Transformations of 2-alkylidene-4-oxothiazolidine vinyl bromides initiated by bromophilic attack of neutral and anionic nucleophiles

Article abstract of DOI:10.1016/j.tet.2010.06.057

Vinyl bromides derived from 2-alkylidene-4-oxothiazolidines represent a class of vinyl halides, which readily undergo a bromophilic attack by a range of nucleophiles. With Ph₃P, AcS^-, CN^-, I ^-, F^-, Ac

Full text of DOI:10.1016/j.tet.2010.06.057

Tetrahedron 66 (2010) 6873e6884
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Transformations of 2-alkylidene-4-oxothiazolidine vinyl bromides initiated
by bromophilic attack of neutral and anionic nucleophiles
,
b,
b
,b,
ꢀ a
ꢀ a
ꢀ b
*
*
Marija Baranac-Stojanovic
, Jovana Tatar , Milovan Stojanovic , Rade Markovic
a Faculty of Chemistry, University of Belgrade, Studentski trg 16, PO Box 158, 11000 Belgrade, Serbia
b Center for Chemistry ICTM, PO Box 473, 11000 Belgrade, Serbia
a r t i c l e i n f o
a b s t r a c t
Article history:
Vinyl bromides derived from 2-alkylidene-4-oxothiazolidines represent a class of vinyl halides, which
readily undergo a bromophilic attack by a range of nucleophiles. With Ph3P, AcSꢀ, CNꢀ, Iꢀ, Fꢀ, Ac2CHꢀ
and Nꢀ3 the attack ends up with reductive debromination, whereas the bromine substitution takes
place with KSCN. When acetate anion and organic bases, such as pyridine, Et3N or morpholine, are
employed as nucleophiles the initial bromophilic attack is followed by bromine migration to the C(5)
position of the ring, allowing the C(5) functionalization of this heterocyclic system.
Ó 2010 Elsevier Ltd. All rights reserved.
Received 8 December 2009
Received in revised form 31 May 2010
Accepted 21 June 2010
Available online 25 June 2010
Keywords:
4-Oxothiazolidine
Vinyl bromide
Bromophilic reaction
Carbanion
Rearrangement
1. Introduction
In contrast to the great amount of experimental and theoretical
work within this central class of carbophilic reactions, the nucleo-
Nucleophilic substitutions occurring by an attack at the carbon
atom of an alkyl halide are among the most widely studied organic
reactions (Scheme 1, route a).1
philic substitutions taking place at the halogen atom X (route b), with
the expulsion of a carbanion 3 as a leaving group, are to date relatively
undeveloped. Referredtoin theliteratureas halophilic reactions,2 they
usually occur with substrates giving rise to a carbanionic leaving
group stabilized by the presence of electron withdrawing groups
(EWGs), for example, in the case of
sulfones,4 -haloketones,5 -halonitriles,6 halogenated nitroalkanes,7
diethyl bromo-8a and diethyl dibromomalonate,8b or selected ortho-
substituted
-dibromoacetophenones.9 Perhaloalkanes are rather
a a-halo-b-keto-
-halosulfones,3
Carbophilic reactions
(SNC) "normal substitution on C"
a
a
R
Nu:
a,a
Y1
Nu
+ X:
(a)
inert towards nucleophilic displacement reactions, but they can un-
dergo a halophilic attack by various nucleophiles, including phen-
oxides and alkoxides,10 thiophenoxides,10c,10d sec-amines or their
salts,10d,11 phosphorous ylides,10d,12 triphenylphosphine,13 enamines
and enolates.10d Halophilic reactions have also been observed in
the case of 3-methyl-5-trichloro-methyl-1,2,4-oxadiazole,14 2-hal-
omethyl-5-nitrofurans,15 pentafluorohalo-benzenes,16 substituted
pentabromo-benzenes,17 geminal5 and vicinal dihalides.5,18 Pro-
tonation of the carbanion 3 to yield 4, i.e., the product of reductive
dehalogenation, is often observed in these reactions.2e4,14,15,17
Synthetically viable, but rather scarce, halophilic reactions of vinyl
halides (VyX) are limited to a couple of examples. In particular, re-
ductive dehalogenation of 1,1-dibromo alkenes leads to the synthesis
of vinyl bromides.19 An efficienthalophilic ring-opening E2elimination
Y2
2
R
Y1
X
Halophilic reactions
(SNX) "rare substitution on X"
Y2
1
R
R
H+
Nu:
Nu
X
Y1
Y1
+
(b)
Y2
3
Y2
4
Scheme 1.
of b-iodo-a,b-unsaturated g-sultones 5 (Scheme 2) to allensulfonate 6
* Corresponding authors. Tel.: þ381 11 3336741; fax: þ381 11 636061; e-mail
in DMSO or acetone, mediated by soft nucleophiles, such as iodide or
ꢀ
addresses: mbaranac@chem.bg.ac.rs (M. Baranac-Stojanovic), markovic@chem.bg.
thioacetate, has been de-scribed by Braverman et al.20
ꢀ
ac.rs (R. Markovic).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.06.057

ꢀ
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M. Baranac-Stojanovic et al. / Tetrahedron 66 (2010) 6873e6884
2. Results and discussion
O
O
O
R1
R
SO3 Na
S
NaI, DMSO
•
On the basis of the established susceptibility of 4-oxothiazo-
R1
lidines (Z)-11 towards electrophilic attack on the enamine24a
(Scheme 5), a number of the starting vinyl bromides 10 were
prepared in moderate to high yields (Table 1) upon bromination
under various experimental conditions. However, the
N-substituted analogues of 5-unsubstituted 4-oxothiazolidines 11
are, due to the steric hindrance, regiospecifically brominated
with molecular bromine or NBS at the C(5) position, yielding
bromides 13.25
I
R
6
5
Scheme 2.
Another example of this chemistry involves a synthesis of halo
(acyl)rhenate complexes 9 (Scheme 3) by a two-step sequence, ini-
tiated by halophilic attack of [Re(CO)5]ꢀNaþ on the halogen of
polyfluorinated alkenyl halides 7.21 The nucleophilic addition of the
resulting alkenyl carbanion intermediate 8 to CO gives rise to salts 9.
R
F
F
R
F
F
X
R
F
F
THF
r.t.
Re(CO)5X
Re(CO)5 Na
+
+
Na
Re(CO)4X
Na
O
7
8
9
(70-90%)
R = (CF3)3C; X = Cl or Br
R = F; X = Br
Scheme 3.
Extensive and systematic reactivity study on nucleophilic vinylic
substitution (SNV), has also been conducted by Rappoport et al.22
on a range of selected substrates Y1Y2C¼CRX, employing oxygen,
sulfur or carbon nucleophiles.
Recently, we have shown that pyridine and a variety of
pyridine derivatives possess chemical potential to rearrange
5-unsubstituted 4-oxothiazolidine vinyl bromides 10 (Scheme
4), via an initial bromophilic step, into a class of new pyr-
idinium salts.23 In this paper, we provide for the first time
a full account on the overall strategy, outlined in Scheme 4, in
which the bromophilic step A has been combined with bromine
transfer (step B), followed by elimination/substitution (step C),
Likewise, upon changing the R substituent in N-methyl pre-
cursors 11 from H to Me, or CH2CO2Et, the corresponding products
15a or 15b, containing the two exocyclic double bonds, were readily
formed in good yields, by dehydrobromination of an initially
formed C(5) alkyl bromide 14.
Regarding the configuration of the exocyclic C]C bond, all vinyl
bromides 10a and 10ceo were isolated as a mixture of the E- and
Z-isomers, and 10b was formed as a single Z-isomer. These vinyl bro-
mides and parent compounds 11 (R¼H), are susceptible to Z/E isom-
erization24 due to the lowering of the rotational barrier. This
isomerization is a result of the electronic interactions between the
donor and acceptor groups via the C]C bond, imparting a partial single
R
R
R
S
S
Br
S
Nu:
C
B
EWG
EWG
EWG
Products of
O
N
H
O
N
H
A
O
N
H
C(5) functionalization
Nu-Br
Br
H
10
H+
R
R
S
S
A : Bromophilic reaction
B : Bromine transfer
C
EWG
EWG
O
O
N
H
N
H
: Substitution or elimination
Nu
H
11
12
Scheme 4.
to allow the functionalization of 5-unsubstituted and
substituted 4-oxothiazolidines. We also report reactions of
bond character, and is controlledby the appropriate choice of solvent. In
accordance to the earlier generalization for a large number of thiazo-
lidines 11 (R¼H), the E-isomers (R¼H) are the dominant species for the
equilibrated Z/E mixtures in nonpolar CDCl3 as the NH/O]C non-
covalent interaction leads to favourable six-membered H-bonding.24b,c
selected substrate 10 with
a series of neutral and anionic
nucleophiles, leading to debromination product 11 and bromine
substitution product 12.
R
R
R
R
S
O
O
O
S
S
S
H
R1
N
H
O
R1
O
R1
O
O
N
H
N
H
N
H
R1
Br
H
H
O
(E)-10
dominant in DMSO-d
(E)-11
dominant in CDCl3
(Z)-11
dominant in DMSO-d
A
6
6
R = H, Me, CH2CO2Et
R' = OEt, Ph, NHPh, NH(CH2)Ph

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M. Baranac-Stojanovic et al. / Tetrahedron 66 (2010) 6873e6884
6875
R
R
E
R
S
S
S
Bromination
R1 = H
EWG
EWG
EWG
O
O
O
N
N
N
R1
(Z)-11a
R1
R1
10a-o
H
H
Br
Bromination
R1 = Me
Bromination
R1 = Me; R = H
R = Me, CH2CO2Et
R2
Br
Br
R
S
S
S
- HBr
EWG
EWG
EWG
O
N
R1
O
O
N
R1
14
N
R1
H
H
H
15a (R2 = H)
13
15b (R2 = CO2Et)
a
11
(Z,E)- if EWG = CN
Scheme 5.
1D nuclear Overhauser effect measurements and an X-ray structural
analysis studies of the selected thiazolidine 11,24 allowed us to carry
out proper structure elucidation of the Z- and E-isomers 10. It suffices
to point out that the reactions of vinyl bromides 10 with various nu-
cleophiles, discussed below, are not influenced by the configuration of
the exocyclic C]C bond.
Table 1
Synthesis of vinyl bromides Z/E-10 from 2-alkylidene-4-oxothiazolidines 11
Substrate
R
EWG
Product (Z/E ratio)
Yielda (%)
R1¼H
11a
11b
11c
11d
11e
11f
11g
11h
11i
11j
11k
11l
11m
11n
11o
CH2CO2Et
CH2CO2Et
CH2CO2Et
CH2CO2Et
CONHPh
CONH(CH2)2Ph
CO2Et
COPh
CN
CONHPh
CONH(CH2)2Ph
CO2Et
COPh
CN
CONHPh
CONH(CH2)2Ph
CO2Et
COPh
CN
10a (39:61)
10b (100:0)
10c (54:46)
10d (14:86)
10e (65:35)b
10f (43:57)
10g (60:40)
10h (7:93)
10i (20:80)
10j (54:46)
10k (85:15)
10l (85:15)
10m (86:14)
10n (18:82)
10o (64:36)
60b
78c
85b
53b
75b; 64c
64d
99d
68d
54d
84d
91e
A range of soft nucleophiles (Ph3P, AcSꢀ, Iꢀ, Ac2CHꢀ), as well as
the intermediate nucleophiles (CNꢀ, N3ꢀ) and one hard nucleophile
(Fꢀ) can debrominate the double bond of vinyl bromide 10k to
parent compound 11k, probably via bromophilic attack, followed
by protonation of the vinyl carbanion (Table 2). To the best of our
knowledge, this is the first example of bromophilic attack exerted
by a fluoride ion.
CH2CO2Et
CH3
CH3
CH3
CH3
CH3
H
H
H
H
H
79e
76e
Table 2
72e
Reductive debromination of vinyl bromide 10k to 11k
65e
Nu:
O
S
O
R1¼CH3
11p
11q
S
H
CH3
CH2CO2Et
CO2Et
CO2Et
CO2Et
13 (100:0)
15a (100:0)
15b (100:0)
98f
71f
63f
O
N
H
N
H
O
N
H
N
H
Br
H
11r
10k
11k
a
Yield of isolated products.
b
c
d
e
f
Nu: = Ph3P, AcS , CN , I , F , Ac2CH , N3
Br2 (1 equiv), dry EtOH, rt.
Br2 (1 equiv), CCl4, reflux.
Br2 (1 equiv), dry EtOH, ꢀ10 ꢁC.
Br2 (1 equiv), CHCl3, reflux.
Br2 (1 equiv), CHCl3, rt.
Nucleophile
Solvent
T
Yielda (%) (Z/E ratio)
Ph3P; 10 equiv
AcSꢀ; 2 equiv
CNꢀ; 10 equiv
Iꢀ; 3 equiv
CHCl3
Me2CO/H2O (7:1)
MeCN
MeCN/H2O
DMF
MeCN
Reflux
rt
88 (49:51)
72 (100:0)
51 (100:0)
71 (100:0)
25b (56:44)
24b (53:47)
34b (41:59)
Reflux
rt
However, an increase of the ground-state polarization of thiazoli-
Fꢀ; 3 equiv
70 ꢁ
rt
C
dines 11 in polar solvents, such as DMSO, enhances the presence of the
Z-isomers because of the favourable 1,5-type electrostatic S/O in-
teractions depicted in structure A. Based on this well-established di-
rection of the Z/E isomerization in polar DMSO, it is obvious that the
corresponding E-isomer will be the major species in the case of vinyl
bromides 10. Therefore, the correlation of the 1H and 13C NMR spec-
troscopic data obtained for vinyl bromides 10 with these of the pre-
viously reported for an extensive series of 11, in combination with the
Ac2CHꢀ; 2 equiv
Nꢀ3 ; 2 equiv
Me2CO/H2O (7:1)
rt
a
Yield of isolated product.
The rest of the organic mixture decomposed.
b
Amongst the tested nucleophiles, it is especially noteworthy
that another reaction pathway was established with KSCN. The first
step of the reaction of vinyl bromide 10k with 1 equiv of KSCN was
O
O
O
S
S
S
KSCN (1 eq.)
Me2CO, r.t.
- KBr
O
N
H
O
N
H
O
N
H
N
H
N
H
N
H
K
Br
SCN
+
10k
16
17
(53%; Z/E 77:23)
BrSCN
Scheme 6.

