Alternative Protocol for the Synthesis of Symmetrical Dibenzyl Diselenides and Disulfides

Article abstract of DOI:10.1055/s-0035-1561579

A one-pot protocol for the preparation of symmetrical dibenzyl diselenides and disulfides from the corresponding benzyl alcohols employing NaBH₂Se₃ and NaBH₂S₃ as selenium-transfer and sulfur-transfer reagent, respectively, is described. Structurally diverse substituted benzyl alcohols afforded the corresponding diselenides and disulfides in good to excellent yields. The protocol is simple and mild, and the products were obtained within a short reaction time.

Full text of DOI:10.1055/s-0035-1561579

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2016, 48, A–H
paper
A
V. Panduranga et al.
Paper
Synthesis
Alternative Protocol for the Synthesis of Symmetrical Dibenzyl
Diselenides and Disulfides
Veladi Panduranga
Girish Prabhu
R
1) DMF, PCl5
Se
Basavaprabhu
MeCN, r.t., 10 min
Se
Nageswara Rao Panguluri
Vommina V. Sureshbabu*
2) NaBH2Se3
THF, r.t., 15 min
R
10 examples, 70–93% yield
OH
R
#109, Peptide Research Laboratory, Department of Studies
in Chemistry, Central College Campus, Bangalore University,
Dr. B. R. Ambedkar Veedhi, Bangalore 560 001, India
hariccb@gmail.com
1) DMF, PCl5
MeCN, r.t., 10 min
R
S
S
2) NaBH2S3
THF, r.t., 25 min
hariccb@hotmail.com
sureshbabuvommina@rediffmail.com
R
9 examples, 66–90% yield
Received: 12.12.2015
Accepted after revision: 15.02.2016
Published online: 22.03.2016
A number of methods are available for the synthesis of
organic diselenides. The majority of the routes involve the
reaction of metal diselenides with alkyl halides or pseudo-
halides under strong reducing and basic conditions,8 the di-
merization of selenocyanates,9 or the oxidation of either the
corresponding selenols10a or selenolates.10b Recently, Singh
and co-workers reported the synthesis of symmetrical
diselenides using a CuO nanopowder catalyzed coupling re-
action of aryl and alkyl iodides with elemental selenium in
the presence of KOH in DMSO at 90 °C.11
DOI: 10.1055/s-0035-1561579; Art ID: ss-2015-n0717-op
Abstract A one-pot protocol for the preparation of symmetrical
dibenzyl diselenides and disulfides from the corresponding benzyl alco-
hols employing NaBH2Se3 and NaBH2S3 as selenium-transfer and sulfur-
transfer reagent, respectively, is described. Structurally diverse substi-
tuted benzyl alcohols afforded the corresponding diselenides and disul-
fides in good to excellent yields. The protocol is simple and mild, and
the products were obtained within a short reaction time.
Some of the important methods for the preparation of
dibenzyl diselenides are summarized in Scheme 1. Tian and
co-workers described the synthesis of symmetrical diben-
zyl diselenides using the reductive selenation of aromatic
aldehydes.12 Wang and co-workers reported the synthesis
of dibenzyl diselenides from benzyl halides under phase-
transfer catalysis using NaOH and Se at 65–70 °C.13 Ming-De
and co-workers obtained dibenzyl diselenides by the reac-
tion of benzyl halides with phenylselenoamides/selenourea
at 70 °C under N2 atmosphere.14 Plano and co-workers re-
ported the synthesis of dibenzyl diselenides from the corre-
sponding selenocyanates in the presence of NaBH4.15 Most
of these methods employ strong reducing agents, basic con-
ditions and/or a toxic gas, and involve multistep sequences,
elevated temperatures, low yields, the formation of mono-
selenides and triselenides as byproducts, and long reaction
duration.
Since the precursor halides are generally made from al-
cohols and sometimes this conversion is tedious, the direct
conversion from alcohol into the corresponding diselenide
would be a significantly useful route. To the best of our
knowledge, there are only a few reports describing disele-
nide formation from the corresponding alcohol (Scheme 2).
