Surface-mediated reactions. 8. Oxidation of sulfides and sulfoxides with tert-butyl hydroperoxide and OXONE

Article abstract of DOI:10.1021/ja9940569

Silica gel and alumina have been found to mediate the oxidation of sulfides and sulfoxides with (CH₃)₃COOH and OXONE. With all combinations except (CH₃)₃COOH/alumina, sulfides were oxidized with reasonably good selectivity to sulfoxides. These studies afforded insights into the mechanisms of surface-mediated processes. Adsorption studies, combined with the effect of partial silylation of silica gel, indicate that oxidation of sulfides by (CH₃)₃COOH/silica gel occurs at least predominantly via nucleophilic attack by the sulfide on (CH₃)₃COOH, which is activated by being bound to isolated silanol sites on the silica gel surface (Scheme 2), whereas oxidation of sulfoxides involves nucleophilic attack by (CH₃)₃COOH on the sulfoxide, which is activated by being bound to associated silanol sites (Scheme 3). Oxidation of sulfoxides by (CH₃)₃COOH/alumina involves attack of (CH₃)₃COO^- on the sulfoxide bound to free Al⁺ sites on the surface (Scheme 4B). Mediation of oxidation by OXONE involves instead activation by its being dispersed on the surface of the adsorbent, providing contact between KOSO₂OOH, the oxidizing component, and the substrate. With silica gel, binding involves the associated silanol sites (Scheme 5). It is proposed that this is a general model for surface mediation of inorganic salts.

Full text of DOI:10.1021/ja9940569

4280
J. Am. Chem. Soc. 2000, 122, 4280-4285
Surface-Mediated Reactions. 8. Oxidation of Sulfides and Sulfoxides
with tert-Butyl Hydroperoxide and OXONE1
Paul J. Kropp,* Gary W. Breton, John D. Fields, Jesse C. Tung, and Brian R. Loomis
Contribution from the Department of Chemistry, UniVersity of North Carolina,
Chapel Hill, North Carolina 27599-3290
ReceiVed NoVember 18, 1999
Abstract: Silica gel and alumina have been found to mediate the oxidation of sulfides and sulfoxides with
(CH3)3COOH and OXONE. With all combinations except (CH3)3COOH/alumina, sulfides were oxidized with
reasonably good selectivity to sulfoxides. These studies afforded insights into the mechanisms of surface-
mediated processes. Adsorption studies, combined with the effect of partial silylation of silica gel, indicate
that oxidation of sulfides by (CH3)3COOH/silica gel occurs at least predominantly via nucleophilic attack by
the sulfide on (CH3)3COOH, which is activated by being bound to isolated silanol sites on the silica gel surface
(Scheme 2), whereas oxidation of sulfoxides involves nucleophilic attack by (CH3)3COOH on the sulfoxide,
which is activated by being bound to associated silanol sites (Scheme 3). Oxidation of sulfoxides by (CH3)3-
COOH/alumina involves attack of (CH3)3COO- on the sulfoxide bound to free Al+ sites on the surface (Scheme
4B). Mediation of oxidation by OXONE involves instead activation by its being dispersed on the surface of
the adsorbent, providing contact between KOSO2OOH, the oxidizing component, and the substrate. With silica
gel, binding involves the associated silanol sites (Scheme 5). It is proposed that this is a general model for
surface mediation of inorganic salts.
The surfaces of silica gel and alumina have proven to be
3a.7,8 Treatment of sulfide 1a with 2.0 mol equiv of (CH3)3-
COOH in the presence of silica gel afforded sulfone 3a in high
yield, which could also be obtained by oxidation of sulfoxide
2a (Table 2). Thus selective oxidation to either the sulfoxide
or sulfone could be attained by simple stoichiometric control.
Despite the usual sensitivity of silica gel to moisture,9 similar
results were obtained using either anhydrous or the less
expensive 70% aqueous (CH3)3COOH. Besides being environ-
mentally benign, silica gel is recyclable; comparable results were
obtained using silica gel that had been previously used and
recycled five times.
remarkably versatile mediators of chemical reactivity. However,
despite numerous useful synthetic applications,2 little is known
about the mechanisms through which these surfaces mediate
reactivity. We report here the novel application of silica gel
and alumina to mediate the oxidation of sulfides and sulfoxides
by tert-butyl hydroperoxide and provide insight into the
mechanisms of these processes.3 Comparison is made with the
role of these surfaces in mediating the oxidation of sulfides and
sulfoxides by OXONE.
