An unexpected formation of 2-aryl-3-benzyl-1,3-thiazolidin-4-ones

Article abstract of DOI:10.1055/s-2006-950213

The reactions of L-valine, arenealdehydes, mercaptoacetic acid and DIPEA produce 2-aryl-3-benzyl-1,3-thiazolidin-4-ones with moderate yields (48-65%). Characterization of the 1,3-thiazolidin-4-ones was achieved by NMR and confirmed by X-ray crystallograph

Full text of DOI:10.1055/s-2006-950213

PAPER
3405
An Unexpected Formation of 2-Aryl-3-benzyl-1,3-thiazolidin-4-ones
A
W
n
U
nexpected Formati
i
on of
2
l
-Aryl-3
s
-benzyl-1
o
,3-thiazolidi
n
n-4-ones Cunico,* Liliane R. Capri, Claudia R. B. Gomes, Rosangela H. Sizilio, Solange M. S. V. Wardell
FioCruz – Fundação Oswaldo Cruz, Instituto de Tecnologia em Fármacos, FarManguinhos R. Sizenando Nabuco,
00 Manguinhos, Rio de Janeiro 21041-250, RJ, Brazil
1
E-mail: wjcunico@far.fiocruz.br
Received 23 May 2006; revised 21 June 2006
A mixture of L-valine, two equivalents of arenealdehyde
Abstract: The reactions of L-valine, arenealdehydes, mercaptoace-
tic acid and DIPEA produce 2-aryl-3-benzyl-1,3-thiazolidin-4-ones
with moderate yields (48–65%). Characterization of the 1,3-thiazo-
2
a–k, and diisopropylethylamine (DIPEA) in toluene was
refluxed for four hours with a Dean–Stark trap. The mer-
lidin-4-ones was achieved by NMR and confirmed by X-ray crys- captoacetic acid was then added and the reaction mixture
tallography.
was heated until the reaction was complete (CG analysis).
Products 3 were obtained in moderate yields after column
chromatography (Table 1). The 1,3-thiazolidin-4-ones
Key words: thiazolidinones, cyclocondensation, valine
3
a–k were also obtained in a one-step reaction when all
reagents were added together in toluene and the reaction
mixture was heated for 16 hours.
Thiazolidinones are an important group of heterocyclic
compounds, having such diverse biological uses as insec-
ticides, anticonvulsants, tuberculostatic, anti-inflammato- A relative molar ratio of 1:2:3 of amino acid–aldehyde–
1
ry and antiviral agents. In recent years, 4-thiazolidinones mercaptoacetic acid, in the presence of DIPEA, proved to
and 4-oxazolidinones have been among the most exten- provide optimum yields. This proportion was the same
sively studied compounds. While oxazolidinones have found for the reaction between amines, aldehydes and
emerged as a new class of antibiotic, represented by lize- mercaptoacetic(propionic) acids.6 The presence of
,7
2
,3
zolid, 1,3-thiazolidin-4-ones have been found to have DIPEA gave dramatically improved yields, as did the use
4
activity against the HIV virus. The biological activity of of elevated temperatures.
1
,3-thiazolidin-4-ones is reported to be associated with
None of the compounds have previously been reported,
with the exception of compound 3a which was synthe-
sized from benzylamine, benzaldehyde and mercapto ace-
tic acid.
their ability to assume a ‘butterfly-like’ conformation.
This imparts a binding mode similar to that provided by
other non-nucleoside reverse transcriptase inhibitors
9
5
(
NNRTIs).
1
,3-Thiazolidin-4-ones have been prepared from three
O
O
components (an aldehyde, an amine and mercaptoacetic
acid), by various one- and two-step syntheses. The reac-
1
HO
N
S
tions proceed by initial imine formation (the nitrogen of
amine attacks the carbonyl of aldehyde), which then un-
dergoes attack by the sulfur nucleophile, followed by in-
tramolecular cyclization on elimination of water. The
most common protocol to remove the water is by azeotro-
pic distillation. DCC, which is extensively used in peptide
synthesis for dehydration, strongly promotes the dehydra-
1
R
Figure 1 3-Methyl-2-(2-aryl-4-oxothiazolinin-3-yl)butanoic acids
1
6
O
tion here too.
