Oxidation of Sulfides to Sulfoxides with Hypervalent (tert-Butylperoxy)iodanes

Article abstract of DOI:10.1021/jo970081q

Oxidation of sulfides with the crystalline (alkylperoxy)iodanes, 1-(tert-butylperoxy)-1,2-benziodoxol-3(1H)-ones 2a and 2b, in acetonitrile-water or in dichloromethane, affords sulfoxides in high yields. Measurement of the relative rates of oxidation for a series of ring-substituted thioanisoles 3b (p-MeO), 3c (p-Me), and 3d (p-Cl) in acetonitrile-water indicates that electron-releasing groups such as p-MeO and p-Me groups increase the rate of oxidation, and Hammett correlation of the relative rate factors with the substituent constants affords the reaction constants ρ⁺ = -2.23 (σ⁺, r = 0.98) for BF₃-catalyzed oxidation and ρ = -3.32 (σ, r = 0.98) for uncatalyzed oxidation. The effects of a free-radical scavenger, galvinoxyl, were examined. A mechanism involving the intermediary formation of the sulfonium species 11 by nucleophilic attack of sulfide toward the iodine(III) atom of 2 is proposed for the oxidation in acetonitrile-water in the presence and the absence of BF₃· Et₂O. On the other hand, the oxidation of sulfoxides in dichloromethane probably proceeds by a radical process, which involves the decomposition at room temperature of 2 via homolytic bond cleavage of the weak iodine(III)-peroxy bond, generating tert-butylperoxy radical and the [9-1-2] iodanyl radical 12.

Full text of DOI:10.1021/jo970081q

J . Org. Chem. 1997, 62, 4253-4259
4253
Oxid a tion of Su lfid es to Su lfoxid es w ith Hyp er va len t
(ter t-Bu tylp er oxy)iod a n es
Masahito Ochiai,* Akinobu Nakanishi, and Takao Ito
Faculty of Pharmaceutical Sciences, University of Tokushima, 1-78 Shomachi, Tokushima 770, J apan
Received J anuary 15, 1997X
Oxidation of sulfides with the crystalline (alkylperoxy)iodanes, 1-(tert-butylperoxy)-1,2-benziodoxol-
3(1H)-ones 2a and 2b, in acetonitrile-water or in dichloromethane, affords sulfoxides in high yields.
Measurement of the relative rates of oxidation for a series of ring-substituted thioanisoles 3b (p-
MeO), 3c (p-Me), and 3d (p-Cl) in acetonitrile-water indicates that electron-releasing groups such
as p-MeO and p-Me groups increase the rate of oxidation, and Hammett correlation of the relative
rate factors with the substituent constants affords the reaction constants ρ+ ) -2.23 (σ+, r ) 0.98)
for BF3-catalyzed oxidation and ρ ) -3.32 (σ, r ) 0.98) for uncatalyzed oxidation. The effects of a
free-radical scavenger, galvinoxyl, were examined. A mechanism involving the intermediary
formation of the sulfonium species 11 by nucleophilic attack of sulfide toward the iodine(III) atom
of 2 is proposed for the oxidation in acetonitrile-water in the presence and the absence of BF3‚
Et2O. On the other hand, the oxidation of sulfoxides in dichloromethane probably proceeds by a
radical process, which involves the decomposition at room temperature of 2 via homolytic bond
cleavage of the weak iodine(III)-peroxy bond, generating tert-butylperoxy radical and the [9-I-2]
iodanyl radical 12.
In spite of extensive studies on the chemistry of
hypervalent organoiodanes, little is known about per-
oxyiodanes, probably because of their high tendency to
decompose.1 Milas and Plesnicar reported the reaction
of iodosylbenzene with tert-butyl hydroperoxide in dichlo-
romethane, and proposed the in situ generation of labile
[bis(tert-butylperoxy)iodo]benzene, which decomposes ho-
molytically even at -80 °C to give tert-butylperoxy radical
and iodobenzene.2 Plesnicar and Russell reported the
first synthesis of (peraroyloxy)iodanes.3 By the reaction
of iodosylbenzene with perbenzoic acids, they obtained
the symmetrically substituted [bis(perbenzoyloxy)iodo]-
benzenes as labile amorphous solids, which undergo
spontaneous ignition or detonation upon manipulation
in the solid state at room temperature. Recently, we
found the Lewis acid-catalyzed ligand exchange of 1-hy-
droxy-1,2-benziodoxol-3(1H)-ones 1a ,b with tert-butyl
hydroperoxide in chloroform affords the crystalline (al-
kylperoxy)iodanes, 1-(tert-butylperoxy)-1,2-benziodoxol-
3(1H)-ones 2a and 2b.4,5 The (alkylperoxy)iodane 2a is
stable in the solid state and can be safely stored at room
temperature for an indefinite period of time.
The (tert-butylperoxy)iodane 2 oxidizes benzyl and allyl
ethers to the esters at room temperature in the presence
of alkali metal carbonates via a radical process.4b Be-
cause this reaction is compatible with other protecting
groups such as MOM, THP, and TBDMS ethers, and
acetoxy groups, and because esters are readily hydrolyzed
under basic conditions, this method provides a convenient
and effective alternative to the usual reductive depro-
tection of benzyl and allyl ethers. We report here the
oxidation of sulfides with the (tert-butylperoxy)iodane 2
in acetonitrile-water or in dichloromethane, yielding
sulfoxides in high yields. Substituent effects were ex-
amined for the oxidation of thioanisoles in acetonitrile-
water in the presence of the absence of BF3‚Et2O as well
as the effects of a free-radical scavenger, galvinoxyl.
X Abstract published in Advance ACS Abstracts, May 15, 1997.
(1) For reviews of organoiodanes, see: (a) Banks, D. F. Chem. Rev.
1966, 66, 243. (b) Koser, G. F. The Chemistry of Functional Groups,
Supplement D; Wiley: New York, 1983; Chapter 18. (c) Varvoglis, A.
Synthesis 1984, 709. (d) Ochiai, M.; Nagao, Y. J . Synth. Org. Chem.,
J pn. 1986, 44, 660. (e) Moriarty, R. M.; Prakash, O. Acc. Chem. Res.
1986, 19, 244. (f) Merkushev, E. B. Russian Chem. Rev. 1987, 56, 826.
(g) Ochiai, M. Revs. Heteroatom Chem. 1989, 2, 92. (h) Moriarty, R.
M.; Vaid, R. K. Synthesis 1990, 431. (i) Moriarty, R. M.; Vaid, R. K.;
Koser, G. F. Synlett. 1990, 365. (j) Stang, P. J . Angew. Chem., Int.
Ed. Engl. 1992, 31, 274. (k) Kita, Y.; Tohma, H.; Yakura, T. Trends
in Organic Chemistry 1992, 3, 113. (l) Kita, Y.; Tohma, H. Farumashia
1992, 28, 984. (m) Varvoglis, A. The Chemistry of Polycoordinated
Iodine; VHC Publishers: New York, 1992. (n) Koser, G. F. The
Chemistry of Functional Groups, Supplement D2; Wiley: New York,
1995; Chapter 21. (o) Kitamura, T. J . Synth. Org. Chem., J pn. 1995,
53, 893. (p) Stang, P. J .; Zhdankin, V. V. Chem. Rev. 1996, 96, 1123.
