Easy access to 4-nitrothiochroman S,S-dioxides via ring-enlargement from 3-nitrobenzo[b]thiophene

Article abstract of DOI:10.1016/j.tet.2004.04.039

The (E)-2-aryl-1-[2-(methylthio)phenyl]-1-nitroethylenes 5 can easily be oxidized to the relevant sulfones 6 and effectively subjected to cyclization via an intramolecular Michael addition after metallation with lithium bis(trimethylsilyl)amide in THF. After quenching with ammonium chloride the 3-aryl-4-nitrothiochroman S,S-dioxides 2 are obtained as diastereomeric mixtures in good to excellent yields. Both yields and stereochemistry of the ring-closure step appear to be influenced by steric effects of the 3-aryl moiety. As sulfides 5 derive from an initial ring opening of 3-nitrobenzo[b]thiophene (1), the overall 1 to 2 process can be considered as an effective 5 to 6 ring enlargement of the sulfur heterocycle. A conformational ¹H NMR and molecular-mechanics investigation on the isolated diastereomeric 2 has also been accomplished.

Full text of DOI:10.1016/j.tet.2004.04.039

Tetrahedron 60 (2004) 4967–4973
Easy access to 4-nitrothiochroman S,S-dioxides via
ring-enlargement from 3-nitrobenzo[b]thiopheneq
Lara Bianchi,a Carlo Dell’Erba,a Massimo Maccagno,a Stefano Morganti,b Marino Novi,a
b
a
a
b
Giovanni Petrillo,a Egon Rizzato, Fernando Sancassan, Elda Severi, Domenico Spinelli
,
*
and Cinzia Tavania
a
`
Dipartimento di Chimica e Chimica Industriale, Universita di Genova, Via Dodecaneso 31, I-16146 Genova, Italy
Dipartimento di Chimica Organica ‘A. Mangini’, Universita di Bologna, Via S. Donato 15, I-40127 Bologna, Italy
b
`
Received 13 February 2004; revised 25 March 2004; accepted 14 April 2004
Abstract—The (E)-2-aryl-1-[2-(methylthio)phenyl]-1-nitroethylenes 5 can easily be oxidized to the relevant sulfones 6 and effectively
subjected to cyclization via an intramolecular Michael addition after metallation with lithium bis(trimethylsilyl)amide in THF. After
quenching with ammonium chloride the 3-aryl-4-nitrothiochroman S,S-dioxides 2 are obtained as diastereomeric mixtures in good to
excellent yields. Both yields and stereochemistry of the ring-closure step appear to be influenced by steric effects of the 3-aryl moiety.
As sulfides 5 derive from an initial ring opening of 3-nitrobenzo[b]thiophene (1), the overall 1 to 2 process can be considered as an effective
5 to 6 ring enlargement of the sulfur heterocycle. A conformational 1H NMR and molecular-mechanics investigation on the isolated
diastereomeric 2 has also been accomplished.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
Some substituted thiochromans have also been prepared
through condensation of dilithiated methylthio- and iso-
propylthio-benzene with a-diketones.10
A number of reports from the recent literature clearly testify
for a renewed interest in the synthetic approach to
thiopyrans and benzothiopyrans (thiochromans).2,3 The
quest for new synthetic routes has been boosted by the
importance which has been attached in the last decade to
such heterocycles, both in pharmacology and in medicine:4
an occurrence which has also contributed to partially fill,
from both a synthetic and applicative point of view, the gap
with the oxygen counterparts (pyrans and benzopyrans,
respectively), whose long-recognised abundance in nature
has always fostered a good deal of research relevant to
preparations and properties.5
Within the framework of our long-standing project on the
synthetic exploitation of the ring-opening of nitro-
thiophenes11 we now report on a novel approach to
thiochroman S,S-dioxides 2 (Scheme 1) which takes
advantage of an intramolecular Michael addition of the
lithium salts of compounds 6 to the nitrovinyl moiety
(Scheme 2) and which can be envisaged, starting from
3-nitrobenzo[b]thiophene (1), as an overall 5 to 6 enlarge-
ment of the sulfur heterocycle. It should be pointed out that,
at least to our knowledge, compounds 2 represent the first
example of thiochroman derivatives with a nitrogroup at
C(4).
Many thiochromans have been synthesized through
reduction of the corresponding thiochromens6 and thio-
chromanones,7 via Claisen rearrangement of allyl phenyl
sulfides,8 or via thermal decomposition of 2-azido-
benzo[b]thiophenes in the presence of alkenes.9 More
recent synthetic approaches to thiochromans utilize the
cycloaddition of sulfur-stabilized carbocations to alkenes.2b
2. Results and discussion
Substrates 6 have been prepared (Scheme 1 and Table 1) by
oxidation of 5, in turn easily obtainable via a preliminary
ring opening of 3-nitrobenzo[b]thiophene (1), according to a
methodology previously described for the preparation of 5d
(Ar¼p-tolyl).12
q See Ref. 1.
Keywords: Thiochromans; Nitrothiophenes; 3-Nitrobenzo[b]thiophene;
Ring-opening/ring-closure reactions; Ring enlargement; Conformations.
Treatment of 6 with lithium bis(trimethylsilyl)amide
(LHMDS) in anhydrous THF at room temperature, followed
by acidic (NH4Cl) quenching allowed us to isolate, in good
*
Corresponding author. Tel.: þ39-10-3536121; fax: þ39-10-3536118;
e-mail address: petrillo@chimica.unige.it
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.04.039

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L. Bianchi et al. / Tetrahedron 60 (2004) 4967–4973
the mesityl-substituted 6e, evidencing that the overall
process is highly sensitive to the bulk of the aryl moiety
in the substrate.
The assignment of the structure to the reaction products is
based both on microanalytical results and on spectral data
[IR, 1H and 13C NMR, MS(ESI): see Experimental Section].
In particular, the same molecular weight as for 6, the
absence of the nitrovinyl and of the CH3SO2 protons, and
1
the presence of a CH–CH–CH2 moiety in the H NMR
spectra represent definitive confirmation of the proposed
structure for 2.
Nitrothiochromans 2 can be reasonably envisaged to
originate from the non isolated nitronates 8, which are in
turn the result of an intramolecular Michael addition
undergone by the initially formed lithium salts 7
(Scheme 2). Consistant with this proposed mechanism, if
the reaction of 6d is quenched with ND4Cl in D2O,
4-deutero-4-nitro-3-(p-tolyl)thiochroman S,S-dioxide (20d)
is formed.