Braga and co-workers reported the preparation of a sym-
metrical diselenide from methylated ephedrine by mesyla-
tion, followed by treatment with Li2Se2 in THF overnight.16
Key words dibenzyl diselenides, dibenzyl disulfides, benzyl alcohols,
selenating agent, NaBH2Se3, NaBH2S3
Organoselenium compounds have a significant role in
biological redox processes, cancer prevention, immunology
and ageing.1a–d Their biological significance is exemplified
by selenium-containing proteins which are the essential
components of certain bacterial and mammalian enzyme
systems.1e–g The use of organoselenium compounds as re-
agents and intermediates in synthesis has increased in the
recent decades, owing to the stability and easy-to-handle
nature of such compounds. They have a broad range of reac-
tivities including cationic, anionic, radical and oxidative
pathways, as well as elimination and rearrangement path-
ways.2 Organodiselenides are convenient reagents for the
functionalization of alkenes allowing a high degree of stereo-
selectivity,3 the stereoselective ring-opening of epoxides,4
1,4-addition of Grignard reagents to enones,5a diethylzinc
addition to aldehydes5b and catalytic selenocyclizations for
the construction of heterocyclic scaffolds.6 In particular,
dibenzyl diselenides are converted into the selenyl chlo-
rides under very mild conditions,7a and benzyl can be an
ideal leaving radical for intramolecular homolytic substitu-
tion at selenium.7b
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V. Panduranga et al.
Paper
Synthesis
Br
Br
ref. 14
X
X
Se
(Et4N)2WSe4 ref. 17
or
Ar-C-NH2
Na2Se2 ref. 13
EtOH, N2, 70 °C
2 Se, NaOH,
PEG-400
CHO
Se
2 Se/3 CO/H2O
Cl
2
benzene, 65 °C
DMF, 95 °C, 1 atm
X
X
X
ref. 13
ref. 12
NaBH4
EtOH
Ar-(CH2)n-SeCN
n = 1, 2
ref. 15
Scheme 1 Literature protocols for the synthesis of symmetrical dibenzyl diselenides
Saravanan and co-workers described the synthesis of disel-
enides from the corresponding alcohols using DCC/CuCl and
tetraethylammonium tetraselenotungstate.17 However,
most of the methods require considerably longer reaction
duration for the conversion into diselenides. We sought an
alternative, simple and mild protocol for the synthesis of
dibenzyl diselenides from commercially available alcohols
as the starting materials.
reducing agent.21 This reagent can be readily prepared us-
ing commercially available starting materials, and so far it
has not been utilized as a selenium-transfer agent.
The selenating reagent NaBH2Se3 was prepared by a
slight modification of the procedure reported by Lalancette
and Arnac.20 Thus, 3 equivalents of selenium powder were
treated with 1 equivalent of NaBH4 suspended in THF at
0 °C under nitrogen atmosphere. Hydrogen gas was evolved
immediately and the conversion of the black selenium pow-
der into a reddish suspension within 10 minutes indicated
the formation of NaBH2Se3. In the initial part of the study,
the model substrate benzyl alcohol was treated with the VR
[generated by reaction of catalytic DMF (0.3 equiv) with
PCl5 (1.0 equiv)] in anhydrous MeCN for 10 minutes to acti-
vate the alcohol. The thus-activated alcohol was immedi-
ately treated with a freshly prepared solution of NaBH2Se3
and the reaction mixture was allowed to stir for 12–15 min-
utes. After reaction completion, as monitored by TLC, the
solvent was evaporated and the residue was hydrolyzed by
stirring with 10% HCl for 5 minutes. The precipitated Se was
filtered off. The expected dibenzyl diselenide (2a) was ob-
tained in 88% yield after silica gel column chromatography.
Alternatively, the hydrolysis can be carried out by direct
treatment of the reaction mixture, without evaporation of
the solvent, with 10% HCl for 5 minutes, followed by multi-
ple extractions with ethyl acetate. The product dibenzyl
diselenide was characterized by NMR and HRMS analysis.
The 77Se NMR spectrum showed a single peak at 398.1 ppm
corresponding to diselenide, indicating the absence of any
triselenide compound.
1) DCC, cat. CuCl
MeCN
1) Et3N, MsCl
0 °C, 30 min
R
OH
R
Se
R
OH
2) Li2Se2, THF
overnight
2
2) (Et4N)2WSe4
71–81%
ref. 16
ref. 17
53%
Scheme 2 Reported syntheses of symmetrical diselenides from alco-
hols
For the conversion of alcohol into the corresponding
diselenide (Scheme 3), the alcohol needs to be activated in
situ. We sought to employ the Vilsmeier reagent (VR) for its
efficient activation towards selenylation. Notably, the VR is
used as the reagent of choice for the formylation of elec-
tron-rich aromatics, the chlorination of alcohols, and the
conversion of carboxylic acids into acid chlorides.18 The
typical procedure for preparation of the VR involves the
treatment of DMF with a chlorinating agent such as PCl5.19
On the other hand, the preparation of sodium selenobo-
rate20 (NaBH2Se3) has been reported by Lalancette and co-
workers, and the reagent has been much less explored as a
R
1) DMF, PCl5
A plausible mechanism for the diselenide formation is
proposed in Scheme 4. Initially, the VR is formed by reac-
tion of DMF with PCl5. The alcohol then attacks the electro-
philic carbon of the VR with the elimination of chloride ion
to form an O-linked imidoyl chloride like intermediate [1A]
(Scheme 4). The formation of intermediate [1A] takes place
MeCN, r.t.,10 min
OH
Se
Se
2) NaBH2Se3
THF, r.t., 15 min
R
1
2
R
Scheme 3 Synthesis of dibenzyl diselenides from the corresponding
benzyl alcohols
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–H

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V. Panduranga et al.