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M. Baranac-Stojanovic et al. / Tetrahedron 66 (2010) 6873e6884
6876
again nucleophilic attack on bromine, furnishing the carbanion 16
(Scheme 6), which then rapidly reacted with BrSCN yielding the
tetra-substituted alkene 17. In support of this mechanism is the
finding that a small amount of 4-oxothiazolidine 11k (6%) was
formed when the reaction was conducted in Me2CO/H2O 7:1 (v/v).
The mechanism for the formation of new pyridinium salts 21, con-
taining 4-oxothiazolidinefragment bonded throughtheC(5)-position
to the pyridine nitrogen, was investigated in more details. The lack of
inhibition in the presence of a strong electron acceptor, such as
p-dinitrobenzene, both in catalytic and equimolar amounts, is in-
O
O
S
11k +
i)
iv) R = H
EWG
O
N
H
R = H
Br
N
O
H
CO2Et
S
18
N
R
EWG
O
S
N
H
S
S
v)
ii)
R = CH2CO2Et
H
EWG
EWG
EWG
O
O
O
N
H
N
H
N
H
R = CH3
21k-m
H
H
19a-e
Br
10a-o
22f-j
iii) R = CH3
S
EWG
H
O
N
H
20f-g
Scheme 7. Reagents and conditions: (i) AcOK (2 equiv), Me2CO/H2O, rt, 5 h; (ii) Method A: pyridine (10 equiv), CHCl3, reflux, 6e59 h; Method B: Et3N (5 equiv), CHCl3, rt,
20 mine12 h; (iii) pyridine (20 equiv), CHCl3, reflux, 21e64 h; (iv) pyridine, (10 equiv), CHCl3, reflux, 4e7 days; (v) morpholine (10 equiv), CHCl3, rt, 4e59 h.
Table 3
Interestingly, on examination of a reductive dehalogenation
ability of the hard acetate nucleophile in the reaction with vinyl
Rearrangement reactions of vinyl bromides 10
Entry Substrate
R
EWG
Product(s)
(Z/E ratio)
Yielda (%)
bromide 10k, the experimental results showed that the same anion
was also capable of inducing rearrangement into the C(5) acetate 18
(Scheme 7, Table 3), though in low yield.
However, we have found that the organic bases, such as pyri-
dine, Et3N and morpholine,26 can be used as the major and very
efficient reagents for rearranging vinyl bromides 10aeo to various C
(5)-functionalized 4-oxothiazolidines 19e22 (Scheme 7). The yields
of the rearranged products are good to high (Table 3).
All these observations are in accordance with an ionic, intra-
molecular process, depicted in Scheme 8 with pyridine acting as
a nucleophile and base. The first step, i.e., the bromophilic reaction,
is followed by the bromine migration27 to the C(5) position of the
ring, which occurs through the base-assisted proton transfer from
the C(5) to the vinylic position of the anion 23. The resulting C(5)-
carbanion 24 is brominated to the C(5) alkyl bromide 25, which
undergoes substitution with pyridine to form salts 21. The mech-
anism for the formation of other C(5)-functionalized products, such
as 19aee, 20feg and 22fej, is probably similar, with the difference
being the last step. Consequently, the last step is either substitution
(when morpholine is used as a nucleophile), or HBr elimination,
occurring in the presence of pyridine and Et3N.
1
2
3
4
5
6
7
10k
10a
10b
10c
10d
10e
10f
H
CONHPh
11k; 18 (91:9) 17b; 28b
CH2CO2Et CONHPh
19a (100:0)c
67c; 91d
51c; 92d
49c; 92d
61c; 89d
76c; 93d
10
35
89
87
77
CH2CO2Et CONH(CH2)2Ph 19b (82:18)c
CH2CO2Et CO2Et
CH2CO2Et COPh
CH2CO2Et CN
CH3
CH3
H
19c (66:34)c
19d (60:40)c
19e (14:86)c
CONHPh
CONH(CH2)2Ph 20g (100:0)
CONHPh
CONH(CH2)2Ph 21l (100:0)
CO2Et
CONHPh
CONH(CH2)2Ph 22g (44:56)
CO2Et
COPh
CN
20f (100:0)
8
9
10g
10k
10l
10m
10f
10g
10h
10i
21k (100:0)
10
11
12
13
14
15
16
H
H
21m (100:0)
22f (13:87)
CH3
CH3
CH3
CH3
CH3
90
62
90
74
22h (60:40)
22i (100:0)
22j (100:0)
10j
83
a
Yield of isolated products.
b
Calculated from 1H NMR spectrum, since a minor part of compound 18 was
isolated in a mixture with 11k.
c
Method A (see Scheme 7 and Experimental section).
Method B (see Scheme 7 and Experimental section).
d
dicative of an ionic mechanism. In order to distinguish between the
intra- and intermolecular process, two separate crossover reactions
have been carried out: (1) a mixture of equimolar amounts of vinyl
bromide 10k and 4-oxothiazolidine 11l, and (2) vinyl bromide 10l and
In theserearrangements the bromophilicreaction/brominetransfer/
elimination(substitution) cascade process implies a multiple role of
nucleophile, bromine transfer agent and base, for the organic base.
Py+-Br
Br
base-assisted
S
S
S
S
pyridine
proton transfer
EWG
Py+-Br
EWG
EWG
EWG
O
O
N
H
N
H
O
O
N
H
N
H
Br
H
H
23
10k-m
25
24
Scheme 8.

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M. Baranac-Stojanovic et al. / Tetrahedron 66 (2010) 6873e6884
6877
Table 4
4-oxothiazolidine 11k were treated with 10-fold molar excess of
Nucleophilic substitution reactions of pyridinium salts 21
pyridine in refluxing CHCl3. In reaction 1 the corresponding pyr-
idinium salt 21k and unchanged 4-oxothiazolidine 11l were isolated,
whereas in the case of reaction 2, the pyridinium salt 21l and
unchanged 4-oxothiazolidine 11k were isolated from the reaction
mixture. Furthermore, monitoring of the reaction of 10k with excess
of pyridine in CDCl3 by 1H NMR spectroscopy revealed that the parent
4-oxothiazolidine 11k is not formed as an intermediate.
Substrate
EWG
Product (Z/E ratio)
Yielda,b (%)
21k
21l
21k
21l
21k
21l
CONHPh
CONH(CH2)2Ph
CONHPh
CONH(CH2)2Ph
CONHPh
CONH(CH2)2Ph
26k (76:24)
26l (20:80)
27k (100:0)
27l (100:0)
28k (9:91)
28l (18:82)
63
86
69
66
91
87
The importance of the ethoxycarbonyl group for stabilization of
the systemwith two exocyclic C]C bonds is clearlyseen on the basis
of the yields of the products 19aee, which depending on the applied
method, range from 49 to 76% or 89 to 93% (Table 3; entries 1e6) and
only 10e35% for 20f and g (entries 7 and 8). In the case of 19aee the
stable, fully conjugated system is formed. In addition, moderate
yields of the products 19aee, obtained by the use of pyridine as the
bromine transfer agent, were later improved by the use of a stronger
base, Et3N. The synthesis of 19aee was optimized by the treatment
of 4-oxothiazolidines 11aee with pyridinium hydrobromide per-
bromide (PHBP),28 allowing quantitative yields (94e100%) to be
obtained. As can be seen fromScheme 7 and Table 3, the formation of
the less stable derivatives 20f and g was restricted to the bromides
10f and g, having an amide substituent at the double bond. Under the
same reaction conditions (20-fold molar excess of pyridine, CHCl3,
reflux) only unchanged vinyl bromide 10h was isolated from the
reaction mixture, whereas bromides 10i and 10j yielded 4-oxo-
thiazolidines 11i and 11j in 23% and 14% yields, respectively. Vinyl
bromides 10n and 10o were not suitable precursors for the synthesis
of pyridinium salts under similar reaction conditions, since 10n
yielded only the product of reductive dehalogenation 11n (18%),
while 10o gave inseparable complex mixture.
a
Yield of isolated products.
Based on vinyl bromides 10k and 10l.
b
3. Conclusion
This paper describes reactions of 2-alkylidene-4-oxothiazoli-
dine vinyl bromides with a variety of ionic and neutral nucleo-
philes, leading to (i) reductive debromination, (ii) bromine
substitution or (iii) efficient C(5) functionalization of the ring, all of
them initiated by the nucleophilic attack on bromine. Combination
of this rare bromophilic reaction with bromine transfer was used
for the first time to achieve a number of synthetically useful
transformations of 4-oxothiazolidines.
4. Experimental
4.1. General
Melting points below 215 ꢁC were determined on a Büchi ap-
paratus and those above 215 ꢁC on a Mikroheitztich Boetius PMHK
05 apparatus and are uncorrected. The IR spectra were recorded on
a PerkineElmer FTIR 1725X spectrophotometer and are reported as
wave numbers (cmꢀ1). Samples for IR spectral measurements were
prepared as KBr discs. The NMR spectra were recorded on a Varian
Gemini 2000 spectrometer (1H at 200 MHz, 13C at 50.3 MHz) in
DMSO-d6 or CDCl3 and on Bruker Avance III 500 (1H at 500.26 MHz,
13C at 125.79 MHz) in DMSO-d6. Chemical shifts are reported in
It is worth noting that pyridine in pyridinium salts 21k and l can
efficiently be replaced by neutral nitrogen and oxygen nucleophiles
to give new 5-amino- and 5-alkoxy-4-oxothiazolidines 26e28
(Scheme 9, Table 4). In spite of the fact that pyridine is a relatively
poor leaving group and susceptibility of the pyridinium ring to
29
nucleophilic attack at the 2-, 4- and 6-positions,
and in some
cases was followed by ring cleavage,30 we have demonstrated that
the pyridinium salts 21 are excellent substrates for substitution
reactions with these neutral nucleophiles.
parts per million (ppm) on the
d scale from TMS as an internal
standard. Elemental analyses were performed at the microanalysis
laboratory at the Centre for Chemistry ICTM. HRMS was carried out
on 6210 TOF LC/MS coupled with HPLC 1200 Series Agilent Tech-
nologies. Thin-layer chromatography (TLC) was carried out on
Kieselgel Gnach Stahl and spots were visualized by iodine or by 50%
H2SO4. Column chromatography was carried out on SiO2 (silica gel
60 Å, 12-26, ICN Biomedicals). Aniline, carbontetrachloride, meth-
anol, toluene, petrolether (40e70 ꢁC) and ethyl acetate were dis-
tilled before use. Pyridine, triethylamine and morpholine were
dried over NaOH or KOH and then distilled. Chloroform was
extracted several times with water, dried over CaCl2 or K2CO3 and
distilled prior to use. Absolute ethanol was obtained by azeotropic
distillation with benzene. 2-Alkylidene-4-oxothiazolidines were
PhHN
S
i)
EWG
EWG
O
N
H
26k,l
H
Br
MeO
O
N
prepared from
a-mercaptoesters and a-substituted nitriles,
S
S
according to our procedure.31 All vinyl bromides 10 should be
stored in a freezer, at ꢀ15 ꢁC.
ii)
EWG
O
N
H
N
H
H
H
21k,l
27k l
,
4.2. General procedure for synthesis of
5-ethoxycarbonylmethyl-4-oxothiazolidine vinyl bromides
10aee
O
iii)
N
S
4.2.1. Method A. To
a suspension of 4-oxothiazolidine 11aee
EWG
(1 mmol) in abs EtOH (20 mL) 2% bromine solution in the same sol-
vent (ca.1 equiv of bromine) was added dropwise at rt until complete
consumption of the starting material (TLC). The bromine solution
should be added at the rate, which is roughly the same as the rate of
disappearance of bromine colour in the reaction mixture, though in
some cases a pale yellow colour can appear before the addition is
O
N
H
H
28k,l
Scheme 9. Reagent and conditions: (i) aniline (excess), MeOH/H2O, rt, 0.5e1.45 h;
(ii) K2CO3, MeOH, reflux, 24 h; (iii) morpholine (excess), CHCl3, rt, 6.5e25 h.

