Synthesis and reactivity of dipropargylic disulfides: tandem rearrangements, cyclization, and oxidative dimerization

Article abstract of DOI:10.1016/j.tet.2010.01.012

Synthesis and facile rearrangement and cyclization reaction of new dipropargylic disulfides are described. A possible mechanism for these transformations involving an initial double [2,3]-sigmatropic rearrangement to the elusive diallenyl disulfides via a thiosulfoxide intermediates is suggested.

Full text of DOI:10.1016/j.tet.2010.01.012

Tetrahedron 66 (2010) 1925–1930
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Tetrahedron
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Synthesis and reactivity of dipropargylic disulfides: tandem rearrangements,
cyclization, and oxidative dimerizationq
*
Samuel Braverman , Marina Cherkinsky, David Meridor, Milon Sprecher
Department of Chemistry, Bar-Ilan University, Ramat-Gan 52900, Israel
a r t i c l e i n f o
a b s t r a c t
Article history:
Synthesis and facile rearrangement and cyclization reaction of new dipropargylic disulfides are de-
scribed. A possible mechanism for these transformations involving an initial double [2,3]-sigmatropic
rearrangement to the elusive diallenyl disulfides via a thiosulfoxide intermediates is suggested.
Ó 2010 Elsevier Ltd. All rights reserved.
Received 21 July 2009
Received in revised form
26 November 2009
Accepted 4 January 2010
Available online 11 January 2010
Keywords:
Disulfides
Thiols
Thioethers
Thiosulfoxides
Thiosulfates
Sigmatropic rearrangement
Desulfurization
1. Introduction
In recent years a major goal of our investigations has been the
use of tandem multiple sigmatropic rearrangements and cycliza-
tions of sulfur and selenium bridged propargylic systems, for the
preparation of novel complex polycyclic heteroatom systems,
which are of synthetic, mechanistic, and probable medicinal in-
terest, in a manner exercising atom economy. Prompted by our
recent discovery of an unprecedented sequence of sigmatropic
rearrangements and cycloadditions transforming dipropargylic
dialkoxy disulfides to novel dithiabicyclic derivatives,2 (Scheme 1)
related to naturally occurring zwiebelanes isolated from allium
species,3–5 we have prepared several dipropargylic disulfides for
further oxidation and propargyl/allene isomerization to the corre-
sponding
a-disulfones. The latter have attracted little attention
relative to the considerable interest in the reactivity of vic-disulf-
oxides.6,7 This may be due in part to the greater thermodynamic
stability of the former. In the event, we were surprised to discover
that dipropargylic disulfides themselves undergo facile rearrange-
ment and cyclization reactions under mild thermal conditions.
Scheme 1. Tandem sigmatropic rearrangements and cyclization of dipropargylic dia-
lkoxy disulfides.
2. Results and discussion
While the preparation of disulfides in general is well docu-
mented,8 only one single dipropargyl disulfide has been pre-
viously reported.9 Furthermore, while the preparation of
q
See Ref. 1.
* Corresponding author. Tel.: þ972 3 5318322; fax: þ972 3 7384053.
E-mail address: bravers@mail.biu.ac.il (S. Braverman).
0040-4020/$ – see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.01.012

1926
S. Braverman et al. / Tetrahedron 66 (2010) 1925–1930
disulfides is usually straightforward, the preparation of prop-
argylic disulfides proved quite challenging. After an extensive
review of literature data, an alcohol–thioacetate–thiol route was
chosen. A variety of literature methods for the transformation of
thioacetate (2) to the corresponding thiol (3) investigated by us,
including reduction with lithium aluminum hydride,9 alkaline
hydrolysis,10,11 and nickel boride catalyzed methanolysis12 proved
unsuccessful. Eventually, we succeeded in preparing several
dipropargyl disulfides (4) in reasonable yields by the method
described in Scheme 2, involving the use of acidic conditions for
the conversion of the propargyl thioacetates (2) to the corre-
sponding thiols 3 and the one-pot oxidation of the latter by iodine
at 0 ꢀC. Though as a rule the disulfides in question exhibit high
reactivity under thermal conditions (see below), the substitution
pattern has a significant effect on their stability and reactivity.
On increasing the polarity of the solvent the reaction is accelerated
and the yield of the thienyl disulfides 6 rises. These results may be
most reasonably explained by the mechanisms presented in
Schemes 4 and 7.
