Reactions of bis(p-methoxyphenyl)trisulfane and its oxides with dimethyldioxirane and (trifluoromethyl)methyldioxirane

Article abstract of DOI:10.1021/jo960995x

The reactions of dimethyldioxirane and (trifluoromethyl)methyldioxirane with bis(p-methoxyphenyl)-trisulfane, its 1-oxide, its 2-oxide, and its 1,1-dioxide derivatives have been investigated. The reactions were followed by careful monitoring of the methox

Full text of DOI:10.1021/jo960995x

J . Org. Chem. 1996, 61, 7911-7917
7911
Rea ction s of Bis(p-m eth oxyp h en yl)tr isu lfa n e a n d Its Oxid es w ith
Dim eth yld ioxir a n e a n d (Tr iflu or om eth yl)m eth yld ioxir a n e
Edward L. Clennan* and Kristina L. Stensaas
Department of Chemistry, University of Wyoming, Laramie, Wyoming 82071
Received May 29, 1996X
The reactions of dimethyldioxirane and (trifluoromethyl)methyldioxirane with bis(p-methoxyphenyl)-
trisulfane, its 1-oxide, its 2-oxide, and its 1,1-dioxide derivatives have been investigated. The
1
reactions were followed by careful monitoring of the methoxy region of the H NMR spectra and
where possible by doping with authentic samples of the products. The decomposition of labile
intermediates and products was investigated. A new mechanism for the rearrangement of a
trisulfane 1,3-dioxide to a trisulfane 1,1-dioxide is proposed.
Interest in the trisulfane linkage has increased rapidly
in the past few years in part as a result of the isolation
and structural assignment1,2 of calicheamicin γ1 and the
Esperamicins.3,4 The trisulfane linkage in these antitu-
mor antibiotics acts as the trigger for a Bergman cycliza-
tion5 of the enediyne unit to give a 1,4-diyl that when
bound in the minor groove of DNA abstracts hydrogen
atoms, resulting in single- and double-stranded scis-
sions.6-9 Despite the occurrence of the trisulfane linkage
oxidations of di-tert-butyltrisulfane and its oxidized
derivatives have started to appear. Di-tert-butyltrisul-
fane was chosen for examination because of the well-
known increase in stability of its oxidized derivatives,
1-6, in comparison to analogues with a lower degree of
substitution (stability sequence; tertiary > secondary >
primary).17,18 These reports provide the impetus for the
disclosure of our analogous study of the oxidations of bis-
(p-methoxyphenyl)trisulfane and its oxidized derivatives.
These latter compounds were chosen for our studies
because the methoxy groups provide a convenient NMR
handle that can be used to identify the products of the
oxidations (vide infra). The results reported here are
different in some respects from those reported for di-tert-
butyltrisulfane and its derivatives. These results also
point out a potential mechanistic dichotomy for which
we propose a possible solution.
in a variety of natural products,10 including these anti-
tumor antibiotics, its chemistry has not been examined
as extensively as its disulfane homologue. The most
prominent reactions of trisulfanes include nucleophilic
attack,11 which leads to desulfurization in the cases of
phosphines,12 phosphites, or chalcogenides,13 and oxida-
tions.14,15
The oxidation chemistry is complicated by the possible
formations of both regio- and stereoisomeric products and
by the well-established lability of many of these com-
pounds. The mono- and bis-oxidations of symmetrical
trisulfanes could presumably lead to a trisulfane 1-oxide
1, a trisulfane 2-oxide 2, diastereomeric trisulfane 1,2-
dioxides 3, diastereomeric trisulfane 1,3-dioxides, 4, a
trisulfane 1, 1-dioxide 5, or a trisulfane 2,2-dioxide, 6.16
Despite the difficulties associated with the studies of
these oxidations, elegant and detailed reports of the
Resu lts
X Abstract published in Advance ACS Abstracts, October 1, 1996.
(1) Lee, M. D.; Dunne, T. S.; Siegel, M. M.; Chang, C. C.; Morton,
G. O.; Borders, D. B. J . Am. Chem. Soc. 1987, 109, 3464-3466.
(2) Lee, M. D.; Dunne, T. S.; Chang, C. C.; Ellestad, G. A.; Siegel,
M. M.; Morton, G. O.; McGahren, W. J .; Borders, D. B. J . Am. Chem.
Soc. 1987, 109, 3466-3468.
The oxidations of bis(4-methoxyphenyl)trisulfane and
its derivatives were monitored by 1H NMR using the
methoxy protons as diagnostic signals. The methoxy
group on the p-methoxyphenyl ring appeared between
3.804 and 3.872 ppm when attached to a sulfenyl sulfur
(-S-), between 3.899 and 3.912 when attached to a
sulfinyl sulfur (-SO-), and between 3.913 and 3.960
when attached to a sulfonyl sulfur (-SO2-), all relative
to TMS at room temperature (Table 1). The only excep-
tion to these generalizations occurred in the bis(4-
methoxyphenyl)trisulfane 1,1,3-trioxide, which exhibited
somewhat unanticipated downfield (3.924 and 3.990 ppm)
chemical shifts. Complicating the analysis, however, was
the tendency of the chemical shifts of the methoxy groups
(3) Golik, J .; Clardy, J .; Dubay, G.; Groenewold, G.; Kawaguchi, H.;
Konishi, M.; Krishnan, B.; Ohkuma, H.; Saitoh, K.; Doyle, T. W. J .