Results and Discussion
Similar results were obtained with the aryl analogues 1b,c
and 2b,c (Table 3) and 4-methylthiane (4) (Table 4). Despite
being surface-mediated, oxidation over silica gel showed no
obvious steric effect; partial oxidation of sulfide 4 afforded the
tert-Butyl Hydroperoxide. Although numerous reagents have
been employed for the oxidation of sulfides,4 there is a
continuing need for ones that are efficient, selective, and
environmentally responsible. One oxidant that meets the last
criterion, along with being inexpensive and safe to handle even
in large quantities,5,6 is tert-butyl hydroperoxide [(CH3)3COOH].
However, used alone it is a poor oxidizing agent. Thus treatment
of dibutyl sulfide (1a) with (CH3)3COOH afforded only very
slow oxidation to the corresponding sulfoxide 2a (Table 1).
However, in the presence of silica gel oxidation occurred rapidly
to afford sulfoxide 2a with minimal over-oxidation to sulfone
(5) (CH3)3COOH is commercially available, has high thermal stability,
and is safer to handle than CH3CO3H or HOOH because of its much lower
sensitivity to decomposition catalyzed by trace metallic impurities.6
Moreover, its byproduct of oxidation, (CH3)3COH, is easily removed from
reaction mixtures by distillation or rotary evaporation, obviating the need
for aqueous workup as required for the traditionally used peroxyacid
oxidants. This is particularly useful since the products of many oxidations
are water soluble.
(6) Sharpless, K. B.; Verhoeven, T. R. Aldrichim. Acta 1979, 12, 63-
73.
(7) To provide qualitative rate data, oxidations were terminated prior to
total conversion. For preparative purposes, complete oxidation can be
effected by using longer reaction times or employing a small excess of
oxidant.
(8) Oxidation with 30% aqueous HOOH gave lower yields of sulfoxide
2a or sulfone 3a. The use of lower ratios of silica gel to (CH3)3COOH
afforded slower oxidation. Tung, J. C. Unpublished results.
(9) See, for example: (a) Kropp, P. J.; Daus, K. A.; Tubergen, M. W.;
Kepler, K. D.; Wilson, V. P.; Craig, S. L.; Baillargeon, M. M.; Breton, G.
W. J. Am. Chem. Soc. 1993, 115, 3071-3079. (b) Kropp, P. J.; Crawford,
S. D. J. Org. Chem. 1994, 59, 3102-3112. (c) Kropp, P. J.; Breton, G. W.;
Craig, S. L.; Crawford, S. D.; Durland, W. F., Jr.; Jones, J. E., III; Raleigh,
J. S. J. Org. Chem. 1995, 60, 4146-4152.
(1) Part 7: Foti, C. J.; Fields, J. D.; Kropp, P. J. Org. Lett. 1999, 1,
903-904.
(2) For reviews, see: (a) PreparatiVe Chemistry Using Supported
Reagents; Laszlo, P., Ed.; Academic: San Diego, 1987. (b) Solid Supports
and Catalysts in Organic Synthesis; Smith, K., Ed.; Ellis Horwood: New
York, 1992. (c) Clark, J. H. Catalysis of Organic Reactions by Supported
Inorganic Reagents; VCH: New York, 1994. (d) Kabalka, G. W.; Pagni,
R. M. Tetrahedron 1997, 53, 7999-8605.
(3) For a preliminary report of a portion of these studies, see: Breton,
G. W.; Fields, J. D.; Kropp, P. J. Tetrahedron Lett. 1995, 36, 3825-3828.
(4) Syntheses of Sulphones, Sulphoxides and Cyclic Sulphides; Patai, S.,
Rappoport, Z., Eds.; Wiley: Chichester, 1994.
10.1021/ja9940569 CCC: $19.00 © 2000 American Chemical Society
Published on Web 04/19/2000

Surface-Mediated Reactions
J. Am. Chem. Soc., Vol. 122, No. 18, 2000 4281
Table 1. Oxidation of Sulfide 1a with (CH3)3COOHa
Table 4. Oxidation of 4-Methylthiane (4) with (CH3)3COOH/Silica
Gela
yield, %b
adsorbent
none
solvent
time, h
1a
2a
3a
CDCl3
24
0.5
0.5
0.5
0.5
0.5
0.5
4
49
1
45
88
92
83
86
86
80
19
13
18
18
SiO2
SiO2
SiO2
SiO2
SiO2
CH2Cl2
CF3C6H5
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
7
5
10
4
6
4
81
47
2
yield, %
equivb
4
5
6
c
d
e
7
3
7
8
1.0
2.0
81c
9
83
SiO2 (OSiMe3)f
SiO2
a Conducted for 4 h according to the standard procedure with CH2Cl2
as solvent. b [(CH3)3COOH]/[4]. c cis-5/trans-5 ) 0.59 at 25% conver-
sion.