S
R1
S
S S
S
S
S S
R1
R1
[3,3]-σ
R1
R1
[2,3]-σ
[2,3]-σ
R1 R1
4a-c
R1
7a-c
8a-c
R1
S
R1
S
R1
[1,3]-H
S
S
S
R1
R1
R1
S
9a-c
5a-c
Thus, while g-substituted disulfides 4b and 4c are stable at room
temperature, unsubstituted compound 4a slowly undergoes de-
Scheme 4. Thieno-thiophenes from dipropargylic disulfides.
composition and should be used soon after preparation. With
regard to a-substituted disulfide 4d, we were able to prepare it by
The proposed mechanism for the formation of compounds 5,
involves an initial double [2,3]-sigmatropic rearrangement via
a thiosulfoxide intermediate 7 to the elusive diallenyl disulfide 8. As
previously shown by us,13 disulfide 8 undergoes a [3,3]-sigmatropic
rearrangement followed by a double Michael type intramolecular
addition to yield 9. Finally, prototropic aromatization converts in-
termediate 9 to the isolated product 5 (Scheme 4). The trans-
formation of 4 to 5 is a remarkable example of a five-step tandem
process and of atom economy.
oxidation of the corresponding thiol at ꢁ78 ꢀC and characterize it
only by low-temperature 1H and 13C NMR spectra. Attempted
isolation or raising the temperature results in complete de-
composition into a mixture of unidentified products.
R2
R2 SH
OH R2 OX R2 SAc
ii iii
R2
R2
S S
i
iv
R1 R1
A double [2,3]-sigmatropic rearrangement of
diallyl disulfides to the thermodynamically more stable
a-substituted
R1
3a-d
R1
R1
1a-d
R1
2a-d
g
-
4a-d
substituted derivatives involving a thiosulfoxide intermediate,
analogous to the rearrangement of 4 to 8, has been previously
reported by Baldwin.14 More recently, the sigmatropic rearrange-
ment of an allylic disulfide followed by desulfurization has been
used by Crich for the preparation of peptide derived allylic sul-
fides.15 To confirm the involvement of the monoallene thiosulfoxide
intermediates in the sigmatropic rearrangement of dipropargylic
disulfides, desulfurization of the postulated thiosulfoxide with tri-
phenylphosphine was attempted. Indeed, on heating of dipropargyl
disulfide 4a in the presence of triphenylphosphine in deuter-
iobenzene (in an NMR-tube), formation of allenyl propargyl sulfide
10 was detected almost immediately (Scheme 5). Conversion of 4a
to sulfide 10 at 40 ꢀC proceeds to completion with t1⁄2 ¼115 min.
However, since 10 proved unstable under attempted chromato-
graphic separation from triphenylphosphine sulfide and excess
triphenylphosphine, it was characterized by its 1H and 13C NMR
spectra only.
a: R1= R2 = H, X = Ms; b: R1=Me, R2 = H, X = Ms; c:
R1= Ph, R2 = H, X = Ms; d: R1= H, R2 = Me, X = Ts;
Scheme 2. Preparation of propargylic disulfides. Reagents and conditions: (i) MeSO2Cl,
Et3N, Et2O,1.5 h, 0 o to rt (1d: p-TosCl, Et2O rt, 5 h); (ii) AcSK, MeOH, 2 h, rt (2d: reflux, 5 h);
(iii) concd HCl, MeOH, reflux, overnight; (iv) I2, MeOH, 0 ꢀC, 0.5 h (4d: ꢁ78 ꢀC, 15 min).
With these compounds at hand, we studied their thermal re-
activity in various organic solvents. Chromatographic separation of
the reaction mixture and extensive spectroscopic determinations,
which included full analysis of 1H and 13C NMR data with the aid of
2D techniques, as well as IR and HRMS, revealed formation of two
products: thieno-thiophene derivatives 5 and thienyl disulfides 6 in
a ratio depending on the reaction conditions (Scheme 3, Table 1).
S S
R1
S
H
O
R1
Δ
+
S
S
O
R1
S S
R1 R1
R1
S
R1
S
R1
H
S S
S
PPh3, C6D6
40 oC, 3 h
- Ph3PS
S
4a-c
5a-c
6a-c
•
[2,3]-σ
•
Scheme 3. Thermal reactivity of dipropargylic disulfides.
4a
7a
10
Table 1
Thermal reactivity of dipropargylic disulfides 4a–c
Scheme 5. Sigmatropic rearrangement and desulfurization of dipropargyl disulfide.
Entry Compound R1
Solvent
T
ꢀC Reaction 5:6 Ratioa Isolated
Further evidence for the proposed mechanism has been
obtained from triphenylphosphine induced sulfur degradation of
a number of mixed propargyl disulfides 12a–c to the allenyl sulfides
13a–c, which were isolated by column chromatography (Scheme 5).
The required mixed disulfide 12a–c were obtained by the reaction
of propargylthiosulfate 11 with the corresponding thiolate
(Scheme 6).16 (Formation of the desired unsymmetrical propargylic
disulfides was usually accompanied by the formation of small
quantities of symmetrical dialkyl or diaryl disulfides. While we
were unable to separate these by-products from disulfides 12a–c by
chromatography, reductive desulfurization was nevertheless
Time (h)
yieldb (%)
1
2
3
4
5
7
8
4a
4ac
4b
4b
4b
4c
H
H
CHCl3
CHCl3
60
60
60
60
70
60
60
1.5
2.0
160
100
24
1:2
10:1
5:1
1:2.6
6b only
6:1
40
80d
65
55
45
Me CHCl3
Me CH3CN
Me DMSO
Ph
Ph
CHCl3
CH3CN
24
53
4c
16
3:1
48
a
b
c
Determined according 1H NMR spectra.
