP single quadrupole mass-selective detector (MSD) with
an installed electrospray ionization (ESI) source. Process
control and data handling were carried out using HP
ChemStation software. The chromatographic studies were
performed using Spherisorb C8/C18 and Spherisorb P (Wa-
ters, U.S.A.) reverse phase columns (250 × 4.6 mm I.D.,
5 ꢃm particle size) protected by a pre-column filter filled
with the corresponding stationary phases. The mobile phase
consisted of water–TFA (0.05%, solvent A) and acetonitrile–
TFA (0.05%, solvent B). Elution was carried out using a lin-
ear gradient, starting from 30% solvent B to 100% solvent B
over 15 min. This gradient was followed by a 5 min isocratic
elution with 100% B before going back to the initial solvent
mixture in 5 min. An interval of 10 min was allowed be-
tween subsequent runs. When the phenyl package was the
selected stationary phase, the gradient elution went from 5 to
65% B over 15 min, while the rest of the chromatographic
parameters were kept as described above. All runs were per-
1
1
H, NH3), 7.08 (m, 1H, H5>), 6.58 (m, 1H, H3>), 6.47 (s,
H, H6), 6.20 (m, 1H, H4>), 3.07 (s, 3H, Me). C NMR
1
3
(
1
DMSO): 164.6 (C4), 152.7 (C2), 126.6 (C2>), 123.9 (C5),
22.0 (C5>), 116.0 (C3>), 110.0 (C4>), 107.9 (C6), 25.7
1
(
Me). 2: H NMR (DMSO): 11.23 (s, 1H, NH1>), 11.20 (s,
1
H, NH3), 6.96 (m, 1H, H5>), 6.52 (s, 1H, H6), 6.46 (m, 1H,
1
3
H3>), 6.17 (m, 1H, H4>), 3.20 (s, 3H, Me). C NMR
DMSO): 164.5 (C4), 155.3 (C2), 125.5 (C5), 123.8 (C2>),
21.3 (C5>), 112.4 (C3>), 110.0 (C4>), 102.3 (C6), 29.3
(
1
+
(
Me). 1, 2: ESI+-MS: 192.1 ([M + H] ).
1
-Phenyl-5-(1H-pyrrol-2-ylmethylene)-imidazolidine-2,4-
dione: E-isomer (3) and Z-isomer (4)
Obtained as an 86:14 E–Z mixture, with 60% overall yield
after purification of the crude product using hexane–EtOAc
1
(
2:1). 3: H NMR (DMSO): 12.01 (s, 1H, NH1>), 11.73 (s,
1
H, NH3), 7.57 (t, 2H, m-protons phenyl), 7.49 (t, 1H, p-
proton phenyl), 7.42 (d, 2H, o-protons phenyl), 7.09 (m, 1H,
H5>), 6.54 (m, 1H, H3>), 6.16 (m, 1H, H4>), 6.07 (s, 1H,
H6). C NMR (DMSO): 164.3 (C4), 152.1 (C2), 133.0,
1
3
1
1
1
29.6, 128.6, 128.5, 126.0 (C2>), 124.8 (C5), 122.6 (C5>),
1
–1
16.6 (C3>), 110.2 (C4>), 108.2 (C6). 4: H NMR (DMSO):
formed at room temperature at a flow rate of 1 mL min .
1.46 (s, 1H, NH3), 11.22 (s, 1H, NH1>), 7.36–7.43 (m, 3H,
The eluent was monitored by PDA detector and the
absorbance spectra (210–400 nm) were recorded continu-
ously during the course of each run.
m- and p-protons phenyl), 7.29 (d, 2H, o-protons phenyl)
.83 (m, 1H, H5>), 6.72 (s, 1H, H6), 5.77 (m, 1H, H4>), 4.51
6
1
3
(
1
(
m, 1H, H3>). C NMR (DMSO): 164.7 (C4), 154.2 (C2),
24.1 (C2>), 134.6, 128.8, 128.5, 127.4, 123.3 (C5>), 116.6
C5), 113.4 (C3>), 110.2 (C4>), 103.4 (C6). 3, 4: ESI+-MS:
Preparative HPLC
Reverse-phase purification was carried out using a Waters
+
TM
2
54.1 ([M + H] ).
Delta Prep
4000 liquid chromatograph (Waters, U.S.A.)
controlled through the Millenium 32 software package.
Purifications were conducted with a 250 × 2 cm Spherisorb
C18 column, using the same eluents as in analytical HPLC
but at a flow rate of 10 mL min . All isomers so obtained
were examined for purity by analytical HPLC.
5
-(1H-Pyrrol-2-ylmethylene)-imidazolidine-2,4-dione: E-
isomer (5) and Z-isomer (6)
–
1
Obtained as a 44:56 E–Z mixture, with 55% overall yield
after purification of the crude product using hexane–EtOAc
1
(
1:3). 5: H NMR (DMSO): 11.93 (s, 1H, NH1>), 11.24 (s,
1
1
H, NH3), 10.12 (s, 1H, NH1), 7.05 (m, 1H, H5>), 6.52 (m,
H, H3>), 6.32 (s, 1H, H6), 6.17 (m, 1H, H4>). C NMR
NMR experiments
1
3
NMR spectra of 1–8 were acquired on a Bruker Avance
(
1
DMSO): 165.3 (C4), 153.2 (C2), 126.7 (C2>), 122.8 (C5),
21.6 (C5>), 115.2 (C3>), 109.7 (C4>), 107.6 (C6). 6: H NMR
5
00 spectrometer in DMSO at 30°C with an inverse probe.
1
Proton spectra were also recorded at 70°C. Proton and car-
bon chemical shifts were referenced to the residual solvent
signals at 2.50 and 39.5 ppm, respectively. Different types of
carbon experiments were performed: standard C NMR spectra
with proton broadband decoupling, the gated H-decoupling
(
DMSO): 11.18 (s, 1H, NH1>), 10.98 (s, 1H, NH3), 10.04 (s,
1
1
1
H, NH1), 6.98 (m, 1H, H5>), 6.80 (m, 1H, H3>), 6.41 (s,
H, H6), 6.19 (m, 1H, H4>). 13C NMR (DMSO): 165.4 (C4),
55.0 (C2), 125.5 (C2>), 122.1 (C5), 121.6 (C5>), 112.3
13
1
(
C3>), 110.5 (C4>), 100.9 (C6). 5, 6: ESI+-MS: 178.0 ([M +
13
version that yields proton-coupled spectra, and C spectra
+
H] ).
1
with H single frequency decoupling. One-dimensional spec-
5
-(1H-Pyrrol-2-ylmethylene)-thiazolidine-2,4-dione: E-
isomer (7) and Z-isomer (8)
Obtained as an 11:89 E–Z mixture, with 75% overall yield
after purification of the crude product using hexane–EtOAc
1
(
(
5:1–1:1). 7: H NMR (DMSO): 12.25 (s, 1H, NH3), 12.16
s, 1H, NH1>), 7.27 (m, 1H, H5>), 7.25 (s, 1H, H6), 6.73 (m,
1
1
1
1
H, H3>), 6.29 (m, 1H, H4>). 8: H NMR (DMSO): 12.25 (s,
H, NH3), 11.67 (s, 1H, NH1>), 7.66 (s, 1H, H6), 7.20 (m,
1
3
H, H5>), 6.47 (m, 1H, H3>), 6.35 (m, 1H, H4>). C NMR
(
DMSO): 167.8 (C2), 167.2 (C4), 126.9 (C2>), 124.3 (C5>),
©
2002 NRC Canada