Mechanism of the second sulfenylation of indole

Article abstract of DOI:10.1021/jo0109220

Sulfenylation of indole using a sulfenyl chloride occurs initially at the 3-position of the ring, leading to a 3-indolyl sulfide. When an excess of sulfenyl chloride is used, a second sulfide group is introduced at the 2-position, and an indolyl 2,3-bis-sulfide results. We have demonstrated that this second sulfenylation occurs not by direct introduction of the second sulfide at the 2-position but via initial formation of an indolenium 3,3-bis-sulfide intermediate, followed by migration of one of the sulfide groups to the 2-position. This was achieved by the isolation of two examples of 3H-indole 3,3-bis-sulfides and by subsequent demonstration that they rearrange to the indolyl 2,3-bis-sulfides by treatment with sulfenyl halides.

Full text of DOI:10.1021/jo0109220

2854
J . Org. Chem. 2002, 67, 2854-2858
Mech a n ism of th e Secon d Su lfen yla tion of In d ole
Pierre Hamel
The Merck Frosst Centre for Therapeutic Research, P.O. Box 1005, Pointe-Claire-Dorval,
Quebec H9R 4P8, Canada
pierre-hamel@merck.com
Received September 14, 2001
Sulfenylation of indole using a sulfenyl chloride occurs initially at the 3-position of the ring, leading
to a 3-indolyl sulfide. When an excess of sulfenyl chloride is used, a second sulfide group is introduced
at the 2-position, and an indolyl 2,3-bis-sulfide results. We have demonstrated that this second
sulfenylation occurs not by direct introduction of the second sulfide at the 2-position but via initial
formation of an indolenium 3,3-bis-sulfide intermediate, followed by migration of one of the sulfide
groups to the 2-position. This was achieved by the isolation of two examples of 3H-indole 3,3-bis-
sulfides and by subsequent demonstration that they rearrange to the indolyl 2,3-bis-sulfides by
treatment with sulfenyl halides.
Sch em e 1
In tr od u ction
One of the most convenient methods for the prepara-
tion of 3-indolyl sulfides 1 is by sulfenylation of indoles
using sulfenyl chlorides.1-5 These are easily generated
from alkyl or aryl disulfides and a source of chlorine,
ideally sulfuryl chloride, in 1,2-dichloroethane or tetra-
chloroethane. In most cases, this reaction is practically
instantaneous and the sulfenyl chloride is produced
nearly quantitatively and used as such in solution, after
a few minutes. The sulfenyl chlorides are extremely
reactive, and sulfenylation of indole occurs rapidly at
room temperature, without the need for the preliminary
generation of the anion of indole, leading to good to
excellent yields of 3-indolyl sulfides. The mechanism of
this sulfenylation is well-known4 and follows the usual
substitution pathway6 depicted in Scheme 1. One draw-
back to the use of sulfenyl chlorides for the sulfenylation
of indoles derives from their exceptional reactivity, and
if the 2-position of the indole is unoccupied, the slightest
excess of reagent leads to a second sulfenylation, and a
full second equivalent leads to excellent yields of 2,3-
indolyl bis-sulfides 2.1,3,4,7
through a transient episulfonium species such as 4? The
latter pathway was suggested several years ago by
Ottenheijm et al.3,4 with no experimental support, and
it intuitively appears more plausible than the direct
introduction into the 2-position, which would require a
temporary disruption of the aromaticity of the ring
system. The 3-position is the most nucleophilic site of the
indole nucleus, and where steric hindrance is not a factor,
the presence of a sulfide group would not be expected to
deactivate the 3-position toward further substitution. The
data that we present herein serve as strong evidence to
demonstrate that indeed the mechanism proceeds via an
initial second sulfenylation at the 3-position followed by
rearrangement.
For the past few years we have been attempting to
establish the mechanism of this second sulfenylation of
indole. The question to be resolved is the following: is
the second sulfide group introduced directly at the
2-position of the indole ring (eq 1), or does the reaction
proceed via a second sulfenylation at the 3-position,
leading to an intermediate 3,3-bis-substituted indolenium
intermediate such as 3 (eq 2), with subsequent migration
Resu lts a n d Discu ssion
In an initial report8 we presented the results of a study
in which we performed a second sulfenylation on a series
(1) Anzai, K. J . Heterocycl. Chem. 1979, 16, 567.