Total yield of products 5 and 6 after column chromatography.
The reaction was performed under Ar.
The yield of product 5a.
d

S. Braverman et al. / Tetrahedron 66 (2010) 1925–1930
1927
carried out upon such mixtures since symmetrical dialkyl or diaryl
THF/H2O,
75 oC, I2
S S
S S
SSO3Na
disulfides are known to be stable to heating with triphenylphos-
phine for long periods.17,18) It should be noted that synthesis of
compound 11 presented a challenge since the conventional pro-
cedure involving interaction of the appropriate bromide with so-
dium thiosulfate in water/methanol mixture19 did not result in any
desired product. This hurdle was overcome by carrying out the
reaction under phase transfer catalysis conditions (Scheme 6).
I I
8a
11
4a
I
I
I
I
I
I
+
S S
15
S S
S S
14
Scheme 8. Synthesis of iodo-dithiins.
S
Br
SSO3Na
ii
S S
S
R
iii
S
i
R
3. Conclusions
R
•
- Ph3PS
•
11
12a-c
13a-c
In summary, we presented here a synthesis of new dipropargylic
disulfides, which undergo facile tandem rearrangements and cy-
clization reaction under mild thermal conditions. The reaction in-
volves elusive thiosulfoxide intermediates and affords novel
thiophene derivatives.
12a, 13a:R = Bn; 12b, 13b: 4-Tol; 12c, 13c: 4-ButC6H4
Scheme 6. Synthesis, rearrangement and desulfurization of propargylic disulfides.
Reagents and conditions: (i) Na2SSO3$5H2O, CHCl3/H2O (4:1), 4 h, reflux, catalyst
BnEt3NCl, yield 78%; (ii) RSH/KOH, H2O, 0.5 h, 0 ꢀC; (iii) PPh3, C6H6, 60 ꢀC.
In order to provide further support of the suggested mechanism
for the transformation of propargyl disulfides to allenyl sulfides, the
effect of substitution on the rate of reaction was investigated. We
have thus found that while both dipropargyl and benzyl propargyl
disulfides 10 and 12a react at the same rate (t1⁄2 ¼115 min), the rate of
the reaction of aryl propargyl disulfides 12b and 12c was consider-
ably slower (t1⁄2 ¼289 min).
4. Experimental section
4.1. General
Melting points were obtained on a Thomas Hoover melting
point apparatus and are uncorrected. IR spectra were recorded on
a Nicolet 60 SXB FTIR instrument. 1H NMR and 13C NMR were
recorded on Bruker AC-200, DPX-300 or DMX-600 spectrometers
in either CDCl3 or other deuterated solvents, using TMS as internal
Formation of disulfides 6 may be explained by air oxidation of
the unstable intermediates 9 followed by dimerization, as shown in
Scheme 7. An alternative mechanism involving hydrolytic cleavage
of one ring of 9 followed by oxidative steps leading to 6 is also
conceivable. To prove the involvement of air oxidation in the for-
mation of compounds 6 we have carried out the thermal rear-
rangement of disulfide 4a under an Ar atmosphere. Under these
conditions the ratio of products 5a/6a changed drastically from 1:2
to 10:1. Compounds of type 6 are related to the thienyl disulfides
found as components of distilled oils and extracts of Allium
species.20
standard. Chemical shifts are reported in
d units, and coupling
constants in Hz. COSY and NOSY experiments have been carried out
in order to assign 1H and 13C spectra and confirmed the structures
of new compounds. High-resolution mass spectra were obtained on
a VG-Fison Autospec instrument. Other mass spectra were obtained
on a Finningan GC/Ms 4021, with either electronic (EI) or chemical
ionization (CI), or on Q ToF micro MS with electrospray (ES). Col-
umn chromatography was performed with Merck silica gel 60
(230–400 mesh), and TLC was run on precoated Merck silica gel
plates 60 F254 (2.00 mm). All commercially available chemicals
were used without further purification. Preparation of propargyl
mesylates and thioacetates were described by us previously.22
S
R1
S
S S
S S
R1
R1
[2,3]-σ
[2,3]-σ
[3,3]-σ
4.2. General procedure for the preparation of disulfides 4a–c
R1 R1
R1
7a-c
To a solution of the respective thioacetate (3.9 mmol) in MeOH
(20 mL), 5 drops of concd HCl were added at room temperature and
the reaction mixture was heated to reflux overnight. After cooling
to 0 ꢀC and 12.5 mL of a 5% solution of I2 (0.49 g, 1.95 mmol) in
MeOH was added slowly. Powdered Na2SO3 was added to the re-
action mixture to destroy excess I2, methanol was evaporated un-
der reduced pressure, and the residue was diluted with diethyl
ether (50 mL). The ether solution was washed with water
(30 mLꢂ2), dried over anhydrous MgSO4, and evaporated to give
the products as yellow oils. Disulfides 4a and 4b were obtained
sufficiently pure, and to avoid possible decomposition upon chro-
matography, were used as it. Disulfide 4c was purified by flash
chromatography on silica gel with EtOAc/hexanes (1:6) as eluent.
