Reduction of sulfur with borohydride exchange resin in methanol: Application to rapid and selective synthesis of disulfides

Article abstract of DOI:10.1016/S0040-4039(01)00789-4

A convenient and rapid method for the synthesis of symmetrical disulfides from alkyl or aryl alkyl halides using sulfurated borohydride exchange resin (SBER) under anhydrous conditions is described. Selective transfer of sulfur to an alkyl group rather than an aryl group is achieved using this methodology.

Full text of DOI:10.1016/S0040-4039(01)00789-4

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 6741–6743
Reduction of sulfur with borohydride exchange resin in methanol:
application to rapid and selective synthesis of disulfides
B. P. Bandgar,* L. S. Uppalla and V. S. Sadavarte
Organic Chemistry Research Laboratory, School of Chemical Sciences, Swami Ramanand Teerth Marathwada University,
Nanded 431 606, Maharashtra, India
Received 8 January 2001; revised 2 May 2001; accepted 11 May 2001
Abstract—A convenient and rapid method for the synthesis of symmetrical disulfides from alkyl or aryl alkyl halides using
sulfurated borohydride exchange resin (SBER) under anhydrous conditions is described. Selective transfer of sulfur to an alkyl
group rather than an aryl group is achieved using this methodology. © 2001 Elsevier Science Ltd. All rights reserved.
The disulfide moiety occurs ubiquitously in proteins
and is also found in a variety of natural products and
pharmacologically active compounds. In addition,
of acyclic and cyclic disulfides from alkyl or aryl alkyl
halides in high yield (Scheme 1).
1
19
cyclic and acyclic disulfides are useful intermediates in
When borohydride exchange resin (BER), sulfur and
a halide or dihalide in methanol is stirred, a sponta-
neous reaction took place (<5 min) giving the corre-
sponding disulfide in good to excellent yield. The results
are presented in the Table 1. The reaction is found to
be general as primary, secondary, tertiary, benzylic,
allylic halides as well as dihalides underwent smooth
reaction giving the corresponding acyclic and cyclic
disulfides. It is important to note that the reaction
appears to be specific only for alkyl halides as aryl
halides failed to undergo the reaction (entries 6–10).
Therefore, it is a method of choice for the synthesis of
disulfides from alkyl halides in the presence of aryl
halides. In this connection it should be mentioned that
2
the synthesis and preparation of adsorbed monolay-
3
4
ers. Acyclic and cyclic disulfides are typically prepared
by the oxidative dimerization of a-v-dithiols (e.g. I ,
2
5
6
7
8
NEt ; Br ; K Fe(CN) ; CCl , NEt ; H O /KI/
AcOH; Pb(OAc) , S; KO2; Caro’s acid supported
on silica gel ) and may also be prepared by reacting
a,v-dihalogenated compounds with Na S/S or from
thiocyanates with base (eg. NaOH or NH ). More
3
2
3
6
4
3
2
2
9
10
11a
4
1
1b
1
2
2
8
13
3
recently, reaction of a,v-bisthiocyanates with samarium
1
4
15
diiodide or tetrathiomolybdate or tetrabutylammon-
1
6
ium fluoride have been employed in the synthesis of
cyclic disulfides. Thus, most of the disulfides are pre-
pared from the corresponding thiols/dithiols by conven-
tional oxidation. The major problem associated with
this strategy is that, in general, it leads to the formation
of dimer, trimer and polymers to an appreciable
amount thereby reducing the yield of the desired
15
1
7
a recent report for the synthesis of disulfides employ-
ing tetrathiomolybdate does not discriminate between
aryl halides and aryl alkyl halides. Another important
feature of this method is that the reaction is very rapid
giving pure products in high yield compared with
1
7a
product considerably. The synthesis of disulfides via
15
reported methods. It must be mentioned that several
other functional groups present in the molecule such as
F (entry 6), Cl (entries 7, 9), Br (entry 10), CN (entries
1
8
bisthiocyanates starting from dihalides is a two step
process and thus the overall yield of the product is
lowered.
1
1, 20), NO2 (entries 12, 21), OMe (entries 8, 18),
methylenedioxy (entry 9), NHCOCH (entry 19), acetal
3
In this communication, we describe our results for the
first time on a facile sulfur transfer reaction using
sulfurated borohydride exchange resin (SBER) in
methanol for a rapid and selective synthesis of a variety
(
entry 22), allylic CꢀC (entries 1, 23) ester (entries 5, 15)
and polyethers (entries 16, 17) remain intact under
these reaction conditions.
Keywords: alkyl halide; disulfide; SBER; selectivity.
*
Corresponding author. Fax: 0091-2462-29245; e-mail: bandgar bp
–
@
yahoo.com
Scheme 1.
0
040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00789-4

