Factors determining the stereochemical structure of 2-(phosphorus substituted) methylidene-thiazolidine- 4-ones in solid state and in solution

Article abstract of DOI:10.1080/10426500802715544

Regioselective synthesis of novel 2-(phosphorus substituted) methylidene-thiazolidine-4-ones 5a-c was performed via condensation of phosphorus-substituted acetic acid thioamides 4a-c with dimethyl acetylenedicarboxylate. Thiazolidine-4-ones 5a,b bearing t

Full text of DOI:10.1080/10426500802715544

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Factors Determining the
Stereochemical Structure of
2-(Phosphorus Substituted)
Methylidene-thiazolidine-
4-ones in Solid State and in
Solution
Vladimir A. Kozlov a , Konstantin A. Lyssenko a ,
Svetlana G. Churusova a , Sergey V. Yarovenko a ,
Pavel V. Petrovskii a & Irina L. Odinets a
a A. N. Nesmeyanov Institute of Organoelement
Compounds, Russian Academy of Sciences , Moscow,
Russian Federation
Published online: 26 Mar 2009.
To cite this article: Vladimir A. Kozlov , Konstantin A. Lyssenko , Svetlana G.
Churusova , Sergey V. Yarovenko , Pavel V. Petrovskii & Irina L. Odinets (2009) Factors
Determining the Stereochemical Structure of 2-(Phosphorus Substituted) Methylidene-
thiazolidine- 4-ones in Solid State and in Solution, Phosphorus, Sulfur, and Silicon and
the Related Elements, 184:4, 830-845, DOI: 10.1080/10426500802715544
To link to this article: http://dx.doi.org/10.1080/10426500802715544
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Phosphorus, Sulfur, and Silicon, 184:830–845, 2009
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500802715544
Factors Determining the Stereochemical Structure of
2-(Phosphorus Substituted) Methylidene-thiazolidine-
4-ones in Solid State and in Solution
Vladimir A. Kozlov, Konstantin A. Lyssenko,
Svetlana G. Churusova, Sergey V. Yarovenko,
Pavel V. Petrovskii, and Irina L. Odinets
A. N. Nesmeyanov Institute of Organoelement Compounds, Russian
Academy of Sciences, Moscow, Russian Federation
Regioselective synthesis of novel 2-(phosphorus substituted) methylidene-
thiazolidine-4-ones 5a–c was performed via condensation of phosphorus-
substituted acetic acid thioamides 4a–c with dimethyl acetylenedicarboxylate.
Thiazolidine-4-ones 5a,b bearing thiophosphoryl or dithiophosphoryl moiety were
obtained as E,Z-isomers while their analog 5c with triphenylphosphonium group
was formed as a Z, Z-isomer. The structures of thiazolidin-4-ones 5a–c obtained
were determined by single crystal X-ray diffraction. According to quantum-
chemical calculations, the isomers observed in the solid state are thermodynami-
cally more stable. In solution, thio- and dithiophosphorylated thiazolidinones 5a, b
2
undergo E,Z → Z,Z isomerization relative to C carbon atom of the heterocycle pro-
ceeding via an imine–enamine mechanism.
Keywords ab initio calculations; dimethyl acetylenedicarboxylate; isomerization;
2-(phosphorus-substituted)methylidene-thiazolidine-4-ones; regioselectivity; (thio)phos-
phoryl acetic acid thioamides
INTRODUCTION
Condensation of thioureas and malonothioamide derivatives with
dimethyl acetylenedicarboxylate (DMAD) is known to be a convenient
Received 20 December 2007; accepted 2 February 2008.
Dedicated to Professor Marian Mikołajczyk, CBMiM PAN in Ło´dz´, Poland, on the
occasion of his 70th birthday.
This work was partially supported by the Russian Basic Research Foundation (grant
No. 05-03-32692). We are grateful to Mrs. N. White (Department of Chemistry and Bio-
chemistry, University of Maryland) for her helpful comments.
Address correspondence to Irina L. Odinets, A. N. Nesmeyanov Institute of Orga-
noelement Compounds, Russian Academy of Sciences, Vavilova str. 28, 119991 Moscow
GSP-1, Russian Federation. E-mail: odinets@ineos.ac.ru
830