4a-c
8a-c
R1
R1
S
R1
S
O2
S
+
OOH
S
S
S
R1
R1
9a-c
H
H
R1
O
OH
O
R1
S
O
R1
S
S
R1
a, R1 = H; b, R1= Me; c, R1= Ph
6a-c
R1
H
S
4.2.1. 3-(Prop-2-ynyldithio)prop-1-yne (4a). Colorless oil (0.18 g,
65%); nmax (neat) 3304, 3277, 2118, 1648, 1400, 1219, 630 cmꢁ1; 1H
Scheme 7. Oxidative dimerization of dipropargylic disulfides.
Supporting the proposed formation of bis-allene intermediates
8, is the finding that in the preparation of unsubstituted dipro-
pargyl disulfide 4a by reaction of sodium propargylthiosulfate 11
with iodine in aqueous THF at 75 ꢀC,21 the two isomeric dihy-
drodithiins 14 and 15 were obtained in moderate yield in a 1:1 ratio
(Scheme 8). Conversion of 14 to 15 may occur by a reversible [1,3]-H
shift.
NMR (300 MHz, CDCl3):
d
3.62 (d, J¼2.6 Hz, 4H), 2.37 (t, J¼2.6 Hz,
2H); 13C (75 MHz, CDCl3):
d 79. 6 (Cq), 72.8 (CH), 27.3 (CH2); m/z (CI,
CH4) 141 (53, [MꢁH]þ); HRMS (CI, CH4): found 140.9832. C6H5S2
requires 140.9833.
4.2.2. 1-(But-2-ynyldithio)but-2-yne (4b). Colorless oil (0.189 g,
57%); nmax (neat) 2242, 1738, 1223, 1156, 1056, 1027 cmꢁ1; 1H NMR

1928
S. Braverman et al. / Tetrahedron 66 (2010) 1925–1930
(300 MHz, CDCl3):
d
3.57 (q, J¼2.6 Hz, 4H), 1.85 (t, J¼2.6 Hz 6H); 13
C
3H); 13C (75 MHz, CDCl3):
d 151.6 (C), 142.96 (C), 128.1 (C), 111.1 (CH)
42.1 (CH), 29.6 (CH2), 23.8 (CH3), 13.5 (CH3); m/z (CI/CH4) 170 (53,
Mþ), 155 (100, MþꢁCH3); HRMS (CI/CH4): found 170.0219. C8H10S2
requires 170.0224.
(75 MHz, CDCl3):
d
80.5 (Cq), 74.6 (Cq), 28.3 (CH2), 3.8 (CH3); m/z
(CI, CH4) 170 (71, Mþ); HRMS (CI/CH4): found 170.0235. C8H10S2
requires 170.0224.
4.2.3. {3-[(3-Phenylprop-2-ynyl)dithio]prop-1-ynyl}benzene
4.3.3. 1,4-Diphenyl-1H,3H-thieno[3,4-c]thiophene (5c). Yellow nee-
dles, mp 119–120 ꢀC (0.133 g, 45.4%, reaction was carried out in
chloroform); Rf (10% EtOAc/hexanes) 0.49; nmax (KBr) 3441, 2927,
1387, 1265, 1056, 759, 698 cmꢁ1; UV (hexane) lmax 284; 1H NMR
(4c). Yellow oil (0.34 g, 60%); Rf (14% EtOAc/hexanes) 0.5; nmax
(neat) 3055, 2306, 1593, 1262, 1094, 1024, 801, 751, 686 cmꢁ1 1H
;
NMR (300 MHz, CDCl3):
d
7.45–7.28 (m, 10H), 3.85 (s, 4H); 13C
(75 MHz, CDCl3):
d
131.8 (CH), 128.5 (CH), 128.4 (CH), 122.9 (C ipso),
(300 MHz, CDCl3):
d
7.54–7.25 (m, 10H), 6.61 (s, 1H), 5.55 (s, 1H),
151.3 (C), 142.7 (C), 141.5 (C),
85.0 (^C–), 84.7 (^C–), 28.9 (CH2); m/z (CI/CH4) 294 (100, Mþ);
4.23 (s, 2H); 13C (50 MHz, CDCl3):
d
HRMS (CI/CH4): found 294.0550. C18H14S2 requires 294.0537.
134.0 (C) 133.6 (C), 128.9 (CH), 128.7 (CH), 127.9 (CH), 127.6 (CH),
127.4 (CH),126.8 (CH),115.2 (CH), 50.5(CH), 32.0 (CH2); m/z (CI/CH4)
295 (100, MHþ), 294 (98, Mþ), 261 (47, [MꢁHS]þ); HRMS (CI/CH4):
found 294.0536. C18H14S2 requires 294.0537.
