Highly Rapid and Direct Synthesis of Diaryl Sulfoxides

Article abstract of DOI:10.1055/s-2003-41461

Aromatic compounds react smoothly with thionyl chloride in the presence of 10 mol% of water at ambient temperature to afford the corresponding symmetrical diaryl sulfoxides in good to excellent yields with high regioselectivity.

Full text of DOI:10.1055/s-2003-41461

LETTER
2029
Highly Rapid and Direct Synthesis of Diaryl Sulfoxides
H
ighly Rapid and
.
D
irect
Synt
P
hesis of
D
iary
.
l
S
ulfoxidesBandgar,* S. N. Kinkar, V. T. Kamble, S. V. Bettigeri
Organic Chemistry Research Laboratory, School of Chemical Sciences, Swami Ramanand Teerth Marathwada University,
Nanded-431 606, India
Fax +91(2462)229245; E-mail: bandgar_bp@yahoo.com
Received 13 June 2003
foxides. Thus there is a need to develop a simple and high
yielding method for the preparation of sulfoxides under
mild reaction conditions.
Abstract: Aromatic compounds react smoothly with thionyl
chloride in the presence of 10 mol% of water at ambient tempera-
ture to afford the corresponding symmetrical diaryl sulfoxides in
good to excellent yields with high regioselectivity.
In this communication, we wish to highlight our results on
Keywords: aryl sulfoxides, arenes, aqueous medium, thionyl the electrophilic sulfinylation of arenes with thionyl chlo-
chloride
ride and 10% of water. Thus, treatment of anisole with this
combination at ambient temperature afforded dianisyl sul-
foxide in excellent yield. In a similar fashion, several are-
nes reacted with thionyl chloride to give the
corresponding diaryl sulfoxides in good to excellent
yields. (Scheme 1 and Table 1).
In organic synthesis increasing attention is being focused
on reactions in aqueous media.1 When solvent must be
used, water is the most acceptable in terms of cost and en-
vironmental impact. However, despite its large liquid
range and extremely high specific heat capacity, it is fre-
quently overlooked as a solvent for organic reactions.
Most catalysts and reagents are deactivated or decom-
posed in water and in general organic compounds are in-
soluble in water. Therefore, carrying out organic reactions
in water poses important challenges in the area of reaction
design.
Scheme 1
In all cases, the reactions proceeded efficiently at ambient
temperature with high regioselectivity. Activated arenes
gave the products in excellent yields in a short reaction
time (entries a–g) and unactivated arenes such as fluo-
robenzene (entry h), chlorobenzene (entry i), bromoben-
zene (entry j), iodobenzene (entry k), p-dichlorobenzene
(entry l) and naphthalene (entry o) also reacted with thio-
nyl chloride to afford the corresponding diaryl sulfoxides
in moderate yields and in short reaction times. However,
deactivated arenes (entries p–t) remain unreacted under
these reaction conditions even after stirring the reaction
mixture for longer time (24 h). It is interesting to note that
even heterocyclic compounds such as thiophene and pyri-
dine were smoothly converted into the corresponding di-
aryl sulfoxides albeit in lower yields (entries m–n), a
conversion which is otherwise problematic in the pres-
ence of strong acid catalysts. It is important to mention
that 10% amount of water is more than sufficient to bring
out this transformation of arenes (8 mmol) with thionyl
chloride (6 mmol). However, in case of solid arene e.g.
naphthalene for effective stirring and complete transfor-
mation into the corresponding sulfoxide, THF (1 mL) was
used as a solvent. It is reported in the literature that in the
absence of catalyst, the sulfinylation of arenes did not
yield any product even at reflux temperature. In this con-
text, the present methodology is superior because under
mild conditions the reaction proceeded smoothly in the
presence of 10% amount of water. This method is simple,
convenient and highly regioselective, affording good
yields of products in a short reaction time and does not
Sulfoxides and sulfones are interesting functional groups
possessing manifold reactivity for conversion of a variety
of organic sulfur compounds in the field of drugs and
pharmaceuticals.2 Sulfoxides have received much atten-
tion as important chiral auxiliaries in asymmetric
synthesis3 and in carbon-carbon bond forming processes.4
In addition, aryl sulfonium salts have also been used ex-
tensively as photoactive cationic initiators5 and for the
photogeneration of protonic acid in the lithographic resist
field.6 Sulfoxides are usually prepared by indirect meth-
ods, which involve the oxidation of sulfides, the reduction
of sulfones and the reaction of organometallic reagents
with sulfinic acid esters, mixed anhydrides or sulfines.7
The direct methods for the preparation of diaryl sulfoxides
involve the Friedel–Crafts sulfinylation of arenes using
Lewis acids8 as well as Brønsted acids.9 Other methods in-
cluding the addition of aryl Grignard reagents to thionyl
chloride, the reaction of SO2 with arenes in the presence
of magic acid10 and the reaction of SOCl2 with arenes in
the presence of, scandium triflate as catalyst,11 also pro-
duce aryl sulfoxides. However, many of these methods
have limited synthetic scope due to the use of expensive
or difficult to handle reagents, lack of selectivity and the
formation of a mixture of products containing sulfonium
salts and chlorinated byproducts along with desired sul-
SYNLETT 2003, No. 13, pp 2029–2032
1
6
.1
0
.2
0
0
3
Advanced online publication: 08.10.2003
DOI: 10.1055/s-2003-41461; Art ID: D13903ST
© Georg Thieme Verlag Stuttgart · New York