Scheme 1. (i) Pyrrolidine (2 mol equiv.)/AgNO3 (2 mol equiv.), abs. EtOH,
rt, overnight; (ii) excess MeI, 0 8C to rt, 2 h; (iii) ArMgX or ArLi
(1.1 mol equiv.), THF, 278 8C, 15–45 min, followed by acidic quenching;
(iv) MCPBA (2 mol equiv.), CH2Cl2, rt; (v) LHMDS (1.1 mol equiv.),
THF, rt, 4 h, followed by NH4Cl quenching.
The 1H NMR spectra of crude nitroderivatives 2 are
consistent with the concomitant presence of two racemic
diastereoisomers, non separable by chromatography, corre-
Scheme 2.
sponding to the trans and cis configurations at the C(3)–
C(4) bond; thus, in order to better rationalize the results, it
seemed worth carrying out an accurate conformational
analysis on such thiochromans. While the sulphur atom and
C(4) have to be coplanar with the condensed benzene
moiety, C(2) and C(3) can be either on opposite sides with
respect to the plane (generating two non equivalent half-
chairs) or on the same side (generating two non equivalent
boats): in the latter case, though, severe eclipsing at the
C(2)–C(3) bond can be expected. Another possibility is
represented by sofa conformations, exhibiting just one
carbon out of the plane and possibly less effective eclipsing
than the boats. For this reason sofa conformations received
much attention as possible competitors of half-chairs in
related systems.2b,13
Table 1. Yields of compounds 5, 6 and 2 (Scheme 1, steps iii, iv and v,
respectively)a
Ar
5
(Yield %) (Yield %)
6
2
(Yield %)b trans/cis Ratioc
a
b
c
d
e
f
Ph
99
95
87
94d
99
97
99
94
99
99
99
99
78
80
80
88
f
1:1.4
1:2.2
1:1.3
1:1.2
2-MeC6H4
3-MeC6H4
4-MeC6H4
2,4,6-Me3C6H2 41 (99)e
4-ClC6H4
1-Naphthyl
2-Thienyl
99
99
99h
78
99g
70
1:1.0
1:3.0
1:0.9
g
h
a
Yields of chromatographically-isolated compounds, if not otherwise
stated.
Yields of crude diastereoisomeric mixtures.
Isomeric ratios have been determined by 1H NMR, on the basis of the
ratios of the H(4) signals in the mixture.
See Ref. 12.
Yield based on the reacted substrate.
Unaltered substrate recovered after 48 h, with no trace of products.
Reaction time: 30 h.
b
c
We have approached the problem by running molecular-
mechanics calculations (PCMODEL program14) for the
trans and cis forms of 2a (Ar¼Ph). Results are collected in
Table 2. In both cases the most stable conformation is
calculated to be one of the two possible half-chairs, the trans
form adopting a pseudo-equatorial (peq) arrangement of the
nitro and the phenyl substituents while the cis form prefers a
pseudo-axial (pax) nitrogroup and a peq phenyl moiety
(Fig. 1). It stands out that the two forms differ mainly for
the orientation of the 4-NO2 substituent and consequently
for the H(3)–C(3)–C(4)–H(4) dihedral angle, which is
d
e
f
g
h
Reaction time: 4 h.
to excellent yields, the 3-aryl-4-nitrothiochroman S,S-
dioxides 2 (Scheme 1 and Table 1). It should be pointed
out that the formation of the product is much slower for the
naphthyl-substituted 6g and even completely suppressed for

L. Bianchi et al. / Tetrahedron 60 (2004) 4967–4973
4969
Table 2. Calculated dihedral angles (8) and dipole moments (D) for the half-chair conformations of trans- and cis-2a
C(4a)–C(8a)–
S(1)–C(2)
C(8a)–C(4a)–
C(4)–C(3)
H(2)pax–C(2)–
C(3)–H(3)
H(2)peq–C(2)–
C(3)–H(3)
H(3)–C(3)–
C(4)–H(4)
Dipole
moment
trans
cis
217.6
216.8
29.0
215.1
172.3
173.4
265.8
265.3
164.3
55.0
5.054
4.341
only, as expected, in J3,4 but also in dH(2) values because of
pax
1,3-pseudodiaxial deshielding interactions between H(2)pax
and 4-NO2 in the cis form. Similarly significant variations are
observed also in the chemical shifts of H(3) and H(4) on going
from cis-2 to trans-2.
From the trans-2/cis-2 ratios observed in the crude final
mixtures (Table 1) it appears that the cyclization occurs with
no significant stereoselectivity but for the 1-naphthyl
derivative: in this case, the ca. threefold predominance of
the cis racemic couple is remarkable and presumably the
result of steric effects. It should be also pointed out that a
crystallization of the crude from ethanol allows, in the case
of the just cited 1-naphthyl derivative, the recovering of an
almost pure cis isomer, while no appreciable alteration of
the trans/cis ratio has been observed in the other cases; on
the other hand, the use of a less polar mixed solvent (viz.
ethanol/dioxane) in the case of the model compound 2d
leads to a significant increase in the percentage of the more
polar trans isomer (see Table 2) in the recovered crystals
(the trans/cis ratio changing from 1:1.2 to 1:0.7 and 1:0.5
after one and two crystallizations, respectively).
Figure 1. Configuration and preferred half-chair conformation of the two
diastereoisomers of 2 (only one enantiomer shown).
calculated to be rather close to 1808 for the trans form and
rather close to 608 for the cis one.
Although other conformations cannot be completely ruled out
and could be present as minor components, nevertheless these
results provide a valuable key to the interpretation of 1H NMR
spectra. In fact, the Karplus-Conroy rule15 predicts high J3,4
values (10–15 Hz) for the quasi-trans 1,2-pseudodiaxial
interaction of H(3) and H(4) in the trans form and low values
(2–5 Hz) for the staggered 1,2-pseudoaxial-pseudoequatorial
interaction of the same protons in the cis form. Thus the non
aromatic 1H NMR signals of the two racemic pairs of 2 can be
fullyinterpretedandassignmentsaregiveninTable 3. Itstands
out that diastereomeric pairs exhibit striking differences not
3. Conclusions
The results herein enlighten an original and attractive access
to the thiochroman S,S-dioxide ring system, which
originates from the ring-opening of 3-nitrobenzo[b]thio-
phene (1) and whose key step is represented by an
intramolecular Michael-type addition of a sulfonyl-stabil-
ized carbanion onto a nitrovinylic moiety (6!2: see
Schemes 1 and 2).
