A novel and efficient 4-oxothiazolidine-1,2-dithiole rearrangement induced by Lawesson's reagent

Article abstract of DOI:10.1016/S0040-4039(03)01721-0

Functionalized 1,2-dithioles have been synthesized by a ring opening-closing process of 5-substituted- and 5-unsubstituted-2-alkylidene-4-oxothiazolidines with Lawesson's reagent. The ¹³C NMR data confirmed the meso-ionic structure of these aromatic-type 1,2-dithioles.

Full text of DOI:10.1016/S0040-4039(03)01721-0

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 7087–7090
A novel and efficient 4-oxothiazolidine-1,2-dithiole rearrangement
induced by Lawesson’s reagent
Rade Markovic,a,b,* Marija Baranaca,b and Stanka Joveticc
aFaculty of Chemistry, University of Belgrade, Studentski trg 16, PO Box 158, 11001 Belgrade, Yugoslavia
bCenter for Chemistry ICTM, PO Box 473, 11000 Belgrade, Yugoslavia
cDepartment of Chemistry, Faculty of Sciences, University of Novi Sad, Trg D. Obradovica 3, 21000 Novi Sad, Yugoslavia
Received 22 May 2003; revised 28 June 2003; accepted 14 July 2003
Abstract—Functionalized 1,2-dithioles have been synthesized by a ring opening–closing process of 5-substituted- and 5-unsubsti-
tuted-2-alkylidene-4-oxothiazolidines with Lawesson’s reagent. The 13C NMR data confirmed the meso-ionic structure of these
aromatic-type 1,2-dithioles.
© 2003 Elsevier Ltd. All rights reserved.
´
Over the past twenty years the thionation of different
carbonyl compounds by Lawesson’s reagent [LR: 2,4-
bis(4-methoxyphenyl)-1,2,3,4-dithiadiphosphetane 2,4-
disulfide]1 has been generally recognized as being
superior versus P4S10 and other thionation reagents.
The application of this reagent has been extended in
recent years to the synthesis of sulfur-containing hete-
rocycles, such as benzothiazol-3-thiones,2 tetra-
hydrothiophen-2-imines and benzothiazines.3 New
developments also include direct conversion of alcohols
to thiols4 and cyclization of unsubstituted and 2-mono-
substituted 3-oxoesters or N-substituted 3-oxoamides
affording 3H-1,2-dithiole-3-thiones.5,6 Angya´n and co-
workers7 have reported that in a large number of the
sulfur-containing acyclic and cyclic compounds, con-
taining the fragment -S-XꢀY-CꢀO with a cis-configura-
tion of XꢀY (X=C; Y=C or N), the 1,5-interaction of
nonbonded S and O, may influence physicochemical
properties and chemical reactivity of these compounds.
In this context, the availability of the (Z)-2-alkylidene-
4-oxothiazolidines of type 18 (Scheme 1) and their
configurational stability, attributed to
a
strong
intramolecular oxygenꢁsulfur interaction of the 1,5-
type, encouraged us to study their reactivity9 and utility
Scheme 1.
Keywords: thiazolidines; rearrangements; dithioles.
* Corresponding author.
0040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)01721-0

