Indium(I) iodide-promoted cleavage of diaryl diselenides and disulfides and subsequent condensation with alkyl or acyl halides. One-pot efficient synthesis of diorganyl selenides, sulfides, selenoesters, and thioesters

Article abstract of DOI:10.1021/jo0493727

Diphenyl diselenides and disulfides undergo facile cleavages by indium(I) iodide and the corresponding generated selenate and thiolate anions condense in situ with alkyl or acyl halides present in the reaction mixture. Thus, a simple, efficient, and general procedure has been developed for the synthesis of unsymmetrical diorganyl selenides, sulfides (thioethers), selenoesters, and thioesters by this one-pot reaction at room temperature.

Full text of DOI:10.1021/jo0493727

SCHEME 1. Syn th esis of Selen id es a n d Su lfid es
In d iu m (I) Iod id e-P r om oted Clea va ge of
Dia r yl Diselen id es a n d Disu lfid es a n d
Su bsequ en t Con d en sa tion w ith Alk yl or
Acyl Ha lid es. On e-P ot Efficien t Syn th esis
of Dior ga n yl Selen id es, Su lfid es,
Selen oester s, a n d Th ioester s
The experimental procedure is very simple. A mixture
of alkyl (or acyl) halide and diaryl selenide (or sulfide)
in methylene chloride was stirred in the presence of
indium(I) iodide at room temperature for a certain period
of time (TLC). Usual workup and extraction with ether
provided the product.
Brindaban C. Ranu* and Tanmay Mandal
Department of Organic Chemistry,
Indian Association for the Cultivation of Science,
J adavpur, Calcutta 700 032, India
ocbcr@iacs.res.in
A wide range of structurally diverse alkyl halides
underwent reactions with diphenyl diselenides and dis-
ulfides by this procedure to produce the corresponding
alkyl phenyl selenides and sulfides (thioethers), respec-
tively, in very high yields. The results are presented in
Table 1 for selenides and in Table 2 for sulfides. As
evident from Tables 1 and 2, primary, secondary, tertiary,
benzylic, and allylic chlorides, bromides, and iodides
readily participate in this reaction to form the corre-
sponding products. The reaction with relatively sterically
congested-bridged halide also proceeds without any dif-
ficulty (entry 23 in Table 1). However, the reaction of
long-chain alkyl bromides is comparatively slow (entries
11,12, Table 1). In general, formation of sulfides took
longer (1-4 h) than those of selenides (<1 h) by this
procedure. Several aromatic and nonaromatic acid chlo-
rides also condense with selenate and thiolate anions
produced by this cleavage reaction to provide the corre-
sponding selenobenzoates and thiobenzoates in good to
high yields. However, aryl halides and vinyl halides
remained inactive in this reaction, and on the other hand,
nonaromatic diselenides and disulfides failed to undergo
any cleavage by this reagent. Several functional groups
such as OMe, Cl, NO2, CdO, CO2R, and methylenedioxy
remained unaffected under the reaction conditions.
It is speculated5 that the reactions are going through
the intermediacy of bis(phenylseleno/thiophenyl)-iodo-
indium(III) (1), formed readily by the reaction of equimo-
lar quantities of InI (use of less than a stoichiometric
amount of InI keeps the reaction incomplete) and di-
phenyl diselenide/diphenyl disulfide, which then releases
selenate/thiolate anion to be alkylated with alkyl/acyl
halide (Scheme 2). However, it cannot be ascertained
whether it is going exclusively through SN1 or SN2 path
as, although several primary halides reacted faster, the
reactions of two aliphatic bromides (entries 11 and 12 in
Table 1) took much longer (300 and 250 min) compared
to those with tertiary halides (entries 24-26, 25-31 min).
When the tertiary halides are added to the preformed
selenide anion, generated by the treatment of indium(I)
iodide and diphenyl diselenide, the reactions were found
to be slightly faster than the one-pot reactions. Thus, it
may be assumed that at least tertiary halides are
undertaking an SN1-type path. However, tertiary halides
remained virtually inert when added to the selenide
Received April 15, 2004
Abstr a ct: Diphenyl diselenides and disulfides undergo
facile cleavages by indium(I) iodide and the corresponding
generated selenate and thiolate anions condense in situ with
alkyl or acyl halides present in the reaction mixture. Thus,
a simple, efficient, and general procedure has been developed
for the synthesis of unsymmetrical diorganyl selenides,
sulfides (thioethers), selenoesters, and thioesters by this one-
pot reaction at room temperature.