(2) Wieland, T.; Ruhl, K. Chem. Ber. 1963, 96, 260.
(3) Plate, R.; Rutger, J . F.; Ottenheijm, H. C. J . Tetrahedron 1986,
42, 4503.
(4) Plate, R.; Nivard, R. J . F.; Ottenheijm, H. C. J . Tetrahedron 1986,
42, 4511.
(5) Raban, M.; Chern, L.-J . J . Org. Chem. 1980, 45, 1688.
(6) J ones, R. A. In Comprehensive Heterocyclic Chemistry; Bird, C.
W., Cheeseman, W. H., Eds.; Pergamon Press: Oxford, 1984; Vol 4, p
201.
(7) Hamel, P.; Zajac, N.; Atkinson, J . G.; Girard, Y. J . Org. Chem.
1994, 59, 6372.
of one of the sulfide groups to the 2-position, possibly
10.1021/jo0109220 CCC: $22.00 © 2002 American Chemical Society
Published on Web 04/11/2002

Mechanism of the Second Sulfenylation of Indole
J . Org. Chem., Vol. 67, No. 9, 2002 2855
Sch em e 2
Sch em e 3
of 3-indolyl sulfides using a different sulfenyl chloride
from the one used for the first sulfenylation. The fact that
in all cases mixtures of two isomeric mixed 2,3-bis-
sulfides were obtained instead of a single isomer bearing
the second sulfide group in the 2-position lent strong
support to the hypothesis of initial second sulfenylation
at the 3-position followed by migration of one of the
sulfide groups. In addition, the presence of the sulfide
bearing the most electron-rich substituent at the 2-posi-
tion of the ring in the major isomer produced was strongly
indicative of a preferential migration induced by the
positive charge on the nitrogen atom of the proposed
indolenium intermediate 3.
of the subsequent events leading to the rearrangement,
the positive charge on the nitrogen of intermediate 7
induces the migration of one of the sulfide groups,
possibly via the formation of the episulfonium species 8
with subsequent cleavage of the three-membered ring to
yield the N-phenylsulfenyl 2,3-bis-sulfide 9. The labile
N-sulfenamide is cleaved during the aqueous workup to
afford 2a . The proposal that the N-substituent remains
throughout the process until workup is supported by the
fact that at least a full equivalent of sulfenyl chloride is
required for the process to go to completion.
As an extension to the concept of quaternization of the
intermediate 5, we proceeded to experiment with the
possibility of provoking the quaternization using alkyl
halides. We expected that if quaternization did occur, the
rearrangement would proceed to afford N-alkylated
analogues of 2a , easily accessible via alkylation for
structural confirmation. Treatment of 5 in DMF with an
excess of benzyl bromide at room temperature showed
no discernible transformation after 2.5 h, and heating
at 85 °C led to the formation of unidentified side products
without generation of the desired end product. Similar
results were obtained with methyl iodide and with the
highly reactive methyl trifluoromethanesulfonate. In the
light of these results, the rearrangement of 5 in the
presence of benzenesulfenyl chloride leads us to assume
that the latter is much more reactive than alkyl halides
or trifluoromethylsulfonates in leading to the quater-
nization of 5. This reactivity of sulfenyl halides is
demonstrated by the facile sulfenylations of indole, where
no base is required for the reaction to occur, whereas the
well-known alkylation of indole6 requires initial genera-
tion of the anion to lead to 1- or 3-alkylated products.
The preceding experiments aimed at the rearrange-
ment of 5 to 2a confirm that it does occur, providing that
a positive charge can be generated on the nitrogen atom
to drive the migration. Under the actual conditions of the
second sulfenylation, where a 3-indolyl sulfide is reacted
with a sulfenyl chloride, our proposal suggests that such
a charged species automatically results in situ when the
3,3-disubstituted indolenium intermediate 3 is formed.