2-P-Substituted Methylidene-thiazolidine-4-ones
831
route to pharmacologically active 2-imino-5-methoxycarbonylthiazo-
lidin-4-ones1–7 and 2,5-bis(substituted methylidene)-thiazolidine-4-
ones,8,9 which are formed usually as a mixture of Z, Z and E, Z isomers.
Recently we demonstrated that phosphoryl acetic acid thioamides 1a–c
or thioanilide 1d also react with DMAD according to a similar conden-
sation scheme yielding 2-(phosphoryl)methylene-thiazolidin-4-ones 2
and 3 in good to high yields (Scheme 1).10
SCHEME 1
In contrast to the condensation of nonphosphorylated malonoth-
ioamide derivatives with DMAD,8,9 compounds 1a–d react with DMAD
regioselectively and yield a single isomer of the final heterocycle,
which is the thermodynamically more favorable according to quantum-
chemical calculations.10 The type of isomer depends on the substituent
R at the nitrogen atom of thiocarbamoyl group in the starting com-
pound 1a–d. Thus, condensation of thioamides 1a–c (R=H) resulted in
the formation of only E, Z-isomers of thiazolidines 2a–c, while the reac-
tion of thioanilide 1d (R = Ph) led to the formation of 3 as Z, Z-isomer.
The structures of these compounds were unambiguously confirmed by
X-ray crystallography. According to the X-ray data, the E,Z isomers of
2a–c are stabilized in a solid state by strong intramolecular hydrogen
. . .
bonds P O HN, which define their structure. According to the NMR
spectroscopic analysis, in CDCl3 and C6D6 solutions phosphorylated
thiazolidin-4-ones 2a–c exist also as the E, Z-isomers, showing one sin-
glet in the 31P NMR spectrum and one set of signals in the 1H and 13
C
NMR spectra in the same solvent. During the time of observation, no
changes were recorded in these spectra. Moreover, the independence of
the NH-chemical shifts on the concentration in the 1H NMR spectra of
these compounds in CDCl3 and C6D6 indicates the conservation of the
intramolecular H-bonds, which stabilize the E, Z-isomers in solution.10
At the same time, when the E,Z-isomer of compounds 2a–c is dissolved
in CD3OD, CD3C(O)CD3, or DMSO-d6, the solutions display the 31P

832
V. A. Kozlov et al.
NMR signals corresponding to two isomers with one of the signals sub-
stantially dominating (84–96%) ca. 10 min after solution and becoming
the minor over time. Therefore, in these solvents, the E,Z-isomers of the
thiazolidin-4-ones 2a–c undergo isomerization at the C2 carbon atom
of the heterocycle.10
Taking into account that regioselectivity of the above condensation,
the stability of the products, and their behavior in solution are asso-
. . .
ciated with the formation of intramolecular P O H-bond, it was of
undoubted interest to determine the stereochemical result of conden-
sation with DMAD for phosphorus substituted acetic acid thioamides
bearing thiophosphoryl, dithiophosphoryl, or phosphonium group, i.e.,
groups that are less inclined to form H-bonds or principally do not form
hydrogen bonding.
RESULTS AND DISCUSSION
The reaction of both thio- and dithiophosphoryl thioacetamides 4a,b
with DMAD in CHCl3 (RT, 6 h) was found to proceed similarly to the
condensation of thioacetamides 2 bearing the phosphoryl moiety and
to give E, Z-isomers of thiophosphorylated thiazolidin-4-ones 5a,b in
high yields, as illustrated in Scheme 2.
SCHEME 2
In the case of thioacetamide 4c with a phosphonium group, the con-
densation also proceeded regioselectively and, as expected, yielded the
final NH-heterocycle 5c as Z, Z-isomer (Scheme 3).
The structures of the compounds 5a–c isolated after the work-up
procedure as crystalline solids (see the Experimental section) were un-
ambiguously confirmed by single crystal X-ray diffraction. According to
the X-ray data (random sampling of at least four crystals), thiazolidin-
4-ones 5a,b were formed with E, Z-configuration at the double bonds,