Am. Chem. Soc. 1987, 109, 3461-3462.
(4) Golik, J .; Dubay, G.; Groenewold, G.; Kawaguchi, H.; Konishi,
M.; Krishnan, B.; Ohkuma, H.; Saitoh, K.; Doyle, T. W. J . Am. Chem.
Soc. 1987, 109, 3462-3464.
(5) Bergman, R. G. Acc. Chem. Res. 1973, 6, 25-31.
(6) Nicolaou, K. C.; Dai, W.-M. Angew. Chem., Int. Ed. Engl. 1991,
30, 1387-1416.
(7) Nicolaou, K. C.; Smith, A. L. Acc. Chem. Res. 1992, 25, 497-
503.
(8) Magnus, P.; Carter, P.; Elliott, J .; Lewis, R.; Harling, J .; Pitterna,
T.; Bauta, W. E.; Fortt, S. J . Am. Chem. Soc. 1992, 114, 2544-2559.
(9) Magnus, P.; Lewis, R.; Bennett, F. J . Am. Chem. Soc. 1992, 114,
2560-2567.
(10) Yomoji, N.; Satoh, S.; Ogawa, S.; Sato, R. Tetrahedron Lett.
1993, 34, 673-676.
(16) We have decided to use the sulfane nomenclature because we
will only discuss a symmetrical trisulfide and its derivatives where it
is less cumbersome than perhaps other alternatives. In addition, it
has been pointed out that the “sulfane” nomenclature can be extended
conveniently to polyoxides and to sulfanes with more than two
contiguous sulfur atoms.15
(11) Sato, R.; Sato, T.; Takikawa, Y.; Takizawa, S. Tech. Rep. Iwate
Univ. 1979, 13, 37-41.
(12) Harpp, D. N.; Ash, D. K.; Smith, R. A. J . Org. Chem. 1980, 45,
5155-5160.
(13) Li, C. J .; Harpp, D. N. Tetrahedron Lett. 1993, 34, 903-906.
(14) Steudel, R.; Latte, J . Chem. Ber. 1977, 110, 423-429.
(15) Steudel, R. Phosphorus Sulfur 1985, 23, 33-64.
(17) Derbesy, G.; Harpp, D. N. J . Org. Chem. 1995, 60, 4468-4474.
(18) Derbesy, G.; Harpp, D. N. J . Org. Chem. 1996, 61, 991-997.
S0022-3263(96)00995-4 CCC: $12.00 © 1996 American Chemical Society

7912 J . Org. Chem., Vol. 61, No. 22, 1996
Clennan and Stensaas
Ta ble 1. P r oton Ch em ica l Sh ifts of p-Meth oxy Gr ou p s
Bou n d to Su lfen yl, Su lfin yl, a n d Su lfon yl Gr ou p s
a
b
R ) p-MeOPh. Proton chemical shifts of methoxy group on
the phenyl ring bound to sulfenyl sulfur. c Same as b but bound
to sulfinyl sulfur. Same as b but bound to sulfonyl sulfur. e At
d
-20 °C.
to fluctuate by (0.03 ppm as a function of several
experimental variables including temperature. As a
result, definitive identification of the products was
obtained in several cases by doping the NMR reaction
mixtures with authentic samples of the potential prod-
ucts.
Dimethyldioxirane (DMD) and (trifluoromethyl)meth-
yldioxirane (TMD) were used as the oxidants. m-CPBA
gave less satisfactory results presumably as a result of
the formation of the very acidic p-methoxybenzoic acid
byproduct. The formation of products that incorporated
the benzoate byproduct has previously been noted during
oxidations of disulfanes.19
F igu r e 1. (a) 1H NMR at -20 °C of the methoxy region
immediately after addition of 1 equiv of DMD to the trisulfane.
Key: (a) trisulfane 1-oxide; (b) trisulfane 1,1-dioxide; (c)
trisulfane; (d) trisulfane 1,1,3-trioxide. (b) 1H NMR at room
temperature of the methoxy region 2-3 h after addition of 0.6
equiv of DMD to the trisulfane. Key: (c) trisulfane; (e)
disulfane-1,1-dioxide; (f) tetrasulfane; (g) disulfane; (h) un-
known. (c) 13C NMR of methoxy region at room temperature
of the sample corresponding to the 1H NMR in Figure 2b.
Key: (c) trisulfane; (e) disulfane 1,1-dioxide; (f) tetrasulfane.
