Sequential reduction and dehydration of phenacyl-(E)-styryl sulfones to unsymmetrical (E,E)-bis(styryl) sulfones

Article abstract of DOI:10.1055/s-2005-918450

β-Keto vinylic sulfones, the key building blocks for the synthesis of the title compounds, were prepared by two different routes. NaBH₄ reduction of these compounds afforded β-hydroxy vinylic sulfones which were dehydrated with acetic anhydride

Full text of DOI:10.1055/s-2005-918450

PAPER
3639
Sequential Reduction and Dehydration of Phenacyl-(E)-Styryl Sulfones to
Unsymmetrical (E,E)-Bis(styryl) Sulfones
Reduction and
Dehydru
r
a
cyl-(
E
)
a
-Styryl Sul
l
f
ones
t
i
E
,
E
)
d
-Bis(styryl)
S
h
ulfones ar Reddy Mallireddigari, Venkat R. Pallela, E. Premkumar Reddy, M. V. Ramana Reddy*
Fels Institute for Cancer Research, Temple University School of Medicine, 3307 North Broad Street, Philadelphia, PA 19140-5101, USA
Fax +1(215)7071454; E-mail: rreddy@temple.edu
Received 27 January 2005; revised 23 June 2005
such as cyclopropanes,19 thiomorpholines,20 dithiane-1,1-
Abstract: b-Keto vinylic sulfones, the key building blocks for the
dioxides,21 pyrazolines,22 isoxazoles,23 1,4-substituted
synthesis of the title compounds, were prepared by two different
routes. NaBH4 reduction of these compounds afforded b-hydroxy
vinylic sulfones which were dehydrated with acetic anhydride and
butadienes24 and spiro heterocyclic systems.25 Recently,
bis(styrylsulfonyl) methanes and bis(styryl) sulfones have
BF3·Et2O to obtain bis(styryl) sulfones. Alternatively, one-pot syn- also been reported as potential HIV-1 integrase
inhibitors26 and anticancer agents, respectively.27
thesis of these bis(styryl) sulfones was also achieved directly from
b-keto vinylic sulfones by treating with NaBH4 in EtOH followed
Although some symmetrical bis(styryl) sulfones (both ar-
by refluxing with concentrated HCl.
omatic rings having the same substituents) with (E,E)-
configuration have been known for some time, the synthe-
Key words: b-keto vinylic sulfones, b-hydroxy-(E)-vinylic sul-
fones, (E,E)-bis(styryl) sulfones, styrylsulfinate, Knoevenagel con-
sis of unsymmetrical (E,E)-bis(styryl) sulfones (with dif-
ferent substitutions on each aromatic rings) are less
familiar. Kamigata et al.28 synthesized E,E-unsymmetri-
cal bis(styryl) sulfones by ruthenium(II) complex cata-
lyzed addition of arylethenesulfonyl chlorides to styrenes.
Earlier, we have reported19 the synthesis of E,E- and Z,E-
unsymmetrical bis(styryl) sulfones by Knoevenagel con-
densation of styryl sulfonyl acetic acids with araldehydes
in the presence of a catalytic amount of benzylamine. En-
couraged by their increasing interest in organic synthesis
and their significant biological activity, we herein report a
novel and convenient method for the synthesis of unsym-
metrical (E,E)-bis(styryl) sulfones. The b-keto vinylic
sulfones 5, which are the key intermediates in the prepa-
ration of bis(styryl) sulfones, were synthesized by two dif-
ferent methods (Schemes 1 and 2).
densation
Sulfone, a functional group that resembles the carbonyl
group, is associated with a high degree of thermodynamic
stability and survives a large number of transformations.
