Convenient one-pot procedure for converting aryl sulfides to nitroaryl sulfones

Article abstract of DOI:10.1055/s-2002-31950

When treated with nitrogen dioxide and ozone in inert solvent at 0°C or below, aryl sulfides underwent smooth oxidative nitration to give nitroaryl sulfones in good yield. Using this methodology, a series of mono- and di-nitrated aryl sulfones were prepared from methyl phenyl sulfide and diphenyl sulfide and their physical data are presented.

Full text of DOI:10.1055/s-2002-31950

PAPER
1065
Convenient One-pot Procedure for Converting Aryl Sulfides to Nitroaryl
Sulfones
One-pot
P
rocedure for
a
A
ryl Sulfid
s
es to
N
itr
a
t
Department of Chemistry, School of Science, Kwansei Gakuin University, Gakuen 2-1, Sanda 669-1337, Japan
Fax +81(795)659077; E-mail: hsuzuki@ksc.kwansei.ac.jp
Received 12 February 2002; revised 25 March 2002
The reaction of diphenyl sulfide (4) with nitric acid has
long been known to involve partial oxidation of the sulfur
atom to afford a mixture of isomeric nitrophenyl sulfides,
sulfoxides and sulfones.7 However, no detailed informa-
Abstract: When treated with nitrogen dioxide and ozone in inert
solvent at 0 °C or below, aryl sulfides underwent smooth oxidative
nitration to give nitroaryl sulfones in good yield. Using this meth-
odology, a series of mono- and di-nitrated aryl sulfones were pre-
pared from methyl phenyl sulfide and diphenyl sulfide and their tion is available on the product composition. Since the sul-
physical data are presented.
fanyl, sulfinyl and sulfonyl groups are known to direct the
entering electrophiles differently in electrophilic aromatic
substitution, the reaction seemed to us to provide a conve-
nient one-step procedure to convert commercially avail-
able sulfides 1a and 4 to isomeric nitroaryl sulfones by
appropriate choice of experimental conditions. Thus, we
have investigated the Kyodai-nitration of aromatic sul-
fides such as 1a and 4, and of aromatic sulfones such as
3a and 6 under a variety of conditions.8 In fact, this meth-
od proved to be quite effective for converting aryl sulfides
directly to nitroaryl sulfones. Six nitroaryl sulfones and
seven dinitro aryl sulfones were isolated from the reaction
mixtures and their physical properties including melting
points, mass, infrared and 1H NMR spectral data are pre-
sented.
Key words: nitro compounds, sulfones, sulfides, nitration, nitrogen
oxides, ozone
Among various types of functional groups commonly
found in organic compounds, the sulfonyl group stands
first in the capacity of withdrawing electrons. Due to this
uniqueness, the sulfonyl group is widely employed for the
activation of C–H bonds as well as the stabilization of car-
banionic species arising from the proton removal of acti-
vated C–H bonds. In connection with our continued
studies on the nonconventional nucleophilic substitution
of nitroarenes,1 where a ring hydrogen atom is replaced by
a nucleophile in preference to the nucleofugal substituent
group present in the same ring (Scheme 1), we became in-
terested in the behavior of nitroaryl sulfones toward nu-
cleophiles under strongly basic conditions. Unfortunately,
these aryl sulfones are not commercially available. Major
known methods for the preparation of nitroaryl sulfones
involve (a) direct nitration of aryl sulfones,2 (b) Friedel–
Crafts type reaction between nitroarylsulfonyl chlorides
and arenes,3 (c) nucleophilic substitution of halonitroare-
nes with sulfinates,4 and (d) oxidation of nitroaryl sul-
fides.5 However, these methods are not free from some
drawbacks. The first method has no choice as to the posi-
tion occupied by nitro group, while the other methods of-
ten suffer from limited scope, difficult access to
commercial material, side reaction and/or low yield.6
To a stirred solution of methyl phenyl sulfide (1a) in
dichloromethane was added an excess of liquid nitrogen
dioxide at –10 °C and the resulting mixture was allowed
to stand for a while. The substrate was cleanly oxidized to
sulfoxide 2a.9 When a stream of ozonized oxygen was
passed slowly to the resulting solution, sulfoxide 2a was
rapidly oxidized to form sulfone 3a (Scheme 2).10 When
this compound was further subjected to the combined ac-
tion of nitrogen dioxide and ozone (NO2–O3), the ring ni-
tration occurred slowly to give a mixture of isomeric
nitroaryl sulfones 3b–d (Tables 1 and 2). The addition of
methanesulfonic acid as catalyst considerably facilitated
the reaction. Sulfone 3a was almost inert toward the ac-
tion of ordinary nitric acid under similar conditions.