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R. Marko6ic et al. / Tetrahedron Letters 44 (2003) 7087–7090
Scheme 2.
as precursors for synthetic purposes. Herein, we report
the first, almost quantitative one-pot transformation of
the (Z)-2-alkylidene-4-oxothiazolidines 1a–b to 1,2-
dithioles 2a–b in the presence of an equimolar amount
of Lawesson’s reagent (Scheme 1).
the 2-thioacylmethylene-3-aryl-5-phenyl-2H-1,3,4-thia-
diazolenes 8 from the carbonyl analogues 7 and phos-
phorous pentasulphide.11
The regioselective character of the ring-closing process
5a–c“6a–c can be rationalized in terms of the strongly
directing interaction between the two sulfur atoms.
Evidence for the very close contact of reactive sulfur
atoms in 5a–c is based on the X-ray analysis of a
representative of the series, i.e. ethyl (Z)-(5-ethoxycar-
bonylmethyl-4-oxothiazolidin-2-ylidene)ethanoate 1d.12
Under identical conditions, the (Z)-4-oxothiazolidine
1c, containing
a b-enaminoamide structural unit,
instead of the b-enaminone fragment in 1a–b, afforded
1,2,4-dithiazole derivative 3c in 40% yield. The
analogous reaction of the b-enamino ester 1d with LR
led to the formation of the corresponding 4-mercap-
tothiazole 4d. The reaction of precursors 1a–c with LR
proceeds in a highly regioselective fashion. The mecha-
nism probably involves the formation of thione inter-
mediates 5a–c by an initial thionation of the C(2%)
oxygen and ring oxygen of the thiazolidin-4-one deriva-
tives 1a–c, as outlined in Scheme 2 for substrate 1a.10
Thioxothiazolidine ring opening, occurring with a con-
comitant 1,2-dithiole closing process, followed by the
H-transfer are subsequent steps.
,
The O···S(1) nonbonded distance in 1d (2.873(2) A) is
,
less than the sum of the van der Waal’s radii (3.22 A).
The C(2) side chain is essentially coplanar with the ring
which brings the carbonyl oxygen into close proximity
to the sulfur atom. The directed p-delocalization of the
typical push–pull unit in intermediates 5 (Scheme 2),
consisting of an electron donor (NH), the intervening
double bond and an electron acceptor (CꢀS), addition-
ally enhances the 5“6 process.13
Characteristic spectroscopic data for the dithioles 2a–b
and 1,2,4-dithiazole 3c are compiled in Table 1. In the
1H NMR spectra the proton at C(4) of dithiole deriva-
tives 2a and 2b absorbs at very low field, i.e. at 8.65 and
8.37 ppm, respectively, which is indicative of the aro-
The intermediacy of thione 5a, though it was not
detected under the experimental conditions employed,
appears very likely. Similar thionation reactions have
been reported previously,3–5 including the formation of
1
Table 1. Selected 13C and H NMR chemical shifts of 1,2-dithioles 2a–b and 1,2,4-dithiazole 3c
Entry
Product
C(2%)
C(3)
C(4)
C(5)
C(4)-H
C(3%)-H
1
2
2aa
2bb
202.76
198.58
187.35
187.31
126.78
125.83
177.89
178.26
8.65
8.37
2.89
2.85
–
–
C(5)c
C(3)c
C(3%)c
CꢀSc
C(3%)-Hc
C(5%)-Hc
NH
3
3ca
182.67
180.45
114.42
184.86
7.46
2.65
11.23
a DMSO-d6.
b CDCl3.
c C(5) atom in 3c should be compared to C(2%) in 2a and 2b, c C(3) atom in 3c should be compared to C(3) in 2a and 2b, etc.

