Thermal solid-state Z/E isomerization of 2-alkylidene-4-oxothiazolidines: Effects of non-covalent interactions

Article abstract of DOI:10.2298/JSC100607038D

Configurational isomerization of stereo-defined 5-substituted and unsubstituted 2-alkylidene-4-oxothiazolidines (1) in the solid state, giving the Z/E mixtures in various ratios, was investigated by ¹H-NMR spectroscopy, X-ray powder crystallography and differential scanning calorimetry (DSC). The Z/E composition can be rationalized in terms of non-covalent interactions, involving intermolecular and intramolecular hydrogen bonding and directional non- -bonded 1,5-type S...O interactions. X-Ray powder crystallography, using selected crystalline (Z)-4-oxothiazolidine substrate, revealed transformation to the amorphous state during the irreversible Z → E process. A correlation between previous results on the Z/E isomerization in solution and now in the solid state was established.

Full text of DOI:10.2298/JSC100607038D

J. Serb. Chem. Soc. 76 (3) 317–328 (2011)
UDC 547.78/.79+547.313:66.095.21:543.422.25
JSCS–4120
Original scientific paper
Thermal solid-state Z/E isomerization of 2-alkylidene-4-
-oxothiazolidines: effects of non-covalent interactions
ZDRAVKO DŽAMBASKI1#, MILOVAN STOJANOVIĆ1#, MARIJA
#
BARANAC-STOJANOVIĆ1,2#, DRAGICA M. MINIĆ1,3# and RADE MARKOVIĆ1,2
*
1Centre for Chemistry, ICTM, P. O. Box 473, 11001 Belgrade, 2Faculty of Chemistry,
University of Belgrade, Studentski trg 16 P. O. Box 158, 11001 Belgrade and 3Faculty of
Physical Chemistry, University of Belgrade, Studentski trg 16, 11000 Belgrade, Serbia
(Received 7 July 2010)
Abstract: Configurational isomerization of stereo-defined 5-substituted and un-
substituted 2-alkylidene-4-oxothiazolidines (1) in the solid state, giving the Z/E
1
mixtures in various ratios, was investigated by H-NMR spectroscopy, X-ray
powder crystallography and differential scanning calorimetry (DSC). The Z/E
composition can be rationalized in terms of non-covalent interactions, invol-
ving intermolecular and intramolecular hydrogen bonding and directional non-
-bonded 1,5-type S⋅⋅⋅O interactions. X-Ray powder crystallography, using se-
lected crystalline (Z)-4-oxothiazolidine substrate, revealed transformation to
the amorphous state during the irreversible Z→E process. A correlation be-
tween previous results on the Z/E isomerization in solution and now in the solid
state was established.
Keywords: 4-thiazolidinones; solid-state isomerisation; non-covalent interac-
tions; dynamic 1H-NMR spectroscopy.
INTRODUCTION
Over the last decade, the chemistry of an extensive series of 5-substituted
and unsubstituted 4-oxothiazolidines (1, Fig. 1), bearing a trisubstituted exocyclic
1
C–C double bond at position C-2 was investigated.
They undergo a number of useful transformations into diverse heterocyclic
2a
2b
systems, including 1,2-dithioles, 1,3-thiazines, pyridinium salts containing a
2c
2d
4-oxothiazolidinyl moiety, tetrahydrofuro[2,3-d]thiazolo derivatives and other
thiazolidine-condensed 5-, 6- and 7-membered heterocycles.
derivatives 1 belong to a class of push-pull compounds, usually represented by
the general formula D-π-A, where D and A denote electron donor(s) and electron
acceptor(s), respectively, bonded to a C–C double bond or a π-conjugating spacer.
2e,f
The thiazolidine
3
4
*Corresponding author. E-mail: markovic@chem.bg.ac.rs
# Serbian Chemical Society member.
doi: 10.2298/JSC100607038D
317
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318
DŽAMBASKI et al.
Fig. 1. 2-Alkylidene-4-oxothiazolidinones.
The strong D−A interactions via C=C bond(s) in various push-pull deri-
4a
vatives, for example in D−A-substituted tetraethynylethenes 2, or benzodithiole
4b
polyenes 3, (Fig. 2) are associated with their interesting electrochemical and
5
non-linear optical properties.
