Chemoselective synthesis of diaryl disulfides via a visible light-mediated coupling of arenediazonium tetrafluoroborates and CS2

Article abstract of DOI:10.3762/bjoc.13.91

A highly efficient and chemoselective method for the synthesis of diaryl disulfides is developed via a visible light-promoted coupling of readily accessible arenediazonium tetrafluoroborates and CS2. This practical and convenient protocol provides a direct pathway for the assembly of a series of disulfides in an environmentally friendly manner with good to excellent yields.

Full text of DOI:10.3762/bjoc.13.91

Chemoselective synthesis of diaryl disulfides via a visible
light-mediated coupling of arenediazonium tetrafluoroborates
and CS2
Jing Leng, Shi-Meng Wang and Hua-Li Qin*
Letter
Open Access
Address:
Beilstein J. Org. Chem. 2017, 13, 903–909.
School of Chemistry, Chemical Engineering and Life Science, Wuhan
University of Technology, 205 Luoshi Road, Wuhan 430070, PR
China
doi:10.3762/bjoc.13.91
Received: 11 January 2017
Accepted: 25 April 2017
Published: 15 May 2017
Email:
Hua-Li Qin* - qinhuali@whut.edu.cn
Associate Editor: J. A. Murphy
* Corresponding author
© 2017 Leng et al.; licensee Beilstein-Institut.
License and terms: see end of document.
Keywords:
arenediazonium tetrafluoroborates; carbon disulfide; chemoselectivity;
diaryl disulfides; photocatalyst
Abstract
A highly efficient and chemoselective method for the synthesis of diaryl disulfides is developed via a visible light-promoted cou-
pling of readily accessible arenediazonium tetrafluoroborates and CS2. This practical and convenient protocol provides a direct
pathway for the assembly of a series of disulfides in an environmentally friendly manner with good to excellent yields.
Findings
The development of methods for the functionalization of abundant chemical, has been widely used as reactant and sol-
peptides and proteins under mild conditions is a current frontier vent in both industry and materials science. For example,
in the fields of chemistry, biology and drug discovery [1-4]. Batanero and co-workers reported an electrochemical transfor-
Most of the pharmaceutically relevant proteins contain disul- mation of carbon disulfide into diaryl disulfides [11]. Sunlight
fide bonds, furthermore, the disulfide ligation and its estab- as abundant and almost infinitely available energy resource has
lished chemoselectivity is of great advantage for proteins’ func- been widely used for chemical transformations in the sense of
tionalization [5]. In addition, disulfides also play valuable roles cost, safety, availability, and environmental friendliness [12-
as versatile building blocks for industrial applications [6-8]. 15]. Herein, we report a visible light-mediated coupling of
Thus, the development of methodologies for the synthesis of arenediazonium tetrafluoroborates and CS2 for the chemoselec-
disulfides is rather desirable and many research groups have tive assembly of diaryl disulfides as our continuing endeavor of
made great contributions to the synthesis of diaryl disulfides utilizing arenediazonium tetrafluoroborates [16] for synthetic
such as the Chandrasekaran group [9] and the Wacharasindhu applications (Scheme 1).
group [10]. Indeed, the design of sustainable and useful trans-
formations with applications in industry is considered of high We conducted our initial study with benzenediazonium tetra-
practical value. In this context, carbon disulfide, a cheap and fluoroborate (1a) and CS2 (2) as model substrates to examine
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Beilstein J. Org. Chem. 2017, 13, 903–909.
Scheme 1: Chemoselective assembly of diaryl disulfides.
the feasibility of the formation of diphenyl disulfide (3a) from aryldiazonium salts under visible light irradiation has also
(Table 1). Various solvents were screened and to our delight, it been studied [14,15] by taking advantage of visible light as
was found that the reaction of 1a and 2 in DMF and DMSO abundant and environmentally friendly energy source for
gave the desired product in a moderate yield of 54% and 53%, organic syntheses. The photochemistry of diazonium salts has