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B. P. Bandgar et al. / Tetrahedron Letters 42 (2001) 6741–6743
Table 1. Synthesis of disulfides using SBER at 25°C
In order to explore the generality and scope of SBER
for the synthesis of disulfides, the procedure has been
extended to the synthesis of an important class of
compounds: macrocyclic disulfides (redox switched
and other reducible groups are found to be unreactive
under these reaction conditions. The obvious advan-
tages of heterogeneous reagent in terms of simple oper-
ation with the ease of work-up and recyclability of the
resin are noteworthy. We believe that this method will
present a better and more practical alternative to the
existing methodologies and should find widespread
applications in organic synthesis.
1
7a,b,20
crown ethers)
in high yield (entries 15 and 17).
In summary, we have demonstrated that SBER serves
as an efficient reagent for the synthesis of acyclic and
cyclic disulfides from the corresponding alkyl or aryl
alkyl halides under mild and essentially neutral condi-
tions. The effectiveness of this protocol is manifested in
its selectivity towards alkyl halides whereas aryl halides
Typical procedure: A mixture of borohydride exchange
resin (5 gm, 5 mmol) and sulfur powder (5 mmol) in
methanol (10 ml) is stirred at room temperature for 10

B. P. Bandgar et al. / Tetrahedron Letters 42 (2001) 6741–6743
6743
min. Then 4-chlorobenzyl chloride (5 mmol) is added
and stirred for 5 min. After completion of the reaction
Fukuyama, T.; Havel, M. J. Am. Chem. Soc. 1973, 95,
6493; (c) Tabashi, K.; Kawashima, Y. Chem. Pharm.
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(
TLC), the resin was filtered off and solvent was
removed under reduced pressure to afford the product,
g in almost pure form which was further purified by
2. (a) Koval’, L. V. Russ. Chem. Rev. 1994, 63, 735; (b)
Billard, T.; Langlois, B. R. Tetrahedron Lett. 1996, 37,
6865.
2
column chromatography on silica gel (hexane:ethyl ace-
tate, 9:1).
3. (a) Nuzzo, R. G.; Allara, D. L. J. Am. Chem. Soc. 1983,
1
05, 4481; (b) Biebuyck, H. A.; Bain, C. D.; Whitesides,
Spectroscopic data of some selected compounds
G. M. Langmuir 1994, 10, 1825 and references cited
therein.
. Capozzi, G.; Modena, G. In The Chemistry of the Thiol
Group, Part II; Patai, S., Ed.; John Wiley and Sons: New
York, 1974; p. 785.
−
1
Compound 2j: mp=149–151°C; IR (KBr, cm ): 600,
4
6
1
76, 876, 1011, 1069, 1095, 1178, 1199, 1264, 1305,
401, 1590, 1699, 1898, 2854, 2920, 2963, 3039;
1
H
NMR (300 MHz, CDCl ): l=3.5 (s, 4H, SCH ); 7.25
3
2
5. (a) Field, L.; Barbee, R. B. J. Org. Chem. 1969, 34, 36;
b) Harpp, D. N.; Gleason, J. G. J. Org. Chem. 1970, 35,
259.
6. Wu, X.; Rieke, R. D.; Zhu, L. Synth. Commun. 1996, 26,
91.
(
d, 4H, J=8.7 Hz, Ar-H); 8.12 (d, 4H, J=8.7 Hz,
(
3
+
Ar-H). Mass: m/z (%)=404 (M , 8); 169 (100). Anal.
calcd for: C H Br S (404): C, 41.58; H, 2.97; Br,
1
4
12
2 2
3
1
9.60; S, 15.84. Found: C, 41.63; H, 3.03; Br, 39.48; S,
5.93.
1
7
8
. Cleland, W. W. Biochemistry 1964, 3, 480.
