Synthesis of polyhydroxylated derivatives of phenyl vinyl sulfone as structural analogs of chalcones

Article abstract of DOI:10.1055/s-2001-15223

A series of polyhydroxylated phenyl vinyl sulfones was prepared by phase transfer condensation of suitable phenyl methyl sulfones with substituted benzaldehydes. The compounds were prepared as structural analogs of biologically active chalcones. One of the compounds was cyclized to a derivative of 2,3-dihydro-2-phenyl-1,4-benzoxathiin-4,4-dioxide, a heterocyclic system closely resembling flavanones.

Full text of DOI:10.1055/s-2001-15223

PAPER
1363
Synthesis of Polyhydroxylated Derivatives of Phenyl Vinyl Sulfone as
Structural Analogs of Chalcones
S
ynthesis of Polyhydro
a
xylated De
r
r
ivatives
e
of Phenyl
kV
inyl Sulfone T. Konieczny,*a Barbara Horowska,a Antoni Kunikowski,a Jerzy Konopa,a Konstanty Wierzba,b Yuji
Yamada,b Tetsuji Asaob
a
Department of Pharmaceutical Technology and Biochemistry, Technical University of Gdansk, 80–952 Gdansk, Poland
Fax +48(58)3493206; E-mail: markon@amedec.amg.gda.pl
b
Taiho Pharmaceutical Company, Hanno Research Center, Yaoroshi, Hanno-city, Saitama, 357, Japan
Received 20 November 2000; revised 22 March 2001
Abstract: A series of polyhydroxylated phenyl vinyl sulfones was
prepared by phase transfer condensation of suitable phenyl methyl
sulfones with substituted benzaldehydes. The compounds were pre-
pared as structural analogs of biologically active chalcones. One of
the compounds was cyclized to a derivative of 2,3-dihydro-2-phe-
nyl-1,4-benzoxathiin-4,4-dioxide, a heterocyclic system closely re-
sembling flavanones.
Key words: phenyl vinyl sulfones, 1,4-benzoxathiin-4,4-dioxide,
chalcones, flavanones
Figure
Chalcones constitute a class of natural products of general at the synthesis of sulfones 2 possessing p-hydroquinone
structure 1. These compounds have been extensively substitution pattern.
studied1 due to their broad spectrum of biological activity,
including bacteriostatic, fungistatic, antiparasitic, cardio-
vascular, antitumor, and others. Constant interest in chal-
Vinyl sulfones 2 can be obtained by condensation of aro-
matic aldehydes with various phenyl sulfones,17–22 includ-
ing alkyl sulfones,17,19 sulfonylacetates or acetic acids,18,22
cones results in syntheses of new derivatives using both
and sulfonylketones.20,21 While hydroxylated benzalde-
classical2,3 as well as combinatorial techniques.4
hydes 7 are commercially available, hydroxylated phenyl
While looking for pharmaceutically promising analogs of sulfones (e.g., 4) are not easily accessible. The desired
chalcones, we paid attention to diphenyl vinyl sulfones 2 precursors of vinyl sulfone 2 were prepared by adaptation
(Figure). The compounds could be considered as deriva- of the reaction of quinone with phenyl sulfinic acids23,24 to
tives of chalcones in which the carbonyl group is replaced methyl sulfinic acid (3) (Scheme 1).
by, possessing similar electrophilic character, sulfone
group. Vinyl sulfones have been intensively studied due
to their synthetic utility,5–8 but their biological activity has
not obtained much attention, to the best of our knowledge,
there is only a single patent by Reddy and Reddy claiming
anticancer activity of styryl sulfones 2.9 Some of the now
reported compounds also possess carcinogenesis-suppres-
ing activity.10
Biologically active flavonoids are usually polyhydroxy-
lated in both A and B rings,1,11,12 and in the case of chal-
cones, hydroxyl substituents in 2 and 5 positions2,3 or
their alkylated equivalents (-OMe, -OEt)13 were found to
be of importance for some types of biological activity. It
is also known that 1,4- and 1,2-hydroquinone structure of
A-ring and/or B-ring of flavonoids is responsible for their
rat liver lipid peroxidation suppressing activity,14 and that
some 5,8-dihydroxythioflavanone derivatives15 have ex-
cellent antitumor activity.16 For these reasons, we aimed
Scheme 1
In spite of instability of the latter reagent, the reaction
gave 2,5-dihydroxyphenyl methyl sulfone (4) in good
yield, and it seems that starting from substituted quinones
a variety of derivatives of 4 could be prepared. Alkylation
Synthesis 2001, No. 9, 29 06 2001. Article Identifier:
1437-210X,E;2001,0,09,1363,1367,ftx,en;P07600SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