(2) (a) Milas, N. A.; Plesnicar, B. J . Am. Chem. Soc. 1968, 90, 4450.
(b) Traylor, T. G.; Xu, F. J . Am. Chem. Soc. 1987, 109, 6201. (c)
Traylor, T. G.; Fann, W.-P.; Bandyopadhyay, D. J . Am. Chem. Soc.
1989, 110, 8009.
Resu lts a n d Discu ssion
Oxid a tion of Su lfid es. Hypervalent organoiodanes
such as iodosylbenzene6 and [bis(acyloxy)iodo]benzenes7
have been known to selectively oxidize sulfides to sul-
foxides. Oxidation with (diacetoxyiodo)benzene in CH3-
(5) Moss and Zhang also reported the synthesis of the peroxyiodane
2a involving a ligand exchange of a labile (phosphoryloxy)iodane,
prepared in situ by the reaction of 1-chloro-1,2-benziodoxol-3(1H)-one
with silver diphenyl phosphate in DMSO, with tert-butyl hydroperox-
ide. See: Moss, R. A.; Zhang, H. J . Am. Chem. Soc. 1994, 116, 4471.
(6) (a) Ford-Moore, A. H. J . Chem. Soc. 1949, 2126. (b) Takaya, T.;
Enyo, H.; Imoto, E. Bull. Chem. Soc. J pn. 1968, 41, 1032. (c) Barton,
D. H. R.; Godfrey, C. R. A.; Morzycki, J . W.; Motherwell, W. B.; Stobie,
A. Tetrahedron Lett. 1982, 23, 957.
(3) (a) Plesnicar, B.; Russell, G. A. Angew. Chem., Int. Ed. Engl.
1970, 9, 797. (b) Plesnicar, B. J . Org. Chem. 1975, 40, 3267.
(4) (a) Ochiai, M.; Ito, T.; Masaki, Y.; Shiro, M. J . Am. Chem. Soc.
1992, 114, 6269. (b) Ochiai, M.; Ito, T.; Takahashi, H.; Nakanishi, A.;
Toyonari, M.; Sueda, T.; Goto, S.; Shiro, M. J . Am. Chem. Soc. 1996,
118, 7716.
S0022-3263(97)00081-9 CCC: $14.00 © 1997 American Chemical Society

4254 J . Org. Chem., Vol. 62, No. 13, 1997
Ta ble 1. Oxid a tion of Th ioa n isole (3a ) w ith (ter t-Bu tylp er oxy)iod a n es 2a
Ochiai et al.
conditions
product (yield,b %)
entry
peroxyiodane 2 (equiv)
solvent
additive (equiv)
temp/°C, time/h
4a
31
37
67 (63)
11
5
6
3a
c
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
2a (1.2)
2b (1.3)
2a (1.2)
2a (1.2)
2a (1.2)
2a (1.1)
2a (1.2)
2a (1.1)
2a (1.1)
2a (1.2)
2a (1.2)
2b (1.1)
2a (2.1)
2a (0.34)
2a (2.5)
CH2Cl2
CH2Cl2
CH2Cl2
25, 8.5
25, 7.5
25, 3
5
7
1
26
22
4
2
2
15
82
17
c
BF3‚Et2O (1.2)
AcOEt-H2O (5:1)c
AcOEt-H2O (5:1)c
CH3CN
25, 72
50, 24
25, 80
50, 10
25, 80
25, 3.5
50, 10
50, 7.5
50, 1
63
64 (48)
60 (56)
94 (84)
100 (100)
100 (97)
100 (100)
98 (61)
(81)
4
3
CH3CN
13
CH3CN-H2O (5:1)
CH3CN-H2O (5:1)
CH3CN-H2O (5:1)
CH3CN-H2O (5:1)c
CH3CN-H2O (5:1)c
CH3CN-H2O (5:1)c
CH3CN-H2O (5:1)c
toluene
BF3‚Et2O (0.3)
50, 4
50, 27
30, 96
36
63
(82)
a
b
Reactions were carried out under nitrogen, unless otherwise noted. Yields were determined by GC. Yields in parentheses are based
on pure isolated materials. c Reactions were carried out under atmospheric conditions.
CN-H2O or AcOH-H2O have been shown to be acid
catalyzed.8 High yields of sulfoxides have been obtained
by the sulfuric acid-catalyzed oxidation with 1-hydroxy-
1,2-benziodoxol-3(1H)-one (1a ), in which the recovered
o-iodobenzoic acid can be reconverted into the oxidizing
agent.9 [Hydroxy(tosyloxy)iodo]benzene can effect the
controlled oxidation of sulfides to sulfoxides.10 (Dichlor-
oiodo)benzene in aqueous pyridine also affords sulfoxides
and/or sulfones, depending on the reaction conditions.11
Catalytic oxidation of sulfides using metalloporphyrin
and iodosylbenzene as a terminal oxidant gives sulfoxides
in high yields.12 Benzeneseleninic acid catalyzes oxida-
tion of sulfides with iodosylbenzene, in which [hydroxy-
(benzeneseleninyloxy)iodo]benzene generated in situ has
been proposed to be an active oxidant.13
important in the reaction. Oxidation of 3a in acetoni-
trile-water (5:1) at room temperature was very slow (80
h) but highly selective and gave rise to the sulfoxide 4a
in 94% yield. In the absence of water, further oxidation
of 4a to the sulfone 5 may compete to a small extent
(compare entries 6 and 8). It has been reported that, in
the oxidation of dibenzyl sulfide to the sulfoxide with
hydrogen peroxide in isopropyl alcohol, the presence of
water decreases the rate of further oxidation to the
sulfone, presumably because of the specific solvation of
the sulfoxide ground state by water.14 This solvation
results in a decrease in nucleophilicity of the sulfur atom,
thereby lowering the reactivity of the sulfoxide toward
peroxide oxidation.
The rate of oxidation was much increased either by the
use of acid catalyst BF3‚Et2O (0.3 equiv) as an additive
in acetonitrile-water (5:1) at room temperature (method
A) or by carrying out the reaction at 50 °C in acetoni-
trile-water (5:1) (method B) (Table 1, entries 9-11). In
spite of the presence of both a peroxy group and a
trivalent iodine in the molecule, the experimental data
on the stoichiometry (Table 1, entry 14) of the reaction
indicate that the (tert-butylperoxy)iodane 2a oxidizes 1
mol equivalent of the sulfides 3a to the sulfoxide 4a .
Interestingly, use of toluene as a solvent and 2.5 equiv
of 2a gave the sulfone 5 in 82% yield, whereas other
solvents such as benzene, fluorobenzene, acetone, ethyl
acetate, and carbon tetrachloride gave poor results for
oxidation to the sulfone 5.
