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R. MARKOVIC ET AL.
120
17.5 Hz, JAX 8.2 Hz), 3.15 (dd, 1H, CHAHBCHXS, JAB
17.5 Hz, JBX 4.3 Hz), 4.19 (q, 2H, CH2O, J 7.2 Hz),
4.22 (dd, 1H, CHXS, JAX 8.2 Hz, JBX 4.3 Hz), 6.85 (s,
—
1H, CH), 7.39–7.53 (m, 3H, m- and p-Ph), 7.88–7.93
—
(m, 2H, o-Ph), 8.88 (s, 1H, NH). 13C NMR (DMSO-d6): ꢀ
14.5 (CH3), 36.4 (CH2COO), 42.5 (CHS), 61.2 (CH2O),
—
94.9 ( CH), 127.5 (o-Ph), 129.3 (m-Ph), 132.6 (p-Ph),
—
138.7 (C-1 Ph), 161.6 [ C(2)], 170.7 (C4), 176.3
—
—
(COester), 187.7 (COexo).
(E)-(5-Ethoxycarbonylmethyl-4-oxothiazolidin-2-ylidene)-
1
1-phenylethanone [(E)-1]. H NMR (CDCl3): ꢀ 1.29 (t,
3H, CH3, J 7.2 Hz), 2.91 (dd, 1H, CHAHBCHXS, JAB
Figure 1. 1H NMR spectra of Z/E mixture of derivative 1,
recorded in CDCl3 at room temperature, at regular 1 h
intervals
17.6 Hz, JAX 10.1 Hz), 3.28 (dd, 1H, CHAHBCHXS, JAB
17.6 Hz, JBX 3.7 Hz), 4.22 (q, 2H, CH2O, J 7.2 Hz), 4.29
—
(dd, 1H, CHXS, JAX 10.1 Hz, JBX 3.7 Hz), 6.32 (s, 1H,
—
CH), 7.41–7.59 (m, 3H, m- and p-Ph), 7.88–7.93 (m, 2H,
o-Ph), 12.06 (s, 1H, NH). 13C NMR (CDCl3): ꢀ 14.0
(CH3), 37.5 (CH2COO), 42.3 (CHS), 61.7 (CH2O), 94.5
upon its dissolution in CDCl3 (designated as zero time in
Fig. 1) contains, as expected, a nearly perfect set of
signals belonging to the single isomer.
The olefinic proton of the (Z)-1 isomer resonates at
considerably higher frequency owing to the deshielding
effect of the syn-lactam nitrogen, relative to the E-
analogue having this proton in a syn position to the less
electronegative sulfur atom. Proper configurational as-
signment, based on the consideration of this effect,
magnetic anisotropy and mesomeric effects, was possi-
ble, not only for the whole series 1–4, but also for
numerous derivatives thereof.9,10 One-dimensional nu-
clear Overhauser effect (NOE) experiments showed that
the irradiation of the singlet at ꢀ 6.85 ppm of the (Z)-1
isomer gave an enhancement of 4.4% to the aromatic
region and an enhancement of 1.7% to the lactam proton
singlet at ꢀ 8.88 ppm. This is in agreement with the Z-
configuration as the correct assignment. Subsequently,
the NOE experiment was conducted on a solution of the
Z/E mixture, containing about 85% of the (E)-1 isomer
after 24 h. Irradiation of the vinyl singlet at ꢀ 6.32 ppm
showed an NOE on the aromatic region, but not on the
singlet at ꢀ 12.06 ppm assigned to the lactam proton of
the (E)-1 isomer. The configurational isomerization of
1 is an intrinsic structural property, based on electronic
n–ꢂ interactions of the two electron-donor substituents
(—NH—,—S—) and one electron-acceptor, i.e. the
—
—
(
CH), 127.8 (o-Ph), 128.6 (m-Ph), 132.6 (p-Ph), 138.0
—
(C-1 Ph), 158.4 [ C(2)], 170.1 (C4), 174.6 (COester),
—
188.29 (COexo).
An analytical sample was obtained by column chro-
matographic purification of the crude (Z)-1 on silica gel,
eluting with a gradient of toluene–ethyl acetate (100 : 0 to
50 : 50, v/v), followed by concentration of the fractions
containing the desired compound 1. Anal. Calcd for
C15H15NO4S: C, 59.00; H, 4.95; N, 4.59; S, 10.50.
Found: C, 58.76; H, 5.02; N, 4.68; S, 10.54%.
RESULTS AND DISCUSSION
Starting with the pure (Z)-1 isomer (0.011 M), the Z/E
process in CDCl3, at 0.011 M concentration, was mon-
itored at 25 ꢁC during a 15 h period at regular time
intervals (1 h) by 1H NMR spectroscopy (Fig. 1).
The progressive decrease in the Z/E ratio with time,
which reached 13 : 87 after 15 h, was based on the
observation of the signals assigned to the (Z)- and (E)-1
lactam protons which initially appear at ꢀ 8.88 and
12.06 ppm, respectively. The isomerization of (Z)-1 to
its counterpart was also followed by the gradual disap-
pearance of the vinylic proton at ꢀ 6.85 ppm and the
simultaneous growth of the signal at ꢀ 6.32 ppm. The 1H
NMR spectrum of (Z)-1 recorded almost immediately
—
COPh substituent, via the C C bond, as found for other
—
push-pull alkenes.20–27 The key factor controlling the Z/E
ratio is the strength of inter- and intramolecular hydrogen
bonds which depends on, among other factors, the polar-
ity of the medium28,29 (Table 2).
Copyright # 2004 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2004; 17: 118–123