1364
M. T. Konieczny et al.
PAPER
Table 2 Compounds of General Formula 23, Obtained by Hydro-
genolysis of Suitable Benzyl Derivatives of 2
Table 1 Derivatives of Phenyl Phenylvinyl Sulfones 2 Prepared
Compd
8
Substitution pattern
Yield %
64
2-OBn
3-OBn
2-OBn
2-OBn
3-OMe
2-OMe
2-OMe
3-OMe
2-OMe
3-OMe
4-OBn
3-OBn
2-OBn
2-OH
3-OBn
4-OBn
4-OBn
3-OMe
4-OBn
3-OMe
4-OMe
4-OMe
3-OMe
4-OMe
2’-OBn
2’-OBn
2’-OBn
2’-OBn
2’-OBn
2'-OBn
2'-OBn
2'-OBn
2'-OMe
2'-OMe
2'-OBn
2'-OMe
2'-OMe
2'-OH
5’-OBn
5’-OBn
5’-OBn
5’-OBn
5’-OBn
5'-OBn
5'-OBn
5'-OBn
9
45
10
11
12
13
14
15
16
17
18
19
20
21
22
23
40
32
Compd
24
Substitution pattern
Yield %
48
77
2-OH
3-OH
2-OH
2-OH
2-OMe
3-OMe
3-OH
2’-OH
2’-OH
2’-OH
2’-OH
2’-OH
2’-OH
5’-OH
5’-OH
5’-OH
5’-OH
5’-OH
5’-OH
22
25
4-OH
94
51
26
4-OH
83
5’-OMe 49
27
3-OMe
3-OMe
4-OMe
63
5'-OMe
5'-OBn
5'-OMe
5'-OMe
5'-OH
15
28
77
30
29
90
4-OBn
3-OBn
3-OH
4-OH
18
22
51a, 60b
41
3-OH
2'-OH
5-'OH
a From 8 using AlCl3/dimethylaniline.
b From 13 or 20 using BF3/(CH3)2S.
Scheme 2 Reagents and conditions: i) TFA, CHCl3, reflux, 38%
of 4 gave methoxy 5 and benzyloxy 6 derivatives, which
were condensed with suitable benzaldehydes 7 under
phase transfer conditions17 to give compounds 8–20
(Scheme 1, Table 1).
2,5-Dihydroxyphenyl Methyl Sulfone (4)
A suspension of Zn (20 g, 0.3 mol) in H2O (50 mL) was cooled to
0°C, and methanesulfonyl chloride (15.4 mL, 0.2 mole) was added
drop-wise to the stirred suspension at 0–5°C. The mixture was
stirred for 30 min with cooling, acidified with concd HCl (50 mL)
at 0–5°C, stirred for 5 min, and filtered. 1,4-Benzoquinone (15 g,
0.14 mol) was added to the filtrate at the low temperature, and the
mixture was stirred for 2 h, while the temperature was allowed to
rise to r.t. The precipitated product was filtered off, washed with hot
CHCl3 to remove a side product, and crystallized from MeOH–
CHCl3 to give 20 g (76%) of white crystals. Alternatively, the prod-
uct was isolated by dilution of the reaction mixture with H2O (200
mL), filtration, and extraction of the filtrate with Et2O. Drying
(MgSO4) and evaporation of the ethereal solution gave crude prod-
uct, which was crystallized from MeOH–CHCl3, mp 121–124°C.