This species presumably has sufficient longevity to allow
the migration of one of the sulfide groups to proceed,
initiating the events leading to the final reaction product,
the indolyl 2,3-bis-sulfide 2.
We then proceeded to examine the possibility of isolat-
ing an intermediate of type 3 bearing the two sulfide
groups at the 3-position of the ring. Although 3-alkythio-
3-alkyl-3H-indoles have been reported previously, as
intermediates of the Gassman synthesis of indoles and
carbazoles9 and also by sulfenylation of 2,3-dialkylin-
doles, 10a,b alkyl substituents were always present at the
2-position. No examples bearing two sulfide groups at the
3-position, with or without a 2-substituent, had been
reported. We successfully isolated two examples11 (5 and
6, Scheme 2) of the neutralized form of 3 from the
reaction of 3-phenylthioindole 1a with either benzene-
sulfenyl chloride or p-toluenesulfenyl chloride in the
presence of triethylamine. We were convinced that
regeneration of the positive charge on the nitrogen atom
of the isolated intermediates by protonation would lead
to immediate rearrangement. However, the molecules
proved to be totally inert to acids and we could not
provoke protonation of the ring at room temperature,
even in neat trifluoroacetic acid, while heating led to
decomposition products. In contrast, when 3,3-bis-phen-
ylthio intermediate 5 is treated with benzenesulfenyl
chloride at room temperature, generation of 2,3-bis-
phenylthioindole 2a results. We did not perform a similar
experiment on the unsymmetrical 3,3-bis-sulfide 6 to
avoid the complications due to the generation of two
different mixed 2,3-bis-sulfides.
It is difficult to rationalize the transformation of 5 to
2a under these conditions other than by proposing that
the interaction consists of initial quaternization of 5 by
the sulfenyl chloride, leading to a charged N-sulfenyl
intermediate such as 7 (Scheme 3). In our representation
(8) Hamel, P.; Preville, P. J . Org. Chem. 1996, 61, 1573.
(9) Gassman, P. G.; van Bergen, T. J .; Gilbert, D. P.; Cue, B. W.,
J r. J . Am. Chem. Soc. 1974, 96, 549
(10) (a) Friesen, R. W.; Vice, S. F.; Findlay, C. E.; Dmitrienko, G. I.
Tetrahedron Lett. 1985, 26, 161. (b) Vice, S. F.; Friesen, R. W.;
Dmitrienko, G. I. Tetrahedron Lett. 1985, 26, 165
As a further extension to this mechanistic study, we
designed an experiment aimed at establishing that the
transformation of the indolenium intermediate 3 to the
bis-sulfide 2 occurs via an intramolecular migration of
one of the sulfide groups, rather than by some more exotic
(11) Hamel, P. Tetrahedron Lett. 1997, 38, 8473.

2856 J . Org. Chem., Vol. 67, No. 9, 2002
Hamel
Sch em e 4
Sch em e 5
The generation of compounds 12 and 13 was quite
puzzling, since they both bear a p-tolylthio group at the
3-position of the ring. This led us to suspect that
sulfenylation with p-toluenesulfenyl chloride could have
occurred at the 3-position of the indole ring at some
point. We propose that the appropriate substrate for
such a process would be intermediate N-sulfenyl-2,3-
indolyl bis sulfide 10 (Scheme 4) and that a second
sulfenylation occurs at the 3-position, leading to 2,3,3-
tris-sulfide indolenium intermediate 16. This would be
followed by migration of one of the sulfide groups from
the 3-position to the 2-position with concomitant ex-
pulsion of the phenylthio substituent already present.
In the case where the p-tolylthio group migrates, this
would lead after workup to compound 11, whereas
migration of the phenylthio group would afford com-
pound 12. A similar exercise on the N-sulfenyl intermedi-
ate of 12 would explain the formation of the 2,3-bis(p-
tolylthio)indole 13. Although 1 equiv of the p-toluene-
sulfenyl chloride was used in this experiment, it is
assumed that the initial quaternization occurs slowly and
thus that significant amounts of the sulfenyl chloride are
available for the competing ring sulfenylations proposed
above.