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M. Baranac-Stojanovic et al. / Tetrahedron 66 (2010) 6873e6884
6878
completed. The reaction mixture was evaporated to a smaller volume
and bromides were allowed to crystallize at rt or in a freezer. The
products were isolated by filtration, as pure substances.
4.2.1.4. 2-Bromo-2-(5-ethoxycarbonylmethyl-4-oxothiazolidin-2-
ylidene)ethanonitrile (10e). Z/E ratio: 65:35; yield: 75%; pale yellow
solid, mp 124e125 ꢁC; IR (KBr, cmꢀ1): nmax 3185, 3116, 2212, 1737,
1713, 1605, 1448, 1313, 1289, 1251, 1214, 1192, 849, 752; 1H NMR
4.2.1.1. 2-Bromo-2-(5-ethoxycarbonylmethyl-4-oxothiazolidin-2-
ylidene)-N-phenylethanamide (10a)24. Z/E ratio: 39:61; yield: 60%;
pale yellow solid, mp 122e123 ꢁC; IR (KBr, cmꢀ1): nmax 3371, 3227,
3180, 3090, 1719, 1634, 1595, 1558, 1528, 1499, 1443, 1378, 1312,
1234, 1195, 858, 834, 801, 755, 691; 1H NMR (200 MHz, DMSO-d6,
(200 MHz, DMSO-d6, 25 ꢁC): (Z isomer)
d
1.18 (t, J¼7.1 Hz, 3H, CH3),
3.08e3.13 (m, 2H, CHAHBCOO), 4.10 (q, J¼7.1 Hz, 2H, CH2O), 4.57 (t,
J¼6.2 Hz, 1H, CHxS), (E isomer)
d
1.18 (t, J¼7.1 Hz, 3H, CH3),
3.08e3.13 (m, 2H, CHAHBCOO), 4.10 (q, J¼7.1 Hz, 2H, CH2O), 4.72 (t,
13
J¼5.9 Hz, 1H, CHxS); C NMR (50.3 MHz, DMSO-d6, 25 ꢁC): (Z iso-
25 ꢁC): (E isomer)
d
1.18 (t, J¼7.2 Hz, 3H, CH3), 2.99e3.03 (m, 2H,
mer) d 14.1 (CH3), 35.9 (CH2COO), 45.6 (CHS), 56.4 (]CBr), 61.0
CHAHBCOO), 4.10 (q, J¼7.2 Hz, 2H, CH2O), 4.34 (dd, JAx¼6.9 Hz,
JBx¼5.1 Hz, 1H, CHxS), 7.09 (t, J¼7.4 Hz, 1H, p-Ph), 7.28e7.35 (m, 2H,
m-Ph), 7.60 (d, J¼8.2 Hz, 2H, o-Ph), 9.29 (s, 1H, NHamide),11.22 (s,1H,
(CH2O), 115.2 (CN), 159.5 (C]), 170.4 (COester), 176.0 (COlactam), (E
isomer) 14.1 (CH3), 36.1 (CH2COO), 45.9 (CHS), 51.3 (]CBr), 61.0
d
(CH2O), 116.7 (CN), 156.3 (C]), 170.3 (COester), 175.5 (COlactam). Anal.
Calcd for C9H9BrN2O3S: C, 35.42; H, 2.97; N, 9.18; S, 10.51; found: C,
35.19; H, 3.08; N, 9.10; S, 10.73.
NHlactam), (Z isomer)
d
1.19 (t, J¼7.1 Hz, 3H, CH3), 3.08e3.13 (m, 2H,
CHAHBCOO), 4.11 (q, J¼7.1 Hz, 2H, CH2O), 4.53 (dd, JAx¼7.5 Hz,
JBx¼4.8 Hz, 1H, CHxS), 7.13 (t, J¼7.4 Hz, 1H, p-Ph), 7.30e7.38 (m, 2H,
m-Ph), 7.60 (d, J¼8.2 Hz, 2H, o-Ph), 9.40 (s, 1H, NHamide), 11.29 (br s,
4.2.2. Method B. To a suspension of 4-oxothiazolidine 11b (or 11e)
(1 mmol) in CCl4 (48 mL) 2% bromine solution in the same solvent
(ca. 1 equiv of bromine) was added dropwise under reflux until
complete disappearance of the starting material (TLC). The bromine
solution should be added at the rate, which is roughly the same as
the rate of disappearance of bromine colour in the reaction mixture,
though in some cases a pale yellow or pale orange colour can ap-
pear before the addition is completed. The reaction mixture was
evaporated to a smaller volume and bromides were allowed to
crystallize at rt. The products were isolated by filtration, as pure
substances.
13
1H, NHlactam); C NMR (50.3 MHz, DMSO-d6, 25 ꢁC): (E isomer)
d
14.2 (CH3), 36.4 (CH2COO), 43.5 (CHS), 60.9 (CH2O), 79.4 (]CBr),
121.4 (o-Ph), 124.2 (p-Ph), 128.7 (m-Ph), 138.6 (C1-Ph), 151.1 (C]),
162.5 (COamide), 170.4 (COester), 175.5 (COlactam), (Z isomer) 14.2
d
(CH3), 36.1 (CH2COO), 43.8 (CHS), 61.0 (CH2O), 83.6 (]CBr), 122.2
(o-Ph), 124.8 (p-Ph), 128.7 (m-Ph), 138.1 (C1-Ph), 153.2 (C]), 162.2
(COamide), 170.4 (COester), 174.8 (COlactam). Anal. Calcd for
C15H15BrN2O4S: C, 45.12; H, 3.79; N, 7.02; S, 8.03; found: C, 45.34; H,
4.01; N, 6.77; S, 7.85.
4.2.1.2. Ethyl 2-bromo-2-(5-ethoxycarbonylmethyl-4-oxothiazo-
lidin-2-ylidene)ethanoate (10c). Z/E ratio: 54:46; yield 85%; pale
yellow crystals, mp 86e88 ꢁC; IR (KBr, cmꢀ1): nmax 3196, 1719, 1671,
1583, 1449, 1374, 1316, 1273, 1235, 886, 858, 813, 756; 1H NMR
4.2.2.1. (Z)-2-Bromo-2-(5-ethoxycarbonylmethyl-4-oxo-
thiazolidin-2-ylidene)-N-(2-phenylethyl)ethanamide (10b)24. Yield:
78%; pale yellow crystals, mp 116e118 ꢁC; IR (KBr, cmꢀ1): nmax 3369,
3176, 3025, 1722, 1609, 1585, 1523, 1451, 1374, 1347, 1308, 1229, 1192,
(200 MHz, DMSO-d6, 25 ꢁC): (Z isomer)
d
1.20 (t, J¼7.0 Hz, 3H, CH3),
1.23 (t, J¼7.0 Hz, 3H, CH3), 3.08e3.12 (m, 2H, CHAHBCOO), 4.16 (q,
858, 749, 705; 1H NMR (200 MHz, DMSO-d6, 25 ꢁC):
d
1.18 (t, J¼7.1 Hz,
J¼7.0 Hz, 2H, CH2O), 4.22 (q, J¼7.0 Hz, 2H, CH2O), 4.53 (dd,
3H, CH3), 2.78 (t, J¼7.5 Hz, 2H, CH2Ph), 3.06e3.11 (m, 2H, CHAHBCOO),
3.33e3.43 (m, 2H, NCH2), 4.10 (q, J¼7.1 Hz, 2H, CH2O), 4.49 (dd,
JAx¼7.5 Hz, JBx¼4.9 Hz, 1H, CHxS), 7.16e7.34 (m, 5H, Ph), 7.89 (t,
J¼5.6 Hz, 1H, NHamide), 11.42 (s, 1H, NHlactam); 13C NMR (50.3 MHz,
JAx¼6.9 Hz, JBx¼5.1 Hz, 1H, CHxS), 10.84 (s, 1H, NH), (E isomer)
d 1.17
(t, J¼7.2 Hz, 3H, CH3), 1.22 (t, J¼7.2 Hz, 3H, CH3), 3.01e3.04 (m, 2H,
CHAHBCOO), 4.09 (q, J¼7.2 Hz, 2H, CH2O), 4.12 (q, J¼7.2 Hz, 2H,
CH2O), 4.41 (dd, JAx¼6.6 Hz, JBx¼5.4 Hz, 1H, CHxS), 11.35 (s, 1H, NH);
DMSO-d6, 25 ꢁC):
d 14.1 (CH3), 35.2 (CH2Ph), 36.2 (CH2COO), 41.4
13C NMR (50.3 MHz, DMSO-d6, 25 ꢁC): (Z isomer)
d
14.2 (CH3), 14.4
(NCH2), 43.7 (CHS), 61.0 (CH2O), 84.2 (]CBr), 126.4 (p-Ph), 128.6 (o-
Ph), 128.9 (m-Ph), 139.4 (C1-Ph), 151.7 (C]), 163.4 (COamide), 170.4
(COester), 174.4 (COlactam). Anal. Calcd for C17H19BrN2O4S: C, 47.78; H,
4.48; N, 6.56; S, 7.50; found: C, 48.14; H, 4.56; N, 6.33; S, 7.60.
(CH3), 36.0 (CH2COO), 44.1 (CHS), 61.0 (CH2O), 61.9 (CH2O), 81.8 (]
CBr), 156.5 (C]), 162.6 (]CHCOO), 170.4 (CH2COO), 175.4 (COlac-
tam), (E isomer)
d 14.2 (CH3), 14.4 (CH3), 36.2 (CH2COO), 43.9 (CHS),
60.9 (CH2O), 61.5 (CH2O), 77.3 (]CBr), 154.6 (C]), 163.9 (]
CHCOO), 170.4 (CH2COO), 175.7 (COlactam). Anal. Calcd for
C11H14BrNO5S: C, 37.51; H, 4.01; N, 3.98; S, 9.10; found: C, 37.34; H,
4.09; N, 4.28; S, 9.05.
4.2.2.2. 2-Bromo-2-(5-ethoxycarbonylmethyl-4-oxothiazolidin-
2-ylidene)ethanonitrile (10e). Yield: 64%.
4.3. General procedure for synthesis of 5-methyl-
4.2.1.3. 2-Bromo-2-(5-ethoxycarbonylmethyl-4-oxothiazolidin-2-
ylidene)-1-phenylethanone (10d)24. Z/E ratio: 14:86; yield: 53%;
pale yellow crystals, mp 87 ꢁC; IR (KBr, cmꢀ1): nmax 3471, 3407,
3061, 1728, 1626, 1542, 1446, 1377, 1316, 1230, 1201, 785, 745, 697;
4-oxothiazolidine vinyl bromides 10fej
A suspension of 4-oxothiazolidine 11fej (1 mmol) in abs EtOH
(49 mL) was cooled in an ice-NaCl bath and 2% bromine solution in
the same solvent (ca. 1 equiv of bromine) was added dropwise until
complete disappearance of the starting material (TLC). The bromine
solution should be added at the rate, which is nearly the same as
the rate of disappearance of bromine colour in the reaction mixture.
In some cases the appearance of pale yellow colour of the formed
solution indicates completion of the reaction. The reaction mixture
was evaporated to a smaller volume, a few drops of water were
added and bromides were allowed to crystallize in a freezer. The
products were isolated by filtration, as pure substances. Vinyl
bromide 10g was isolated by extraction with CH2Cl2 and could not
be crystallized or chromatographically purified.
1H NMR (200 MHz, DMSO-d6, 25 ꢁC): (E isomer)
d
1.19 (t, J¼7.0 Hz,
3H, CH3), 3.08 (d, J¼5.9 Hz, 2H, CH2COO), 4.11 (q, J¼7.0 Hz, 2H,
CH2O), 4.44 (t, J¼5.9 Hz, 1H, CHS), 7.41e7.63 (m, 5H, Ph), 11.61 (s,
1H, NH), (Z isomer)
d
1.19 (t, J¼7.0 Hz, 3H, CH3), 3.14e3.18 (m, 2H,
CHAHBCOO), CH2O is masked by the signal of the E isomer, 4.58
(dd, JAx¼6.8 Hz, JBx¼5.2 Hz, 1H, CHxS), 7.41e7.63 (m, 5H, Ph), 11.61
13
(s, 1H, NH); C NMR (50.3 MHz, DMSO-d6, 25 ꢁC): (E isomer)
d
14.2 (CH3), 35.8 (CH2COO), 43.5 (CHS), 61.0 (CH2O), 85.8 (]CBr),
127.9 (o-Ph), 128.2 (m-Ph), 131.0 (p-Ph), 139.4 (C1-Ph), 157.4 (C]),
170.4 (COester), 176.0 (COlactam), 190.4 (COketone), (Z isomer) 14.2
d
(CH3), 35.8 (CH2COO), 44.0 (CHS), 61.1 (CH2O), 89.8 (]CBr), 127.9
(o-Ph), 128.3 (m-Ph), 131.6 (p-Ph), 138.9 (C1-Ph), 159.0 (C]), 170.4
(COester), 176.2 (COlactam), 189.6 (COketone). Anal. Calcd for
C15H14BrNO4S: C, 46.88; H, 3.65; N, 3.65; S, 8.34; found: C, 46.58;
H, 3.63; N, 3.41; S, 8.27.
4.3.1. 2-Bromo-2-(5-methyl-4-oxothiazolidine-2-ylidene)-N-phenyl-
ethanamide (10f). Z/E ratio: 43:57; yield: 64%; white solid with no
sharp mp; IR (KBr, cmꢀ1): nmax 3434, 3393, 3251, 1721, 1627, 1586,