Fig. 2. D−A-Substituted tetraethynylethenes and benzodithiole polyenes.
It was previously shown that electronic interactions in the (Z)-4-oxothiazo-
lidine derivatives 1 in solution, between the two electron-releasing substituents
–NH and –S–, and an electron-withdrawing substituent (COPh, CO Et, CONHPh,
2
etc.) through the π-conjugated bond, have a decisive influence on lowering the
6
rotational barrier of the exocyclic C=C bond at position C-2. As a result of the
partial single bond character of the C=C bond, configurational isomerization of
these highly dipolar compounds, controlled by an appropriate choice of solvent,
occurs in solution. On the other hand, the literature contains only a few examples
7
describing the Z/E isomerization of organic compounds in the solid state.
1
It is the intent of this paper to report herein i) a H-NMR investigation of the
stereodynamic behaviour of the stereo-defined 2-alkylidene-4-oxothiazolidines 1
in the solid state, proving that a rare type of thermally induced configurational
isomerization occurs to form Z/E mixtures in different ratios. This is combined
with ii) X-ray powder analysis and DSC measurements in terms of an evaluation
of the crystallinity change occurring during the heating process of a representta-
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SOLID-STATE ISOMERIZATION OF 2-ALKYLIDENE-4-OXOTHIAZOLIDINES
319
tive of the push-pull alkenes 1, i.e., (Z)-ethyl 4-oxo-2-[2-oxo-2-[(2-phenyl-
ethyl)amino]ethylidene]-5-thiazolidineacetate (1d) (Fig. 3).
Fig. 3. Structures of 2-alkylidene-4-oxothiazolidines.
RESULTS AND DISCUSSION
Several structural features of compounds 1, that is, their polyfunctional na-
ture, the stereogenic centre at the C-5 position of the thiazolidine ring, the Z- or
E-geometry of the exocyclic donor–acceptor substituted C=C bond, and, impor-
tantly, the cis-configured –S–C=C–C=O unit of the Z-isomers, make them inte-
resting substrates for investigating their properties and reactivity. To probe the
impact of inter- and intramolecular interactions on the solid state thermal Z/E-iso-
merization of the structurally related (Z)-5-substituted and unsubstituted 2-alkyli-
dene-4-oxothiazolidines 1a–f (Fig. 3), the behaviour of ethyl (Z)-ethyl 2-[2-
-(ethoxycarbonyl)ethylidene]-4-oxo-5-thiazolidineacetate (1a) was examined first.
The Z-configuration of the thiazolidines 1a–f, obtained from the correspond-
1a,b
1
ing β-oxonitriles and α-mercaptoesters,
was previously elucidated from H-
-NMR spectroscopic data, including 1D nuclear Overhauser effect measurements
in the case of the enaminoketone 1e. X-ray structural analysis confirmed the
configuration of the trisubstituted C=C bond in 1a, having the lactam hydrogen
involved in intermolecular hydrogen bonding to the C-4 carbonyl oxygen of an
adjacent molecule. Upon slow heating of the solid crystalline compound 1a (1–2
–1
°C min ), from room temperature to 120 °C, which is slightly above its melting
point, followed by fast cooling of the melt to 0 °C, the extent of the Z/E process
1
was determined by H-NMR spectroscopy, employing DMSO-d or CDCl as
6
3
solvents. As Fig. 4 depicts, the spectrum of 1a in DMSO-d contained two sets of
6
signals, including typical resonances of the olefinic protons at δ 5.44 ppm for the
original Z-isomer and δ 5.21 ppm assigned to the newly formed E-isomer (the
characteristic δ values of the olefinic protons are given in Experimental). The Z/E
ratio, determined by integration of the corresponding chemical shifts, was 83/17.
Likewise, the composition of the Z/E mixtures of all thiazolidines 1a–g,
based on assignments of the characteristic signals for the vinylic protons in the
1
corresponding H-NMR spectra, recorded in DMSO-d and/or CDCl , is com-
6
3
piled in Table I.
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DŽAMBASKI et al.
Fig. 4. 1H-NMR spectrum of the Z/E mixture of thiazolidine derivative 1a, recorded in
DMSO-d6 after thermal solid-state isomerization.