1
Table 3. H NMR Data (see Section 4) for the non-aromatic protons of the diastereomeric cis/trans racemic pairs of thiochromans 2a
Isomer
dH(2)
dH(2)
dH(3)
dH(4)
J2
J2
pax;3
J2
peq;3
J3,4
pax;2peq
pax
peq
trans-2a
cis-2a
trans-2b
cis-2b
trans-2c
cis-2c
trans-2d
cis-2d
3.73(dd)
4.74 (app t)
3.60 (dd)
4.76 (app t)
3.71 (dd)
4.72 (app t)
3.71 (dd)
4.72 (app t)
3.70 (dd)
4.70 (app t)
4.23 (br app t)
4.78 (app t)
4.21 (dd)
3.60 (dd)
3.56 (dd)
3.48b
4.62 (app td)
4.45 (ddd)
4.99 (app td)
4.62 (dd)
6.13 (d)
6.00 (d)
6.30 (d)
5.94 (d)
6.14 (d)
5.99 (d)
6.10 (d)
5.97 (d)
6.09 (d)
5.97 (d)
7.03 (d)
6.59 (d)
6.57 (d)
6.47 (d)
14.2
13.6
14.3
12.4
13.8
13.6
14.3
13.4
14.2
13.6
14.1
14.0
14.2
13.6
12.0
13.8
12.1
14.0
12.5
13.8
12.0
13.6
11.8
13.8
13e
4.0
2.2
4.2
c
11.4
4.4
11.0
4.0
11.0
4.1
11.0
4.4
11.0
4.4
10.6
4.1
10.2
4.4
3.48b
3.55b
4.56 (app td)
4.39 (ddd)
4.57 (app td)
4.40 (ddd)
4.60 (app td)
4.42 (ddd)
5.61 (br app t)
5.36 (ddd)
4.9b
3.5
2.4
4.1
2.2
4.4
2.2
2.6
2.2
3.0
2.6
3.55b
3.58 (dd)
3.54 (dd)
3.58 (dd)
3.52 (dd)
3.86 (dd)
3.88 (dd)
3.87 (dd)
3.91 (dd)
trans-2f
cis-2f
trans-2gd
cis-2gd
trans-2hd
cis-2hd
13.2
12.6
13.5
4.57 (app t)
4.9b
a
Chemical shifts as d ppm from internal TMS, coupling constants in Hz. Solvent: CDCl3, unless otherwise specified; pax¼pseudoaxial,
peq¼pseudoequatorial. No long-range coupling between non-aromatic and aromatic protons could be detected at 200 MHz (see Ref. 16).
Overlapping signals.
b
c
In this product J2 ;3 is very low and not detectable, possibly because of some little difference in ring conformation as a consequence of the steric requirement
of the 2-MeC6H4 group.
peq
d
e
In acetone-d6.
Broadening of the relevant triplets does not allow a more accurate measurement.

4970
L. Bianchi et al. / Tetrahedron 60 (2004) 4967–4973
A
1H NMR study, together with molecular-mechanics
calculations, has allowed to gain insights into the configur-
ation of compounds 2 and their conformation.
(4H, m), 7.42–7.53 (2H, m), 8.51 (1H, s); 13C NMR
(CDCl3) d 16.04, 20.15, 125.64, 125.94, 126.84, 129.00,
130.00, 130.23, 130.39, 130.51, 130.58, 131.46, 134.21,
139.10, 140.14, 148.93. Anal. Calcd for C16H15NO2S: C,
67.3; H, 5.3; N, 4.9%. Found: C, 67.5; H, 5.2; N, 4.8%.
It should be finally emphasized that the overall 1!2
protocol described herein represents a further example of
heterocyclic synthesis by means of a ring-opening/ring-
closing procedure which takes advantage of the non-
benzenoid behaviour of nitrothiophene derivatives towards
secondary nucleophilic amines.11
4.2.3. (E)-1-[2-(Methylthio)phenyl]-1-nitro-2-(m-tolyl)-
ethylene (5c). (0.94 g, 87%). Yellow solid, mp 65–66 8C
(petroleum ether); nmax (Nujol) 1646, 1581, 1504, 1314,
1
1173, 1070 cm21; H NMR (CDCl3) d 2.22 (3H, s), 2.42
(3H, s), 6.84 (1H, app d), 6.95 (1H, s), 7.05–7.32 (4H, m),
7.38–7.58 (2H, m), 8.27 (1H, s); 13C NMR (CDCl3) d
15.99, 21.25, 125.93, 126.92, 127.80, 128.70, 130.23,
130.81, 130.95, 131.16, 131.88, 132.16, 136.48, 138.48,
140.07, 147.80. Anal. Calcd for C16H15NO2S: C, 67.3; H,
5.3; N, 4.9%. Found: C, 67.2; H, 5.2; N, 4.8%.
4. Experimental
4.1. General
1H NMR and 13C NMR spectra were recorded at 200 and
50 MHz, respectively; chemical shifts (TMS as internal
reference) are reported as d values (ppm). MS(ESI) analyses
were recorded on a Micromass Z0MD Waters instrument
(30 V, 13.2 kV). Melting points were determined with a
Bu¨chi 535 apparatus and are uncorrected. Petroleum ether
and light petroleum refer to the fractions with bp 40–60 and
80–100 8C, respectively. Silica gel 230–400 mesh was used
for column chromatography, all solvents being distilled
before use. Tetrahydrofuran (THF) was purified by standard
methods and distilled over potassium benzophenone ketyl
before use. Compound 4 was synthesized as previously
reported.12 Commercial lithium bis(trimethylsilyl)amide
(LHMDS, 1 M in THF) was used as received. All other
commercially available reagents were used as received.
4.2.4. (E)-1-[2-(Methylthio)phenyl]-1-nitro-2-(p-tolyl)-
ethylene (5d). (1.02 g, 94%). Yellow solid, mp 56–57 8C
(light petroleum).12
4.2.5. (E)-1-[2-(Methylthio)phenyl]-1-nitro-2-(2,4,6-tri-
methylphenyl)ethylene (5e). [0.49 g, 41% (99% based on
the unreacted substrate)]. Yellow solid, mp 128–129 8C
(light petroleum); nmax (Nujol) 1645, 1609, 1585, 1518,
1
1328, 1172, 1067, 1040 cm21; H NMR (CDCl3) d 2.08
(6H, s), 2.22 (3H, s), 2.44 (3H, s), 6.75–6.83 (3H, m), 7.00
(1H, td, J¼7.3, 1.4 Hz), 7.31 (1H, td, J¼7.5, 1.4 Hz), 7.40
(1H, dd, J¼7.8, 1.4 Hz), 8.18 (1H, s); 13C NMR (CDCl3) d
17.40, 20.36, 21.01, 125.78, 127.82, 128.59, 129.12, 130.36,
130.93, 131.39, 135.51, 136.16, 138.61, 139.31, 151.87.