The uncatalyzed (50 °C) and the BF3-catalyzed oxida-
tions (25 °C) of a variety of sulfides with the (tert-
butylperoxy)iodane 2a in acetonitrile-water afforded the
corresponding sulfoxides in high yields (Table 2). In
general, oxidation of dialkyl sulfides is fast, being com-
pleted within 1 h. The rate of oxidation decreases in the
order dialkyl > alkyl aryl > diaryl sulfides, which would
suggest an electrophilic nature of the oxidant under these
conditions.15 Allylic oxidation4b as well as epoxidation4a
of a double bond cannot compete with the sulfide oxida-
tion (Table 2, entries 11 and 12). The oxidation of
diphenyl sulfide (3e) under these conditions is very slow;
for instance, even after 26 h at 50 °C (method B), a large
amount of the sulfide 3e was recovered unchanged (Table
The results of oxidation of thioanisole (3a ) with the
(tert-butylperoxy)iodanes 2 under a variety of conditions
are summarized in Table 1. Exposure of 3a to the
peroxyiodane 2a in dichloromethane at room temperature
afforded a mixture of products consisting of the sulfoxide
4a (31%), methyl phenyl sulfone (5) (5%), and chloro-
methyl phenyl sulfoxide (6) (26%). A similar mixture of
products was obtained when the (p-nitroperoxy)iodane
2b was employed (Table 1, entry 2). Use of BF3‚Et2O as
an additive led to selective formation of the sulfoxide 4a
in 67% yield (Table 1, entry 3). The choice of solvents is
(7) Szmant, H. H.; Lapinski, R. L. J . Am. Chem. Soc. 1956, 78, 458.
For asymmetric oxidation of sulfides with (diacyloxyiodo)benzenes,
see: (a) Imamoto, T.; Koto, H. Chem. Lett. 1986, 967. (b) Ray, D. G.,
III; Koser, G. F. J . Org. Chem. 1992, 57, 1607.
(8) (a) Humffray, A. A.; Imberger, H. E. J . Chem. Soc., Perkin Trans.
2 1981, 382. (b) Srinivasan, C.; Chellamani, A.; Kuthalingam, P. J .
Org. Chem. 1982, 47, 428.
(9) Folsom, H. E.; Castrillon, J . Synth. Commun. 1992, 22, 1799.
(10) (a) Koser, G. F.; Kokil, P. B.; Shah, M. Tetrahedron Lett. 1987,
28, 5431. (b) Miyata, O.; Nishiguchi, A.; Ninomiya, I.; Naito, T. Chem.
Pharm. Bull. 1996, 44, 1285.
(11) Barbieri, G.; Cinquini, M.; Colonna, S.; Montanari, F. J . Chem.
Soc. (C) 1968, 659.
(12) (a) Ando, W.; Tajima, R.; Takata, T. Tetrahedron Lett. 1982,
23, 1685. (b) Pautet, F.; Daudon, M. Tetrahedron Lett. 1991, 32, 1457.
For catalytic asymmetric oxidation of sulfides with (salen)manganese-
(III) complexes and iodosylbenzene, see: Noda, K.; Hosoya, N.; Yanai,
K.; Irie, R.; Katsuki, T. Tetrahedron Lett. 1994, 35, 1887.
(13) Roh, K. R.; Kim, K. S.; Kim, Y. H. Tetrahedron Lett. 1991, 32,
793.
(14) (a) Overberger, C. G.; Cummins, R. W. J . Am. Chem. Soc. 1953,
75, 4783. (b) Curci, R.; DiPrete, R. A.; Edwards, J . O.; Modena, G. J .
Org. Chem. 1970, 35, 740.
(15) (a) Kice, J . L. Acc. Chem. Res. 1968, 1, 58. (b) Pryor, W. A.;
Bickley, H. T. J . Org. Chem. 1972, 37, 2885.

Oxidation of Sulfides to Sulfoxides
J . Org. Chem., Vol. 62, No. 13, 1997 4255
Ta ble 2. Oxid a tion of Su lfid es to Su lfoxid es w ith
Ta ble 3. Rela tive Rea ctivity of Th ioa n isoles 3 to
P er oxyiod a n e 2a
(ter t-Bu tylp er oxy)iod a n e 2a
entry
sulfide
methoda
time/h
yield,b %
krel
b
c
a
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
n-BuSCH2Ph
n-BuSCH2Ph
i-BuSCH2Ph
i-BuSCH2Ph
s-BuSCH2Ph
s-BuSCH2Ph
(PhCH2)2S
(PhCH2)2S
Me(CH2)4SPh
Me(CH2)4SPh
CH2dCHCH2SPh
CH2dCHCH2SPh
p-MeOC6H4SMe 3b
p-MeOC6H4SMe 3b
p-MeC6H4SMe 3c
p-MeC6H4SMe 3c
p-ClC6H4SMe 3d
p-ClCC6H4SMe 3d
PhSCH2P(O)(OEt)2
PhSCH2P(O)(OEt)2
Ph2S 3e
A
B
A
B
A
B
A
B
A
B
A
B
A
B
A
B
A
B
A
B
A
B
C
C
C
C
C
0.7
0.25
0.7
0.25
0.4
0.25
0.5
0.7
3
100
78
87
80
90
75
85
78
99
82
82
77
79
90
75
97
92
substrate
with BF3
without BF3
Ep
3a
3b
3c
3d
(H)
1.0
31.25
3.70
0.23
1.0
13.38
3.17
0.24
1.53
1.26
1.41
1.55
(p-MeO)
(p-Me)
(p-Cl)
a
One-electron oxidation potentials (V vs SCE in CH3CN)
reported by Oae.17 BF3‚Et2O (0.3 equiv), CH3CN-H2O (5:1), 30
b
°C, 3 h, N2. c CH3CN-H2O (5:1), 40 °C, 5 h, air.
2
3.5
2.5
3
2.25
3
2
6
8
38
11
28
26
11
4
5.5
77
60
3d (p-Cl) were measured in acetonitrile-water either at
30 °C in the presence of BF3‚Et2O or at 40 °C without an
additive by examining competitive reactions in which a
mixture of each 25-fold excess of two competing sub-
strates was used. Table 2 shows that aryl methyl sulfox-
ides 4b-d were formed in high yields under similar con-
ditions, regardless of the substitution of the phenyl ring.
The reaction rate was found to be very sensitive to the
nature of substituents, and electron-releasing groups
such as p-MeO and p-Me groups increased the rate of
oxidation in both reaction conditions; the effect of sub-
stituents on the rate of oxidation is shown in Table 3.
The BF3-catalyzed reaction exhibited a greater depen-
dence on the nature of substituents as compared to the
uncatalyzed reaction. A Hammett correlation plot for the
BF3-catalyzed oxidation of these thioanisoles 3 presented
in Table 3 shows a better correlation of relative rate
factors with the σ+- rather than the σ-constants of
substituents in the aromatic ring, and afforded a negative
reaction constant ρ+ ) -2.23 (r ) 0.98).18 The uncata-
lyzed oxidation of 3 also showed a large negative reaction
constant ρ ) -3.32 (σ, r ) 0.98). These negative ρ values
are greater than those found for the oxidation of 3 with
(diacetoxyiodo)benzene in CH3CN-H2O (ρ ) -0.8),8b but
appear to be comparable to that for the oxidation with
N2O4 in carbon tetrachloride ρ ) -2.7,19 with dimeth-
ylphenylsilyl hydrotrioxides in acetone ρ ) -2.0,20 and
with bromine in aqueous methanol ρ ) -3.2.21 In these
reactions with negative ρ values, a mechanism involving
the intermediacy of sulfonium species via nucleophilic
attack of sulfides is proposed. The relatively large
negative Hammett ρ values obtained in our reactions
indicate that the peroxyiodane 2a is a highly electrophilic
oxidant in acetonitrile-water.