TABLE I. Configurational isomerization of compounds 1a–g in the solid state
Z/E ratio
(DMSO-d6)b
83/17
Z/E ratio
Temperature
Entry Substrate
R
EWG
range, °Ca
(CDCl3)b
Z-1a
CH2CO2Et
CO2Et
rtc–120
rt–120
rt–110d
rt–195
rt–203
rt–166
rt–90
78/22
49/51e
90/10
1
e,f
2
3
4
5
6
7
a
Z-1b
Z-1c
Z-1d
Z-1e
Z-1f
CH2CO2Et
CH3
CH2CO2Et CONH(CH2)2Ph
CH2CO2Et
H
CONHPh
CONHPh
41/59
48/52
58/42
100/0
100/0
–
–
–
COPh
COPh
CO2Et
57/43
69/31
–
rt–245
2E,5Z-1g =CHCO2Et
rt–180 70/30 (2E,5Z/2Z,5Z)
b
From room temperature to ≈5–10 °C above the melting point; 0 time (1–2 min after dissolution of a sample);
room temperature precursor heated below the melting point; 2 heating; insoluble in CDCl3
nd
c
; d
e
f
It is interesting to note that in the case of substrates 1e or 1f of the thiazo-
lidine series 1a–f with one exocyclic C=C bond, the corresponding Z-isomers
1
were the only species at the end of the heating process, as detected by H-NMR
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SOLID-STATE ISOMERIZATION OF 2-ALKYLIDENE-4-OXOTHIAZOLIDINES
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in DMSO-d (Table I, entries 5 and 6). Apparently, the precursors Z-1e and Z-1f
6
are either unable to undergo thermally induced solid state Z/E isomerization (vide
infra) or, more likely, the E-isomer of the Z/E mixture formed during the iso-
merization, as found for 4-oxothiazolidines 1a–d (Table I, entries 1–4), trans-
forms in a rapid DMSO-induced E→Z interconversion back to original Z-form.
1
Indeed, the observation of two H-NMR vinylic signals at δ 6.83 and 6.32 ppm in
non-polar CDCl for substrate 1e, ascribed to the Z- and E-isomer, respectively,
3
in a 57/43 ratio (Table I, entry 5), verifies that the solid state isomerization does
1
occur. This is consistent with the finding that the H-NMR spectrum of the se-
cond enaminoketone 1f, similarly to 1e, displayed a pair of =CH signals in
1
CDCl at δ 6.78 ppm for Z-1f and at δ 6.33 ppm for E-1f, whereas the H-NMR
3
spectrum in DMSO-d of the same sample 1f after heating, showed only the vi-
6
nylic proton of the Z-isomer at δ 6.82 ppm. This is in line with the fact that the
1
H-NMR spectra of the highly dipolar compounds 1a–f, or, in principle, related
8
13
push-pull compounds, are solvent-dependent. The C values of C-2 at rather
low field for a vinylic carbon (151–163 ppm) of compounds 1a–f, together with a
high field position for vinylic C-2’ atom (89–95 ppm) reflect their dipolar cha-
1,3
racter and hydrogen bonding ability. In some cases, depending on the relative
rate of the configurational isomerization pertinent to dipolar compounds of the
type 1, the Z/E ratio can be appreciably affected in accordance to the general
Scheme 1, even during the shortest NMR recording time possible.
Scheme 1. Configurational isomerization of compounds 1a–g in solvents of different polarity.
In accordance to earlier generalization, the E-isomers 1a–f are the preferred
species for equilibrated Z/E mixtures in non-polar CDCl , as the NH⋅⋅⋅O=C non-
3
6a,b
-covalent interaction leads to favourable six-membered H-bonding.