2-P-Substituted Methylidene-thiazolidine-4-ones
833
SCHEME 3
i.e., trans-orientation of the phosphorus-containing substituent and
the ring sulfur atom and cis-orientation of the carbomethoxy group
relative to the latter one (Figures 1 and 2, respectively). In con-
trast, heterocycle 5c displays Z, Z-configuration at these double bonds
(Figure 3). The principal geometric parameters in all molecules un-
der investigation (see Table I) are close to typical values of nonphos-
phorylated thizolidine-4-one derivatives6,7,11–13 and those bearing the
phosphoryl group.10 In particular, the 5-methoxycarbonyl group in
5a–c is also characterized by Z-orientation stabilized by intramolec-
. . .
. . .
ular (O)C O S contact with S O distance varying in the range
of 2.769(2)–2.823(2) Å. These contacts are characterized by a pro-
nounced degree of directionality with O(5)S(1)C(2) angle varying in the
range 163.5(1)–164.8(1)◦. Therefore, this contact can be interpreted as
FIGURE 1 View of E, Z-5a in the crystal; thermal ellipsoids are drawn at 50%
probabilty level.

834
V. A. Kozlov et al.
. . .
FIGURE 2 View of the N H O bonded dimer of E, Z-5b; thermal ellipsoids
are drawn at 50% probability level.
a charge transfer from the oxygen-lone pair to the S-C antibonding
orbital.
In the case of 5a, the E, Z-isomer is stabilized by an intramolecular
. . .
. . .
N H S hydrogen bond with N S distance of 3.165(2) Å. Further-
. . .
more, in addition to the intramolecular N H S bond in the crys-
tal, molecules E, Z-5a are assembled into centrosymmetric dimers via
. . .
. . .
rather strong C(8)-H(8) O(5) interaction. The H(8) O(5) distance
is equal to 2.09 Å, which can affect the strength of intermolecular
interaction.
As one can expect, there is no similar specific interaction that can
be the reason of E, Z-isomer stabilization in the case of 5b, where the
phosphorus atom and the double bond are separated with the addi-
tional sulfur atom. In this case the stabilization of the E, Z-isomer is
. . .
achieved via formation of N(3)-H(3N) O(4A) intermolecular H-bond
. . .
with N(3) O(4A) distance of 2.879(2) Å.

2-P-Substituted Methylidene-thiazolidine-4-ones
835
FIGURE 3 View of Z, Z-5c in the crystal; thermal ellipsoids are drawn at 50%
probability level.
In the crystal of Z, Z-5c, the isomer is stabilized by interionic H-
bonds formed by the ring NH-proton and the hydrogen atom H(8) of
the C(2)–C(8) double bond with the chlorine anion. The correspond-
. . .
. . .
ing N(3) Cl(1) and C(8) Cl(1) distances are equal to 3.101(2) and
3.501(2) Å, respectively.
Considering that stabilization of a particular isomer can be the con-
sequence of crystal packing effects, we performed DFT calculations
of E, Z and Z, Z isomers of compounds 5a and 5b. Calculations for
both compounds (PBE/TZ2P) revealed that E, Z-isomers observed in
the solid state correspond to energy minima. At the same time, the
differences in energy between E, Z and Z, Z forms for 5a and 5b are
significantly different. For thiazolidinone 5b, in which no specific in-
tramolecular interactions occur, the E, Z-isomer is more stable by 1.2
kcal/mol, while for 5a the difference in energy is 6.9 kcal/mol. The
reasons of such a pronounced stabilization of E, Z-5a are believed to be
the same as that occurs for its phosphorylated analogs E, Z-2. Although
. . .
P S H N intramolecular H-bond must be significantly weaker than
. . .
the corresponding P O H N bond in E, Z-2 (see ref. [14]), we cannot
. . .
exclude that the corresponding P S S C intramolecular interaction
. . .
would be also weakened or even absent. Despite a shortened S(1) S(2)