R. Marko6ic et al. / Tetrahedron Letters 44 (2003) 7087–7090
7089
Scheme 3.
Table 2. Thionation of 2-alkylidene-4-oxothiazolidines 1a–d
Entry
Thiazolidine
R1
R2
Reaction time (h)
Product
Mp (°C)
Yield (%)a,b
1
2
3
4
1a
1b
1c
1d
CH2CO2Et
H
H
Ph
Ph
NHPh
OEt
1
1
1.5
2.5
2a
64
97
92
99
2b16
3c
217c
Oil
40
CH2CO2Et
4d
50d
a Yields refer to isolated yields by column chromatography.
b All of the compounds gave satisfactory 1H and 13C NMR and MS spectra.
c Decomposition point.
d In addition to 4d a large amount of polymeric material was isolated.
matic nature of the dithiole ring. This is confirmed by
the 13C shifts for C(3), C(4) and C(5) in the highly
delocalized derivatives 2a–b as indicated by the dipolar
resonance structures A and B. These values matched
those obtained in similar 1,2-dithiole-3-thiones.5,14 The
assignment of values above 195 ppm show undoubtedly
the presence of a thioketone carbon C(2%).
trithia-5-azapentalene structure 9 as a more adequate
representation, implying the dominant contribution of
1,2,4-dithiazole 3c to the ground-state of the system.
The results of thionation of precursors 1a–d using LR
are summarized in Table 2.
The typical procedure for the preparation of ethyl
3 - (5 - phenyl - [1,2]dithiol - 3 - ylidenethiocarbamoyl)pro-
panoate 2a is as follows: a colorless solution of (Z)-2-
alkylidene-4-oxothiazolidine 1a (0.164 mmol) and LR
(0.164 mmol) in dry toluene (3 mL) was heated in an oil
bath at 90–95°C. After a few minutes, the color of the
reaction mixture turned dark reddish brown. The mix-
ture was stirred at this temperature for an additional
hour when TLC indicated the complete consumption of
substrate 1a. After cooling to room temperature, the
solvent was evaporated in vacuo. The residue was
chromatographed (toluene/ethyl acetate, 10:0“8:2, v/v)
affording the dark orange crystalline 1,2-dithiole 2a in
92% yield.
Careful analysis of MS, 1H and 13C NMR spectro-
scopic data for 3c, isolated by the thionation of b-
enamino amide 1c, under the same experimental
conditions as for 1a–b, revealed spectral features which
correlated with the 1,2,4-dithiazole structure. The com-
pound had an MS spectrum consistent with an elemen-
tal composition of C11H10N2S3 for either the expected
1,2-dithiole 2c, or the actual 1,2,4-dithiazole derivative
3c. However, the upfield shifts of the C(3%) and C(5%)
1
protons observed in the H NMR spectrum for 1,2,4-
dithiazole 3c (Table 1, entry 3) in comparison with the
C(4) and C(3%) protons of 1,2-dithioles 2a and 2b
(entries 1 and 2), suggest greater magnetic shielding by
the surrounding moiety. The same effect was noted in
the 13C NMR spectrum of 3c, which shows the upfield
shifts for the C(5) and C(3) carbon nuclei versus the
chemical shifts of the C(2%) and C(3) carbon nuclei,
respectively, of either 2a or 2b.
In conclusion, we have demonstrated that the one-pot,
high yielding reaction of cyclic b-enamino ketones with
LR can be applied as a rapid and new route to highly
functionalized 1,2-dithiole derivatives in high yields. A
pathway for the formation of these compounds and
1,2,4-dithiazole, obtained from the b-enamino amide
precursor, is suggested. It is noteworthy that the thion-
ation of the thiazolidine substrate having the b-enam-
ino ester fragment, resulted in an aromatization
reaction.
Additionally, the chemical shift of the NH proton at
11.23 ppm, which is not in the expected range for
structure 2c, indicates the presence of the thioamide
group.15 1,2-Dithioles 2a–b exhibit two identical max-
ima in UV–vis spectra at 333 and 446 nm which are
responsible for the orange color. The different ring
system in 1,2,4-dithiazole 3c was confirmed by the
presence of two strong absorptions at umax 345 and 435
nm. Obviously, in situ generated dithiole 2c, as the key
intermediate en route to the 1,2,4-dithiazole 3c (Scheme
3) readily participates in another opening–closing pro-
cess, dictated by (i) the favorable positions of a pair of
sulfur atoms and (ii) the electron donating ability of the
nitrogen atom. It is tempting to propose the 1,6,6al4-
Acknowledgements
This work was partially assisted by the Ministry of
Science, Technology and Development of the Republic
of Serbia, grant no. 1709 (to R.M.).

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R. Marko6ic et al. / Tetrahedron Letters 44 (2003) 7087–7090
opening–closing process occurring simultaneously with
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