Upon in-
creasing the ground-state polarization of thiazolidines 1a–f in polar DMSO, the
neutral, intramolecularly H-bonded structure of E-1a–f is no longer the dominant
one. The strong 1,5-type electrostatic S⋅⋅⋅O interaction due to the maximum char-
ge stabilization in DMSO, as depicted in Scheme 1, enhances the contribution of
9
the resonance form A. Thus, the intramolecular H-bonding in the original E-
-isomer is suppressed at the expense of its Z-counterpart. The formation of com-
petitive intermolecular H-bonding between the solvent and corresponding Z-1,
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DŽAMBASKI et al.
acting in the same direction, favouring the Z-form, further attenuates the fast pro-
cess of C=C bond isomerization. This is obviously a draw-back of using DMSO-
1
-d for H-NMR determination of the Z/E composition for 1e and 1f after heat-
6
ing, due to the rapid E→Z isomerization. Fortunately, in contrast to the counter-
-effect of DMSO on reliable determination of the Z/E ratio, the kinetic data
obtained for the configurational isomerization at room temperature of (Z)-ethyl 4-
-oxo-2-(2-oxo-2-phenylethylidene)-5-thiazolidineacetate (1e), and a series of
related compounds, in CDCl show that the configurational change at room tem-
3
perature is rather slow. More precisely, starting from the pure (Z)-1e isomer, the
t
, i.e., the time needed to obtain a 50:50 mixture of the isomers during the Z/E
1/2
process in CDCl at 25 °C, monitored at regular time intervals (1 h) by dynamic
3
1
1
H-NMR, was 5 h. The variable-temperature H-NMR data for the isomerization
of 1e in CDCl indicated that the rotational barrier ΔG , separating the (Z)-1e and
(E)-1e isomers, is 98.5 kJ mol (at 298 K).
#
3
–1
6a,b
The use of CDCl can actually
3
circumvent the problem of rapid E→Z isomerization, or specifically that of the
enaminoketones (E)-1e or (E)-1f (EWG = COPh) in DMSO. Thus, an accurate
estimate of the relative amounts of each isomer and, consequently, an evaluation
of the extent of the thermally induced configurational isomerization of 1a–f in
the solid state is possible.
An interesting point concerning the different percentages of the Z-isomers in
1
the Z/E mixtures 1a–f, as determined by H-NMR in DMSO-d , revealed clearly
6
the influence of the EWGs on an extent of the dictated E→Z isomerization in po-
lar solvents, as illustrated in Scheme 1. Namely, an increase of the Z-isomers in
the order 1e, 1f > 1a > 1b (Table I, entries 5, 6, 1 and 2, respectively) parallels
the order COPh > CO Et > CONHR in terms of the stronger electron with-
2
drawing effect of the keto group present in 1e and 1f, vs. the ester group in 1a,
with the amido group in 1b being somewhat weaker. Consequently, the better
electron withdrawing ability of the keto group to decrease the double bond cha-
racter at C-2 enhances the contribution of the resonance forms A and B, enabling
1
faster E→Z isomerization. This is indicated by the fact that the H-NMR spec-
trum of 1e (EWG = COPh) after the thermal process showed the presence of only
the Z-isomer, whereas a Z/E ratio of 57/43 was determined for the same com-
pound in CDCl . In contrast, the corresponding Z/E ratio was 78/22 for 1a (EWG
3
= CO Et) in CDCl and only slightly higher (83/17) in DMSO-d , which con-
2
3
6
vincingly suggest a slower E/Z interconversion on the NMR scale. On a second
heating of the melt 1a under identical conditions (Experimental), the Z/E com-
1
position, as determined by H-NMR in CDCl , as for the other substrates 1b–f,
3
amounted to 49/51 (Table I, entry 1). Obviously, the greater percentage of the E-
isomer in the second melt vs. that of the first melt proves the progressive extent
of the Z→E process. When the thermal process, employing 1a was performed
from rt to 110 °C, which is below its melting point, the Z/E ratio was 90/10.
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SOLID-STATE ISOMERIZATION OF 2-ALKYLIDENE-4-OXOTHIAZOLIDINES
323
For stereodefined ethyl (2E,5Z)-ethyl 2-[2-[2-(ethoxycarbonyl)ethylidene)-4-
-oxo-5-thiazolidinylilidene]acetate (1g), possessing two exocyclic C=C bonds at
positions C-2 and C-5, a 2E,5Z/2Z,5Z ratio of 70/30 was observed in DMSO-d
6
after thermal isomerization (Table I, entry 7). The Z-configuration at the C-5
position stayed intact due to the unfavourable steric interactions in the respective
10
1
E-configuration. By analysis of variable-temperature H-NMR data for the
solvent-initiated isomerization of 2E,5Z-1g into 2Z,5Z-1g in DMSO-d from
6
room temperature (Fig. 5) to 55 °C, the reliability of the extent of this isome-
rization occurring in the solid state was assessed.