Although the results of this experiment failed to
provide the desired information on the pathway of the
migration of the sulfide, the proposed sulfenylation to
afford intermediate 16 actually represents an extension
of the concept of a second sulfenylation at the 3-position
and thus provides additional support for the mechanistic
proposal that is the subject of this paper.
Evidence that such a third sulfenylation can indeed
occur was provided by a closer examination of the
mixtures obtained when 5 was treated with benzene-
sulfenyl chloride. In the crude mixtures, a minor com-
ponent was always observed in variable amounts but not
isolated. In one experiment a 19% yield of this component
was isolated, and its structure was established as being
2,3,3-tris-phenylthio-3H-indole 17 (Scheme 6). This com-
pound is proposed to derive from sulfenylation of inter-
mediate 9 at the 3-position, with subsequent eviction of
the N-sulfenyl substituent as benzenesulfenyl chloride
in a “retroquaternization” step.
intermolecular pathway. For this purpose, we reacted the
isolated 3,3-bis-sulfide 5 with 1 equiv of p-toluenesulfenyl
chloride with the expectation that quaternization would
occur and that the process would lead, after the migration
of one of the phenylthio groups, to intermediate 10
(Scheme 4), similar to 9 but bearing an N-p-tolylsulfenyl
substituent. Upon aqueous workup, the N-tolylsulfenyl
substituent would be cleaved, leading to the 2,3-bis-
phenylthioindole 2a with no incorporation of a p-tolylthio
group on the indole nucleus, as might be expected to
result if an intermolecular event were proceeding. How-
ever, after workup and chromatography, what appeared
to be a single spot product on TLC, corresponding to 2a ,
was revealed by proton NMR to consist of a mixture of
components, and multiple signals corresponding to meth-
yl groups indicated the presence of components bearing
p-tolylthio groups. The pattern of the protons on the
phenyl portion of the indole ring appeared intact, indicat-
ing that no substitution had occurred on that portion of
the molecule. The obvious conclusion was that one or both
of the phenylthio groups had been displaced by a p-
tolylthio group, leading to compounds such as 11-13.
This was confirmed by mass spectral analysis of the
compound mixture, where mass units of 347 and 361
were observed, corresponding to compounds 11 and/or 12
and 13, respectively.
To provide confirmation of these results, authentic
samples of these three compounds were prepared for
comparison of their NMR data, and their syntheses are
reported in Scheme 5. Sulfenylation of 2-phenylthioindole
1412,13 with p-toluenesulfenyl chloride cleanly affords
2-phenylthio-3-(p-tolylthio)indole 12, whereas 2,3-bis(p-
tolylthio)indole 13 results from double sulfenylation of
indole with the same sulfenyl chloride. Access to the
isomeric 3-phenylthio-2-(p-tolylthio)indole 11 is achieved
via initial regiospecific desulfenylation7 of 13 in trifluo-
roacetic acid in the presence of thiosalicylic acid, leading
to 2-(p-tolylthio)indole 15, which is sulfenylated with
benzenesulfenyl chloride to yield 11. The 1H NMR spectra
of these compounds confirmed that they were indeed all
present in the above compound mixture.
(12) Atkinson, J . G.; Hamel, P.; Girard, Y. Synthesis 1988, 480.
(13) Hamel, P.; Girard, Y.; Atkinson, J . G. J . Org. Chem. 1992, 57,
2994.
The isolation of compounds such as 5 and 6 and the
formation of compounds such as 11-13 and 17 demon-

Mechanism of the Second Sulfenylation of Indole
J . Org. Chem., Vol. 67, No. 9, 2002 2857
solution and considered to have the theoretical concentration
corresponding to a complete conversion. A rough confirmation
was provided by the following titration.
Sch em e 6
Titr a tion of th e Ben zen esu lfen yl Ch lor id e Solu tion .
A freshly prepared 0.4 M solution was titrated by using it in
a sulfenylation experiment with 2-methylindole as substrate.