87c
82c
69c
98
Ph2S 3e
Ph2S 3e
Ph2S 3e
(p-MeOC6H4)2S
(p-MeOC6H4)2S
(p-ClC6H4)2S
24d
90
74e
69f
86g
73h
a
Method A: 2a (1.1 equiv), BF3‚Et2O (0.3 equiv), CH3CN-H2O
(5:1), 25 °C, N2. Method B: 2a (1.2 equiv), CH3CN-H2O (5:1), 50
b
°C, air. Method C: 2a (1.2 equiv), CH2Cl2, 25 °C, N2. Yields are
based on pure isolated materials. c A small amount of sulfides (3-
d
6%) was recovered. 66% of sulfide was recovered unchanged.
e Instead of 2a , 2b was used. f 21% of sulfone was obtained.
g
h
Reaction was carried out using 2a (1 equiv) at 0 °C. 20% of
sulfide was recovered unchanged.
2, entry 22), a finding that is compatible with the
decreased nucleophilicity of aryl sulfides as compared to
alkyl sulfides. However, in dichloromethane, oxidation
of 3e occurred smoothly even at room temperature
(method C) and diphenyl sulfoxide (4e) was obtained in
90% yield after 11 h.
The (tert-butylperoxy)iodane 2a was found to undergo
deprotection of dithioacetals, regenerating the parent
carbonyl function. For instance, treatment of dithioac-
etals 7 and 8 with 2a in aqueous acetonitrile at room
temperature or at 0 °C gave the parent ketones in good
yields. Stork and Zhao reported that dithioacetals are
efficiently cleaved to carbonyl compounds by [bis(trifluo-
roacetoxy)iodo]benzene at room temperature.16 Their
method is especially useful for selective deprotection and
is compatible with a variety of other functional groups,
such as amines, thioesters, alcohols, amides, alkenes, and
nitriles.
Effects of Ra d ica l In h ibitor s. We have reported
that the benzylic and allylic oxidation of benzyl and allyl
ethers to the esters with the alkylperoxyiodane 2a
proceeds via a radical mechanism involving the genera-
tion of R-oxy carbon-centered radicals, which were de-
tected by nitroxyl radical trapping.4b These results
suggest the occurrence of a radical process in this sulfide
oxidation. Indeed, the alkylperoxyiodane oxidation of
sulfides 3 in dichloromethane (method C) was exclusively
inhibited by the use of a free-radical scavenger (Table 4,
entries 6 and 7); thus, treatment of thioanisole (3a ) or
diphenyl sulfide (3e) with 2a in the presence of 1.3-1.5
equiv of galvinoxyl22 resulted in the recovery of more than
Su bstitu en t Effects. To gain some insight into the
mechanism of this oxidation of sulfides with the peroxy-
iodane 2a , the relative rates of oxidation for a series of
ring-substituted thioanisoles 3b (p-MeO), 3c (p-Me), and
(17) Watanabe, Y.; Iyanagi, T.; Oae, S. Tetrahedron Lett. 1980, 21,
3685.
(18) Brown, H. C.; Okamoto, Y. J . Am. Chem. Soc. 1958, 80, 4979.
(19) Hauthal, H. G.; Onderka, H.; Pritzkow, W. J . Prakt. Chem.
1969, 311, 82.
(16) (a) Stork, G.; Zhao, K. Tetrahedron Lett. 1989, 30, 287. (b)
Uenishi, J .; Kawachi, Y.; Wakabayashi, S. J . Chem. Soc., Chem.,
Commun. 1990, 1033. (c) Rychnovsky, S. D.; Griesgraber, G.; Kim, J .
J . Am. Chem. Soc. 1994, 116, 2621.
(20) Plesnicar, B.; Cerkovnik, J .; Koller, J .; Kovac, F. J . Am. Chem.
Soc. 1991, 113, 4946.
(21) Miotti, U.; Modena, G.; Sedea, L. J . Chem. Soc. (B) 1970, 802.
(22) Bartlett, P. D.; Funahashi, T. J . Am. Chem. Soc. 1962, 84, 2596.

4256 J . Org. Chem., Vol. 62, No. 13, 1997
Ochiai et al.
Ta ble 4. Effects of Ad d ed Ga lvin oxyl for Oxid a tion of Su lfid es w ith (ter t-Bu tylp er oxy)iod a n e 2a a
additive (equiv)
BF3‚Et2O galvinoxyl
conditions
product (yield,b %)
peroxyiodane
2a (equiv)
entry
sulfide 3
solvent
temp/°C,
time/h
4
3
1
2
4
5
6
7
3a
3a
3e
3e
3a
3e
1.2
1.1
1.2
1.1
1.0
1.2
CH3CN-H2O (5:1)
CH3CN-H2O (5:1)
CH3CN-H2O (5:1)
CH3CN-H2O (5:1)
CH2Cl2
1.5
1.5
1.5
1.5
1.3
1.5
50
25
50
25
25
25
10
3.5
28
28
8.5
26
4a (72)
4a (87)
4e (3)
4e (71)
4a (1)
4e (2)
3a (28)
3a (2)
3e (97)
3e (31)
3a (99)
3e (98)
0.3
0.3
CH2Cl2
a
b
Reactions were carried out under nitrogen. Yields were determined by GC.
Ta ble 5. Rea ction of Th ioa n isole (3a ) w ith
Hyd r oxyiod a n e 1a a n d /or ter t-Bu tyl Hyd r op er oxid ea
98% of the sulfides unchanged, and the corresponding
sulfoxides were obtained in less than 2% yield. (Compare
these results with Table 1, entry 1, and Table 2, entry
23.)
yield,b %
iodane 1a t-BuOOH
additive
(equiv)
entry
(equiv)
(equiv)
3a
4a
On the other hand, for the reaction of 3a in CH3CN-
H2O, addition of the radical scavenger only slightly
inhibited oxidation. Uncatalyzed reaction of 3a in CH3-
CN-H2O at 50 °C in the presence of added galvinoxyl
afforded the sulfoxide 4a in 72% yield with the 28%
recovered sulfide 3a (Table 4, entry 1). The BF3-
catalyzed oxidation of 3a to 4a in CH3CN-H2O at 25 °C
is even less sensitive to the radical scavenger, and only
a trace amount of 3a was recovered (Table 4, entry 2).
Similarly, the BF3-catalyzed oxidation of 3e in CH3CN-
H2O is less sensitive to the radical scavenger than the
uncatalyzed oxidation, although the oxidations of 3e are
more effectively inhibited by the added galvinoxyl than
those of 3a . These results imply that the oxidation of
sulfides 3a and 3e in dichloromethane proceeds exclu-
sively by a radical process, while a nonradical process
becomes important for the oxidation of 3a in CH3CN-
H2O, especially in the BF3-catalyzed oxidation.
