2-Alkylidene-4-oxothiazolidine vinyl bromides: Versatile precursors for C(5) functionalization via pyridine-assisted bromine transfer

Article abstract of DOI:10.1055/s-2006-933136

A series of structurally diverse vinyl bromides, derived from push-pull 2-alkylidene-4-oxoffciazolidines, undergoes pyridine-assisted bromine transfer from the C=C bond to the C(5) position, enabling different C(5) functionalization. The type of the produ

Full text of DOI:10.1055/s-2006-933136

LETTER
729
2-Alkylidene-4-oxothiazolidine Vinyl Bromides: Versatile Precursors for C(5)
Functionalization via Pyridine-Assisted Bromine Transfer
2
-Alkylidene-4-Oxothi
a
azolidine
V
r
inyl
B
ro
i
mides:
j
Precur
a
sors for
C
(5)-Fun
B
ctionalization aranac Stojanović,*a,b Rade Markovića,b
a
Faculty of Chemistry, University of Belgrade, Studentski trg 16, P.O. Box 158, 11001 Belgrade, Serbia and Montenegro
b
Centre for Chemistry ICTM, P.O. Box 473, 11000 Belgrade, Serbia and Montenegro
Fax +381(11)636061; E-mail: mbaranac@helix.chem.bg.ac.yu
Received 1 December 2005
To our knowledge, only one example of an intramolecular
bromine migration has been reported, i.e., from uracil
to phenyl ring as a side reaction in the S→N-type
Smiles rearrangement of 5-bromo-3-methyl-6-[2-(methyl-
Abstract: A series of structurally diverse vinyl bromides, derived
from push–pull 2-alkylidene-4-oxothiazolidines, undergoes pyri-
dine-assisted bromine transfer from the C=C bond to the C(5) posi-
tion, enabling different C(5) functionalization. The type of the
product depends on the C(5) substituent and, in some cases, the amino)phenylthio]uracil,17 however, without further
transformation is affected by the substituent at the C=C bond.
examination.
Key words: push–pull alkenes, 2-alkylidene-4-oxothiazolidines,
pyridine, bromine transfer, functionalization
We report herein a generality of this rare bromine transfer
reaction by demonstrating its applicability to 2-alkyl-
idene-4-oxothiazolidine vinyl bromides 2, 5 and 6, with
different substitution pattern at the C(5) position and exo-
Vinyl bromides, in which bromine is attached to an a-po-
sition of a double bond possessing push–pull character,
have been widely used in metal-catalyzed coupling reac-
tions, some being steps toward a synthesis of different
biologically active substances.1–7 Nucleophilic substitu-
tion of bromine in compounds of this type has also been
reported,8–11 whereas debromination has been achieved by
catalytic hydrogenization,12,13 or by Bu3SnH.14 Our recent
studies15,16 on reactivity of push–pull (Z)-2-alkylidene-5-
ethoxycarbonylmethyl-4-oxothiazolidines 1 have shown
that preformed, or in situ formed vinyl bromides 2 under-
go an easy cleavage of the C–Br bond and bromine trans-
fer to the C(5) position, yielding, after HBr elimination, 4-
oxothiazolidines 4 with two exocyclic double bonds
(Scheme 1).
cyclic C=C bond. In addition, the synthetic potential of
this methodology, affording new pyridinium salts 7 when
applied on precursors 5 (Figure 1), was directed towards
the preparation of C(5)-functionalized 4-oxothiazolidines
by nucleophilic displacement of pyridine as a notoriously
poor leaving group.
H
O
H
R
N
H
N
H
N
O
O
Br
R
Br
R
+
N
S
–
Br
S
S
Me
5
6
7
Figure 1
Consequently, an efficient regioselective bromination of
5-unsubstituted and 5-methyl-2-alkylidene-4-oxothiazol-
idines was extended to unreported precursors 5 and 6
(Table 1),18 by making appropriate changes in the reaction
conditions previously employed for the preparation of
vinyl bromides 2 (Scheme 1). The regioselectivity is at-
tributed to a higher nucleophilic reactivity of the electron-
rich center Ca toward various brominating reagents as
compared to the nucleophilic position C(5). According to
Satzinger19,20 and Zaleska21 the corresponding N-sub-
stituted 2-alkylidene-4-oxothiazolidines were brominated
exclusively at the C(5) position.