Paper
Synthesis
N
H
O
PCl5
POCl3
Cl
Cl
H
B
Na
H
Se
N
Cl
Se
Se
H
H
OH
Se
O
N
r.t.,10 min
[1A]
DMF + NaCl
H
B
hydrolysis
3 H2O
oxidation
Se
SeH
Se
Se
H
2
[1B]
H3BO3
2 Se
2 H2
Scheme 4 Plausible mechanism for the formation of dibenzyl diselenide from benzyl alcohol
within 10 minutes of reaction duration as monitored by
ESI-MS, indicated by the m/z value of 234.24 [M + HCl]+, and
no benzyl chloride was observed during this period. On ad-
dition of the selenium-transfer reagent NaBH2Se3, BH2Se3– ion
adds to the benzylic carbon with the extrusion of DMF to
form [1B] which then undergoes hydrolysis to form benzyl
selenol. Finally, oxidation of benzyl selenol results in sym-
metrical diselenide.
The efficacy of the methodology was demonstrated by
employing differently substituted benzyl alcohols which af-
forded the corresponding diselenides in moderate to excel-
lent yields (Table 1). In the case of halogen-substituted ben-
zyl alcohols, the reaction proceeded smoothly irrespective
of the nature and position of the halide group (Table 1, en-
tries 5 and 6). In addition, substrates possessing electron-
donating substituents like Me and 4-OMe were also con-
verted into the corresponding diselenides in excellent yields
(Table 1, entries 2–4). The presence of electron-withdraw-
ing groups like NO2 and CN resulted in somewhat moderate
yields of the corresponding products (Table 1, entries 7–9).
Interestingly, these functional groups were tolerant under
the present conditions, giving the product diselenides che-
moselectively. To further demonstrate the efficacy of the
protocol, a scaled up reaction was carried out on a 20-mmol
scale using 4-methylbenzyl alcohol as the substrate. To our
gratification, a satisfactory yield of 86% was obtained under
the present conditions.
Then, allylic and cinnamyl alcohols were subjected to
the aforementioned conditions. Though the allyl alcohol
failed to produce the desired diselenide, cinnamyl alcohol
gave the corresponding diselenide in 88% yield (Table 1, en-
try 10). Also, aliphatic alcohols such as n-butanol did not
generate the target diselenides under the present protocol.
In the latter part of the study, we extended the chemis-
try described above to the preparation of organodisulfides.
Like diselenides, the disulfide moiety occurs ubiquitously in
proteins and many other bioactive molecules.22a It is also
found in a variety of natural products and pharmacological-
ly active compounds.22b–d In organic chemistry, a great deal
of attention has been paid to the synthesis and application
of disulfides. Sulfur–sulfur-bond-containing compounds
serve as important auxiliaries in the synthesis of 3-(ar-
ylthio)indoles,23 thia-Michael adducts,24 and β-hydroxy
thioethers,25 and also in the preparation of organosulfur
compounds via C–S bond formation.26 Also, disulfides find
wide applications as vulcanizing agents for rubbers and
elastomers, to improve tensile strength.27
The oxidative coupling of thiols to the corresponding di-
sulfides is a commonly used method for disulfide bond for-
mation.28 Although effective, this method has environmen-
tal and safety concerns with thiols being volatile and foul-
smelling. There are several other methods which make use
of non-thiolic precursors29 such as halides29a–i and to-
sylates.29j,k However, halides/tosylates are made from alco-
hols and the conversion of alcohols into the corresponding
1) P(NMe2)3, CCl4
CH2Cl2, –78 °C to r.t., 2.5 h
1) DCC, cat. CuCl
R
OH
R
OH
R
S
2) (BnNEt3)2MoS4
MeCN, 11–14 h
2
2) (BnNEt3)2MoS4
CH2Cl2, r.t., 3 h
ref. 30
ref. 30
Scheme 5 Reported methods for the preparation of disulfides from alcohols
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–H

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V. Panduranga et al.
Paper
Synthesis
halides/tosylates requires an additional step. Hence, the di-
rect conversion of an alcohol into the corresponding disul-
fide would be significantly useful.