Fig. 5. Spectral evidence for the pre-
sence of the 2E,5Z-1g isomer (olefinic
signals at δ 5.63 and 6.68 ppm, and
2Z,5Z-1g isomer (olefinic signals at δ
5.69 and 6.59 ppm) in DMSO-d6 at rt;
1
30 min H-NMR recording interval;
1
partial H-NMR spectrum 1 at initial
recording time indicates the presence
of the starting 2E,5Z-1g isomer, based
on the observation of the olefinic sig-
nals at δ 5.63 and 6.68 ppm; partial
1H-NMR spectrum 11, recorded after
5 h, indicates the presence of both iso-
mers, 2E,5Z-1g and 2Z,5Z-1g, in the
72/28 ratio; partial 1H-NMR spectrum
21 (not given), recorded after 10 h, in-
dicates that the signals of 2E,5Z-1g at
δ 5.63 and 6.68 ppm, and these of
2Z,5Z-1g at δ 5.69 and 6.59 ppm,
have almost the same intensities.
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DŽAMBASKI et al.
1
Thus, Fig. 5, displaying the partial H-NMR spectra of 2E,5Z-1g and 2Z,5Z-
-1g isomers recorded during a 5-h period at 30-min intervals at room tempera-
ture, indicates only the characteristic signals of the olefinic protons. As seen from
Fig. 5, the 2E,5Z/2Z,5Z ratio reached a value of 72/28 after 5 h (spectrum 11). By
monitoring the kinetics of the configurational isomerization during an extended
period (20 h), a relatively long isomerization half-life (t ) of around 10 h was
1/2
observed. An equilibrated 2E,5Z/2Z,5Z ratio of 10/90 was established after 20 h.
These data clearly suggest that the 2E,5Z→2Z,5Z process in DMSO-d is rather
6
slow at room temperature. Accordingly, it was concluded that the overall esti-
mate of the thermally induced isomerization of isomer 2E,5Z-1g (Table I, entry
7), based on the determination of the 2E,5Z/2Z,5Z ratio in this polar solvent, is
quite accurate. The same conclusion applies to the 4-oxothiazolidine 1a, differing
2
3
from 2E,5Z-1g only at the C-5 atom that is not sp but sp hybridized.
The solid-state Z→E process of (Z)-ethyl 4-oxo-2-[2-oxo-2-[(2-phenylethyl)-
amino]ethylidene]-5-thiazolidineacetate (1d) was also studied by powder X-ray
11
diffraction and DSC in the temperature interval from rt to m.p. The crystalline
structure of Z-1d was stable up to approximately 136 °C when a breakdown of
the ordered crystal structure and melting occurred (t = 145 °C at a heating rate β
p
–1
1
= 5 °C min ). The diffractogram of the melted structure, characterized by H-
NMR as the expected E-isomer, indicated the formation of an amorphous com-
pound. The observation of a sharp peak of very low intensity was evidence for
the presence of a small quantity of the crystalline E-isomer in a matrix of amor-
phous material. An analysis of the X-ray diffraction data obtained for a melt
stored under inert conditions for four months showed an increase in the intensity
of this peak. This fact suggested a slow and progressive conversion of the
amorphous E-isomer into the crystalline form.
DSC measurements of the E-isomer 1d demonstrated that, in comparison to
the Z-isomer, the E-isomer melts at a significantly lower temperature (t = 130.9 °C
p
–1
for β = 5 °C min ). The volume fraction, α, i.e., the fractional conversion of the
Z→E process from the starting Z-isomer, was determined from the DSC curves
as a function of the temperature (Fig. 6a). A consistent shifting of the DSC cur-
ves towards higher temperatures with increasing heating rate indicates that the
well-defined endothermic peak on each DSC curve involves, in addition to the
melting of the compound and the Z→E process, other thermally activated steps,
such as cleavage of the crystal lattice, disruption of the stabilizing non-bonded
1,5-type S⋅⋅⋅O interaction and inter-molecular hydrogen bonds, as integral parts
of the phase transformation.