836
V. A. Kozlov et al.
TABLE I Selected Bond Lengths (Å) and
Angles (◦) in E,Z Isomers of 5a-c and in Z,Z-2a
E, Z-5a
E, Z-5b
E, Z-5c
Z,Z-2a
S(1)-C(2)
S(1)-C(5)
C(2)-N(3)
N(3)-C(4)
C(4)-C(5)
C(2)-C(8)
C(5)-C(6)
C(8)-P(1)
P(1)-X(1)a
C(7)-O(5)
O(4)-C(4)
1.779(2)
1.740(2)
1.387(2)
1.368(2)
1.508(2)
1.336(2)
1.344(2)
1.794(2)
1.9678(6)
1.216(2)
1.206(2)
2.871(2)
n/a
1.766(3)
1.741(3)
1.385(4)
1.357(4)
1.495(4)
1.335(4)
1.339(4)
1.753(3)
n/a
1.217(4)
1.221(3)
2.769(2)
n/a
1.762(4)
1.763(4)
1.388(5)
1.364(6)
1.505(6)
1.329(6)
1.327(6)
1.771(4)
n/a
1.232(6)
1.215(5)
2.823
n/a
n/a
1.768(1)
1.745(1)
1.385(2)
1.365(2)
1.498(2)
1.344(2)
1.340(2)
1.750(2)
1.477(1)
1.214(2)
1.219(2)
2.803(1)
2.989(2)
n/a
. . .
O(5) S(1)
. . .
O(1) S(1)
. . .
N(3)
S
3.165(2)
n/a
aX is sulfur in E,Z-5a and oxygen in Z, Z-2a.
distance (3.242 Å) in the Z, Z-5a isomer, the DFT calculations exhibit
the torsion angle S(2)P(1)C(8)C(2) of 10.4◦. In order to estimate the
. . .
. . .
role of H-bonding and O S and S S intramolecular contacts in the
stabilization of the particular isomer, we have preformed the analysis
of electron density distribution function (ρ(r)) within the PBE1PBE/6-
311G* energy calculation for E, Z-5a and Z, Z-5a isomers according to
Bader’s “atoms in molecules” theory.15 According to topological analysis
of ρ(r), all mentioned intramolecular contacts in E, Z and Z, Z isomers
of 5a correspond to bonding interatomic interactions of an intermedi-
ate type with ρ(r) values in critical point (3,-1) varying in the range of
0.09–0.13 eÅ−3. The energies of the contacts estimated using the cor-
relation scheme of Espinosa et al.16 are slightly different and vary in
. . .
. . .
S
the range of 2.5–5.5 kcal/mol. It should be noted that H S and O
interactions in E, Z-5a are characterized by high energy values of 5.5
. . . . . .
and 4.2 kcal/mol, while the corresponding values for S S and O
S
contacts, which may be realized in Z, Z-5a, are 2.5 and 3.9 kcal/mol.
Thus, we can conclude that the prevalence of the E, Z-5a isomer in the
crystal is the consequence of a higher energy of the H-bonding in com-
. . .
parison with S S intermolecular contact. At the same time, estimated
. . .
energies clearly show that disruption of P S H N interaction will in
turn lead to almost equal energies of the E,Z and Z,Z isomers.
To investigate the behavior of compounds 5a–c in solution, their 31
P
and 1H NMR spectra were recorded from the moment of dissolving the

2-P-Substituted Methylidene-thiazolidine-4-ones
837
compound in CDCl3 and DMSO-d6/CCl4(1:1) mixture until the process
reached equilibrium. In contrast to the phosphorylated analogs E, Z-
2a–c, for which in nonpolar solvents the equilibrium is fully shifted
to the E, Z-isomer while retaining the strong intramolecular H-bond,10
mono- and dithiosubstituted derivatives 5a,b form a mixture of E, Z
and Z, Z isomers immediately after dissolving in CDCl3 (∼ 2 min). At
that moment, we observed two singlet signals in the 31P NMR spectra
with one of them substantially dominating as well as two sets of cor-
1
responding signals in the H and 13C NMR spectra. In both cases, the
signal at low field dominating in the 31P NMR spectrum immediately
after dissolving the compound was assigned to the corresponding E, Z-
isomer. The ratio E, Z:Z, Z 2 min after dissolving was 92:8 (5a) and
88:12 (5b) and reached equilibrium at 70:30 and 60:40 for 5a and 5b,
respectively (Table II). The time required to reach the equilibrium in
CDCl3 was approximately 48 h.
As mentioned above, the E, Z-isomers of phosphorylated 2a–c
are stabilized in solution by the intramolecular H-bond. Therefore,
the difference in behavior in solution for phosphorylated 2a–c and
thiphophorylated 5a,b thiazolidinones is obviously connected with the
. . .
. . .
difference in strength of the PO H and PS H intramolecular H-
bonds (the latter is usually weaker14) in the case of 5a and with the
absence of such a H-bond in the thiazolidinone 5b with dithiophospho-
ryl moiety.
In the DMSO-d6/CCl4 mixture, the ratio E, Z:Z, Z was 70:30 (5a)
and 60:40 (5b) in 2 min after dissolving the compound and the equi-
librium was fully shifted to the Z, Z-isomer within 6 h (Table II). It
1
should be noted that in the H NMR spectra both in the CDCl3 and
the DMSO-d6/CCl4mixture, the position of the C8H doublet signal is
shifted downfield for E, Z-5a,b as compared to the signal for the Z, Z-
isomer. As for C6H, the signals for both isomers 5a,b appear very close
in CDCl3 solution, while in DMSO-d6/CCl4 solution the chemical shift
to the lower field corresponds to C6H in E, Z-5a,b.
At the same time, phosphonium-substituted thiazolidinone 5c
showed a singlet in the 31P NMR spectrum and one set of signals in the
1H and 13C NMR spectra in both CDCl3 and DMSO solutions. During
the time of observation (2 min to 30 days) no changes were noted in the
NMR spectra; therefore one may conclude that 5c exists both in the
solid state and in solution as the Z,Z-isomer.
Most probably in the case of 5a,b, the E,Z → Z,Z transformation
proceeds via imine–enamine mechanism similar to that of the phos-
phorylated analogs 2. This is confirmed by the fact that the intensities
1
of the H NMR signals for C8H and NH of the E, Z- and Z, Z-isomers

