Evidence for intermolecular interaction between sulfonium and sulfide sulfur atoms and its application to synthesis of cyclic bis(disulfide) dimer

Article abstract of DOI:10.1021/jo001645k

On the basis of the remote Pummerer reaction of p-bis(alkylthio)-aromatic S-oxide, the intermolecular interaction between the sulfonium and sulfide sulfur atoms is described. (1) In marked contrast to the Pummerer reaction of 1b-d₃ with (CF₃CO)₂O (J. Org. Chem. 1999, 64, 3190-3195), the reaction of 3,3′,5,5′-tetramesityl-4-(trideuteriomethylsulfinyl)-4′- (methylthio)biphenyl (1a-d3) as a sterically hindered analogue of 1b gave only 2a-d2. (2) Both reactions of the two unsymmetrical regioisomers of 1-(ethylthio)-4-(methylthio)benzene S-oxide (5a and 5b) with (CF₃CO)₂O afforded a mixture of the mono-Pummerer products 6a and 6b, the bis-Pummerer product 7, and the bissulfide 8 in a similar ratio. The quenching at the initial stage of both reactions produced 5a, 5b, 8, and the bis-sulfoxide 10 in a similar ratio. These results indicate the equilibrium in the intermolecular interaction between the sulfur atoms. (3) The reaction of the p-bis(benzylthio)aromatic S-oxide 16 with (CF₃SO₂)₂O gave the cyclic bis(disulfide) dimer 17 for the diphenyl sulfide and diphenylmethane spacers or the cyclic tetrakis(disulfide) tetramer 19 for the benzene and biphenyl spacers via the debenzylation of an intermolecular dithia dication. The cyclic bis(dithia dication) dimer A resulting from the intermolecular interaction between the sulfonium and sulfide sulfur atoms is proposed as an intermediate throughout the present reactions.

Full text of DOI:10.1021/jo001645k

J . Org. Chem. 2001, 66, 2085-2090
2085
Evid en ce for In ter m olecu la r In ter a ction betw een Su lfon iu m a n d
Su lfid e Su lfu r Atom s a n d Its Ap p lica tion to Syn th esis of Cyclic
Bis(d isu lfid e) Dim er
Kenji Kobayashi,* Emiko Koyama, Chihiro Kono, Kazuhiko Namatame,
Kazunori Nakamura, and Naomichi Furukawa*,†
Department of Chemistry, University of Tsukuba, Tsukuba, Ibaraki 305-8571, J apan
kenjinor@staff.chem.tsukuba.ac.jp
Received November 20, 2000
On the basis of the remote Pummerer reaction of p-bis(alkylthio)-aromatic S-oxides, the inter-
molecular interaction between the sulfonium and sulfide sulfur atoms is described. (1) In marked
contrast to the Pummerer reaction of 1b-d 3 with (CF3CO)2O (J . Org. Chem. 1999, 64, 3190-3195),
the reaction of 3,3′,5,5′-tetramesityl-4-(trideuteriomethylsulfinyl)-4′-(methylthio)biphenyl (1a -d 3)
as a sterically hindered analogue of 1b gave only 2a -d 2. (2) Both reactions of the two unsymmetrical
regioisomers of 1-(ethylthio)-4-(methylthio)benzene S-oxide (5a and 5b) with (CF3CO)2O afforded
a mixture of the mono-Pummerer products 6a and 6b, the bis-Pummerer product 7, and the bis-
sulfide 8 in a similar ratio. The quenching at the initial stage of both reactions produced 5a , 5b,
8, and the bis-sulfoxide 10 in a similar ratio. These results indicate the equilibrium in the
intermolecular interaction between the sulfur atoms. (3) The reaction of the p-bis(benzylthio)-
aromatic S-oxide 16 with (CF3SO2)2O gave the cyclic bis(disulfide) dimer 17 for the diphenyl sulfide
and diphenylmethane spacers or the cyclic tetrakis(disulfide) tetramer 19 for the benzene and
biphenyl spacers via the debenzylation of an intermolecular dithia dication. The cyclic bis(dithia
dication) dimer A resulting from the intermolecular interaction between the sulfonium and sulfide
sulfur atoms is proposed as an intermediate throughout the present reactions.
Ch a r t 1
In tr od u ction
Despite the accumulation of a large body of information
about dithia dications formed by intramolecular through-
space interactions between sulfur atoms,1 dithia dications
formed by intermolecular interactions have not been
studied intensively because a transannular effect is not
available.2 Such formation of dithia dications by inter-
molecular interactions is worth pursuing from the view-
point of molecular assembly,3 as well as from the per-
spective of organosulfur conducting materials.4 Recently,
we have reported a remote Pummerer reaction of p-bis-
(methylthio)-aromatic S-oxides with (CF3CO)2O and have
proposed a cyclic bis(dithia dication) dimer A and/or a
linear dithia dication dimer B as intermediates (Chart
1, R ) CH3, X- ) CF3CO2-), arising via intermolecular
through-space interaction between the sulfonium and
sulfide sulfur atoms.5-7 To elucidate the intermolecular
interaction between sulfur atoms more clearly, and to
show its generality, other approaches and molecular
designs are required.
