A new approach to the reduction of sulfoxides to sulfides with 1,3-dithiane in the presence of electrophilic bromine as catalyst

Article abstract of DOI:10.1021/jo016027y

A new, mild, and novel method is described for the efficient deoxygenation of sulfoxides to their corresponding sulfides with 1,3-dithiane at room temperature in the presence of catalytic amounts of N-bromosuccinimide (NBS), 2,4,4,6-tetrabromo-2,5-cyclohexadienone (TABCO), or Br₂ as the source of electrophilic bromine.

Full text of DOI:10.1021/jo016027y

2
826
J . Org. Chem. 2002, 67, 2826-2830
A New Ap p r oa ch to th e Red u ction of Su lfoxid es to Su lfid es w ith
1
,3-Dith ia n e in th e P r esen ce of Electr op h ilic Br om in e a s Ca ta lyst
Nasser Iranpoor,* Habib Firouzabadi,* and Hamid Reza Shaterian
Department of Chemistry, Shiraz University, Shiraz 71454, Iran
iranpoor@chem.susc.ac.ir
Received August 13, 2001
A new, mild, and novel method is described for the efficient deoxygenation of sulfoxides to their
corresponding sulfides with 1,3-dithiane at room temperature in the presence of catalytic amounts
of N-bromosuccinimide (NBS), 2,4,4,6-tetrabromo-2,5-cyclohexadienone (TABCO), or Br as the
2
source of electrophilic bromine.
In tr od u ction
Reduction of sulfoxides to the corresponding sulfides
Sch em e 1
1
2
is an important organic and biological reaction and has
found wide applications in various synthetic transforma-
3
tions as well as asymmetric synthesis. d-Block metals
have been widely used as low-valent oxophilic reagents
in deoxygenation of various types of organic substrates
as well as sulfoxides.1
f,g,4-11
Very recently, we have
times suffers from serious disadvantages, such as use of
an expensive reagent, difficult workup procedures, harsh
reported the use of WCl
6
/NaI as another example of a
d-block metal reductive system.12
acidic conditions (e.g., mixture of CF
CO H, H SO in refluxing acetic acid and or aqueous 4
M HCl or 4-6 M HClO
3 3 3
SO H and CF -
An alternative approach to the reduction of sulfoxides
1
3a
2
2
4
is the use of sulfur compounds, e.g., thiols; hydrogen
1
a,13a
), very high reaction
and long reaction times.
sulfide;1 carbodithionic acids; thiophosphinic, thio-
3b
13c
4
temperatures (200-280 °C),1
a,17b
13
phosphonic, and thiophosphoric acids;1 sulfides;
3d
14,15
In this work, we report a new, novel, and efficient
reduction of sulfoxides to their corresponding sulfides
using 1,3-dithiane, a commercially available sulfur com-
pound and catalytic amounts of N-bromosuccinimide
1
6
17a
sulfenyl, sulfinyl, and sulfonyl chlorides; disulfides;
1
7b
17c
elemental sulfur (S
8
); and thionyl chloride. However,
the reduction of sulfoxides with these compounds some-
(
NBS), 2,4,4,6-tetrabromo-2,5-cyclohexadienone (TAB-
(
1) For reviews, see: (a) Madesclaire, M. Tetrahedron 1988, 44, 6537.
b) Drabowicz, J .; Numata, T.; Oae, S. Org. Prep. Proced. Int. 1977, 9,
3. For recent leading references, see: (c) Drabowicz, J .; Dudzinski,
1
8,19
(
6
CO),
or molecular bromine as the source of electro-
philic halogen (Scheme 1).