O
H
The reaction of an amino acid ester hydrochloride, an
aldehyde and mercaptoacetic acid has been reported to
R
O
R
N
S
NH2
i, ii
produce
3-methyl-2-[2-alkyl(aryl)-4-oxathiazolinin-3-
O
+
HO
4
8–65%
yl]butanoic acids 1 (Figure 1), in two steps, after de-ester-
3
a–k
H
7
R
ification. These reactions have also been carried out us-
R
ing microwave radiation.8
2a–k
We attempted to synthesize such heterocycles directly
Scheme 1 Reagents and conditions: (i) DIPEA, toluene, Dean–
from L-valine in one step. However, our products were not Stark trap, 130 °C, 4 h; (ii) HSCH COOH, 1 h.
2
the expected compounds 1, but rather 3 (Scheme 1). We
now wish to report the results of this unexpected reaction.
In the absence of L-valine, the reaction between an arene-
carboxaldehyde and mercaptoacetic acid, on refluxing in
toluene for four hours, led to the formation of 2-aryl-1,3-
oxathiolan-5-ones 4b, which was obtained in 88% yield
after recrystallization from hexane (Scheme 2).1
SYNTHESIS 2006, No. 20, pp 3405–3408
x
x.
x
x
.
2
0
0
6
Advanced online publication: 21.08.2006
DOI: 10.1055/s-2006-950213; Art ID: M03506SS
Georg Thieme Verlag Stuttgart · New York
0,11
©

3
406
W. Cunico et al.
PAPER
Table 1 Yields and Selected Physical Properties of Compounds 3a–k
a
b
Product
R
Mp (°C)
Yield (%)
CG-MS m/z (%)
c
61 (89c)
65
3
3
3
3
3
3
3
3
3
3
3
a9
b
c
H
145–148 (Lit. 153–154)
174–176
171–173
141–143
81–83
269 (15) [M], 194 (56), 178 (85), 147 (42), 91 (100)
359 (25) [M], 223 (100), 175 (65), 136 (45), 89 (80)
359 (46) [M], 223 (100), 192 (76), 175 (50), 136 (42)
2-NO2
3-NO2
4-NO2
2-F
62
d
e
59
359 (10) [M], 223 (100), 192 (58), 175 (55), 136 (56), 89 (38)
305 (45) [M], 230 (50), 196 (42), 165 (100), 109 (85)
305 (23) [M], 230 (20), 196 (30), 165 (78), 109 (100)
305 (18) [M], 230 (35), 196 (14), 165 (68), 109 (100)
329 (48) [M], 254 (56), 208 (64), 177 (82), 146 (68), 121 (92), 91 (100)
329 (5) [M], 254 (26), 208 (100), 177 (15), 121 (83), 91 (20)
329 (25) [M], 254 (20), 177 (68), 146 (41), 121 (100)
319 (18) [M], 244 (30), 203 (29), 172 (59), 116 (100)
58
f
3-F
86–88
61
g
h
i
4-F
88–90
60
2-OMe
3-OMe
4-OMe
4-CN
103–105
97–99
61
65
j
85–87
62
k
194–196
48
a
b
c
Melting points are uncorrected.
Yields of isolated compounds.
Literature data.9
O
tramolecular interaction favors one of the two possible
conformations. Such an interaction does occur with re-
spect to F2 in the benzyl ring: the intramolecular interac-
tion with H12b (F2–H12b = 2.432 Å), cements the
conformation shown. The thiazolidin-4-one ring is near
planar and is almost orthogonal to the two aryl rings, an-
gles being 89.05(8)° [to C6–C11] and 89.20(7)° [to C13–
C18]. The molecule overall has a U-shape. Selected geo-
metric parameters are listed in Figure 2.
NO2
O
O
S
H
i
+
HSCH2COOH
NO2
8
8%
2b
4b
Scheme 2 Reagents and conditions: (i) DIPEA, toluene, Dean–
Stark trap, 130 °C, 4 h.