The importance of indium metal and its salts has been
well demonstrated through novel protocols for carbon-
carbon bond formation, rearrangements, and a variety
of useful reactions over the past decade.1 Thus, the search
for new indium derivatives for more improvement in
organic transformations is of much current interest.2 As
a part of our activities in indium-mediated reactions,1e,3
we are also in this race, and recently we reported the
use of indium(I) iodide for the cleavage of diphenyl
diselenides followed by in situ condensation of selenate
anion with alkyl halides to produce diorganyl selenides
in a preliminary communication.4 We demonstrate here
further extension of this work together with application
of this indium reagent for the cleavage of diaryl disulfides
and subsequent reaction with alkyl or acyl halides to
provide diorganyl sulfides and thioesters (Scheme 1).
* Fax: 91-33-24732805.
(1) (a) Cintas, P. Synlett 1995, 1087. (b) Li, C.-J . Tetrahedron 1996,
52, 5643. (c) Li, C.-J .; Chan, T. H. Tetrahedron 1999, 55, 11149. (d)
Chauhan, K. K.; Frost, C. G. J . Chem. Soc., Perkin Trans. 1 2000, 3015.
(e) Ranu, B. C. Eur. J . Org. Chem. 2000, 2347. (f) Babu, G.; Perumal,
P. T. Aldrichimica Acta 2000, 33, 16. (g) Podelech, J .; Maier, T. C.
Synthesis 2003, 633.
(2) (a) Chauhan, K. K.; Frost, C. G.; Love, I.; Waite, D. Synlett 1999,
1743. (b) Ali, T.; Chauhan, K. K.; Frost, C. G. Tetrahedron Lett. 1999,
40, 5621. (c) Abernethy, C. D.; Cole, M. L.; Davies, A. J .; J ones, C.
Tetrahedron Lett. 2000, 41, 7567. (d) Cooper, I. R.; Grigg, R.; Ma-
cLachlan, W. S.; Sridharan, V.; Thornton-Pett, M. Tetrahedron Lett.
2003, 44, 403. (e) Villalva-Servin, N. P.; Melekov, A.; Fallis, A. G.
Synthesis 2003, 790.
(3) (a) Ranu, B. C.; Hajra, A.; J ana, U. J . Org. Chem. 2000, 65, 6270.
(b) Ranu, B. C.; Hajra, A.; J ana, U. Tetrahedron Lett. 2000, 41, 531.
(c) Ranu, B. C.; Samanta, S.; Hajra, A. Synlett 2002, 987. (d) Ranu, B.
C.; Das, A.; Samanta, S. Synlett 2002, 727. (e) Ranu, B. C.; Dey, S. S.;
Hajra, A. Tetrahedron 2002, 58, 2529. (f) Ranu, B. C.; Hajra, A.; Dey,
S. S.; J ana, U. Tetrahedron 2003, 59, 813. (g) Ranu, B. C.; Samanta,
S. J . Org. Chem. 2003, 68, 7130. (h) Ranu, B. C.; Das, A.; Hajra, A.
Synthesis 2003, 1012. (i) Ranu, B. C.; Samanta, S. Tetrahedron 2003,
59, 7901.
(5) Nobrega, J . A.; Goncalves, S. M. C.; Peppe, C. Tetrahedron Lett.
2000, 41, 5779; 2001, 42, 4745.
(4) Ranu, B. C.; Mandal, T.; Samanta, S. Org. Lett. 2003, 5, 1439.