Intramolecular dithia dications with flexible or strained
conformations, which are generated from bis-sulfide
S-oxides and 1 equiv of (CF3SO2)2O in CH3CN, cause a
facile dealkylation to form the corresponding thiasulfo-
nium salt and alkyl cation.7,8 In particular, a dithia
dication with benzyl groups causes a double-debenzyla-
tion to form the corresponding disulfide.7,9 In the remote
Pummerer reaction of p-bis(methylthio)-aromatic S-ox-
ides with (CF3CO)2O, if a cyclic bis(dithia dication) dimer
A is truly an intermediate, it should be possible to form
† Present address: Foundation for Advancement of International
Science, 586-9 Akatsuka-Ushigahuchi, Tsukuba, Ibaraki 305-0062,
J apan.
(1) (a) Musker, W. K. Acc. Chem. Res. 1980, 13, 200-206. (b)
Furukawa, N. Bull. Chem. Soc. J pn. 1997, 70, 2571-2591 and
references therein.
(2) Nenajdenko, V. G.; Shevchenko, N. E.; Balenkova, E. S. Tetra-
hedron 1998, 54, 5353-5362.
(3) Lehn, J .-M. Supramolecular Chemistry: Concepts and Perspec-
tives; VCH: Weinheim, 1995.
(4) (a) Nakasuji, K.; Sasaki, M.; Kotani, T.; Murata, I.; Enoki, T.;
Imaeda, K.; Inokuchi, H.; Kawamoto, A.; Tanaka, J . J . Am. Chem. Soc.
1987, 109, 6970-6975. (b) Heywang, G.; Roth, S. Angew. Chem., Int.
Ed. Engl. 1991, 30, 176-177. (c) Adam, D.; Schuhmacher, P.; Sim-
merer, J .; Ha¨ussling, L.; Siemensmeyer, K.; Etzbach, K. H.; Ringsdorf,
H.; Haarer, D. Nature 1994, 371, 141-143.
(5) Kobayashi, K.; Koyama, E.; Namatame, K.; Kitaura, T.; Kono,
C.; Goto, M.; Obinata, T.; Furukawa, N. J . Org. Chem. 1999, 64, 3190-
3195.
(6) Koyama, E.; Kobayashi, K.; Horn, E.; Furukawa, N. Tetrahedron
Lett. 1999, 40, 8833-8836.
(7) Furukawa, N.; Kobayashi, K.; Sato, S. J . Organomet. Chem.
2000, 611, 116-126.
(8) (a) Shima, H.; Kobayashi, R.; Nabeshima, T.; Furukawa, N.
Tetrahedron Lett. 1996, 37, 667-670. (b) Naka, H.; Maruyama, T.;
Sato, S.; Furukawa, N. Tetrahedron Lett. 1999, 40, 345-348.
(9) Kobayashi, K.; Koyama, E.; Goto, M.; Noda, C.; Furukawa, N.
Chem. Commun. 2000, 1667-1668.
10.1021/jo001645k CCC: $20.00 © 2001 American Chemical Society
Published on Web 03/01/2001

2086 J . Org. Chem., Vol. 66, No. 6, 2001
Kobayashi et al.
Sch em e 1
a cyclic bis(disulfide) dimer or corresponding cyclic di-
sulfide oligomers10-14 via the debenzylation of A (Chart
1, R ) CH2Ph, X- ) CF3SO3-) by using a combination of
a benzyl group and (CF3SO2)2O in place of the methyl
group and (CF3CO)2O. Herein, we report an essential role
for the intermolecular through-space interaction between
the sulfonium and sulfide sulfur atoms in the remote
Pummerer reaction5-7 by using substrates with bulky and
unsymmetrical substituents. We also describe the syn-
theses of a cyclic bis(disulfide) dimer and a cyclic tetrakis-
(disulfide) tetramer as the result of the debenzylation of
the cyclic bis(dithia dication) dimer A (R ) CH2Ph, X- )
CF3SO3-).
Resu lts a n d Discu ssion
Evid en ce for In ter m olecu la r In ter a ction betw een
Su lfon iu m a n d Su lfid e Su lfu r Atom s: Rea ction
betw een p-Bis(m eth ylth io)-Ar om a tic S-Oxid e w ith
a Bu lk y Su bstitu en t a n d (CF 3CO)2O. To elucidate the
intermolecular through-space interaction between the
sulfur atoms more clearly, we have designed 3,3′,5,5′-
tetramesityl-4-(methylsulfinyl)-4′-(methylthio)biphenyl
(1a )15 as a sterically hindered analogue of 4-(methylsul-
finyl)-4′-(methylthio)biphenyl (1b).5,7 From consideration
of the model of 1a , we infer that the mesityl groups at
the 3,5-positions of the biphenyl spacer could completely
inhibit the intermolecular interaction between the sulfur
atoms.
chosen the two unsymmetrical regioisomers of 1-(eth-
ylthio)-4-(methylthio)benzene S-oxide (5) as a model
substrate for the remote Pummerer reaction.