Oxidation of Bis(p-m eth oxyph en yl)tr isu lfan e. One
equiv of DMD was added to an acetone-d6 NMR sample
of the trisulfane at -20 °C, and the 400 MHz proton NMR
spectrum was immediately recorded. Two new singlets
at 3.910 and 3.848 ppm (peaks a in Figure 1a) were
observed consistent with formation of the trisulfane
1-oxide. In addition, a small amount of the trisulfane
1,1-dioxide (peaks b in Figure 1a), residual trisulfane
(peak c), and two peaks at 3.92 and 3.99 ppm (peaks d),
which we assign to the trisulfane 1,1,3-trioxide (vide
infra), were also detected in the reaction mixture. This
regiochemistry is consistent with that observed in the
m-CPBA oxidations of dimethyl,20 diethyl,20 dipropyl,20
di-tert-butyl,14,20,21 dibenzyl,20 and diallyl trisulfanes.22
Only in the case of some cyclic trisulfanes such as 723
and 824 have nonregiospecific reactions been observed.
The thermal lability of sulfane 1-oxides has been noted
in the literature, and it has been pointed out that the
stability increases with the degree of substitution (ter-
tiary > secondary > primary).17 Indeed, warming the
(20) Auger, J .; Koussourakos, Y.; Thibout, E. Chim. Chron., New
Ser. 1985, 14, 263-264.
(21) Derbesy, G.; Harpp, D. N. Sulfur Lett. 1995, 18, 167-172.
(19) Freeman, F.; Angeletakis, C. N. J . Am. Chem. Soc. 1982, 104,
5766-5774.

Reactions of Bis(p-methoxyphenyl)trisulfane
J . Org. Chem., Vol. 61, No. 22, 1996 7913
Sch em e 1
NMR reaction mixture containing bis(p-methoxyphenyl)-
trisulfane 1-oxide to room temperature resulted in its
decomposition. Kinetic experiments at room temperature
conducted by following the disappearance of the trisul-
fane 1-oxide resulted in a clean first-order decay with a
rate constant of (1.67 ( 0.22) × 10-4 s-1 corresponding
to a half-life of 69 min at room temperature. Greater
than 95% of the trisulfane 1-oxide had decomposed within
5 h at 25 °C. For comparison, Derbesy and Harpp17
reported that di-tert-butyltrisulfane 1-oxide required 12
h at 45 °C to completely decompose.
The reaction of the sulfinyl anion and cation (c in
Scheme 1) is somewhat unusual since it has been pointed
out that this dimerization is very sensitive to steric effects
and does not occur at all during the decomposition of di-
tert-butyltrisulfane 1-oxide, 9.17 Consequently, 9, de-
composed to give a more complex reaction mixture (eq
2) than observed in our system via a more complicated
mechanism.17
NMR examination of a reaction mixture (Figure 1b)
containing the trisulfane and 0.6 equiv of DMD after 2-3
h revealed formation of a 1:1 mixture of the bis(p-
methoxyphenyl)disulfane 1,1-dioxide (peaks e) and bis-
(p-methoxyphenyl) tetrasulfane (peak f) as a result of the
decomposition of the transient trisulfane 1-oxide (eq 1).
( )
(
)
Oxid a t ion of Bis(p -m et h oxyp h en yl)t r isu lfa n e
1-Oxid e. This oxidation was the most complex of those
that we have examined, and its analysis was exacerbated
by our inability to completely oxidize the starting mate-
rial without concomitant overoxidation. As a result, the
products from decompositions of the trisulfane 1-oxide
and trisulfane 1,1,3-trioxide (vide infra) were unavoidably
formed in every reaction mixture complicating the analy-
sis. Nevertheless, useful conclusions could be drawn by
careful examinations of the reactions under a variety of
conditions.
One equiv of DMD was added to the preformed
trisulfane 1-oxide at -20 °C followed by immediate
analysis of the reaction mixture by low-temperature
NMR. (Figure 2a). A major new peak was observed at
3.912 (peak i) and a minor new peak at 3.899 (peak j),
and the peaks at 3.838, 3.920, 3.960, and 3.990 ppm
(peaks b and d), which were present to a minor extent in
the preformed trisulfane 1-oxide (Figure 1a) increased
in intensity. Peaks d were also formed as the overwhelm-
ing product during the oxidation of the trisulfane 1,1-
dioxide with DMD at -20 °C and are consequently
assigned to the overoxidation product, the trisulfane
1,1,3-trioxide. Warming the reaction mixture to room
temperature (Figure 2b) resulted in the increase of peaks
b and the formation of new peaks, e, f, g, and u, at the
expense of the major peak at 3.912 (peak i), the residual
trisulfane 1-oxide (peaks a), and the trisulfane 1,1,3-
trioxide (peaks d), which completely disappeared. Der-
besy and Harpp have pointed out that the diastereomeric
di-tert-butyltrisulfane 1,3-dioxides are barely stable at
Small amounts of the disulfane (peak g) and an unknown
reaction component (peak h) were also observed in
addition to unreacted trisulfane (peak c). This assign-
ment was corroborated by the methoxy region of the 13C
NMR (Figure 1c), which showed formation of the same
major products in approximately the same ratio as in the
1H NMR.