10.1021/jo0493727 CCC: $27.50 © 2004 American Chemical Society
Published on Web 07/24/2004
J . Org. Chem. 2004, 69, 5793-5795
5793

TABLE 1. Syn th esis of Alk yl P h en yl Selen id es a n d
Alk yl Selen oben zoa tes
TABLE 2. Syn th esis of Alk yl Ar yl Su lfid es a n d Alk yl
Th ioben zoa tes
a
Yields refer to those of pure isolated products characterized
by IR and 1H and 13C NMR spectroscopic data and elemental
analysis.
anion generated by other reagents such as NaBH4 or
lanthanum metal and iodine.8c The free radical pathway,
although not ruled out, is not favored, as no dimerization
was observed during the reactions of benzoyl chloride and
iodide, which produced phenyl selenobenzoate (entries 30
a
Yields refer to those of pure isolated products characterized
by IR and 1H and 13C NMR spectroscopic data and elemental
analysis.
5794 J . Org. Chem., Vol. 69, No. 17, 2004

SCHEME 2. P ossible Rea ction P a th w a y for th e
F or m a tion of Selen id es a n d Su lfid es
Con clu sion
It can be concluded that a one-pot procedure for the
synthesis of alkyl phenyl selenides, sulfides (thioethers),
selenoesters, and thioesters has been developed involving
indium(I) iodide-mediated cleavage of diorganyl selenides
and sulfides and subsequent reaction with alkyl or acyl
halides. The significant advantages offered by this method
are operational simplicity, faster reaction, neutral and
mild (room temperature) reaction conditions, general
applicability (coupling with tertiary alkyl halides and acyl
halides), and high isolated yields of products, and thus
it provides a better and practical alternative to the
existing procedures.8,9 Moreover, this strategy demon-
strates the synthetic potential of indium(I) iodide, and
further synthetic applications of this reagent are in
progress.
and 31, Table 1) or phenyl thiobenzoate (entries 22-25,
Table 2) as sole products. The isolation of only the
R-addition products from the reactions of crotyl bromide
(entry 17 in Table 1 and entry 8 in Table 2) and cinnamyl
bromide (entry 18 in Table 1 and entry 10 in Table 2)
also does not support the free radical pathway.
In general, the reactions are fast, clean, and high-
yielding, leading to the synthesis of diorganyl selenides,
selenoesters, sulfides (thioethers), and thioesters. Organic
selenides are of considerable interest in academia as well
as in industry because of their wide involvement as key
intermediates in various organic transformations and use
as a food supplement.6 On the other hand, disufides
(thioethers) and thioesters are very versatile building
blocks for the synthesis of various organo-sulfur com-
pounds, and they also play important roles in biological
and chemical processes.7 Although quite a number of
procedures for the synthesis of organoselenium com-
pounds have already been published,8 most of them
usually require the handling of unstable reagents, strongly
basic or acidic reaction conditions, and two-step proce-
dures. A recent one-step procedure8c using lanthanum
metal and iodine, although convenient and efficient for
simple substrates, demonstrates virtually no reaction
with tertiary alkyl halides and low yield (43% by GC)
with benzoyl chloride (no other acid chloride has been
addressed). On the other hand, although there are
numerous methods available in the literature9 for the
preparation of thioethers and thioesters, the majority of
them are carried out under basic conditions with a
limited scope and yields are not always satisfactory.
However, the present procedure addresses a large num-
ber of structurally different substrates, including tertiary
alkyl halides and acid chlorides, and involves a new
strategy.
Exp er im en ta l Section
Gen er a l Exp er im en ta l P r oced u r e for th e Syn th esis of
Dior gan yl Selen ides, Su lfides, Selen oester s, an d Th ioester s.
Rep r esen ta tive P r oced u r e for Ben zyl P h en yl Su lfid e
(Th ioeth er ). To a stirred solution of benzyl bromide (171 mg,
1 mmol) and diphenyl disulfide (109 mg, 0.5 mmol) in dry
methylene chloride (2 mL) was added indium(I) iodide (121 mg,
0.5 mmol) at room temperature under argon. The reaction
mixture was stirred for 2.5 h (TLC) and quenched with a few
drops of H2O. The mixture was then extracted with ether (3 ×
15 mL), and the combined ether extract was washed with brine,
dried (Na2SO4), and evaporated to leave the crude product, which
was purified by column chromatography over silica gel (hexane/
ether 95:5) to furnish the pure benzyl phenyl sulfide (thioether)
as a colorless liquid (low melting solid) (160 mg, 80%).9f The
spectroscopic data (1H and 13C NMR) of this compound are in
good agreement with those reported.10
This procedure was followed for the synthesis of all products
listed in Tables 1 and 2. Although this procedure is described
in mmol scale, a few gram scale reactions are also carried out
with comparable yields. The known compounds were identified
by comparison of their spectral data with those reported (Tables
1 and 2), and the new compounds were properly characterized
by their IR, 1H NMR, and 13C NMR spectroscopic data and
elemental analysis. One representative example (entry 4, Table
1) is given below, and data for other unknown products are
provided in Supporting Information in the order of their entries
in Tables 1 and 2.