Resu lts a n d Discu ssion
In the course of our studies on the dethioacetalization
B.; Mikolajczyk, M. Synlett 1992, 252. (d) Mohanazadeh, F.; Momeni,
A. R.; Ranjbar, Y. Tetrahedron Lett. 1994, 35, 6127. (e) Lee, G. H.;
Choi, E. B.; Lee, E.; Pak, C. S. Tetrahedron Lett. 1994, 35, 2195. (f)
Zhang, Y.; Yu, Y.; Bao, W. Synth. Commun. 1995, 25, 1825. (g) Wang,
J . Q.; Zhang, Y. M. ibid. 1995, 25, 3545. (h) Nicolas, E.; Vilaseca, M.;
Giralt, E. Tetrahedron 1995, 51, 5701. (i) Fujiki, K.; Kurita, S.; Yoshida,
E. Synth. Commun. 1996, 19, 3619. (g) Wang, Y.; Koreeda, M. Synlett
of carbonyl compounds with NBS, TABCO, and Br in
2
1
996, 885.
2) Black, S.; Harte, E. M.; Hudson, B.; Wartofsky, L. J . Biol. Chem.
960, 235, 2910.
3) a) Soladie, G. Synthesis 1981, 185. (b) Carreno, M. C. Chem. Rev.
995, 95, 1717. (c) Davies, S. G.; Loveridge, T.; Clough, J . M. Synlett
997, 66.
DMSO, we observed that DMSO was reduced to dimethyl
sulfide. This finding encouraged us to develop a simple
method for the reduction of sulfoxides to their corre-
sponding sulfides. To optimize the reaction conditions,
we first studied the reduction of dibenzyl sulfoxide using
(
1
(
1
1
(4) Cintas, P. Activated Metals in Organic Synthesis; CRC: Boca
1
,3-dithiane as the sulfur compound and different quan-
Raton, FL, 1993.
(
(
(
(
(
5) Drabowicz, J .; Mikolajczyk, M. Synthesis 1976, 527.
6) Drabowicz, J .; Mikolajczyk, M. Synthesis 1978, 138.
7) Baliki, R. Synthesis 1991, 155.
8) Akita, Y.; Inaba, M.; Uchida, H.; Ohta, A. Synthesis 1977, 792.
9) Nuzzo, R. G.; Simon, H. G.; Sanfilippo, J . J . Org. Chem. 1977,
tities of compounds carrying electrophilic holonium ions
such as NBS, NCS (N-chlorosuccinimide), TABCO, and
TCCA (trichlorocyanuric acid) as well as molecular
bromine and iodine in dry chloroform. The results are
shown in Table 1.
4
2, 568.
(10) Olah, G. A.; Surya Prakash, G. K.; Ho, T. L. Synthesis 1976,
8
10.
(
(
(
11) Ho, T. L.; Wong, C. M. Synthesis 1973, 206.
12) Firouzabadi, H.; Karimi, B. Synthesis 1999, 3, 500.
13) (a) Wallace, T. J .; Mahon, J . J . Org. Chem. 1965, 30, 1502. (b)
(17) (a) Oae, S.; Tsuchida, Y.; Nakai, M. Bull. Chem. Soc. J pn. 1971,
44, 451. (b) Oae, S.; Kawamura, S. Bull. Chem. Soc. J pn. 1963, 36,
163. (c) Grossert, J . S.; Hardstaff, W. R.; Langler, R. F. Can. J . Chem.
1977, 55, 421.
(18) (a) Ho, T. L.; Hall, T. W.; Wong, C. M. Synthesis 1974, 873. (b)
Saito, A.; Saito, K.; Tanaka, A.; Oritani, T. Tetrahedron Lett. 1997,
38, 3955. (c) Tanaka, A.; Oritani, T. Tetrahedron Lett. 1997, 38, 1955.
(19) (a) Tanaka, A.; Oritani, T. Tetrahedron Lett. 1997, 38, 7223.
(b) Ting, P. C.; Bartlett, P. A. J . Am. Chem. Soc. 1984, 106, 2668. (c)
Hino, T.; Uehara, H.; Takashima, M.; Kawate, T.; Seki, H. Chem.
Pharm. Bull. 1990, 38, 2632.
Mehmet, Y.; Hyne, J . B. Phosphorous Sulfur 1976, 1, 47. (c) Mikola-
jezyk, M. Angew. Chem. 1966, 78, 393. (d) Oae, S.; Nakanishi, A.;
Tsujimoto, T. Tetrahedron 1972, 28, 2981.