A mechanism consistent with formation of a 1:1
mixture of the tetrasulfane and disulfane 1,1-dioxide is
shown in Scheme 1. The first step involves a heterolytic
cleavage of the 1-oxide to give the (p-methoxyphenyl)-
sulfinyl cation and a disulfide anion. A heterolytic
cleavage of di-tert-butyltrisulfane 1-oxide was suggested
by Derbesy and Harpp17 on the basis of the inability of
radical inhibitors to affect the rate of decomposition and
crystallographic data, which shows that S(O)-S bonds
are longer than either S-S or S(O)2-S bonds. Step b in
Scheme 1 is supported by the observation that thiolates
are known to attack at the sulfenyl sulfur in phenyl
benzenethiolsulfinate (PhS(O)SPh) rather than at the
harder sulfinyl sulfur.25 In step c of the mechanism,
annihilation of the sulfinyl cation and anion would
ultimately result in formation of the 1,1-dioxide via a
mechanism similar to that suggested for the rearrange-
ments of R-disulfoxides.26
(22) Freeman, F.; Ma, X.-B.; Lin, R. I.-S. Sulfur Lett. 1993, 15, 253-
262.
(23) Ghosh, T.; Bartlett, P. D. J . Am. Chem. Soc. 1988, 110, 7499-
7506.
(24) Yomojii, N.; Takahashi, S.; Chida, S.; Ogawa, S.; Sato, R. J .
Chem. Soc., Perkin Trans. 1 1993, 1995-2000.
(25) Kice, J . L. In Advances in Physical Organic Chemistry; Gold,
V., Bethell, D., Ed.; Academic Press: London, 1980; Vol. 17; pp 65-
181.
(26) Folkins, P. L.; Harpp, D. N. J . Am. Chem. Soc. 1993, 115, 3066-
3070.

7914 J . Org. Chem., Vol. 61, No. 22, 1996
Clennan and Stensaas
Sch em e 2
decomposition of di-tert-butyltrisulfane 1,3-dioxide18 was
not observed to any extent under any of our experimental
conditions.
The mechanism in Scheme 2 was suggested by Harpp18
to explain the formation of di-tert-butyltrisulfane 1,1-
dioxide from decomposition of the 1,3-dioxide precursor
and could also be invoked in this case to provide an
explanation for formation of the 1,1-dioxide as the major
product from decomposition of (p-methoxyphenyl)trisul-
fane 1,3-dioxide. (See, however, oxidation of the trisul-
fane 2-oxide; vide infra.) Similar rearrangements have
been convincingly demonstrated to occur during decom-
positions of disulfane 1,2-dioxides.26
Oxid a t ion of Bis(p -m et h oxyp h en yl)t r isu lfa n e
2-Oxid e. Oxidations of the trisulfane 2-oxide with DMD
in acetone or in acetone/CH2Cl2 and with TFD in acetone/
trifluoroacetone or in CH2Cl2/trifluoroacetone solvent
mixtures at room temperature resulted in formation of
the bis(p-methoxyphenyl)disulfane (peak g) and trisul-
fane (peak c) as the overwhelming products (Figure 3a).
A small amount of bis(p-methoxyphenyl)disulfane 1,1-
dioxide (peaks e), the tetrasulfane (peak f), and decom-
position products of trisulfane 1,1,3-trioxide (peaks u),
along with residual trisulfane 2-oxide (peak k), were also
detected in the reaction mixtures in acetone, benzene,
CH2Cl2, and anhydrous diethylether. In all these sol-
vents the disulfane appeared to form in slight excess of
the trisulfane. A complete and clean conversion of the
trisulfane 2-oxide to the di- and trisulfanes was never
achieved since these products are more easily oxidized
than the starting material. However, in several solvents,
1 equiv of dioxirane resulted in both complete decomposi-
tion of the trisulfane 2-oxide and formation of overoxi-
dation products. (Figure 3b).
F igu r e 2. (a) 1H NMR of methoxy region at -20 °C im-
mediately after addition of 1 equiv of DMD to preformed
trisulfane 1-oxide. Key: (a) trisulfane 1-oxide; (b) trisulfane
1,1-dioxide; (d) trisulfane 1,1,3-trioxide; (i) trisulfane 1,3-
dioxide; (j) unknown. (b) 1H NMR of methoxy region of a
sample similar to that shown in panel a after several hours
at room temperature. Key: (b) trisulfane 1,1-dioxide; (e)
disulfane 1,1-dioxide; (f) tetrasulfane; (g) disulfane; (u) un-
known.
room temperature, and consequently, we assign the
intense peak at 3.912 ppm to bis(p-methoxyphenyl)-
trisulfane 1,3-dioxide. This new trisulfane 1,3-dioxide is
likely to exist as a pair of diastereomers,21 which unfor-
tunately, cannot be verified since only one methoxy peak
is resolvable.
The intensity ratios of the NMR peaks at room tem-
perature (Figure 2b) were a sensitive function of the
sample treatment and fluctuated as a function of whether
the 2 equiv of DMD were both administered at room
temperature or stepwise at low temperature. In addition,
the relative intensities of the peaks changed as a function
of the time between addition of the dioxirane and the
time of analysis. In particular, peaks e, the disulfane-
1,1-dioxide, increase dramatically with increasing time.