838

2-P-Substituted Methylidene-thiazolidine-4-ones
839
correspond to the isomer ratio estimated from the 31P NMR spectrum,
but do not correspond to the intensity of the signals of the other protons
for the same isomer due to the fast prototropic exchange on the NMR
time scale between the two isomers of the heterocyclic amine 5 via the
corresponding imine.
It is interesting to note that we failed to isolate the individual Z, Z-
2 isomers by recrystallization from alcohol, in which the equilibrium
is shifted to the corresponding Z, Z-isomer due to the rupture of the
. . .
intramolecular P O H N bond and formation of intermolecular H-
bonds with the solvent. However, the addition of one molar equiva-
lent of NiCl2 to the MeOH solution of compound E, Z-2a bearing a
diethoxyphosphoryl group resulted in crystallization of the less favor-
able Z, Z-2a isomer (the difference in energy between the two isomers
for compound 2a is 8.3 kcal/mol[10]) (Scheme 4). In the 31P NMR spec-
trum of the reaction mixture (before crystallization), a broad singlet at
25.3 ppm was observed. The downfield shift of the signal in compari-
son to those of E, Z-2a and Z, Z-2a observed in the same solvent (20.2
and 19.2 ppm, respectively) confirmed the formation of an intermediate
nickel complex, which is stable only in solution.
SCHEME 4
The structure of Z, Z-2a was unambiguously confirmed by single
crystal X-ray analysis (Figure 4) and coincided well with the calculated
one (see ref. [10]). In this case the presence of nickel ions either favored
a fast rupture of the intramolecular H-bond due to complexation with
the phosphoryl moiety or further formation of a complex with partici-
pation of P O and ester C O groups as coordination sites. Both factors
should stabilize the Z, Z-2a isomer crystallized from solution and give
the possibility of the realization of the thermodynamically unfavorable
process.

840
V. A. Kozlov et al.
FIGURE 4 View of Z, Z-2a in the crystal; thermal ellipsoids are drawn at 50%
probability level.
At the same time, we cannot exclude that crystallization of the Z, Z-
2a isomer may be solely due to kinetics of crystal growth in the pres-
ence of cations. Indeed, it is known that some substances can serve as
nucleation inhibitors and thus prevent crystal growth of a particular
polymorph or isomer at the stage of nucleation and hence assist in the
formation of the less thermodynamically stable crystal.17 In order to
investigate the role of nickel ions, we are going to perform additional
experiments with other compounds 2 and other metal ions, as well as
to check the formation of any coordination bonds between nickel and
the ligand by spectroscopic techniques.
To summarize the results, we can conclude that although stabiliza-
tion of a particular isomer of 2-(phosphorus substituted)methylidene-
thiazolidine-4-one is dictated by the particular intramolecular interac-
tion in a solid state, the specific conditions, i.e., specific salvation, can
facilitate the formation of the thermodynamically less favorable isomer.
EXPERIMENTAL
The 1H, 13C, and 31P NMR spectra were recorded with a Bruker AMX-
400 spectrometer using the signals of the solvent as internal standard
(1H, 13C) and 85% H3PO4 (31P) as external standard. The 13C NMR
spectra were recorded using the JMODECHO mode, the signals for the