Irrespective of the substrate employed, 1a or 3a, 3-nitro-
phenyl sulfone (3c) was the predominant product from the
Kyodai-nitration. In contrast, the nitration of 1a by the tra-
ditional method gave a product considerably rich in the 4-
nitro derivative 3d. Particularly, when sulfide 1a was
treated with fuming nitric acid using 97% sulfuric acid as
the reaction medium, 4-nitrophenyl sulfone 3d increased
up to 38% in the isomer proportion. Such a marked differ-
ence in the isomer distribution suggests the involvement
of different reaction pathways in the nitration with the
NO2–O3 and the mixed acid systems. In the former type of
nitration where sulfone 3c is the major product, the oxida-
tion of sulfide 1a to sulfoxide 2a to sulfone 3a would pre-
NO2
NO2
NO2
X
H
NO2
NO2
NO2
H
X
X
Scheme 1
Synthesis 2002, No. 8, 04 06 2002. Article Identifier:
1437-210X,E;2002,0,08,1065,1071,ftx,en;F01702SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

1066
M. Nose, H. Suzuki
PAPER
Table 1 Nitration of Aryl Sulfides 1a,4,10,14 and Sulfoxide 2a with NO2–O3 and Other Nitrating Systemsa
Substrate
Reagent
Solvent
Reaction time (h)/ Products
Temp (°C)
Yieldb/%
(Isomer ratio)c
d
1a
NO2
CH2Cl2
CH2Cl2
CH2Cl2
MeNO2
CH2Cl2
CH2Cl2
CH2Cl2
MeNO2
97%-H2SO4
Ac2O
0.5/–10
1.0/–10
3.0/–10
2.5/–10
24/r.t.
2a
98
e
NO2/O3
NO2/O3
NO2/O3
3a
97
e
e
3b+3c+3d
3b+3c+3d
2a
81 (14:83:3)
83 (11:87:2)
94
f
f
Fum-HNO3
Fum-HNO3
24/80
3a
92
Fum-HNO3/97%-H2SO4g
Fum-HNO3/97%-H2SO4g
12/80
3b+3c+3d
3b+3c+3d
3b+3c+3d
3a
88 (7:76:17)
87 (10:75:15)
72 (8:54:38)
98
12/80
f
Fum-HNO3
12/r.t.
f
Fum-HNO3
6.0/0
e
2a
4
NO2–O3
CH2Cl2
97%-H2SO4
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
Ac2O
2.5/–10
6/100
3b+3c+3d
3b+3c+3d
5
82 (12:86:2)
86 (1:81:18)
89
f
Fum-HNO3
d
NO2
2.0/–10
2.0/–10
4.5/–10
12/80
e
NO2/O3
6
81
e
NO2/O3
8a+8b+8c
6
76 (11:84:5)
90
f
Fum-HNO3
Fum-HNO3/97%-H2SO4g
12/80
8a+8b+8c+9
6
91 (8:54:17:21)
90
f
Fum-HNO3
6.0/0
d
10
14
NO2
CH2Cl2
CH2Cl2
CH2Cl2
2.0/–10
4.5/ 10
3.0/–10
12
26h,i
e
NO2/O3
8a+13a+13b
17+18
72 (48:23:29)
43 (15:28)j, k
e
NO2/O3
a Except compound 14, all reactions were carried out under the conditions indicated in the table, using a substrate (3 mmol) and a given solvent
(30 mL). For 14, see the experimental section.
b Sum of all products.
c Isomer ratio was estimated by 1H NMR.
d Liquid NO2 (1.5 mL) was used.
e Ozonized oxygen was introduced at a rate of 10 mmol/h.
f Fum-HNO3 (3 mL, d = 1.50) was used.
g A mixture of fum-HNO3 (2 mL, d = 1.50) and 97%-H2SO4 (2 mL, d = 2.0) was used.
h Isolated yield.
i Major product was sulfoxide 11, isolated in 70% yield.
j Ring nitration preceded the oxidation of sulfur atom.
k Accompanied by minor amounts of isomeric nitro sulfones.
cede the ring nitration. However, in the latter type of served in the nitration of sulfoxide 2a with the NO2–O3
nitration where sulfone 3d becomes important, the ring ni- and the mixed acid systems. Although the carbonyl group
tration is supposed to proceed in parallel with the oxida- is known to favor the ortho-substitution in the Kyodai-ni-
tion of sulfur atom, probably due to the partial protonation tration,11 the sulfonyl group showed little ortho specificity
of the sulfur atom in a strong acid medium such as sulfuric in site selection. Changing the solvent from dichlor-
acid. In accordance with the respective meta-para and omethane to nitromethane gave little or no effect on the
meta-orientating nature of the sulfinyl and sulfonyl site selectivity, but interestingly this change was found to
groups, the reversal of the ortho/para isomer ratio was ob- halt the reaction at mononitration stage.