g
Al2O3
4
4
4
37
75
76
Al2O3 (neut)h
Al2O3 (C5H5N)i
Table 5. Oxidation of Sulfides 7 with (CH3)3COOH/Silica Gela
a Conducted using 1.0 mol equiv of 70% aqueous (CH3)3COOH
according to the standard procedure with solvent described in the
Experimental Section unless otherwise indicated. b Isolated yields except
for the run conducted in CDCl3 solution, in which case the reaction
mixture was analyzed by 1H NMR spectroscopy relative to an internal
standard. c Run on a 6.0-mmol scale with silica gel that had been
previously used and recycled five times. d Anhydrous solution of
(CH3)3COOH in decane used. e Fisher S-157. f Partially silylated as
described in the Experimental Section. g 2.0 mol equiv of (CH3)3COOH
used. h Pretreated with 0.08 mmol/g (0.20 mmol) of CH3SO3H in 5
mL of CH2Cl2. i Pretreated with 0.08 mmol/g (0.20 mmol) of pyridine
in 5 mL of CH2Cl2.
yield, %
R
time, min
7
8
9
4-OCH3
H
3-OCH3
4-NO2
5
15
20
30
4
3
3
7
94
94
95
89
2
3
2
4
Table 2. Oxidation of Sulfoxide 2a with (CH3)3COOHa
yield, %
adsorbent
noneb
2a
3a
a Conducted according to the standard procedure with CH2Cl2 as
solvent.
96
1
50
6
97
80
83
SiO2
93
24
92
3
20
16
effects revealed the following relative rates of oxidation of the
phenyl sulfides 7: R ) 4-OCH3 > R ) H > R ) 3-OCH3 >
R ) 4-NO2 (Table 5).
Somewhat different behavior was observed over alumina,
which afforded slow oxidation of sulfide 1a (Table 1) but readily
mediated the oxidation of sulfoxide 2a to sulfone 3a (Table 2).
Similarly, oxidation of thianthrene 5-oxide (10) over alumina
gave principally the sulfone 11, whereas over silica gel the
bissulfoxide 12 was the major product (Table 5).
OXONE. This commercial oxidant consists of a 2:1:1 mixture
of the active ingredient KOSO2OOH, along with KHSO4 and
K2SO4, respectively. Although reactive toward a variety of
functional groups, it has received relatively little use in organic
synthesis because it is only soluble in very polar solvents, thus
usually necessitating the use of aqueous conditions.11 It has been
reported, however, that OXONE dispersed on “wet alumina”
suspended in organic solvents effects oxidation of phenyl alkyl
sulfides to the corresponding sulfoxides and sulfones.12 We have
found that oxidation of sulfide 1a and sulfoxide 2a occurs
equally well whether the OXONE is dispersed on either alumina
or silica gel (Table 7).13
SiO2 (OSiMe3)c
Al2O3
Al2O3 (neut)d
Al2O3 (C5H5N)e
f
Al2O3
a Conducted for 4 h according to the standard procedure with CH2Cl2
as solvent unless otherwise indicated. b Run in CDCl3 solution for 24
1
h; analyzed by H NMR spectroscopy relative to diphenylmethane as
an internal standard. c Partially silylated as described in the Experimental
Section. d Pretreated with 0.08 mmol/g (0.20 mmol) of CH3SO3H in 5
mL of CH2Cl2. e Pretreated with 0.08 mmol/g (0.20 mmol) of pyridine
in 5 mL of CH2Cl2. f Reverse order of addition; (CH3)3COOH added
before sulfoxide 2a.
Table 3. Oxidation of Sulfides 1b,c and Sulfoxides 2b,c with
(CH3)3COOH/Silica Gela
yield, %
substrate
time, h
1
2
3
1b
2b
1c
2c
1
6
6
5
93
5
trb
95
14
95
8
73
24
trb
a Conducted according to the standard procedure with CH2Cl2 as
solvent. b Trace.
Solvent-Free Oxidations. Surface-mediated reactions have
traditionally been conducted using a stirred suspension of the
(11) Kennedy, R. J.; Stock, A. M. J. Org. Chem. 1960, 25, 1901-1906.
(12) Greenhalgh, R. P. Synlett 1992, 235-236. See also: Ceccherelli,
P.; Curini, M.; Marcotullio, M. C.; Epifano, F.; Rosati, O. Synlett 1996,
767-768.