The important properties of sulfones thus culminated in
the synthesis and structural studies of a vast number of
compounds incorporating such a moiety.1–4 It is only with-
in the last two or three decades that a more diverse range
of sulfur chemistry has been explored. Sulfones have also
acquired importance chemotherapeutically as this moiety
is found to be a potential pharmacophore in many car-
bocyclic and heterocyclic systems.5–8 b-Keto vinyl sul-
fones have also served as a class of compounds of proven
value in organic synthesis as excellent acceptors for the
9
Michael additions and 2p partners in cycloaddition
The first step of the sequence is a reaction between phen-
acyl bromide (1) and mercaptoacetic acid (2) to generate
phenacylthioacetic acid (3), which on oxidation, yielded
phenacylsulfonylacetic acid (4).29 Condensation of 4 with
substituted benzaldehydes in glacial AcOH in the pres-
ence of a catalytic amount of benzylamine produced phen-
reactions6 due to the activation of the double bond by the
sulfone group.
b-Hydroxy sulfones are useful chiral synthons in organic
synthesis.10 Their preparation in enantiomerically pure
form has attracted considerable interest.11–13 They have
been successfully used in the synthesis of biologically ac-
tive molecules such as g-butenolides,14 g-butyrolac-
tones,14,15 d-valerolactones16 and other b-hydroxy
substituted sulfones.17 They are also useful synthetic in-
termediates for the preparation of enantiomerically pure
2,5-disubstituted tetrahydrofuran18 units found in many
natural products. While looking for pharmaceutically
promising analogs of sulfones, and as part of our ongoing
interest on styryl sulfones, we paid attention to the synthe-
sis of unsymmetrical (E,E)-bis(styryl) sulfones. These
compounds have been used as valuable precursors in the
synthesis of various carbocyclic and heterocyclic systems
acyl (E)-styryl sulfones
5
(Scheme 1, Table 1).
Alternatively, 5 were also prepared by the condensation of
sodium (E)-styrylsulfinates 8 with phenacyl bromides, es-
sentially following the procedure as described by Reddy
et al.29 Sodium (E)-styrylsulfinates 8 were made from (E)-
styrylsulfonyl chlorides 7 which are prepared by treating
sulfuryl chloride with styrene 6 in DMF at 0 °C
(Scheme 2, Table 1). NaBH4 reduction of phenacyl (E)-
styryl sulfones 5 that were prepared following Method A
(Scheme 1) produced b-hydroxy vinylic sulfones 9 in ex-
cellent yields (Table 1).
A number of reagents have been employed for dehydra-
tion of alcohols, such as phosphorus pentoxide,30 ceri-
um(III) chlorides,31 chromium dichloride32 and phthalic
anhydride.30 Some of these dehydrations were carried out
by first acetylating the hydroxyl group followed by elim-
SYNTHESIS 2005, No. 20, pp 3639–3643
Advanced online publication: 27.10.2005
DOI: 10.1055/s-2005-918450; Art ID: M00605SS
© Georg Thieme Verlag Stuttgart · New York
x
x.
x
x
.
2
0
0
5

3640
M. R. Mallireddigari et al.
PAPER
O
O
O
O
S
Br
NaOH, MeOH
OH
HS
+
R
R
OH
0 to 5 °C, 4–5 h, 85–90%
3
1
2
30% H2O2,
AcOH, 24 h
80–95%
O
O
O
O
O
O
O
R1C6H4CHO, C6H5CH2NH2
AcOH, reflux, 3 h, 72–85%
S
S
OH
R
R
R1
5
4
Scheme 1
O
O
S
SO2Cl2, DMF, 0 °C
N2, 3 h, 70–85%
Cl
R
R
7
6
NaHCO3,
80–90 °C,
2–3 h, 90–95% Na2SO3
O
O
O
O
O
R1C6H4COCH2Br
MeOH, r.t., 3 h, 62–64%
S
S
Na
R
R
R1
5
8
Scheme 2
ination with NaOAc. Dehydration of alcohols was also
achieved by mesylation of the hydroxyl group, followed
by the basic elimination of methanesulfonic acid with
Et3N.33 However, in our experience the yields obtained
using these methods were low and variable. Conversely,
when 9 were dehydrated with Ac2O/BF3·Et2O at 0 °C, the
dehydration process proceeded rapidly with complete dia-
stereoselectivity, resulting in (E,E)-bis(styryl) sulfones 10
(Scheme 3, Table 1). All the yields reported in the Table 1
for 10 (Scheme 3) are based on the molar equivalents of
b-hydroxy (E)-vinyl sulfones 9 (Scheme 3) taken in the
reaction. Alternatively 10 were also obtained directly
from 5 (Scheme 1) by one-pot NaBH4 reduction in EtOH
followed by dehydration with concentrated HCl.