. Wenschuh, E.; Heydenreich, M.; Runge, R.; Fischer, S.
Sulfur Lett. 1988, 8, 251.
−
1
Compound 2l: mp=83°C; IR (KBr, cm ): 620, 721,
7
1
69, 832, 865, 935, 984, 1036, 1117, 1176, 1233, 1253,
360, 1413, 1479, 1503, 1619, 2892, 3010; H NMR
9
1
. Field, L.; Khim, Y. H. J. Org. Chem. 1972, 37, 2710.
1
0. Cragg, R. H.; Weston, A. F. Tetrahedron Lett. 1973,
55.
1. (a) Crank, G.; Makin, M. I. H. Aust. J. Chem. 1984, 37,
331; (b) Movassagh, B.; Lakourag, M. M.; Ghodreti, K.
(300 MHz, CDCl ): l=3.6 (s, 4H, SCH ); 7.29 (d, 4H,
3
2
6
J=7.5 Hz, Ar-H); 8.17 (d, 4H, J=7.5 Hz, Ar-H).
1
+
Mass: m/z (%)=336 (M , 5); 136 (100). Anal. calcd for:
2
C H N O S (336.3944): C, 49.99; H, 3.95; N, 8.33; S,
1
4
12
2
4 2
Synth. Commun. 1999, 29, 3597.
19.07. Found: C, 49.91; H, 3.65; N, 8.28; S, 19.14.
1
2. (a) McCormick, J. E.; McElhinney, R. S. J. Chem. Soc.,
Perkin Trans. 1 1972, 2795; (b) For use of a,v-dimesyl-
ates, see: Gopalan, A. S.; Jacobs, H. K. J. Chem. Soc.,
Perkin Trans. 1 1990, 1897.
3. Guy, R. G. In The Chemistry of Cyanates and their Thio
Derivatives, Part II; Patai, S., Ed.; Wiley: New York,
−
1
Compound 2o: Viscous liquid; IR (neat, cm ): 760,
1
1
120, 1220, 1450, 1500, 1602, 1740, 2822, 3017;
H
NMR (300 MHz, CDCl ): l=1.1–1.8 (m, 16H); 2.4–2.8
3
1
(
7
1
t, J=2.4 Hz, 4H); 4.2 (t, 4H, J=3.1 Hz, CH O);
2
.50–7.80 (M, 4H, Ar-H). Mass: m/z (%)=396.57 (M+,
1
977; p. 867.
4. Jia, X.; Zhang, Y.; Zhou, X. Tetrahedron Lett. 1994, 35,
833.
4); 149 (100). Anal. calcd for: C H O S (396.5728):
2
0
28
4 2
1
1
1
1
C, 60.57; H, 7.12; S, 16.17. Found: C, 60.64; H, 7.05; S,
6.23.
8
1
5. Prabhu, K. R.; Ramesha, A. R.; Chandrasekaran, S. J.
Org. Chem. 1995, 60, 7142.
−
1
Compound 2q: mp=127–128°C; IR (KBr, cm ): 753,
050, 1120, 1222, 1250, 1460, 1505, 1597, 2830, 3020;
6. Burns, C. J.; Field, L. D.; Morgan, J.; Ridley, D. D.;
Vignerich, V. Tetrahedron Lett. 1999, 40, 6489.
7. (a) Shinkai, S.; Inuzuka, K.; Hara, K.; Takaaki, S.;
Manabe, O. Bull. Chem. Soc. Jpn. 1984, 57, 2150; (b)
Shinkai, S.; Inuzuka, K.; Miyazaki, O.; Manabe, O. J.
Am. Chem. Soc. 1985, 107, 3950; (c) Beer, D. D. Chem.
Soc. Rev. 1989, 18, 409; (d) Raban, M.; Greenblatt, J. J.
Chem. Soc., Chem. Commun. 1983, 1409.
1
1
H NMR (300 MHz, CDCl ): l=3.22 (t, 4H, J=4.5
3
Hz, CH S); 3.85–4.30 (m, 12H, CH O); 6.92 (s, 8H,
2
2
Ar-H). Mass: m/z (%)=408.54 (M+, 100); 136 (73).
Anal. calcd for: C H O S (408.5411): C, 58.80; H,
20
24
5 2
5.52; S, 16.70. Found: C, 58.82; H, 5.84; S, 16.61.
1
1
8. Bisthiocyanates were prepared by treatment of the corre-
sponding dibromides with KSCN in DMF following
literature procedure: Guy, R. G. In The Chemistry of
Cyanates and Their Thio Derivatives; Patai, S., Ed.; John
Wiley and Sons: New York, 1977; p. 819.
9. Borohydride exchange resin (BER) was prepared using
reported procedure: Bandgar, B. P.; Modhave, R. K.;
Wadgaonkar, P. P.; Sande, A. R. J. Chem. Soc., Perkin
Trans. 1 1996, 1993.
Acknowledgements
V.S.S. thanks CSIR, New Delhi for Junior Research
Fellowship.
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