2030
B. P. Bandgar et al.
LETTER
require any added promoters. This protocol is advanta- In summary, a novel and highly efficient methodology for
geous in terms of high yields of products, mild reaction the synthesis diaryl sulfoxides from arenes and thionyl
conditions, greater selectivity, short reaction times and chloride in the presence of 10% amount of water under
operational simplicity. In the absence of water sulfinyl- mild conditions is reported. In addition to its efficiency
ation did not proceed even after stirring the mixture for and simplicity, this protocol provides excellent yields of
longer time (24 h).
products with high regioselectivity.
Table 1 Synthesis of Diaryl Sulfoxides in 10 mol% of Water
Entry
Arene
Product
Time [min (h)]
Yielda,b (%)
93
a
5
b
c
d
5
5
5
85
92
94
e
f
5
5
91
97
g
h
i
5
5
5
5
5
95
75
97
90
75
j
k
Synlett 2003, No. 13, 2029–2032 © Thieme Stuttgart · New York

LETTER
Highly Rapid and Direct Synthesis of Diaryl Sulfoxides
2031
Table 1 Synthesis of Diaryl Sulfoxides in 10 mol% of Water (continued)
Entry
l
Arene
Product
Time [min (h)]
Yielda,b (%)
5
82
m
n
5
5
46
50
o
35
53c
p
q
r
1-Nitronapthalene
Nitrobenzene
No reaction
No reaction
No reaction
No reaction
No reaction
(24)
(24)
(24)
(24)
(24)
–
–
–
–
–
4-Nitroanisole
s
t
4-Nitrotoluene
4-Nitrofluorobenzene
a Isolated and unoptimized yields.
b Products were characterized by 1H NMR, IR spectroscopy, elemental analysis and by comparison with authentic samples.
c THF (1 mL) was used as a solvent for effective stirring and complete transformation into the corresponding sulfoxide.
di-(2,4-Dimethylphenyl) sulfoxide (2d): IR (KBr): 610, 765, 1035,
1
1215, 1330, 1450, 1580, 2845, 2925 cm–1. H NMR (300 MHz,
General Procedure for Sulfinylation of Liquid Arenes: To a
mixture of liquid arene (8 mmol) and H2O (0.8 mmol), SOCl2 (6
mmol) was added dropwise (Caution: the reactions were vigorous
and highly exothermic. Therefore cooling of the reaction mixture in
ice is required) and the reaction mixture was stirred at r.t. for 5 min.
After completion of the reaction (TLC), the product was extracted
with Et2O (3 × 10 mL) and removal of the solvent under reduced
pressure furnished crude product, which was purified by column
chromatography (silica gel, petroleum ether).
CDCl3): d = 2.35 (s, 12 H, 4 × Me), 6.9 (d, 2 H, J = 1.4 Hz, Ar-H),
7.20 (dd, 2 H, J = 1.4 and 8.1 Hz, Ar-H), 7.7 (d, 2 H, J = 8.1 Hz, Ar-