The reaction of 1a with 5 equiv of (CF3CO)2O in CH2-
Cl2, at -20 °C to room temperature, produced the mono-
Pummerer product 2a exclusively in 88% yield. The
reaction of trideuterium-labeled 1a -d 3 with (CF3CO)2O
quantitatively produced only 2a-d2 (Scheme 1), in marked
contrast to 1b-d 3, wherein the mono-Pummerer products
2b-d 3 and 2b-d 2, the bis-Pummerer product 3b-d 2, and
the bis-sulfide 4b-d 3 occur in a 5.0:0.5:1.0:0.8 ratio.5 This
shows that a normal Pummerer reaction at the methyl-
sulfinyl group dominates exclusively in 1a . These results
clearly indicate that neither the intermolecular through-
space nor the intramolecular through-bond interactions
between the sulfur atoms are available for the reaction
of 1a . Therefore, in the remote Pummerer reaction of
p-bis(methylthio)-aromatic S-oxide with (CF3CO)2O,5 the
intermolecular through-space interaction between the
sulfur atoms, which forms the intermediates A and/or
B, is essentially a much more favorable process than the
intramolecular through-bond interaction between the
sulfur atoms leading to the intermediate C (Chart 1).
Equ ilibr iu m in In ter m olecu la r In ter a ction be-
tw een Su lfu r Atom s: Rea ction of Un sym m etr ica l
p-Bis(su lfid e)-Ar om a tic S-Oxid e w ith (CF 3CO)2O. To
identify an equilibrium in the intermolecular through-
space interaction between the sulfur atoms, we have
The reaction of 1-(ethylsulfinyl)-4-(methylthio)benzene
(5a ) with 5 equiv of (CF3CO)2O in CDCl3, at -20 °C to
room temperature, produced a mixture of the mono-
Pummerer products 6a and 6b, the bis-Pummerer prod-
uct 7, and the bis-sulfide 8, in a quantitative ratio of 1.0:
2.2:0.2:0.1 (Scheme 2). The formation of 6a results from
the reaction at the ethyl group, whereas 6b results from
the reaction at the methyl group. Treatment of 1-(eth-
ylthio)-4-(methylsulfinyl)benzene (5b ) with (CF3CO)2O
under the same conditions also exclusively produced a
mixture of 6a , 6b, 7, and 8, in a ratio of 1.0:2.5:0.6:0.4.
In general, the Pummerer reaction occurs at the alkyl-
sulfinyl group, but not at the alkylthio group. However,
both Pummerer reactions of 5a and 5b take place at both
groups, and give approximately similar product ratios.
Both reactions were monitored by 1H NMR spectroscopy
in CDCl3 at -20 °C, as shown in Figure 1. Upon addition
of (CF3CO)2O, 5a and 5b disappeared immediately. In
reactions both of 5a after 1 h (Figure 1b), and 5b after
40 min (Figure 1d), both trifluoroacetoxysulfonium salts
9a and 9b were observed as intermediates, together with
the products. In Figures 1b and 1d, it is noted that the
ratio of the intermediates is 9a > 9b, whereas the
product ratio is 6a < 6b. These results strongly suggest
that the equilibrium between 9a and 9b occurs via the
same intermediates, such as A and/or B, as a result of
the intermolecular through-space interaction between the
sulfonium and sulfide sulfur atoms (Scheme 2).
(10) Wong, D. T.-M.; Marvel, C. S. J . Polym. Sci. 1976, 14, 1637-
1644.
(11) Raasch, M. S. J . Org. Chem. 1979, 44, 2629-2632.
(12) (a) Houk, J .; Whitesides, G. M. J . Am. Chem. Soc. 1987, 109,
6825-6836. (b) Houk, J .; Whitesides, G. M. Tetrahedron 1989, 45, 91-
102.
(13) Ding, Y.; Hay, A. S. Macromolecules 1996, 29, 6386-6392.
(14) (a) Bottino, F.; Foti, S.; Pappalardo, S. Tetrahedron 1976, 32,
2567-2570. (b) Pahor, N. B.; Calligaris, M.; Randaccio, L.; Bottino,
F.; Pappalardo, S. Gazz. Chim. Ital. 1980, 110, 227-231.