To a solution of 131 mg of 2-methylindole (1 mmol) in 2.5 mL
of DMF was added incremental amounts of the benzenesulfe-
nyl chloride solution, until the complete disappearance of the
starting material and clean formation of 2-methyl-3-phenylth-
ioindole3 had resulted, as indicated by TLC. Isolation of the
product in 90% yield after chromatography indicated a con-
centration of at least 0.36 M. Taking into account probable
small losses of material in the workup and chromatography,
the concentration of this and other sulfenyl chloride solutions
was considered to be close enough to the theoretical value to
be used as such.
Isola tion of 3,3-Bis(p h en ylth io)-3H-in d ole (5). To a
solution of 2.25 g of 3-phenylthioindole 1a 4,5 (10 mmol) in 20
mL of DMF at room temperature was added 1.21 g of
triethylamine (1.67 mL, 12 mmol). The mixture was cooled to
0 °C and 25 mL of a freshly prepared 0.4 M solution of
benzenesulfenyl chloride (10 mmol) was added slowly. The
mixture was stirred at 0 °C for 1 h, then it was partitioned
between ether and water. The crude product from the organic
phase was chromatographed by eluting with a 1:9 mixture of
ethyl acetate and hexane. After elution of residual diphenyl
disulfide, 1.11 g (33%) of the product 5 was obtained as a white
solid, followed by 1.25 g (55%) of recovered 1a . Only a trace of
2,3-bis(phenylthio)indole 2a 5 was observed by TLC.
strate that in 3-indolyl sulfides the strong nucleophilic
character of the 3-position of the indole ring is indeed
retained, despite the presence of the sulfide substituent,
allowing a second sulfenylation to occur at the same
position.
Data for 5: mp 114-116 °C; 1H NMR δ 7.12-7.31 (m, 9H),
7.36-7.41 (m, 3H), 7.53 (d, J ) 7.9 Hz, 1H), 7.73 (d, J ) 8.3
Hz, 1H), 7.88 (s, 1H); HRMS calcd for C20H15NS2 333.0646,
found 333.0648. Anal. Calcd: C, 72.04; H, 4.53; N, 4.20; S,
19.23. Found: C, 71.91; H, 4.57; N, 3.83; S, 19.11.
Con clu sion
We believe that the data presented herein and in our
preceding papers strongly support the proposal that the
mechanism of the second sulfenylation of indole, as was
proposed by Ottenheijm et al., proceeds initially via a
second sulfenylation at 3-position, leading to in situ
formation of a 3,3-bis-substituted indolenium intermedi-
ate. Studies on an isolated 3H-indole 3,3-bis-sulfide
demonstrate that the positive charge on the nitrogen
atom of the 3,3-disubstituted indolenium species provides
the driving force that initiates the migration of one of
the sulfide groups to the 2-position. The intermediacy of
a transient episulfonium species remains at this time a
plausible scenario for this migration.
Isola tion of 3-P h en ylth io-3-(p-tolylth io)-3H-in d ole (6).
Following the same procedure, using a freshly prepared
solution of p-toluenesulfenyl chloride (from p-tolyl disulfide
and sulfuryl chloride), a 27% yield of 6 was obtained: mp 112-
114 °C; 1H NMR δ 2.30 (s, 3H), 7.11-7.16 (m, 3H), 7.20-7.25
(m, 5H), 7.28 (d, J ) 6.4 Hz, 2H), 6.36 (m, 1H), 7.51 (d, J )
7.9 Hz, 1H), 7.77 (d, J ) 8.3 Hz, 1H), 7.88 (s, 1H); HRMS calcd
for C21H17NS2 347.03802, found 347.0800. Anal. Calcd: C,
72.58; H, 4.93; N, 4.03; S, 18.45. Found: C, 72.20; H, 4.90; N,
3.99; S, 18.64.
Rea r r a n gem en t of 5 to 2,3-Bis(p h en ylth io)in d ole (2a )
a n d Isola tion of 2,3,3-Tr is(p h en ylth io)-3H-in d ole (17).