(Scheme 3, Method B, Table 1) and the yields of forma-
tion of 10 are based on 5.
Table 1 Synthesis and Overall Yields of Prepared Compounds 5, 9
and 10
Com-
pound
R
R1
Mp (°C)
Yield (%)
Method A Method B
5a
5b
H
4-Cl
4-Cl
135–136
190–192
80
85
72
73
76
86
92
81
84
82
91
87
89
92
87
–
4-Cl
–
5c
4-CH3
4-CH3
4-CH3
H
4-OCH3 126–127
62
64
–
5d
4-H
142–143
165–166
122–124
177–179
5e
4-Cl
4-Cl
4-Cl
9a
–
9b
4-Cl
–
In conclusion, we report two new, mild and convenient
approaches for the synthesis of b-keto vinylic sulfones
which are the common precursors for both b-hydroxy vi-
nylic sulfones and E,E-asymmetrical bis(styryl) sulfones.
Also, we have developed a novel one-pot synthesis of
bis(styryl) sulfones from b-keto vinylic sulfones. The new
methods herein reported are straightforward, tolerate a va-
riety of functional groups and gave good yields with com-
plete diastereoselectivity.
9c
4-CH3
4-CH3
4-CH3
4-H
4-OCH3 110–111
–
9d
4-H
122–123
147–148
146–147
218–219
–
9e
4-Cl
4-Cl
4-Cl
–
10a
10b
10c
10d
10e
73
75
68
65
66
4-Cl
4-CH3
4-CH3
4-CH3
4-OCH3 166–168
4-H
119–121
151–153
All chemicals and solvents were purchased from commercial sourc-
es and were used without further treatment unless otherwise indicat-
ed. Solvents were dried using standard procedures and reactions
requiring anhydrous conditions were performed under N2. Reac-
tions were monitored by TLC on silica gel plates (60 Å; Aldrich)
and visualized under 254 nm UV light. Yields were of purified
product and were not optimized. Melting points were determined in
4-Cl
Synthesis 2005, No. 20, 3639–3643 © Thieme Stuttgart · New York

PAPER
Reduction and Dehydration of Phenacyl-(E)-Styryl Sulfones to (E,E)-Bis(styryl) Sulfones
3641
OH
O
O
O
O
O
S
S
NaBH4, EtOH, 0 °C
30 min, 81–92%
R
R
9
R1
R1
5
Ac2O, BF3⋅Et2O
0 °C, 87–92%
1. NaBH4, EtOH, 0.5 h
2. HCl, reflux, 6.5 h
OH
O
O
O
O
S
S
– H2O, 65–75%
R
R
10
R1
R1
Scheme 3
open capillary tubes using a Mel-Temp® electro thermal apparatus
and are uncorrected. IR spectra were recorded on a Perkin-Elmer
FT-IR 240-C spectrophotometer using KBr optics. 1H (400 MHz)
and 13C (100 MHz) NMR spectra were recorded on a Bruker
Avance 400 spectrometer using TMS as an internal standard.
Chemical shifts are expressed in ppm and the values are given in d
scale, multiplicity (s = singlet, d = doublet, m = multiplet, br s =
broad singlet), integration, coupling constant (J, Hz). Elemental
analyses were performed by Quantitative Technologies Inc. White
House, New Jersey. Phenacylsulfonylacetic acids were prepared ac-
cording to the procedure reported in the literature.29
5a
Solid; mp 135–136 °C.