The structures of the 1,3-thiazolidin-4-ones 3, were sug-
gested from the NMR spectra (Table 2) and confirmed by
the single-crystal structure determination of 3e. Since the
NMR spectra clearly indicated that all products 3 were
similar, this crystal structure enabled us to sufficiently
characterize the remaining compounds in the series. Pro-
ton H2 gave rise to a doublet at d = 6 ppm with long-range
1
coupling to H5a (J = 1.5 Hz). The two doublets in the H
NMR spectra in the range of d = 3.97 to 3.74 ppm were
assigned to the diastereotopic protons H5a and H5b. The
signals for the benzyl methylene protons also showed as
two doublets (at d = 5.0 and 3.5 ppm). The aromatic sig-
nals had the relative integration expected for two arene-al-
1
3
dehyde moieties. The C NMR spectra exhibited
carbonyl carbon signals at d = 170 ppm and other, general
1
3
C NMR signals, occurring about d = 32 (C5, methylene Figure 2 Molecular structure and selected geometric parameters
of the thiazolidinone ring), d = 45 (methylene) and d = 60 (Å, °) for 2-(2-fluorophenyl)-3-(2-fluorobenzyl)-1,3-thiazolidin-4-
(
one 3e. Ellipsoids, for non-hydrogen atoms, are drawn at the 50% pro-
bability level: H atoms are drawn as arbitrary spheres.
C2) ppm.
The molecular structure of the major conformation of 3e
1
2
is shown in Figure 2. The fluorine atom in the C6–C11
ring is disordered over two sites, on C7 and C11, designat-
ed F1b and F1a, with occupancies of 67.55(5)% and
In summary, we have developed a new 1,3-thiazolidin-4-
one synthesis. The structure of these compounds has been
1
13
confirmed by H, C NMR and X-ray analysis. Further
investigations into the details of the reactions are in
progress.
3
2.45(5)%, respectively. Such a disorder for the relatively
small fluorine atom has been variously reported for other
compounds containing 2-FC H groups in which no in-
6
4
Synthesis 2006, No. 20, 3405–3408 © Thieme Stuttgart · New York

PAPER
An Unexpected Formation of 2-Aryl-3-benzyl-1,3-thiazolidin-4-ones
3407
1
13
a
Table 2 Selected H and C NMR Data of Compounds 3a–k
Compd d (ppm) for H NMR and 13C NMR
1
3
a
7.41–7.22 (m, 8 H, Ph), 7.09 (m, 2 H, Ph), 5.38 (d, J = 1.5 Hz, 1 H, H2), 5.15 (d, J = 14.5 Hz, 1 H, CH a), 3.90 (dd, J = 15.5 Hz,
2
2
J = 1.5 Hz, 1 H, H5a), 3.76 (d, J = 15.5 Hz, 1 H, H5b), 3.54 (d, J = 14.5 Hz, 1 H, CH b)
2
1
