Scandium triflate catalyzed one-pot synthesis of diaryl sulfoxides

Article abstract of DOI:10.1055/s-2002-25330

Arenes react smoothly with thionyl chloride in the presence of a catalytic amount of scandium triflate at ambient temperature to afford the corresponding symmetrical diaryl sulfoxides in excellent yields with high regioselectivity.

Full text of DOI:10.1055/s-2002-25330

7
84
LETTER
Scandium Triflate Catalyzed One-Pot Synthesis of Diaryl Sulfoxides
S
J
candium
h
Triflate Cata
i
lyzed
O
l
ne-Po
l
t
Synth
u
esis of Diaryl
S
ulfo
S
xides . Yadav,* Basi V. Subba Reddy, R. Srinivasa Rao, S. Praveen Kumar, K. Nagaiah
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad–500007, India
Fax +91(40)7160512; E-mail: yadav@iict.ap.nic.in
Received 7 January 2002
ing reactions and have found wide applications in organic
synthesis.11
Abstract: Arenes react smoothly with thionyl chloride in the pres-
ence of a catalytic amount of scandium triflate at ambient tempera-
ture to afford the corresponding symmetrical diaryl sulfoxides in In this report we wish to highlight our results on the elec-
excellent yields with high regioselectivity.
trophilic sulfinylation of arenes with thionyl chloride us-
Key words: scandium reagents, sulfinylation, arenes, aryl sulfox- ing a catalytic amount of scandium triflate. Thus
ides
treatment of anisole with thionyl chloride in the presence
of 5% Sc(OTf) at ambient temperature afforded dianisyl
3
sulfoxide in 90% yield (Scheme).
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
1
pharmaceuticals. Especially, sulfoxides deserved much
attention as important chiral auxiliary in asymmetric syn-
2
thesis, and particularly in carbon-carbon bond forming Scheme
3
processes. In addition, aryl sulfonium salts have also
been used extensively as photoactive cationic initiators4
In a similar fashion, several arenes reacted smoothly with
and for the photogeneration of protonic acid in the litho-
thionyl chloride to give the corresponding diaryl sulfox-
ides in high yields. In all cases, the reactions proceeded ef-
ficiently at ambient temperature with high regioselec-
tivity. The extent of electron density and the nature of the
substituent on the aromatic ring show some effect on this
conversion. The activated arenes gave the products in ex-
cellent yields in a short reaction time (Table). However,
unactivated arenes such as benzene, biphenyl, fluoroben-
zene, xylene and naphthalene also reacted well with thio-
5
graphic resist field. In view of the importance of sulfox-
ides as chiral synthons in organic synthesis, a simple and
high yielding one-pot approach for their synthesis is high-
ly desirable. Sufoxides are usually prepared by indirect
methods, which involve the oxidation of sulfides, the re-
duction of sulfones and the reaction of organometallic re-
agents with sulfinic acid esters, mixed anhydrides or
6
sulfines. The direct methods for the preparation of diaryl
sulfoxides involve the Friedel–Crafts sulfinylation of ar-
nyl chloride in the presence of 5% Sc(OTf) to afford the
3
7
8
enes using Lewis acids as well as Brønsted acids. Other
corresponding aryl sulfoxides in high yields. In contrast,
metal halides such as InCl , ZrCl , BiCl , YbCl and
methods including the addition of aryl Grignard reagents
3
4
3
3
6
to thionyl chloride and the reaction of SO with arenes in
2
CeCl gave the products in moderate yields. The best re-
3
9
the presence of Magic acid also produce aryl sulfoxides.
sults were obtained when metal triflates were used as cat-
alysts. Similar yields and selectivity were also obtained
However, many of these methods have limited synthetic
scope due to the use of corrosive, hazardous, oxidizing
and 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-
foxides. Thus there is a need to develop a simple, conve-
nient and high yielding method for the preparation of
sulfoxides under mild reaction conditions. Metal triflates
are unique Lewis acids that are currently of great research
with 5% In(OTf) under the present reaction conditions.
3
However, in the absence of catalyst, the reaction did not
yield any product even at reflux temperature. The lower-
ing of the reaction temperature was detrimental to the ef-
ficiency of this procedure. The scope of scandium triflate
catalyzed sulfinylation of arenes was investigated with re-
spect to the activated and unactivated aromatics and the
results are presented in the Table. This method is simple,
convenient and highly regioselective, affording high
yields of products in a short reaction time. In addition, this
method does not require any promoters or anhydrous con-
ditions and no precautions need to be taken to exclude
moisture from the reaction media. Scandium triflate was
found to be the best catalyst for the synthesis of aryl su-
lfoxides from activated arenes, and surprisingly, the only
catalyst effective for the sulfinylation of unactivated aro-
matics, albeit requiring longer reaction time (3–5 h).
1
0
interest. In particular, scandium salts are attractive be-
cause they are quite stable to water and reusable and in ad-
dition, they are highly effective for the activation of
arenes in electrophilic substitution reactions. Therefore,
scandium reagents are efficient catalysts compared to tra-
ditional Lewis acids in several carbon-carbon bond-form-
Synlett 2002, No. 5, 03 05 2002. Article Identifier:
1
©
437-2096,E;2002,0,05,0784,0786,ftx,en;D00302ST.pdf.
Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214
There are many advantages in the use of Sc(OTf) for this
3