As depicted in Figs. 6a and 6b, all curves, depending on the heating rate,
exhibit a slow initial period ranging from 7–27 min, which corresponded to the
dominant transformation step, followed by the faster steps of the transformation.
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SOLID-STATE ISOMERIZATION OF 2-ALKYLIDENE-4-OXOTHIAZOLIDINES
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The well-shaped sigmoid pattern of the fractional conversion curves (Fig. 6a) in-
dicates that the overall transformation occurs in the bulk of material.
(a)
Fig. 6 a) Fractional conversion, α, as a
function of temperature for the Z→E
process of (Z)-1d and b) differential
rate curves at different heating rates:
(b)
5, 10, 15 and 20 °C/min.
For a preliminary determination of the kinetic model of the phase transfor-
12
mation, the Dollimore method was applied. The procedure was applied to the
conversion and differential rate curves for the thiazolidine derivative 1d (Figs. 6a
and 6b), the asymmetry of which was observed between the initial temperature
(t ) and final temperature (t ) for the differential rate curves. The other parame-
i
f
ters, such as the conversion at the rate of maximum crystallization, α , peak
max
temperature, t , at (dα/dt) , and asymmetry (shape factor), which is the ratio
p
max
between the low and high temperature at the half-width of the differential rate
curve peak, are presented in Table II.
Fig. 6b depicts that the position of the broad endotherms, which are pertinent
to the phase transformation, involving the Z→E isomerization, are shifted to-
wards higher temperatures with increasing heating rate (Table II, column 4). Si-
multaneously, the symmetry of curves decreased (column 3). These features sug-
gest that the investigated process should not be characterized by a definite critical
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DŽAMBASKI et al.
temperature independent of the heating rate. The determined values of α
for
max
all heating rates were 0.58 and the values of the half-width of peaks were in the
range of 5.4–8.0 °C. Thus, the sharpness of the initial and final part of differential
curve, together with other parameters presented in Table II, indicate that the
investigated process corresponds to the Avrami–Erofe’ev Equation, f(α) =
1/n
n(1–α)(–ln(1–α)) , where n = 2, 3 or 4, describes the random nucleation and
growth of the nuclei. In the case of continuous heating, the generalization of the
13
Avrami–Erofe’ev Equation, by applying the Kissinger equation, gives the rela-
tions:


dα
dt


E
k RT
a
β
=1 and
= 0.37nk
p










2
p
p
p
where n is the Avrami exponent, T is the peak temperature and k is the rate
p
p
constant at the peak temperature.
TABLE II. Parameters describing the asymmetry of the differential curves
(dα/dt)max
Half-width
°C
Shape of Shape of final
β / °C min-1
Asymmetry
αmax
°C-1
initial part
part
5
0.20
0.15
0.13
0.12
0.78
0.75
0.67
0.64
5.4
5.5
6.5
8.0
Sharp
Sharp
Sharp
Sharp
Sharp
Sharp
Sharp
Sharp
0.58
0.58
0.58
0.58
10
15
20
The average value of n = 1.83 obtained by applying these relations is very
close to the value n = 2, suggesting the validity of the Avrami–Erofe’ev equation,
1/n
f(α) = n(1–α)(–ln(1–α)) (n = 2), for a description of the whole phase trans-
formation occurring in the bulk of the material. Based on previously reported
8
kinetic parameters, the overall structural transformation, including the Z→E iso-
merization of (Z)-ethyl 4-oxo-2-(2-oxo-2-[(2-phenylethyl)amino]ethylidene]-5-thi-
azolidineacetate (1d), can be described by the kinetic triplet, i.e., E = 317.7 kJ
a
–1
–1
1/2
mol , ln A = 93.4 min and f(α) = 2(1–α)(–ln(1–α))
.
In summary, it has been shown that an irreversible configurational isomeri-
zation of a series of stereo-defined 2-alkylidene-4-oxothiazolidines occurs in the
solid state.