Rea ction of Th ioa n isole (3a ) w ith Hyd r oxyiod a n e
1a a n d /or ter t-Bu tyl Hyd r op er oxid e. We have re-
ported a ligand exchange of the tert-butylperoxy group
of 2a with an alcohol: for instance, treatment of 2a with
methanol at room temperature for 2 days gives the
methoxyiodane 9 in 50% yield.4b It seems reasonable to
assume, therefore, that in CH3CN-H2O the peroxyiodane
2a undergoes a ligand exchange with water on the
hypervalent iodine atom, generating the hydroxyiodane
1a and tert-butyl hydroperoxide. Furthermore, these
species generated in situ may oxidize the sulfides to the
sulfoxides under the conditions used here. As mentioned
above, it has been reported that the hydroxyiodane 1a
oxidizes of thioanisole (3a ) in acetic acid to give 4a in
71% yield, although the reaction requires sulfuric acid
as a catalyst.9 Similarly, tert-butyl hydroperoxide can
effect the oxidation of alkyl sulfides to the corresponding
sulfoxides; in such reactions, the addition of acids in-
creases the rate of oxidation.23
1
2
3
4
1
0
0
1
0
1.2
1.2
1.2
0.6
0
92
93
94
98
0
56
0
47
1
2
1
1.2
0
1.2
0.6
1.2
1.1
o-IC6H4CO2H (1)
o-IC6H4CO2H (1.2)
2
5
98
34
90
53
6
7c
8d
BF3‚Et2O (0.3)
a
Reactions were carried out in CH3CN-H2O (5:1) at 50 °C for
7.5 h under atmospheric conditions, unless otherwise noted.
Yields are determined by GC. c Reaction time: 49 h. Reaction
b
d
was carried out in CH3CN-H2O (5:1) at 25 °C for 3.5 h under
nitrogen.
recovery of a large amount of the sulfide 3a unchanged,
and only a trace amount of 4a (less than 2%) was
detected. In the oxidation of sulfides to sulfoxides shown
in Table 2, the oxidant 2a was always converted to
o-iodobenzoic acid; therefore, this acid may catalyze the
oxidation with 1a or tert-butyl hydroperoxide, because
o-iodobenzoic acid is known to be a relatively strong acid
with a pKa value of 2.85.24,25 However, this acid was not
able to catalyze the reaction of 3a with 1a or tert-butyl
hydroperoxide under these conditions (Table 5, entries
3 and 4). A moderate yield of the sulfoxide 4a was
obtained by the reaction with 1a when BF3‚Et2O was
used as an acid catalyst (Table 5, entry 8).
It is noteworthy that a combination of the hydroxy-
iodane 1a and tert-butyl hydroperoxide makes the oxida-
tion of the sulfide 3a possible (Table 5, entry 5). Thus,
reaction of 3a with 2a (1.2 equiv) and tert-butyl hydro-
peroxide (1.2 equiv) in CH3CN-H2O (5:1) at 50 °C for
7.5 h afforded the sulfoxide 4a in 98% yield. Using less
1a or tert-butyl hydroperoxide led to less effective oxida-
tion of 3a (Table 5, entries 6 and 7).
1H NMR experiments indicated that an extensive
ligand exchange of the (tert-butylperoxy)iodane 2a with
water takes place in CD3CN-D2O (5:1); after heating for
5.5 h at 50 °C, formation of a large amount of tert-butyl
hydroperoxide was observed along with deposition of a
white precipitate of the hydroxyiodane 1a , and the ratio
of tert-butyl hydroperoxide to 2a was found to be 97:3.
On the other hand, a mixture of 1a and tert-butyl
hydroperoxide in CD3CN-D2O under the same conditions
resulted in the formation of 2a in 2% yield. These results
The results of the attempted oxidation of thioanisole
(3a ) with the hydroxyiodane 1a and/or tert-butyl hydro-
peroxide are summarized in Table 5. Exposure of 3a to
either the hydroxyiodane 1a or tert-butyl hydroperoxide
in CH3CN-H2O (5:1) at 50 °C for 7.5 h resulted in the
(24) Lide, D. R., Ed. CRC Handbook of Chemistry and Physics, 73rd
ed; CRC Press: Boca Raton, FL, 1992; pp 8-39.
(25) The cyclic hydroxyiodane 1a with a pKa of 7.0 is less acidic than
o-iodobenzoic acid and the estimated pKa of the noncyclic tautomer,
2-iodosylbenzoic acid o-OIC6H4CO2H, is 3.7. The iodane 1a has been
shown to exist predominantly in this cyclic structure, both in solution
and in the solid state. See: (a) Katritzky, A. R.; Savage, G. P.; Palenik,
G. J .; Qian, K.; Zhang, Z. J . Chem. Soc., Perkin Trans. 2 1990, 1657.
(b) Moss, R. A.; Kim, K. Y.; Swarup, S. J . Am. Chem. Soc. 1986, 108,
788.
(23) (a) Bateman, L.; Hargrave, K. R. Proc. R. Soc. A 1954, 224,
389. (b) Bateman, L.; Hargrave, K. R. Proc. R. Soc. A 1954, 224, 399.
(c) Oae, S.; Asada, K.; Yoshimura, T. Tetrahedron Lett. 1983, 24, 1265.
(d) Madesclaire, M. Tetrahedron 1986, 42, 5459.

Oxidation of Sulfides to Sulfoxides
J . Org. Chem., Vol. 62, No. 13, 1997 4257
Sch em e 1. Ion ic Mech a n ism for Rea ction in
sulfonium species 11. These data may further suggest
that formation of the sulfonium species 11 is likely to be
the rate-determining step for the oxidation to the sul-
foxides.
CH3CN-H2O
In marked contrast to 2a , the hydroxyiodane 1a does
not undergo oxidation of the sulfide 3a in CH3CN-H2O
at 50 °C even in the presence of o-iodobenzoic acid (Table
5). This reactivity difference between the hydroxyiodane
1a and the (tert-butylperoxy)iodane 2a for the oxidation
is partly attributable to the limited solubility of 1a under
these conditions. Furthermore, the more acidic nature
of tert-butyl hydroperoxide (pKa ) 12.8 in water) com-
pared to water (pKa ) 15.7) may make the tert-butylp-
eroxy group a better leaving group than the hydroxy
group.28
As an alternative mechanism, single electron transfer
(SET) process from the sulfides to the peroxyiodane 2a
or to the activated species 10 could be envisioned.
Oxidation of substituted thioanisoles 3a -d by a recon-
stituted system of purified cytochrome P-450 to give
sulfoxides involves one-electron transfer from the sulfides
to the active species of the enzyme, generating the sulfide
cation radical.17 This SET oxidation shows a small
negative reaction constant ρ+ ) -0.16 (σ+), which is in
marked contrast to the large negative values in the BF3-
catalyzed (ρ+ ) -2.23) and the uncatalyzed oxidations
(ρ ) -3.32) by 2a .29 Logarithms of relative reactivity of
thioanisoles 3a -d toward 2a , however, were found to be
correlated linearly with the reported one-electron oxida-
tion potentials of the sulfides,17 shown in Table 3, with
the following correlation coefficients: r ) 0.97 (with BF3)
and 0.95 (without BF3). Furthermore, the oxidation of
3a with 2a at 50 °C was considerably inhibited by the
addition of SET quencher 1,4-dimethoxybenzene (the
oxidation potential Ep ) 1.28 V vs SCE in CH3CN),30 but
not by the addition of methoxybenzene (Ep ) 1.96 V vs
SCE in CH3CN).31
imply that an equilibrium between 2a and 1a , which
strongly favors formation of 1a , is probably established
under these conditions.