However, under all the conditions examined the initial
major product of the reaction with peaks at 3.838 and
3.960 ppm (peaks b) is the trisulfane 1,1-dioxide. The
remaining peaks belong to the disulfane 1,1-dioxide
(peaks e) and tetrasulfane (peak f), which are the
decomposition products of the residual trisulfane 1-ox-
ide,27 the disulfane (peak g), and unknowns (peaks u),
which appear to be products of the decomposition of the
very labile trisulfane 1,1,3-trioxide. The disulfane 1-ox-
ide (thiolsulfinate) that formed as a major product in the
Initial attempts to identify reactive intermediates
responsible for the formation of the di- and trisulfanes
using DMD as the oxidant at low temperatures failed as
a result of its low reactivity. Fortunately, the more
potent oxidant TFD reacted with the trisulfane 2-oxide
even at -80 °C (Figure 3c). To our surprise, however,
the disulfane (peak g) was the only product observed at
these low temperatures.
Discu ssion
The oxidized derivatives of bis(p-methoxyphenyl)trisul-
fane appear to be considerably less stable than the
oxidized derivatives of di-tert-butyltrisulfane. Neverthe-
less, several primary oxidation products are still observ-
able. Bis(p-methoxyphenyl)trisulfane 1-oxide is stable for
nearly 5 h at room temperature, and the trisulfane 1,3-
dioxide (4, R ) p-MeOPh-) can be seen at -20 °C but
decomposes as the sample is warmed to room tempera-
ture. Only in the case of bis(p-methoxyphenyl)trisulfane
2-oxide were we unable to detect a primary oxidation
product.
(27) The disulfane 1,1-dioxide/tetrasulfane ratio was not 1/1 as
anticipated from decomposition of the trisulfane 1-oxide; however,
Harpp has pointed out that trisulfane 1,1-dioxides spontaneously
extrude sulfur to form disulfane 1,1-dioxides: Harpp, D. N.; Ash, D.
K.; Smith, R. A. J . Org. Chem. 1979, 44, 4135-4140.

Reactions of Bis(p-methoxyphenyl)trisulfane
J . Org. Chem., Vol. 61, No. 22, 1996 7915
Sch em e 3
Sch em e 4
similar to that proposed by Field and Lacefield28 (Scheme
3b). We have independently demonstrated that this
catalysis with the p-methoxyphenyl derivative is effective
at room temperature but does not occur at an appreciable
rate at -40 °C. These results preclude low-temperature
formation of the catalyzed products as experimentally
observed. In addition, the operation of the catalyzed
route also provides an explanation why 1 equiv of
dioxirane at room temperature is capable of completely
decomposing the trisulfane 2-oxide and producing over-
oxidation products.
The proposed key intermediate in the formation of both
the trisulfane 1,1-dioxide (Scheme 2) and the trisulfane
2,2-dioxide (Scheme 3a) at low temperatures is the
trisulfane 1,2-dioxide. Either these key intermediates
are diastereomers, which we feel is unlikely, or one of
the two mechanisms (Scheme 2 or 3) is wrong.29 The key
intermediate, 10, in Scheme 2 is an ambident nucleophile
that is unlikely to attack with either the nucleophilic
sulfur or oxygen at the electron-rich oxygen atom of the
sulfinyl cation as shown in step A. An alternative
mechanism to explain the formation of the trisulfane 1,1-
dioxide from the trisulfane 1,3-dioxide is shown in
Scheme 4. This mechanism invokes a more palatable
attack of nucleophile 10 at the more electron-deficient
F igu r e 3. (a) 1H NMR of the methoxy region at room
temperature of a sample of the trisulfane 2-oxide that had been
treated with 1.0-1.5 equiv of TFD in methylene chloride.
Key: (b) trisulfane 1,1-dioxide; (c) trisulfane; (e) disulfane-1,1-
dioxide; (f) tetrasulfane; (k) trisulfane 2-oxide; (g) disulfane;
(u) unknown. (b) 1H NMR of the methoxy region at room
temperature of a sample of the trisulfane 2-oxide that had been
treated with 1 equiv of DMD in benzene. Key: (b) trisulfane
1,1-dioxide; (c) trisulfane; (e) disulfane-1,1-dioxide; (f) tetra-
sulfane; (g) disulfane; (u) unknown. (c) 1H NMR of the reaction
of TFD with the trisulfane 2-oxide at -80 °C. Key: (g)
disulfane; (k) trisulfane 2-oxide.
Reaction of the trisulfane 2-oxide (2, R ) p-MeOPh-)
at low temperature with TFD to form the disulfane is
consistent with oxidation to give the trisulfane 1,2-dioxide
(3, R ) p-MeOPh-) followed by rearrangement to the
trisulfane 2,2-dioxide (6, R ) p-MeOPh-) and loss of SO2
(Scheme 3a). At room temperature, however, we suggest
that the results can be rationalized by the SO2-catalyzed
decomposition of the trisulfane 2-oxide by the route
(28) Field, L.; Lacefield, W. B. J . Org. Chem. 1966, 31, 3555-3561.
(29) (Trifluoromethyl )methyldioxirane (TFD) has a tendency to give
more sulfone than observed in reactions of dimethyldioxirane (DMD).