H
N
H
N
O
O
Br
R
H
R
Br2
β
α
S
S
O
O
EtO
EtO
2
1
H
N
H
N
O
O
H
R
H
– HBr
Br
S
S
R
O
O
EtO
EtO
3
4
Scheme 2 illustrates the most relevant results obtained in
pyridine-assisted bromine transfer of vinyl bromides 2, 5
and 6, giving rise to the C(5)-functionalized derivatives 4,
7 and 8, respectively, involving also the conversion of the
piridinium salts 7 to 5-substituted derivatives 9–11.22 Re-
ferring to our preceding results,15,16 all vinyl bromides 2,
irrespective of the type of the substituent at the C=C bond,
were transformed to the stable 4-oxothiazolidines 4
(Scheme 1). Vinyl bromides 6, having methyl group at the
R = CONHPh, CONHCH2CH2Ph, COPh
Scheme 1
SYNLETT 2006, No. 5, pp 0729–0732
Advanced online publication: 09.03.2006
DOI: 10.1055/s-2006-933136; Art ID: G36905ST
© Georg Thieme Verlag Stuttgart · New York
1
7.
0
3.
2
0
0
6

730
M. Baranac Stojanović, R. Marković
LETTER
H
N
H
N
C(5) position, were similarly converted to the less stable
5-methylidene-4-oxothiazolidines 8 (Scheme 2). How-
ever, this transformation is restricted to the bromides 6a,b
containing an amide substituent at the C=C bond. Com-
pared to the facile rearrangement of 5-ethoxycarbonyl-
methyl-4-oxothiazolidine vinyl bromides 2, favored by
the easy HBr elimination of the intermediates 3 and for-
mation of the stable derivatives 4, the analogous reaction
of 5-unsubstituted vinyl bromides 5 was rather slow. The
presence of an amide, or ester substituent at the C=C bond
was necessary for this transformation.
O
O
Br
R
Br
R
S
S
Me
6a,b
5a–c
2a–e
pyridine (20 equiv)
CHCl3, reflux
24–48 h
pyridine (10 equiv)
CHCl3, reflux
6-59 h
pyridine (10 equiv)
CHCl3, reflux
3–7 d
4a–e
H
H
O
O
H
N
H
N
a: R = CONHPh
b: R = CONH(CH2)2Ph
c: R = CO2Et
+
N
S
R
S
R
H2C
Br–
d: R = COPh
e: R = CN
Table 1 Synthesis of Vinyl Bromides 5 and 6
7a,c
ii
8a,b
iii
i
Compound
R
Mp (°C)
139–140
140–142
103–105
118–120
163
Yield (%)
H
N
H
N
H
(Z)- + (E)-5a
(Z)- + (E)-5b
(Z)- + (E)-5c
(Z)- + (E)-5d
(Z)- + (E)-5e
(Z)- + (E)-6a
(Z)- + (E)-6b
(Z)- + (E)-6c
(Z)- + (E)-6d
(Z)- + (E)-6e
a Oily compound.
CONHPh
CONH(CH2)2Ph
CO2Et
91
79
76
72
65
64
99b
68
54
84
O
O
N
O
H
H
R
H
S
R
S
N
S
R
O
HN
Ph
CH3
O
9a,b
10a,b
11a,b
COPh
Scheme 2 Reagents and conditions: (i) morpholine (excess),
CHCl3, r.t., 6.5–25 h; (ii) aniline (excess), MeOH–H2O, r.t., 0.5–1.45
h; (iii) MeOH, K2CO3, reflux, 24 h.
CN
CONHPh
CONH(CH2)2Ph
CO2Et
188–194
a
–
bond, were then employed as substrates for replacing
pyridine by selected nucleophiles (Scheme 2, i–iii).The
relevant study by Hutchinson and Tarbell,25 regarding the
determination of the equilibrium constants between N-
benzyl-N-methylpiperidinium halides and pyridine and N-
benzylpyridinium salts and N-methylpiperidine suggested
that unsubstituted pyridine in pyridinium salts can be a
potential leaving group. A couple of examples involving
nucleophilic displacements with pyridine as a leaving
group has been reported so far.26,27
75–77
211–212
124
COPh
CN
b Yield of the crude product.
Under the conditions defined,23 5b was transformed into
1
a single product, proved convincingly by H NMR and
13C NMR data to be the new pyridinium salt, (Z)-[4-oxo-
5-(pyridinium-1-yl)thiazolidine-2-ylidene)-N-(2-phenyl-
ethyl)ethanamide bromide (7b, Table 2).