4.2.4. But-3-yne-2-thiol (3d). To a solution of S-(1-methylprop-2-
ynyl) ethanethioate (0.2 g, 1.56 mmol) in CD3OD (2 mL), 0.1 mL of
concd HCl was added at room temperature and the reaction mix-
ture was heated at 50 ꢀC until completion of the reaction as in-
dicated by NMR determination (overnight). According to its NMR
spectrum thiol 3d was obtained as a pure compound and was used
4.3.4. 4-({[(4-Formylthien-3-yl)methyl]dithio}methyl)thiophene-3-
carbaldehyde (6a). Light-brown solid, mp 130–132 ꢀC (0.084 g,
26.6%, reaction was carried out in chloroform); Rf (25% hexanes/
CH2Cl2) 0.15; nmax (KBr) 3092, 2924, 1676(C]O), 1268, 915,
753 cmꢁ1; UV (hexane) lmax 232, 345; 1H NMR (600 MHz, CDCl3):
without isolation. 1H NMR (200 MHz, CD3OD)
d
3.73 (qd, J¼6.9,
2.4 Hz, 1H), 2.68 (d, J¼2.4 Hz, 1H), 1.52 (d, J¼6.9 Hz, 3H); 13C NMR
(75 MHz, CD3OD)
d
87.3 (Cq), 71.6 (CH), 26.9 (CH), 20.6 (CH3).
d
9.98 (d, J¼1.2 Hz, 2H), 8.10 (d, J¼3.6 Hz, 2H), 7.19 (dd, J¼3.6, 1.2 Hz,
2H), 4.01 (s, 4H); 13C (75 MHz, CDCl3):
d
185.3 (HC]O), 140.3 (CH),
4.2.5. 3-[(1-Methylprop-2-ynyl)dithio]but-1-yne (4d). To a stirred
solution of but-3-yne-2-thiol 3d prepared from 0.2 g of S-(1-
methylprop-2-ynyl) ethanethioate in CD3OD (2 mL) cooled to
ꢁ78 ꢀC, a 5% solution of I2 (0.2 g, 0.78 mmol) in CD3OD (2 mL) was
slowly added dropwise. Powdered Na2SO3 was added to the re-
action mixture to destroy excess I2, following filtration. This
methanolic solution of pure disulfide 4d (obtained as a mixture of
two diastereomers) could be stored at ꢁ78 ꢀC for 24 h.
139.2 (C), 137.1 (C), 126.2 (CH), 36.3 (CH2); m/z (CI, CH4): 315 (10,
MHþ), 157 (35, Mþ/2), 125 (100); HRMS (CI, CH4) found 314.9651.
C12H11O2S4 requires 314.9642.
4.3.5. 1-[4-({[(4-Acetyl-2-methylthien-3-yl)methyl]dithio}methyl)-5-
methylthien-3-yl]ethanone (6b). Light-brown solid, mp 160–162 ꢀC
(0.04 g, 10.8%, reaction was carried out in chloroform); Rf (14%
EtOAc/hexanes) 0.18; nmax (KBr) 3082, 2922, 1660(C]O), 1263,
1047, 755 cmꢁ1; UV (hexane) lmax 232, 345; 1H NMR (600 MHz,
1H NMR (200 MHz, CD3OD):
d
3.93 and 3.92 (qd, J¼7.2, 2.4 Hz,
1H each), 2.81 (d, J¼2.4 Hz, 1H for both diastereomers), 1.53 and
CDCl3):
(75 MHz, CDCl3): d 193.5(C]O), 139.7 (C), 138.3 (C), 134.2 (C), 131.7
d
7.80 (s, 2H), 4.14 (s, 4H), 2.50 (s, 6H), 2.45 (s, 6H); 13C
1.52 (d, J¼7.2 Hz, 3H each), 13C (75 MHz, CD3OD):
d
84.9 (^C– for
both diastereomers), 73.9 (^CH for both diastereomers), 36.8 and
36.5 (–CH– each), 21.7 and 20.5 (–CH3 each).
(CH), 36.0 (CH2), 28.4 (CH3), 13.6 (CH3); m/z (CI/CH4): 370 (11, Mþ),
185 (24, Mþ/2), 153 (100, MþꢁC8H9S3O), HRMS (CI, CH4) found
370.0152. C16H18O2S4 requires 370.0190.
4.3. General procedure for the rearrangement of disulfides
4a–c
4.3.6. Bis(2-Phenyl-4-benzoyl-3-thienylmethylene)disulfide
(6c). Orange solid, mp 220–223 ꢀC (0.047 g, 7.6%, reaction was
carried out in chloroform); Rf (10% EtOAc/hexanes) 0.12; nmax (KBr)
3061, 1648)C]O), 1445, 1250, 1076, 907, 697 cmꢁ1; UV (hexane)
The disulfide (1 mmol) was dissolved in the appropriate dry
solvent (5 mL) and heated under stirring at 60–70 ꢀC until disap-
pearance of the starting material as shown by TLC (for solvents and
time see Table 1). After evaporation of the solvent (CHCl3 or CH3CN)
the crude reaction mixture was subjected to column chromatog-
raphy on silica gel. In the case of entry 4 (Table 1), the DMSO so-
lution was diluted with dichloromethane (30 mL) and washed with
water (20 mLꢂ3). The combined organic phase was dried over
MgSO4 and evaporated to give the mixture of compounds 5a–c and
6a–c, which were separated by column chromatography on silica
gel.