(
(
14) Bordwell, F. G.; Pitt, B. M. J . Am. Chem. Soc. 1955, 77, 572.
15) Tanikaga, R.; Nakayama, K.; Tanaka, K.; Kaji, A. Chem. Lett.
1
1
977, 395.
16) Fukamiya, N.; Okano, M.; Arantani, T. Chem. Ind. (London)
982, 199.
(
1
0.1021/jo016027y CCC: $22.00 © 2002 American Chemical Society
Published on Web 04/10/2002

A New Approach to the Reduction of Sulfoxides
J . Org. Chem., Vol. 67, No. 9, 2002 2827
Ta ble 1. Con ver sion of Diben zyl Su lfoxid es (1.0 m m ol)
to Diben zyl Su lfid e w ith 1,3-Dith ia n e (1.1 m m ol) in th e
P r esen ce of Differ en t Ca ta lysts (NBS, NCS, TABCO,
TCCA, Br 2, a n d I2) in CHCl3 a t Room Tem p er a tu r e
Sch em e 2
catalyst/
time
%
catalyst/
time
%
entry molar equiv (min) yielda entry molar equiv (min) yielda
1
2
3
4
5
6
7
8
9
0
1
NBS/0.05
NBS/0.1
NBS/0.15
NBS/0.2
250
110
45
94
93
95
94
90
95
94
92
91
92
94
12
13
14
15
16
17
18
19
20
21
22
NCS/0.2
55
250
200
120
50
92
89
92
90
96
95
10
15
25
30
40
TCCA/0.1
TCCA/0.15
TCCA/0.2
30
TABCO/0.05 300
Br
Br
2
/0.1
/0.2
TABCO/0.1
TABCO/0.15
TABCO/0.2
NCS/0.05
NCS/0.1
NCS/0.15
100
71
35
460
180
120
2
20
I
I
I
I
I
2
2
2
2
2
/0.1
/0.15
/0.2
/0.3
/1.2
24h
24h
24h
24h
12h
1
1
a
Isolated yield.
Ta ble 2. Red u ction of Diben zyl Su lfoxid e (1.0 m m ol)
Ca ta lyzed w ith NBS, TABCO, a n d Also Br 2 (0.2 m m ol)
Usin g Cyclic a n d Acyclic Dith ioa ceta ls (1.1 m m ol) in
CHCl3 a t Room Tem p er a tu r e
entry
reagent
catalyst time (min) % yielda
1
2
3
4
5
6
7
8
8
2,2-dimethyl-1,3-dithiane NBS
2,2-dimethyl-1,3-dithiane Br2
2,2-dimethyl-1,3-dithiane TABCO
85
60
130
30
20
35
30
30
45
60
50
65
83
84
81
94
95
92
90
91
90
82
83
81
1,3-dithiane
1,3-dithiane
1,3-dithiane
1,3-dithiolane
1,3-dithiolane
1,3-dithiolane
NBS
Br2
TABCO
NBS
Br2
TABCO
1
1
1
0
1
2
acetone diethylthioacetal NBS
acetone diethylthioacetal Br2
acetone diethylthioacetal TABCO
mixture, due to its ease of polymerization to an unidenti-
fied polymer upon concentrating of the reaction mixture.
A mechanism has been proposed to show the catalytic
role of the electrophilic bromine in these reactions
21
a
Isolated yield.