Catalytic hydrogenation (Pd/C, ethyl acetate) of benzyl
derivatives resulted in deprotection of benzyl-protected
groups along with reduction of the double bond, leading
to the formation of compounds of general formula 23
(Table 2). The same products were obtained by hydrogen
transfer method (Pd/C, cyclohexene, ethyl alcohol, re-
flux).
Deprotected derivatives of 2 were prepared by nonreduc-
tive methods. Reaction of benzyl derivatives 8, 9 with alu-
minum chloride/dimethylaniline gave tetrahydroxy
derivatives 21 and 22, respectively (Table 1), and reaction
of compounds 13 and 20 with boron trifluoride/methyl
sulfide complex gave cleanly the same product 21. As it
could be expected,18 deprotection of benzyl protected
groups under acidic conditions was accompanied by cy-
clization closely resembling those of 2'-hydroxychalcones
to flavanones. Thus, reflux of dibenzyl derivative 15 in
TFA–chloroform solution gave cyclic derivative 30
(Scheme 2). Synthesis of hydroxylated analogs of 2,3-di-
hydro-2-phenyl-1,4-benzoxathiin-4,4-dioxide seems to be
potentially important as the compounds can be considered
as analogs of flavanone. Beside, methods of synthesis of
1,4-benzoxathiin-4,4-dioxide system are scarce.18,25–29
1H NMR (80 MHz, DMSO-d6): = 3.20 (s, 3H, CH3), 6.89–7.12 (m,
3H, Ar-H), 9.3 (br s, 1H, OH), 10.1 (br s, 1H, OH).
2,5-Dimethoxyphenyl Methyl Sulfone (5)
2,5-Dihydroxyphenyl methyl sulfone (4) (1.88 g, 10 mmol), methyl
iodide (1.5 mL, 24 mmol), and anhyd K2CO3 (4.15 g, 30 mmol) in
acetone (50 mL) were refluxed with stirring for 4 h. The cooled re-
action mixture was treated with H2O (100 mL) and extracted with
Et2O (3 80 mL). The ethereal solution was dried (MgSO4) and
evaporated to dryness to give 1.7 g (78%) of crude product. Crys-
tallization from EtOH–H2O gave 1.08 g (50%) of compound 5, mp
72–74°C.
1H NMR (80 MHz, CDCl3): = 3.22 (s, 3H, SO2CH3), 3.82 (s, 3H,
OCH3), 3.96 (s, 3H, OCH3), 7.00–7.12 (m, 2H, H-3, H-4), 7.51 (d,
1H, J = 2.8 Hz, H-6).
Synthesis 2001, No. 9, 1363–1367 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Synthesis of Polyhydroxylated Derivatives of Phenyl Vinyl Sulfone
1365
2,5-Dibenzyloxyphenyl Methyl Sulfone (6)
J = 15.7 Hz, H- ), 6.68–7.45 (m, 15H, Ar-H), 7.64 (d, 1H, J = 3.1
Hz, H-6'), 7.76 (d, 1H, J = 15.7 Hz, H- ).
2,5-Dihydroxyphenyl methyl sulfone (4) (1.88 g, 10 mmol), benzyl
bromide (2.8 mL, 24 mmole), and anhyd K2CO3 (4.15 g, 30 mmol)
in acetone (50 mL) were refluxed with stirring for 4 h. The resulted
mixture was cooled to r.t. and the product was precipitated with
H2O. The solid was filtered off, washed with H2O, and crystallized
from MeOH to give 6 as white needles, 2.95 g (80%), mp 119–
121°C.
2',5'-Dibenzyloxyphenyl (2,4-Dimethoxyphenyl)vinyl Sulfone (14)
Yield: 22%; mp 165–167°C (toluene–MeOH).
1H NMR (200 MHz, CDCl3): = 3.60 (s, 3H, OCH3), 3.76 (s, 3H,
OCH3), 5.00 (s, 2H, CH2Ph), 5.09 (s, 2H, CH2Ph), 7.18 (d, 1H,
J = 15.4 Hz, H- ), 6.28–7.48 (m, 15H, Ar-H), 7.58 (d, 1H, J = 15.4
Hz, H- ), 7.65 (d, 1H, J = 3.1 Hz, H-6').