(15) Yoshifuji and co-workers reported the synthesis of 3,3′,5,5′-
tetramesityl-4,4′-diiodobiphenyl as a new sterically protecting group
which is the starting material for 1a . Tsuji, K.; Sasaki, S.; Yoshifuji,
M. Tetrahedron Lett. 1999, 40, 3203-3206.
Further evidence that the equilibrium between 9a and
9b occurs via the same intermediates, such as A and/or
B, is drawn from the quenching experiment at the initial
stage of the Pummerer reaction, which acts as a snapshot
of the reaction.5 When the reaction of 5a with 5 equiv of
(CF3CO)2O in CH2Cl2 at -20 °C was quenched quickly,
in ∼10 s, with aqueous NaHCO3, a mixture of 5a , 5b, 8,
and the bis-sulfoxide 10 was obtained exclusively in 47%,

Interaction between Sulfonium and Sulfide Sulfur Atoms
J . Org. Chem., Vol. 66, No. 6, 2001 2087
Sch em e 2
similar product ratio in both cases indicates that the
equilibrium between 9a and 9b occurs via the same
intermediates, such as A and/or B. No formation of
Pummerer products at the initial stage indicates that this
intermolecular interaction between the sulfur atoms is
a much more favorable process than the abstraction of
an R-proton from the sulfonium group that leads to the
Pummerer products.
Evid en ce for Cyclic Bis(d ith ia d ica tion ) Dim er
A: Syn th eses of Cyclic Bis(d isu lfid e) Dim er a n d
Cyclic Tetr a k is(d isu lfid e) Tetr a m er via Deben zy-
la tion of In ter m olecu la r Dith ia Dica tion . We have
extended the debenzylation of intramolecular dithia
dications7-9 to that of intermolecular dithia dications to
prove that a cyclic bis(dithia dication) dimer A is an
intermediate (R ) CH2Ph, X- ) CF3SO3-). The reaction
of a 1:1 mixture of 4-methylbenzyl-4′-methylphenyl sul-
fide (11) and its sulfoxide (12) with 1 equiv of (CF3SO2)2O
in CH2Cl2-CH3CN (v/v 4:1), at -20 °C to room temper-
ature for 2 h, quantitatively produced bis(4-methylphen-
yl) disulfide (13) and N-(4-methylbenzyl)acetamide (14b)
in a 1:2 ratio after quenching with H2O. This result shows
that double-debenzylation is also applicable to inter-
molecular dithia dications.
Based on this result, the reaction of the p-bis(benz-
ylthio)-aromatic S-oxide (16) (aromatic spacer ) benzene
(a ), biphenyl (b), diphenyl sulfide (c), and diphenyl-
methane (d )) with (CF3SO2)2O was carried out. The
mono-sulfoxide 16a (50 mM) in CH2Cl2-CH3CN (v/v 4:1)
was treated with 1 equiv of (CF3SO2)2O at -40 °C, and
the resulting mixture was allowed to warm to room
temperature (Scheme 3). The reaction was also monitored
by 1H NMR spectroscopy in CDCl3-CD3CN (v/v 2:1)
(Figure 2). Upon addition of (CF3SO2)2O at -40 °C, 16a
immediately disappeared and the corresponding sulfo-
nium salt was observed. At -20 °C, the 1H NMR
spectrum of the yellow homogeneous solution showed
F igu r e 1. 1H NMR spectra for the reaction mixture of 5 (68
mM) with (CF3CO)2O (5 equiv) in CDCl3 at -20 °C. (a) 5a , (b)
5a + (CF3CO)2O after 1 h, (c) 5a (or 5b) + (CF3CO)2O after 4
h, (d) 5b + (CF3CO)2O after 40 min, and (e) 5b.
29%, 8%, and 4% yields, respectively, instead of Pum-
merer products. The quenching of the reaction of 5b
under the same conditions gave a mixture of 5a , 5b, 8,
and 10 in 49%, 28%, 2%, and 6% yields, respectively. In
both cases, the product ratio of 5a /5b is almost the same
(approximately 1.7:1). The formation of 8 and 10 should
result from intermediates A and/or B. The fact of a

2088 J . Org. Chem., Vol. 66, No. 6, 2001
Kobayashi et al.
Ta ble 1. Rea ction s of 16 w ith (CF 3SO2)2O a n d of a 1:1
Mixtu r e of 20 a n d 21 w ith (CF 3SO2)2Oa
yield, %
entry substrateb
spacer
benzene
biphenyl
diphenyl sulfide
diphenyl sulfide
Ar
Ph
Ph
Ph
17 18 19 14
1
2
3
4
5
6
7
16a
16b
16c
16c′
16d
0
0
0
0
0
0
0
0
0
81 93
45 61
51
0
0
0
64
67
50
p-tolyl 34
diphenylmethane Ph
63
0
20a + 21a benzene
20c′ + 21c′ diphenyl sulfide
Ph
71 76
39
p-tolyl 27
0
a
Carried out in a ratio of 16:(CF3SO2)2O ) 1:1 or in a ratio of
20:21:(CF3SO2)2O ) 1:1:2 in CH2Cl2-CH3CN (v/v 4:1) at -40 °C
b
to room temperature for 4 h. [16] ) 50 mM and [20] ) [21] ) 25
mM.