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M. Baranac-Stojanovic et al. / Tetrahedron 66 (2010) 6873e6884
6879
1528, 1441, 1372, 1313, 1238, 1209, 1170, 898, 822, 756, 694; 1H NMR
(200 MHz, DMSO-d6, 25 ꢁC): (E isomer)
(KBr, cmꢀ1): nmax 3149, 2203, 1721, 1596, 1446, 1377, 1320, 1247,
1115, 888, 797, 734; 1H NMR (200 MHz, DMSO-d6, 25 ꢁC): (Z isomer)
d
1.46 (d, J¼7.2 Hz, 3H, CH3),
4.12 (q, J¼7.2 Hz, 1H, CHS), 7.05e7.13 (m, 1H, p-Ph), 7.27e7.35 (m,
d
1.51 (d, J¼7.2 Hz, 3H, CH3), 4.34 (q, J¼7.2 Hz, 1H, CHS), 12.30 (s,
NH), (E isomer)
1.53 (d, J¼7.2 Hz, 3H, CH3), 4.49 (q, J¼7.2 Hz, 1H,
CHS), 12.30 (s, NH); C NMR (50.3 MHz, DMSO-d6, 25 ꢁC): (Z iso-
mer) 18.4 (CH3), 44.7 (CHS), 56.5 (]CBr), 115.3 (CN), 158.9 (C]),
177.7 (CO), (E isomer) 18.6 (CH3), 45.1 (CHS), 51.4 (]CBr), 116.7
2H, m-Ph), 7.58e7.62 (m, 2H, o-Ph), 9.28 (s, 1H, NHamide), 11.12 (s,
d
13
1H, NHlactam), (Z isomer)
d
1.54 (d, J¼7.2 Hz, 3H, CH3), 4.30 (q,
J¼7.2 Hz, 1H, CHS), 7.09e7.16 (m, 1H, p-Ph), 7.30e7.37 (m, 2H, m-
d
Ph), 7.58e7.62 (m, 2H, o-Ph), 9.39 (s, 1H, NHamide), 11.22 (s, 1H,
d
13
NHlactam); C NMR (50.3 MHz, DMSO-d6, 25 ꢁC): (E isomer)
d
18.5
(CN), 155.7 (C]), 177.2 (CO). Anal. Calcd for C6H5BrN2OS: C, 30.92;
(CH3), 42.3 (CHS), 79.4 (]CBr), 121.4 (o-Ph), 124.2 (p-Ph), 128.7 (m-
Ph), 138.6 (C1-Ph), 150.2 (C]), 162.4 (COamide), 177.2 (COlactam), (Z
H, 2.16; N, 12.02; S, 13.76; found: C, 31.27; H, 2.18; N, 12.08; S, 13.94.
isomer)
d
18.5 (CH3), 42.8 (CHS), 83.7 (]CBr), 122.1 (o-Ph), 124.7 (p-
4.4. General procedure for synthesis of 4-oxothiazolidine
Ph), 128.7 (m-Ph), 138.1 (C1-Ph), 152.6 (C]), 162.1 (COamide), 176.5
(COlactam). Anal. Calcd for C12H11BrN2O2S: C, 44.05; H, 3.39; N, 8.56;
S, 9.80; found: C, 44.35; H, 3.44; N, 8.46; S, 9.95.
vinyl bromides 10keo
To a suspension of 4-oxothiazolidine 11keo (1 mmol) in CHCl3
(37 mL) 2% bromine solution in the same solvent (ca. 1 equiv of
bromine) was added dropwise under reflux until complete disap-
pearance of the starting material (TLC). The bromine solution
should be added at the rate, which is roughly the same as the rate of
disappearance of bromine colour in the reaction mixture, though in
some cases a pale yellow or pale orange colour can appear before
the addition is completed. The reaction mixture was evaporated to
dryness, bromides were precipitated with EtOH (in some cases
a few drops of water were also added) and filtered.
4.3.2. 2-Bromo-2-(5-methyl-4-oxothiazolidine-2-ylidene)-N-(2-phe-
nylethyl)ethanamide (10g). Z/E ratio: 60:40; yield: 99% (crude
product); colourless oil; IR (KBr, cmꢀ1): nmax 3445, 3410, 3260,
3028, 1725, 1622, 1582, 1523, 1452, 1372, 1308, 1263, 1218, 749, 703;
1H NMR (200 MHz, DMSO-d6, 25 ꢁC): (Z isomer)
d
1.52 (d, J¼7.2 Hz,
3H, CH3), 2.74e2.81 (m, 2H, CH2Ph), 3.29e3.43 (m, 2H, CH2N), 4.26
(q, J¼7.2 Hz, 1H, CHS), 7.16e7.34 (m, 5H, Ph), 7.88 (t, J¼5.7 Hz, 1H,
NHamide), 11.37 (s, 1H, NHlactam), (E isomer)
d
1.43 (d, J¼7.2 Hz, 3H,
CH3), 2.72e2.78 (m, 2H, CH2Ph), 3.29e3.43 (m, 2H, CH2N), 4.05 (q,
J¼7.2 Hz, 1H, CHS), 7.16e7.34 (m, 5H, Ph), 7.75 (t, J¼5.6 Hz, 1H,
NHamide), 10.94 (s, 1H, NHlactam); 13C NMR (50.3 MHz, DMSO-d6,
4.4.1. 2-Bromo-2-(4-oxothiazolidine-2-ylidene)-N-phenyl-
ethanamide (10k). Z/E ratio: 85:15; yield: 91%; white solid, mp
139e140 ꢁC (decomp.); IR (KBr, cmꢀ1): nmax 3400, 3215, 3184, 1728,
1642, 1597, 1574, 1532, 1492, 1441, 1317, 1239, 1212, 1171, 834, 758,
25 ꢁC): (Z isomer)
d 18.5 (CH3), 35.2 (CH2Ph), 41.4 (NCH2), 42.7
(CHS), 84.3 (]CBr), 126.4 (p-Ph), 128.6 (o-Ph), 128.9 (m-Ph), 139.5
(C1-Ph), 151.2 (C]), 163.4 (COamide), 176.1 (COlactam), (E isomer)
733, 690; 1H NMR (200 MHz, DMSO-d6, 25 ꢁC): (Z isomer)
d 3.99 (s,
d
18.6 (CH3), 35.4 (CH2Ph), 41.4 (NCH2), 42.1 (CHS), 80.2 (]CBr),
2H, CH2), 7.09e7.17 (m, 1H, p-Ph), 7.30e7.38 (m, 2H, m-Ph),
7.58e7.63 (m, 2H, o-Ph), 9.36 (s, 1H, NHamide), 11.24 (s, 1H, NHlactam),
(E isomer) d 3.86 (s, 2H, CH2), 7.06e7.13 (m, 1H, p-Ph), 7.28e7.36 (m,
126.4 (p-Ph), 128.6 (o-Ph), 129.0 (m-Ph), 139.6 (C1-Ph), 148.0 (C]),
163.4 (COamide), 177.2 (COlactam); HRMS: calcd for C14H16BrN2O2S
(MþH)þ: 355.0110; found: 355.0119.
2H, m-Ph), 7.58e7.63 (m, 2H, o-Ph), 9.26 (s, 1H, NHamide), 11.14 (s,
13
1H, NHlactam); C NMR (50.3 MHz, DMSO-d6, 25 ꢁC): (Z isomer)
4.3.3. Ethyl 2-bromo-2-(5-methyl-4-oxothiazolidin-2-ylidene)etha-
noate (10h). Z/E ratio: 7:93; yield 68%; white solid, mp 75e77 ꢁC; IR
(KBr, cmꢀ1): nmax 3175, 1720, 1669, 1567, 1458,1367, 1306, 1269, 1193,
d
33.4 (CH2), 83.6 (]CBr), 122.1 (o-Ph), 124.7 (p-Ph), 128.7 (m-Ph),
138.1 (C1-Ph), 154.4 (C]), 162.1 (COamide), 173.8 (COlactam), (E iso-
mer) 34.0 (CH2), 79.2 (]CBr), 121.4 (o-Ph), 124.2 (p-Ph), 128.7 (m-
d
1
1172, 881, 822, 788, 753; H NMR (200 MHz, DMSO-d6, 25 ꢁC): (E
Ph), 138.6 (C1-Ph), 152.3 (C]), 162.6 (COamide), 174.4 (COlactam).
Anal. Calcd for C11H9BrN2O2S: C, 42.19; H, 2.90; N, 8.94; S, 10.24;
found: C, 42.36; H, 3.16; N, 9.00; S, 10.01.
isomer)
d
1.23 (t, J¼7.2 Hz, 3H, CH3CH2),1.47 (d, J¼7.2 Hz, 3H, CH3CH),
4.16(q, J¼7.2 Hz,3H, CH2OandCHS),11.27(s,1H, NH), (Zisomer)
d
1.24
(t, J¼7.1 Hz, 3H, CH3CH2), 1.53 (d, J¼7.2 Hz, 3H, CH3CH), 4.21 (q,
J¼7.1 Hz, 2H, CH2O), 4.31 (q, J¼7.2 Hz,1H, CHS), 10.77 (s, 1H, NH); 13
C
4.4.2. 2-Bromo-2-(4-oxothiazolidine-2-ylidene)-N-(2-phenylethyl)
ethanamide (10l)26. Z/E ratio: 85:15; yield: 79%; white crystals, mp
140e142 ꢁC; IR (KBr, cmꢀ1): nmax 3360, 3139, 3022, 1723, 1615, 1585,
1517, 1452, 1431, 1350, 1312, 1257, 1219, 1190, 887, 786, 750, 699; 1H
NMR (50.3 MHz, DMSO-d6, 25 ꢁC): (E isomer)
d 14.4 (CH3CH2), 18.4
(CH3CH), 42.7 (CHS), 61.5 (CH2O), 77.3 (]CBr), 153.8 (C]), 163.8
(COester), 177.3 (COlactam), (Z isomer) 14.4 (CH3CH2), 18.4 (CH3CH),
d
43.1 (CHS), 61.8 (CH2O), 81.8 (]CBr),156.0 (C]),162.6 (COester),177.1
(COlactam). Anal. Calcd for C8H10BrNO3S: C, 34.30; H, 3.60; N, 5.00; S,
11.45; found: C, 34.56; H, 3.62; N, 5.05; S, 11.65.
NMR (200 MHz, DMSO-d6, 25 ꢁC): (Z isomer)
d
2.78 (t, J¼7.3 Hz, 2H,
CH2Ph), 3.33e3.43(m, 2H, NCH2), 3.95(s, 2H, CH2S), 7.19e7.34 (m, 5H,
Ph), 7.84 (t, J¼5.6 Hz, 1H, NHamide), 11.37 (s, 1H, NHlactam), (E isomer,
visible signals, others are masked by the signals of the Z isomer) d 3.79
4.3.4. 2-Bromo-2-(5-methyl-4-oxothiazolidin-2-ylidene)-1-phenyl-
ethanone (10i). Z/E ratio: 20:80; yield: 54%; pale yellow solid with
no sharp mp; IR (KBr, cmꢀ1): nmax 3208, 3068, 1717, 1609, 1576,
(s, 2H, CH2S), 7.17 (t, J¼5.2 Hz,1H, NHamide),10.93 (s,1H, NHlactam); 13
C
NMR (50.3 MHz, DMSO-d6, 25 ꢁC): (Z isomer)
d 33.2 (CH2S), 35.1
(CH2Ph), 41.4 (NCH2), 84.2 (]CBr), 126.3 (p-Ph), 128.6 (o-Ph), 128.8
(m-Ph), 139.4 (C1-Ph), 152.8 (C]), 163.3 (COamide), 173.3 (COlactam), (E
isomer) d 33.8 (CH2S), 35.4 (CH2Ph), 41.4 (NCH2), 80.0 (]CBr), 126.3
1545, 1507, 1449, 1375, 1318, 1275, 1221, 1177, 842, 794, 764, 733,
1
701; H NMR (200 MHz, DMSO-d6, 25 ꢁC): (E isomer)
d
1.50 (d,
J¼7.2 Hz, 3H, CH3), 4.21 (q, J¼7.2 Hz, 1H, CHS), 7.41e7.63 (m, 5H,
(p-Ph), 128.6 (o-Ph), 128.8 (m-Ph), 139.4 (C1-Ph), 149.9 (C]), 163.3
(COamide),174.3 (COlactam). Anal. Calcd for C13H13BrN2O2S: C, 45.76; H,
3.84; N, 8.21; S, 9.40; found: C, 45.94; H, 3.90; N, 8.16; S, 9.56.
Ph),11.52 (s,1H, NH), (Z isomer)
d
1.57 (d, J¼7.2 Hz, 3H, CH3), 4.35 (q,
J¼7.2 Hz, 1H, CHS), 7.41e7.63 (m, 5H, Ph), 11.52 (s, 1H, NH); 13C NMR
(50.3 MHz, DMSO-d6, 25 ꢁC): (E isomer)
d 18.0 (CH3), 42.4 (CHS),
85.9 (]CBr), 128.0 (o-Ph), 128.1 (m-Ph), 131.0 (p-Ph), 139.4 (C1-Ph),
156.5 (C]), 177.6 (COlactam), 190.4 (COketone), (Z isomer, visible sig-
4.4.3. Ethyl
2-bromo-2-(4-oxothiazolidin-2-ylidene)ethanoate
(10m). Z/E ratio: 86:14; yield 76%; white solid, mp 103e105 ꢁC; IR
(KBr, cmꢀ1): nmax 3251, 1735, 1708, 1665, 1590, 1444, 1371, 1307,
1271, 1230, 1183, 868, 824, 757, 715; 1H NMR (200 MHz, DMSO-d6,
nals)
d 18.2 (CH3), 43.0 (CHS), 128.1 (o-Ph), 128.2 (m-Ph), 131.6 (p-
Ph),177.8 (COlactam). Anal. Calcd for C12H10NO2S: C, 46.17; H, 3.23; N,
4.49; S, 10.27; found: C, 46.32; H, 3.22; N, 4.53; S, 10.26.
25 ꢁC): (Z isomer)
d
1.24 (t, J¼7.1 Hz, 3H, CH3), 4.01 (s, 2H, CH2S),
4.21 (q, J¼7.1 Hz, 2H, CH2O), 10.76 (s, 1H, NH), (E isomer)
d
1.24 (t,
4.3.5. 2-Bromo-2-(5-methyl-4-oxothiazolidin-2-ylidene)ethanoni-
trile (10j). Z/E ratio: 54:46; yield: 84%; white crystals, mp 124 ꢁC; IR
J¼7.1 Hz, 3H, CH3), 3.93 (s, 2H, CH2S), 4.16 (q, J¼7.1 Hz, 2H, CH2O),
11.27 (s, 1H, NH); 13C NMR (50.3 MHz, DMSO-d6, 25 ꢁC): (Z isomer)