A mechanism to explain the excess sulfone formation that invokes a
sulfurane intermediate has been suggested. Asensio, G.; Mello, R.;
Gonza´lez-Nu´n˜ez, M. E. Tetrahedron Lett. 1996, 37, 2299-2302.
Consequently, it is conceivable that TFD reacts via
a different
mechanism than DMD. However, we consider this unlikely because
at room temperature where the two reagents can be compared directly
the oxidations of the trisulfane 2-oxide gave identical product mixtures.

7916 J . Org. Chem., Vol. 61, No. 22, 1996
Clennan and Stensaas
mp 44-45 °C). 1H NMR (acetone-d6): δ 3.80 (s, 6H), 6.93 (m,
4H), 7.42 (m, 4H). 13C NMR (acetone-d6): δ 55.84, 115.74,
128.75, 133.39, 161.28.
center in the sulfinyl cation to either return to starting
material or to give intermediate 12. A potential draw-
back to the mechanistic scenario depicted in Scheme 4
is the formation of the electronically destabilized sulfonyl
cation 11 in step B. The formation of this energetically
costly intermediate, however, could be circumvented by
a four-centered direct conversion of 12 to the trisulfane
1,1-dioxide (step C). On the other hand, the possibility
that oxidation occurs at the oxidized sulfur in 2 com-
pletely bypassing formation of the trisulfane 1,2-dioxide
to give directly the trisulfane 2,2-dioxide, 6 (Scheme 3a)
cannot be unambiguously eliminated from consideration.
Bis(p-methoxyphenyl)disulfane 1-oxide was prepared by
oxidation of the disulfane with dimethyldioxirane. Purification
(lit.35 mp 96 °C) was achieved using a 2 mm silica gel plate on
the chromatotron eluting with 3:2 hexanes/ethyl acetate. 1H
NMR (acetone-d6): δ 3.87 (s, 3H), 3.90 (s, 3H), 7.01 (m, 2H),
7.13 (m, 2H), 7.44 (m, 2H), 7.63 (m, 2H). 13C NMR (acetone-
d6): δ 55.97, 56.16, 115.44, 115.81, 121.32, 126.97, 136.62,
138.22, 162.84, 163.47.
Bis(p-methoxyphenyl)disulfane 1,1 dioxide was synthesized
from the disulfane using 2 equiv of m-CPBA. Purification by
chromatotron using a 2 mm silica gel plate (4:1 hexanes/ethyl
acetate) produced white crystals. Mp: 89-89.5 °C (lit.36 mp
92-94 °C). 1H NMR (acetone-d6): δ 3.85 (s, 3H), 3.91 (s, 3H),
6.96 (m, 2H), 7.06 (m, 2H), 7.26 (m, 2H), 7.50 (m, 2H). 13C
NMR (acetone-d6): δ 56.05, 56.40, 115.08, 115.97, 119.72,
130.76, 135.77, 139.16, 163.49, 164.88.
Exp er im en ta l Section
Gen er a l Asp ects. Proton and carbon NMR were obtained
either on a 270 or 400 MHz NMR and are referenced internally
to TMS. Melting points were taken in open capillaries on a
Thomas-Hoover melting point apparatus and are uncorrected.
Silica gel chromatography was carried out on silica gel 60 PF254
purchased from EM Science. Combustion analysis was ob-
tained from Atlantic Microlabs, Inc., in Norcross, GA. IR
analysis was obtained on a Perkin-Elmer 1600 Series FTIR.
Oxone (2KHSO5, KHSO4, K2SO4), sulfur dioxide (lecture
bottle), thioanisole (99%), 4-methoxybenzenethiol (97%), m-
chloroperoxybenzoic acid (80-90%), sodium sulfide nonahy-
drate (98%), 4-methoxybenzenesulfonyl chloride (99%), ethyl-
enediaminetetraacetic acid disodium salt dihydrate (99%), and
sulfuryl chloride (97%), SO2Cl2, were obtained from Aldrich
and used without further purification. Anhydrous potassium
carbonate and sodium bicarbonate were purchased from J . T.
Baker and used as received. Anhydrous diethyl ether (Mallin-
krodt), anhydrous magnesium sulfate (Spectrum), and absolute
ethanol (McCormick distilling Co., Inc.) were used as received.
Sulfur dichloride, SCl2, (Aldrich, 80% technical) was twice
distilled under N2 into a flask containing phosphorus pen-
tachloride. Thionyl chloride, SOCl2 (Aldrich, 97%), was re-
fluxed over S8, distilled, and redistilled over boiled linseed oil.
Sulfur monochloride, S2Cl2 (Aldrich, 98%), was distilled at
reduced pressure prior to use. Pyridine was purchased from
Fisher and stored over potassium hydroxide. Dimethyl sul-
foxide (Fisher Biotech.) was stirred over calcium hydride,
distilled under reduced pressure, and stored under nitrogen
over 4A sieves. Acetone (Spectrum) was refluxed over potas-
sium permanganate, distilled, dried over potassium carbonate,
filtered, and redistilled. (Storing purified acetone over mo-
lecular sieves is not recommended.) A mixture of hexanes (n-
hexane, 2-methylpentane, 3-methylpentane, 2,3-dimethylbu-
tane, methylcyclopentane, and 2,2-dimethylpentane (Fisher))
was dried over anhydrous calcium chloride, distilled, and
stored over 4A sieves. Methylene chloride (J . T. Baker) was
also dried over calcium chloride and distilled prior to use.