However, reports on the one-pot conversion of alcohols
into disulfides are very scant (Scheme 5). Chandrasekaran
and co-workers employed DCC in the presence of catalytic
CuCl for the in situ activation of alcohol, followed by treat-
ment with benzyltriethylammonium tetrathiomolybdate in
MeCN for 11 hours.30 Alcohols can also be treated with
P(NMe2)3/CCl4 in CH2Cl2 at –78 °C and subsequently with
the tetrathiomolybdate to obtain disulfides in moderate
yields.30 In another example, when a mixture of benzoic
acid and benzyl alcohol was treated with Ph3P/NBS fol-
lowed by the tetrathiomolybdate, benzyl alcohol preferen-
tially reacted to form dibenzyl disulfide instead of the thio-
ester of benzoic acid.31 Inspired by the results obtained
with the diselenides, we envisaged in situ activation of ben-
zyl alcohols by the VR followed by treatment with sulfurat-
ed borohydride,32 NaBH2S3, as a sulfur-transfer reagent to
obtain the corresponding disulfides. NaBH2S3 can be readily
synthesized using NaBH4 and elemental sulfur, and is gen-
erally employed for the reduction of aldehydes, oximes, ke-
tones, and nitro, nitrile, amide and nitroso compounds.21,32
However, its sulfurating ability has been less explored.29c,l
The sulfur-transfer reagent NaBH2S3 was prepared by a
slight modification of the literature procedure, by treating
sulfur powder with a suspension of NaBH4 in anhydrous
THF at room temperature under nitrogen atmosphere.32 Af-
ter 10 minutes, the evolution of hydrogen gas ceased and
the thus-formed NaBH2S3 was directly used in the next
step. Initially, benzyl alcohol was treated with the VR and
the mixture was allowed to stir for 10 minutes at room
temperature, followed by the addition of a freshly prepared
solution of NaBH2S3. After a further 20–25 minutes, com-
plete consumption of the starting material was observed, as
monitored by TLC. After evaporation of the solvent, the res-
idue was treated with 10% HCl and precipitated sulfur pow-
der was filtered off. The product dibenzyl disulfide (3a) was
isolated in 90% yield after silica gel column chromatogra-
phy. Further, the generality of the protocol was demonstrat-
ed by using various substituted benzyl alcohols which af-
forded the corresponding disulfides 3b–i in moderate to ex-
cellent yields within short reaction duration (Scheme 6). All
the products were characterized by NMR and HRMS analy-
sis, and found to contain the disulfides as the only product
without any trace of thiols/trisulfides. Scaleup of the reac-
Table 1 Dibenzyl Diselenides Prepared from Benzyl Alcoholsa
Entry Alcohol 1
Diselenide product 2
Yieldb
(%)
OH
Se
Se
1
88
93
OH
Se
Se
2
OMe
OH
OH
Se
Se
3
92
81
75
Se
MeO
MeO
MeO
MeO
4
Se
OMe
I
OH
Se
Se
5
I
I
Cl
OH
Se
6
80
Se
Cl
Cl
NO2
OH
Se
7
74
70
89
88
Se
O2N
O2N
NO2
NO2
Se
8
OH
Se
NO2
CN
OH
Se
9
Se
NC
NC
R
1) DMF, PCl5
MeCN, r.t.,10 min
S
S
OH
OH
Se
10
2) NaBH2S3
Se
R
THF, r.t., 25 min
R
3a–i
1
3a: R = H (90%); 3b: R = 4-Me (86%); 3c: R = 4-OMe (90%); 3d: R = 3-OMe (86%);
3e: R = 2-I (84%); 3f: R = 4-Cl (87%); 3g: R = 4-NO2 (70%); 3h: R = 2-NO2 (66%);
3i: R = 4-CN (70%)
a Reaction conditions: benzyl alcohol (1 mmol), anhydrous MeCN (5 mL), PCl5
(1 mmol), DMF (0.02–0.03 mL), r.t., 10 min; then addition of NaBH2Se3 (1
mmol) in THF, r.t., 15 min.
b Isolated yield after silica gel (100–200 mesh) column chromatography.
Scheme 6 Synthesis of dibenzyl disulfides from benzyl alcohols
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–H

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V. Panduranga et al.
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Synthesis
tion to a 20-mmol scale for 4-methoxybenzyl alcohol led to
bis(4-methoxybenzyl) disulfide (3c) in a satisfactory yield
of 85% under the present conditions.
A similar mechanism as illustrated in Scheme 4 for
diselenides supposedly also holds good for the present
transformation, except that sulfurated borohydride is em-
ployed instead of selenated borohydride. However, detailed
analysis of the mechanistic pathway for both reaction types
is underway.