H). Anal. Calcd for C16H18SO (258.39): C, 74.37%; H, 7.02%; S,
12.41%. Found: C, 74.31%; H, 7.18%; S, 12.35%.
di-(2,5-Dimethylphenyl) sulfoxide (2e): IR (KBr): 605, 770, 1045,
1
1210, 1325, 1445, 1585, 2850, 2915 cm–1. H NMR (300 MHz,
CDCl3): d = 2.40 (s, 12 H, 4 × Me), 7.1 (d, 2 H, J = 8.2 Hz, Ar-H),
7.4 (dd, 2 H, J = 1.2 and 8.2 Hz, Ar-H), 7.65 (d, 2 H, J = 1.2 Hz, Ar-
H). Anal. Calcd for C16H18SO (258.39): C, 74.37%; H, 7.02%; S,
12.41%. Found: C, 74.43%; H, 7.12%; S, 12.47%.
General Procedure for Sulfinylation of Naphthalene (Solid Are-
ne): To a mixture of naphthalene (8 mmol), H2O (0.8 mmol) and
THF (1 mL), was added SOCl2 (6 mmol) dropwise (Caution: the re-
actions were vigorous and highly exothermic. Therefore, cooling of
the reaction mixture in ice is required) and the reaction mixture was
stirred at r.t. for 35 min. After completion of the reaction (TLC), the
product was extracted with Et2O (3 × 10 mL) and removal of the
solvent under reduced pressure furnished crude product which was
purified by column chromatography (silica gel, petroleum ether).
di-(2-Thiophenyl) sulfoxide (2m): IR (neat): 1030, 1510, 1600,
3010 cm–1. 1H NMR (300 MHz, CDCl3): d = 7.2–7.5 (m, 3 H, Ar-
H). Anal. Calcd for C8H6S3O (214.34): C, 44.83%; H, 2.82%; S,
44.88%; Found: C, 44.77%; H, 2.91%; S, 44.79%.
di-(3-Pyridinyl) sulfoxide (2n): IR (neat): 720, 1040, 1500, 1600,
3005 cm–1. 1H NMR (300 MHz, CDCl3): d = 7.1–7.4 (m, 8 H, Ar-
H). Anal. Calcd for C10H8N2SO (204.25): C, 58.80%; H, 3.94%; N,
13.7; S, 15.69%. Found: C, 58.95%; H, 4.02%; N, 13.82%; S,
15.58%.
Representative Analytical Data:
di-(3,4-Dimethylphenyl) sulfoxide (2c): IR (neat): 600, 775, 1024,
1325, 1452, 1585, 2850, 2920 cm–1. 1H NMR (300 MHz, CDCl3):
d = 2.40 (s, 12 H, 4 × Me), 7.25 (d, 2 H, J = 1.2 Hz, Ar-H), 7.30 (d,
2 H, J = 8.0 Hz, Ar-H), 7.75 (dd, 2 H, J = 1.2 8.0 Hz, Ar-H). Anal.
Calcd for C16H18SO (258.39): C, 74.37%; H, 7.02%; S, 12.41%.
Found: C, 74.49%; H, 6.95%; S, 12.36%.
di-(2-Naphthyl) sulfoxide (2o): IR (KBr): 1050, 1120, 1590, 3010
cm–1. 1H NMR (300 MHz, CDCl3): d = 6.90 (m, 8 H, Ar-H), 7.2 (m,
1 H, Ar-H), 7.4 (m, 4 H, Ar-H). Anal. Calcd for C20H14SO (302.39):
C, 79.44%; H, 4.67%; S, 10.%. Found: C, 79.35; H, 4.72; S, 1053%.
Synlett 2003, No. 13, 2029–2032 © Thieme Stuttgart · New York

2032
B. P. Bandgar et al.
LETTER
(5) Crivello, J. V.; Lam, J. H. W. Macromolecules 1977, 10,
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