(4-Ch lor oph en yl)m eth yl P h en yl Selen ide (En tr y 4, Table
1): pale yellow liquid; IR 1475, 1577, 1595 cm-1; 1H NMR δ 4.04
(s, 2H), 7.1 (d, J ) 8.4 Hz, 2H), 7.20 (m, 2H), 7.28-7.33 (m, 3H),
7.42-7.45 (m, 2H); 13C NMR δ 31.8, 128.0, 128.9 (2C), 129.4 (2C),
130.2, 130.5 (2C), 132.9, 134.3 (2C), 137.7. Anal. Calcd for C13H11
SeCl: C, 55.44; H, 3.93. Found: C, 55.49; H, 3.91.
(6) (a) Krief, A.; Hevesi, L. In Organoselenium Chemistry; Springer-
Verlag: Berlin, 1998; Vol. 1. (b) Krief, A. In Comprehensive Organo-
metallic Chemistry; Trost, B. M., Eds.; Pergamon Press: Oxford, 1991;
pp 85-192.
-
(7) (a) Peach, M. E. Thiols as Nucleophiles. In The Chemistry of the
Thiol Groups; Patai, S., Ed.; J ohn Wiley & Sons: London, 1979; pp
721-756. (b) Organic Sulfur Chemistry: Structure and Mechanism;
Oae, S., Ed.; CRC Press: Boca Raton, FL, 1991. (c) Cremlyn, R. J . An
Introduction to Organo-sulfur Chemistry; Wiley & Sons: New York,
1996.
Ack n ow led gm en t. We are pleased to acknowledge
the financial support from CSIR, New Delhi [Grant No.
01(1739)/02] for this investigation. T.M. is also thankful
to CSIR for his fellowship.
(8) (a) Bieber, L. W.; Sa, A. P. F. de; Menezes, P. H.; Goncalves, S.
M. C. Tetrahedron Lett. 2001, 42, 4597. (b) Krief, A.; Derock, M.
Tetrahedron Lett. 2002, 43, 3083 and references therein. (c) Nishino,
T.; Okada, M.; Kuroki, T.; Watanabe, T.; Nishiyama, Y.; Sonoda, N. J .
Org. Chem. 2002, 67, 8696 and references therein. (d) Grieco, P. A. J .
Org. Chem. 1978, 43, 1283.
(9) (a) Polshettiwar, V.; Nivasarkar, M.; Acharya, J .; Kaushik, M.
P. Tetrahedron Lett. 2003, 44, 887 and references therein. (b) Karimi,
B.; Zareyee, D. Synthesis 2003, 1875. (c) Shah, S. T. A.; Khan, K. M.;
Heinrich, A. M.; Voelter, W. Tetrahedron Lett. 2002, 43, 8281 and
references therein. (d) Meshram, H. M.; Reddy, G. S.; Bindu, K. H.;
Yadav, J . S. Synlett 1998, 877. (e) Lee, G. H.; Choi, E. B.; Lee, E.;
Pak, C. S. Tetrahedron Lett. 1994, 35, 2195.
Su p p or tin g In for m a tion Ava ila ble: General experimen-
tal requirements and spectroscopic (IR, 1H NMR, and 13C
NMR) data and elemental analysis of all new products listed
in Tables 1 and 2. This material is available free of charge via
the Internet at http://pubs.acs.org.
J O0493727
(10) Pouchert, C. J . The Aldrich Library of NMR Spectra, 2nd ed.;
Vols. 1 and 2; Aldrich Chemical Co., Inc.: Milwaukee, 1983.
J . Org. Chem, Vol. 69, No. 17, 2004 5795