EXPERIMENTAL
General Procedures
The configurational isomerization of the stereo-defined 5-substituted and unsubstituted 2-
alkylidene-4-oxothiazolidines 1a–g was investigated by the slow heating (1–2 °C min-1) of the
corresponding solid crystalline compounds from room temperature to a temperature which is 5–
–10 °C above the melting point, followed by fast cooling to 0 °C. The extent of the isomeriza-
tion process was determined by 1H-NMR spectroscopy, employing DMSO-d6 or CDCl3 as sol-
vents. The structural assignments of all configurational isomers of 4-oxothiazolidines 1a–g were
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SOLID-STATE ISOMERIZATION OF 2-ALKYLIDENE-4-OXOTHIAZOLIDINES
327
made based on reported spectroscopic data (IR, 1H- and 13C-NMR, MS and UV) and elemen-
1
tal analysis.1a,6b The H-NMR data for the characteristic olefinic hydrogens of the configura-
tional isomers 1a–g, employed for monitoring the extent of the solid state isomerization, are
listed in Table III.
TABLE III. Diagnostic 1H-NMR chemical shifts (the 1H-NMR spectra were recorded on a Va-
rian Gemini 2000 instrument (1H at 200 MHz); the chemical shifts are given in ppm downfield
from TMS as the internal standard) of the olefinic hydrogens in the configurational isomers 1a–g
Substrate
R
EWG
DMSO-d6
CDCl3
Z-1a
E-1a
Z-1b
E-1b
Z-1c
E-1c
Z-1d
E-1d
Z-1e
E-1e
Z-1f
E-1f
2Z,5Z-1g
2E,5Z-1g
a
CH2CO2Et
CH2CO2Et
CH2CO2Et
CH2CO2Et
CH3
CO2Et
CO2Et
5.44
5.21
5.79
5.36
5.80
5.36
5.55
5.15
6.78
5.59
5.12
–
–
–
CONHPh
CONHPh
CONHPh
CONHPh
CONH(CH2)2Ph
CONH(CH2)2Ph
COPh
CH3
–
CH2CO2Et
CH2CO2Et
CH2CO2Et
CH2CO2Et
H
5.44
4.88
6.83
6.32
6.78
6.33
5.83
5.35
a
COPh
COPh
COPh
CO2Et
–
6.82
a
H
–
=CHCO2Et
=CHCO2Et
5.68
5.64
CO2Et
Due to the instantaneous E→Z isomerisation, there were no signals for the olefinic E-1e and E-1f isomers in
DMSO-d
6
The overall thermally induced process of the structural transformation of (Z)-ethyl 4-
-oxo-2-(2-oxo-2-[(2-phenylethyl)amino]ethylidene]-5-thiazolidineacetate (1d) was also inves-
tigated non-isothermally by differential scanning calorimetry (DSC) using a DuPont Thermal
analyzer (model 1090). Samples weighing several milligrams (3–7 mg) were heated in the
DSC cell from room temperature to 170 °C, at heating rates in the range 5–20 °C min-1, in a
stream of nitrogen at normal pressure. The temperature peaks (tp) were determined from the
DSC curves using the program Interactive DSC V1.1. Then X-ray powder diffraction patterns
of the Z- and E-isomer 1d were investigated.
Acknowledgements. This research was partially supported by the Ministry of Science and
Technological Development of the Republic of Serbia, Grant No. 142007 (to R. M.).
И З В О Д
ТЕРМАЛНА Z/Е ИЗОМЕРИЗАЦИЈА 2-АЛКИЛИДЕН-4-ОКСОТИАЗОЛИДИНА У
ЧВРСТОМ СТАЊУ: УТИЦАЈ НЕКОВАЛЕНТНИХ ИНТЕРАКЦИЈА
ЗДРАВКО ЏАМБАСКИ1, МИЛОВАН СТОЈАНОВИЋ1, МАРИЈА БАРАНАЦ-СТОЈАНОВИЋ1,2
ДРАГИЦА М. МИНИЋ1,3 и РАДЕ МАРКОВИЋ1,2
,
1Centar za hemiju, IHTM, p. pr. 473, 11001 Beograd, 2Hemijski fakultet, Univerzitet u Beogradu,
Studentski trg 16, p. pr. 158, 11001 Beograd i 3Fakultet za fizi~ku hemiju,
Univerzitet u Beogradu, Studentski trg 12, 11000 Beograd
Конфигурациона изомеризација стереодефинисаних 5-супституисаних и несупституи-
саних 2-алкилиден-4-оксотиазолидина 1 у чврстом стању, при чему се ствара Z/Е смеса у
1
различитим односима, проучавана је помоћу H-NMR спектроскопије, рендгенске кристало-
Available online at www.shd.org.rs/JSCS
________________________________________________________________________________________________________________________________________
2011 Copyright (CC) SCS

328
DŽAMBASKI et al.