Table 2 C(5) Functionalization of Parent 4-Oxothiazolidines via
Bromine Transfer of Vinyl Bromides 5 and 6
Compound
(Z)-7a
R
Mp (°C)
198–200
127–128
Yield (%)a
89
The equally slow rearrangement of vinyl bromide 5a af-
forded, through visibly progressive precipitation, the cor-
responding pyridinium salt (Z)-7a24 (Table 2), while in
the case of the enamino ester 5c (R = CO2Et) the identical
conversion to 7c took place with low efficiency (14%).
CONHPh
(Z)-7b
CONH(CH2)2Ph
CONHPh
87
b
(Z)-8a
–
7
b
Taking into account the structural similarities of 5 and 7,
the main diagnostic difference in 1H NMR and 13C NMR
spectra, apart from the signals of the pyridine ring in 7, is
observed in the position of HC(5) and C(5) signals. For
example, the HC(5) chemical shifts of 5a and 5b are ob-
served at d = 3.86–3.99 and 3.79–3.95 ppm (DMSO-d6),
whereas the corresponding downfield shifts in 7a and 7b
at d = 7.06 and 7.09 ppm, respectively, indicate the s-neg-
ative effect of the pyridinium ring. In addition, the C(5)
signals of 7a and 7b at around d = 72 ppm and upfield
chemical shifts (ca. 38 ppm) in the case of 5a and 5b fit
the above correlation.
(Z)-8b
CONH(CH2)2Ph
CONHPh
–
19
(Z)- + (E)-9a
(Z)- + (E)-9b
(Z)- + (E)-10a
(Z)- + (E)-10b
(Z)-11a
160–162
114–115
180–184
189–191
155–158
147–149
91,c 82d
87,c 69d
63,c 57d
86,c 68d
69,c 63d
66,c 65d
CONH(CH2)2Ph
CONHPh
CONH(CH2)2Ph
CONHPh
(Z)-11b
CONH(CH2)2Ph
a Yield of chromatographed product.
b The mp is not sharp.
c Yield based on vinyl bromides 5a,b.
The unsubstituted pyridinium salts 7a and 7b, with the 4-
oxothiazolidine moiety connected through the C(5)–N
d Yield based on the parent unbrominated 4-oxothiazolidines.
Synlett 2006, No. 5, 729–732 © Thieme Stuttgart · New York

LETTER
2-Alkylidene-4-oxothiazolidine Vinyl Bromides: Versatile Precursors for C(5) Functionalization
731
However, Katritzky et al.28 reported in a series of papers nucleophilic pyridine leads to synthetically useful pyri-
the substitution of 2,4,6-triphenylpyridine by neutral and dinium salts 7.
anionic nucleophiles from various N-substituted 2,4,6-
Finally, when a better nucleophile, such as morpholine,
triphenylpyridinium cations. Within this context, the reac-
was used as the bromine transfer agent, 5-methyl deriva-
tion of unsubstituted pyridinium salts 7a and 7b with
tives 6a–e were transformed, presumably via the alkyl
neutral nucleophiles, such as morpholine, aniline and
bromide 15, into the substitution products 5-methyl-5-
methanol, forming the substitution products 9–11 in good
morpholino-4-oxothiazolidines 16a–e in high yields
to excellent yields (Table 2), represents an extension of
(Table 3).
the pyridinium salt chemistry. Spectroscopic data and
elemental analyses were consistent with the structures
Table 3 Morpholine-Assisted Bromine Transfer of 2-Alkylidene-5-
9–11.29 Despite the fact that pyridine is a poor leaving methyl-4-oxothiazolidine Vinyl Bromides 6
group and that the pyridinium ring is susceptible to
H
N
O
O
N
nucleophilic attack at the 2-, 4- and 6-positions,30 in some
H
R
H
cases followed by ring cleavage,31,32 we did not observe a
decrease in effectiveness of these substitution reactions
affording new 5-amino and 5-alkoxy-2-alkylidene-4-
oxothiazolidines.
O
Br
R
(10 equiv)
N
N
S
Me
H
CHCl3, r.t., 4–50 h
O
S
Me
16a–e
6a–e
Yield (%)a
The most likely pathway for the pyridine-assisted vinyl
bromide rearrangement of 5 and 6 to the C(5)-functional-
ized 4-oxothiazolidines is depicted in Scheme 3.