2a + H2O u 1a + t-BuOOH
Rea ction Mech a n ism . A. Oxid a tion in Aceton i-
tr ile-Wa ter . The fact that neither the hydroxyiodane
1a nor tert-butyl hydroperoxide itself undergoes oxidation
of the sulfide 3a to the sulfoxide 4a in CH3CN-H2O at
50 °C, and a combination of 1a and tert-butyl hydroper-
oxide is required for the oxidation, combined with the
existence of an equilibrium between 2a and 1a under
these conditions, strongly suggest that the (tert-butyl-
peroxy)iodane 2a or its activated species is responsible
for the oxidation as the actual oxidant.
A mechanism shown in Scheme 1, which is consistent
with our results, involves formation of the activated
peroxyiodane 10 by protonation to the apical oxygen atom
of 2a . The protonation increases the leaving group ability
of tert-butylperoxy group as well as a positive charge on
the hypervalent iodine. Formation of the activated
peroxyiodane 10 is anticipated by considering the polar-
ization of 2a expected by a theory for electronic structure
of hypervalent molecules in which the hypervalent bond
(the three-center, four-electron bond) has an accumula-
tion of negative charge on the apical ligands and positive
charge on the central atom.26 The BF3-catalyzed reaction
(method A) will lead to a higher concentration of the
activated species 10 than the uncatalyzed reaction (method
B), in which the resulting o-iodobenzoic acid with a pKa
value of 2.85 will act as a mild acid catalyst. Ligand
exchange of the peroxyiodane 10 by nucleophilic attack
of sulfides toward the iodine(III) atom would produce the
sulfonium species 11, which, in turn, reacts with water
to give sulfoxides. Formation of the iodine(III)-sulfo-
nium ions like 11 has been proposed for the oxidation of
sulfides with [bis(acyloxy)iodo]benzenes,8 1-hydroxy-1,2-
benziodoxol-3(1H)-one (1a ),9 and [bis(trifluoroacetoxy)-
iodo]benzene.27
The negligible effect (see Table 4, entry 2) of the added
free-radical scavenger in the BF3-catalyzed oxidation
(method A) of 3a suggests these ionic mechanisms.
Inhibition of the uncatalyzed oxidation (method B) of 3a ,
and the catalyzed and uncatalyzed oxidation of 3e with
added galvinoxyl to a small but discernible extent, may
suggest a simultaneous occurrence of a radical process
as a competing pathway.
B. Oxid a tion in Dich lor om eth a n e. The attempted
oxidation of diphenyl sulfide (3e) with the hydroxyiodane
1a or tert-butyl hydroperoxide in dichloromethane re-
sulted in the recovery of a large amount (more than 80%)
of the sulfide 3e and only 1-2% yield of diphenyl
sulfoxide (4e). A 24% yield of the sulfoxide 4e was
obtained in a similar reaction using a combination of the
The large negative Hammett ρ values observed for the
oxidation of thioanisoles 3 in CH3CN-H2O (ρ+ ) -2.23
for the BF3-catalyzed and ρ ) -3.32 for the uncatalyzed
reactions) are in good agreement with a mechanism
shown in Scheme 1, involving the intermediacy of the
(28) Richardson, W. H. The Chemistry of Peroxides; Wiley: New
York, 1983; Chapter 5.
(29) Pryor, W. A.; Hendrickson, W. H. J . Am. Chem. Soc. 1983, 105,
7114.
(30) Kamata, M.; Otogawa, H.; Hasegawa, E. Tetrahedron Lett.
1991, 32, 7421.
(26) (a) Musher, J . I. Angew. Chem., Int. Ed. Engl. 1969, 8, 54. (b)
Martin, J . C. Science 1983, 221, 509.
(27) Barbas, D.; Spyroudis, S.; Varvoglis, A. J . Chem. Res. (S) 1985,
186.
(31) Fukuzumi, S.; Kochi, J . K. J . Am. Chem. Soc. 1981, 103, 7240.

4258 J . Org. Chem., Vol. 62, No. 13, 1997
Ochiai et al.
hydroxyiodane 1a and tert-butyl hydroperoxide in dichlo-
romethane. These results again suggest that the actual
oxidant for the reaction in dichloromethane is (tert-
butylperoxy)iodane 2a rather than the hydroxyiodane 1a
and tert-butyl hydroperoxide.
The formation of a considerable amount of the R-chlo-
romethyl sulfoxide 6 in the oxidation of thioanisole (3a )
in dichloromethane deserves attention. The decomposi-
tion of 2a in chloroform at room temperature affords
1-chloro-1,2-benziodoxol-3(1H)-one (16) through ligand
exchange in high yield.4a Furthermore, it has been
shown that alkyl sulfides undergo R-monochlorination
with (dichloroiodo)arenes, which act as a controlled
source of chlorine, to give R-chloro sulfides and R-chloro
sulfoxides.36 Therefore, it seems reasonable to assume
that the chloroiodane 16 generated in situ from 2a in
dichloromethane could be responsible for the formation
of the R-chloromethyl sulfoxide 6.
In marked contrast to the reaction in CH3CN-H2O,
the radical nature of the oxidation of 3a and 3e in
dichloromethane was substantiated by the exclusive
inhibition of the reaction with the added free-radical
scavenger (Table 4). The (tert-butylperoxy)iodane 2a
could generate iodine-centered radicals at room temper-
ature in solution, and the first-order rate constant for
the decomposition of 2a in dichloromethane at 30 °C has
been reported to be kobsd ) 2.62 × 10-5 s-1 4b
.
The initial
step of the decomposition of 2a would involve the ho-
molytic bond cleavage of the weak iodine(III)-peroxy
bond, generating tert-butylperoxy radical and the [9-I-2]
iodanyl radical 12. In analogy to a mechanism recently
shown to occur in the oxidation of sulfides to sulfoxides
by hydroxy32 and peroxy radicals,33 addition of these
radicals to sulfides leading to the intermediary formation
of the [9-S-3] sulfuranyl radicals 13-15 might constitute
one of the possible reaction pathways. The tert-butyl-
peroxy radical has been shown to be an efficient radical
oxidant with the highly electrophilic nature for the
conversion of sulfides to sulfoxides.34
Exp er im en ta l Section
IR spectra were recorded on J ASCO IRA-1 and Perkin
Elmer 1720 FT-IR spectrometers. 1H and 13C NMR were
recorded on J EOL FX-200 and J MN-GCX 400 spectrometers.
Chemical shifts were reported in parts per million (ppm)
downfield from internal Me4Si. Mass spectra (MS) were
obtained on a J EOL J MS-DX300 spectrometer. Melting points
were determined with a Yanaco micro melting points ap-
paratus and are uncorrected. Analytical gas chromatography
(GC) was carried out on a Shimadzu GC-14A gas chromato-
graph with a column (1 or 3 m) of 15% FFAP and 20% Silicon
GE SF-96 on Chromosorb W-AWDMCS. Preparative thin-
layer chromatography (TLC) was carried out on precoated
plates of silica gel (Merck, silica gel F-254). Kielselgel 60
(Merck, 230-400 mesh) was used for flash chromatography.
Purification of solvents was carried out under nitrogen.
Acetonitrile and dichloromethane were dried over CaH2 and
distilled. Toluene was distilled from sodium benzophenone
ketyl. BF3-Et2O was distilled from CaH2. Hydroxyiodane
(1a ), thioanisoles 3a -d , diphenyl sulfide (3e), and dibenzyl
sulfide are commercially available. Commercially unavailable
phenyl and benzyl sulfides were prepared by reactions of alkyl
halides with potassium salts of thiols in methanol or ethanol.