1H NMR (80 MHz, DMSO-d6): = 3.24 (s, 3H, CH3), 5.12 (s, 2H,
CH2), 5.26 (s, 2H, CH2), 7.4–7.3 (m, 13H, Ar-H).
2',5'-Dibenzyloxyphenyl (3,4-Dimethoxyphenyl)vinyl Sulfone (15)
Yield: 51%; mp 179–180°C (toluene–MeOH).
1H NMR (200 MHz, CDCl3): = 3.69 (s, 3H, OCH3), 3.83 (s, 3H,
OCH3), 5.02 (s, 2H, CH2Ph), 5.08 (s, 2H, CH2Ph), 6.84 (d, 1H,
J = 15.4 Hz, H- ), 6.65–7.50 (m, 16H, Ar-H, H- ), 7.64 (d, 1H,
J = 3.0 Hz, H-6').
Condensation of Benzaldehydes with Methyl Phenyl Sulfone
Derivatives (5 or 6) under Phase Transfer Conditions; General
Procedure
A suspension of a suitably protected sulfone (10 mmol), substituted
benzaldehyde (1.2 mmol) and tetrabutylammonium bromide (2
mmol) in CH2Cl2 (15 mL) and 40% NaOH (20 mL) was stirred for
several days (2–5). CH2Cl2 (100 mL) was added, the organic layer
separated, washed with H2O until neutral (4 50 mL), brine (1 50
mL), and dried (MgSO4). Evaporation of solvent gave a residue,
which, typically, was washed with MeOH, and crystallized from a
suitable solvent.
2',5'-Dimethoxyphenyl (2,3-Dimethoxyphenyl)vinyl Sulfone (16)
Yield: 49%; mp 138–139°C (toluene–MeOH).
1H NMR (200 MHz, CDCl3): = 3.83 (s, 3H, OCH3), 3.87 (s, 3H,
OCH3), 3.88 (s, 3H, OCH3), 3.91 (s, 3H, OCH3), 6.90–7.14 (m, 5H,
Ar-H), 7.25 (d, 1H, J = 15.6 Hz, H- ), 7.56 (d, 1H, J = 3 Hz, H-6'),
7.94 (d, 1H, J = 15.6 Hz, H- ).
2',5'-Dibenzyloxyphenyl (2,3-Dibenzyloxyphenyl)vinyl Sulfone
(8)
Yield: 64%; mp 126–128°C (toluene–MeOH).
2',5'-Dimethoxyphenyl (3,4-Dimethoxyphenyl)vinyl Sulfone (17)
Yield: 15%; mp 169–170°C (benzene–cycloxehane).
1H NMR (200 MHz, CDCl3): = 3.77 (s, 3H, OCH3), 3.84 (s, 3H,
OCH3), 3.86 (s, 6H, 2 OCH3), 6.76–7.3 (m, 6H, Ar-H, H- ), 7.49
(d, 1H, J = 3.0 Hz, H-6'), 7.56 (d, 1H, J = 15.4 Hz, H- ).
1H NMR (200 MHz, CDCl3): = 4.98 (s, 2H, CH2Ph), 5.07 (s, 2H,
CH2Ph), 5.10 (s, 2H, CH2Ph), 5.12 (s, 2H, CH2Ph), 6.75–7.50 (m,
26H, Ar-H, H- ), 7.68 (d, 1H, J = 3.1 Hz, H-6'), 7.84 (d, 1H, J = 15.7
Hz, H- ).
2',5'-Dibenzyloxyphenyl (3,4-Dibenzyloxyphenyl)vinyl Sulfone
(9)
2',5'-Dibenzyloxyphenyl (4-Benzyloxyphenyl)vinyl Sulfone (18)
Yield: 30%; mp 178–179°C (toluene).
Yield: 45%; mp 132–133°C (toluene–MeOH).
1H NMR (200 MHz, CDCl3): = 5.02 (s, 4H, 2 CH2Ph), 5.07 (s,
2H, CH2Ph), 6.77–7.44 (m, 23H, Ar-H, olefinic), 7.63 (d, 1H,
J = 3.0 Hz, H-6').