2-P-Substituted Methylidene-thiazolidine-4-ones
841
C atom bearing odd and even numbers of protons have the opposite po-
larities. IR spectra were recorded in KBr pellets with a Magna-IR750
Fourier spectrometer (Nicolet), resolution 2 cm−1, 128 scans. The as-
signment of the absorption bands in the IR spectra was made according
to the literature.18,19 Melting points are uncorrected.
The thioacetamides 4b,c were obtained by the standard procedure20
described earlier.
2-(Diphenylthiophosphoryl)ethanethioamide (4a)
Compound 4a was obtained following the general procedure for the
transformation of a cyano group to the corresponding thioamide re-
ported by us previously.20 A mixture of diphenylthiophosphorylacetoni-
trile (1.28 g, 5 mmol) and diisopropyldithiophosphoric acid (1.07 g, 5
mmol) in 2 mL of MeOH was kept at approximately 20◦C for 7 days.
Then Et2O was added to the reaction mixture, and the precipitate was
filtered off and recrystallized from ethyl acetate to yield 4a (0.89 g,
61%) as a light-yellow solid. Mp 203–204◦C. 31P NMR (DMSO-d6): δ =
41.7 ppm. 1H NMR (DMSO-d6): δ = 4.14 (d, 2JPH = 14.2 Hz, 2H, CH2P),
7.46–7.97 (m, 10H, C6H5P), 8.95 (s, 1H, NH2), 9.48 (s, 1H, NH2). IR
(KBr, ν/cm−1): 491, 565, 612 (P=S), 690, 735, 984, 1100, 1433 (N C S
+ CH2), 1628, 3141 (NH2), 3263, 3311. Found: C 57.68; H 4.71; N 4.76.
Calcd. for C14H14NPS2: C 57.71, H 4.84; N 4.81%.
(E)-2-[(Diphenylthiophosphoryl)methylene]-(Z)-5-
(methoxycarbonyl-methylene)-thiazolidin-4-one (5a)
Dimethylacetylendicarboxilate (0.38 g, 2.7 mmol) was added to a
suspension of 2-(diphenylthiphosphoryl)ethanethioamide4a (0.8 g, 2.7
mmol) in CHCl3 (10 mL), and the mixture was stirred overnight at room
temperature. Over this time, a clear orange solution was formed. It was
refluxed for 8 h. The solvent was evaporated in vacuo, and the residue
was recrystallized from EtOAc to afford the thiazolidin-4-one E, Z-5a
as light-yellow crystalline solid. Yield 0.3 g (80%); mp 153–154◦C. IR
(KBr, ν/cm−1): 694 (P S), 1203, 1217 (νas CNC), 1310 (νs CNC), 1604
(C C), 1684 (C7 O), 1724, 1734 (C4 O), 3071 (br, NH). Found: C 56.99;
H 3.91; N 3.54. Calcd. for C19H16NO3PS2: C 56.85, H 4.02; N 3.49%.13C
NMR (CDCl3,100.61 MHz): E, Z-5a: δ = 52.4 (s, OCH3), 89.3 (d, 1JPC
=
89.1 Hz, C8), 114.4 (s, C6), 128.8 (d, 3JPC = 13.0 Hz, C-mof C6H5P), 130.8
2
(d, JPC = 11.0 Hz, C-o of C6H5P), 131.75 (s, C-p of C6H5P), 131.76 (s,
1
C-p of C6H5P), 133.5 (d, JPC = 89.0 Hz, C-i of C6H5P), 140.3 (s, C5),
150.2 (s, C2), 164.3 (s, C7), 166.6 (s, C4); Z, Z-5a: δ = 53.7 (s, OCH3),