respectively (Table 1, entries 7 and 8). Unfortunately, under the been widely studied since the early 19th century, at which time,
applied conditions, the chemoselectivity of the reaction was it was noticed that benzenediazonium nitrate turns red upon
poor, affording a mixture of unexpected diphenyl sulfide (4a) exposure to sunlight due to decomposition and formation of
and diphenyl polysulfides (5a) as byproducts. Thus, a study to radical species [20]. Subsequently, the photodecomposition of
optimize the reaction conditions with regard to chemoselectivi- diazonium salts by loss of nitrogen upon exposure to light has
ty and to minimize the formation of the byproducts was con- been utilized in organic synthesis for example to remove amino
ducted.
groups from anilines [21] or for arylation reactions [15,22].
As recently surveyed, photoredox catalysts are widely em- Based on the above research results, we envisioned that a
ployed for the generation of radicals for diverse radical reac- radical pathway may facilitate the formation of diaryl disul-
tions [19]. Further, the application of aryl radicals generated fides. Therefore the photocatalyst Ru(bpy)3(PF6)2 (bpy = 2,2’-
Table 1: Solvent screening for the coupling of benzenediazonium tetrafluoroborate (1a) and CS2 (2).a
Entry
Solvents
Yield 3a (%)b
Yield 4a (%)b
Yield 5a (%)b
1
2
3
4
5
6
7
8
9
MeOH
THF
n.d.
36
n.d.
5
n.d.
n.d.
n.d.
n.d.
19
dioxane
acetone
DCM
n.d.
n.d.
n.d.
n.d.
54
14
n.d.
n.d.
n.d.
3
acetonitrile
DMF
n.d.
31
DMSO
hexane
53
3
27
n.d.
n.d.
24
aReaction conditions: 1a (0.1 mmol), 2 (0.2 mmol), solvent (2 mL), rt, 6 h; byields were determined by HPLC using 3a and 4a as the external stan-
dards; the yield of 5a is based on the integration of the corresponding HPLC peaks [17,18]; n.d. = not determined.
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Beilstein J. Org. Chem. 2017, 13, 903–909.
bipyridine) [23] and a 20 W blue-light LED were chosen as 8). However, when the iridium-based photocatalysts Ir(ppy)3
catalyst and the source of visible light, respectively for our [24], [Ir(ppy)2(bpy)]PF6 and [Ir(ppy)2(dtbbpy)]PF6 (bpy = 2,2’-
model reaction (Table 2). A variety of solvents was evaluated bipyridine, ppy = 2-phenylpyridine, dtbbpy = 4,4’-di-tert-butyl-
and eventually, it was found that the coupling of benzene- 2,2’-bipyridine) [25,26] were used, the product yield of
diazonium tetrafluoroborate (1a) and CS2 (2) in ethanol as the diphenyl disulfide (3a) was much lower compared to reactions
solvent gave the desired product diphenyl disulfide (3a) in 77% performed in the presence of ruthenium catalysts (Table 3,
yield accompanied by only 8% of the undesired diphenyl poly- entries 9–11).
sulfides (Table 2, entry 4). Switching to DMSO as the solvent
for the reaction afforded exclusively the desired product 3a in A plausible reaction mechanism has been proposed and is
excellent yield (88%, Table 2, entry 6). Next, other sulfur depicted in Scheme 2. We envision that the phenyl radical I was
sources were also examined, such as S8, NaSH, Na2S, Na2S2O3, initially generated under visible light irradiation [14,15]. Subse-
Na2S2O4 and K2S2O8, however, none of them provided the quently, the radical I attacked the sulfur atom of carbon disul-
desired product in an acceptable yield (Table 2, entries 7–13). fide to provide the intermediate II which can be converted to
radical intermediate III through the cleavage of the
In order to maximize the yields, varying amounts of CS2 (2) carbon–sulfur bond accompanied with the release of a carbon
were also tested (Table 3) and it was found that the CS2 loading sulfide [11]. The active radical intermediate III can transform
had a considerable influence on the reaction. By decreasing the into three types of products through different pathways. Firstly,
loading of CS2 from 2 equiv to 0.5 equiv, the yield of the prod- diaryl disulfide 3 is obtained through a dimerization of radical
uct 3a dropped to 42%, whereas increasing amounts of CS2 did intermediates III, whereas the reaction of radical III with phe-
not significantly increase the yield of the product. Subsequently, nyl radical I is leading to byproduct 4. Finally, radical III can