1H NMR (200 MHz, CDCl3): = 4.96 (s, 2H, CH2Ph), 5.01 (s, 2H,
CH2Ph), 5.06 (s, 2H, CH2Ph), 5.11 (s, 2H, CH2Ph), 6.65–7.45 (m,
27H, Ar-H, olefinic), 7.63 (d, 1H, J = 3 Hz, H-6').
2',5'-Dimethoxyphenyl (3,4-Dibenzyloxyphenyl)vinyl Sulfone (19)
Yield: 18%; mp 189–191°C (toluene–hexane).
2',5'-Dibenzyloxyphenyl (2,4-Dibenzyloxyphenyl)vinyl Sulfone
(10)
1H NMR (200 MHz, CDCl3): = 3.76 (s, 3H, OCH3), 3.81 (s, 3H,
OCH3), 5.11 (s, 2H, CH2Ph), 5.14 (s, 2H, CH2Ph), 6.80–7.42 (m,
16H, Ar-H, H- ), 7.47 (d, 1H, J = 15.4 Hz, H- ), 7.47 (d, 1H, J = 3.1
Hz, H-6').
Yield: 23%; mp 133–135°C (MeOH).
1H NMR (200 MHz, CDCl3): = 4.91 (s, 2H, CH2Ph), 4.95 (s, 2H,
CH2Ph), 4.99 (s, 4H, 2 CH2Ph), 6.40–7.40 (m, 26H, Ar-H, H- ),
7.62 (d, 1H, J = 3.1 Hz, H-6'), 7.67 (d, 1H, J = 15.6 Hz, H- ).
2',5'-Dimethoxyphenyl (2,3-Dibenzyloxyphenyl)vinyl Sulfone (20)
Yield: 22%; mp 103–105°C (MeOH).
1H NMR (200 MHz, CDCl3): = 3.71 (s, 3H, OCH3), 3.76 (s, 3H,
OCH3), 4.97 (s, 2H, CH2Ph), 5.08 (s, 2H, CH2Ph), 7.19 (d, 1H,
J = 15.6 Hz, H- ), 6.80–7.43 (m, 15H, Ar-H), 7.47 (d, 1H, J = 3.0
Hz, H-6'), 7.85 (d, 1H, J = 15.6 Hz, H- ).
2',5'-Dibenzyloxyphenyl (2-Benzyloxy-3-methoxyphenyl)vinyl
Sulfone (11)
Yield: 40%; mp 91–93°C (toluene–MeOH).
1H NMR (200 MHz, CDCl3): = 3.88 (s, 3H, OCH3), 4.95 (s, 2H,
CH2Ph), 5.07 (s, 2H, CH2Ph), 5.10 (s, 2H, CH2Ph), 7.20 (d, 1H,
J = 15.7 Hz, H- ), 6.74–7.50 (m, 20H, Ar-H), 7.67 (d, 1H, J = 3.1
Hz, H-6'), 7.83 (d, 1H, J = 15.7 Hz, H- ).
Catalytic Hydrogenation of Phenyl Vinyl Sulfones 2; General
Procedure
2',5'-Dibenzyloxyphenyl (4-Benzyloxy-3-methoxyphenyl)vinyl
Sulfone (12)
Yield: 32%; mp 142–143°C (acetone–MeOH).
1H NMR (200 MHz, CDCl3): = 3.70 (s, 3H, OCH3), 5.01 (s, 2H,
CH2Ph), 5.07 (s, 2H, CH2Ph), 5.11 (s, 2H, CH2Ph), 6.82 (d, 1H,
J = 15.4 Hz, H- ), 6.60–7.47 (m, 21H, Ar-H, H- ), 7.63 ( d, 1H,
J = 3 Hz, H-6').
A suspension of the appropriate benzyl derivative of phenyl vinyl
sulfone 2 (1 mmol) and 5% Pd on charcoal (100 mg) in EtOAc was
hydrogenated at r.t. for 1–4 h. The reaction mixture was filtered and
evaporated to give a crude product, which was purified by crystalli-
zation or chromatography.
2',5'-Dihydroxyphenyl (2,3-Dihydroxyphenyl)ethyl Sulfone (24)
Purified on silica gel column (CHCl3–MeOH, 10:1) followed by
crystallization from isopropyl alcohol–toluene.