Synthesis 2002, No. 8, 1065–1071 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
One-pot Procedure for Aryl Sulfides to Nitroaryl Sulfones
1067
could not be detected in the double Kyodai-nitration of 4
(Table 1), and neither in the single Kyodai-nitration of 6
(Table 2). The sulfanyl function is para-directing, there-
fore, a noticeable difference in the product composition
suggests a significant competition between the ring car-
bon and the sulfur atoms for the nitronium ion at initial
stage of the traditional nitration of 4.
Me
S
O
Me
SMe
S
O
O
R1
R2
R1
R2
R1
R2
NO2
NO2, O3
R3
R3
R3
1a - d
2a - d
3a - d
a: R1 = R2 = R3 = H
When 2-nitrodiphenyl sulfide (10) was subjected to the
action of the NO2–O3 system, 2,3 -dinitrodiphenyl sulfone
(8a) was obtained as the main product, together with ap-
preciable amounts of 2,2 -dinitro- and 2,4 -dinitrodiphe-
nyl sulfones (13a) and (13b) (Scheme 4). When sulfide 10
was allowed to stand in contact with nitrogen dioxide
alone, a slow ring nitration took place in parallel with the
oxidation of sulfur atom, giving a mixture of sulfoxide 11
and sulfide 12 in good combined yield (Table 1). Forma-
tion of 12 is consistent with the para-directing nature of
the sulfanyl function and two nitro groups in 12 were
enough to prevent this sulfide from being oxidized to sul-
foxide.
b: R1 = NO2, R2 = R3 = H
c: R2 = NO2, R1 = R3 = H
d: R3 = NO2, R1 = R2 = H
Scheme 2
The Kyodai and traditional methods observed a signifi-
cant contrast in the nitration of diphenyl sulfide (4). The
former type of nitration of sulfide 4 and sulfone 6 gave the
dinitration products of similar isomeric composition
(Table 1 and Table 2). This means that the oxidation of
sulfide 4 to sulfone 6 preceded the ring nitration. Thus, the
action of NO2–O3 on sulfide 4 at low temperature readily
gave nitrosulfone 7, which underwent the second nitration
at the opposite ring to afford a mixture of isomeric dini-
troaryl sulfones 8a–c (Scheme 3). Rather unexpectedly,
the second nitration was found to be facile and ran parallel
with the initial nitration. Hence, it was difficult to obtain
the mononitro derivative 7 as the sole initial product. The
initial nitration occurred almost exclusively at 3-position
of 6 and other isomers were detected only in a slight
amount. In contrast, the second nitration took place at all
positions of the unsubstituted ring of 7, giving three pos-
sible dinitroaryl sulfones 8a–c in a good combined yield.
On the other hand, the traditional nitration of sulfide 4 us-
ing an excess of mixed acid at elevated temperature pro-
duced a considerable amount of 3,4 -dinitrophenyl and
4,4 -dinitrodiphenyl sulfones 8c and 9. The latter isomer
A previous paper reported that phenyl trifluoromethyl sul-
fide (14) reacted with nitric and sulfuric acids to form 4-
nitro and 2,4-dinitro derivatives with the sulfur atom in-
tact.12 In our case, treatment of sulfide 14 with excess of
mixed acid gave an oily product, in which 2,4-dinitrophe-
nyl trifluoromethyl sulfide and sulfoxide were found to be
major components. Unfortunately, the product was poorly
crystallized from common organic solvents and so it was
oxidized to sulfone 18 before isolation. The Kyodai-nitra-
tion of 14 gave nitroaryl sulfoxides 15 and 16 as an insep-
arable mixture. Hence, after the oxidation to sulfones, the
product was subjected to chromatographic separation to
obtain 4-nitrophenyl and 2,4-dinitrophenyl trifluorometh-
yl sulfones 17 and 18. In contrast, the Kyodai nitration of
phenyl trifluoromethyl sulfone (19) afforded two isomeric
Table 2 Nitration of Phenyl Sulfones 3a,6,19 with NO2–O3 and Mixed Acid Systemsa
Substrate
Reagent
Solvent
Reaction time (h) / Products
Temp (°C)
Yieldb /%
(Isomer ratio)c
e
3a
NO2/O3 , MeSO2Hl
CH2Cl2
MeNO2
CH2Cl2
MeNO2
CH2Cl2
CH2Cl2
MeNO2
CH2Cl2
CH2Cl2
2.5/ 10
2.0/ 10
12/80
3b+3c+3d
3b+3c+3d
3b+3c+3d
3b+3c+3d
7
87 (9:90:1)
89 (10:89:1)
89 (8:91:1)
94 (14:84:2)
59h, k
NO2/O3 e, MeSO2Hl
Fum-HNO2/97% H2SO4 g
Fum-HNO2/97% H2SO4 g
12/80
e
6
NO2/O3
2.5/ 10
4.0/ 10
3.0/ 10
12/r.t.