Benzene (Spectrum) was refluxed over phosphorus pentoxide
and distilled prior to use. 1,1,1-Trifluoroacetone (Acros, 98+%)
was distilled at low temperature before use. Acetone-d6,
99.9%, was purchased from Cambridge Isotope Laboratories.
P r ep a r a tion of Dioxir a n es. Dimethyldioxirane (DMD)
and (trifluoromethyl)methyldioxirane (TFD) were prepared
according to literature procedures.30-32 These dioxiranes were
stored at -20 °C and protected from light. The concentrations
of the pale yellow solutions were determined by titration with
thioanisole to its sulfoxide/sulfone and quantifying by 1H NMR.
The very reactive TFD was used immediately after prepara-
tion.
P r ep a r a tion of Bis(p-m eth oxyp h en yl)tr isu lfa n e. Bis-
(p-methoxyphenyl) trisulfane was prepared according to Harpp’s
procedure.37 The product was purified by recrystallization
with hexanes and obtained in a 68% yield. Mp: 73-74 °C
(lit.5 mp 73-74 °C). 1H NMR (acetone-d6): δ 3.81 (s, 6H), 6.90
(m, 4H), 7.50 (m, 4H). 13C NMR (acetone-d6): δ 55.87, 115.79,
127.65, 134.82, 161.77.
P r ep a r a tion of Bis(p-m eth oxyp h en yl)tetr a su lfa n e. A
literature procedure38 was followed producing a 98% yield of
crystals with mp 54-56.5 °C (lit.39 mp 56.5-58.5 °C). 1H NMR
(acetone-d6): δ 3.84 (s, 6H), 6.98 (m, 4H), 7.53 (m, 4H). 13C
NMR (acetone-d6): δ 55.93, 115.95, 127.31, 135.09, 162.11.
P r ep a r a tion of Bis(p-m eth oxyp h en yl)tr isu lfa n e 2-Ox-
id e. The Field method28 was followed, and the product was
obtained in
a 75% yield after recrystallization from 1:1
hexanes/methylene chloride. Mp: 94-97 °C (lit.28 mp 101-
101.5 °C). When further purification was necessary, the
chromatotron was used with a 2 mm silica gel plate and 4:1
hexanes/ethyl acetate as eluant. 1H NMR (acetone-d6): δ 3.87
(s, 6H), 7.06 (m, 4H), 7.57 (m, 4H). 13C NMR (CDCl3): δ 55.43,
115.03, 120.16, 138.08, 161.96.
P r ep a r a tion of Bis(p-m eth oxyp h en yl)tr isu lfa n e 1,1-
Dioxid e. A literature method40 was used to prepare the
sodium thiosulfonate salt (p-MeOPhSO2S-Na+). After recrys-
tallization with absolute ethanol, a 19% yield (not optimized)
was obtained. Both IR and NMR data were consistent with
formation of this salt. An Organic Synthesis41 procedure was
used to make p-methoxyphenylsulfenyl chloride. This dark,
orange-red compound distilled at 2 mmHg (99-103 °C) in a
71% yield. Following a 1927 procedure,42 the sodium thiosul-
fonate salt was first ground into a powder and then added to
the p-methoxyphenylsulfenyl chloride, which was dissolved in
anhydrous diethyl ether under a nitrogen atmosphere. After
workup and recrystallization with hexanes, a 50.4% yield of
clear crystals was collected. Mp: 59-61.5 °C. 1H NMR
(acetone-d6): δ 3.83 (s, 3H), 3.95 (s, 3H), 6.89 (m, 2H), 7.12
(m, 2H), 7.46 (m, 2H), 7.87(m, 2H). 13C NMR (acetone-d6): δ
55.95, 56.48, 115.55, 115.84, 125.34, 131.36, 134.77, 135.30,
162.18, 165.47. IR: (KBr) 1138, 1324 cm-1 (SO2 stretching).
(33) Yiannios, C. N.; Karabinos, J . V. J . Org. Chem. 1963, 28, 3246-
3248.
(34) Fehe´r, F.; Kurz, D. Z. Naturforsch. 1968, 23b, 1030-1033.
(35) Vinkler, E.; Klivenyi, F. Acta Chim. Acad. Sci. 1957, 11, 15-
22.
(36) Palumbo, G.; Caputo, R. Synthesis 1981, 11, 888-890.
(37) Harpp, D. N.; Smith, R. A. J . Org. Chem. 1979, 44, 4140-4144.
(38) Derbesy, G.; Harpp, D. N. Tetrahedron Lett. 1994, 35, 5381-
5384.
(39) Kawamura, S.; Horii, T.; Tsurugi, J . J . Org. Chem. 1971, 36,
3677-3680.
(40) Mintel, R.; Westley, J . J . Biol. Chem. 1966, 241, 3381-3385.