2',5'-Dibenzyloxyphenyl (2,3-Dimethoxyphenyl)vinyl Sulfone (13)
Yield: 77%; mp 151–153°C (toluene).
Yield: 48%; mp 177–180°C.
1H NMR (200 MHz, CDCl3): = 3.66 (s, 3H, OCH3), 3.79 (s, 3H,
1H NMR (80 MHz, DMSO-d6): = 2.79 (m, 2H, H- ), 3.51 (m, 2H,
OCH3), 5.01 (s, 2H, CH2Ph), 5.11 (s, 2H, CH2Ph), 7.21 (d, 1H,
H- ), 6.4 7.2 (m, 6H, aromatic), 9.3 (br s, OH).
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M. T. Konieczny et al.
PAPER
Deprotection of Phenyl Vinyl Sulfones 13 and 20 with Boron
2’,5’-Dihydroxyphenyl (3,4-Dihydroxyphenyl)ethyl Sulfone (25)
Yield: 94%; mp 197–198°C (benzene–MeOH).
Trifluoride Methyl Sulfide Complex
Boron trifluoride methyl sulfide complex solution in CH2Cl2 (Ald-
rich) (8 mmol) was added to a stirred solution of the suitable deriv-
ative of 2 (13 or 20, 128 mg, 0.25 mmol) in CH2Cl2 (2 mL), and the
mixture was stirred at r.t. for 2 h. The solution was quenched with
H2O (5 mL), diluted with EtOAc (50 mL), washed with H2O (4 20
mL), brine (1 20 mL), and dried (MgSO4). Evaporation of the so-
lution gave a crude product which was purified on a silica gel col-
umn (CHCl3–MeOH, 20:1) to give compound 21, yield 60%,
identical with product obtained by deprotection of compound 8 with
aluminum chloride/dimethylaniline mixture.
1H NMR (80 MHz, DMSO-d6): = 2.68 (m, 2H, H- ), 3.53 (m, 2H,
H- ), 6.3–7.2 (m, 6H, Ar-H), 8.75 (br s, 2H, 2 OH), 9.35 (br s, 1H,
OH), 10.21 (br s, 1H, OH).
2',5'-Dihydroxyphenyl (2,4-Dihydroxyphenyl)ethyl Sulfone (26)
Yield: 83%; mp 213–217°C (MeOH–Et2O).
1H NMR (80 MHz, DMSO-d6): = 2.73 (m, 2H, H- ), 3.52 (m, 2H,
H- ), 6.0 7.1 (m, 6H, Ar-H), 9.05 (br s, 1H, OH), 9.33 (br s, 2H, 2
OH), 10.12 (br s, 1H, OH).
2',5'-Dihydroxyphenyl (2-Hydroxy-3-methoxyphenyl)ethyl
Sulfone (27)
Yield: 63%; mp 138–139°C (EtOH–H2O).
1H NMR (80 MHz, DMSO-d6): = 2.76 (m, 2H, H- ), 3.59 (m, 2H,
H- ), 3.76 (s, 3H, OCH3), 6.6–7.2 (m, 6H, Ar-H), 8.62 (br s, 1H,
OH), 9.32 (br s, 1H, OH), 10.14 (br s, 1H, OH).
2,3-Dihydro-2-(3’,4’dimethoxyphenyl)-6-hydroxy-1,4-
benzoxathiin-4,4-dioxide (30)
TFA (1.5 mL) was added to a solution of 2',5'-dibenzyloxyphenyl
(3,4-dimethoxyphenyl)vinyl sulfone (15) (250 mg, 0.44 mmol) in
CHCl3 (3 mL) and the solution was stirred for 24 h at r.t., and then
refluxed for 4 h. The solution was evaporated, the residue dissolved
in CHCl3, washed with H2O, dried (MgSO4), and evaporated under
vacuum. The residue was purified by silica gel column chromatog-
raphy (CHCl3) to give a crude product (112 mg, 77%). Crystalliza-
tion from MeOH gave 57 mg (38%) of the product; mp 207–209°C.