842
V. A. Kozlov et al.
1
3
84.2 (d, JPC = 91.5 Hz, C8), 114.4 (s, C6), 128.5 (d, JPC = 12.6 Hz,
C-mof C6H5P), 130.7 (d, 3JPC = 10.2 Hz, C-o of C6H5P), 131.5 (s, C-p of
C6H5P), 134.1 (d, 1JPC = 85.8 Hz, C-i of C6H5P), 140.3 (s, C5), 152.4 (s,
C2), 166.6 (s, C7), 172.6 (s, C4).
(E)-2-[(Diethoxythiophosphoryl)thio]methylene-(Z)-5-
(methoxycarbonyl-methylene)thiazolidin-4-one (5b)
Compound 5b was prepared using the procedure described for 5a, ex-
cept that 0.292 g (2.7 mmol) of S-(2-amino-2-thioxoethyl) O,O-diethyl
phosphodithioate 4b was used instead of thioamide 4a, and the reaction
was performed at room temperature over 6 h. Thiazolidinone E, Z-5b
was obtained in 57% yield after purification by column chromatography
(acetone-hexane 2:3); mp 120–121◦C. IR (KBr, ν/cm−1): 656 (P S), 1606
(C C), 1698 (C7 O and C4 O), 3138 (br, NH). 13C NMR (CDCl3,100.61
3
MHz): δ = 15.8 (d, JPC = 8.4 Hz, CH3CH2O), 52.4 (s, OCH3), 64.6 (d,
2
2JPC = 5.0 Hz, OCH2), 91.5 (d, JPC = 7.6 Hz, C8), 113.9 (s, C6), 142.8
(s, C5), 143.2 (d, 3JPC = 10.8 Hz, C2), 166.6 (s, C7), 166.7 (s, C4). Found:
C 35.84; H 4.41; N 3.75. Calcd. for C11H16NO5PS3: C 35.76, H 4.36; N
3.79%.
(Z)-2-[(Triphenylphosphonio)methylene]-(Z)-5-
(methoxycarbonylmethylene)-thiazolidin-4-one Chloride (5c)
A suspension of 2.7 g (7.26 mmol) of triphenylphosphonium salt 4c
and 1.03 g (7.26 mmol) of DMAD in 15 mL of MeOH was stirred over
12 h at ambient temperature. Diethyl ether (15 mL) was added to the
reaction mixture, and the obtained precipitate was filtered and air-
dried to give 3.18 g (81%) of 5c·MeOH, mp 179–180◦C. Found: C 60.78;
H 4.67; N 2.74. Calcd. for C26H25ClNO4PS: C 60.76, H 4.90; N 2.72%.
After drying in vacuo, Z, Z-5c was isolated in 75% yield; mp 252–254◦C.
IR (KBr, ν/cm−1): 1106, 1177, 1194 (νas CNC), 1329 (νs CNC), 1438,
1568, 1585 (C C), 1692 (C7 O), 1716 (C4 O), 2987 (br, NH). 13C NMR
(CDCl3,100.61 MHz): δ = 52.4 (s, OCH3), 75.8 (d, 1JPC = 110.8 Hz, C8),
1
3
116.5 (s, C6), 119.5 (d, JPC = 92.3 Hz, C-i of C6H5P), 130.4 (d, JPC
=
13.2 Hz, C-m of C6H5P), 133.6 (d, 2JPC = 11.0 Hz, C-o of C6H5P), 135.5
(s, C-p of C6H5P), 140.5 (s, C5), 160.2 (d, 2JPC = 9.7 Hz, C2), 163.2 (s, C7),
166.2 (s, C4). Found: C 62.18; H 4.51; N 3.01. Calcd. for C25H21ClNO3PS:
C 62.30, H 4.39; N 2.91%.