Sch em e 4
F igu r e 2. 1H NMR spectra for the reaction mixture of 16 (50
mM) with (CF3SO2)2O (1 equiv) in CDCl3-CD3CN (v/v 2:1).
(a) 16a at -20 °C, (b) 16a + (CF3SO2)2O at -20 °C for 40 min,
(c) 16a + (CF3SO2)2O at 0 °C for 20 min, (d) 16c at 0 °C, (e)
16c + (CF3SO2)2O at 0 °C for 30 min, and (f) 16c + (CF3SO2)2O
at room temperature for 40 min.
Sch em e 3
complete debenzylation, wherein the only N-benzyl-
acetonitrile adduct was observed at δ 5.38 in the region
of the benzyl groups (Figure 2b). At 0 °C, a pale yellow
solid precipitated while the solution color faded. Treat-
ment of the supernatant with aqueous NaHCO3 produced
N-benzylacetamide (14a ) in 93% yield. The pale yellow
solid (81% yield) was found to be the cyclic tetrakis-
dimer 17 and the cyclic tris(disulfide) trimer 18 were not
observed. (2) On the other hand, the reaction of 16,
bearing the diphenyl sulfide (c) and diphenylmethane (d )
spacers, with (CF3SO2)2O produced the cyclic bis(disul-
fide) dimers 17c and 17d , respectively (entries 3 and 5).
The corresponding cyclic trimer 18 and the cyclic tet-
1
(disulfide) tetramer 19a , which was characterized by H
1
ramer 19 were not observed. In the H NMR spectra, the
and 13C NMR spectra and FAB-MS and MALDI-TOF-
MS spectra. Treatment of 19a with NaBH4 in THF,
followed by the addition of iodomethane, produced 1,4-
bis(methylthio)benzene (15) in 56% yield.
debenzylation of 16c proceeded in approximately 55% of
molecules, at 0 °C over 30 min (Figure 2e), and to
completion at room temperature over 40 min (Figure 2f)
to give 17c (51% yield) and 14a (64% yield). Thus, the
debenzylation of 16c is slower than that of 16a . The
reaction mixture remained homogeneous during the
course of the reaction of 16c. (3) The reaction of a 1:1
mixture of the bis-sulfide 20 and the bis-sulfoxide 21 with
2 equiv of (CF3SO2)2O was also observed. The reaction
of 20a and 21a (spacer ) benzene, Ar ) phenyl) produced
19a (entry 6), whereas the reaction of 20c′ and 21c′
(spacer ) diphenyl sulfide, Ar ) p-tolyl) gave 17c (entry
7).
Several representative results obtained under the same
conditions are summarized in Table 1 and Scheme 4.16
The following features are noteworthy. (1) The reaction
of the mono-sulfoxides 16, bearing the benzene (a ) and
biphenyl (b) spacers, with (CF3SO2)2O gave the cyclic
tetrakis(disulfide) tetramers 19a and 19b, respectively
(entries 1 and 2). The corresponding cyclic bis(disulfide)
(16) The other products except for the cyclic dimer 17 and cyclic
tetramer 19 were unidentified linear oligomers.

Interaction between Sulfonium and Sulfide Sulfur Atoms
Sch em e 5
J . Org. Chem., Vol. 66, No. 6, 2001 2089
The oxidation of 1,4-benzenedithiol with iodine10,12b or
Cu(I)-O2-TMEDA13 gives the corresponding cyclic tris-
(disulfide) trimer 18a as a main product, but does not
produce the cyclic tetramer 19a .17 The oxidation of 4,4′-
biphenyldithiol also produces the cyclic trimer 18b
without formation of 19b.13 The oxidation of 4,4′-thiobis-
(benzenethiol) gives an approximately 1:1 mixture of the
cyclic dimer 17c and the cyclic trimer 18c.13 The oxida-
tion of 2,2-bis(4-mercaptophenyl)propane also gives a
similar result.13 These results are in marked contrast to
those for the present reaction of 16 with (CF3SO2)2O. It
is noted that the reaction of 16a ,b with (CF3SO2)2O gives
the cyclic tetramers 19a ,b, respectively, whereas the
reaction of 16c,d with (CF3SO2)2O produces the cyclic
dimers 17c,d , respectively. In none of the present reac-
tions are cyclic trimers 18 formed.