(13) We have found that the need to add water varies from batch to
batch of OXONE, which is hygroscopic. Thus the reagent might better be
described as “moist” OXONE supported on alumina or silica gel.
diastereomeric sulfoxides 5 in a cis/trans ratio similar to that
obtained previously by solution-phase oxidation of sulfide 4 with
(CH3)3COOH at 50 °C for 100 h.10 Finally, a study of substituent
(10) Johnson, C. R.; McCants, D., Jr. J. Am. Chem. Soc. 1965, 87, 1109-
1114.

4282 J. Am. Chem. Soc., Vol. 122, No. 18, 2000
Kropp et al.
Table 6. Oxidation of Thianthrene 5-Oxide (10) with
Scheme 1
(CH3)3COOHa
heating, sulfide 1a exhibited similar rates of oxidation with either
anhydrous or aqueous (CH3)3COOH, whether the silica gel was
pretreated with additional water or not. However, the amount
of over-oxidation to sulfone 3a decreased with increasing
amounts of water.14
yield, %
11-13
distribution, %
b
catalyst
10
11
cis-12
trans-12
13
ÌSO
Supported reagents have traditionally been prepared by
evaporating a solution of the reagent on the adsorbent and
solvent-free reactions conducted by first evaporating a solution
of the substrate on the supported reagent. We have found that
evaporative deposition is unnecessary. Simply mixing the neat
reagent and substrate with the adsorbent is adequate. It is not
even critical that initial coverage of the surface be uniform; a
split run in which sulfoxide 2a and (CH3)3COOH were initially
adsorbed to separate portions of silica gel that were then mixed
afforded sulfone 3a in a yield comparable to that obtained by
the conventional procedure (Table 8).
Mechanisms. A. Surface Structures. γ-Alumina is prepared
by flash calcination of hydrated aluminas (Scheme 1).15
Although the initially formed surface is totally hydroxylated,
at the temperatures required for the preparation some chemi-
sorbed water is subsequently lost through condensation of
adjacent OH groups, leaving oxide ions in the outermost layer
and exposed aluminum ions in the next lower layer.16 Thus
activated alumina is amphoteric, containing basic and Lewis
acidic sites in close proximity, along with residual OH groups.
The involvement of O- sites in surface-mediated processes can
be probed by neutralization with acid and Al+ sites by
complexation with pyridine.17
SiO2
Al2O3
12
39
81
58
19
79
4
59
18
21
0.31
0.83
a Conducted as described in the Experimental Section. b (11 + 13)/
(11 + 13) + (12 + 13); see ref 24.
Table 7. Oxidation of Sulfide 1a and Sulfoxide 2a with OXONEa
yield, %
substrate
adsorbent
time, h
1a
2a
3a
1a
1a
1a
2a
2a
1a
1a
1a
2a
2a
2a
4
1
1
100
7
64
SiO2
88
22
14
96
89
95
78
11
54
5
86
4
SiO2(OSiMe3)b
SiO2
16
16
4
SiO2(OSiMe3)b
Al2O3
6
5
6
Al2O3(neut)c
Al2O3(C5H5N)d
Al2O3
4
4
16
89
42
98
16
16
16
Al2O3(neut)c
Al2O3(C5H5N)d
a Conducted according to the standard procedure with CH2Cl2 as
solvent unless otherwise indicated. b Partially silylated as described in
the Experimental Section. c Pretreated with 0.08 mmol/g (0.20 mmol)
of CH3SO3H in 5 mL of CH2Cl2. d Pretreated with 0.08 mmol/g (0.20
mmol) of pyridine in 5 mL of CH2Cl2.
The surface of silica gel consists of silanol groups that fall
into two classes.16 The majority of the groups have O-O
distances of approximately 500 pm, well beyond the limit for
internal hydrogen bonding, and are thus isolated (14). For silica
gel that has been equilibrated at 120 °C, approximately 15% of
the silanol sites are geminal and hence sufficiently close to form
hydrogen-bonded chains through interaction with adjacent
groups (15).18 Little attention has been given to which sites are
involved in the adsorption of various types of substrates and in
various types of surface-mediated reactivity.19 However, the
Table 8. Solvent-Free Oxidation of Sulfide 1a and Sulfoxide 2a
with (CH3)3COOH/Silica Gela
yield, %
substrate
(CH3)3COOH
time, s
1a
2a
3a
1a
1a
1a
2a
2a
anhydrous
anhydrous
70% aqueous
70% aqueous
70% aqueousc
b
2
4
5
88
78
86
5
6
14
6
91
90
40
40
80
80
10
a Conducted according to the standard solvent-free procedure
described in the Experimental Section with microwave heating unless
otherwise indicated. b Maintained at 25 °C for 0.5 h. c Sulfoxide 2a
and (CH3)3COOH adsorbed to separate 1.25-g samples of silica gel
that were combined and mixed by tumbling prior to heating.