Variable results were obtained in several experiments. The
best yield of 17 was obtained in the following experiment. To
a solution of 166.5 mg of 5 (0.5 mmol) in 1.5 mL of DMF at
room temperature was added 1.25 mL of a 0.4 M solution of
benzenesulfenyl chloride in 1,2-dichloroethane (0.5 mmol). The
resulting yellow solution was stirred for 5 h and quenched with
water. The mixture was partitioned between ether and water,
and the crude product from the organic phase was chromato-
graphed by eluting with a 1:9 mixture of ethyl acetate and
hexane, affording 43 mg (19%) of trisulfide 17 as an off-white
Exp er im en ta l Section
Commercial reagents were used without further purification
or drying. The DMF and 1,2-dichloroethane used had water
content <50 ppm. The solvents used for chromatography were
of HPLC grade. 1H NMR spectra were recorded on a 500 MHz
instrument in acetone-d6 solution, and chemical shifts are
reported in ppm. Elemental analyses were performed at the
Laboratoire d’analyse elementaire, Universite de Montreal.
High-resolution mass spectra at 10 000 resolution were ob-
tained in-house using a J EOL HX110 mass spectrometer with
electron impact source. Progress of the reactions was moni-
tored on TLC silica gel plates, and purifications were carried
out using flash silica gel chromatography.
Stock Solu tion of Ben zen esu lfen yl Ch lor id e. In all
experiments the benzenesulfenyl chloride was prepared im-
mediately prior to its use by the following method: To a
solution of 1.2 g of diphenyl disulfide (5.5 mmol) in 15 mL of
1,2-dichloroethane at room temperature was added 667 mg of
sulfuryl chloride (0.40 mL, 5 mmol), the resulting yellow
solution was stirred for 5 min, and then the volume was
completed to 25 mL with 1,2-dichloroethane. The solution was
used as such, assuming a concentration of 0.4 M benzene-
sulfenyl chloride. In some cases a 0.5 M solution was prepared.
An attempt to obtain the sulfenyl chloride in pure form by
distillation led to decomposition, so it was used as such in
1
solid: mp 101-103 °C; H NMR δ 7.05 (d, J ) 7.2 Hz, 2H),
7.13-7.30 (m, 14H), 7.45 (m, 1H), 7.57 (d, J ) 7.9 Hz, 1H),
7.78 (d, J ) 8.3 Hz, 1H); HRMS calcd for C26H19NS3 441.0680,
found 441.0695. Anal. Calcd: C, 70.71; H, 4.34; N, 3.17; S,
21.78. Found: C, 70.39; H, 4.44; N, 3.08; S, 21.67. Further
elution yielded 84 mg of the rearranged 2,3-bis(phenylthio)-
indole 2a 1 (50.5%) as a beige solid.
Rea ction of 5 w ith p-Tolu en esu lfen yl Ch lor id e. To a
solution of 113 mg of 5 (0.4 mmol) in 1.5 mL of DMF at room
temperature was added 1 mL of a 0.4 M solution of p-
toluenesulfenyl chloride in 1,2-dichloroethane. The resulting
yellow solution was stirred for 2.5 h, quenched with water,
and then partitioned between ether and water. The crude
product from the organic phase was chromatographed by
eluting with a 1:9 mixture of ethyl acetate and hexane, and
101 mg of the major product was obtained as a yellow-brown
syrup. The complex proton NMR spectrum (in acetone-d6)
contained four signals between 2.22 and 2.44 ppm, attributable

2858 J . Org. Chem., Vol. 67, No. 9, 2002
Hamel
to methyl groups on tolyl residues. Mass spectral analysis of
the mixture revealed signals indicating molecular masses of
347 (11 and/or 12) and 361 (13) as well as 333 (2a ).
of thiosalicylic acid (2.5 mmol) and the suspension was stirred
at 60 °C for 30 min. The TFA was evaporated away and the
residue was stirred with ethyl acetate and 1 N aqueous NaOH.
The organic phase was washed several times with water, dried,
and evaporated. The residue was chromatographed by eluting
with a 1:7 mixture of ethyl acetate and hexane to afford 275
mg of 15 (92%) as a white solid: mp 61-64 °C; 1H NMR δ
2.29 (s, 3H), 6.79 (s, 1H), 7.07 (m, 1H), 7.14 (s, 4H), 7.17 (m,
1H), 7.40 (d, J ) 8.2 Hz, 1H), 7.59 (d, J ) 8.0 Hz, 1H), 10.55
(br, NH); HRMS calcd for C15H13NS 239.0769, found 239.0761.