These results undoubtedly indicate that the present
reaction of 16 with (CF3SO2)2O does not involve the
oxidative coupling of the corresponding aromatic dithiols
or dithiyl radicals during the course of the reaction.10-14
The debenzylation of 16 with (CF3SO2)2O should require
the formation of a dithia dication.7-9 On the basis of these
results, the following mechanism is plausible, as shown
in Scheme 5. At first, the reaction of the p-bis(benzylthio)-
aromatic S-oxide 16 with (CF3SO2)2O gives the trifluo-
romethanesulfonyloxysulfonium salt D. Subsequently,
the intermolecular interaction between the sulfonium
sulfur atom of one D molecule and the sulfide sulfur atom
of another D could produce the cyclic bis(dithia dication)
dimer A as an intermediate. Finally, the debenzylation
of A could produce the cyclic bis(disulfide) dimer 17. This
could explain why no detectable cyclic tris(disulfide)
trimer 18 was formed in the present reaction. The cyclic
bis(disulfide) dimers 17a ,b, bearing the benzene and
biphenyl spacers, would be highly strained due to aro-
matic-aromatic repulsion and hence would be easily
expanded to produce the cyclic tetrakis(disulfide) tet-
ramers 19a ,b. Thus, the formation of the cyclic tetrakis-
(disulfide) tetramers 19a ,b from 16a ,b, and of the cyclic
bis(disulfide) dimers 17c,d from 16c,d , strongly supports
the role of cyclic bis(dithia dication) dimer A as an
intermediate in the intermolecular through-space inter-
action between the sulfonium and sulfide sulfur atoms.
Further evidence for this intermediate comes from the
reaction of bis-sulfide 20 and bis-sulfoxide 21. In fact,
the reaction of a 1:1 mixture of 20a and 21a gave the
same cyclic tetramer 19a as the reaction of the mono-
sulfoxide 16a , and the reaction of a 1:1 mixture of 20c′
and 21c′ gave the same cyclic dimer 17c as the reaction
of 16c′.
Con clu sion
By using substrates bearing bulky and unsymmetrical
substituents, we have demonstrated that the inter-
molecular through-space interaction between the sulfo-
nium and sulfide sulfur atoms plays an essential role in
the remote Pummerer reaction of the p-bis(alkylthio)-
aromatic S-oxides with (CF3CO)2O. There is an equilib-
rium in the intermolecular interaction between the
sulfonium and sulfide sulfur atoms. This intermolecular
through-space interaction is a much more favorable
process than the intramolecular through-bond interaction
between sulfur atoms and the abstraction of an R-proton
from the sulfonium group that leads to the Pummerer
products. We have proposed the cyclic bis(dithia dication)
dimer A as an intermediate in the remote Pummerer
reaction, resulting from the intermolecular through-space
interaction between the sulfonium and sulfide sulfur
atoms. On the basis of these results, we have demon-
strated the syntheses of the cyclic bis(disulfide) dimer
and the cyclic tetrakis(disulfide) tetramer via the deben-
zylation of the cyclic bis(dithia dication) dimer A that
arises from the reaction of p-bis(benzylthio)-aromatic
S-oxides and (CF3SO2)2O. The results presented here may
provide a basis for the use of the intermolecular sulfur-
sulfur interaction as a supramolecular synthon3,18 and
for a greater understanding of the electric conductivity
mechanisms of materials bearing sulfur functional-
ities.4,19
(18) Desiraju, G. R. Angew. Chem., Int. Ed. Engl. 1995, 34, 2311-
2327.
(19) (a) Miller, L. L.; Mann, K. R. Acc. Chem. Res. 1996, 29, 417-
423. (b) Graf, D. D.; Duan, R. G.; Campbell, J . P.; Miller, L. L.; Mann,
K. R. J . Am. Chem. Soc. 1997, 119, 5888-5899. (c) Barclay, T. M.;
Cordes, A. W.; de Laat, R. H.; Goddard, J . D.; Haddon, R. C.; J eter, D.
Y.; Mawhinney, R. C.; Oakley, R. T.; Palstra, T. T. M.; Patenaude, G.
W.; Reed, R. W.; Westwood, N. P. C. J . Am. Chem. Soc. 1997, 119,
2633-2641.
(17) The oxidation of tetrafluoro-1,4-benzenedithiol with dimethyl
sulfoxide gives the cyclic tetramer 19, whereas 1,4-benzenedithiol by
this oxidation method forms polymers.11

2090 J . Org. Chem., Vol. 66, No. 6, 2001
Kobayashi et al.
N-(4-Meth ylben zyl)a ceta m id e (14b): 1H NMR (CDCl3) δ
2.00 (s, 3H), 2.33 (s, 3H), 4.37 (d, J ) 5.7 Hz, 2H), 5.83 (brs,
1H), 7.15 (s, 4H); EI-MS m/z 163 (M+).
Exp er im en ta l Section
Gen er a l. 1H NMR spectra were recorded at 270 or 400
MHz, and 13C NMR spectra were taken at 67.5 or 100 MHz.
Mass spectra were obtained by EI, FAB (m-nitrobenzyl alcohol
as a matrix), or MALDI-TOF (dithranol as a matrix) methods.