(14) Solvent-free oxidation of sulfide 1a with (CH3)3COOH/alumina or
OXONE over either silica gel or alumina gave inferior results.
(15) Diddams, P. In Solid Supports and Catalysts in Organic Synthesis;
Smith, K., Ed.; Ellis Horwood and PTR Prentice Hall: New York, 1992;
p 13.
(16) For descriptions of current models for the surfaces of alumina and
silica gel, see: (a) Kno¨zinger, H. In The Hydrogen Bond. III. Dynamics,
Thermodynamics and Special Systems; Schuster, P., Zundel, G., Sandorfy,
C., Eds.; North-Holland: Amsterdam, 1976; Chapter 27. (b) Dufour, P.;
Houtman, C.; Santini, C. C.; Ne´dez, C.; Basset, J. M.; Hsu, L. Y.; Shore,
S. G. J. Am. Chem. Soc. 1992, 114, 4248-4257.
adsorbent in an organic solvent.2 Although the choice of solvent
can affect the rate or selectivity of reaction,9 indicating that the
solvent can play a role, it has become increasingly evident that
a solvent is frequently unnecessary.2 Indeed, direct adsorption
of sulfide 1a, followed by (CH3)3COOH, onto silica gel with
tumbling at 25 °C resulted in formation of sulfoxide 2a in 0.5
h (Table 8), the same time required for oxidation in the presence
of CH2Cl2. Reaction time was dramatically reduced to 40 s by
microwave irradiation. Although microwave-assisted reactions
are normally conducted with moistened adsorbent to facilitate
(17) For a review of the quenching of Al+ sites on alumina surfaces,
see: Kno¨zinger, H. AdV. Catal. 1976, 25, 184-271. The A540 Fisher
alumina used in the current study has 0.08 mmol/g of strongly basic sites
and, presumably, an equivalent number of Al+ sites. Foti, C. J. Unpublished
results.
(18) Sindorf, D. W.; Maciel, G. E. J. Am. Chem. Soc. 1983, 105, 1487-
1493.

Surface-Mediated Reactions
J. Am. Chem. Soc., Vol. 122, No. 18, 2000 4283
Table 9. Adsorption onto Silica Gel and Aluminaa
Scheme 3
adsorption, %
substrate
adsorbent
substrate
(CH3)3COOH
SiO2
88
71
79
81c
80
78
70
25
49
75
SiO2(OSiMe3)b
Al2O3
1a
1a
1a
2a
2a
2a
3a
SiO2
82c
29
trd
99
64
20
6
SiO2(OSiMe3)b
Al2O3
SiO2
SiO2(OSiMe3)b
Al2O3
Al2O3
a Conducted using 1.0 mmol of substrate/2.5 g of alumina as
described in the Experimental Section unless otherwise indicated.
b Partially silylated as described in the Experimental Section. c Analyzed
5 min after the addition of (CH3)3COOH. d Trace.
Scheme 2
In principle, oxidation of sulfoxides to sulfones could occur
via an analogous mechanism. However, under the reaction
conditions sulfoxide 2a was quantitatively adsorbed to the
surface (Table 9). Adsorption at the more acidic, associated sites
apparently activates the sulfoxide for nucleophilic attack by
unbound (CH3)3COOH (Scheme 3) since partial silylation of
these sites substantially reduced the rate of oxidation (Table
2). Hence, there is a reversal in mechanism, from electrophilic
to nucleophilic,22 on going from sulfide to sulfoxide.
Oxidation of sulfide 1a by (CH3)3COOH occurred only
sluggishly over alumina and afforded substantial over-oxidation
to sulfoxide 2a (Table 1), while oxidation of sulfoxide 2a
occurred readily (Table 2). In both cases neutralization
substantially quenched oxidation. Hence the active species in
the predominant pathway for each oxidation is apparently
(CH3)3COO-, formed by reaction of (CH3)3COOH with O- sites
of the basic alumina. This is consistent with the ÌSO value of
0.83 obtained on oxidation of thianthrene 5-oxide (10) (Table
6), which is quite different from the value of 0.31 observed for
(CH3)3COOH/silica gel but in the range (0.5-1.0) exhibited by
nucleophilic oxidants in solution.23 Oxidation of sulfoxide 2a
was also substantially quenched by adsorption of pyridine to
the alumina. Hence the sulfoxide is apparently activated toward
nucleophilic attack by (CH3)3COO- through adsorption to the
Al+ sites (Scheme 4B), in analogy with its activation toward
nucleophilic attack by (CH3)3COOH on adsorption to the
associated sites of silica gel.24
hydrogen-bonded silanol groups are more acidic (pKa 5-7) than
their isolated counterparts (pKa 9.5) and react preferentially with
hexamethyldisilazane,20 affording a convenient method for
probing their involvement.