71.2 (C=O), 139.2, 135.3, 129.2–127.2, 62.7 (C2), 46.3 (CH ), 33.0 (C5)
2
2
2
3
b
8.17 (dd, J = 8.0 Hz, J = 1.0 Hz, 1 H, Ph), 8.01 (dd, J = 8.0 Hz, J = 1.0 Hz, 1 H, Ph), 7.74 (t, J = 8.0 Hz, 1 H, Ph), 7.69 (t, J = 8.0
2
2
Hz, 1 H, Ph), 7.57 (td, J = 8.0 Hz, J = 1.0 Hz, 1 H, Ph), 7.49 (m, 2 H, Ph), 7.34 (dd, J = 8.0 Hz, J = 1.0 Hz, 1 H, Ph), 6.16 (d, J = 1.0
Hz, 1 H, H2), 5.43 (d, J = 16.5 Hz, 1 H, CH a), 4.25 (d, J = 16.5 Hz, 1 H, CH b), 3.80 (dd, J = 16.0 Hz, J = 1.0 Hz, 1 H, H5a), 3.69
2
2
2
(
d, J = 16.0 Hz, 1 H, H5b)
1
73.4 (C=O), 148.5, 147.1, 136.4, 134.9, 134.5, 130.8, 129.7, 129.3, 129.2, 126.5, 125.7, 125.6, 58.9 (C2), 44.1 (CH ), 31.2 (C5)
2
3
3
cb
d
8.21 (m, 1 H, Ph), 8.13 (m, 1 H, Ph), 8.08 (m, 1 H, Ph), 7.84 (m, 1 H, Ph), 7.57 (m, 2 H, Ph), 7.51–7.48 (m, 2 H, Ph), 5.53 (d, J = 1.6
Hz, 1 H, H2), 4.99 (d, J = 15.2 Hz, 1 H, CH a), 3.97 (d, J = 15.2 Hz, 2 H, H5a and CH b), 3.84 (d, J = 15.6 Hz, 1 H, H5b)
2
2
1
71.4 (C=O), 148.7, 148.4, 141.1, 137.2, 134.3, 133.1, 130.4, 130.1, 124.4, 123.2, 123.0, 122.3, 62.4 (C2), 46.3 (CH ), 32.6 (C5)
2
8.26 (d, J = 8.0 Hz, 2 H, Ph), 8.19 (d, J = 9.0 Hz, 2 H, Ph), 7.41 (d, J = 9.0 Hz, 2 H, Ph), 7.28 (d, J = 8.5 Hz, 2 H, Ph), 5.46 (d, J = 1.5
2
Hz, 1 H, H2), 5.20 (d, J = 15.5 Hz, 1 H, CH a), 3.95 (dd, J = 16.0 Hz, J = 1.5 Hz, 1 H, H5a), 3.83 (d, J = 16.0 Hz, 1 H, H5b), 3.73
2
(
d, J = 15.5 Hz, 1 H, CH b)
2
1
71.4 (C=O), 148.4, 147.8, 145.9, 142.1, 128.9, 127.9, 124.6, 124.2, 61.7(C2), 45.9 (CH ), 32.4 (C5)
2
3
3
e
f
7.33–6.96 (m, 8 H, Ph), 5.75 (d, J = 1.5 Hz, 1 H, H2), 4.99 (d, J = 15.2 Hz, 1 H, CH a), 3.93 (d, J = 15.0 Hz, 1 H, CH b), 3.89 (dd,
2 2
2
J = 15.0 Hz, J = 1.5 Hz, 1 H, H5a), 3.69 (d, J = 15.0 Hz, 1 H, H5b).
4
1
1
5
70.9 (C=O), 160.5 (d, J = 245.9 Hz), 159.3 (d, J = 248.6 Hz), 130.6, 130.5, 130.7–129.8, 127.9 (d, J = 4.0 Hz), 126.8, 126.7,
C
F
C
F
C
F
4
4
2
2
2
24.6 (d, J = 4.0 Hz), 124.4 (d, J = 4.0 Hz), 122.3, 121.7 (d, J = 22.0 Hz), 116.1 (d, J = 22.0 Hz), 115.4 (d, J = 22.5 Hz),
CF
CF
CF
CF
CF
7.1 (C2), 40.2 (CH ), 32.5 (C3), 32.4 (C5)
2
7.36 (m, 1 H, Ph), 7.28 (m, 1 H, Ph), 7.07 (m, 1 H, Ph), 7.01–6.94 (m, 3 H, Ph), 6.85 (m, 2 H, Ph), 5.38 (d, J = 1.0 Hz, 1 H, H2), 5.01
2
(
d, J = 15.0 Hz, 1 H, CH a), 3.91 (dd, J = 15.0 Hz, J = 1.5 Hz, 1 H, H5a), 3.77 (d, J = 15.0 Hz, 1 H, H5b), 3.60 (d, J = 15.0 Hz, 1 H,
2
CH b)
1
2