(41) Barrett, A. G. M.; Dhanak, D.; Graboski, G. G.; Taylor, S. J . In
Organic Synthesis; White, D., Ed.; J ohn Wiley & Sons: New York,
1989; Vol. 68; pp 8-13.
(42) Brooker, L. G. S.; Child, R.; Smiles, S. J . Chem. Soc. 1927,
1384-1388.
P r ep a r a tion of Bis(p-m eth oxyp h en yl)d isu lfa n e a n d
Its Oxid ized Der iva tives. Bis(p-methoxyphenyl)disulfane
was synthesized by a dimethyl sulfoxide oxidation33 of p-
methoxythiophenol in a 76% yield. Mp: 42.5-43.5 °C (lit.34
(30) Adam, W.; Bialas, J .; Hadjiarapoglou, L. Chem. Ber. 1991, 124,
2377.
(31) Mello, R.; Fiorentino, M.; Sciacovelli, O.; Curci, R. J . Org. Chem.
1988, 53, 3890-3891.
(32) Mello, R.; Fiorentino, M.; Fusco, C.; Curci, R. J . Am. Chem. Soc.
1989, 111, 6749-6757.

Reactions of Bis(p-methoxyphenyl)trisulfane
J . Org. Chem., Vol. 61, No. 22, 1996 7917
Anal. Calcd for C14H14O4S3: C, 49.10; H, 4.12; S, 28.09.
Found: C, 49.17; H, 4.20; S, 27.99.
was removed under reduced pressure followed by dissolution
into an NMR tube.
Gen er a l Tr isu lfa n e Dioxir a n e Oxid a tion P r oced u r es.
Room-temperature reactions were carried out by adding 0.2-
3.0 equiv amounts of dioxirane to 0.10 mmol of the trisulfane
dissolved in 2 mL of acetone (0.05 M). The mixture was stirred
from 2 to 24 h in the dark. The solvent was removed under
reduced pressure followed by dissolution into an NMR tube.
Acetone-d6 was employed as the NMR solvent as it afforded
the best separation of peaks in the spectra.
Low-temperature TFD reactions were carried out by dis-
solving 0.05 M trisulfane 2-oxide in a 4 mm NMR tube
containing acetone-d6. Both the TFD and 2-oxide were main-
tained at -78 °C in a Dewar. TFD (0.5 equiv) was added to
the tube and immediately placed in the NMR at -80 °C. The
solution turned a deep yellow color upon TFD addition. The
temperature was then raised at 20 °C intervals, and the
spectra observed.
Low-temperature reactions were carried out by dissolving
0.02 mmol (0.037 M) of trisulfane in a 4 mm NMR tube
containing acetone-d6, cooling the NMR to -30 °C in 20 °C
intervals while tuning the probe on the sample, ejecting the
sample, quickly adding the dioxirane (within 15 s), followed
by immediate acquisition (16 transients). The temperature
was then raised at 10 °C intervals, and the spectra were
observed.
Low-temperature DMD reactions were attempted by adding
1 equiv of DMD to the trisulfane 2-oxide at -78, -43, and
-29 °C for at least 24 h. In each case, the reaction was very
sluggish with mainly starting material appearing in the NMR
spectrum.
Su lfu r Dioxid e Ca ta lysis of Bis(p-m eth oxyp h en yl)-
tr isu lfa n e 2-Oxid e. Approximately 1 equiv of SO2 (bp -10
°C ) was condensed into a mixture of 0.03 mmol of 2-oxide and
2 mL of acetone. This was stirred for 24 h with a -42 °C (CH3-
CN/dry ice) condensor attached. Only minimal decomposition
was observed. The sample was then allowed to stand at room
temperature for 24 h. Total decomposition did not occur, but
a 65% conversion to disulfane and trisulfane in a 1:1 ratio was
observed. A purified 2-oxide sample was stored in the freezer
(-20 °C) for 2 months with no added SO2, and only 50% of the
starting material had decomposed to disulfane and trisulfane.
NMR Ra te Mea su r em en ts. Rates were calculated by
measuring the disappearance of the 1-oxide as a function of
1
time at room temperature using H NMR. The spectra were
cut and weighed to determine the decrease in the amount of
the 1-oxide.
Gen er a l Tr isu lfa n e 2-Oxid e Dioxir a n e Oxid a tion P r o-
ced u r es. Room-temperature DMD reactions were carried out
by adding 0.2-1.0 equiv amounts of dioxirane to 0.05 M of
the trisulfane 2-oxide dissolved in various solvents (benzene,
ether, acetone, methylene chloride). The mixture was stirred
from 2-24 h in the dark. The solvent was removed under
reduced pressure followed by dissolution into an NMR tube.
Room-temperature TFD reactions were carried out by
adding 0.2-1.0 equiv of dioxirane to 0.003 M of the trisulfane
2-oxide dissolved in acetone or methylene chloride. The
mixture was stirred from 2 to 24 h in the dark. The solvent
Ack n ow led gm en t. We thank the National Science
Foundation and the donors of the Petroleum Research
Fund, administered by the American Chemical Society,
for their generous support of this research.
J O960995X