In conclusion, a one-pot protocol for the preparation of
symmetrical dibenzyl diselenides and disulfides from the
corresponding benzyl alcohols employing NaBH2Se3 and
NaBH2S3 as selenium- and sulfur-transfer reagent, respec-
tively, has been developed. The selenium- and sulfur-trans-
fer agents can be easily prepared from readily available pre-
cursors. Structurally diverse substituted benzyl alcohols af-
forded the corresponding diselenides and disulfides in good
to excellent yields. The protocol is simple and mild, and the
products were obtained within a short reaction time. We
hope that the present protocol will be of interest to organic
chemists working on sulfur and selenium chemistry.
ly prepared THF solution of NaBH2Se3 or NaBH2S3 (1 mmol) was added
and stirring was continued at the same temperature. After the reac-
tion was complete, as monitored by TLC analysis, the solvent was
evaporated under reduced pressure. The crude trichalcogenide [1B]
residue was hydrolyzed by stirring with 10% HCl in the presence of
EtOAc for 5 min. The precipitated Se/S was filtered off and the filtrate
was extracted repeatedly with EtOAc. Alternatively, the hydrolysis can
be carried out by direct treatment of the reaction mixture, without
evaporation of the solvent, with 10% HCl for 5 min, followed by multi-
ple extractions with EtOAc. The combined organic fraction was then
dried over anhydrous Na2SO4. The organic layer was filtered and con-
centrated under reduced pressure. The crude reaction mixture was
then purified by silica gel (100–200 mesh) column chromatography
using hexane–EtOAc (9.5:0.5) as the eluent to obtain the desired
product.
Dibenzyl Diselenide (2a)
Yellow solid; yield: 299 mg (88%); mp 92–94 °C (Lit.12 92–93 °C).
IR (neat): 3040, 2872, 810, 760, 700 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.20–7.29 (m, 10 H), 3.82 (s, 2JSeH = 10.7
Hz, 4 H).
77Se NMR (76.31 MHz, CDCl3): δ = 398.1.
HRMS (ESI): m/z [M + H]+ calcd for C14H15Se2: 342.9504; found:
342.9503.
All chemicals were used as obtained from Sigma Aldrich Company,
USA. The particle size of selenium powder (>99.5% trace metals basis)
and sulfur powder was ≤100 mesh. All solvents were dried and puri-
fied using recommended literature procedures, whenever necessary.
High-resolution mass spectra were recorded on a Micromass Q-TOF
spectrometer using electrospray ionization mode. 1H NMR and 13C
NMR spectra were recorded in CDCl3 with tetramethylsilane (TMS) as
reference on a Bruker AMX 400 spectrometer operating at 400 MHz
and 100 MHz, respectively, at the Indian Institute of Science, Banga-
lore. 77Se NMR (76.31 MHz) spectra were recorded in CDCl3 with
Me2Se as external reference. Melting points were determined in open
capillaries and are uncorrected. TLC experiments were done using
Merck TLC aluminum sheets (silica gel 60 F254) and chromatograms
were visualized by exposure in an iodine chamber or under a UV
lamp. Column chromatography was performed on silica gel (100–200
mesh) using EtOAc–hexane mixtures as the eluent.
Bis(4-methylbenzyl) Diselenide (2b)
Yellow solid; yield: 345 mg (93%); mp 58–60 °C (Lit.12 58–59 °C).
IR (neat): 3042, 2922, 2853, 836, 706 cm–1
1H NMR (400 MHz, CDCl3): δ = 7.16–7.23 (m, 8 H), 3.77 (s, 2JSeH = 10.9
Hz, 4 H), 2.33 (s, 6 H).
77Se NMR (76.31 MHz, CDCl3): δ = 392.8.
HRMS (ESI): m/z [M + H]+ calcd for C16H19Se2: 370.9817; found:
370.9820.
.
Bis(4-methoxybenzyl) Diselenide (2c)
Yellow solid; yield: 370 mg (92%); mp 72–73 °C (Lit.12 73–75 °C).
IR (neat): 3003, 2835, 1027, 820, 736 cm–1
1H NMR (400 MHz, CDCl3): δ = 7.16 (d, J = 8 Hz, 4 H), 6.83 (d, J = 4 Hz,
4 H), 3.82 (s, 2JSeH = 11.1 Hz, 4 H), 3.78 (s, 6 H).
.
77Se NMR (76.31 MHz, CDCl3): δ = 388.2.
NaBH2Se3
HRMS (ESI): m/z [M + H]+ calcd for C16H19O2Se2: 402.9715; found:
402.9715.
To a solution of NaBH4 (1 mmol) in anhydrous THF (5 mL), black sele-
nium powder (3 mmol) was added at 0 °C under an N2 atmosphere.