71.4 (C=O), 163.3 (d, J = 247.6 Hz), 163.1 (d, JCF = 247.3 Hz), 141.8 (d, J = 6.0 Hz), 137. 8 (d, 3JCF = 7.2 Hz), 131.0 (d,
3
CF
3
CF
3
4
2
2
JCF = 9.0 Hz), 130.5 (d, J = 9.0 Hz), 124.1, 122.9 (d, J = 3.2 Hz), 116.6 (d, J = 22.0 Hz), 115.4 (d, J = 15.0 Hz), 115.2 (d,
JCF = 15.0 Hz), 114.2 (d, J = 22.0 Hz), 62.4 (C2), 46.1 (CH ), 32.9 (C3), 32.8 (C5)
CF
2
CF
CF
CF
2
CF
2
3
3
g
7.23–7.20 (m, 2 H, Ph), 7.09–7.03 (m, 4 H, Ph), 7.00–6.97 (m, 2 H, Ph), 5.37 (d, J = 1.0 Hz, 1 H, H2), 5.04 (d, J = 15.0 Hz, 1 H, CH a),
2
2
3
1
.88 (dd, J = 15.0 Hz, J = 1.0 Hz, 1 H, H5a), 3.77 (d, J = 15.0 Hz, 1 H, H5b), 3.57 (d, J = 15.0 Hz, 1 H, CH b)
2
4
4
71.3 (C=O), 164.3 (d, J = 248.4 Hz), 162.6 (d, J = 246.2 Hz), 134.8 (d, J = 3.5 Hz), 131.2 (d, J = 3.3 Hz), 130.3 (d,
CF
3
CF
CF
CF
3
2
2
JCF = 9.0 Hz), 129.4 (d, J = 9.0 Hz), 116.3 (d, J = 22.0 Hz), 115.9 (d, J = 21.0 Hz), 62.4 (C2), 45.8 (CH ), 33.2 (C3), 33.0
CF
CF
CF
2
(
C5)
2
h
7.29 (td, J = 8.5 Hz, J = 1.5 Hz, 1 H, Ph), 7.23 (td, J = 8.0 Hz, J = 1.5 Hz, 1 H, Ph), 7.16 (d, J = 7.0 Hz, 1 H, Ph), 7.08 (dd, J = 7.5
2
2
Hz, J = 1.0 Hz, 1 H, Ph), 6.95 (dd, J = 7.5 Hz, J = 7.5 Hz, 1 H, Ph), 6.80 (m, 2 H, Ph), 6.80 (d, J = 8.5 Hz, 1 H, Ph), 5.85 (s, 1 H,
2
H2), 4.97 (d, J = 15.0 Hz, 1 H, CH a), 3.94 (d, J = 15.0 Hz, 1 H, CH b), 3.79 (s, 3 H, OMe), 3.78 (dd, J = 15.5 Hz, J = 1.5 Hz, 1 H,
2
2
H5a), 3.68 (s, 3 H, OMe), 3.62 (d, J = 15.0 Hz, 1 H, H5b)
1
4
72.3 (C=O), 157.4, 156.8, 129.6, 129.5, 128.9, 128.2, 126.0, 123.7, 120.6, 120.5, 110.8, 110.1, 58.1 (C2), 55.1 (OMe), 55.0 (OMe),
1.7 (CH ), 32.4 (C5)
2
2
3
i
7.30 (t, J = 8.0 Hz, 1 H, Ph), 7.22 (d, J = 8.0 Hz, 1 H, Ph), 6.90 (dd, J = 8.0 Hz, J = 2.0 Hz, 1 H, Ph), 6.81 (m, 2 H, Ph), 6.76 (m, 1 H,
Ph), 6.69 (d, J = 8.0 Hz, 1 H, Ph), 6.65 (m, 1 H, Ph), 5.38 (d, J = 1.5 Hz, 1 H, H2), 5.12 (d, J = 15.0 Hz, 1 H, CH a), 3.89 (dd, J = 15.5
2
2
Hz, J = 1.5 Hz, 1 H, H5a), 3.80 (s, 3 H, OMe), 3.77 (s, 3 H, OMe), 3.75 (d, J = 15.0 Hz, 1 H, H5b), 3.55 (d, J = 15.0 Hz, 1 H, CH b)
2
1
4
71.9 (C=O), 160.8, 160.6, 141.4, 137.5, 130.8, 130.4, 121.3, 120.0, 115.4, 114.6, 114.1, 113.1, 63.4 (C2), 56.0 (OMe), 55.9 (OMe),
6.9 (CH ), 33.6 (C5)
2
3
3
jb
k
7.20 (d, J = 8.8 Hz, 2 H, Ph), 7.02 (d, J = 8.8 Hz, 2 H, Ph), 6.91 (d, J = 8.8 Hz, 2 H, Ph), 6.82 (d, J = 8.8 Hz, 2 H, Ph), 5.36 (d, J = 1.6
2
Hz, 1 H, H2), 5.07 (d, J = 14.8 Hz, 1 H, CH a), 3.87 (dd, J = 15.6 Hz, J = 1.6 Hz, 1 H, H5a), 3.84 (s, 3 H, OMe), 3.80 (s, 3 H, OMe),