Phenyl (diethoxyphosphinyl)methyl sulfide was prepared ac-
cording to literature procedure.37
To investigate the fate of the tert-butylperoxy group
1
of 2a , H NMR experiments were carried out in dichlo-
romethane-d2 at room temperature, and the products
from the reaction of 3e with 2a were carefully analyzed:
in addition to formation of the sulfoxide 4e (75%) and
o-iodobenzoic acid (86%), a 27% yield of acetone and a
54% yield of tert-butyl alcohol were detected. The tert-
butoxy radical could be generated from tert-butylperoxy
radical and is well-known to (1) undergo â-scission
yielding acetone and methyl radical, or (2) to abstract a
hydrogen atom yielding tert-butyl alcohol.35 Thus, the
formation of acetone as well as tert-butyl alcohol provides
firm evidence for the intervention of tert-butoxy radical
in this reaction.
Gen er a l P r oced u r e for Oxid a tion of Th ioa n isole (3a )
w ith (ter t-Bu tylp er oxy)iod a n es (2). To a stirred solution
(4 mL) of peroxyiodane 2a 4 or 2b5 was added thioanisole (3a )
(25 mg, 0.20 mmol), and the mixture was stirred for the
conditions shown in Table 1. Water was added and the
mixture was extracted with dichloromethane three times, and
the combined organic phase was washed with water and brine.
The yields of methyl phenyl sulfoxide (4a ), methyl phenyl
sulfone (5), and chloromethyl phenyl sulfoxide (6) were deter-
mined by analytical GC using a column of 15% FFAP (200 °C,
eicosane as the internal standard), and are given in Table 1.
These products were isolated by preparative TLC (1:1:1
hexane-dichloromethane-diethyl ether). 4a :38 colorless oil;
IR (film) 3056, 1718, 1444, 1090, 1049, 749, 693 cm-1; 1H NMR
(CDCl3) δ 7.74-7.44 (m, 5H), 2.74 (s, 3H); MS m/z (relative
intensity) 140 (93, M+), 125 (100), 97 (51), 77 (62), 51 (56).
5:38 colorless plates; mp 88-89 °C (recrystallized from dichlo-
romethane-diethyl ether-hexane); IR (KBr) 3024, 1449, 1285,
751, 690, 529 cm-1 1H NMR (CDCl3) δ 8.02-7.87 (m, 2H),
;
(32) (a) Schoneich, C.; Aced, A.; Asmus, K.-D. J . Am. Chem. Soc.
1993, 115, 11376. (b) Bonifacic, M.; Mockel, H.; Bahnemann, D.;
Asmus, K.-D. J . Chem. Soc., Perkin Trans 2 1975, 675.
(33) Schoneich, C.; Aced, A.; Asmus, K.-D. J . Am. Chem. Soc. 1991,
113, 375.
(34) Adam, W.; Haas, W.; Lohray, B. B. J . Am. Chem. Soc. 1991,
113, 6202.
(36) (a) Schneider, K. C.; Fernandez, V. P. J . Org. Chem. 1961, 26,
2478. (b) Vilsmeier, E.; Sprugel, W. J ustus liebigs Ann. Chem. 1971,
749, 62. (c) Cinquini, M.; Colonna, S. J . Chem. Soc., Perkin Trans. 1
1972, 1883. (d) Cinquini, M.; Colonna, S.; Fornasier, R.; Montanari,
F. J . Chem. Soc., Perkin Trans. 1 1972, 1886. (e) Cinquini, M.;
Colonna, S.; Landini, D. J . Chem. Soc., Perkin Trans. 2, 1972, 296.
(37) Green, M. J . Chem. Soc. 1963, 1324.
(35) Howard, J . A. The Chemistry of Peroxides; Wiley: New York,
1983; Chapter 8.
(38) Cutress, N. C.; Grindley, T. B.; Katritzky, A. R.; Shome, M.;
Tompson, R. D. J . Chem. Soc., Perkin Trans. 2 1974, 268.

Oxidation of Sulfides to Sulfoxides
J . Org. Chem., Vol. 62, No. 13, 1997 4259
7.73-7.48 (m, 3H), 3.06 (s, 3H); MS m/z (relative intensity)
156 (26, M+), 141 (29), 94 (35), 77 (100), 51 (26). 6: colorless
oil; IR (film) 3003, 2935, 1445, 1087, 1054, 759, 741, 690, 518
Gen er a l P r oced u r e for Oxid a tion of Su lfid es w ith 2a
in th e P r esen ce of Ra d ica l In h ibitor s. To a stirred
solution (3 mL) of sulfide 3 (0.2 mmol) and galvinoxyl (127
mg, 0.3 mmol) was added a solution (3 mL) of peroxyiodane
2a (0.24 mmol) under nitrogen, and the mixture was stirred
for the periods shown in Table 4. The yields of products were
determined by analytical GC and are given in Table 4.
1
cm-1; H NMR (CDCl3) δ 7.82-7.40 (m, 5H), 4.40 (s, 2H); 13C
NMR (CDCl3) δ 140.89 (s), 132.18 (d), 129.35 (d), 124.80 (d),
61.33 (t); MS m/z (relative intensity) 174 (28, M+), 125 (100),
97 (91), 91 (38), 77 (100), 51 (81). HRMS Calcd for C7H7ClOS
(M+) 173.9906. Found 173.9836. The authentic sample of 6
was prepared by oxidation of thioanisole (3a ) with (dichlor-
oiodo)benzene according to literature procedure.39
Gen er a l P r oced u r e for Oxid a tion of Su lfid es to Su l-
foxid es w ith (ter t-Bu tylp er oxy)iod a n e (2a ). (a ) Meth od
A. To a stirred solution of peroxyiodane 2a (74 mg, 0.22 mmol)
in 4.8 mL of CH3CN-H2O (5:1) were added a sulfide (0.2 mmol)
and BF3-Et2O (9 mg, 0.06 mmol) under nitrogen at room
temperature, and the mixture was stirred for the periods
shown in Table 2. Water was added, the mixture was
extracted with dichloromethane three times, and the combined
organic phase was washed with 5% aqueous NaOH solution,
water, and then brine. The solution was dried over anhydrous
Na2SO4 and concentrated to give an oil, which was purified
by preparative TLC (1:1 hexane-ethyl acetate). The yields
of pure products are given in Table 2.
(b) Meth od B. To a stirred solution of peroxyiodane 2a
(81 mg, 0.24 mmol) in 4.8 mL of CH3CN-H2O (5:1) was added
a sulfide (0.2 mmol) under atmosphere at room temperature,
and the mixture was stirred for the periods shown in Table 2
at 50 °C. A finely dispersed precipitate appeared during the
first 0.5 h. The isolated yields of pure products are given in
Table 2.
(c) Meth od C. To a stirred solution of peroxyiodane 2a
(40 mg, 0.12 mmol) in dichloromethane (3 mL) was added a
sulfide (0.1 mmol) under nitrogen at room temperature, and
the mixture was stirred for the periods shown in Table 2. The
isolated yields of pure products are given in Table 2.