(
Scheme 2). The bromination of 1,3-dithiane (I) produces
Among the catalysts we used for this reduction, those
compounds carrying electrophilic bromine (NBS and
TABCO; Table 1, entries 1-8) were found to be more
efficient than those having electrophilic chlorine (NCS
and TCCA; Table 1, entries 9-15). The reduction in the
presence of catalytic amounts of molecular bromine was
found to be as fast as using NBS and TABCO (Table 1,
entries 16, 17); however, the reactions using molecular
iodine as catalyst were found to be very slow and
uncompleted, even when excess of iodine was used (Table
an intermediate (II), which reacts with a molecule of
sulfoxide to give another intermediate (III). Sulfenyl
halides have been reported to dissociate in polar solvents
20
to sulfonium and halide ions. In our proposed mecha-
nism, intermediate III could produce formaldehyde, 1,2-
dithiacyclopetane (IV), and intermediate V as another
source of electrophilic bromine in this catalytic cycle. For
this reaction, dry solvent should be used. When we used
wet choroform in this reaction, a water molecule attacks
intermediate II instead of sulfoxide and results in the
formation of formaldehyde, 1,2-dithiacyclopetane, and
HBr in the reaction mixture. 1,2-Dithiacyclopetane (IV)
was detected in the crude reaction mixture and identified
by comparison of its H and C NMR spectral data to
that reported in the literature.21 In addition, its spectral
data and GC retention time were also compared with
those of a known sample obtained from intramolecular
coupling of 1,3-propandithiol.22
1
, entries 18-22).
To observe the effect of different sulfur compounds on
the rate and the yield of this reduction, we choose NBS,
TABCO, and Br (20 mol %) as preferred catalysts and
1
13
2
continued our study by using structurally different cyclic
and acyclic dithioacetals for reduction of dibenzyl sul-
foxide. The results obtained for this reduction using
different dithioacetals are compared in Table 2.
To show that formaldehyde has been formed in this
reaction, we have studied the reduction of dibenzyl
sulfoxide in the presence of 2-phenyl-1,3-dithiane, which
should produce benzaldehyde (according to the proposed
mechanism) in the process of the reaction. In fact,
benzaldehyde was isolated as its 2,4-dinitrophenylhydra-
zone derivative in 96% yield from the reaction mixture.
According to the results of Table 2, the reactions with
,3-dithiane and 1,3-dithiolane are somewhat faster and
with higher yields in comparison with the reactions when
other thioacetals are used. Due to better availability of
,3-dithiane, we choose it as the preferred sulfur com-
1
1
pound and continued our study on the reduction of
different sulfoxides.
Using this method, efficient deoxygenation of dibenzyl,
dialkyl, benzyl alkyl, phenyl alkyl, and benzyl phenyl
sulfoxides to their sulfides was achieved in excellent
yields at room temperature (Table 3).
(
20) (a) Peach, M. E. Int. J . Sulfur Chem. 1973, 8, 151. (b) Field, L.;
White, J . E. Proc. Nat. Acad. Sci. 1973, 70, 328.
21) Harpp, D. N.; Gleason, J . G. J . Org. Chem. 1970, 35, 3259.
(
(22) Harpp, D. N.; Gleason, J . G.; Snyder, J . P. J . Am. Chem. Soc.
1
968, 90, 4181. Spectral data for 1,2-dithiacyclopetane is as follows:
UV absorption band at 330 nm (ꢀ 147); H NMR (δ, ppm) 2.81 (t, 4H),
2.01 (m, 2H); C NMR (δ, ppm) 29.9, 26.6.
The formation of 1,2-dithiacyclopetane as a product of
the reaction can be easily removed from the reaction
1
1
3

2
828 J . Org. Chem., Vol. 67, No. 9, 2002
Iranpoor et al.
Ta ble 3. Red u ction of Su lfoxid es to Su lfid es w ith 1,3-Dith ia n e in th e P r esen ce of TABCO (A), NBS (B), or Br 2 (C) in
CHCl3 a t Room Tem p er a tu r e
a
The ratio of sulfoxide/1,3-dithiane/catalyst is 1/1.1/0.2, unless otherwise stated. b The ratio of sulfoxide/1,3-dithiane/catalyst is 1/1.2/
0
.3. c Isolated yield. The products were purified by column chromatography and were identified by the comparison of their melting point,
IR, MS, and NMR data with those reported in the literature.