2
3
1
.74 (d, J = 15.6 Hz, 1 H, H5b), 3.47 (d, J = 14.4 Hz, 1 H, CH b)
71.7 (C=O), 160.9, 159.9, 131.5, 130.5, 129.4, 128.2, 115.1, 114.8, 63.1 (C2), 56.1 (OMe), 56.0 (OMe), 46.2 (CH ), 33.9 (C5)
2
2
7.69 (d, J = 8.5 Hz, 2 H, Ph), 7.62 (d, J = 8.0 Hz, 2 H, Ph), 7.33 (d, J = 8.5 Hz, 2 H, Ph), 7.20 (d, J = 8.0 Hz, 2 H, Ph), 5.39 (d, J = 1.5
2
Hz, 1 H, H2), 5.13 (d, J = 15.5 Hz, 1 H, CH a), 3.90 (dd, J = 15.5 Hz, J = 1.5 Hz, 1 H, H5a), 3.79 (d, J = 16.0 Hz, 1 H, H5b), 3.67
2
(
d, J = 15.5 Hz, 1 H, CH b)
2
1
71.4 (C=O), 144.1, 140.2, 133.1, 132.7, 128.8, 127.7, 118.2 (CN), 117.9 (CN), 113.4, 112.3, 62.1 (C2), 46.2 (CH ), 32.5 (C5)
2
a
NMR spectra were recorded on a Bruker Avance 500 in CDCl /TMS.
3
b
NMR spectra on a Bruker DRX 400 in CDCl /TMS.
3
Synthesis 2006, No. 20, 3405–3408 © Thieme Stuttgart · New York

3
408
W. Cunico et al.
PAPER
Unless otherwise indicated, all common reagents and solvents were
used as obtained from commercial suppliers without further purifi-
cation. All melting points were determined on a Buchi Melting
Monforte, P.; Pannecouque, C.; Rao, A.; Zapallà, M. J. Med.
Chem. 2002, 45, 5410. (b) Rao, A.; Balzarini, J.; Carbone,
A.; Chimirri, A.; De Clercq, E.; Monforte, A. M.; Monforte,
P.; Pannecouque, C.; Zapallà, M. Farmaco 2004, 59, 33.
(c) Rao, A.; Balzarini, J.; Carbone, A.; Chimirri, A.; De
Clercq, E.; Monforte, A. M.; Monforte, P.; Pannecouque, C.;
Zapallà, M. Antivir. Res. 2004, 63, 79. (d) Rawal, R. K.;
Prabhakar, Y. S.; Katti, S. B.; De Clercq, E. Bioorg. Med.
Chem. 2005, 13, 6771.
1
13
Point B-545 and are uncorrected. H and C NMR spectra were re-
1
corded on a Bruker DRX 400 spectrometer ( H at 400.14 MHz and
1
3
C at 100.61 MHz) and/or on a Bruker Avance 500 spectrometer
(1
H at 500.13 MHz and 13C at 125.75 MHz) in CDCl containing
3
TMS as an internal standard.
Preparation of 2-Aryl-3-benzyl-1,3-thiazolidin-4-ones 3a–k;
General Procedure
A mixture of L-valine (5 mmol), arenealdehyde (10 mmol), and
DIPEA (6 mmol) in toluene (50 ml) was heated at 130 °C with a
Dean–Stark trap for 4 h. The reaction was cooled to r.t. and mercap-
toacetic acid (15 mmol) was added. The mixture was heated at
(
5) Barreca, M. L.; Carotti, A.; Carrieri, A.; Chimirri, A.;
Monforte, A. M.; Pellegrini Calace, M. L.; Rao, A. Bioorg.
Med. Chem. 1997, 7, 2283.