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M. Baranac-Stojanovic et al. / Tetrahedron 66 (2010) 6873e6884
6880
d
14.4 (CH3), 33.9 (CH2S), 61.8 (CH2O), 81.6 (]CBr), 157.7 (C]),
165.0 (COlactam), 167.2 (COester); HRMS: calcd for C18H23N2O6S2
162.6 (COester), 174.2 (COlactam), (E isomer)
d
14.4 (CH3), 34.2 (CH2S),
(2MþH)þ: 427.09920; found: 427.10366.
61.4 (CH2O), ]CBr uncertain, 155.8 (C]), 164.0 (COester), 174.5
(COlactam). Anal. Calcd for C7H8BrNO3S: C, 31.59; H, 3.03; N, 5.26; S,
12.05; found: C, 31.58; H, 3.10; N, 5.23; S, 12.01.
4.7. Synthesis of (2Z,5Z)-ethyl-2-(N-methyl-
5-ethoxycarbonylmethylidene-4-oxothiazolidin-2-ylidene)
ethanoate (15b)
4.4.4. 2-Bromo-2-(4-oxothiazolidin-2-ylidene)-1-phenylethanone
(10n). Z/E ratio: 18:82; yield: 72%; light pink-coloured crystals, mp
118e120 ꢁC; IR (KBr, cmꢀ1): nmax 3220, 3063, 1724,1620, 1603, 1576,
1532, 1445, 1319, 1277, 1221, 1181, 880, 790, 723, 698; 1H NMR
To a solution of 4-oxothiazolidine 11r (104.4 mg, 0.37 mmol) in
CHCl3 (5 mL) 2% bromine solution in the same solvent (ca. 1 equiv of
bromine) was added dropwise at rt until the complete disappearance
of the starting material (TLC). The reaction mixture was washed with
5% Na2S2O3, water, stirredwith5% NaHCO3 for 1 h, washed with water,
dried with anhydrous Na2SO4, evaporated and chromatographed
(eluent: gradient petrolether/ethyl acetate 100:0 to 80:20) to give 15b
(66.1 mg, 63%), as a pale yellow solid, mp 130e131 ꢁC. IR (KBr, cmꢀ1):
nmax 1719,1691,1592,1315,1178,1030, 819; 1H NMR (200 MHz, CDCl3,
(200 MHz, DMSO-d6, 25 ꢁC): (E isomer)
7.41e7.65 (m, 5H, Ph), 11.53 (s, 1H, NH), (Z isomer)
CH2), 7.41e7.65 (m, 5H, Ph), 11.53 (s, 1H, NH); 13C NMR (50.3 MHz,
DMSO-d6, 25 ꢁC):
(E isomer) 34.00 (CH2), 85.62 (]CBr), 127.92 (o-
d
3.96 (s, 2H, CH2),
4.06 (s, 2H,
d
d
Ph), 128.12 (m-Ph), 130.96 (p- Ph), 139.44 (C1- Ph), 158.65 (C]),
174.75 (COlactam), 190.30 (COketone), (Z isomer, visible signals) 33.75
(CH2), 75.44 (]CBr), 128.03 (o- Ph), 128.21 (m-Ph), 131.54 (p- Ph),
175.05 (COlactam), COketone. Anal. Calcd for C11H8BrNO2S: C, 44.31; H,
2.70; N, 4.70; S, 10.75; found: C, 44.64; H, 2.79; N, 4.76; S, 10.89.
25 ꢁC):
d
1.32 (t, J¼7.2 Hz, 3H, CH3), 1.36 (t, J¼7.2 Hz, 3H, CH3), 3.32 (s,
3H, NCH3), 4.25 (q, J¼7.2 Hz, 2H, CH2O), 4.31 (q, J¼7.2 Hz, 2H, CH2O),
5.65 (s,1H, ]C(2)H), 6.83 (s,1H, ]C(5)H); 13C NMR (50.3 MHz, CDCl3,
25 ꢁC):
d 14.1 (CH3),14.2 (CH3), 29.7 (NCH3), 60.4 (CH2O), 61.4 (CH2O),
4.4.5. 2-Bromo-2-(4-oxothiazolidin-2-ylidene)ethanonitrile
(10o).
93.7 (]C(2)H), 116.7 (]C(5)H), 141.6 (C(5)]), 152.9 (C(2)]), 164.7
(CO), 165.6 (CO), 166.3 (CO). Anal. Calcd for C12H15NO5S: C, 50.52; H,
5.30; N, 4.91; S, 11.24; found: C, 50.12; H, 5.23; N, 4.77; S, 10.87.
Z/E ratio: 64:36; yield: 65%; brownish solid, mp 163 ꢁC (decomp.);
IR (KBr, cmꢀ1): nmax 3452, 3136, 2202, 1713, 1595, 1417, 1318, 1248,
1
787; H NMR (200 MHz, DMSO-d6, 25 ꢁC):
d 4.03 (s, 2H, CH2), 4.16
(s, 2H, CH2, E isomer), 12.38 (br s, 2H, NH); 13C NMR (50.3 MHz,
DMSO-d6, 25 ꢁC): (Z isomer)
35.3 (CH2), 56.4 (]CBr), 115.3 (CN),
160.6 (C]), 174.4 (CO), (E isomer) 35.3 (CH2), 51.1 (]CBr), 116.8
4.8. Reductive debrominations of vinyl bromide 10k
d
d
4.8.1. Reaction with Ph3P. A mixture of vinyl bromide 10k (25 mg,
0.08 mmol) and Ph3P (209.6 mg, 0.8 mmol) in CHCl3 (1.6 mL) was
heated under reflux for 2 h. The mixture was evaporated and chro-
matographed (eluent: gradient toluene/ethyl acetate 90:10 to 50:50)
to give 11k (16.5 mg, 88%) as a white solid, mp 287e289 ꢁC; Z/E ratio:
49:51; IR (KBr, cmꢀ1): nmax 3291, 3250, 3200, 3138, 3084, 1707, 1666,
1618, 1583, 1550, 1319, 1246, 1155, 836, 814, 780, 752, 694; 1H NMR
(CN),157.4 (C]),174.9 (CO). Anal. Calcd for C5H3BrN2OS: C, 27.41; H,
1.38; N, 12.79; S, 14.64; found: C, 27.35; H, 1.51; N, 12.51; S, 14.72.
4.5. Synthesis of (Z)-ethyl 2-(N-methyl-5-bromo-
4-oxothiazolidin-2-ylidene)ethanoate (13)
To a solution of 4-oxothiazolidine 11p (180.7 mg, 0.9 mmol) in
CHCl3 (4 mL) 2% bromine solution in the same solvent (ca.1 equiv of
bromine) was added dropwise at rt until the complete disappear-
ance of the starting material (TLC). The reaction mixture was di-
luted with CHCl3 (6 mL), washed with 5% Na2S2O3, water, dried
with anhydrous Na2SO4 and evaporated to give 13 (245.5, 98%), as
a pale yellow solid, mp 72e73 ꢁC. IR (KBr, cmꢀ1): nmax 1719, 1679,
1576, 1430, 1278, 1188, 1120, 804; 1H NMR (200 MHz, CDCl3, 25 ꢁC):
(200 MHz, DMSO-d6, 25 ꢁC): (Z isomer)
d 3.70 (s, 2H, CH2), 5.80 (s,1H,
]CH), 6.98 (t, J¼7.6 Hz,1H, p-Ph), 7.26 (t, J¼7.6 Hz, 2H, m-Ph), 7.59 (d,
J¼7.6 Hz, 2H, o-Ph), 9.82 (s, 1H, NHamide), 11.37 (s, 1H, NHlactam), (E
isomer)
d
3.91 (s, 2H, CH2), 5.35 (s, 1H, ]CH), 7.03 (t, J¼7.6 Hz, 1H, p-
Ph), 7.29(t, J¼7.6 Hz,2H, m-Ph), 7.59(d, J¼7.6 Hz,2H, o-Ph),9.91(s,1H,
NHamide), 11.26 (s, 1H, NHlactam); 13C NMR (50.3 MHz, DMSO-d6,
25 ꢁC): (Z isomer)
d 32.3 (CH2), 92.8 (]CH),118.8 (o-Ph),122.6 (p-Ph),
128.9 (m-Ph), 140.1 (C1-Ph), 154.7 (C]), 165.6 (COamide), 174.5
(COlactam). Anal. Calcd for C11H10N2O2S: C, 56.39; H, 4.30; N, 11.96; S,
13.69; found: C, 56.17; H, 4.38; N, 11.92; S, 13.65.
d
1.31 (t, J¼7.2 Hz, 3H, CH3), 3.25 (s, 3H, NCH3), 4.23 (q, J¼7.2 Hz, 2H,
CH2O), 5.62 (s, 1H, ]CH), 5.72 (s, 1H, CHS); 13C NMR (50.3 MHz,
CDCl3, 25 ꢁC):
14.3 (CH3), 30.7 (NCH3), 41.8 (CHS), 60.6 (CH2O),
d
93.2 (]CH), 153.9 (C]), 167.1 (COester), 169.9 (COlactam). Anal. Calcd
for C8H12BrNO4S (13ꢂH2O): C, 32.23; H, 4.06; N, 4.70; S, 10.75;
found: C, 31.89; H, 3.86; N, 4.53; S, 10.79.
4.8.2. Reaction with AcSK. A mixture of vinyl bromide 10k (51.7 mg,
0.16 mmol) and AcSK (37.7 mg, 0.32 mmol) in Me2CO/H2O 7:1 (v/v)
(3.9 mL) was stirred at rt for 24 h. The product 11k was precipitated
by the addition of water and isolated by filtration (24.9 mg, 72%); Z/E
ratio: 100:0.
4.6. Synthesis of (Z)-ethyl 2-(N-methyl-5-methylidene-
4-oxothiazolidin-2-ylidene)ethanoate (15a)
4.8.3. Reaction with KCN. A mixture of vinyl bromide 10k (12.7 mg,
0.04 mmol) and KCN (26.4 mg, 0.04 mmol) in MeCN (0.7 mL) was
heated under reflux for 2 h. The reaction mixture was cooled,
evaporated and the residue was partitioned between ethyl acetate
and water. The organic layer was dried with anhydrous Na2SO4 and
evaporated to give 11k (4.8 mg, 51%); Z/E ratio: 100:0.
To a solution of 4-oxothiazolidine 11q (22.0 mg; 0.1 mmol) in
CHCl3 (2 mL) 2% bromine solution in the same solvent (ca.1 equiv of
bromine) was added dropwise at rt until complete disappearance
of the starting material (TLC). The reaction mixture was diluted
with CHCl3 (10 mL), washed with water and dried with anhydrous
Na2SO4 for 3 days. During this period the initially formed C(5)
bromide 14 was completely dehydrobrominated to 15a. The extract
was evaporated and chromatographed (eluent: gradient petro-
lether/ethyl acetate 100:0 to 70:30) to give 15a (15.5 mg, 71%), as
a white solid, mp 133e134 ꢁC; IR (KBr, cmꢀ1): nmax 1717, 1681, 1569,
4.8.4. Reaction with KI. A mixture of vinyl bromide 10k (14.3 mg,
0.046 mmol) and KI (22.7 mg, 0.137 mmol) in MeCN/H2O 5:1 (v/v)
(1.1 mL) was stirred at rt for 24 h. The product 11k was precipitated
by the addition of water and isolated by filtration (7.6 mg, 71%); Z/E
ratio: 100:0.
1422, 1271, 1178, 1036, 790; 1H NMR (200 MHz, CDCl3, 25 ꢁC):
(t, J¼7.2 Hz, 3H, CH3), 3.28 (s, 3H, NCH3), 4.23 (q, J¼7.2 Hz, 2H,
CH2O), 5.55 (s, 1H, ]CH), 5.75 (s, 1H, ]CH2), 6.42 (s, 1H, ]CH2); 13
NMR (50.3 MHz, CDCl3, 25 ꢁC):
14.3 (CH3), 30.1 (NCH3), 60.3
(CH2O), 90.8 (]CH), 116.5 (]CH2), 132.6 (C(5)]), 152.9 (C(2)]),
d 1.31
C
4.8.5. Reaction with NaF. A mixture of vinyl bromide 10k (28.3 mg,
0.09 mmol) and NaF (11.4 mg, 0.27 mmol) in DMF (1.4 mL) was
heated at 70 ꢁC for 46 h. The reaction mixture was cooled, water
d