LETTER
Scandium Triflate Catalyzed One-Pot Synthesis of Diaryl Sulfoxides
785
transformation which include high yields of products, Table Sc(Otf)
-Catalyzed Synthesis of Diaryl Sulphoxides
3
(
continued)
cleaner reaction profiles, mild reaction conditions, greater
selectivity, short reaction times and operational simplici-
ty. Finally, scandium triflate was recovered from aqueous
layer during the work-up and reused in subsequent reac-
tions with gradual decrease in activity; for example, ani-
sole and thionyl chloride gave 90%, 85% and 81% yields
over three cycles.
a
Entry Arene 1
Product 2
Time Yield
b
(
h)
(%)
l
3.5
70
Table Sc(Otf) -Catalyzed Synthesis of Diaryl Sulphoxides
m
n
3.5
78
82
90
3
a
Entry Arene 1
Product 2
Time Yield
b
(
h)
(%)
a
1.5
1.0
1.5
90
3.0
2.5
b
c
92
95
o
a
1
All products were characterized by H NMR, IR and Mass
1
2,
spectroscopy.
b
d
e
1.0
1.5
90
93
Isolated and unoptimized yields.
In summary, scandium triflate is a novel and highly effi-
cient Lewis acid for the synthesis of diaryl sulfoxides
from arenes and thionyl chloride under mild reaction con-
ditions. In addition to its efficiency and simplicity, this
method provides excellent yields of products with high re-
gioselectivity.
f
1.5
89
Acknowledgement
B. V. S. R., R. S. R. and S. P. K. thank CSIR, New Delhi for the
award of fellowships.
g
2.0
2.0
87
85
References
(
1) (a) Holland, H. L. Chem. Rev. 1988, 88, 473. (b) Block, E.
Angew. Chem., Int. Ed. Engl. 1992, 31, 1135.
h
(
2) (a) Solladie, G. Synthesis 1981, 185. (b) Carreno, M. C.
Chem. Rev. 1995, 95, 1717. (c) Davis, S. G.; Loveridge, T.;
Clough, J. M. Synlett 1997, 66.
(
(
(
(
3) (a) Magnus, P. D. Tetrahedron 1977, 33, 2019.
(b) Madesclaire, M. Tetrahedron 1988, 44, 6537.
4) Crivello, J. V.; Lam, J. H. W. Macromolecules 1977, 10,
i
2.5
3.0
4.0
80
82
75
1
307.
5) Miller, R. D.; Renaldo, A. F.; Ito, J. J. Org. Chem. 1988, 53,
571.
5
j
6) Drabowicz, J.; Kielbasinski, P.; Mikolajczyk, M. In The
Chemistry of Sulfones and Sulfoxides, Chap. 8; Patai, S.;
Rappoport, Z.; Stirling, C. J. M., Eds.; Wiley: New York,
1
988.
7) (a) Olah, G. A.; Nishimura, J. J. Org. Chem. 1974, 39, 1203.
b) Chaser, O. W.; Pratt, T. M. Phosphorus Sulfur Relat.
Elem. 1978, 5, 35.
k
(
(
Synlett 2002, No. 5, 784–786 ISSN 0936-5214 © Thieme Stuttgart · New York