(
(
(
(
6) Srivastava, T.; Haq, W.; Katti, S. B. Tetrahedron 2002, 58,
7619.
7) Homes, C. P.; Chinn, J. P.; Look, C. G.; Gordon, E. M.;
Gallop, M. A. J. Org. Chem. 1995, 60, 7328.
8) Gudurudu, V.; Nguyen, V.; Dalton, J. T.; Miller, D. D.
Synlett 2004, 2357.
1
30 °C until the reaction was complete (GC). Two phases were
formed upon cooling and the organic layer was separated, washed
with sat NaHCO (3 × 100 mL), dried with MgSO and concentrated
3
4
to give an oil that was purified by column chromatography on silica
gel using hexane–EtOAc (8:2) as eluent.
9) Troutman, H. D.; Long, L. M. J. Am. Chem. Soc. 1948, 70,
3436.
(10) Satsumabayashi, S.; Irioka, S.; Kudo, H.; Tsujimoto, K.;
Motoki, S. Bull. Chem. Soc. Jpn. 1972, 45, 913.
Acknowledgment
(
11) Selected data for 2-(2-nitrophenyl)-1,3-oxathiolan-5-one
The authors thank FarManguinhos for financial support of the re-
search and Dr J. L. Wardell (University of Aberdeen, Scotland) for
the data collection.
1
(
4b): H NMR (500 MHz, CDCl ): d = 8.35 (dd, J = 8.0
3
HH
2
2
Hz, J = 2.0 Hz, 1 H), 8.27 (d, JHH = 8.0 Hz, J = 1.0
HH
HH
Hz, 1 H), 7.81 (d, JHH = 7.5 Hz, 1 H), 7.63 (dd, J = 8.0 Hz,
1
3
H), 6.55 (s, 1 H, H2), 3.93 (d, H4a, J = 16.5 Hz, 1 H),
.82 (d, H4b, JHH = 16.5 Hz, 1 H); C NMR (125 MHz,
HH
1
3
References
CDCl ): d = 171.7 (C=O), 148.4, 138.8, 132.3, 130.1, 124.7,
3
121.6 (Ph), 80.6 (C2), 32.7 (C4); CG-MS: m/z (%) = 225
(
1) Singh, S. P.; Parmar, S. S.; Raman, K.; Stenberg, V. I. Chem.
Rev. 1981, 81, 175.
(
10) [M], 152 (100), 105 (20), 74 (70), 51 (25).
(
12) X-ray crystal data for 3e; CCDC 603430; Empirical formula
(
2) Brickner, S. J.; Hutchinson, D. K.; Barbachyn, M. R.;
Manninen, M. N.; Ulanowicz, D. A.; Garmon, S. A.; Grega,
K. C.; Hendges, S. K.; Troops, D. S.; Ford, C. W.; Zurenko,
G. E. J. Med. Chem. 1996, 39, 673.
C H F NOS; Formula weight 302.81; T = 120 K;
l = 0.71073 Å; Crystal system = monoclinic; Space group
P21/a; Unit cell dimensions a = 10.1491 (4), b = 10.1236
16 11
2
(
3), c = 13.9981 (6) Å, b = 106.333 (2)°; V = 1380.20 (9)
3 –3 –1
(3) de Souza, M. V. N. Recent Patents on Anti-Infective Drug
Discovery 2006, 1, 33.
Å ; z-2; D = 1.457 gcm ; m = 0.254 mm ; Theta range for
data collection 1.52° to 27.45°; Reflections collected 15114;
Independent reflections 3128 [R(int) = 0.0340]; Refinement
method Full-matrix least-squares on F2; R1 = 0.0680,
wR2 = 0.1729 [I>2sI]. Structure solution and refinement
were achieved using SHELX97 and SHELXL97 (Sheldrick,
G. M. SHELXS97 and SHELXL97, University of Göttingen,
Germany, 1997).
(
4) (a) Barreca, M. L.; Balzarini, J.; Chimirri, A.; De Clercq, E.;
De Luca, L.; Holtje, H. D.; Holtje, M.; Monforte, A. M.;
Synthesis 2006, No. 20, 3405–3408 © Thieme Stuttgart · New York