lmax 284; 1H NMR (200 MHz, CDCl3):
20H), 3.91 (s, 4H); 13C (75 MHz, CDCl3):
d
7.84 (s, 2H), 7.60–7.35 (m,
191.7 (C]O), 139.8 (C),
d
138.6 (C), 133.8 (C) 133.1 (CH), 132.5 (CH), 130.1 (CH), 129.9 (CH),
129.6 (CH), 128.7 (CH), 128.3 (CH), 53.4 (CH2); m/z (CI/CH4) 619 (82,
MHþ), 309 (86, Mþ/2); HRMS (CI, CH4) found 619.0943. C36H27O2S4
requires 619.0894.
4.4. Preparation of sodium propargylthiosulfate 11
To a solution of propargyl bromide (0.96 mL, 9 mmol) in chlo-
roform (8 mL), a solution of sodium thiosulfate pentahydrate (2.7 g,
9 mmol) and benzyltriethylammonium chloride (0.2 g, 0.9 mmol)
in water (2 mL) was added and the reaction mixture was heated at
60 ꢀC with vigorous stirring for 4 h. The reaction mixture was then
evaporated to dryness and the residue was extracted with MeOH
(2ꢂ50 mL). The combined methanol extract was evaporated and
the residue was washed with CH2Cl2 to remove the catalyst and the
remaining propargyl bromide. The resulting solid was dried in
vacuum to give the title compound 11 (1.22 g, 78%) as a white-
cream solid; nmax (KBr) 3289, 2952, 2951, 2252, 2117, 1621, 1404,
4.3.1. 1H,3H-Thieno[3,4-c]thiophene (5a)23. White solid, mp 59–
60 ꢀC (0.019 g, 13.4%); Rf (25% CH2Cl2/hexanes) 0.24; nmax (KBr):
2925, 2371, 1388, 1262, 1034, 804 cmꢁ1; UV (hexane) lmax 230; 1H
NMR (300 MHz, CDCl3):
d
6.83 (s, 2H), 3.92 (s, 4H); 13C (75 MHz,
CDCl3):
d 146.3 (C), 115.1 (CH), 30.7 (CH2); m/z (CI, CH4) 143 (21,
MHþ), 142 (23, Mþ), 141 (16, [MꢁH]þ); HRMS (CI/CH4): found
142.9991. C6H7S2 requires 142.9989.
4.3.2. 1,4-Dimethyl-1H,3H-thieno[3,4-c]thiophene (5b). White solid,
mp 49–50 ꢀC (0.092 g, 54.2%, reaction was carried out in chloro-
form); Rf (14% EtOAc/hexanes) 0.84; nmax (KBr) 3391, 2927, 1510,
1255, 1058, 806, 746 cmꢁ1; UV (hexane) lmax 232; 1H NMR
1237, 1204, 1042, 653 cmꢁ1
;
1H NMR (300 MHz, D2O)
d
¼2.88 (t,
J¼2.6 Hz, 2H), 4.03 (d, J¼2.6 Hz, 2H); 13C NMR (75 MHz, D2O)
d
22.9
(300 MHz, CDCl3):
1H), 3.79 (q, J¼1.2 Hz, 2H), 2.30 (t, J¼1.2 Hz, 3H), 1.56 (d, J¼6.6 Hz,
d
6.53 (d, J¼1.2 Hz,1H), 4.45 (qq, J¼6.6 Hz,1.2 Hz,
(CH2), 72.9 (C), 80.1 (C); ToF ES-MS m/z (%) 151 (100,
HC^CCH2SSOꢁ3 ), 113 (41, HS–SOꢁ3 ).

S. Braverman et al. / Tetrahedron 66 (2010) 1925–1930
1929
4.5. General procedure for the preparation of disulfides 12a–c
124 (64, [C7H8S]þ); HRMS(CI, CH4) found 163.0582. C10H11S re-
quires 163.0581.
The respective thiol (1.61 mmol) was added under stirring to an
aqueous solution (5 mL) of KOH (0.1 g, 1.78 mmol) and the reaction
mixture was heated to reflux for 1 h. After cooling to 0 ꢀC an
aqueous solution (5 mL) of sodium propargylthiosulfate 11 (0.56 g,
3.22 mmol) was added. The resulting mixture was further stirred at
room temperature for 1 h, diluted with diethyl ether (50 mL),
washed with 10% KOH (15 mL) and H2O (15 mL), dried over MgSO4,
and evaporated to give the crude product (12a–c). The NMR spectra
showed the presence of small amounts of the corresponding
symmetrical benzyl or aryl disulfides.