NO2/O3 e, MeSO2Hl
NO2/O3 e, MeSO2Hl
Fum-HNO2/97% H2SO4 g
NO2/O3 e, MeSO2Hl
8a+8b+8c
8a+8b+8c
8a+8b+8c
20+21
74 (10:87:3)
78 (13:81:6)
90 (15:78:7)
94 (6:93)
19
2.5/ 10
a
c, e, g, h, k See footnotes of Table 1.
l Methanesulfonic acid (2 mmol) was added as catalyst.
Synthesis 2002, No. 8, 1065–1071 ISSN 0039-7881 © Thieme Stuttgart · New York

1068
M. Nose, H. Suzuki
PAPER
NO2
O
S
O
S
O
S
NO2, O3
NO2, O3
NO2
O
O
7
5
6
S
NO2
NO2-O3
8a - c
HNO3-H2SO4
R3
O
S
O
S
4
O2N
NO2
O
O
R2
R1
8a - c
9
a: R1 = NO2, R2 = R3 = H
b: R2 = NO2, R1 = R3 = H
c: R3 = NO2, R1 = R2 = H
Scheme 3
O2N
O2N
O
NO2
S
O2N
S
O2N
11
12
S
O2N
O
8a: R2 = NO2, R1 = R3 = H
13a: R1 = NO2, R2 = R3 = H
13b: R3 = NO2, R1 = R2 = H
10
NO2, O3
R3
S
O
R2
R1
8a, 13a,b
Scheme 4
mononitro derivatives again as an inseparable mixture,
where the major component was 3-nitrophenyl trifluo-
romethyl sulfone (21), accompanied by small amounts of
2-nitro isomer 20 (Scheme 5). Compound 21 could be iso-
lated in pure form only after repeated chromatography on
silica gel. Compound 20 was quite low in yield and iden-
tified by GC-MS, NMR and IR. The formation of 2,4-
dinitro sulfoxide (16) as the main product from the Kyo-
dai-nitration of sulfide 14 implies that the double ring ni-
tration became more favored over the oxidation of
sulfur(IV) to sulfur(VI) atom in the presence of a power-
ful electron-withdrawing trifluoromethyl group. This
group is not stable in strong acid media and tends to be hy-
drolyzed to the carboxylic acid function.
CF3
O
CF3
O
CF3
S
S
S
NO2
NO2, O3
+
14
NO2
NO2
15
16
[ O ]
CF3
CF3
O
S
O
O
S
O
[ O ]
NO2
In conclusion, a convenient and effective one-pot proce-
dure has been developed for the conversion of aryl sul-
fides into nitroaryl sulfones, in which aryl sulfides were
simply treated with the NO2–O3 system at low tempera-
ture. Yields were generally good and in many cases a no-
ticeable difference of the isomer proportion was observed
between the products from the nitration with the NO2–O3
and the mixed acid systems. The Kyodai-nitration fol-
lowed by chromium trioxide oxidation of deactivated sul-
fide 14 gave 2,4-dinitrophenyl sulfone 18 as the major
product, which would be laborious to obtain by other
methods.
+
NO2
NO2
17
18
CF3
CF3
CF3
O
S
O
O
S
O
O
S
O
NO2
NO2, O3
NO2
19
20
21
Scheme 5
Synthesis 2002, No. 8, 1065–1071 ISSN 0039-7881 © Thieme Stuttgart · New York

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One-pot Procedure for Aryl Sulfides to Nitroaryl Sulfones
1069
Table 3 Physical Data of Nitration Products 2b–d, 3b–d, 7, 8a–c, 9, 12, 13a–b, 17, 18 and 21
Prod-
uct
Mp (°C)
100–102
Lit.