Oxid a tive Dep r otection of Acetop h en on e Dith ioa ceta l
(7). To a stirred solution of peroxyiodane 2a (353 mg, 1.05
mmol) in 6 mL of CH3CN-H2O (9:1) was added a solution of
dithioacetal 7 (105 mg, 0.50 mmol) in 7 mL of CH3CN-H2O
(9:1) under nitrogen at 0 °C, and the mixture was stirred for
5 h. Analytical GC using a column of 15% FFAP (200 °C,
eicosane as the internal standard) showed the formation of
acetophenone in 84% yield.
Oxid a tive Dep r otection of Hexa n op h en on e Dith ioa c-
eta l (8). To a stirred solution of peroxyiodane 2a (50 mg, 0.15
mmol) in 3 mL of CH3CN-H2O (9:1) was added a solution of
dithioacetal 8 (27 mg, 0.10 mmol) in 2 mL of CH3CN-H2O
(9:1) under nitrogen at room temperature, and the mixture
was stirred for 3 h. Analytical GC using a column of 20%
Silicon GE SF-96 (150 °C, n-hexadecane as the internal
standard) showed the formation of hexanophenone in 77%
yield.
Gen er a l P r oced u r e for th e Com p etition Exp er im en ts.
(a ) In th e P r esen ce of BF 3-Et2O. To a stirred solution of
thioanisole (3a ) (155 mg, 1.25 mmol) and a substituted
thioanisole (1.25 mmol) in 3 mL of CH3CN-H2O (5:1) were
added a solution of peroxyiodane 2a (17 mg, 0.05 mmol) in 3
mL of CH3CN-H2O (5:1) and then BF3-Et2O (2.1 mg, 0.015
mmol) under nitrogen. The reaction was allowed to proceed
at 30 ( 0.2 °C for 3 h. After addition of 10% aqueous Na2S2O3
solution at 0 °C, the mixture was stirred for 10 min and
analyzed for the two sulfoxides by GC using a column of 15%
FFAP (200 °C, docosane as the internal standard). The results
are reported in Table 3.
Rea ction of Th ioa n isole (3a ) w ith Hyd r oxyiod a n e 1a
a n d ter t-Bu tyl Hyd r op er oxid e. To a stirred suspension of
hydroxyiodane 1a (63 mg, 0.24 mmol) in 4 mL of CH3CN-
H2O (5:1) were added thioanisole (3a ) (25 mg, 0.20 mmol) and
70% aqueous tert-butyl hydroperoxide (31 mg, 0.24 mmol) at
50 °C under atmosphere, and the mixture was stirred for 7.5
h. Analytical GC using a column of 15% FFAP showed the
formation of 4a in 98% yield (Table 5, entry 5).
Liga n d Exch a n ge of P er oxyiod a n e 2a w ith Wa ter . A
solution of peroxyiodane 2a (34 mg, 0.1 mmol) in 2.4 mL of
CD3CN-D2O (5:1) was heated at 50 °C under atmosphere. A
finely dispersed precipitate of hydroxyiodane 1a appeared
during the first 0.5 h. Formation of tert-butyl hydroperoxide-
d1 by ligand exchange of 2a with D2O was detected by 1H NMR
spectra, and the reaction time and the ratios of peroxyiodane
2a to tert-butyl hydroperoxide are as follows: 0.5 h, 83:17; 1
h, 5:95; 5.5 h, 3:97; 8.5 h, 3:97; 13 h, 3:97. In a separate
experiment, hydroxyiodane 1a was isolated in 80% yield by
heating at 50 °C for 5.5 h.
Liga n d Exch a n ge of Hyd r oxyiod a n e 1a w ith ter t-
Bu tyl Hyd r op er oxid e. A suspension of hydroxyiodane 1a
(26 mg, 0.10 mmol) and 70% aqueous tert-butyl hydroperoxide
(13 mg, 0.10 mmol) in 2.4 mL of CD3CN-D2O (5:1) was heated
at 50 °C under atmosphere. Formation of a small amount of
peroxyiodane 2a was detected by 1H NMR spectra, and the
reaction time and the ratios of peroxyiodane 2a to tert-butyl
hydroperoxide-d are as follows: 0.3 h, 2:98; 5.5 h, 2:98; 10 h,
2:98.
Oxid a tion of Th ioa n isole (3a ) in th e P r esen ce of 1,4-
Dim eth oxyben zen e. To a stirred solution of thioanisole (3a )
(12 mg, 0.10 mmol) and 1,4-dimethoxybenzene (17 mg, 0.12
mmol) in 2.5 mL of CH3CN-H2O (5:1) was added a solution
of peroxyiodane 2a (47 mg, 0.12 mmol) in 2 mL of CH3CN-
H2O (5:1) under atmosphere at 50 °C, and the mixture was
stirred for 7.5 h. Analytical GC using a column of 15% FFAP
showed the formation of sulfoxide 4a (33%) along with the
recovered 3a (64%).
Oxid a t ion of Th ioa n isole (3a ) in t h e P r esen ce of
Meth oxyben zen e. To a stirred solution of thioanisole (3a )
(12 mg, 0.1 mmol) and methoxybenzene (13 mg, 0.12 mmol)
in 2.5 mL of CH3CN-H2O (5:1) was added a solution of
peroxyiodane 2a (47 mg, 0.12 mmol) in 2 mL of CH3CN-H2O
(5:1) under atmosphere at 50 °C, and the mixture was stirred
for 7.5 h. Analysis by GC indicated a 97% yield of sulfoxide
4a and a small amount of 3a (3%).
Oxid a tion of Dip h en yl Su lfid e (3e) w ith 2a in Dich lo-
r om eth a n e-d 2. Oxidation of diphenyl sulfide (3e) (9 mg, 0.05
mmol) with peroxyiodane 2a (17 mg, 0.05 mmol) in CD2Cl2
(0.5 mL) was carried in NMR tube at room temperature, and
the mixture was allowed to stand for 11 days with occasional
shaking. 1H NMR analysis showed the formation of sulfoxide
4e (75%), o-iodobenzoic acid (86%), tert-butyl alcohol (54%),
and acetone (27%).
Su p p or tin g In for m a tion Ava ila ble: Spectroscopic data
for 4b-e, benzyl n-butyl sulfoxide, benzyl isobutyl sulfoxide,
benzyl sec-butyl sulfoxide, dibenzyl sulfoxide, n-pentyl phenyl
sulfoxide, allyl phenyl sulfoxide, phenyl (diethoxyphosphinyl)-
methyl sulfoxide, bis(p-methoxyphenyl) sulfoxide, bis(p-chlo-
rophenyl) sulfoxide, and bis(p-methoxyphenyl) sulfone (4
pages). This material is contained in libraries on microfiche,
immediately follows this article in the microfilm version of the
journal, and can be ordered from the ACS; see any current
masthead page for ordering information.
(b) With ou t BF 3-Et2O. To a stirred solution of thioanisole
(3a ) (155 mg, 1.25 mmol) and a substituted thioanisole (1.25
mmol) in 6 mL of CH3CN-H2O (5:1) was added peroxyiodane
2a (17 mg, 0.05 mmol) under atmosphere. The reaction was
allowed to proceed at 40 ( 0.2 °C for 5 h. After addition of
10% aqueous Na2S2O3 solution at 0 °C, the mixture was stirred
for 10 min and analyzed for the two sulfoxides by GC using a
column of 15% FFAP. The results are reported in Table 3.
(39) Cinquini, M.; Colonna, S. J . Chem. Soc., Perkin Trans. 1 1972,
1883.
J O970081Q