Anal. Calcd: C, 75.27; H, 5.47; N, 5.85; S, 13.40. Found: C,
74.94; H, 5.45; N, 5.64; S, 13.45.
2-P h en ylth io-3-(p-tolylth io)in d ole (12). To a solution of
225 mg of 2-phenylthioindole12,13 (14, 1 mmol) in 2 mL of DMF
at room temperature was added 2.2 mL of a 0.5 M solution of
p-toluenesulfenyl chloride in 1,2-dichloroethane (1.1 mmol),
and the mixture was stirred for 30 min. The dichloroethane
was evaporated off and the residual solution was partitioned
between ether and water. The crude organic product was
chromatographed by eluting with a 1:5 mixture of ethyl acetate
and hexane to afford 290 mg of 12 (84%) as a colorless syrup;
1H NMR δ 2.21 (s, 3H), 6.99 (s, 4H), 7.11 (m, 1H), 7.18-7.29
(m, 6H), 7.45 (d, J ) 8.2 Hz, 1H), 7.50 (d, J ) 7.9 Hz, 1H),
11.05 (br, NH). HRMS calcd for C21H17NS2 347.0802, found
347.0800. Anal. Calcd: C, 72.58; H, 4.93; N, 4.03. Found: C,
72.70; H, 4.91; N, 4.04.
3-P h en ylth io-2-(p-tolylth io)in d ole (11). To a solution of
80 mg of 15 (0.33 mmol) in 1 mL of DMF was added at 0 °C
0.8 mL of a 0.5M solution of benzenesulfenyl chloride in 1,2-
dichloroethane (0.4 mmol). The resulting solution was stirred
at 0 °C for 5 min and then at room temperature for 1 h. The
mixture was worked up as in the preparation of compound
12, and the product was purified by chromatography, eluting
with a 1:7 mixture of ethyl acetate and hexane to afford 93
mg of 11 (81%) as a light yellow syrup:
1H NMR δ 2.28 (s, 3H), 7.01-7.15 (m, 6H), 7.18-7.27 (m,
5H), 7.47 (d, J ) 8.2 Hz, 1H), 7.50 (d, J ) 8.0 Hz, 1H), 11.05
(br, NH); HRMS calcd for C21H17NS2 347.0802, found 347.0807.
Anal. Calcd: C, 72.58; H, 4.93; N, 4.03. Found: C, 72.56; H,
4.84; N, 3.97.
2,3-Bis(p-tolylth io)in d ole (13). To a solution of 234 mg
of indole (2 mmol) in 4 mL of DMF was added at 0 °C 10 mL
of a 0.5 M solution of p-toluenesulfenyl chloride in 1,2-
dichloroethane (5 mmol), and the resulting mixture was stirred
at 0 °C for 30 min and then at room temperature for 18 h.
The 1,2-dichloroethane was evaporated away and the residue
was partitioned between ether and water. The crude organic
product was chromatographed by eluting with a 1:5 mixture
of ethyl acetate and hexane to afford 736 mg of 13 (quant) as
a yellow syrup: 1H NMR δ 2.24 (s, 3H), 2.29 (s, 3H), 7.01 (s,
4H), 7.11-7.14 (m, 3H), 7.20 (d, J ) 8.2 Hz, 2H), 7.24 (dd, J
) 8.2 and 1.1 Hz, 1H), 7.45 (d, J ) 8.2 Hz, 1H), 7.51 (d, J )
8.1 Hz, 1H), 11.0 (br, NH); HRMS calcd for
C
22H19NS2
Ack n ow led gm en t. The author wishes to express his
gratitude to Mrs Chun Li for performing the HRMS
experiments.
361.0959, found 361.0964. Anal. Calcd: C, 73.09; H, 5.30; N,
3.87. Found: C, 73.01; H, 5.20; N, 3.82.
2-(p-Tolylth io)in d ole (15). To a solution of 450 mg of 13
(1.25 mmol) in 5 mL of trifluoroacetic acid was added 384 mg
J O0109220