mp (°C)
MS (70 eV) m/z (%)
IR (KBr, cm–1)
1H NMR (CDCl3/TMS), , J (Hz)
2b
101–10214
185 (M+, 48), 135 (8),
109 (100)
1518 (NO2), 1346
(NO2), 1065, 1034, 972 8.35 (dd, J = 8.0, 1.6, 1 H), 7.98–8.02 (m,
8.37–8.39 (dd, J = 8.0, 1.6, 1 H), 8.33–
1 H), 7.73–7.77 (m, 1 H), 2.97 (s, 3 H, Me)
2c
114–116
115–11616
185 (M+, 100), 170
(97), 139 (23), 124 (54) (NO2), 1073, 1044
1524 (NO2), 1348
8.51 (t, J = 2.0, 1 H), 8.36–8.39 (m, 1 H),
8.01–8.04 (m, 1 H), 7.76–7.80 (t, J = 8.0,
1 H), 2.82 (s, 3 H, Me)
2d
3b
152–153
105–106
152–15314
104–10517
185 (M+, 100), 170
1520 (NO2), 1345
8.39–8.41 (d, J = 8.4, 2 H), 7.83–7.86 (d,
(41), 140 (23), 124 (17) (NO2), 1088, 1047, 853 J = 8.4, 2 H), 2.80 (s, 3 H, Me)
201 (M+, 46), 186 (74),
139 (100), 122 (25),
109 (26)
1547 (NO2), 1360
(NO2), 1306, 1154,
1121
8.21–8.23 (m, 1 H), 7.80–7.86 (m, 3 H),
3.44 (s, 3 H, Me)
3c
3d
7
144–146
142–144
79–81
148.52a
142.518
84–8519
201 (M+, 40), 186 (27),
139 (100), 122 (51),
109 (8)
1530 (NO2), 1356
(NO2), 1319, 1302,
1161
8.81 (t, J = 1.6, 1 H), 8.52–8.55 (m, 1 H),
8.30–8.32 (m, 1 H), 7.82–7.86 (t, J = 8.0,
1 H), 3.15 (s, 3 H, Me)
201 (M+, 32), 186 (23),
139 (100), 122 (56)
1530 (NO2), 1350
(NO2), 1323, 1304,
1154
8.43–8.45 (d, J = 9.2, 2 H), 8.16–8.18 (d,
J = 9.2, 2 H), 3.13 (s, 3 H, Me)
263 (M+, 64), 170
(100), 152 (14), 141
(26), 125 (94)
1524 (NO2), 1354
(NO2), 1327, 1308,
1159, 1132
8.77 (t, J = 2.0, 1.6, 1 H), 8.41–8.43 (m, 1
H), 8.27–8.29 (m, 1 H), 7.98–8.01 (m, 2
H), 7.72–7.76 (t, J = 8.0, 1 H), 7.62–7.64
(m, 1 H), 7.55–7.59 (m, 2 H)
8a
8b
8c
177–179
199–201
181–184
173–1754a
202–20315
182–1844a
308 (M+, 1), 170 (100),
151 (6), 139 (6), 122
(12)
1535 (NO2), 1372,
1356 (NO2), 1327,
1163, 590
8.73 (t, J = 2.0, 1 H), 8.48–8.50 (m, 2 H),
8.35–8.37 (m, 1 H), 7.80–7.92 (m, 4 H),
308 (M+, 13), 170
(100), 139 (6), 122 (12) 1352 (NO2), 1335,
1167, 1109, 671
1609, 1535 (NO2),
8.81 (t, J = 2.0, 2 H), 8.48–8.50 (m, 2 H),
8.33–8.35 (m, 2 H), 7.80–7.84 (t, J = 8.4,
2 H)
308 (M+, 13), 170
(100), 139 (5), 122 (8)
1532 (NO2), 1354
(NO2), 1312, 1163
8.81 (t, J = 2.0, 1 H), 8.48–8.50 (m, 1 H),
8.39–8.41 (d, J = 9.2, 2 H), 8.30–8.32 (m,
1 H), 8.18–8.21 (d, J = 9.2, 2 H), 7.78–
7.82 (t, J = 8.0, 1 H)
9
281–282
158–161
280–28120
16221
308 (M+, 14), 278 (4),
170 (100), 140 (10),
122 (19)
1547 (NO2), 1352
(NO2), 1308, 1161,
1105
8.39–8.41 (d, J = 9.2, 4 H), 8.16–8.19 (d,
J = 9.2, 4 H)
12
276 (M+, 17), 195 (12),
183 (11), 171 (19), 166
(100), 139 (47)
1593, 1566, 1518
(NO2), 1337 (NO2),
1306, 1256, 855, 743
8.26–8.28 (d, J = 9.2, 2 H), 8.20–8.22 (dd,
J = 8.0, 1.6, 1 H), 7.66–7.68 (d, J = 9.2, 2
H), 7.43–7.48 (m, 1 H), 7.35–7.39 (m, 1
H), 7.05–7.08 (dd, J = 8.0, 1.6, 1 H)
13a
13ba
17b
180–182
204–208
78–80
1835a
170 (100), 139 (5), 122
(6)
1539 (NO2), 1358
(NO2), 1321, 1155,
1121
8.47–8.49 (dd, J = 8.0, 1.6, 2 H), 7.97–
7.99 (dd, J = 8.0, 1.6, 2 H), 7.88–7.93 (m,
2 H), 7.80–7.85 (m, 2 H)
–
–
–
308 (M+, 2), 170 (100),
152 (6), 139 (7), 122
(13)
1535 (NO2), 1364
(NO2), 1327, 1161,
1125
8.45–8.48 (m, 1 H), 8.39–8.41 (d, J = 8.8,
2 H), 8.14–8.16 (d, J = 8.8, 2 H), 7.85–
7.91 (m, 3 H)
255 (M+, 3), 186(100),
131 (4), 122 (73),
1547 (NO2), 1375
(NO2), 1318, 1213,
1132, 1071, 627
8.27–8.29 (d, J = 8.8, 2 H), 8.51–8.54 (d,
J = 8.8, 2 H)
18c
92–93
300 (M+, 3), 231 (100),
186 (4)
1564 (NO2), 1379
(NO2), 1352, 1213,
1123, 1094, 625
8.50–8.52 (d, J = 8.8, 1 H), 8.68–8.71 (dd,
J = 8.8, 2.0, 1 H), 8.74 (d, J = 2.0, 1 H)
Synthesis 2002, No. 8, 1065–1071 ISSN 0039-7881 © Thieme Stuttgart · New York

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M. Nose, H. Suzuki
PAPER
Table 3 Physical Data of Nitration Products 2b–d, 3b–d, 7, 8a–c, 9, 12, 13a–b, 17, 18 and 21 (continued)
Prod-
uct
Mp (°C)
54–56
Lit.