графије праха и диференцијалне скенирајуће калориметрије (ДСK). Однос Z/Е изомера може
се објаснити у контексту нековалентних интеракција, које обухватају интермолекулско и ин-
трамолекулско водонично везивање и усмерене невезивне S⋅⋅⋅О интеракције 1,5-типа. Ренд-
генска кристалографија праха одабраног кристалног (Z)-4-оксотиазолидинског супстрата,
потврдила је трансформацију у аморфно стање у току иреверзибилног Z→Е процеса. Постав-
љена је корелација између претходних резултата који се односе на Z/Е изомеризацију у рас-
твору, и сада, у чврстом стању.
(Примљено 7. јула 2010)
REFERENCES
1. a) R. Marković, M. Baranac, Z. Džambaski, M. Stojanović, P. J. Steel, Tetrahedron 59
(2003) 7803; b) R. Marković, M. M. Pergal, M. Baranac, D. Stanisavljev, M. Stojanović,
Arkivoc (2006) 1; c) G. Satzinger, Liebigs Ann. Chem. (1978) 473
2. a) R. Marković, M. Baranac, S. Jovetić, Tetrahedron Lett. 44 (2003) 7087; b) A. Rašović,
P. J. Steel, E. Kleinpeter, R. Marković, Tetrahedron 63 (2007) 1937; c) M. Baranac-Sto-
janović, J. Tatar, E. Kleinpeter, R. Marković, Synthesis (2008) 2117; d) R. Marković, M.
Baranac, P. J. Steel, E. Kleinpeter, M. Stojanović, Heterocycles 65 (2005) 2635; e) R.
Marković, M. Stojanović, Synlett (2009) 1997; f) A. V. Tverdokhlebov, A. P. Andrushko,
A. A. Tolmachev, Synthesis (2006) 1433
3. a) E. Kleinpeter, S. Klod, W.-D. Rudorf, J. Org. Chem. 69 (2004) 4317; b) E. Kleinpeter,
J. Serb. Chem. Soc. 71 (2006) 1; c) J. Sandström, Top. Stereochem. 14 (1983) 83
4. a) M. Kivala, F. Diederich, Acc. Chem. Res. 42 (2009) 235; b) J.-M. Lehn, Angew. Chem.
Int. Ed. Engl. 29 (1990) 1304 (and references therein)
5. а) J. L. Brédas, G. B. Street, Acc. Chem. Res. 48 (1985) 309; b) A. O. Patil, A. J. Heeger,
F. Wudl, Chem. Rev. 88 (1988) 183
6. a) R. Marković, A. Shirazi, Z. Džambaski, M. Baranac, D. Minić, J. Phys. Chem. 17
(2004) 118; b) R. Marković, M. Baranac, N. Juranić, S. Macura, I. Cekić, D. Minić, J.
Mol. Struct. 800 (2006) 85
7. G. Kaupp, Top. Stereochem. 25 (2006) 303 (and references therein)
8. a) E. Kleinpeter, B. A. Stamboliyska, J. Org. Chem. 73 (2008) 8250; b) A. Basheer, Z.
Rappoport, Org. Biomol. Chem. 6 (2008) 1071
9. a) J. G. Ángyán, R. A. Poirier, Á. Kucsman, I. G. Csizmadia, J. Am. Chem. Soc. 109
(1987) 2237; b) S. Wu, A. Greer, J. Org. Chem. 65 (2000) 4883
10. S. F. Tan, K. P. Ang, G. F. How, J. Chem. Soc. Perkin Trans. 2 (1988) 2045
11. D. M. Minić, Z. Nedić, R. Marković, J. Therm. Anal. Cal. 95 (2009) 167
12. Y. F. Lee, D. Dollimore, Thermochim. Acta 323 (1998) 75
13. D. S. dos Santos, R.S. de Biasi, J. Alloy Compd. 335 (2002) 266.
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