4
-17,23,24

A New Approach to the Reduction of Sulfoxides
J . Org. Chem., Vol. 67, No. 9, 2002 2829
Ta ble 4. Red u ction of Su lfoxid es to Su lfid es in th e P r esen ce of Com p ou n d s Ha vin g Differ en t F u n ction a l Gr ou p s w ith
,3-Dith ia n e a n d NBS a s Ca ta lyst in CHCl3 a t Room Tem p er a tu r ea
1
a
Yields based on NMR and GC (n-heptane was used as an internal standard).
This is strong evidence in support of the formation of
aldehydes when 1,3-dithianes are used as reducing
agents in these reactions.
functionality could not occur, due to the ready coupling
of thiol to its corresponding disulfide (Table 4, entry 7).
In summary, we have presented a new and novel
method for the reduction of sulfoxides with electrophilic
bromine as catalyst in the presence of dithioacetals as
the sulfur compound. High yields of the desired products,
short reaction times, easy workup, and mild reaction
conditions in comparison with the other sulfur-based
reduction methods are the strong points of the presented
procedure.
To show the scope and limitation of this method for
the reduction of sulfoxides, the reduction of dibenzyl
sulfoxide in the presence of urea, thiourea, benzamide,
ethylcarbamate, and carbonyl groups was studied. The
results of this study (Table 4) indicate that the reduction
of the sulfoxide in the presence of these functional groups
performs well with a slight decrease in the rate of the
reaction. This decrease in the rate of the reaction in the
presence of -NH- containing compounds (Table 4,
entries 1-4) could be due to the possibility of bromine
exchange between NBS and the -NH- functionality.
However, this reduction in the presence of the -SH
Exp er im en ta l Section
All yields refer to isolated products. The products were
purified by column chromatography, and the purity determi-
nation of the products was accomplished by GLC on a Shi-

2
830 J . Org. Chem., Vol. 67, No. 9, 2002
Iranpoor et al.
madzu model GC-8A instrument or by TLC on silica gel
polygrams SIL G/UV254 plates. Chloroform was dried by
refluxing over anhydrous calcium chloride for 48 h, followed
by distillation, and stored over 4A molecular sieve. Mass
spectra were run on a Shimadzu GC MS-QP 1000EX at 20 or
the appropriate time (Table 3). The reaction was monitored
by TLC on a silica gel plate using n-hexane as eluent. After
completion of the reaction, CHCl
reaction mixture and the mixture was washed with a solution
O (2
3
(25 mL) was added to the
of NaOH (5%, 2 × 10 mL), brine solution (10 mL), and H
2
7
5 eV. IR spectra were recorded on a Perkin-Elmer 781
× 10 mL) subsequently. The organic layer was separated and
spectrophotometer. The NMR spectra were recorded on a
Bruker Avance DPX 250 MHz instrument. Melting points were
determined in open capillary tubes in a Buchi-510 circulating
oil melting point apparatus and are uncorrected.
Gen er a l P r oced u r e for th e Red u ction of Su lfoxid es
to th e Cor r esp on d in g Su lfid es w ith 1,3-Dith ia n e Usin g
a Ca ta lytic Am ou n t of Electr op h ilic Ha logen s in Ch lor o-
for m .
dried over anhydrous Na SO and the solvent was evaporated.
2
4
Further purification was performed using chromatography
over a short column of silica gel using n-hexane as eluent. The
sulfides were characterized by comparison of their physical
data (melting point and IR, 1H NMR, C NMR, and MS
13
spectra) with those of known samples.4-17,23,24
Typ ica l P r oced u r e for th e Red u ction of Diben zyl
Su lfoxid e to Diben zyl Su lfid e w ith 1,3-Dith ia n e Usin g
Ca ta lytic Am ou n ts of TABCO.