Immediate gas evolution was observed and the reaction was exother-
mic. Consumption of the selenium powder in less than 10 min indi-
cated the formation of NaBH2Se3. The reagent was directly used as
such in the next step for the present studies.
Bis(3-methoxybenzyl) Diselenide (2d)
Yellow solid; yield: 326 mg (81%); mp 74–76 °C.
IR (neat): 3050, 2832, 1040, 855, 776 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.22–7.30 (m, 3 H), 7.10 (d, J = 4 Hz, 3
H), 6.89 (t, J = 12 Hz, 2 H), 3.93 (s, 6 H), 3.75 (s, 2JSeH = 12.2 Hz, 4 H).
13C NMR (100 MHz, CDCl3): δ = 156.95, 137.98, 128.73, 118.87,
112.18, 111.98, 110.02, 53.66, 38.03.
77Se NMR (76.31 MHz, CDCl3): δ = 361.5.
NaBH2S3
The reagent was prepared as described for NaBH2Se3, except that sul-
fur powder was used in place of the selenium powder. Cooling with a
water bath can be used to control the exotherm during the addition of
sulfur powder (3 mmol) to NaBH4 (1 mmol) in anhydrous THF (5 mL).
HRMS (ESI): m/z [M + H]+ calcd for C16H19O2Se2: 402.9715; found:
402.9719.
Dibenzyl Diselenides and Disulfides; General Procedure
To a stirred suspension of a benzyl alcohol (1 mmol) in anhydrous
MeCN (5 mL) was added PCl5 (1 mmol) and DMF (0.02–0.03 mL) at r.t.
A clear yellow solution formed within 10 min. Without delay, a fresh-
Bis(2-iodobenzyl) Diselenide (2e)
Yellow solid; yield: 446 mg (75%); mp 80–82 °C.
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V. Panduranga et al.
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IR (neat): 3038, 2853, 749, 746, 614 cm–1
.
77Se NMR (76.31 MHz, CDCl3): δ = 410.1.
1H NMR (400 MHz, CDCl3): δ = 7.65 (t, J = 7 Hz, 2 H), 7.52 (t, J = 12 Hz,
2 H), 7.36 (d, J = 8 Hz, 2 H), 6.98 (d, J = 8 Hz, 2 H), 3.78 (s, 2JSeH = 13.4
Hz, 4 H).
HRMS (ESI): m/z [M]+ calcd for C18H18Se2: 393.9735; found: 393.9743.
Dibenzyl Disulfide (3a)
Yellow solid; yield: 222 mg (90%); mp 72–74 °C (Lit.29d 71–72 °C).
13C NMR (100 MHz, CDCl3): δ = 149.52, 137.33, 126.43, 125.71,
124.46, 95.26, 37.59.
77Se NMR (76.31 MHz, CDCl3): δ = 362.5.
HRMS (ESI): m/z [M + H]+ calcd for C14H13I2Se2: 594.7437; found:
594.7440.
IR (neat): 3023, 2850, 799, 748, 448 cm–1
1H NMR (400 MHz, CDCl3): δ = 7.11–7.19 (m, 10 H), 3.73 (s, 4 H).
13C NMR (100 MHz, CDCl3): δ = 141.16, 129.46, 128.82, 127.28, 44.82.
.
HRMS (ESI): m/z [M + H]+ calcd for C14H15S2: 247.0615; found:
247.0618.
Bis(4-chlorobenzyl) Diselenide (2f)
Yellow solid; yield: 328 mg (80%); mp 75–77 °C (Lit.12 73–75 °C).
Bis(4-methylbenzyl) Disulfide (3b)
Yellow solid; yield: 236 mg (86%); mp 42–44 °C (Lit.28j 40–42 °C).
IR (neat): 3021, 2920, 2854, 813, 742, 718 cm–1
1H NMR (400 MHz, CDCl3): δ = 7.14–7.26 (m, 8 H), 3.79 (s, 4 H), 2.33
IR (neat): 3038, 2862, 810, 700, 480 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.38 (d, J = 8 Hz, 4 H), 7.19 (d, J = 8 Hz,
4 H), 3.75 (s, 2JSeH = 10.9 Hz, 4 H).
77Se NMR (76.31 MHz, CDCl3): δ = 399.3.
HRMS (ESI): m/z [M + H]+ calcd for C14H13Cl2Se2: 410.8725; found:
410.8731.
.
(s, 6 H).
HRMS (ESI): m/z [M + H]+ calcd for C16H19S2: 275.0928; found:
275.0925.
Bis(4-nitrobenzyl) Diselenide (2g)
Yellow solid; yield: 320 mg (74%); mp 97–99 °C (Lit.15 99–100 °C).