Compound
(Z)- + (E)-16a
(Z)- + (E)-16b
(Z)- + (E)-16c
(Z)-16d
R
Mp (°C)
165-167
CONHPh
CONH(CH2)2Ph
CO2Et
90
62
90
74
78c
b
–
H
N
H
N
Py–Br+–Py
O
O
Br
R
b
pyridine (xs)
–
–
+
Py+–Br + Py
S
S
R1
R1
R
COPh
160–162
5 (R1 = H)
6 (R1 = Me)
13
12
b
(Z)-16e
CN
–
pyridine-assisted
proton transfer
a Yield of chromatographed product.
b Oily compound.
H
N
H
O
O
H
R
H
R
N
c Decomposition occurred during purification.
13
Br
R1
–
S
R1
S
14
15
In conclusion, we have shown that the bromine transfer
from the C=C bond to the C(5) position, as a general pro-
cess for a number of 2-alkylidene-4-oxothiazolidine vinyl
bromides, can be efficiently used for the C(5) functional-
ization of push–pull 2-alkylidene-4-oxothiazolidines. We
hope that the synthetic potential and scope of the bromine
transfer can be expanded to other structurally related
push–pull enaminones and enamino nitriles.
pyridine
– HBr
(R1 = Me)
Py
H
O
H
N
(R1 = H)
H
N
O
H
R
+
N
S
R
–
Br
S
8
H2C
7
Scheme 3
Heterolytic cleavage of the C–Br bond, initiated by pyri-
dine, results in carbanion 12 and bis(pyridine)bromonium
cation 13 [in equilibrium with mono(pyridine)bromonium
species]. Similar cleavage of C–Br bond, formation of a
vinyl anion, represented by an allene-type structure, and
its subsequent protonation was reported by Singh et al.11
in the reaction of a-benzoyl-a-bromoketene S,S-acetal
with morpholine. In the next step, carbanion 14, formed
from 12 by the pyridine-assisted C(5)-proton transfer to
the vinylic position, is brominated by bromonium species
13 to form alkyl bromide 15. After completion of the bro-
mine transfer, the next step depends on the type of the sub-
stituent present at the C(5) atom and, in some cases, on the
substituent at the exocyclic double bond. In the systems 2
and 6, bearing CH2CO2Et or CH3 group respectively, de-
hydrobromination occurs and another C=C bond is intro-
duced into the C(5) position. Since elimination is not
possible for the intermediate 15, generated from 5
(R1 = H), then the slow bromide substitution with weakly
Acknowledgment
Partial financial support by the Ministry of Science of the Republic
of Serbia, grant no. 1709 (to R.M.) is acknowledged.
References and Notes
(1) Pontillo, J.; Chen, C. Bioorg. Med. Chem. Lett. 2005, 15,
1407.
(2) Bellur, E.; Langer, P. Synlett 2004, 2169.
(3) Kulesza, A.; Ebetino, F. H.; Mishra, R. K.; Cross-Doersen,
D.; Mazur, A. W. Org. Lett. 2003, 5, 1163.
(4) Foote, K. M.; Hayes, C. J.; John, M. P.; Pattenden, G. Org.
Biomol. Chem. 2003, 1, 3917.
(5) Kuethe, J. T.; Wong, A.; Wu, J.; Davies, I. W.; Dormer, P.
G.; Welch, C. J.; Hillier, M. C. J. Org. Chem. 2002, 67,
5993.
(6) Rossi, R.; Bellina, F.; Carpita, A. Synlett 1996, 356.
(7) Torri, S.; Xu, L. H.; Okumoto, H. Synlett 1991, 695.
(8) Cocco, M. T.; Congiu, C.; Onnis, V.; Ianelli, S. Heterocycles
2004, 63, 259.
Synlett 2006, No. 5, 729–732 © Thieme Stuttgart · New York

732
M. Baranac Stojanović, R. Marković
LETTER
(9) Kameswaran, V.; Jiang, B. Synthesis 1997, 530.
(10) Akiyama, T.; Simeno, F.; Murakami, M.; Yoneda, F. J. Am.
Chem. Soc. 1992, 114, 6613.
(11) Singh, G.; Ila, H.; Junjappa, H. Synthesis 1985, 165.
(12) Haddad, N.; Abramovich, Z.; Ruhman, I. Tetrahedron Lett.