B. tert-Butyl Hydroperoxide. Under the conditions used,
(CH3)3COOH was substantially adsorbed from solution onto the
silica gel surface (Table 9). Since the extent of adsorption was
almost identical onto silica gel that had been partially silylated,
adsorption evidently occurs predominantly at the isolated sites s
presumably because there it can occur via reciprocal hydrogen
bonding, in which both the silanol group and the hydroperoxide
each serve as a hydrogen bond donor and acceptor (Scheme 2),
without disrupting existing hydrogen bonding as would be
required at the associated sites.21 The resulting complex is poised
for nucleophilic attack by the sulfide at the surface-solution
interface (electrophilic oxidation22), resulting in two proton shifts
and the transfer of an oxygen atom to the sulfide (Scheme 2).
As expected for a process centered at the isolated sites, partial
silylation of the silica gel had no significant effect on the rate
of oxidation of sulfide 1a (Table 1). Electrophilic oxidation is
supported by the value of 0.31 for ÌSO observed on oxidation
of thianthrene 5-oxide (10) (Table 6),23 as well as by the relative
rates of oxidation of the substituted sulfides 7: R ) 4-OCH3
> R ) H > R ) 3-OCH3 > R ) 4-NO2 (Table 5).
The order of addition to alumina is critical; adsorption of
(CH3)3COOH first substantially quenched oxidation of sulfoxide
2a (Table 2). This is undoubtedly due to association of the
initially formed (CH3)3COO- with the Al+ sites (Scheme 4,
A), both rendering the anion unavailable for reaction and
blocking the Al+ sites from adsorption by the sulfoxide.25 Little
attention has previously been given to the order of addition of
the reagent and substrate in surface-mediated reactivity. Most
often the reagent is adsorbed first, which is deleterious in this
case.
(23) Thianthrene 5-oxide (10) has been proposed as a model system for
differentiating between nucleophilic and electrophilic oxidation: Adam, W.;
Golsch, D. J. Org. Chem. 1997, 62, 115-119. Nucleophilic oxidants
typically display ÌSO values >0.5 and electrophilic oxidants values
<0.5.
(24) Only 20% of sulfoxide 2a was adsorbed (Table 9), corresponding
to coverage of all of the Al+ sites.17 However, since sulfone 3a is less
strongly adsorbed, it will equilibrate with remaining sulfoxide 2b, permitting
further oxidation.
(19) See, however, ref 9.
(20) Sindorf, D. W.; Maciel, G. E. J. Phys. Chem. 1982, 86, 5208-
5219.
(21) For a proposed similar cyclic hydrogen-bonded interaction of (CH3)3-
COOH with alcohols, see: Dankleff, M. A. P.; Curci, R.; Edwards, J. O.;
Pyun, H.-Y. J. Am. Chem. Soc. 1968, 90, 3209-3218.
(22) By convention, the mechanisms of oxidation reactions are character-
ized in terms of the mode of action of the oxidant.
(25) See: (a) Leffler, J. E.; Miller, D. W. J. Am. Chem. Soc. 1977, 99,
480-483. (b) Rebek, J.; McCready, R. Tetrahedron Lett. 1979, 45, 4337-
4338.

4284 J. Am. Chem. Soc., Vol. 122, No. 18, 2000
Kropp et al.
Scheme 4
Scheme 5
Scheme 6
C. Solvent-Free Oxidations. Presumably the oxidations of
sulfide 1a and sulfoxide 2a in the absence of solvent (Table 8)
occur via analogous mechanisms. The split run in which
sulfoxide 2a and (CH3)3COOH were adsorbed to separate
portions of silica gel indicates that substantial migration occurs
on the surface.26 Since similar, although slower, oxidation
occurred without heating, the effect of microwave irradiation
is most likely simply thermal.27
D. OXONE. Amazingly, simple mixing of solid OXONE
with moist silica gel or alumina, either as a suspension in CH2-
Cl2 or solvent-free, apparently results in its dispersion, or at
least dispersion of the active component KOSO2OOH, on the
surface of the adsorbent, facilitating oxidation. A small amount
of water must be present to facilitate adsorption,28 as well as
promote heating when microwave irradiation is used. Although
a suspension of moist OXONE in CH2Cl2 will effect oxidation
of sulfide 1a without an adsorbent present,1 reaction is
substantially faster in the presence of silica gel. Moreover,
silylation of the associated sites of silica gel slowed the oxidation
of sulfide 1a and quenched that of sulfoxide 2a (Table 7). Thus,
when present, silica gel is involved s through adsorption at the
associated sites (Scheme 5),29 facilitating contact between the
reactants for electrophilic oxidation. Sulfoxide 2a underwent
substantially slower oxidation than sulfide 1a with OXONE over
both silica gel and alumina (Table 7), as expected from both
its weaker nucleophilicity and its higher degree of adsorption
to the surfaces (Table 9).