Preparative HPLC was performed on a J apan Analytical
Industry Co., Ltd., model LC-908. CH2Cl2 and CH3CN were
distilled from CaH2 under N2, and THF was distilled from
sodium-benzophenone ketyl under N2. NMR solvents for
monitoring reactions were dried over molecular sieves 4A.
(CF3CO)2O and (CF3SO2)2O were purchased from Wako Pure
Chemical Industries, Ltd. and used without further purifica-
tion.
P u m m er er Rea ction of 1a w ith (CF 3CO)2O. To a solu-
tion of 1a (30.0 mg, 0.0408 mmol) in CH2Cl2 (5 mL) at -20 °C
under an Ar atmosphere was added (CF3CO)2O (29 µL, 0.21
mmol). The reaction mixture was allowed to warm to room
temperature for 2 h, and saturated aqueous NaHCO3 was
added to the mixture. The aqueous layer was quickly extracted
with CH2Cl2. The organic layer was washed with brine and
dried over MgSO4. After evaporation of solvent, an analytically
pure sample of 2a was obtained (29.7 mg, 88%) as a pale yellow
solid.
3,3′,5,5′-Tetr am esityl-4-[(tr iflu or oacetoxy)m eth ylth io)]-
4′-(m eth ylth io)bip h en yl (2a ): mp 216-218 °C; 1H NMR
(CDCl3) δ 1.65 (s, 3H), 1.98 (s, 12H), 2.00 (s, 12H), 2.25 (s,
12H), 4.79 (s, 2H), 6.86 (s, 4H), 6.87 (s, 4H), 7.24 (s, 2H), 7.31
(s, 2H); 13C NMR (CDCl3) δ 17.4, 20.4, 20.6, 20.8, 21.2, 71.0,
114.1 (1J CF ) 283.8 Hz), 127.5, 127.9, 128.1, 128.4, 129.0, 135.0,
135.5, 135.7, 136.9, 137.2, 137.4, 138.2, 138.5, 140.5, 145.5,
145.7, 156.8 (2J CF ) 42.5 Hz); FAB-MS m/z 830 (M+). Anal.
Calcd for C52H53F3O2S2: C, 75.15; H, 6.43. Found: C, 74.94;
H, 6.75.
P u m m er er Rea ction of 5a w ith (CF 3CO)2O. To a solu-
tion of 5a (5.37 mg, 0.027 mmol) in CDCl3 (0.40 mL) at -40
°C under an Ar atmosphere in a NMR tube was added (CF3-
CO)2O (19 µL, 0.13 mmol). The resulting mixture was moni-
tored by 1H NMR spectroscopy at -20 °C. The product ratio
of 6a , 6b, 7, and 8 was determined by the integration of the
1H NMR spectrum as shown in Figure 1. Pummerer products
6a , 6b, and 7 were unstable and could not be isolated.
Qu en ch a t th e In itia l Sta ge of P u m m er er Rea ction of
5a w ith (CF 3CO)2O. To a solution of 5a (100 mg, 0.499 mmol)
in CH2Cl2 (8 mL) at -20 °C under an Ar atmosphere was
added (CF3CO)2O (350 µL, 2.48 mmol). After 10 s, saturated
aqueous NaHCO3 was added to the reaction mixture for
quenching the reaction. The aqueous layer was extracted with
CH2Cl2. The organic layer was washed with brine and dried
over MgSO4. After evaporation of solvent, the residual mixture
was separated with preparative HPLC eluted by CHCl3 to give
5a (47.0 mg, 47%), 5b (29.0 mg, 29%), 8 (7.4 mg, 8%), and 10
(4.3 mg, 4%).
R ea ct ion of 16 w it h (CF 3SO2)2O. Typ ica l P r oced u r e
(Sch em e 4, Ta ble 1, En tr y 1). To a solution of 16a (100 mg,
0.295 mmol) in CH2Cl2-CH3CN (v/v 4:1, 6.0 mL) at -40 °C
under an Ar atmosphere was added (CF3SO2)2O (56 µL, 0.33
mmol). The reaction mixture was allowed to warm to room
temperature for 4 h, and a pale yellow solid precipitated. The
resulting heterogeneous mixture was filtered and washed with
saturated aqueous NaHCO3, H2O, MeOH, Et2O, and CH2Cl2
to give 19a (33.4 mg, 81%) as a pale yellow solid. The filtrate
was extracted with CH2Cl2, and the organic layer was washed
with brine and dried over MgSO4. After evaporation of
solvents, the residual mixture was purified with preparative
HPLC eluted by CHCl3 to give 14a (81.6 mg, 93%).
Cyclic Tet r a k is(d isu lfid e) Tet r a m er (19a ), b en zen e
1
sp a cer : yield 81%; mp 251-253 °C; H NMR (CDCl3) δ 7.35
(s, 16H); 13C NMR (CDCl3) δ 127.6, 135.1; FAB-MS m/z 560
(M+); TOF-MS m/z 560 (M+). Anal. Calcd for C24H16S8‚H2O:
C, 49.79; H, 3.13. Found: C, 49.84; H, 3.09.