Sulfoxide (1.0 mmol) was added to a stirred solution of the
appropriate catalyst (NBS, TABCO, or Br ; 0.2-0.3 mmol) in
2
Dibenzyl sulfoxide (1.0 mmol) was added to a stirred
solution of TABCO (0.2 mmol) in dry CHCl (3 mL). 1,3-
3
Dithiane (1.1 mmol) was then added to the resulting solution
and the mixture was stirred for 35 min. After completion of
dry chloroform (3 mL). Then, 1,3-dithiane (1.1 mmol) was
added to the resulting solution and stirring was continued for
(
23) Tenca, C.; Dossena, A.; Marchelli, R. Synthesis 1981, 141.
the reaction, CHCl
and washed with a solution of NaOH (5%, 2 × 10 mL), brine
solution (10 mL), and H
O (2 × 10 mL). The organic layer was
separated and dried over anhydrous Na SO and the solvent
3
(25 mL) was added to the reaction mixture
(24) Selected spectral data for some sulfides. (a) Methyl phenyl
1
sulfide (Table 3, entry 1): H NMR (δ, ppm) 7.24-7.10 (m, 5H), 2.42
1
3
(
1
3
s, 3H);+ C NMR (δ, ppm) 138.4, 128.7, 126.5, 124.9, 15.6; MS (75 eV)
2
24 (M , 100), 109 (34), 91 (26), 78 (31). (b) Benzyl phenyl sulfide (Table
2
4
, entry 4): 1H NMR (δ, ppm) 7.44-7.00 (m, 10H), 4.09 (s, 2H);
13
C
was evaporated. The residue was purified by column chroma-
tography on silica gel using n-hexane as an eluent. Dibenzyl
sulfide was isolated in 92% yield (Table 3, entry 7): mp 48 °C
NMR (δ, ppm) 137.4, 136.4, 129.7, 128.7, 128.3, 127.0, 126.2, 38.9; MS
+
-1
(
75 eV) 200 (M , 24), 91 (100); IR (cm ) 3061, 3047, 3031, 1686, 1571,
1
495, 1481, 1454, 1438, 1091, 1070, 1023, 730, 716, 701, 694, 687. (c)
1
23
1
Diphenyl sulfide (Table 3, entry 5): H NMR (δ, ppm) 7.44-7.08 (m,
1
(lit. mp 49-50 °C); H NMR (CDCl
3
, 250 MHz) (δ, ppm) 7.27
0H); 13C NMR (δ, ppm) 135.8, 131.0, 129.1, 126.9; MS (75 eV) 187 (M
13
(
s, 10H), 3.59 (s, 4H); C NMR (CDCl , 62 MHz) (δ, ppm)
38.1, 128.9, 128.3, 126.8, 35.5; MS (75 eV), m/z: 214 (M ,
28), 123 (23), 92 (21), 91 (100); IR (KBr) (ν, cm ) 3083, 3059,
3039, 3026, 2953, 2920, 1493, 1453, 1412, 1073, 704, 696.
3
+
-1
+
1, 16), 186 (M , 100), 185 (66), 184 (25); IR (cm ) 3073, 3059, 3020,
+
1
1
580, 1476, 1439, 1081, 1068, 1024, 749, 738, 689. (d) Benzyl methyl
-
1
1
sulfide (Table 3, entry 8): H NMR (δ, ppm) 7.45-7.04 (m, 5H), 3.64
1
3
(s, 2H), 1.96 (s, 3H); C NMR (δ, ppm) 138.2, 128.7, 128.3, 126.8, 38.2,
+
-1
1
1
6
4.7; MS 138 (M , 31), 91(100); IR (cm ) 3084, 3062, 3028, 2972, 2916,
602, 1494, 1453, 1436, 1426, 1240, 1072, 1029, 979, 771, 726, 699,
1
Ack n ow led gm en t. We thank the Shiraz University
Research Council for the partial support of this work.
77, 666. (e) Dibutyl sulfide (Table 3, entry 10): H NMR (δ, ppm) 2.5
1
3
(tt, 4H), 1.55 (m, 4H), 1.41 (m, 4H), 0.92 (tt, 6H); C NMR (δ, ppm)
+
3
2
1.95, 22.13, 13.74; MS (20 eV) 146 (M , 37), 61 (94), 56 (100), 41 (40),
9 (38); IR (cm- ) 2961, 2931, 2874, 2862, 1462, 1467, 1379, 1272, 1222.
1
J O016027Y