Anal. Calcd for C18H19NO2S: C, 69.0; H, 6.1; N, 4.5%.
Found: C, 69.2; H, 6.0; N, 4.4%.
Organometallic reagents. All the reagents were THF or
Et2O solutions titrated17 just before use. Phenyl-, 4-methyl-
phenyl-, 2,4,6-trimethylphenyl-, 1-naphthyl-magnesium
bromides, 2-methylphenyl-, 3-methylphenyl-magnesium
chlorides were commercial solutions in THF; 4-chloro-
phenylmagnesium bromide and 2-thienyllithium were
commercial solutions in Et2O.
4.2.6. (E)-2-(4-Chlorophenyl)-1-[2-(methylthio)phenyl]-
1-nitroethylene (5f). (1.14 g, 99%). Yellow solid, mp
96–98 8C (light petroleum); nmax (Nujol) 1655, 1583, 1519,
1491, 1407, 1325, 1207, 1166, 1092, 1069, 1011 cm21; 1H
NMR (CDCl3) d 2.42 (3H, s), 7.02 (2H, d, J¼8.4 Hz), 7.14–
7.31 (4H, m), 7.40 (1H, d, J¼7.8 Hz), 7.52 (1H, td, J¼7.5,
1.4 Hz), 8.24 (1H, s); 13C NMR (CDCl3) d 15.79, 125.94,
126.73, 129.18, 129.43, 129.50, 131.01, 131.06, 132.03,
134.87, 137.17, 140.09, 148.29. Anal. Calcd for C15H12-
ClNO2S: C, 58.9; H, 4.0; N, 4.6%. Found: C, 59.1; H, 3.9;
N, 4.7%.
4.2. Reactions of 4 with aromatic organometallic
reagents
The reactions were performed on 1 g of compound 412
(3.78 mmol) following the procedure previously reported
for the synthesis of 5d.12 Yields of compounds 5 are
collected in Table 1.
4.2.7. (E)-1-[2-(Methylthio)phenyl]-2-(1-naphthyl)-1-
nitroethylene (5g). (1.20 g, 99%). Yellow solid, mp 158–
159 8C (toluene/light petroleum); nmax (Nujol) 1641, 1584,
1518, 1355, 1322, 1243, 1169, 1071, 1017 cm21; 1H NMR
(CDCl3) d 2.44 (3H, s), 7.05–7.27 (4H, m), 7.33–7.48 (2H,
m), 7.50–7.69 (2H, m), 7.74–7.90 (2H, m), 8.16 (1H, d,
J¼8.4 Hz), 9.01 (1H, s); 13C NMR (CDCl3) d 16.07, 123.52,
125.13, 125.60, 126.45, 126.77, 127.27, 128.05, 128.21,
128.87, 129.98, 130.55, 130.86, 131.41, 131.95, 133.33,
133.78, 140.31, 150.14. Anal. Calcd for C19H15NO2S: C,
71.0; H, 4.7; N, 4.4%. Found: C, 71.2; H, 4.6; N, 4.4%.
4.2.1. (E)-1-[2-(Methylthio)phenyl]-1-nitro-2-phenyl-
ethylene (5a). (1.02 g, 99%). Yellow solid, mp 95–96 8C
(light petroleum); nmax (Nujol) 1649, 1584, 1513, 1324,
1
1212, 1166, 1069 cm21; H NMR (CDCl3) d 2.41 (3H, s),
7.09 (2H, app d), 7.17–7.56 (7H, m), 8.30 (1H, s); 13C NMR
(CD3SOCD3) d 14.52, 125.58, 125.99, 128.78, 128.95,
130.70, 130.78, 130.97, 131.02, 131.21, 136.20, 139.50,
147.44. Anal. Calcd for C15H13NO2S: C, 66.4; H, 4.8; N,
5.2%. Found: C, 66.3; H, 4.7; N, 5.2%.
4.2.8. (E)-1-[2-(Methylthio)phenyl]-1-nitro-2-(2-
thienyl)ethylene (5h). [1.04 g, 99% (reaction time: 4 h)].
Yellow solid, mp 106–108 8C (light petroleum); nmax
(Nujol) 1632, 1583, 1500, 1415, 1311, 1286, 1250, 1237,
1214, 1052, 1040 cm21; 1H NMR (CD3SOCD3) d 2.40 (3H,
4.2.2. (E)-1-[2-(Methylthio)phenyl]-1-nitro-2-(o-tolyl)-
ethylene (5b). (1.02 g, 95%). Yellow solid, mp 94–96 8C
(light petroleum); nmax (Nujol) 1647, 1581, 1513, 1323,
1
1288, 1228, 1161, 1070 cm21; H NMR (CD3COCD3) d
2.47 (3H, s), 2.51 (3H, s), 6.80–6.99 (2H, m), 7.15–7.32

L. Bianchi et al. / Tetrahedron 60 (2004) 4967–4973
4971
s), 7.16 (1H, dd, J¼4.8, 3.8 Hz), 7.33–7.40 (2H, m), 7.51
(1H, app d, J¼8.2 Hz), 7.56–7.68 (1H, m), 7.74–7.83 (2H,
m), 8.75 (1H, s); 13C NMR (CD3COCD3) d 15.45, 126.90,
127.69, 128.55, 129.80, 131.13, 132.30, 132.75, 135.24,
135.83, 138.07, 141.58, 145.90. Anal. Calcd for
C13H11NO2S2: C, 56.3; H, 4.1; N, 5.1%. Found: C, 56.3;
H, 4.0; N, 5.0%.
4.3.5. (E)-1-[2-(Methylsulfonyl)phenyl]-1-nitro-2-(2,4,6-
trimethylphenyl)ethylene (6e). (684 mg, 99%). Pale
yellow solid, mp 202–203 8C (ethanol); nmax (Nujol)
1649, 1611, 1530, 1339, 1305, 1265, 1156, 1119,
1
1071 cm21; H NMR (CD3SOCD3) d 2.07 (6H, s), 2.17
(3H, s), 3.20 (3H, s), 6.80 (2H, s), 6.94 (1H, dd, J¼7.7,
1.5 Hz), 7.53 (1H, td, J¼7.5, 1.3 Hz), 7.69 (1H, td, J¼7.7,
1.4 Hz), 8.12 (1H, dd, J¼7.9, 1.3 Hz), 8.36 (1H, s); 13C
NMR (CD3SOCD3) d 19.87, 20.47, 43.23, 127.51, 128.26,
128.32, 130.40, 131.32, 132.90, 133.45, 135.59, 135.83,
138.30, 139.21, 149.99. Anal. Calcd for C18H19NO4S: C,
62.6; H, 5.6; N, 4.1%. Found: C, 62.4; H, 5.5; N, 4.0%.