Cyclic Tet r a k is(d isu lfid e) Tet r a m er (19b ), b ip h en yl
sp a cer : yield 45%; mp >300 °C; 1H NMR (CDCl3) δ 7.47 (d, J
) 8.6 Hz, 16H), 7.52 (d, J ) 8.6 Hz, 16H); 13C NMR (CDCl3) δ
127.5, 128.5, 131.0, 136.4; TOF-MS m/z 865 (M+). Anal. Calcd
for C48H32S8‚3H2O: C, 62.71; H, 4.17. Found: C, 63.01; H, 3.95.
Cyclic Bis(d isu lfid e) Dim er (17c), d ip h en yl su lfid e
1
sp a cer : yield 51%; mp 266-268 °C; H NMR (CDCl3) δ 7.12
(d, J ) 8.2 Hz, 8H), 7.26 (d, J ) 8.2 Hz, 8H); 13C NMR (CDCl3)
δ 128.2, 129.0, 130.3, 132.1; FAB-MS m/z 496 (M+). Anal. Calcd
for C24H16S6‚0.5H2O: C, 56.99; H, 3.39. Found: C, 57.04; H,
3.38.
Cyclic Bis(d isu lfid e) Dim er (17d ), d ip h en ylm eth a n e
1
sp a cer : yield 63%; mp 204-206 °C; H NMR (CDCl3) δ 3.83
(s, 4H), 6.91 (d, J ) 8.1 Hz, 8H), 7.22 (d, J ) 8.1 Hz, 8H); 13
C
NMR (CDCl3) δ 41.0, 127.0, 128.1, 132.4, 134.0; TOF-MS m/z
460 (M+). Anal. Calcd for C26H20S4‚0.5H2O: C, 66.48; H, 4.51.
Found: C, 66.54; H, 4.45.
N-Ben zyla ceta m id e (14a ): 1H NMR (CDCl3) δ 2.03 (s, 3H),
4.43 (d, J ) 5.7 Hz, 2H), 5.85 (brs, 1H), 7.22-7.37 (m, 5H);
EI-MS m/z 149 (M+).
Reaction of a 1:1 Mixtu r e of 20 an d 21 with (CF 3SO2)2O.
Typ ica l P r oced u r e (Sch em e 4, Ta ble 1, En tr y 7). To a
solution of 20c′ (101 mg, 0.220 mmol) and 21c′ (108 mg, 0.220
mmol) in CH2Cl2-CH3CN (v/v 4:1, 8.8 mL) at -40 °C under
an Ar atmosphere was added (CF3SO2)2O (80 µL, 0.48 mmol).
The reaction mixture was allowed to warm to room temper-
ature for 4 h, and saturated aqueous NaHCO3 was added to
the mixture. The aqueous layer was extracted with CHCl3. The
organic layer was washed with brine and dried over MgSO4.
After evaporation of solvents, the residual mixture was puri-
fied with preparative HPLC eluted by CHCl3 to give 17c (29.4
mg, 27%) as a pale yellow solid and 14b (56.1 mg, 39%).
Reaction of a 1:1 Mixtu r e of 11 an d 12 with (CF 3SO2)2O.
To a solution of 11 (114 mg, 0.499 mmol) and 12 (122 mg, 0.499
mmol) in CH2Cl2-CH3CN (v/v 4:1, 10 mL) at -20 °C under
an Ar atmosphere was added (CF3SO2)2O (93 µL, 0.55 mmol).
The reaction mixture was allowed to warm to room temper-
ature for 2 h, and saturated aqueous NaHCO3 was added to
the mixture. The aqueous layer was extracted with CH2Cl2.
The organic layer was washed with brine and dried over
MgSO4. After evaporation of solvents, the residue was sub-
jected to column chromatography on silica gel to give 13 (109
mg, 89%) and 14b (153 mg, 94%).
Ack n ow led gm en t. We thank Professor M. Yoshifuji
and Dr. S. Sasaki (Tohoku University) for their kind
advice to the synthesis of 3,3′,5,5′-tetramesityl-4,4′-
diiodobiphenyl. This work was supported in part
by grants-in-aid from the Ministry of Education, Sci-
ence, Sports and Culture, J apan (Nos. 11440186 and
11640523).
Su p p or tin g In for m a tion Ava ila ble: Spectral dada of
starting materials 1a , 5, 8, 10, 16, 20, and 21. This material
is available free of charge via the Internet at http://pubs.acs.org.
1
Bis(4-m eth ylp h en yl) d isu lfid e (13): H NMR (CDCl3) δ
2.32 (s, 6H), 7.10 (d, J ) 7.8 Hz, 4H), 7.38 (d, J ) 7.8 Hz, 4H);
EI-MS m/z 246 (M+).
J O001645K