1996, 37, 3521.
added and mixture refluxed for 7 d. Reaction mixture was
then cooled to r.t. and evaporated to dryness under reduced
pressure. Column chromatography (SiO2, MeOH as an
eluent) of the crude product yielded 7b (0.541 g, 87%) as a
pale brown solid. 1H NMR (200 MHz, DMSO-d6): d = 2.75
(t, 2 H, CH2Ph, J = 7.2 Hz), 3.31–3.40 (m, 2 H, NCH2), 5.94
(s, 1 H, =CH), 7.09 (s, 1 H, CHS), 7.17–7.35 (m, 5 H, Ph),
(13) Seebach, D.; Gysel, U.; Job, K.; Beck, A. K. Synthesis 1992,
39.
8.24 (t, 2 H, m-pyridine, J = 7.2 Hz), 8.33 (t, 1 H, NHamide
,
(14) Medici, A.; Fogagnolo, M.; Pedrini, P.; Dondoni, A. J. Org.
Chem. 1982, 47, 3844.
(15) Marković, R.; Baranac, M. Synlett 2000, 607.
(16) Marković, R.; Džambaski, Z.; Baranac, M. Tetrahedron
2001, 57, 5833.
(17) Maki, J.; Sako, M.; Tanabe, M.; Suzuki, M. Synthesis 1981,
462.
(18) Typical Procedure for Synthesis of 2-Bromo-2-(4-oxo-
thiazolidin-2-ylidene)-N-(2-phenylethyl)ethanamide
(5b).
J = 5.4 Hz), 8.75 (t, 1 H, p-pyridine, J = 7.8 Hz), 9.30 (d, 2
H, o-pyridine, J = 5.6 Hz), 12.30 (br s, 1 H, NHlactam). 13
NMR (50.3 MHz, DMSO-d6): d = 35.4 (CH2Ph), 40.4
C
(NCH2), 71.8 (CHS), 96.5 (=CH), 126.4 (p-Ph), 128.6 (o-
Ph), 128.7 (m-pyridine), 128.9 (m-Ph), 139.7 (C1–Ph), 144.8
(o-pyridine), 146.3 (C=), 148.0 (p-pyridine), 166.4
(COamide), 168.2 (COlactam). IR (KBr): n = 3271, 3051, 3025,
1722, 1656, 1597, 1545, 1484, 1448, 1298, 1246, 1198,
1173, 832, 754, 703 cm–1. ESI-MS: m/z 340 [M+], 261.
(24) Marković, R.; Pavlovich, J. G.; Baranac, M. Phosphorus,
Sulfur Silicon Relat. Elem. 2005, 180, 1411.
(25) Hutchinson, R. E. J.; Tarbell, D. S. J. Org. Chem. 1969, 34,
66.
(26) Lane, T. H.; Speier, J. L. Org. Chem. 1976, 41, 2714.
(27) Anders, E.; Hertlein, K.; Meske, H. Synthesis 1990, 323.
(28) Katritzky, A. R.; Marson, C. M. Angew. Chem., Int. Ed.
Engl. 1984, 23, 420; and references cited therein.
To a suspension of 1 mmol of the parent 4-oxothiazolidine
in CHCl3 (37 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. The
progress of the reaction was monitored by TLC. The reaction
mixture was evaporated to dryness, EtOH (2–3 mL) and a
few drops of H2O were added and bromide was allowed to
crystallize in a freezer. In the case of preparation of vinyl
bromides 6a–e, EtOH (50 mL) was used as a solvent and
bromine addition was carried out at ca. –5 °C. The reaction
mixture was evaporated to several mL, a certain amount of
H2O was added and bromides were allowed to crystallize in
a freezer. Only vinyl bromide 6b was isolated by extraction
with CH2Cl2 and could not be crystallized. All crystallized
vinyl bromides 5a–e and 6a–e were isolated as pure
substances.
(29) Typical Procedure for Synthesis of (Z,E)-(5-Morpholino-
4-oxothiazolidin-2-ylidene)-N-(2-phenylethyl)ethan-
amide (9b).