4.6.3. 1-Methyl-4-(propa-1,2-dienylthio)benzene (13b). Yellow oil
(0.04 g, 50%); Rf (hexanes) 0.58; nmax (neat) 2922, 1943 (]C]),
1897, 1493, 805, 708 cmꢁ1 1H NMR (600 MHz, C6D6):
; d AA‘XX’
system: 7.25 and 6.87 (d, J¼7.8 Hz, 2H each), 5.83 (t, J¼6.5 Hz, 1H),
4.64 (d, J¼6.5 Hz, 2H), 2.01 (s, 3H); 13C (200 MHz, C6D6):
d 208.1
(]C]), 137.2 (Cipso), 134.6 (Cipso), 130.0 (CH), 129.8 (CH), 87.3
(]CH), 78.7 (]CH2), 20.6 (CH3); m/z (CI, CH4) 163 (73, MHþ), 123
(63, MHþꢁ‘C3H4þ’), 91 (91, MHþꢁ‘C3H4Sþ’); HRMS (CI, CH4) found
163.0579. C10H11S requires 163.0580.
4.5.1. [(Prop-2-ynyldithio)methyl]benzene (12a). Total yield 65%,
benzyl disulfide content 12%. nmax (neat) 3094, 3071, 3026, 2924,
2564, 2054, 1954, 1881, 1749, 1698, 1620, 1447, 1411, 1259, 1221,
4.6.4. 1-tert-Butyl-4-(propa-1,2-dienylthio)benzene (13c). Yellow oil
(0.058 g, 57%); Rf (hexanes) 0.62; nmax (neat) 3061, 2959, 1942
(]C]), 1898, 1105, 822, 704 cmꢁ1 1H NMR (600 MHz, C6D6):
;
1070, 1032, 916, 761, 703 cmꢁ1
;
1H NMR (200 MHz, C6D6):
d
7.16–
7.00 (m, 5H), 3.69 (s, 2H), 2.80 (d, J¼2.6 Hz, 2H), 1.88 (t, J¼2.6 Hz,
1H), 13C (200 MHz, C6D6):
137.5 (C ipso), 129.6 (CH), 128.6 (CH),
d
AA‘XX’ system: 7.31 and 7.17 (d, J¼8.4 Hz, 2H each), 5.86 (d,
J¼6.4 Hz, 1H), 4.65 (d, J¼6.4 Hz, 2H), 1.17 (s, 9H); 13C (200 MHz,
d
C6D6): d 209.0 (]C]), 150.4 (Cipso), 135.1 (Cipso), 133.1 (Cipso), 129.7
127.5 (CH), 80.1 (^C–), 72.6 (^CH), 43.4 (CH2), 27.1 (CH2); m/z (CI,
CH4) 194 (3, Mþ), 91 (100, C7H7þ); HRMS (CI, CH4) found 194.0211.
C10H10S2 requires 194.0224.
(CH), 126.2 (CH), 87.2 (]CH), 78.8 (]CH2), 34.3 (C(CH3)3), 31.2
(CH3); m/z (CI, CH4) 204 (7, Mþ), 166 (51), 151 (100); HRMS (CI, CH4)
found 204.0999. C13H16S requires 204.0973.
Iodo-dithiins. To a solution of freshly prepared sodium prop-
argylthiosulfate 11 (0.0435 g, 0.25 mmol) in 1:1 THF/H2O (3 mL) I2
(0.0635 g, 0.25 mmol) was added and the mixture was heated with
stirring at 75 ꢀC for 3 h. The reaction mixture was then diluted with
dichloromethane (20 mL) and washed with water (10 mLꢂ3). The
combined organic phase was dried over MgSO4 and evaporated.
Pure iodo-dithiins 14 and 15 were isolated by column chromatog-
raphy on silica gel, with CH2Cl2/hexanes (1:6) as eluent.
4.5.2. 1-Methyl-4-(prop-2-ynyldithio)benzene (12b). Total yield
60%, 4-tolyl disulfide content 10%; nmax (neat) 3300, 3018, 2919,
2863, 2118, 1896, 1683, 1634, 1489, 1398, 1302, 1220, 1078, 957, 805,
643 cmꢁ1 1H NMR (600 MHz, C6D6):
; d AA‘XX’ system: 7.38 and
6.82 (d, J¼8.2 Hz, 2H each), 3.13 (d, J¼2.6 Hz, 2H), 2.04 (s, 3H), 1.95
(t, J¼2.6 Hz, 1H), 13C (200 MHz, C6D6):
d 137.8 (C ipso), 133.0 (C ipso),
129.9 (CH), 129.3 (CH), 79.0 (^C–), 72.8 (^CH), 27.1 (CH2), 21.1
(CH3); m/z (CI, CH4) 194 (77, Mþ); HRMS (CI, CH4) found 194.0258.
C10H10S2 requires 194.0224.