(Table 7). Oxidation in this case evidently involves competing
reaction of the sulfoxide with KOSO2OOH as in Scheme 5 and
with KOSO2OO- as in Scheme 6. Neutralization quenches the
latter process, which is faster. Treatment of the alumina with
pyridine quenches competitive binding of the sulfoxide with
Al+ sites, which normally slows oxidation. This contrasts with
oxidation by (CH3)3COOH/alumina, which involves attack of
(CH3)3COO- on sulfoxide bound to Al+ sites (Scheme 4B) and
is accelerated by the binding. Being surface-bound itself,
KOSO2OO- is unable to react with bound sulfoxide.
Concluding Remarks
In summary, oxidation of sulfides to sulfoxides occurs readily
with (CH3)3COOH over silica gel or with OXONE over either
silica gel or alumina; reaction is fastest with (CH3)3COOH over
silica gel, whereas the greatest selectivity is afforded by OXONE
over neutralized alumina. Oxidation of sulfoxides to sulfones
occurs with both (CH3)3COOH and OXONE over either silica
gel or alumina but more rapidly with (CH3)3COOH.
In addition to providing convenient, environmentally benign
methods for the oxidation of sulfides and sulfoxides, the present
studies have afforded significant insights into the mechanistic
aspects of surface-mediated behavior. Mediation by silica gel
has been found to involve principally either the isolated or
associated sites, depending on the reagent and substrate. Also,
despite the common concept of a “supported reagent”, either
the reagent or the substrate may be the bound species involved
in reaction. Similarly, the O- and Al+ sites of alumina may be
involved or not. Thus each surface-mediated reaction requires
individual mechanistic analysis. Depending on the mechanism,
the order of adsorption to the surface may be critical for optimal
results, as in the oxidation of sulfoxides with (CH3)3COOH/
alumina. It has also been shown that surface-mediated reactions
can be conducted by simple mixing of the adsorbent, reagent,
and substrate in the dry state followed by appropriate heating,
without any use of solvent except to extract the product from
the adsorbent s thereby extending the flexibility and environ-
mental friendliness of these reactions. Our studies in the
fascinating realm of surface-mediated reactivity continue,
Oxidation of sulfide 1a by OXONE/alumina was insensitive
to either neutralization of the O- sites or the presence of
pyridine, which complexes with the Al+ sites (Table 7). On the
other hand, oxidation of sulfoxide 2a was partially quenched
by neutralization but accelerated by the presence of pyridine
(26) For a summary of other studies showing mobility of molecules on
the surfaces of silica gel and alumina, see: Worrall, D. R.; Williams, S.
L.; Wilkinson, F. J. Phys. Chem. B 1997, 101, 4709-4716.
(27) Also, see: Raner, K. D.; Strauss, C. R.; Vyskoc, F.; Mokbel, L. J.
Org. Chem. 1993, 58, 950-953.
(28) The role of water in facilitating reactions involving solid reagents
has been attributed to breakup of the crystal lattice: (a) Carpino, L. A.;
Sau, A. C. J. Chem. Soc., Chem. Commun. 1979, 514. (b) Tanaka, M.;
Koyanagi, M. Synthesis 1981, 973-975. (c) Hirano, M.; Yakabe, S.;
Monobe, H.; Morimoto, T. Can. J. Chem. 1977, 75, 1905-1912.
(29) Alternatively, adsorption might be viewed as involving OXONE
and adsorbed water at the associated sites.

Surface-Mediated Reactions
J. Am. Chem. Soc., Vol. 122, No. 18, 2000 4285
Oxidation of Thianthrene 5-Oxide (10). Oxidations were conducted
for 24 h according to the standard procedure except that the product
mixture was dissolved in CH2Cl2 and analyzed by HPLC (5-µm
LiChrosorb S 60 column, 1% CH3OH in CH2Cl2, flow rate of 1 mL/
min, UV detection at 254 nm) relative to a known amount of thianthrene
added as an internal standard.