mp (°C)
MS (70 eV) m/z (%)
IR (KBr, cm–1)
1H NMR (CDCl3/TMS), , J (Hz)
21
56–5722
255 (M+, 2), 187 (8),
186(100), 122 (60)
1607, 1543 (NO2),
1372, 1356 (NO2),
1209, 1152, 1109,
1065, 880, 606
7.96–8.00 (t, J = 8.1 8.3, 1 H), 8.39–8.41
(d, J = 7.80, 1 H), 8.70–8.73 (m, 1 H), 8.89
(s, 1 H)
a Anal. Calcd for C12H8N2O6S (308.26): C, 46.75; H, 2.62; N, 9.09. Found: C, 46.60; H, 2.71; N, 9.01.
b Anal. Calcd for C7H4F3NO4S (255.18): C, 32.95; H, 1.58; N, 5.50. Found: C, 32.61; H, 1.54; N, 6.10.
c Anal. Calcd for C7H3F3N2O6S (300.18): C, 28.01; H, 1.01; N, 9.33. Found: C, 28.01; H, 1.11; N, 9.72.
All melting points were measured on a YANACO MP-S3 apparatus
and are uncorrected. H NMR spectra were obtained with a JEOL
Kyodai-Nitration of Aromatic Sulfides 1a,4 and Sulfones
3a,6,10; Typical Procedure
1
JNM-A400 spectrometer at 400 MHz for CDCl3 solutions with
TMS as an internal standard. J values are given in Hz. IR measure-
ments were made on a JEOL FTIR-5300 spectrophotometer for KBr
pellets and only prominent peaks below 2000 cm–1 were recorded.
Electron ionization (EI) mass spectra were obtained on a Shimadzu
GCMS QP-5000 instrument at ionization potential of 70 eV. Merck
precoated silica gel sheets 60F-254 were used for TLC monitoring.
Chromatographic separation and purification were performed with
Wakogel 200 (100–200 mesh) using hexane–EtOAc, 1 5:1 as the
eluent. Products were identified by NMR, IR, MS and elemental
analyses or by direct comparison with the authentic samples.
A soln of diphenyl sulfide [(4), 0.56 g, 3 mmol] in freshly distilled
CH2Cl2 (30 mL) was stirred at –10 °C and liquid nitrogen dioxide
(2.0 mL, 60 mmol) was introduced in one portion. After 15 min, a
stream of ozonized oxygen was introduced slowly with vigorous
stirring. Ozonized oxygen was continuously fed for 3–4 h at this
temperature and the progress of the reaction intermittently moni-
tored by TLC. When the reaction was almost complete, the cooling
bath was removed and excess nitrogen dioxide was expelled by
blowing air into the solution to collect in a cold trap for reuse. The
reaction mixture was washed with sat. aq NaHCO3 and the organic
phase was extracted with CH2Cl2 (3 50 mL). The combined ex-
tracts were washed with brine, dried over MgSO4, and evaporated
under reduced pressure to leave a solid residue (0.76 g), which was
recrystallized from EtOH to obtain 3,3 -dinitrodiphenyl sulfone
[(8b), 0.46 g] as yellow plates, mp 199–201 °C (Lit.15 mp 202–
203 °C). The mother liquor was evaporated to dryness and the resi-
due was chromatographed on silica gel using hexane EtOAc as the
solvent to elute 3,4 -dinitrodiphenyl sulfone 8c, 8b and 2,3 -dini-
trodiphenyl sulfone (8a) respectively.