4.3. Oxidation of compounds 5 to 6
The reaction was performed on 2 mmol of the appropriate 5,
according to the conditions described in Ref. 11. Yields are
reported in Table 1.
4.3.6. (E)-2-(4-Chlorophenyl)-1-[2-(methylsulfonyl)-
phenyl]-1-nitroethylene (6f). (670 mg, 99%). Yellow
solid, mp 149–150 8C (ethanol); nmax (Nujol) 1649, 1584,
1527, 1407, 1313, 1208, 1151, 1120, 1089, 1011 cm21; 1H
NMR (CD3SOCD3) d 3.04 (3H, s), 7.12 (2H, d, J¼8.6 Hz),
7.41 (2H, d, J¼8.6 Hz), 7.54–7.63 (1H, m), 7.83–7.97 (2H,
m), 8.19–8.27 (1H, m), 8.43 (1H, s); 13C NMR (CD3-
SOCD3) d 43.26, 128.84, 129.16, 129.42, 130.32, 131.92,
132.58, 133.32, 133.95, 134.87, 135.99, 139.67, 146.83.
Anal. Calcd for C15H12ClNO4S: C, 53.3; H, 3.6; N, 4.1%.
Found: C, 53.2; H, 3.6; N, 4.2%.
4.3.1. (E)-1-[2-(Methylsulfonyl)phenyl]-1-nitro-2-
phenylethylene (6a). (600 mg, 99%). Yellow solid, mp
116–117 8C (ethanol); nmax (Nujol) 1643, 1598, 1512,
1
1322, 1306, 1213, 1152, 1122 cm21; H NMR (CDCl3) d
2.97 (3H, s), 7.02 (2H, d, J¼7.2 Hz), 7.18–7.40 (4H, m),
7.67–7.83 (2H, m), 8.22 (1H, dd, J¼7.3, 1.9 Hz), 8.37 (1H,
s); 13C NMR (CD3SOCD3) d 43.23, 128.99, 129.24, 130.26,
130.39, 131.01, 131.27, 131.75, 133.39, 134.78, 135.09,
139.63, 146.35. Anal. Calcd for C15H13NO4S: C, 59.4; H,
4.3; N, 4.6%. Found: C, 59.3; H, 4.3; N, 4.5%.
4.3.2. (E)-1-[2-(Methylsulfonyl)phenyl]-1-nitro-2-(o-
tolyl)ethylene (6b). (616 mg, 97%). Yellow solid, mp
174–175 8C (ethanol); nmax (Nujol) 1650, 1530, 1336,
4.3.7. (E)-1-[2-(Methylsulfonyl)phenyl]-2-(1-naphthyl)-
1-nitroethylene (6g). (707 mg, 99%). Yellow solid, mp
213–214 8C (ethanol/dioxane); nmax (Nujol) 1646, 1510,
;
1310, 1243, 1153, 1119, 1069 cm21 1H NMR (CD3-
1305, 1266, 1232, 1151, 1121, 1073 cm21
;
1H NMR
(CD3SOCD3) d 2.47 (3H, s), 3.09 (3H, s), 6.61 (1H, d,
J¼7.6 Hz), 6.95 (1H, t, J¼7.3 Hz), 7.18–7.33 (2H, m),
7.45 (1H, app dd, J¼7.0, 1.8 Hz), 7.69–7.86 (2H, m),
8.17 (1H, app dd, J¼7.4, 1.8 Hz), 8.49 (1H, s); 13C NMR
(CD3SOCD3) d 19.54, 43.09, 125.82, 128.60, 128.82,
129.88, 130.06, 130.37, 130.61, 131.46, 133.38, 133.74,
134.19, 139.23, 139.99, 147.78. Anal. Calcd for
C16H15NO4S: C, 60.6; H, 4.8; N, 4.4%. Found: C, 60.4;
H, 4.7; N, 4.3%.
SOCD3) d 3.12 (3H, s), 7.03 (1H, d, J¼7.4 Hz), 7.27–7.39
(2H, m), 7.57–7.80 (4H, m), 7.96 (2H, app t, J¼8.8 Hz),
8.15 (1H, dd, J¼7.9, 1.3 Hz), 8.22 (1H, d, J¼7.6 Hz), 8.97
(1H, s); 13C NMR (CDCl3) d 43.16, 124.06, 125.12, 126.72,
127.39, 127.88, 128.19, 128.63, 128.73, 130.05, 130.62,
131.16, 131.43, 132.89, 133.02, 133.57, 134.08, 140.06,
149.23. Anal. Calcd for C19H15NO4S: C, 64.6; H, 4.3; N,
4.0%. Found: C, 64.4; H, 4.2; N, 4.0%.
4.3.8. (E)-1-[2-(Methylsulfonyl)phenyl]-1-nitro-2-(2-
thienyl)ethylene (6h). (612 mg, 99%). Yellow solid, mp
151–152 8C (ethanol); nmax (Nujol) 1627, 1337, 1305,
4.3.3. (E)-1-[2-(Methylsulfonyl)phenyl]-1-nitro-2-(m-
tolyl)ethylene (6c). (630 mg, 99%). Yellow solid, mp
155–156 8C (ethanol); nmax (Nujol) 1646, 1523, 1337,
1
1246, 1152, 1120, 1052 cm21; H NMR (CDCl3) d 2.93
1307, 1246, 1181, 1150, 1124 cm21
;
1H NMR (CD3-
(3H, s), 7.06 (1H, dd, J¼5.1, 3.7 Hz), 7.38 (1H, d,
J¼3.7 Hz), 7.42 (1H, dd, J¼5.1, 0.7 Hz), 7.46–7.55 (1H,
m), 7.77–7.89 (2H, m), 8.20–8.29 (1H, m), 8.58 (1H, s);
13C NMR (CD3SOCD3) d 43.48, 128.13, 128.31, 129.88,
130.54, 132.24, 134.04, 134.18, 135.06, 135.27, 138.58,
139.72, 143.04. Anal. Calcd for C13H11NO4S2: C, 50.5; H,
3.6; N, 4.5%. Found: C, 50.5; H, 3.5; N, 4.4%.