IR (KBr): 1680, 1620, 1315, 1140, 1010 cm–1.
1H NMR (CDCl3): d = 4.74 (s, 2 H, CH2), 7.03 (d, J = 15.6 Hz, 1 H),
7.17–8.00 (m, 10 H).
13C NMR (CDCl3): d = 187.9 (C=O), 144.6 (4-ClC6H4CH=), 141.8,
138.2, 134.4 (=CHSO2), 131.0, 130.8, 130.4, 129.9, 129.8, 125.6,
63.0 (CH2).
Anal. Calcd for C16H13ClO3S: C, 59.91; H, 4.08. Found: C, 60.32;
H, 4.04.
Phenacyl (E)-Styryl Sulfones 5, General Procedure
Method A
5b
Solid; mp 190–192 °C.
IR (KBr): 1670, 1625, 1340, 1130, 1015 cm–1.
IH NMR (CDCl3): d = 4.78 (s, 2 H, CH2), 7.12 (d, J = 15.4 Hz, 1 H),
7.21–8.05 (m, 9 H).
13C NMR (CDCl3): d = 188.0 (C=O), 144.6 (4-ClC6H4CH=), 141.8,
138.2, 134.4 (=CHSO2), 131.0, 130.8, 130.4, 129.9, 129.8, 125.6,
63.1 (CH2).
A mixture of phenacylsulfonylacetic acid (4; 10 mmol), araldehyde
(10 mmol), AcOH (10 mL), and a catalytic amount of benzyl amine
(2–3) drops was refluxed for about 3 h. After cooling, the precipi-
tated product was filtered and washed with i-PrOH. If solid was not
formed, the reaction mixture was diluted with Et2O. The organic
layer was washed with sat. NaHCO3, dilute HCl and dried over
Na2SO4. The solvent was removed under vacuum to obtain the de-
sired product 5.
Anal. Calcd for C16H12Cl2O3S: C, 54.10; H, 3.40. Found: C, 54.14;
H, 3.37.
Method B
Sodium (E)-Styrylsulfinate (8)
Sulfuryl chloride (0.5 mol) was added dropwise to stirred anhyd
DMF (37 mL) cooled to 0 °C under N2. After the addition was com-
pleted, the mixture was warmed to r.t. and stirred further for 0.5 h.
Styrene 6 (0.25 mol) was then added in three portions and the reac-
tion mixture was gradually heated on a water bath at 90 °C for 3 h.
The reaction mixture was cooled and then poured onto the crushed
ice and the separated oily layer was extracted with Et2O and dried.
Evaporation of the solvent gave 7 (70–85%) as colorless crystals.
Recrystallization from CHCl3–light petroleum ether mixture yield-
ed pure product of sodium (E)-styrylsulfinate.
5c
Solid; mp 126–127 °C.
IR (KBr): 1690, 1625, 1335, 1145, 1015 cm–1.
1H NMR (CDCl3): d = 2.26 (s, 3 H, ArCH3), 3.82 (s, 3 H, ArOCH3),
4.72 (s, 2 H, CH2), 7.01 (d, J = 15.5 Hz, 1 H), 7.19–8.02 (m, 9 H).
13C NMR (CDCl3): d = 189.4 (C=O), 145.1 (4-CH3OC6H4CH=),
141.9, 138.1, 134.0 (=CHSO2), 131.5, 130.8, 130.3, 129.8, 129.4,
126.0, 62.2 (CH2), 53.2 (4-CH3OC6H4), 21.4 (4-CH3C6H4).
Anal. Calcd for C18H18O4S: C, 65.43; H, 5.49. Found: C, 65.39; H,
5.52.
A solution of sodium sulfite (0.3 mol) and NaHCO3 (0.31 mol) in
water (200 mL) was stirred on water bath maintained at 80–90 °C.