4.6.5. 5-Iodo-3-(1-iodovinyl)-3,4-dihydro-1,2-dithiine (14). Dark oil
(0.0077 g, 15.5%); Rf (14% CH2Cl2/hexanes) 0.69; nmax (neat) 2921,
4.5.3. 1-tert-Butyl-4-(prop-2-ynyldithio)benzene (12c). Total yield
56%, 4-tert-butylphenyl disulfide content 15%; nmax (neat) 3291,
2970, 2952, 2902, 2359, 1902, 1650, 1592, 1483, 1397, 1362, 1267,
1606, 1464, 1408, 1248, 1214, 1136, 1029, 950, 736, 715 cmꢁ1 1H
;
NMR (600 MHz, CDCl3)
d
¼3.03 (ddd, J¼18.6, 7.7, 1.8 Hz, 1H), 3.08
(ddd, J¼18.6, 5.0, 1.8 Hz, 1H), 3.81 (ddd, J¼7.7, 5.0, 1.0 Hz, 1H), 6.00
1202, 1082, 961, 823, 634 cmꢁ1; 1H NMR (600 MHz, C6D6):
d AA‘XX’
(d, J¼2.5 Hz, 1H), 6.20 (dd, J¼2.5, 1.0 Hz, 1H), 6.98 (s, 1H); 13C NMR
system: 7.45 and 7.16 (d, J¼8.6 Hz, 2H each), 3.14 (d, J¼2.4 Hz, 2H),
(75 MHz, CDCl3) d 44.5 (C-4), 57.8 (C-3), 88.7 (C-5), 105.6 (C-vinyl),
1.95 (t, J¼2.4 Hz, 1H), 1.16 (s, 9H), 13C (200 MHz, C6D6):
d
151.1 (C
126.0 (C-6), 128.6 (CH2-vinyl); m/z (CI, CH4) 395.8 (20, Mþ), 269.9
(40, [MꢁI]þ),143.0 (38.0); HRMS (CI, CH4) found 395.7995. C6H6I2S2
requires 395.8000.
ipso), 133.1 (C ipso), 129.0 (CH), 126.2 (CH), 79.09 (^C–), 72.9
(^CH), 34.7 (C(CH3)3), 31.4 (CH3), 27.2 (CH2); m/z (CI, CH4) 236 (5.5,
Mþ); HRMS (CI, CH4) found 236.0687. C13H16S2 requires 236.0693.
4.6.6. 5-Iodo-3-(1-iodovinyl)-3,6-dihydro-1,2-dithiine (15). Dark oil
(0.007 g, 14%); Rf (14% CH2Cl2/hexanes) 0.57; nmax (neat) 2921, 2851,
4.6. General procedure for the desulfurization of disulfides
12a–c and 4a
1678, 1464, 1087, 908, 812 cmꢁ1 1H NMR (600 MHz, CDCl3)
; d 3.47
(dd, J¼17.8, 1.8 Hz, 1H), 3.60 (dt, J¼17.8, 1.0 Hz, 1H), 4.84 (br, 1H),
Triphenylphosphine (0.26 g, 1 mmol) was added to a solution
of the corresponding disulfide (0.5 mmol) in benzene (10 mL) and
the reaction mixture was heated at 60 ꢀC. After completion the
reaction (TLC), benzene was evaporated to give the crude reaction
mixture as a viscous oil, from which the pure sulfides 13a–c were
separated by column chromatography on silica gel with hexane as
eluent.
6.04 (d, J¼2.4 Hz, 1H), 6.40 (dd, J¼2.4, 1.2 Hz, 1H), 6.78 (br, 1H); 13C
NMR (75 MHz, CDCl3)
d 34.4 (C-6), 52.3 (C-3), 77.2 (C-5), 104.8 (C-
vinyl), 125.6 (C-4), 130.5 (CH2-vinyl); m/z (CI, CH4) 395.8 (26, Mþ),
324.8 (18), 279.1 (54), 268.9 (38, [MꢁI]þ), 198.9 (100), 142.0 (59);
HRMS (CI, CH4) found 395.7998. C6H6I2S2 requires 395.8000.
Acknowledgements
4.6.1. 1-(Prop-2-ynylthio)allene (10)24 1H NMR (700 MHz, C6D6):
.
This work has been supported by a grant from the Israel Science
Foundation (Grant No. 919-05).
d
5.61 (t, J¼6.3 Hz, 1H), 4.70 (d, J¼6.3 Hz, 2H), 2.92 (d, J¼2.6 Hz, 2H),
1.87 (t, J¼2.6 Hz, 1H); 13C (700 MHz, C6D6):
d 206.12 (]C]), 86.58
(]CH), 80.44 (]CH2), 79.56 (^C–), 71.69 (^CH), 20.47 (CH2).
References and notes
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4.6.2. [(Propa-1,2-dienylthio)methyl]benzene
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1891, 1481, 1432, 1097, 746, 698, 508 cmꢁ1 1H NMR (600 MHz,
C6D6):
7.16–7.00 (m, 5H), 5.59 (t, J¼6.3 Hz, 1H), 4.66 (d, J¼6.3 Hz,
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206.7 (]C]), 137.6 (Cipso),
129.1 (CH), 128.6 (CH), 127.3 (CH), 87.1 (]CH), 80.4 (]CH2), 37.2
(CH2); m/z (CI, CH4) 163 (22, MHþ), 162 (17, Mþ), 161 (14, [MꢁH]þ),
(13a). Yellow
oil
;
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