different photocatalysts were investigated and it turned out that react with various equivalents of CS2 with release of carbon
the choice of catalyst also had a significant impact on our model sulfide to generate aryl-polythio radicals IV and V. The combi-
reaction. Ru(bpy)3Cl2 catalyzed this coupling to afford the nation of the latter intermediates with radical I then finally
desired product 3a in a moderate yield of 65% (Table 3, entry affords polysulfides 5.
Table 2: Screening of the solvents and sulfur sources for the visible light-mediated coupling of benzenediazonium tetrafluoroborate (1a) and CS2 (2)
and other sulfur sources in the presence of Ru(bpy)3(PF6)2 as the photocatalyst.a
Entry
Solvent
Sulfur source
Yield 3a (%)b
Yield 4a (%)b
Yield 5a (%)b
1
MeOH
H2O
CS2
88
<1
5
10
20
8
2
CS2
47
3
THF
CS2
87
<1
n.d.
7
4
EtOH
CS2
77
8
5
acetone
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
CS2
79
3
6
CS2
88
n.d.
9
<1
67
11
n.d.
n.d.
4
7
S8
14
8
Na2S
Na2S2O3
Na2S2O4
K2S2O8
NaSH
(NH4)2S2O8
n.d.
n.d.
n.d.
n.d.
22
43
9
n.d.
n.d.
n.d.
28
10
11
12
13
14
4
n.d.
n.d.
aReaction conditions: 1a (0.1 mmol), sulfur sources (0.2 mmol), Ru(bpy)3(PF6)2 (0.001 mmol), blue light (20 W), solvents (2 mL), rt, 6 h; byields were
determined by HPLC using 3a and 4a as the external standards, the yield of 5a is based on the integration of the corresponding HPLC peaks [17,18];
n.d. = not determined.
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Beilstein J. Org. Chem. 2017, 13, 903–909.
Table 3: Screening of photocatalysts for the visible light-mediated coupling of benzenediazonium tetrafluoroborate (1a) and CS2 (2).a
Entry
2 (equiv)
photocatalyst
solvent
Yield 3a (%)b
1
0.5
1
Ru(bpy)3(PF6)2
Ru(bpy)3(PF6)2
Ru(bpy)3(PF6)2
Ru(bpy)3(PF6)2
Ru(bpy)3(PF6)2
Ru(bpy)3(PF6)2
Ru(bpy)3(PF6)2
Ru(bpy)3Cl2
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
CS2
42
47
53
88
55
57
n.d.
65
57
73
8
2
3
1.5
2
4
5
2.5
3
6
7
–
8
2
DMSO
DMSO
DMSO
DMSO
DMSO
9
2
Ir(ppy)3
10
11
12
2
Ir(ppy)2(bpy)(PF6)
Ir(ppy)2(dtbbpy)(PF6)
none
2
2
53
aReaction conditions: 1a (0.1 mmol), photocatalyst (0.001 mmol), blue light (20 W), solvent (2 mL), rt, 6 h; byields were determined by HPLC using 3a
as the external standard.
Scheme 2: A plausible reaction mechanism.
To demonstrate the scope of the reaction, a series of arene- (3d, 3f, 3g, 3i, 3m and 3n) and functional groups such as
diazonium tetrafluoroborates was utilized in the reaction with chloro, bromo, ester, methyl, nitro, and phenyl groups were also
CS2 to generate the corresponding diaryl disulfides (Table 4). compatible with the reaction conditions.
Arenediazonium tetrafluoroborates 1b–p with both, electron-
withdrawing and donating groups successfully underwent trans- Conclusion
formation, affording the corresponding coupling products 3b–p In conclusion, we have developed an efficient method for the
in good to excellent yields (42–99%). Also sterically synthesis of diaryl disulfides through the coupling of arene-
demanding substrates gave the desired products in good yields diazonium tetrafluoroborates and CS2. This straightforward
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Beilstein J. Org. Chem. 2017, 13, 903–909.
Table 4: Reaction scope of the visible light-mediated coupling of arenediazonium tetrafluoroborates 1 with CS2 (2).
Substrate 1a
Product 3, yieldb
Substrate 1a
Product 3, yieldb
1a
1b
1c
3i, 94%, 82%c
3a, 80%, 50%c
1i
1j
3b, 81%, 78%c
3c, 85%, 72%c
3j, 99%, 85%c
1k
3k, 70%
1d
1e
1f
1l
3d, 94%
3l, 76%
1m
1n
3m, 56%
3e, 90%
3n, 42%
3f, 88%
1o
3g, 88%
1g
3o, 56%
907

Beilstein J. Org. Chem. 2017, 13, 903–909.
Table 4: Reaction scope of the visible light-mediated coupling of arenediazonium tetrafluoroborates 1 with CS2 (2). (continued)
1h
1p
3h, 76%
3p, 90%c, 92%c,d
aReaction conditions: 1 (0.1 mmol), CS2 (0.2 mmol), Ru(bpy)3(PF6)2 (0.001 mmol), blue light (20 W), DMSO (2 mL), rt, 6 h; bisolated yields after chro-
matography on silica gel; cthe reactions were carried out with the diazonium salts 1 at a 5 mmol scale; dacetone was used as the solvent.
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