The appropriate (E)-styrylsulfonyl chloride 7 (0.16 mol) was added
to this solution in portions over a period of 0.5 h with stirring. After
completion of the addition, the mixture was stirred at 80–90 °C for
a further period of 2–3 h and then allowed to cool to r.t. The sodium
(E)-styrylsulfinate 8 thus separated as long colorless crystals was
collected on a Buchner filter and dried.
5d
Solid; mp 142–143 °C.
IR (KBr): 1670, 1610, 1320, 1140, 1000 cm–1.
1H NMR (CDCl3): d = 2.28 (s, 3 H, ArCH3), 4.71 (s, 2 H, CH2), 7.04
(d, J = 15.6 Hz, 1 H), 7.21–8.03 (m, 10 H).
13C NMR (CDCl3): d = 188.8 (C=O), 145.6 (C6H4CH=), 142.1,
138.1, 134.5 (=CHSO2), 131.9, 131.0, 130.5, 129.9, 129.6, 125.8,
62.8 (CH2), 21.6 (4-CH3C6H4).
A mixture of phenacyl bromide (10 mmol), sodium (E)-styrylsulfi-
nate (12 mmol) and aq MeOH (3:1, 100 mL) was stirred at r.t. for 3
h and then poured onto crushed ice. The solid that separated out was
filtered, washed with excess water and dried. The product, phenacyl
(E)-styryl sulfone 5 was recrystallized from i-PrOH.
Anal. Calcd for C17H16O3S: C, 67.97; H, 5.37. Found: C, 68.02; H,
5.35.
Synthesis 2005, No. 20, 3639–3643 © Thieme Stuttgart · New York

3642
5e
M. R. Mallireddigari et al.
PAPER
1H NMR (CDCl3): d = 1.92 (br s, 1 H, OH), 2.29 (s, 3 H, ArCH3),
3.11–3.30 (m, 2 H, CH2), 5.15 (d, 1 H, CH), 6.82 (d, J = 15.4 Hz, 1
H), 7.09–7.72 (m, 10 H).
13C NMR (CDCl3): d = 145.1 (CH=), 143.9, 138.2, 134.1
(=CHSO2), 130.8, 130.7, 129.9, 129.6, 127.3, 126.9, 69.3 (CHOH),
63.8 (CH2), 21.5 (4-CH3C6H4).
Solid; mp 165–166 °C.
IR (KBr): 1690, 1625, 1340, 1130, 1020 cm–1.
1H NMR (CDCl3): d = 2.30 (s, 3 H, ArCH3), 4.75 (s, 2 H, CH2), 7.05
(d, J = 15.4 Hz, 1 H), 7.19–8.00 (m, 9 H).
13C NMR (CDCl3): d = 188.8 (C=O), 145.6 (4-ClC6H4CH=), 142.0,
138.5, 134.4 (=CHSO2), 131.6, 130.9, 130.6, 129.9, 129.5, 125.5,
62.8 (CH2), 21.5 (4-CH3C6H4).
Anal. Calcd for C17H18O3S: C, 67.52; H, 6.09. Found: C, 67.56; H,
5.99.
Anal. Calcd for C17H15ClO3S: C, 60.98; H, 4.52. Found: C, 60.95;
H, 4.56.
9e
Solid; mp 147–148 °C.
IR (KBr): 3450, 1620, 1340, 1130, 1020 cm–1.
b-Hydroxy-(E)-vinylic Sulfone (9); General Procedure
To an ethanolic solution (20 mL) of phenacyl (E)-styryl sulfones 5
(from Method A) (10 mmol) maintained at 0 °C, was slowly added
NaBH4 (10 mmol) under N2 atmosphere. The reaction mixture was
maintained at 0 °C for 0.5 h. After completion of the reaction (mon-
itored by TLC), the contents were poured on to the crushed ice. The
solid separated out was filtered, washed with water and dried under
vacuum to get the desired product 9.