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M. Baranac-Stojanovic et al. / Tetrahedron 66 (2010) 6873e6884
6881
was added and the product extracted with ethyl acetate. The or-
ganic layer was dried with anhydrous Na2SO4, evaporated and
chromatographed (eluent: gradient toluene/ethyl acetate 90:10 to
50:50) to give 11k (5.2 mg, 25%); Z/E ratio: 56:44.
95.1 (]CH), 119.0 (o-Ph), 123.1 (p-Ph), 128.9 (m-Ph), 139.5 (C1-Ph),
149.8 (C]), 165.0 (COamide), 170.1 (COester), 174.4 (COlactam); HRMS:
calcd for C13H13N2O4S (MþH) 293.05905, found 293.05909.
4.11. General procedure for synthesis of
4.8.6. Reaction with NaN3. A mixture of vinyl bromide 10k
(20.0 mg, 0.064 mmol) and NaN3 (8.3 mg, 0.13 mmol) in Me2CO/
H2O 7:1 (v/v) (1.5 mL) was stirred at rt for 24 h. The reaction mix-
ture was evaporated and the residue was partitioned between ethyl
acetate and water. The organic layer was dried with anhydrous
Na2SO4, evaporated and chromatographed (eluent: gradient tolu-
ene/ethyl acetate 90:10 to 50:50) to give 11k (5.0 mg, 34%); Z/E
ratio: 41:59.
5-ethoxycarbonylmethylidene-4-oxothiazolidines 19aee24,28
4.11.1. Method A. To a suspension, or a solution of 4-oxothiazoli-
dine 11aee (0.37 mmol) in CHCl3 (8 mL) 2% bromine solution in the
same solvent (ca. 1 equiv of bromine) was added dropwise at 0 ꢁC
(an ice bath) until complete disappearance of the starting material
(TLC). The bromine solution should be added at the rate, which is
nearly the same as the rate of disappearance of bromine colour in
the reaction mixture, though a yellow or orange colour can appear
before the addition is completed. The reaction mixture was
warmed to rt, pyridine (3.7 mmol) was added and the mixture
refluxed until the complete disappearance of the vinyl bromide
(TLC). Only in the case of compound 11d the mixture should be
stirred at rt for 24 h without pyridine added. In all cases the re-
action mixture was evaporated to dryness and the crude product
purified by column chromatography.
4.8.7. Reaction with acetylacetone. A mixture of acetylacetone
(22.1 mg, 0.22 mmol) and K2CO3 (30.5 mg, 0.22 mmol) in MeCN
(2.4 mL) was stirred at rt for 15 min and vinyl bromide 10k
(34.6 mg, 0.11 mmol) was added at once. The mixture was stirred at
rt for additional 30 h, evaporated and the residue was partitioned
between ethyl acetate and water. The organic layer was dried with
anhydrous Na2SO4, evaporated and chromatographed (eluent:
gradient toluene/ethyl acetate 90:10 to 50:50) to give 11k (6.1 mg,
24%); Z/E ratio: 53:47.
4.11.2. Method B. To a suspension, or a solution of vinyl bromide
10aee (0.21 mmol) in CHCl3 (2 mL) 2% solution of Et3N in the same
solvent (5 equiv of Et3N) was added dropwise at rt and the mixture
stirred at rt for additional period until complete disappearance of
the starting material (TLC). The reaction mixture was evaporated to
dryness and the crude product purified by column
chromatography.
4.9. Reaction of vinyl bromide 10k with KSCN
A mixture of vinyl bromide 10k (30.6 mg, 0.098 mmol) and
KSCN (9.5 mg, 0.098 mmol) in acetone (2.1 mL) was stirred at rt for
50 h. The mixture was evaporated and partitioned between ethyl
acetate and water. The organic layer was dried with anhydrous
Na2SO4, evaporated and chromatographed (eluent: gradient tolu-
ene/ethyl acetate 100:0 to 70:30) to give 17 (15.0 mg, 53%), as
a white solid, mp 197 ꢁC; Z/E ratio: 77:23; IR (KBr, cmꢀ1): nmax 3367,
3348, 3139, 2154, 1732, 1627, 1596, 1528, 1492, 1440, 1324, 1207,
4.12. General procedure for synthesis of 5-methylidene-
4-oxothiazolidines 20feg
1
1168, 840, 763, 694; H NMR (200 MHz, DMSO-d6, 25 ꢁC): (E iso-
To a suspension of vinyl bromide 10feg (0.2 mmol) in CHCl3
(4.4 mL) a 20-fold molar excess of pyridine was added and the
mixture refluxed until the disappearance of the vinyl bromide
(TLC). The reaction mixture was then cooled to rt and filtered (if
there was a precipitate). The filtrate was evaporated to 1.5e2.5 mL
and chromatographed.
mer)
2H, m-Ph), 7.63 (d, J¼7.4 Hz, 2H, o-Ph), 9.70 (s, 1H, NHamide), 11.78
(br s, 1H, NHlactam), (Z isomer)
d
3.93 (s, 2H, CH2), 7.13 (t, J¼7.4 Hz, 1H, p-Ph), 7.35 (t, J¼7.4 Hz
d
4.10 (s, 2H, CH2), 7.13 (t, J¼7.4 Hz,
1H, p-Ph), 7.35 (t, J¼7.4 Hz 2H, m-Ph), 7.63 (d, J¼7.4 Hz, 2H, o-Ph),
9.85 (s, 1H, NHamide), 12.09 (s, 1H, NHlactam); 13C NMR (50.3 MHz,
DMSO-d6, 25 ꢁC): EþZ isomer
d 34.4 (CH2), 80.3 and 82.1 (]CSCN),
112.0 (SCN), 121.4 and 121.8 (o-Ph), 124.1 and 124.4 (p-Ph), 128.7
(m-Ph), 138.4 and 138.8 (C1-Ph), 163.2 and 164.0 (C]), 167.9
(COamide), 175.0 (COlactam). Anal. Calcd for C12H9N3O2S2: C, 49.47; H,
3.11; N, 14.42; S, 22.01; found: C, 49.38; H, 3.26; N, 14.08; S, 21.63.
4.12.1. (Z)-(5-Methylidene-4-oxothiazolidin-2-ylidene)-N-phenyl-
ethanamide (20f). Reflux time: 21 h; purification: gradient toluene/
ethyl acetate 30:20 to 10:90; yield: 10%; pale yellow solid with no
sharp mp; IR (KBr, cmꢀ1): nmax 3303, 3209, 3065, 1709, 1663, 1596,
1549, 1500, 1314, 1244, 1157, 789, 752, 695; 1H NMR (200 MHz,
4.10. Reaction of vinyl bromide 10k with AcOK
DMSO-d6, 25 ꢁC):
d 5.84 (s, 1H, ]C(2)H), 5.93 (s, 1H, ]C(5)H), 6.10
(s, 1H, ]C(5)H), 7.01 (t, J¼7.2 Hz, 1H, p-Ph), 7.28 (t, J¼7.8 Hz, 2H, m-
A mixture of vinyl bromide 10k (24.9 mg, 0.08 mmol) and AcOK
(15.6 mg, 0.16 mmol) in acetone/H2O 7:1 v/v (1.4 mL) was stirred at
rt for 5 h. The mixture was evaporated and the residue was parti-
tioned between ethyl acetate and water. The organic layer was
dried with anhydrous Na2SO4, evaporated and chromatographed
(eluent: gradient toluene/acetone 100:0 to 80:20) to give 18
(6.5 mg, 28%; 4.4 mg was isolated pure, Z/E 91:9, and 2.1 mg in
a mixture with 11k), as a white solid, mp 103e105 ꢁC and 11k
(3.2 mg, 17%; isolated in a mixture with 18); IR (KBr, cmꢀ1): nmax
3353, 3271, 3208, 3145, 1715, 1671, 1623, 1598, 1547, 1499, 1443,
Ph), 7.60 (d, J¼7.8 Hz, 2H, o-Ph), 10.05 (s, 1H, NHamide), 12.06 (s, 1H,
13
NHlactam); C NMR (50.3 MHz, DMSO-d6, 25 ꢁC):
d 94.1 (]CH),
114.9 (]CH2), 119.0 (o-Ph), 123.1 (p-Ph), 129.0 (m-Ph), 134.8 (C
(5)]), 139.7 (C1-Ph), 147.6 (C(2)]), 165.0 and 165.9 (COamide and
COlactam); HRMS: calcd for C12H11N2O2S (MþH)þ : 247.0536; found:
247.0543.
4.12.2. (Z)-(5-Methylidene-4-oxothiazolidin-2-ylidene)-N-(2-phe-
nylethyl)ethanamide (20g). Reflux time: 64 h; purification: gradi-
ent petrolether/ethyl acetate 100:0 to 60:40; yield: 35%; pale
yellow solid with no sharp mp; IR (KBr, cmꢀ1): nmax 3288, 3090,
1
1317, 1210, 761, 693; H NMR (200 MHz, DMSO-d6, 25 ꢁC): (E iso-
mer)
d
2.15 (s, 3H, CH3), 5.45 (s, 1H, ]CH), 6.36 (s, 1H, CHS), 7.00 (t,
3060, 1697, 1652, 1586, 1498, 1455, 1308, 1188, 867, 828, 788, 746,
1
J¼7.2 Hz, 1H, p-Ph), 7.27 (t, J¼7.2 Hz, 2H, m-Ph), 7.56 (d, J¼7.2 Hz,
699; H NMR (200 MHz, DMSO-d6, 25 ꢁC):
d
2.72 (t, J¼7.4 Hz, 2H,
2H, o-Ph), 10.08 (s, 1H, NHamide), 11.98 (s, 1H, NHlactam), (Z isomer)
CH2Ph), NCH2 is masked by water, 5.70 (s, 1H, ]C(2)H), 5.76 (s, 1H,
]C(5)H), 6.04 (s, 1H, ]C(5)H), 7.16e7.34 (m, 5H, Ph), 8.08 (t,
J¼5.4 Hz, 1H, NHamide), 11.80 (s, 1H, NHlactam); 13C NMR (50.3 MHz,
d
2.13 (s, 3H, CH3), 5.88 (s, 1H, ]CH), 6.16 (s, 1H, CHS), 7.00 (t,
J¼7.2 Hz,1H, p-Ph), 7.27 (t, J¼7.2 Hz 2H, m-Ph), 7.56 (d, J¼7.2 Hz, 2H,
o-Ph), 10.02 (s, 1H, NHamide), 11.98 (s, 1H, NHlactam); 13C NMR
DMSO-d6, 25 ꢁC):
d 35.5 (CH2Ph), 40.3 (NCH2), 94.0 (]CH), 113.9 (]
(125 MHz, DMSO-d6, 25 ꢁC): (Z isomer)
d
20.4 (CH3), 73.3 (CHS),
CH2), 126.3 (p-Ph), 128.6 (o-Ph), 128.9 (m-Ph), 135.2 (C(5)]), 139.8