Reagents and solvents were all reagent-grade commercial products.
Dichloromethane and 1,2-dichloroethane were distilled from CaH2
prior to use. Nitrogen dioxide (99% purity, impurities involving ni-
trogen monoxide and small amounts of nitrogen) was purchased
from Sumitomo Seika Co. Ltd. and used after transfer distillation.
An apparatus (Nippon Ozone Co. Ltd., type ON-1–2) was used for
the generation of ozone. The machine produced ozone at a rate of
10 mmol h–1 under the conditions of oxygen flow rate 10 dm3 h–1
and applied voltage 80 V. Aryl sulfides 1a, 4 and 14 were purchased
from Aldrich and aryl sulfoxides 2b–d prepared by the oxidation of
sulfides 1b–d with nitrogen dioxide. Sulfone 19 was obtained by the
oxidation of 14 with chromium trioxide in sulfuric acid.
Kyodai-Nitration of Phenyl Trifluorometyl Sulfide (14)
Phenyl trifluoromethyl sulfide [(14), 0.35 g, 2 mmol] was dissolved
in freshly distilled CH2Cl2 (30 mL) and subjected to the Kyodai-ni-
tration in a manner similar to that described above. The resulting
mixture was worked up as usual to give nitroaryl sulfoxides 15 and
16 as an oily mixture (0.5 g). The mixture was suspended in a mix-
ture of 97% H2SO4 (0.6 mL) and H2O (1 mL) then heated with CrO3
(0.6 g) at 100 °C for 8 h. The organic phase was extracted with
CH2Cl2 (2 50 mL) and the combined extracts were washed succes-
sively with brine, sat. aq NaHCO3, dried over MgSO4, and evapo-
rated under reduced pressure. The solid residue was
chromatographed on silica gel using hexane EtOH, 5:1 as the sol-
vent to afford 4-nitrophenyl trifluoromethyl sulfone 17 (74 mg,
15%) as colorless needles.
Phenyl 2-Nitrophenyl Sulfide (10)
To a mixture of thiophenol (0.66 g, 6 mmol) and sodium hydride
(0.32 g, 13 mmol) in DMF (40 mL) was added 2-chloronitroben-
zene (0.95 g, 6 mmol) and the resulting deep purple soln was stirred
at 10 °C for 24 h under argon. The mixture was diluted with ice H2O
and the organic phase was extracted with CH2Cl2 (2 50 mL). The
combined extracts were washed with brine, dried over MgSO4, and
evaporated under reduced pressure to leave a solid residue, which
was recrystallized from EtOH to give sulfide 10 (1.14 g, 83%) as
yellow needles, mp 79–80 °C (Lit.13 mp 80.2 °C).
Anal. Calcd for C7H4F3NO4S: C, 32.95; H, 1.58; N, 5.50. Found: C,
32.61; H, 1.54; N, 6.10.
Methyl Nitrophenyl Sulfoxides 2b d; Typical Procedure
To a soln of methyl 4-nitrophenyl sulfide [(1d), 0.085 g, 0.5 mmol]
in CH2Cl2 (15 mL) was added liquid nitrogen dioxide (0.5 mL, 15
mmol) in one portion. The resulting mixture was stirred at –10 °C
for 30 min, then diluted with ice H2O, and washed with sat. aq
NaHCO3. The organic phase was extracted with CH2Cl2 (2 50
mL) and the combined extracts were washed with brine, dried over
MgSO4, and evaporated under reduced pressure. A solid residue
was recrystallized from EtOH to give sulfoxide 2d (89 mg, 96%) as
pale yellow needles, mp 152–153 °C (Lit.14 mp 152–153 °C).
Further elution gave 2,4-dinitrophenyl trifluoromethyl sulfone
[(18), 165 mg, 28%] as white crystals.
Anal. Calcd for C7H3F3N2O6S: C, 28.01; H, 1.01; N, 9.33. Found:
C, 28.05; H, 1.11; N, 9.72.
Acknowledgement
Financial support of this work by a Grant-in-Aid for Scientific Re-
search No. 12640576 from the Ministry of Education, Science,
Sports and Culture, Japan is gratefully acknowledged. We also
thank Mr. Akinori Yamamoto of Daikin Chemical Co. Ltd. for a ge-
nerous gift of phenyl trifluoromethyl sulfide.
Synthesis 2002, No. 8, 1065–1071 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
One-pot Procedure for Aryl Sulfides to Nitroaryl Sulfones
1071
(9) For oxidation of sulfides with nitrogen dioxide, see
References
Buddenberg, O. In Houben-Weyl’s Methoden der
(1) (a) Uehata, K.; Kawakami, T.; Suzuki, H. J. Chem. Soc.,
Perkin Trans. 1 2002, 696. (b) Kawakami, T.; Suzuki, H. J.