1H NMR (CDCl3): d = 1.95 (br s, 1 H, OH), 2.27 (s, 3 H, ArCH3),
3.16–3.33 (m, 2 H, CH2), 5.16 (d, 1 H, CH), 6.81 (d, J = 15.6 Hz, 1
H), 7.10–7.81 (m, 9 H).
13C NMR (CDCl3): d = 145.1 (CH=), 143.5, 138.4, 134.0
(=CHSO2), 131.1, 131.0, 129.9, 129.2, 128.9, 126.9, 69.3 (CHOH),
61.6 (CH2), 21.4 (4-CH3C6H4).
Anal. Calcd for C17H17ClO3S: C, 60.62; H, 5.09. Found: C, 60.65;
H, 5.08.
9a
Solid; mp 122–124 °C.
IR (KBr): 3450, 1615, 1310, 1145, 1010 cm–1.
(E,E)-Bis(styryl) Sulfones (10); General Procedure
Method A
1H NMR (CDCl3): d = 1.91 (br s, 1 H, OH), 3.10–3.31 (m, 2 H,
CH2), 5.16 (d, 1 H, CH), 6.83 (d, J = 15.5 Hz, 1 H), 7.07–7.77 (m,
10 H).
13C NMR (CDCl3): d = 143.9 (CH=), 139.6, 138.1, 134.8
(=CHSO2), 130.9, 130.2, 129.9, 129.5, 127.5, 126.3, 68.8 (CHOH),
63.2 (CH2).
BF3·Et2O (5 mmol) was added to a solution of 9 (5 mmol) in Ac2O
(10 mL) at 0 °C. The mixture was stirred for 0.5 h and poured into
CHCl3 (25 mL). The organic layer was washed with sat. NaHCO3
(2 × 25 mL), water (2 × 25 mL) and dried over Na2SO4. The solvent
was removed under vacuum and the residue was recrystallized from
i-PrOH to get the desired product 10 in excellent yields. The yields
of 10 were calculated from 9.
Anal. Calcd for C16H15ClO3S: C, 59.53; H, 4.68. Found: C, 59.67;
H, 4.63.
10a
Solid; mp 146–147 °C.
IR (KBr): 1615, 1330, 1125, 1020 cm–1.
1H NMR (CDCl3): d = 6.57 (d, J = 15.4 Hz, 1 H), 7.29 (d, J = 15.5
Hz, 1 H), 7.16–7.58 (m, 11 H).
13C NMR (CDCl3): d = 151.4 (C6H5CH=), 142.6 (4-ClC6H4CH=),
141.6, 134.9, 130.8, 128.8, 128.4, 127.7, 126.4 (SO2CH=), 126.2,
123.7, 118.2 (=CHSO2).
9b
Solid; mp 177–179 °C.
IR (KBr): 3465, 1620, 1320, 1140, 1015 cm–1.
1H NMR (CDCl3): d = 1.94 (br s, 1 H, OH), 3.11–3.36 (m, 2 H,
CH2), 5.17 (d, 1 H, CH), 6.87 (d, J = 15.6 Hz, 1 H), 7.05–7.81 (m,
9 H).
13C NMR (CDCl3): d = 143.9 (CH=), 139.6, 138.1, 134.8
(=CHSO2), 130.9, 130.2, 129.9, 129.5, 127.5, 126.3, 68.7 (CHOH),
63.2 (CH2).
Anal. Calcd for C16H13ClO2S: C, 63.04; H, 4.30. Found; C, 63.22;
H, 4.26.
Anal. Calcd for C16H14Cl2O3S: C, 53.79; H, 3.95. Found: C, 53.81;
H, 3.96.
10b
Solid; mp 218–219 °C.
IR (KBr): 1620, 1325, 1130, 1010 cm–1.
1H NMR (CDCl3): d = 6.75 (d, J = 15.4 Hz, 1 H), 7.34 (d, J = 15.3
Hz, 1 H), 7.16–7.58 (m, 10 H).
13C NMR (CDCl3): d = 152.3 (4-ClC6H4CH=), 143.9, 139.6, 134.8,
128.8, 127.6, 125.3 (=CHSO2CH=), 119.4.