Adsorption Studies. Into a 25-mL round-bottomed flask was
weighed 2.5 g of Merck 10181 chromatographic silica gel or Fisher
A540 chromatographic alumina that had been equilibrated to the
atmosphere at 120 °C for at least 48 h. The flask was stoppered, and
the contents allowed to cool to 25 °C. A solution of 1.0 mmol each of
substrate and diphenylmethane, as an internal standard, in 5 mL of
CH2Cl2 was added to the flask with stirring. After 5 min 137 µL (1.0
mmol) of 70% aqueous (CH3)3COOH was added. The slurry was stirred
at 25 °C for 20 min, after which a 250-µL aliquot was removed from
the supernatant liquid, evaporated to dryness, and analyzed by 1H NMR
spectroscopy.
Silylation of Silica Gel. In a modification of the procedure by
Maciel,20 20.0 g of Fisher S-157 silica gel that had been equilibrated
with the atmosphere at 120 °C for at least 48 h was weighed into a
200-mL round-bottomed flask. The flask was then stoppered and the
contents allowed to cool to 25 °C. A solution of 3.0 mL (14.2 mmol)
of hexamethyldisilazane in 40 mL of toluene was added and the
resulting slurry was mixed slowly on a rotary evaporator at 25 °C for
20 h. The solvent was then removed under aspirator pressure at 65 °C
for 1.5 h and then 0.5 mmHg at 120 °C for 1.5 h. After being
equilibrated with the atmosphere at 120 °C for at least 48 h, the silylated
silica gel was weighed. The increase in weight for several runs was
1.45-1.57 g, corresponding to 102-110% silylation of the available
associated silanol sites.
including pursuing spectroscopic evidence for the mechanisms
proposed here.
Experimental Section
Standard Procedure with Solvent. Into a 25-mL round-bottomed
flask was weighed 2.5 g of Merck 10181 silica gel or Fisher A540
alumina that had been equilibrated with the atmosphere at 120 °C for
at least 48 h. The flask was stoppered and the contents allowed to cool
to 25 °C. For oxidations with OXONE, 0.5 mL of water was added
and the adsorbent was tumbled on a rotary evaporator at atmospheric
pressure until uniformly free-flowing.30 A solution of 1.0 mmol of
sulfide or sulfoxide in 5 mL of CH2Cl2 was added with stirring followed
by 137 µL (1.0 mmol) of 70% aqueous (CH3)3COOH or 462 mg of
OXONE (1.5 mmol of KOSO2OOH). The slurry was stirred at 25 °C
for the specified amount of time. The adsorbent was then removed by
vacuum filtration and washed with 100 mL of ethyl acetate. The
combined organic fractions were washed with 30 mL of a saturated,
aqueous solution of FeSO4, dried several hours over anhydrous Na2-
SO4, and concentrated under reduced pressure. The residue was
chromatographed through silica gel by elution with 4:1 hexanes-ethyl
acetate.
Standard Solvent-Free Procedure. Into a 25-mL round-bottomed
flask was weighed 2.5 g of Merck 10181 chromatographic silica gel
that had been equilibrated with the atmosphere at 120 °C for at least
48 h. The flask was stoppered and the contents allowed to cool to 25
°C. The substrate was added without solvent and the resulting mixture
tumbled on a rotary evaporator at atmospheric pressure until uniformly
free-flowing. The oxidant was then added and the mixture again
tumbled. After being heated for the specified period of time,31 the
mixture was allowed to cool to 25 °C and was washed with 100-200
mL of ethyl acetate. The adsorbent was collected by vacuum filtration
and the filtrate concentrated under reduced pressure. The residue was
Acknowledgment. Generous financial support by the donors
of the Petroleum Research Fund, administered by the American
Chemical Society, and by the University of North Carolina at
Chapel Hill/Hoechst Celanese Corporation Discovery Awards
Program is gratefully acknowledged, as is a PPG Summer
Internship awarded to B.R.L.
1
weighed and analyzed by H NMR spectroscopy.
Partial Oxidation of Tetrahydro-4-methyl-2H-thiopyran (4).
Oxidation was conducted according to the standard procedure over SiO2
with 0.25 equiv of (CH3)3COOH. The ratio of the diastereomeric
sulfoxides 5 was determined by integration of the diagnostic signals at
δ 3.18 (trans-5) and 2.88 (cis-5).
Supporting Information Available: Description of starting
sulfides and characterization of products (PDF). This material
is available free of charge via the Internet at http://pubs.acs.org.
(30) The need for this step varied from batch to batch of OXONE.
(31) Microwave heating was conducted using a commercial 500-W Little
Litton oven.
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