A mixture of the crude pyridinium salt 7b (94.3 mg) and
morpholine (0.08 mL, 0.91 mmol) in CHCl3 (8.7 mL) was
stirred at r.t. for 6.5 h in dry atmosphere. After evaporation
of the solvent under reduced pressure, the residue was
purified by column chromatography (SiO2, gradient
toluene–EtOAc, 4:6 v/v to pure EtOAc) to give a pale yellow
solid as a mixture of isomers (Z)- and (E)-9b (69.4 mg, 87%
based on vinyl bromide 5b). 1H NMR (200 MHz, DMSO-
d6): d (Z isomer) = 2.24–2.30 (m, 2 H, NCHax), 2.62–2.74
(m, 4 H, NCHeq and CH2Ph), 3.24–3.34 (m, 2 H, NCH2),
3.57–3.60 (m, 4 H, CH2O), 5.30 (s, 1 H, CHS), 5.58 (s, 1 H,
=CH), 7.16–7.34 (m, 5 H, Ph), 7.90 (t, 1 H, NHamide, J = 5.5
Hz), 11.42 (s, 1 H, NHlactam); d (E isomer) = 2.21–2.31 (m, 2
H, NCHax), 2.57–2.76 (m, 4 H, NCHeq and CH2Ph), NCH2 is
shielded, 3.61 (t, 4 H, CH2O, J = 4.4 Hz), 5.23 (s, 1 H, =CH),
5.72 (s, 1 H, CHS), 7.16–7.34 (m, 5 H, Ph), 8.02 (t, 1 H,
NHamide, J = 5.6 Hz), 11.70 (s, 1 H, NHlactam). 13C NMR (50.3
MHz, DMSO-d6): d (Z isomer) = 35.6 (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); d (E
isomer) = 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). IR (KBr, Z and E): n = 3437,
3267, 3212, 3077, 1718, 1635, 1565, 1454, 1280, 1249,
1113, 858, 831, 768, 703 cm–1. MS (CI): m/z 348 [M + 1].
UV (DMSO, Z and E): lmax (e) = 283.8 nm (25.700). Anal.
Calcd for C17H23N3O4S (9b·H2O): 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.
(30) Katritzky, A. R.; Bapat, J. B.; Blade, R. J.; Leddy, B. P.; Nie,
P.-L.; Ramsden, C. A.; Thind, S. S. J. Chem. Soc., Perkin
Trans. 1 1979, 418.
Spectroscopic Data for (Z)- and (E)-5b.
1H NMR (200 MHz, DMSO-d6): d (Z isomer) = 2.78 (t, 2 H,
CH2Ph, J = 7.3 Hz), 3.33–3.43 (m, 2 H, NCH2), 3.95 (s, 2 H,
CH2S), 7.19–7.34 (m, 5 H, Ph), 7.84 (t, 1 H, NHamide, J = 5.6
Hz), 11.37 (s, 1 H, NHlactam); d (E-isomer) = CH2Ph and
NCH2 are shielded, 3.79 (s, 2 H, CH2S), Ph is shielded, 7.17
(t, 1 H, NHamide, J = 5.2 Hz), 10.93 (s, 1 H, NHlactam). 13
C
NMR (50.3 MHz, DMSO-d6): d (Z-isomer) = 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); d (E isomer) = 33.8
(CH2S), 35.4 (CH2Ph), 41.4 (NCH2), 80.0 (=CBr), 126.3 (p-
Ph), 128.6 (o-Ph), 128.8 (m-Ph), 139.4 (C1–Ph), 149.9 (C=),
163.3 (COamide), 174.3 (COlactam). IR (KBr, Z and E):
n = 3360, 3139, 3022, 1723, 1615, 1585, 1517, 1452, 1431,
1350, 1312, 1257, 1219, 1190, 887, 786, 750, 699 cm–1. MS
(CI): m/z = 341/343 [M + 1]. UV (DMSO, Z and E): lmax
(e) = 296.6 nm (18.900). 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.
(19) Satzinger, G. Justus Liebigs Ann. Chem. 1963, 665, 150.
(20) Satzinger, G. Liebigs Ann. Chem. 1978, 473.
(21) Zaleska, B.; Ciez, D.; Winnik, W.; Chaczatrion, K.
Pharmazie 1995, 50, 537.
(22) Baranac, M. PhD Thesis; University of Belgrade: Serbia and
Montenegro, 2005.
(23) Typical Procedure for Synthesis of (Z)-[4-Oxo-5-(pyr-
idinium-1-yl)thiazolidin-2-ylidene]-N-(2-phenyl-
ethyl)ethanamide Bromide (7b) by Pyridine-Assisted
Bromine Transfer Reaction.
(31) Gromov, S. P.; Kurchavov, N. A. Eur. J. Org. Chem. 2002,
4123.
(32) Van der Plas, H. C. J. Heterocycl. Chem. 2000, 37, 427.
To a suspension of 1.48 mmol of vinyl bromide 5b (0.505 g)
in CHCl3 (31 mL) a tenfold molar excess of pyridine was
Synlett 2006, No. 5, 729–732 © Thieme Stuttgart · New York