9c
Solid; mp 110–111 °C.
IR (KBr): 3445, 1625, 1335, 1145, 1015 cm–1.
1H NMR (CDCl3): d = 1.92 (br s, 1 H, OH), 2.26 (s, 3 H, ArCH3),
3.09–3.29 (m, 2 H, CH2), 3.80 (s, 3 H, ArOCH3), 5.16 (d, 1 H, CH),
6.83 (d, J = 15.5 Hz, 1 H), 7.06–7.78 (m, 9 H).
13C NMR (CDCl3): d = 145.1 (CH=), 139.0, 137.8, 134.1
(=CHSO2), 130.8, 130.4, 129.9, 129.7, 127.3, 126.7, 69.3 (CHOH),
63.4 (CH2), 53.7 (4-CH3OC6H4), 21.5 (4-CH3C6H4).
Anal. Calcd for C16H12Cl2O2S: C, 56.65; H, 3.56. Found; C, 56.82;
H, 3.57.
10c
Solid; mp 166–168 °C.
IR (KBr): 1610, 1320, 1110, 1020 cm–1.
1H NMR (CDCl3): d = 2.26 (s, 3 H, ArCH3), 3.75 (s, 3 H, ArOCH3),
6.50 (d, J = 15.4 Hz, 1 H), 7.33 (d, J = 15.4 Hz, 1 H), 6.77–7.47 (m,
10 H).
Anal. Calcd for C18H20O4S: C, 65.04; H, 6.06. Found: C, 65.02; H,
6.04.
9d
Solid; mp 122–123 °C.
IR (KBr): 3480, 1610, 1320, 1140, 1010 cm–1.
13C NMR (CDCl3): d = 162.4, 144.6 (4-CH3C6H4CH=), 141.6 (4-
CH3OC6H4CH=), 140.7, 139.8, 133.1, 130.5, 130.2, 129.3, 125.5
Synthesis 2005, No. 20, 3639–3643 © Thieme Stuttgart · New York

PAPER
Reduction and Dehydration of Phenacyl-(E)-Styryl Sulfones to (E,E)-Bis(styryl) Sulfones
3643
(SO2CH=), 123.7, 114.8 (=CHSO2), 55.8 (4-CH3OC6H4), 21.8 (4-
CH3C6H4).
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Genet, J.-P.; Touati, A. R.; Homri, T.; Hossine, B. B.
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(12) Gotor, V.; Rebolledo, F.; Liz, R. Tetrahedron: Asymmetry
2001, 12, 513.
Anal. Calcd for C18H18O3S: C, 68.76; H, 5.77. Found; C, 69.00; H,
5.69.
10d
Solid; mp 119–121 °C.
IR (KBr): 1615, 1330, 1115, 1020 cm–1.
1H NMR (CDCl3): d = 2.25 (s, 3 H, ArCH3), 6.64 (d, J = 15.4 Hz, 1
H), 7.38 (d, J = 15.4 Hz, 1 H), 7.01–7.50 (m, 11 H).
13C NMR (CDCl3): d = 145.6 (4-CH3C6H4CH=), 143.6 (C6H5CH=),
141.9, 136.9, 135.5, 131.9, 129.1, 128.4, 127.8 (SO2CH=), 125.8,
119.6 (=CHSO2), 21.7 (4-CH3C6H4).
Anal. Calcd for C17H16O2S: C, 71.80; H, 5.67. Found; C, 72.02; H,
5.74.
(13) Zhao, G.; Hu, J.-B.; Qian, Z.-S.; Yin, W.-X. Tetrahedron:
Asymmetry 2002, 13, 2095.
(14) Pahsavath, P. B.; Ratovelomanana-Vidal, V.; Genet, J. P.;
Touati, A. R.; Hornri, T.; Hassine, B. B. Tetrahedron:
Asymmetry 1999, 10, 1369.
10e
Solid; mp 151–153 °C.