IR (neat): 3074, 2930, 2839, 1506, 855, 792, 748 cm–1
1H NMR (400 MHz, CDCl3): δ = 8.17 (d, J = 8 Hz, 4 H), 7.41 (d, J = 8 Hz,
4 H), 3.80 (s, 2JSeH = 9.8 Hz, 4 H).
77Se NMR (76.31 MHz, CDCl3): δ = 480.0.
HRMS (ESI): m/z [M + H]+ calcd for C14H13N2O4Se2: 432.9206; found:
Bis(4-methoxybenzyl) Disulfide (3c)
Yellow solid; yield: 276 mg (90%); mp 75–77 °C (Lit.29k 75–78 °C).
IR (neat): 3012, 2833, 1031, 827, 728, 476 cm–1
1H NMR (400 MHz, CDCl3): δ = 7.24 (d, J = 8 Hz, 4 H), 6.95 (d, J = 4 Hz,
4 H), 3.92 (s, 4 H), 3.88 (s, 6 H).
HRMS (ESI): m/z [M + H]+ calcd for C16H19O2S2: 307.0826; found:
307.0829.
.
.
432.9209.
Bis(3-methoxybenzyl) Disulfide (3d)
Bis(2-nitrobenzyl) Diselenide (2h)
Yellow solid; yield: 303 mg (70%); mp 72–74 °C (Lit.15 72–74 °C).
IR (neat): 3064, 2971, 2872, 1511, 882, 797, 748 cm–1
1H NMR (400 MHz, CDCl3): δ = 7.95 (d, J = 8 Hz, 4 H), 7.56 (t, J = 12 Hz,
2 H), 7.22 (t, J = 8 Hz, 2 H), 3.98 (s, 2JSeH = 11.2 Hz, 4 H).
Yellow solid; yield: 263 mg (86%); mp 78–80 °C.
IR (neat): 3045, 2852, 781, 699, 445 cm–1
1H NMR (400 MHz, CDCl3): δ = 7.24–7.33 (m, 3 H), 7.22 (d, J = 4 Hz, 3
H), 7.09 (t, J = 12 Hz, 2 H), 3.98 (s, 6 H), 3.87 (s, 4 H).
13C NMR (100 MHz, CDCl3): δ = 159.62, 139.84, 129.47, 119.84,
.
.
77Se NMR (76.31 MHz, CDCl3): δ = 527.6.
112.18, 111.78, 55.76, 44.34.
HRMS (ESI): m/z [M + H]+ calcd for C14H13N2O4Se2: 432.9206; found:
HRMS (ESI): m/z [M + H]+ calcd for C16H19O2S2: 307.0826; found:
432.9209.
307.0822.
Bis(4-cyanobenzyl) Diselenide (2i)
Yellow solid; yield: 347 mg (89%); mp 127–129 °C (Lit.15 129–131 °C).
Bis(2-iodobenzyl) Disulfide (3e)
Yellow solid; yield: 419 mg (84%); mp 84–86 °C.
IR (neat): 3028, 2842, 2229, 825, 740, 718 cm–1
.
IR (neat): 3052, 2852, 758, 719, 610, 573 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.24 (d, J = 11.2 Hz, 4 H), 6.85 (d, J =
11.6 Hz, 4 H), 3.72 (s, 2JSeH = 10.4 Hz, 4 H).
1H NMR (400 MHz, CDCl3): δ = 7.82 (d, J = 8 Hz, 2 H), 7.52 (d, J = 8 Hz,
2 H), 7.38 (t, J = 12 Hz, 2 H), 7.03 (t, J = 7.4 Hz, 2 H), 3.82 (s, 4 H).
77Se NMR (76.31 MHz, CDCl3): δ = 427.1.
13C NMR (100 MHz, CDCl3): δ = 151.62, 139.27, 129.53, 128.71,
HRMS (ESI): m/z [M + H]+ calcd for C16H13N2Se2: 392.9409; found:
128.46, 96.31, 41.62.
HRMS (ESI): m/z [M + H]+ calcd for C14H13I2S2: 498.8548; found:
392.9403.
498.8552.
Dicinnamyl Diselenide (2j)
Bis(4-chlorobenzyl) Disulfide (3f)
Yellow solid; yield: 346 mg (88%); mp 132–134 °C.
White solid; yield: 274 mg (87%); mp 62–64 °C (Lit.29d 59–60 °C).
IR (neat): 3059, 2853, 1494, 793, 740, 692 cm–1
1H NMR (400 MHz, CDCl3): δ = 7.30–7.41 (m, 10 H), 6.70 (d, J = 16.0
Hz, 2 H), 6.32–6.38 (m, 2 H), 4.27 (d, J = 11.2 Hz, 2JSeH = 10.8 Hz, 4 H).
.