2-P-Substituted Methylidene-thiazolidine-4-ones
843
(Z)-2-[(Diethoxyphosphoryl)methylene]-(Z)-5-
(methoxycarbonylmethylene)-thiazolidin-4-one(Z,Z-2a)
NiCl2 hexahydrate (119 mg, 0.5 mmol) was added to a solu-
tion of (E)-2-[(diethoxyphosphoryl)methylene]-(Z)-5-(methoxycarbonyl-
methylene)thiazolidin-4-one E, Z-2a (160 mg, 0.5 mmol) obtained as
described previously10 in MeOH (3 mL). Yellowish crystals, which pre-
cipitated from the yellow-green solution over time (14 days), were fil-
tered and air-dried to give 104 mg (65%) of Z,Z-2a. Mp 95–96 ◦C. Found:
C 41.18; H 4.99; N 4.03. Calcd. for C11H16NO6PS: C 41.12, H 5.02; N
4.36%.
X-Ray Crystallography
X-ray diffraction experiments were carried out with a Bruker SMART
1000 CCD area detector, using graphite monochromic Mo-Kα radiation
(λl = 0.71073 Å, ω-scans) at 110 K. The low temperature of the crystals
was maintained with a Cryostream (Oxford Cryosystems) open-flow
N2 gas cryostat. Reflection intensities were integrated using SAINT
software21 and absorption correction was applied semi-empirically us-
ing SADABS program.22 The structures were solved by direct method
and refined by the full-matrix least-squares method against F2 in
anisotropic approximation for no-hydrogen atoms. NH hydrogen atoms
were located from the Fourier density synthesis and refined in isotropic
approximation. Analysis of Fourier density synthesis has revealed that
half of the methanol molecule in E, Z-5c is disordered over two positions
with equal occupancies (0.25). The hydrogen atom of the OH group for
one-quarter of the methanol molecule was not located. The positions of
all other hydrogen atoms were calculated geometrically. Crystal data
and structure refinement parameters for E, Z-isomers of 5a–c and Z, Z-
2a are presented in Table III. All calculations were performed using the
SHELXTL software.23
Theoretical Calculations
Geometry optimization was carried out using the PBE/TZ2p basis set
implemented in the Priroda program package.24 Electron density func-
tion of E,Z- and Z,Z-isomers of 5a were calculated within PBE1PBE1/6-
311G* single point calculation using Gaussian 98.25 The topological
analysis of the ρ(r) was performed using the MORPHY98 program
package.26 The energy of interactions (Econt) was estimated from the
values of potential energy density, v(r), using the correlation scheme
Econt = 0.5 v(r) in accordance with the literature.16

844
V. A. Kozlov et al.
TABLE III Crystallographic Data for E,Z-5a, E,Z-5b, E,Z-5c, and
Z,Z-2a
E,Z-5a
E,Z-5b
E,Z-5c
Z,Z-2a
CCDCa
669810
669808
669809
669811
Formula
C
19H16NO3PS2 C11H16NO5PS3 C25H21ClNO3PS · C11H16NO6PS
0.5 CH3OH
Formula weight
T (K)
401.42
120
369.40
120
497.93
120
321.28
120
Crystal system
Space group
Z (Zꢀ)
Monoclinic
P21/c
Monoclinic
P21/c
Triclinic
P-1
2(1)
Monoclinic
P21/c
4(1)
4(1)
4(1)
a (Å)
b (Å)
9.7626(6)
7.7805(5)
7.0220(9)
27.940(4)
11.150(2)
11.180(2)
16.279(8)
9.237(4)
c (Å)
α(◦)
β(◦)
γ(◦)
24.3248(15)
90.00
92.167(2)
90.00
8.6975(10)
90.00
105.744(3)
90.00
12.720(3)
90.30(3)
113.60(3)
116.60(3)
9.690(4)
90.00
101.232(6)
90.00
V (Å3)
1846.3(2)
1.444
3.94
1642.4(3)
1.494
5.66
1265.9(4)
1.306
3.26
1429.2(11)
1.493
3.62
dcalc (g·cm−3
)
µ(ñm−1
)
F(000)
832
57
768
60
518
50
672
57
2θ
(◦)
max
Reflections
measured
10389
15934
4665
6729
Independent
reflections
Observed
reflections [I >
2σ(I)]
4794
4017
4765
2560
4348
2969
3510
3043
Number of
parameters
R1
wR2
GOF
299
193
306
245
0.0416
0.0941
1.082
0.0595
0.1368
1.024
0.0630
0.1625
1.049
0.0348
0.0806
0.987
ꢀρmax/ꢀρ
(e
0.405/–0.279
0.667/–0.403 0.691/–0.539
0.362/–0.279
min
Å−3
)
aThe crystallographic data have been deposited with the Cambridge Crystallographic
Data Center. Copies of this information may be obtained free of charge from: The
Director, CCDC, 12 Union Road, Cambridge, CB2 1EZ, UK (Fax: +44-1223-336033;
e-mail: deposit@ccdc.cam.ac.uk or http://www.ccdc.cam.ac.uk).
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