SOCD3) d 2.16 (3H, s), 3.00 (3H, s), 6.81 (1H, d, J¼7.4 Hz),
6.98 (1H, s), 7.13–7.27 (2H, m), 7.56–7.63 (1H, m), 7.84–
7.97 (2H, m), 8.19–8.26 (1H, m), 8.36 (1H, s); 13C NMR
(CD3SOCD3) d 20.69, 43.25, 127.80, 128.85, 129.39,
130.26, 130.33, 131.71, 131.96, 132.07, 133.41, 134.76,
135.19, 138.27, 139.60, 146.23. Anal. Calcd for
C16H15NO4S: C, 60.6; H, 4.8; N, 4.4%. Found: C, 60.7;
H, 4.7; N, 4.4%.
4.4. Reaction of compounds 6 with LHMDS
4.3.4. (E)-1-[2-(Methylsulfonyl)phenyl]-1-nitro-2-(p-
tolyl)ethylene (6d). (600 mg, 94%). Yellow solid, mp
160–161 8C (ethanol); nmax (Nujol) 1655, 1605, 1513,
In a flask, the appropriate 6 (0.3 mmol) was dissolved under
Argon in THF (19 mL) and LHMDS 1 M (1.1 mol equiv.,
0.33 mL) was added by a syringe under magnetic stirring.
The proceeding of the reaction was followed by TLC and,
after completion, the mixture was poured into saturated
aqueous NH4Cl (50 mL), and extracted with dichloro-
methane (2£20 mL), the organic extracts being dried over
Na2SO4. The crude solid residue, obtained by filtration and
removal of the solvent under reduced pressure, was
generally pure by 1H NMR analysis, being a diastereomeric
cis/trans mixture of compounds 2. Yields of compounds 2
1330, 1314, 1192, 1168, 1156, 1125 cm21 1H NMR
;
(CDCl3) d 2.30 (3H, s), 2.95 (3H, s), 6.89 (2H, d,
J¼8.3 Hz), 7.05 (2H, d, J¼8.3 Hz), 7.35–7.41 (1H, m),
7.67–7.83 (2H, m), 8.18–8.27 (1H, m), 8.35 (1H, s); 13C
NMR (CD3SOCD3) d 20.79, 43.23, 127.48, 129.43, 129.56,
130.15, 130.98, 131.54, 133.30, 134.65, 135.09, 139.59,
141.70, 145.47. Anal. Calcd for C16H15NO4S: C, 60.6; H,
4.8; N, 4.4%. Found: C, 60.5; H, 4.8; N, 4.3%.

4972
L. Bianchi et al. / Tetrahedron 60 (2004) 4967–4973
are reported in Table 1 together with the relevant cis/trans
ratios. As mentioned in the text, the crystallization of the
crude residues from ethanol brings about only minor
variations in the diastereomeric ratio in all cases but for
the 1-naphthyl derivative 2g, for which the pure cis
stereoisomer can be recovered: therefore, the spectroscopic
data reported below refer to the crystallized mixture in every
(1H cis and 1H trans, overlapping multiplets), 3.71 (1H
trans, dd, J¼13.8, 12.5 Hz), 4.39 (1H cis, ddd, J¼13.8, 4.1,
2.4 Hz), 4.56 (1H trans, app td, J¼12.5, 11.0, 3.5 Hz), 4.72
(1H cis, app t, J¼13.8, 13.6 Hz), 5.99 (1H cis, d, J¼4.1 Hz),
6.14 (1H trans, d, J¼11.0 Hz), 6.98–7.78 (7H cis and 7H
trans, m), 8.09 (1H cis and 1H trans, m); 13C NMR
(CD3COCD3) d 21.38, 41.54, 44.64, 49.24, 53.41, 89.70,
91.88, 124.69, 124.76, 125.19, 125.47, 128.09, 128.86,
129.18, 129.39, 129.81, 130.04, 130.08, 130.32, 130.89,
131.81, 132.84, 134.16, 134.45, 137.54, 138.15, 139.53,
139.84, 139.88, 140.53 (two pairs of carbons are acciden-
tally isochronous); MS(ESI): m/z 340.2 (MþNa)þ, 316.1
(M21). Anal. Calcd for C16H15NO4S: C, 60.6; H, 4.8; N,
4.4%. Found: C, 60.4; H, 4.7; N, 4.4%.
1
case but for 2g. For the latter, H NMR data for the crude
residue, where both diastereoisomers are present, are
reported, together with a full spectroscopic characterization
of the crystallized cis stereoisomer. In the 1H NMR spectra
of compounds 2 some signals appeared as triplets, as a
consequence of the similar values of the two coupling
constants involved; in these cases, as the frequency
difference between the outer lines corresponds to the sum
of the two J values, if one of them was known the other was
calculated accordingly.
4.4.4. 4-Nitro-3-(p-tolyl)thiochroman S,S-dioxide (2d).
(84 mg, 88%, mixture of trans:cis isomers 1:1.2). White
solid, mp 194–196 8C (ethanol); nmax (Nujol) 1553, 1513,
1402, 1366, 1343, 1302, 1264, 1247, 1225, 1158, 1131,
1073 cm21; 1H NMR (CDCl3) d 2.37 (3H cis and 3H trans,
2 s overlapped), 3.54 (1H cis, dd, J¼13.4, 2.2 Hz), 3.58 (1H
trans, dd, J¼14.3, 4.1 Hz), 3.71 (1H trans, dd, J¼14.3,
12.0 Hz), 4.40 (1H cis, ddd, J¼13.6, 4.4, 2.2 Hz), 4.57 (1H
trans, app td, J¼12.0, 11.0, 4.1 Hz), 4.72 (1H cis, app t,
J¼13.6, 13.4 Hz), 5.97 (1H cis, d, J¼4.4 Hz), 6.10 (1H
trans, d, J¼11.0 Hz), 7.06–7.78 (7H cis and 7H trans, m),
8.04–8.18 (1H cis and 1H trans, m); 13C NMR (CDCl3) d
21.14, 41.05, 42.80, 48.67, 53.57, 88.64, 90.87, 124.47,
124.54, 126.83, 127.03, 127.07, 127.71, 128.58, 129.52,
130.23, 130.34, 131.03, 132.10, 132.45, 133.21, 133.37,
133.68, 138.17, 139.05, 139.12, 139.21 (the methyl carbons
of the two isomers are accidentally isochronous); MS(ESI):
m/z 340.3 (MþNa)þ, 316.1 (M21). Anal. Calcd for
C16H15NO4S: C, 60.6; H, 4.8; N, 4.4%. Found: C, 60.5;
4.4.1. 4-Nitro-3-phenylthiochroman S,S-dioxide (2a).