7
86
J. S. Yadav et al.
LETTER
anhyd Na SO , concentrated in vacuo and the resulting
(
8) (a) Yamamoto, K.; Miyatake, K.; Nishimura, Y.; Tsuchida,
E. J. Chem. Soc., Chem. Commun. 1996, 2099. (b) Olah, G.
A.; Marinez, E. R.; Surya Prakash, G. A. Synlett 1999, 1397.
9) Lalli, K. K.; Nagvekar, D. S. J. Org. Chem. 1991, 56, 1867.
2
4
product was purified by column chromatography on silica
gel (Merck, 100–200 mesh, ethyl acetate–hexane, 2:8) to
afford pure diaryl sulfoxides. Spectral data for products:
(
1
(
10) (a) Kobayashi, S. Eur. J. Org. Chem. 1999, 15.
b) Kobayashi, S. Synlett 1994, 689. (c) Kobayashi, S. J.
Di-(3,4-dimethoxyphenyl) Sulfoxide (2b): H NMR (200
(
MHz, CDCl ): 3.98 (s, 12 H), 6.97 (d, 2 H, J = 8.0 Hz), 7.40
3
Synth. Org. Chem. Jpn. 1995, 53, 370.
(d, 2 H, J = 2.3 Hz), 7.65 (dd, 2 H, J = 2.3, 8.0 Hz). EIMS:
+
(
11) (a) Yadav, J. S.; Reddy, B. V. S.; Rao, T. P. Tetrahedron
Lett. 2000, 41, 7943. (b) Yadav, J. S.; Reddy, B. V. S.;
Murthy, C. V. S. R.; Kumar, G. M. Synlett 2000, 1450.
m/z: 336 (M ), 321, 293, 155, 69, 57. IR (KBr): 2925, 2855,
–1
1585, 1474, 1359, 1254, 1208, 1033, 840, 778 cm .
1
Di-(3,4-dimethylphenyl) Sulfoxide (2i): H NMR (200
(
c) Yadav, J. S.; Reddy, B. V. S.; Chand, P. K. Tetrahedron
MHz, CDCl ): 2.40 (s, 12 H), 7.25 (d, 2 H, J = 1.2 Hz), 7.30
3
Lett. 2001, 42, 4057. (d) Yadav, J. S.; Reddy, B. V. S.;
Geetha, V. Tetrahedron Lett. 2001, 42, 4407.
12) Experimental procedure: A mixture of arene (10 mmol),
(d, 2 H, J = 8.0 Hz), 7.78 (dd, 2 H, J = 1.2 and 8.0 Hz). EIMS:
+
m/z: 258 (M ), 240, 226, 169, 141, 105, 77, 43. IR (KBr):
–1
(
2924, 2853, 1585, 1450, 1325, 1124, 772, 601 cm .
1
thionyl chloride (6 mmol) and Sc(OTf) (5 mol%) in
Di-(2-methoxy-1-naphthyl) Sulfoxide (2o): H NMR (200
3
dichloromethane (15 mL) was stirred at ambient temperature
MHz, CDCl3): 4.0 (s, 6 H), 7.23 (d, 2 H, J = 8.0 Hz), 7.38
(t, 2 H, J = 7.8 Hz), 7.57 (t, 2 H, J = 7.8 Hz), 7.70 (d, 2 H, J
= 8.0 Hz), 7.78 (d, 2 H, J = 8.0 Hz), 8.20 (d, 2 H, J = 8.0 Hz).
under N atmosphere for an appropriate time (Table). After
2
complete conversion, as indicated by TLC, the reaction
mixture was diluted with water (10 mL), neutralized with
sat. sodium bicabonate and extracted with dichloromethane
+
FAB Mass: 362 (M ), 346, 192, 177, 149, 126, 114, 63. IR
(KBr): 2923, 2845, 1585, 1495, 1430,1355, 1320, 1255,
–
1
(
2
15 mL). The combined organic layers were dried over
1210, 1178, 1024, 840 cm .
Synlett 2002, No. 5, 784–786 ISSN 0936-5214 © Thieme Stuttgart · New York