M. Abbasi, A. Sabet / Journal of Organometallic Chemistry 833 (2017) 10e17
11
2.2.1. Typical scale-up procedure for the conversion of n-butyl
bromide into disulfide in PEG-200(Table 1, entry 5)
In a round-bottom flask (250 mL) equipped with a condenser, a
solution of n-butyl bromide (30.0 mmol, 4.111 g), thiourea
(33.0 mmol, 2.512 g), H2O (1.5 mL) and Europhtal (8020) catalyst
solution (1.05 mL) in PEG-200 (15 mL) was prepared. Then, NaHCO3
(45.0 mmol, 3.780 g) was added to this solution and the resulting
mixture was stirred magnetically in an oil bath at 80e90 ꢀC. The
starting halide was consumed within 1.5 h, however, the reaction
mixture was stirred under that conditions for 3.5 h to ensure the
completion of the reaction. Afterwards, the mixture was diluted
with H2O (7.5 mL) and extracted with 1:2 n-hexane/EtOAc
(4 ꢁ 10 mL). The organic layers were decanted, combined, and
concentrated. The crude product was purified by silica gel chro-
matography, using n-hexane as eluent to provide dibutyl disulfide.
in 88% (2.354 g) yield.
Fig. 1. Structural formula of Europhtal catalyst [94].
One of the main advantages of such reactions is that they are
free from the thiolic foul-smells. In this strategy, the intermediate
S-alkylisothiouronium salt is produced primarily by reacting alkyl
halide with thiourea which subsequently undergoes basic hydro-
lysis to generate the corresponding thiol moiety. This moiety can
react with an alkyl halide molecule to produce the corresponding
symmetric sulfide or can react with applied oxidant to produce the
corresponding symmetric disulfide. To obtain symmetric disulfide
without contamination with symmetric sulfide, the thiol moiety
should be oxidized before it gets a chance to react with a free alkyl
halide molecule. As another trouble, many oxidizing reagents can
destroy thiourea or can convert a part of thiol to side products.
Hence, the selection of a proper oxidant is crucial to achieve
disulfides in high yields. Up to now, MnO2, BaMnO4 [95,96],
elemental sulfur [97], CCl4 [98], and dimethyl sulfoxide (DMSO) in
conjunction of hexamethyldisilazane (HMDS) [99] are successfully
applied for this purpose.
2.3. General procedure for preparation of disulfides from alkyl
halides in SDS micellar solution
To a micellar solution of SDS (1 mL H2O þ 0.1 mmol SDS) in a
round-bottom flask (25 mL) equipped with a condenser, an alkyl
halide (2.0 mmol), thiourea (2.2 mmol), Europhtal (8020) catalyst
solution (0.07 mL) and NaHCO3 (3.0 mmol) were added. The
resulting mixture was stirred magnetically in an oil bath at
80e90 ꢀC up to 2 h after the complete consumption of the starting
halide. Thereafter, the mixture was directly extracted with EtOAc
(3 ꢁ 1 mL). The upper layers were combined, and concentrated. The
crude product underwent silica gel chromatography with n-hexane
to provide the desired symmetric disulfide in pure form.
2.3.1. Typical scale-up procedure for the preparation of dibutyl
disulfide from n-butyl bromide in SDS micellar solution (Table 1,
entry 5)
2. Experimental
2.1. Catalyst information
To a micellar solution of SDS (15 mL H2O þ0.75 mmol SDS), in a
round-bottom flask (250 mL) equipped with a condenser, thiourea
(33.0 mmol, 2.512 g), n-butyl bromide (30.0 mmol, 4.111 g), Euro-
phtal catalyst (1.15 mL), and NaHCO3 (45.0 mmol, 3.780 g) were
added. The resulting mixture was stirred magnetically in an oil bath
at 80e90 ꢀC. The starting halide was consumed within 5 h however,
the stirring was continued under such conditions for further 2 h.
Next, the mixture was extracted with EtOAc (3 ꢁ 10 mL). The
organic layers were decanted, combined, dried over Na2SO4,
filtered and concentrated to yield the crude product, which was
further purified by silica gel column chromatography, using n-
hexane to provide the desired product in 2.300 g (86% yield).
Europhtal catalyst solution additive 8020, an industrial catalyst,
containing both bis- and tris-sulfonated cobalt phthalocyanine
complexes (Fig. 1), supplied by the Europhtal company (Cavaillon,
France) was used in this study. After heating of the solution for 2 h
in an oven at 100 ꢀC, a dark-blue solid residue sticking to the beaker
floor was obtained in 0.344 g/mL.
2.2. General procedure for conversion of alkyl halides to disulfides
in PEG
In a round-bottom flask (25 mL) equipped with a condenser,
Europhtal (8020) catalyst solution (0.07 mL) was added to a
mixture of an alkyl halide (2.0 mmol), thiourea (2.2 mmol), H2O
(0.1 mL), and NaHCO3 (3.0 mmol) in PEG 200 (1 mL) and the
mixture was stirred magnetically in an oil bath at 80e90 ꢀC. The
stirring was continued under such conditions up to 2 h after the
complete consumption of the starting halide. Next, the mixture
was diluted with water (0.5 mL) and extracted with 1:2 n-hex-
ane/EtOAc (3 ꢁ 1 mL). The organic layers were decanted, com-
bined, and concentrated to yield the crude product, which was
further purified by silica gel chromatography, using n-hexane as
eluent.
2.3.1.1. Didecyl disulfide (Table 1, entry 1). Colorless oil; 1HNMR
(250 MHz, CDCl3):
d
2.63 (t, J ¼ 7.3 Hz, 4H), 1.76e1.61 (m, 4H), 1.21
(broad band, 28H), 0.82 (t, J ¼ 6.2, 6H); 13CNMR (62.5 MHz, CDCl3):
d
39.2, 31.9, 29.6, 29.5, 29.3, 29.3, 29.2, 28.5, 22.7, 14.1; Anal. Calcd
for C20H42S2: C, 69.29; H, 12.21; S, 18.50%. Found: C, 69.40; H, 12.23;
S, 18.37%.
2.3.1.2. Dioctyl disulfide (Table 1, entry 3). Colorless oil; 1HNMR
(250 MHz, CDCl3):
d
2.61 (t, J ¼ 7.3 Hz, 4H), 1.66e1.54 (m, 4H),
1.30e1.21 (broad band, 20H), 0.81 (t, J ¼ 6.2, 6H); 13CNMR
(62.5 MHz, CDCl3): d 39.2, 31.8, 29.2, 29.2, 29.1, 28.5, 22.6,14.1; Anal.
Calcd for C16H34S2: C, 66.14; H, 11.79; S, 22.07%. Found: C, 66.07; H,
11.81; S, 22.12%.
2.3.1.3. Dibutyl disulfide (Table 1, entry 5). Colorless oil; 1HNMR
(250 MHz, CDCl3):
d
2.69 (t, J ¼ 7.4, 4H), 1.71e1.66 (m, 4H),
1.48e1.40 (m, 4H), 0.93 (t, J ¼ 7.3, 6H); 13CNMR (62.5 MHz, CDCl3):
Scheme 1. Synthesis of disulfides by oxidation of in situ generated thiols.
d 39.3, 31.7, 22.0, 14.0. Anal. Calcd for C8H18S2: C, 53.88; H, 10.17; S,