(71 mg, 78%, mixture of trans:cis isomers 1:1.4). White
solid, mp 162–170 8C (ethanol); nmax (Nujol) 1556, 1296,
1
1247, 1225, 1158, 1126, 1070 cm21; H NMR (CDCl3) d
3.56 (1H cis, dd, J¼13.6, 2.2 Hz), 3.60 (1H trans, dd,
J¼14.2, 4.0 Hz), 3.73 (1H trans, dd, J¼14.2, 12.0 Hz), 4.45
(1H cis, ddd, J¼13.8, 4.4, 2.2 Hz), 4.62 (1H trans, app td,
J¼12.0, 11.4, 4.0 Hz), 4.74 (1H cis, app t, J¼13.8, 13.6 Hz),
6.00 (1H cis, d, J¼4.4 Hz), 6.13 (1H trans, d, J¼11.4 Hz),
7.18–7.80 (8H cis and 8H trans), 8.04–8.18 (1H cis and 1H
trans, m); 13C NMR (CDCl3) d 41.40, 43.13, 48.57, 53.48,
88.55, 90.72, 124.51, 124.59, 127.02, 127.08, 127.25,
127.65, 128.54, 129.21, 129.28, 129.54, 129.61, 129.73,
131.09, 132.16, 133.43, 133.75, 135.45, 136.25, 138.16,
139.05; MS(ESI): m/z 326.3 (MþNa)þ, 302.0 (M21). Anal.
Calcd for C15H13NO4S: C, 59.4; H, 4.3; N, 4.6%. Found: C,
59.2; H, 4.3; N, 4.5%.
1
H, 4.8; N, 4.4%. The H NMR for the 4-deutero-4-nitro-3-
(p-tolyl)thiochroman S,S-dioxide (20d) is analogous to that
of 2d but for the signals at d 4.40 and 4.57 which are (1H cis,
dd, J¼13.6, 2.2 Hz) and (1H trans, dd, J¼12.2, 4.3 Hz),
respectively.
4.4.2. 4-Nitro-3-(o-tolyl)thiochroman S,S-dioxide (2b).
(76 mg, 80%, mixture of trans:cis isomers 1:2.2). White
solid, mp 187–189 8C (ethanol); nmax (Nujol) 1552, 1413,
1327, 1306, 1267, 1253, 1234, 1197, 1166, 1156, 1132,
1072 cm21; 1H NMR (CDCl3) d 2.44 (3H trans, s), 2.48 (3H
cis, s), 3.48 (1H cis and 1H trans, overlapping multiplets),
3.60 (1H trans, dd, J¼14.3, 12.1 Hz), 4.62 (1H cis, dd,
J¼14.0, 4.0 Hz), 4.76 (1H cis, app t, J¼14.0, 12.4 Hz), 4.99
(1H trans, app td, J¼12.1, 11.0, 4.2 Hz), 5.94 (1H cis, d,
J¼4.0 Hz), 6.30 (1H trans, d, J¼11.0 Hz), 6.98 (1H cis, d,
J¼7.0 Hz), 7.20–7.34 (3H cis and 4H trans, m), 7.43 (1H
trans, m), 7.52 (1H cis, m), 7.61–7.79 (2H cis and 2H trans,
m), 8.05–8.19 (1H cis and 1H trans, m); 13C NMR (CDCl3)
d 19.41, 37.64, 38.40, 49.02, 53.97, 86.64, 89.57, 124.52,
124.68, 125.40, 125.81, 127.01, 127.25, 127.44, 127.73,
128.78, 128.83, 129.05, 129.59, 131.08, 131.36, 131.81,
132.14, 133.42, 133.59, 133.69, 134.49, 135.35, 136.44,
139.10 (two pairs of carbons are accidentally isochronous);
MS(ESI): m/z 340.2 (MþNa)þ, 316.2 (M21). Anal. Calcd
for C16H15NO4S: C, 60.6; H, 4.8; N, 4.4%. Found: C, 60.6;
H, 4.7; N, 4.5%.
4.4.5. 3-(p-Chlorophenyl)-4-nitrothiochroman S,S-
dioxide (2f). (79 mg, 78%, mixture of trans:cis isomers
ca. 1:1). White solid, mp 189–195 8C (ethanol); nmax
(Nujol) 1552, 1308, 1157, 1131, 1096, 1015 cm21; 1H NMR
(CDCl3) d 3.52 (1H cis, dd, J¼13.6, 2.2 Hz), 3.58 (1H trans,
dd, J¼14.2, 4.4 Hz), 3.70 (1H trans, dd, J¼14.2, 11.8 Hz),
4.42 (1H cis, ddd, J¼13.8, 4.4, 2.2 Hz), 4.60 (1H trans, app
td, J¼11.8, 11.0, 4.4 Hz), 4.70 (1H cis, app t, J¼13.8,
13.6 Hz), 5.97 (1H cis, d, J¼4.4 Hz), 6.09 (1H trans, d,
J¼11.0 Hz), 7.13–7.80 (7H cis and 7H trans, m), 8.04–
8.17 (1H cis and 1H trans, m); 13C NMR (CDCl3) d 40.85,
42.56, 48.44, 53.28, 88.28, 90.53, 124.53, 124.64, 127.02,
127.34, 128.26, 128.41, 128.66, 129.55, 129.86, 129.99,
131.20, 132.28, 133.54, 133.86, 134.70, 135.38, 138.01,
138.90 (two pairs of carbons are accidentally isochronous);
MS(ESI): m/z 360.2 (MþNa)þ, 336.2 (M21). Anal. Calcd
for C15H12ClNO4S: C, 53.3; H, 3.6; N, 4.2%. Found: C,
53.2; H, 3.5; N, 4.1%.
4.4.3. 4-Nitro-3-(m-tolyl)thiochroman S,S-dioxide (2c).
(76 mg, 80%, mixture of trans:cis isomers 1:1.3). White
solid, mp 179–180 8C (ethanol); nmax (Nujol) 1552, 1300,
1265, 1244, 1219, 1195, 1155, 1129, 1073 cm21; 1H NMR
(CDCl3) d 2.37 (3H cis and 3H trans, 2 s overlapped), 3.55
4.4.6. 3-(1-Naphthyl)-4-nitrothiochroman S,S-dioxide
(2g). (105 mg, 99%, mixture of trans:cis isomers 1:3.0).