1H NMR (200 MHz, CDCl3): = 3.49 (dd, 1H, J = 14.0, 1.7 Hz, H-
3), 3.7 (dd, 1H, J = 12.0, 14 Hz, H-3), 3.93 (s, 3H, OCH3), 3.92 (s,
3H, OCH3), 5.68 (dd, 1H, J = 12.0, 1.5 Hz, H-2), 6.9–7.1 (m, 6H,
Ar-H).
2',5'-Dihydroxyphenyl (2,3-Dimethoxyphenyl)ethyl Sulfone (28)
Yield: 77%; mp 102–105°C (EtOH–H2O).
1H NMR (80 MHz, DMSO-d6): = 2.75 (m, 2H, H- ), 3.49 (m, 2H,
H- ), 3.62 (s, 3H, OCH3), 3.77 (s, 3H, OCH3), 6.7–7.2 (m, 6H, Ar-
H), 9.31 (br s, 1H, OH), 10.20 (br s, 1H, OH).
2',5'-Dihydroxyphenyl (3,4-Dimethoxyphenyl)ethyl Sulfone (29)
Yield: 90%; mp 159 160°C (benzene–MeOH).
1H NMR (200 MHz, CDCl3): = 2.76 (m, 2H, H- ), 3.35 (m, 2H,
H- ), 3.76 (s, 6H, 2 OCH3), 6.54–7.1 (m, 6H, Ar-H), 8.35 (br s, H,
OH).
Acknowledgement
The authors wish to thank Taiho Pharmaceutical Company, Japan,
for financial support.
Transfer Hydrogenation of Phenyl Vinyl Sulfones 2; General
Procedure
References
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lated by standard procedures, and were identical with those ob-
tained by catalytic hydrogenation (see above).
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Deprotection of Phenyl Vinyl Sulfones 8 and 9 with AlCl3
Dimethylaniline System; General Procedure
The appropriate benzyl derivative of 2 (1.5 mmol) and N,N-dimeth-
ylaniline (1.1 mL, 9 mmol) were dissolved in dry CH2Cl2 (40 mL)
cooled to 0°C, and AlCl3 (1.6 g, 12 mol) was added. The mixture
was stirred at 0°C for 3 h under Ar. The mixture was concentrated
by half, poured into ice cooled 5% HCl (50 mL) and extracted with
EtOAc (100 mL). The organic layer was washed with H2O (2 30
mL), dried, and evaporated. The residue was purified by silica gel
column chromatography (CHCl3–MeOH, 10:1).
2',5'-Dihydroxyphenyl (2,3-Dihydroxyphenyl)vinyl Sulfone (21)
Yield: 51%; mp 173–176°C.
1H NMR (200 MHz, DMSO-d6): = 6.64 (t, 1H, J = 7.8 Hz, H-5),
6.80 (d, 1H, J = 8.8 Hz, H-3'), 6.84 (d, 1H, J = 6.6 Hz, H-4), 6.89
(dd, 1H, J = 8.8, 2.9 Hz, H-4'), 7.00 (dd, 1H, J = 7.7 Hz, H-6), 7.16
(d, 1H, J = 2.9 Hz, H-6'), 7.39 (d, 1H, J = 15.5 Hz, H- ), 7.70 (d, 1H,
J = 15.6 Hz, H- ), 9.4 (very br s, OH).
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Miyaichi, Y.; Tomimori, T. Yakugaku Zasshi 1993, 113,
133.
2',5'-Dihydroxyphenyl (3,4-Dihydroxyphenyl)vinyl Sulfone (22)
Yield: 41%; mp 189–193°C.
1H NMR (200 MHz, DMSO-d6): = 6.7–7.05 (m, 5H, Ar-H), 7.05
(d, 1H, J = 15.5 Hz, H- ), 7.15 (d, 1H, J = 3.0 Hz, H-6'), 7.36 (d, 1H,
J = 15.5 Hz, H- ), 9.4 (br s, OH).
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Synthesis of Polyhydroxylated Derivatives of Phenyl Vinyl Sulfone
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Synthesis 2001, No. 9, 1363–1367 ISSN 0039-7881 © Thieme Stuttgart · New York