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M. Baranac-Stojanovic et al. / Tetrahedron 66 (2010) 6873e6884
6882
(C1-Ph), 145.2 (C(2)]), 165.8 and 166.2 (COamide and COlactam);
HRMS: calcd for C14H15N2O2S (MþH)þ : 275.0849; found: 275.0856.
123e125 ꢁC; Z/E ratio: 60:40; IR (KBr, cmꢀ1): 3445,1730,1674,1598,
1450, 1371, 1274, 1223, 1184, 1143, 1119, 868, 740; 1H NMR
(200 MHz, DMSO-d6, 25 ꢁC): (Z isomer)
CH3CH2), 1.69 (s, 3H, CH3CS), 2.15e2.25 (m, 2H, NCHA), 2.61e2.72
(m, 2H, NCHB), 3.60e3.64 (m, 4H, CH2O), 4.06 (q, J¼7.1 Hz, 2H,
d
1.18 (t, J¼7.1 Hz, 3H,
4.13. General procedure for synthesis of pyridinium salts
21kem23b
CH3CH2O), 5.47 (s, 1H, ]CH), 11.70 (br s, 1H, NH), (E isomer)
d 1.20
To a suspension, or a solution of vinyl bromide 10kem
(0.5 mmol) in CHCl3 a 10-fold molar excess of pyridine was added
and the mixture refluxed, or heated at 50 ꢁC, until the disappear-
ance of the starting bromide (TLC). The reaction mixture was
evaporated to dryness to afford the crude product.
(t, J¼7.0 Hz, 3H, CH3CH2), 1.76 (s, 3H, CH3CS), 2.15e2.25 (m, 2H,
NCHA), 2.61e2.72 (m, 2H, NCHB), 3.60e3.64 (m, 4H, CH2O), 4.10 (q,
J¼7.0 Hz, 2H, CH3CH2O), 5.28 (s, 1H, ]CH), 10.84 (br s, 1H, NH); 13
C
NMR (50.3 MHz, DMSO-d6, 25 ꢁC): (Z isomer)
d 14.6 (CH3CH2), 25.9
(CH3CS), 47.3 (CH2N), 59.3 (CH3CH2O), 65.8 (CH2O), 80.8 (C(CH3)S),
90.3 (]CH), 154.1 (C]), 166.8 (COester), 174.8 (COlactam), (E isomer)
4.14. General procedure for synthesis of 5-methyl-
d 14.6 (CH3CH2), 26.0 (CH3CS), 47.5 (CH2N), 59.8 (CH3CH2O), 65.6
5-morpholino-4-oxothiazolidines 22fej
(CH2O), 83.1 (C(CH3)S), 89.0 (]CH), 152.9 (C]), 166.8 (COester),
173.8 (COlactam). Anal. Calcd for C12H18N2O4S: C, 50.33; H, 6.34; N,
9.78; S, 11.20; found: C, 50.32; H, 6.26; N, 9.49; S, 11.33.
A mixture of vinyl bromide 10fej (0.2 mmol) and morpholine
(0.18 mL; 2.0 mmol) in CHCl3 (8.7 mL) was stirred at rt for 1.5e50 h
in dry atmosphere. The reaction mixture was then evaporated to
dryness and purified by column chromatography.
4.14.4. (Z)-(5-Methyl-5-morpholino-4-oxothiazolidin-2-ylidene)-1-
phenylethanone (22i). Reaction time: 6 h; purification: gradient
toluene/ethyl acetate 70:30 to 60:40; yield: 74%; white solid, mp
160e162 ꢁC (decomp.); IR (KBr, cmꢀ1): 3169, 3088, 1706, 1637, 1601,
4.14.1. (5-Methyl-5-morpholino-4-oxothiazolidin-2-ylidene)-N-phe-
nylethanamide (22f). Reaction time: 50 h; purification: gradient
toluene/ethyl acetate 60:40 to 0:100; yield: 90%; white solid, mp
165e167 ꢁC (decomp.); Z/E ratio: 13:87; IR (KBr, cmꢀ1): 3456, 3329,
3250, 3056,1720,1643,1596,1539,1498,1446,1382,1314,1245,1181,
1578, 1531, 1469, 1373, 1316, 1281, 1193, 1176, 1116, 857, 792, 762,
1
695; H NMR (200 MHz, DMSO-d6, 25 ꢁC):
d 1.72 (s, 3H, CH3),
2.21e2.31 (m, 2H, NCHA), 2.66e2.76 (m, 2H, NCHB), 3.60e3.62 (m,
4H, CH2O), 6.80 (s, 1H, ]CH), 7.48e7.60 (m, 3H, m- and p-Ph),
7.80e7.85 (m, 2H, o-Ph), 11.98 (br s, 1H, NH); 13C NMR (50.3 MHz,
1
1118, 849, 782, 736, 694; H NMR (200 MHz, DMSO-d6, 25 ꢁC): (E
isomer)
d
1.78 (s, 3H, CH3), 2.20e2.28 (m, 2H, NCHA), 2.66e2.72 (m,
DMSO-d6, 25 ꢁC):
d 25.6 (CH3), 47.3 (CH2N), 65.9 (CH2O), 79.7 (C
2H, NCHB), 3.61e3.65 (m, 4H, CH2O), 5.45 (s, 1H, ]CH), 7.04 (t,
J¼7.3 Hz, 1H, p-Ph), 7.31 (t, J¼7.8 Hz, 2H, m-Ph), 7.59 (d, J¼7.8 Hz, 2H,
(CH3)S), 95.9 (]CH), 127.2 (o-Ph), 129.0 (m-Ph), 132.4 (p-Ph), 138.6
(C1-Ph), 157.0 (C]), 175.4 (COlactam), 187.6 (COketone). Anal. Calcd for
C16H18N2O3S: C, 60.36; H, 5.70; N, 8.80; S, 10.07; found: C, 60.51; H,
5.77; N, 8.67; S, 10.27.
o-Ph), 9.95 (s,1H, NHamide),11.51 (s,1H, NHlactam), (Z isomer) d 1.68 (s,
3H, CH3), 2.20e2.28 (m, 2H, NCHA), 2.66e2.72 (m, 2H, NCHB),
3.61e3.65 (m, 4H, CH2O), 5.82 (s, 1H, ]CH), 6.99 (t, J¼7.4 Hz, 1H, p-
Ph), 7.27 (t, J¼7.8 Hz, 2H, m-Ph), 7.61 (d, J¼7.8 Hz, 2H, o-Ph), 9.88 (s,
1H, NHamide), 11.66 (s, 1H, NHlactam); 13C NMR (50.3 MHz, DMSO-d6,
4.14.5. (Z)-(5-Methyl-5-morpholino-4-oxothiazolidin-2-ylidene)
ethanonitrile (22j). Reaction time: 1.5 h; purification: gradient tol-
uene/ethyl acetate 100:0 to 20:80; yield: 83%; light brown oil; IR
(KBr, cmꢀ1): 3446, 3200, 2204, 1727, 1599, 1449, 1240, 1116, 796; 1H
25 ꢁC): (E isomer)
d
26.2 (CH3), 47.5 (CH2N), 65.7 (CH2O), 83.1 (C(CH3)
S), 92.6 (]CH), 119.5 (o-Ph), 123.5 (p-Ph), 129.0 (m-Ph), 139.2 (C1-
Ph), 148.8 (C]), 165.4 (COamide), 173.2 (COlactam), (Z isomer) 26.0
d
NMR (200 MHz, DMSO-d6, 25 ꢁC):
d 1.77 (s, 3H, CH3), 2.14e2.24 (m,
(CH3), 47.2 (CH2N), 65.9 (CH2O), 79.1 (C(CH3)S), 94.3 (]CH), 118.9 (o-
Ph), 122.8 (p-Ph), 128.9 (m-Ph), 140.0 (C1-Ph), 149.5 (C]), 165.2
(COamide), 174.8 (COlactam). Anal. Calcd for C16H19N3O3S: C, 57.64; H,
5.74; N, 12.60; S, 9.62; found: C, 57.88; H, 5.62; N, 12.27; S, 9.64.
2H, NCHA), 2.62e2.72 (m, 2H, NCHB), 3.60e3.64 (m, 4H, CH2O), 5.00
(s, 1H, ]CH), 10.54 (br s, 1H, NH); 13C NMR (50.3 MHz, DMSO-d6,
25 ꢁC):
d 29.2 (CH3), 49.4 (CH2N), 66.2 (CH2O), C(CH3)S uncertain,
65.9 (]CH), 119.2 (CN), 155.5 (C]), 169.8 (COlactam); HRMS; calcd
for C10H14N3O2S (MþH)þ: 240.0801; found: 240.0791.
4.14.2. (5-Methyl-5-morpholino-4-oxothiazolidin-2-ylidene)-N-(2-
phenylethyl)ethanamide (22g). Reaction time: 48 h; purification:
gradient toluene/ethyl acetate 60:40 to 0:100; yield: 62%; yellowish
oil; Z/E ratio: 44:56; IR (KBr, cmꢀ1): 3310, 3230, 3084, 3028, 1720,
1637, 1592, 1546, 1452, 1371, 1277, 1177, 1119, 869, 747, 701; 1H NMR
4.15. General procedure for synthesis of 5-anilino-
4-oxothiazolidines 26kel
A mixture of the crude pyridinium salt 21kel and aniline in
a MeOH/H2O was stirred at rt. The reaction mixture was filtered,
brown precipitate was washed with water, dried and purified by
column chromatography.
(200 MHz, DMSO-d6, 25 ꢁC): (E isomer)
d 1.75 (s, 3H, CH3), 2.16e2.27
(m, 2H, NCHA), 2.63e2.76 (m, 4H, NCHB and CH2Ph), NCH2 is masked
by water, 3.59e3.64 (m, 4H, CH2O), 5.22 (s, 1H, ]CH), 7.20e7.36 (m,
5H, Ph), 8.03 (t, J¼5.6 Hz, 1H, NHamide), 11.70 (br s, 1H, NHlactam), (Z
isomer)
d
1.63 (s, 3H, CH3),2.17e2.26(m, 2H, NCHA), 2.63e2.74(m, 4H,
4.15.1. (5-Anilino-4-oxothiazolidin-2-ylidene)-N-phenylethanamide
(26k). Pyridinium salt 21k (22 mg), aniline (0.005 mL, 0.056 mmol),
MeOH (1 mL)/H2O (0.5 mL); stirred for 1 h and 45 min; crude 26k-Z
(78%), mp 180e184 ꢁC; purification: gradient petrolether/ethyl ace-
tate 60:40 to 0:100; yield 63%; pale orange solid, mp 180e184 ꢁC; Z/E
ratio: 76:24; IR (KBr, cmꢀ1): nmax 3464, 3412, 3298, 3056, 1704, 1658,
1600,1578,1539,1496,1440,1318,1244,1154, 796, 754, 693; 1H NMR
NCHB andCH2Ph),NCH2 ismaskedbywater, 3.56e3.63(m, 4H, CH2O),
5.56 (s, 1H, ]CH), 7.20e7.33 (m, 5H, Ph), 7.89 (t, J¼5.6 Hz, 1H,
NHamide),11.38(s,1H, NHlactam);
13CNMR(50.3 MHz,DMSO-d6, 25 ꢁC):
(E isomer) d 26.2 (CH3), 35.4 (CH2Ph), 40.8 (NHCH2) 47.5 (CH2N), 65.7
(CH2O), 83.1 (C(CH3)S), 92.3 (]CH), 126.4 (p-Ph), 128.6 (o-Ph), 128.9
(m-Ph), 139.6 (C1-Ph), 146.6 (C]), 166.9 (COamide), 172.9 (COlactam), (Z
isomer)
d
26.1 (CH3), 35.6 (CH2Ph), 40.4 (NHCH2), 47.1 (CH2N), 65.9
(200 MHz, DMSO-d6, 25 ꢁC): (Z isomer)
d 5.84 (s, 1H, ]CH), 5.91 (d,
(CH2O), 78.7 (C(CH3)S), 94.2 (]CH), 126.3 (p-Ph), 128.6 (o-Ph), 128.9
(m-Ph), 139.9 (C1-Ph), 146.9 (C]), 166.3 (COamide), 174.6 (COlactam);
HRMS: calcd for C18H23N3O3S (Mþ): 361,1460, found: 361,1466.
J¼10.0 Hz, 1H, CHS), 6.65e6.75 (m, 3H, o- and p-aniline), 6.79 (d,
J¼10.0 Hz, 1H, NHamine), 6.97 (t, J¼7.4 Hz,1H, p-Ph), 7.13e7.29 (m, 4H,
m-aniline and m-Ph), 7.57 (d, J¼7.4 Hz, 2H, o-Ph), 9.87 (s, 1H, NHa-
mide), 11.71 (s, 1H, NHlactam), (E isomer, visible signals, others are
4.14.3. Ethyl
(5-methyl-5-morpholino-4-oxothiazolidin-2-ylidene)
masked by the signals of the Z isomer) d 5.41 (s, 1H, ]CH), 6.30 (d,
ethanoate (22h). Reaction time: 6 h; purification: gradient toluene/
ethyl acetate 80:20 to 50:50; yield: 90%; white solid, mp
1H, CHS, J¼10.6 Hz), 9.94 (s, 1H, NHamide), 11.52 (s, 1H, NHlactam); 13
C
NMR (50.3 MHz, DMSO-d6, 25 ꢁC): (Z isomer)
d 60.0 (CHS), 94.0