(15) Sato, T.; Okumura, Y.; Itai, J.; Fujisawa, T. Chem. Lett.
IR (KBr): 1620, 1335, 1130, 1015 cm–1.
1H NMR (CDCl3): d = 2.25 (s, 3 H, ArCH3), 6.84 (d, J = 15.5 Hz, 1
H), 7.66 (d, J = 15.5 Hz, 1 H), 6.92–7.72 (m, 10 H).
13C NMR (CDCl3): d = 149.9 (4-CH3C6H4CH=), 145.4 (4-
ClC6H4CH=), 143.4, 141.0, 134.5, 133.0, 128.4, 127.6 (SO2CH=),
126.0, 125.5, 119.2 (=CHSO2), 21.7 (4-CH3C6H4).
1988, 1537.
(16) Kozikowski, A. P.; Mugrage, B. B.; Li, C. S.; Felder, L.
Tetrahedron Lett. 1986, 27, 4817.
(17) Tanikaga, R.; Hosoya, K.; Kaji, A. J. Chem. Soc., Perkin
Trans. 1 1988, 2397.
(18) Tanikaga, R.; Hosoya, K.; Kaji, A. J. Chem. Soc., Perkin
Trans. 1 1987, 1799.
(19) Reddy, D. B.; Reddy, P. V. R.; Vijayalakshmi, S.; Reddy, M.
V. R. Phosphorus, Sulfur Silicon 1993, 84, 63.
(20) Gnanadeepam, M.; Selvaraj, S.; Perumal, S.; Renuga, S.;
Selvaraj, S. Phosphorus, Sulfur Silicon Relat. Elem. 2002,
177, 431.
(21) Reddy, D. B.; Reddy, S.; Padmavathi, V.; Reddy, M. V. R.
Sulfur Lett. 1990, 11, 281.
Anal. Calcd for C17H15ClO2S: C, 64.04; H, 4.74. Found; C, 64.29;
H, 4.84.
Method B
To a cooled solution of phenacyl (E)-styryl sulfone 5a (from Meth-
od A) (5 mmol) in EtOH (50 mL), NaBH4 (5 mmol) was added and
stirred for 30 min. A few crystals of bromocresol blue were added
as pH indicator and the mixture was refluxed for 1 h. A few drops
of concd HCl was added to the solution until the color changed to
yellow. After refluxing for 5 h, the solution was diluted with water
(50 mL), cooled to 0 °C and stirred for 0.5 h. The solid formed was
filtered, washed with water (2 × 25 mL) and dried to give a colorless
solid which is identical to the compound 10a reported in the Method
A. The yields of 10 were calculated based on the starting material 5.
(22) Reddy, D. B.; Padmaja, A.; Reddy, P. V. R. Sulfur Lett.
1993, 16, 227.
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Reddy, D. B. Heteroat. Chem. 2002, 13, 677.
(24) Reddy, M. V.; Manjubhashini, A. B.; Reddy, S.; Reddy, P.
V. R.; Reddy, D. B. Synth. Commun. 1991, 21, 1589.
(25) Reddy, D. B.; Reddy, M. M.; Padmavathi, V. Indian J.
Heterocycl. Chem. 1995, 5, 11.
(26) Gervay-Hague, J.; Meadows, D. C.; Hadd, M. J. Abstracts of
Papers, 225th ACS National Meeting, New Orleans, 2003;
American Chemical Society: Washington, 2003.
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20020022666A1, 2002; Chem. Abstr. 2002, 136, 183608.
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50, 5045.
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Sambri, L.; Torregiani, E. Org. Lett. 2000, 2, 1791.
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Tetrahedron Lett. 2004, 45, 2977.
Acknowledgment
The authors wish to thank Fels Foundation, Philadelphia and Onco-
nova Therapeutics Inc., New Jersey for their financial support and
encouragement.
References
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Synthesis 2005, No. 20, 3639–3643 © Thieme Stuttgart · New York