Chem. Soc., Perkin Trans. 1 2000, 1259. (c) Kawakami, T.;
Suzuki, H. J. Chem. Soc., Perkin Trans. 1 2000, 3640.
(d) Suzuki, H.; Kawakami, T. J. Org. Chem. 1999, 64, 3361.
(e) Kawakami, T.; Suzuki, H. Tetrahedron Lett. 1999, 40,
1157.
Organischen Chemie, Vol. 4/1a; Muller, E.; Bayer, O., Eds.;
Georg Thieme: Stuttgart, 1981, 809–811.
(10) Horner, L.; Schaefer, H.; Ludwig, H. Chem. Ber. 1958, 91,
75.
(11) (a) Suzuki, H.; Murashima, T. J. Chem. Soc., Perkin Trans.
1 1994, 903. (b) Suzuki, H.; Murashima, T.; Tatsumi, A.;
Kozai, I. Chem. Lett. 1993, 1421.
(2) (a) Courtin, A. Helv. Chim. Acta 1981, 64, 1849. (b) Olah,
G. A.; Orlinkov, A.; Oxyzoglou, A. B.; Prakash, G. K. S. J.
Org. Chem. 1995, 60, 7348. (c) Koloneitsev, A.; Movchun,
V. N.; Kondratenko, N. V.; Yagupolski, Y. L. Synthesis
1990, 1151.
(12) Yagupolsky, L. M.; Marenets, M. S. J. Gen. Chem. U.S.S.R.
1956, 26, 99.
(13) Kornblum, N.; Cheng, L.; Kerber, R. C.; Kestner, M. M.;
Newton, B. N.; Pinnick, H. W.; Smith, R. G.; Wade, P. A. J.
Org. Chem. 1976, 41, 1560.
(3) (a) Ono, M.; Nakamura, Y.; Sato, S.; Itoh, I. Chem. Lett.
1988, 395. (b) Takubo, Y. J. Pharm. Soc. Jpn. 1942, 62, 518.
(4) (a) Baker, B. R.; Kadish, A. F.; Querry, M. V. J. Org. Chem.
1950, 15, 400. (b) Loudon, J. D. J. Chem. Soc. 1936, 218.
(5) (a) Michel, K.; Matter, M. Helv. Chim. Acta. 1961, 44,
2204. (b) Johnson, F. E.; Hamilton, C. S. J. Am. Chem. Soc.
1949, 71, 74.
(6) For a review of preparative methods, see Schank, K. In
Houben-Weyl’s Methoden der Organischen Chemie, Vol.
E11/2.; Klamann, D., Ed.; Georg Thieme: Stuttgart, 1985,
1132–1298.
(7) Ciocca, B.; Canonica, L. Gazz. Chim. Ital. 1946, 76, 113.
(8) For a survey of the Kyodai-nitration, see (a)Nonoyama, N.;
Mori, T.; Suzuki, H. Zh. Org. Khim. 1998, 34 1591.
(b) Ridd, J. H. Acta Chem. Scand. 1998, 52, 11. (c) Suzuki,
T.; Noyori, R. Chemtracts 1997, 10, 813. (d) Mori, T.;
Suzuki, H. Synlett 1995, 383. (e) Matsunaga, M. Chimica
Oggi 1994, 58.
(14) Rabai, J.; Kapovits, I.; Tanacs, B.; Tamas, J. Synthesis 1990,
847.
(15) Buehler, C. A.; Masters, J. E. J. Org. Chem. 1938, 4, 262.
(16) Andersen, K. K.; Edmonds, W. H.; Biasotti, J. B.; Strecker,
R. A. J. Org. Chem. 1966, 31, 2859.
(17) Foster, G. F.; Reid, E. E. J. Am. Chem. Soc. 1924, 46, 1936.
(18) Waldron, W. R.; Reid, E. E. J. Am. Chem. Soc. 1923, 45,
2404.
(19) Adams, R.; Reifschneider, W.; Nair, M. D. Croat. Chem.
Acta 1957, 29, 277, Chem. Abstr. 1959, 53, 16146a.
(20) Su, W. Tetrahedron Lett. 1994, 28, 4955.
(21) Tanikaga, R.; Kaji, A. Bull. Chem. Soc. Jpn. 1973, 46, 3814.
(22) Kolomeitsev, A. A.; Movchun, V. N.; Kondratenko, N. V.;
Yagupolski, Yu. L. Synthesis 1990, 1151.
Synthesis 2002, No. 8, 1065–1071 ISSN 0039-7881 © Thieme Stuttgart · New York