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M. Baranac-Stojanovic et al. / Tetrahedron 66 (2010) 6873e6884
6883
(]CH), 113.6 (o-aniline),118.3 (p-aniline), 118.8 (o-Ph), 122.7 (p-Ph),
128.9 (m-Ph), 129.4 (m-aniline), 140.0 (C1-Ph), 146.2 (C1-aniline),
(m, 5H, Ph), 8.00 (s, J¼5.6 Hz, 1H, NHamide), 11.54 (s, 1H, NHlactam);
13C NMR (50.3 MHz, DMSO-d6, 25 ꢁC):
35.5 (CH2Ph), 40.3 (NCH2),
d
151.3 (C]), 165.2 (COamide), 172.8 (COlactam), (E isomer)
d
61.8 (CHS),
55.0 (CH3), 81.9 (CHS), 95.1 (]CH), 126.3 (p-Ph), 128.6 (o-Ph), 128.9
(m-Ph), 139.8 (C1-Ph), 147.3 (C]), 166.1 (COamide), 171.3 (COlactam).
Anal. Calcd for C14H16N2O3S: C, 57.52; H, 5.52; N, 9.58; S, 10.97;
found: C, 57.20; H, 5.50; N, 9.51; S, 11.08.
92.7 (]CH),113.8 (o-aniline), 119.2 (p-aniline), 119.5 (o-Ph), 123.5 (p-
Ph),129.1 (m-Ph),129.5 (m-aniline),139.2 (C1-Ph),145.6 (C1-aniline),
150.3 (C]), 165.2 (COamide), 171.2 (COlactam). Anal. Calcd for
C17H15N3O2S: C, 62.75; H, 4.65; N, 12.91; S, 9.85; found: C, 62.58; H,
4.76; N, 12.79; S, 9.91.
4.17. General procedure for synthesis of 5-morpholino-
4-oxothiazolidines 28kel
4.15.2. (5-Anilino-4-oxothiazolidin-2-ylidene)-N-(2-phenylethyl)
ethanamide (26l). Pyridinium salt 21l (30.3 mg), aniline (0.006 mL,
0.071 mmol), MeOH (1.3 mL)/H2O (0.65 mL); stirred for 30 min; crude
26l-E (89%), mp 189e191 ꢁC; purification: gradient toluene/ethyl ac-
etate 60:40 to 0:100; yield 86%; pale yellow solid, mp 189e191 ꢁC; Z/E
ratio: 20:80; IR (KBr, cmꢀ1): nmax 3338, 3284, 3062, 1712, 1629, 1598,
1563, 1314, 1281, 1227, 1190, 1137, 812, 749, 698; 1H NMR (200 MHz,
A mixture of the crude pyridinium salt 21kel and morpholine in
CHCl3 was stirred at rt in dry atmosphere. After evaporation of the
solvent under reduced pressure, the residue was purified by col-
umn chromatography.
4.17.1. (5-Morpholino-4-oxothiazolidin-2-ylidene)-N-phenyl-
ethanamide (28k). Pyridinium salt 21k (90.4 mg), morpholine
(0.08 mL, 0.91 mmol), CHCl3 (9 mL); stirred for 25 h; purification:
gradient toluene/ethyl acetate 80:20 to 0:100; yield 91%; pale or-
ange solid, mp 160e162 ꢁC (decomp.); Z/E ratio: 9:91; IR (KBr, cmꢀ1):
nmax 3345, 3172, 3033,1718,1655,1599,1545,1490, 1441,1310,1254,
1182, 1131, 1108, 857, 776, 750, 700; 1H NMR (200 MHz, DMSO-d6,
DMSO-d6, 25 ꢁC): (E isomer)
d
2.74 (t, J¼7.3 Hz, 2H, CH2Ph), NCH2 is
masked by water, 5.19 (s, 1H, ]CH), 6.24 (d, J¼10.5 Hz, 1H, CHS), 6.68
(d, J¼7.5 Hz, 2H, o-aniline), 6.75 (t, J¼7.5 Hz, 1H, p-aniline), 7.03 (d,
J¼10.5 Hz, 1H, NHamine), 7.15e7.34 (m, 7H, m-aniline and Ph), 8.01 (t,
J¼5.6 Hz, 1H, NHamide), 11.72 (s, 1H, NHlactam), (Z isomer)
d 2.69 (t,
J¼7.4 Hz, 2H, CH2Ph), NCH2 is masked by water, 5.60 (s,1H, ]CH), 5.82
(d, J¼9.4 Hz, 1H, CHS), 6.63e6.76 (m, 4H, o-aniline, p-aniline and
NHamine), 7.12e7.32 (m, 7H, m-aniline and Ph), 7.88 (t, J¼5.5 Hz, 1H,
NHamide),11.44 (s,1H, NHlactam); 13C NMR (50.3 MHz, DMSO-d6, 25 ꢁC):
25 ꢁC): (E isomer)
d 2.24e2.38 (m, 2H, NCHA), 2.59e2.70 (m,
Jaxeeq¼11.4 Hz, 2H, NCHB), 3.60e3.65 (m, 4H, CH2O), 5.44 (s, 1H,
]CH), 5.78 (s, 1H, CHS), 7.04 (t, J¼7.3 Hz, 1H, p-Ph), 7.31 (t, J¼7.9 Hz,
2H, m-Ph), 7.58 (d, J¼7.9 Hz, 2H, o-Ph), 9.94 (s, 1H, NHamide),11.49 (s,
(E isomer) d 35.3 (CH2Ph), NCH2 is masked by DMSO, 61.7 (CHS), 92.5
(]CH), 113.8 (o-aniline), 119.0 (p-aniline), 126.4 (p-Ph), 128.6 (o-Ph),
128.9 (m-Ph),129.5 (m-aniline),139.6(C1-Ph),145.7(C1-aniline),148.2
1H, NHlactam), (Z isomer) d 2.26e2.36 (m, 2H, NCHA), 2.65e2.72 (m,
2H, NCHB), 3.59e3.63 (m, 4H, CH2O), 5.38 (s, 1H, CHS), 5.82 (s, 1H,
]CH), 6.99 (t, J¼7.3 Hz, 1H, p-Ph), 7.27 (t, J¼7.8 Hz, 2H, m-Ph), 7.60
(d, J¼7.8 Hz, 2H, o-Ph), 9.89 (s, 1H, NHamide), 11.71 (s, 1H, NHlactam);
(C]),166.9 (COamide),170.9 (COlactam), (Z isomer) d 35.6 (CH2Ph), NCH2
is masked by DMSO, 59.8 (CHS), 93.9 (]CH),113.6 (o-aniline),118.2 (p-
aniline), 126.3 (p-Ph), 128.6 (o-Ph), 128.8 (m-Ph), 129.3 (m-aniline),
139.8 (C1-Ph), 146.2 (C1-aniline), 148.7 (C]), 166.4 (COamide), 172.6
(COlactam). Anal. Calcd for C19H19N3O2S: C, 64.57; H, 5.42; N, 11.89; S,
9.07; found: C, 64.50; H, 5.43; N, 11.83; S, 9.43.
13C NMR (50.3 MHz, DMSO-d6, 25 ꢁC): (E isomer)
d 48.7 (CH2N), 65.6
(CH2O), 75.2 (CHS), 92.9 (]CH),119.5 (o-Ph),123.5 (p-Ph),129.0 (m-
Ph), 139.2 (C1-Ph), 149.9 (C]), 165.3 (COamide), 170.3 (COlactam), (Z
isomer)
d 48.5 (CH2N), 65.9 (CH2O), 72.8 (CHS), 94.6 (]CH), 118.9
(o-Ph), 122.8 (p-Ph), 128.9 (m-Ph), 140.0 (C1-Ph), 150.8 (C]), 165.2
(COamide), 171.9 (COlactam). Anal. Calcd for C15H17N3O3S: C, 56.41; H,
5.37; N, 13.16; S, 10.04; found: C, 56.41; H, 5.24; N, 12.97; S, 10.07.
4.16. General procedure for synthesis of 5-methoxy-
4-oxothiazolidines 27kel
A mixture of the crude pyridinium salt 21kel and anhydrous
K2CO3 in MeOH was refluxed for 24 h in dry atmosphere. After
cooling to rt the reaction mixture was evaporated to dryness and
purified by column chromatography.
4.17.2. 5-Morpholino-4-oxothiazolidin-2-ylidene-N-(2-phenylethyl)
ethanamide (28l)26. Pyridinium salt 21l (94.3 mg), morpholine
(0.08 mL, 0.91 mmol), CHCl3 (8.7 mL); stirred for 6.5 h; purification:
gradient toluene/ethyl acetate 40:60 to 0:100; yield 87%; pale
yellow solid, mp 114e115 ꢁC; Z/E ratio: 18:82; IR (KBr, cmꢀ1): nmax
3437, 3267, 3212, 3077,1718,1635, 1565, 1454, 1280, 1249, 1113, 858,
4.16.1. (Z)-(5-Methoxy-4-oxothiazolidin-2-ylidene)-N-phenyl-
ethanamide (27k). Pyridinium salt 21k (50.2 mg), anhydrous K2CO3
(7.0 mg, 0.05 mmol), MeOH (3.7 mL); purification: gradient petro-
lether/ethyl acetate 20:80 to 0:100; yield 69%; yellowish solid, mp
155e158 ꢁC; IR (KBr, cmꢀ1): nmax 3319, 3146, 3098, 3021, 1720, 1656,
1599, 1549, 1497, 1441, 1315, 1242,1194, 1156, 850, 802, 752, 689; 1H
1
831, 768, 703; H NMR (200 MHz, DMSO-d6, 25 ꢁC): (E isomer)
d
2.21e2.31 (m, 2H, NCHA), 2.57e2.76 (m, 4H, NCHB and CH2Ph),
NCH2 is masked by water, 3.61 (t, J¼4.4 Hz, 4H, CH2O), 5.23 (s, 1H,
]CH), 5.72 (s, 1H, CHS), 7.16e7.34 (m, 5H, Ph), 8.02 (t, J¼5.6 Hz, 1H,
NHamide), 11.70 (s, 1H, NHlactam), (Z isomer) 2.24e2.30 (m, 2H,
NCHA), 2.62e2.74 (m, 4H, NCHB and CH2Ph), 3.24e3.34 (m, 2H,
NCH2), 3.57e3.60 (m, 4H, CH2O), 5.30 (s, 1H, CHS), 5.58 (s, 1H,
]CH), 7.16e7.34 (m, 5H, Ph), 7.90 (t, J¼5.5 Hz,1H, NHamide), 11.42 (s,
NMR (200 MHz, DMSO-d6, 25 ꢁC): CH3 is masked by water,
d 5.66 (s,
1H, CHS), 5.86 (s, 1H, ]CH), 7.00 (t, J¼7.4 Hz, 1H, p-Ph), 7.27 (t,
J¼7.8 Hz, 2H, m-Ph), 7.59 (d, J¼7.6 Hz, 2H, o-Ph), 9.96 (s, 1H,
NHamide), 11.79 (s, 1H, NHlactam); 13C NMR (50.3 MHz, DMSO-d6,
13
1H, NHlactam); C NMR (50.3 MHz, DMSO-d6, 25 ꢁC): (E isomer)
25 ꢁC):
d
55.2 (CH3), 82.0 (CHS), 95.2 (]CH), 118.9 (o-Ph), 123.0
d
35.3 (CH2Ph), 40.3 (NHCH2), 48.6 (CH2N), 65.8 (CH2O), 75.1 (CHS),
92.7 (]CH), 126.4 (p-Ph), 128.6 (o-Ph), 128.8 (m-Ph), 139.6 (C1-Ph),
147.7 (C]), 166.8 (COamide), 170.0 (COlactam), (Z isomer) 35.6
(p-Ph), 128.9 (m-Ph), 139.7 (C1-Ph), 149.8 (C]), 165.0 (COamide),
171.4 (COlactam). Anal. Calcd for C12H12N2O3S: C, 54.53; H, 4.58; N,
10.60; S, 12.13; found: C, 54.27; H, 4.57; N, 10.52; S, 12.24.
d
(CH2Ph), 40.4 (NHCH2), 48.4 (CH2N), 65.9 (CH2O), 72.6 (CHS), 94.5
(]CH),126.3 (p-Ph),128.6 (o-Ph),128.8 (m-Ph),139.8 (C1-Ph),148.1
(C]), 166.3 (COamide), 171.7 (COlactam). Anal. Calcd for C17H23N3O4S
(9gꢂH2O): C, 55.87; H, 6.34; N, 11.50; S, 8.77; found: C, 55.90; H,
6.34; N, 11.42; S, 9.05.
4.16.2. (Z)-(5-Methoxy-4-oxothiazolidin-2-ylidene)-N-(2-phenyl-
ethyl)ethanamide (27l). Pyridinium salt 21l (40.4 mg), anhydrous
K2CO3 (5.3 mg, 0.04 mmol), MeOH (2.8 mL); purification: gradient
toluene/ethyl acetate 60:40 to 0:100; yield 66%; yellowish solid, mp
147e149 ꢁC; IR (KBr, cmꢀ1): nmax 3312, 3196, 3055, 1722, 1641, 1563,
1461, 1305, 1186, 1101, 817, 761, 699; 1H NMR (200 MHz, DMSO-d6,
Acknowledgements
25 ꢁC):
masked by water, 5.60 and 5.64 (2ꢂs, 1H, ]CH and CHS), 7.19e7.34
d
2.71 (t, J¼7.3 Hz, 2H, CH2Ph), 3.30 (s, 3H, CH3), NCH2 is
This research was partially supported by the Ministry of Science
of the Republic of Serbia, Grant No. 142007 (to R.M.).

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M. Baranac-Stojanovic et al. / Tetrahedron 66 (2010) 6873e6884
20. Braverman, S.; Pechenick-Azizi, T.; Major, D. T.; Sprecher, M. J. Org. Chem. 2007,
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