1H NMR (CD3COCD3) d 3.86 (1H trans, dd, J¼14.1,
2.6 Hz), 3.88 (1H cis, dd, J¼14.0, 2.2 Hz), 4.23 (1H trans,

L. Bianchi et al. / Tetrahedron 60 (2004) 4967–4973
4973
Boulton, A. J., McKillop, A., Eds.; Pergamon: Oxford, 1984;
Vol. 3, pp 885–942. (b) Ingall, A. H. Comprehensive
Heterocyclic Chemistry II; McKillop, A., Ed.; Pergamon:
Oxford, 1996; Vol. 5, p 501.
br t, J¼13 Hz), 4.78 (1H cis, app t, J¼14.0, 13.2 Hz), 5.36
(1H cis, ddd, J¼13.2, 4.1, 2.2 Hz), 5.61 (1H trans, br t,
J¼13 Hz), 6.59 (1H cis, d, J¼4.1 Hz), 7.03 (1H trans, d,
J¼10.6 Hz), 7.1–8.8 (11H cis and 11H trans, m) (assign-
ments supported by decoupling experiments). A crystal-
lization from ethanol afforded a white solid, mp 224–
226 8C, which was identified as the pure cis-diastereoisomer
by spectroscopic data; nmax (Nujol) 1551, 1509, 1415, 1305,
4. (a) Al-Nakib, T.; Bezjak, V.; Rashid, S.; Fullam, B.; Meegan,
M. J. Eur. J. Med. Chem. 1991, 26, 221–230. (b) Al-Nakib, T.;
Bezjak, V.; Meegan, M. J.; Chandy, R. Eur. J. Med. Chem.
1990, 25, 455–457. (c) Van Vliet, L. A.; Rodenhuis, N.;
Dijkstra, D.; Wikstroem, H.; Pugsley, T. A.; Serpa, K. A.;
Meltzer, L. T.; Heffner, T. G.; Wise, L. D.; Lajiness, M. E.;
Huff, R. M.; Svensson, K.; Sundell, S.; Lundmark, M. J. Med.
Chem. 2000, 43, 2871–2882. (d) Pigini, M.; Brasili, L.;
1
1252, 1160, 1133, 1073 cm21; H NMR (CD3COCD3) d
3.88 (1H, dd, J¼14.0, 2.2 Hz), 4.78 (1H, app t, J¼14.0,
13.2 Hz), 5.36 (1H, ddd, J¼13.2, 4.1, 2.2 Hz), 6.59 (1H, d,
J¼4.1 Hz), 7.43 (1H, d, J¼7.0 Hz), 7.50–7.94 (6H, m),
7.98–8.10 (2H, m), 8.15 (1H, m), 8.56 (1H, m); 13C NMR
(CD3COCD3) d 37.69, 49.84, 88.78, 123.36, 124.66,
125.54, 126.44, 127.13, 128.17, 129.54, 130.19, 130.28,
131.24, 131.46, 132.80, 133.40, 134.17, 134.92, 140.57;
MS(ESI): m/z 376.3 (MþNa)þ, 352.2 (M21). Anal. Calcd
for C19H15NO4S: C, 64.6; H, 4.3; N, 4.0%. Found: C, 64.4;
H, 4.2; N, 3.9%.
`
Giannella, M.; Giardina, D.; Gulini, U.; Quaglia, W.;
Melchiorre, C. J. Med. Chem. 1988, 31, 2300–2304.
(e) Baurmgarth, M.; Beier, N.; Gericke, R. J. Med. Chem.
1998, 41, 3736–3747. (f) Philip, A.; Jirkovsky, I.; Martel, R. R.
J. Med. Chem. 1980, 23, 1372–1376. (g) Ramalingam, K.;
Thyvelikakath, G. X.; Berlin, K. D.; Chesnut, R. W.; Brown,
R. A.; Durham, N. N.; Ealick, S. E.; van der Helm, D. J. Med.
Chem. 1977, 20, 647–650. (h) Holshouser, M. H.; Loeffler,
L. J.; Hill, I. H. J. Med. Chem. 1981, 24, 853–858.
(i) Holshouser, M. H.; Loeffler, L. J. J. Pharm. Sci. 1982,
71, 715–717. (j) For less recent reports on the pharmacologi-
cal (antipyretic, antidepressant and analgesic) properties of
thiochromans see: Adv. Heterocycl. Chem. 1975, 18, 59–97.
5. (a) Brogden, P. J.; Gabbutt, C. D.; Hepworth, J. D.
Comprehensive Heterocyclic Chemistry; Boulton, A. J.,
McKillop, A., Eds.; Pergamon: Oxford, 1984; Vol. 3,
pp 573–883. (b) Miyazaki, H.; Honda, K.; Asami, M.;
Inoue, S. J. Org. Chem. 1999, 64, 9507–9511. (c) Yadav, J. S.;
Reddy, B. V. S.; Rao, C. V.; Rao, K. V. J. Chem. Soc., Perkin
Trans. 1 2002, 1401–1404.
4.4.7. 4-Nitro-3-(2-thienyl)thiochroman S,S-dioxide (2h).
(65 mg, 70%, mixture of trans:cis isomers 1:0.9). Pale green
solid, mp 113–117 8C (ethanol); nmax (Nujol) 1552, 1300,
1
1246, 1155, 1127, 1069 cm21; H NMR (CD3COCD3) d
3.87 (1H trans, dd, J¼14.2, 3.0 Hz), 3.91 (1H cis, dd,
J¼13.6, 2.6 Hz), 4.21 (1H trans, dd, J¼14.2, 12.6 Hz), 4.57
(1H cis, app t, J¼13.6, 13.5 Hz), 4.83–4.97 (1H cis and 1H
trans, m), 6.47 (1H cis, d, J¼4.4 Hz), 6.57 (1H trans, d,
J¼10.2 Hz), 7.10 (1H cis and 1H trans, m), 7.21 (1H cis,
m), 7.27 (1H trans, m), 7.48–7.57 (2H cis and 1H trans, m),
7.68–8.12 (3H cis and 4H trans, m); 13C NMR (CDCl3) d
37.24, 38.73, 49.56, 53.90, 88.35, 91.32, 124.43, 124.50,
126.09, 126.20, 126.35, 127.00, 127.14, 127.26, 127.58,
127.66, 127.90, 129.63, 131.22, 132.27, 133.47, 133.78,
137.36, 138.07, 138.43, 138.83; MS(ESI): m/z 332.2
(MþNa)þ, 308.2 (M21). Anal. Calcd for C13H11NO4S2:
C, 50.5; H, 3.6; N, 4.5%. Found: C, 50.5; H, 3.5; N, 4.6%.
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Financial support was provided by grants from the
Universities of Genova and of Bologna, and from Ministero
`
dell’Istruzione, dell’Universita e della Ricerca (MIUR,
PRIN-2002).
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