IR (neat): 3032, 2853, 829, 719, 475 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.34–7.55 (m, 8 H), 3.79 (s, 4 H).
13C NMR (100 MHz, CDCl3): δ = 137.06, 132.78, 129.26, 128.91, 39.89.
13C NMR (100 MHz, CDCl3): δ = 136.01, 134.19, 128.73, 128.34,
126.81, 125.01, 45.47.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–H

G
V. Panduranga et al.
Paper
Synthesis
HRMS (ESI): m/z [M + H]+ calcd for C14H13Cl2S2: 314.9836; found:
314.9839.
6255. (e) Stadtman, T. C. Science 1974, 183, 915. (f) Illman, D.
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Synthesis, In Topics in Current Chemistry; Vol. 208; Wirth, T., Ed.;
Springer: Berlin, 2000.
Bis(4-nitrobenzyl) Disulfide (3g)
Yellow solid; yield: 234 mg (70%); mp 108–110 °C (Lit.29d 109–
111 °C).
(3) (a) Fukuzawa, S.; Takahashi, K.; Kato, H.; Yamazaki, H. J. Org.
Chem. 1997, 62, 7711. (b) Tomoda, S.; Iwaoka, M. J. Chem. Soc.,
Chem. Commun. 1988, 1283. (c) Tiecco, M.; Testaferri, L.; Santi,
C.; Tomassini, C.; Marini, F.; Bagnoli, L.; Temperini, A. Tetrahe-
dron: Asymmetry 2000, 11, 4645. (d) Tiecco, M.; Testaferri, L.;
Marini, F.; Sternativo, S.; Santi, C.; Bagnoli, L.; Temperini, A. Tet-
rahedron: Asymmetry 2001, 12, 3053. (e) Back, T. G.; Moussa, Z.;
Parvez, M. J. Org. Chem. 2002, 67, 499. (f) Freudendahl, D. M.;
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Soc., Perkin Trans. 1 1995, 2871.
IR (neat): 3052, 2916, 838, 802, 798, 720 cm–1
1H NMR (400 MHz, CDCl3): δ = 8.29 (d, J = 8 Hz, 4 H), 7.69 (d, J = 8 Hz,
4 H), 3.87 (s, 4 H).
13C NMR (100 MHz, CDCl3): δ = 147.85, 146.82, 130.43, 126.01, 43.09.
HRMS (ESI): m/z [M + Na]+ calcd for C14H12N2O4S2Na: 359.0136;
found: 359.0135.
.
Bis(2-nitrobenzyl) Disulfide (3h)
Yellow solid; yield: 222 mg (66%); mp 106–107 °C (Lit.29d 105–
106 °C).
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Silveira, C. C.; Rocha, J. B. T.; Wessjohann, L. A. Tetrahedron Lett.
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1999, 10, 1019.
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3169.
IR (neat): 3077, 2957, 1536, 855, 801, 756 cm–1
1H NMR (400 MHz, CDCl3): δ = 8.05 (d, J = 8 Hz, 4 H), 7.66 (t, J = 12 Hz,
2 H), 7.34 (t, J = 8 Hz, 2 H), 4.04 (s, 4 H).
13C NMR (100 MHz, CDCl3): δ = 147.82, 138.77, 134.73, 129.83,
125.08, 121.01, 34.04.
.
HRMS (ESI): m/z [M + H]+ calcd for C14H13N2O4S2: 337.0317; found:
337.0313.
(7) (a) Iwaoka, M.; Katsuda, T.; Komatsu, H.; Tomoda, S. J. Org.
Chem. 2005, 70, 321. (b) Schiesser, C. H.; Sutej, K. J. Chem. Soc.,
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Bis(4-cyanobenzyl) Disulfide (3i)
Yellow solid; yield: 207 mg (70%); mp 134–136 °C.
IR (neat): 3012, 2855, 2218, 820, 732, 723 cm–1
1H NMR (400 MHz, CDCl3): δ = 7.38 (d, J = 16 Hz, 4 H), 7.10 (d, J = 16
Hz, 4 H), 3.82 (s, 4 H).
13C NMR (100 MHz, CDCl3): δ = 144.35, 132.30, 128.52, 115.84,
111.24, 42.32.
HRMS (ESI): m/z [M + H]+ calcd for C16H13N2S2: 297.0520; found:
297.0524.
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.
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Acknowledgment
We sincerely thank the Council of Scientific and Industrial Research
for financial support. V.P., N.R.P. and B.P. thank CSIR for Senior Re-
search Fellowships.
Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0035-1561579.
S
u
p
p
ortioInfgrmoaitn
S
u
p
p
ortiInfogrmoaitn
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J. Organomet. Chem. 1995, 485, 19.
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–H