Oxidation of aromatic sulfides with molecular oxygen: Controllable synthesis of sulfoxides or sulfones

Article abstract of DOI:10.1016/j.cclet.2020.03.030

The recent development of selective oxidation of aromatic sulfides with molecular oxygen was highlighted. The sulfoxides and sulfones could be obtained by simply switching the reaction media, i.e., bis(2-butoxyethyl)ether (BBE) or poly(ethylene glycol)dimethyl ether (PEGDME). The application of the high-boiling-point polyether as an initiator and green media can eliminate the need of large quantities of additives and volatile solvents. This strategy represents an economic and eco-friendly method that could find potential applications.

Full text of DOI:10.1016/j.cclet.2020.03.030

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Oxidation of aromatic sulfides with molecular oxygen: Controllable
synthesis of sulfoxides or sulfones
Lili Tang, Kejie Du, BingYu, Liangnian He
PII:
S1001-8417(20)30149-2
https://doi.org/10.1016/j.cclet.2020.03.030
CCLET 5528
DOI:
Reference:
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Chinese Chemical Letters
Accepted Date:
11 March 2020
Please cite this article as: Tang L, Du K, BingYu, He L, Oxidation of aromatic sulfides with
molecular oxygen: Controllable synthesis of sulfoxides or sulfones, Chinese Chemical Letters
(2020), doi: https://doi.org/10.1016/j.cclet.2020.03.030
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Oxidation of aromatic sulfides with molecular oxygen: Controllable synthesis of
sulfoxides or sulfones
Lili Tanga, Kejie Dud, BingYub,, Liangnian Hec,*
a College of Chemistry & Materials Engineering, Huaihua University, Huaihua 418008, China
b Green Catalysis Center, College of Chemistry, Zhengzhou University, Zhengzhou 450001, China
c State Key Laboratory of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China
d Hunan Key Laboratory for the Design and Application of Actinide Complexes, University of South China, Hengyang 421001, China
Graphical Abstract
The recent development of selective oxidation of aromatic sulfides with molecular oxygen was highlighted.
ARTICLE INFO
ABSTRACT
Article history:
The recent development of selective oxidation of aromatic sulfides with molecular oxygen was
highlighted. The sulfoxides and sulfones could be obtained by simply switching the reaction
media, i.e., bis(2-butoxyethyl)ether (BBE) or poly(ethylene glycol)dimethyl ether (pegdme).
The application of the high-boiling-point polyether as an initiator and green media can
eliminate the need of large quantities of additives and volatile solvents. This strategy represents
an economic and eco-friendly method that could find potential applications.
Received 4 February 2020
Received in revised form 3 March 2020
Accepted 10 March 2020
Available online
Keywords:
Oxidation
Sulfides
Sulfoxides
Sulfones
Catalyst-free
Sulfur-containing compounds are a class of important building blocks in organic synthesis and pharmaceuticals. For example,
sulfoxides and sulfones are important moieties in the marketed drugs such as Provigil, Dapsone, Vioxx and Fensulfothion (Fig. 1).
Selective oxidation of sulfides to the corresponding sulfoxides or sulfones is one of the most useful transformations for the construction
of sulfoxides and sulfones. However, most of the previous reports rely on the strong oxidants (e.g., peroxides and inorganic salts) and
excess amount of volatile solvents, which inextricably lead to large amount of waste. The past decades have witnessed the significant
achievements of green chemistry. In this context, the exploration of highly controllable synthetic methods with sustainable reagents in
green solvents under mild conditions is a longstanding goal for clean organic synthesis [1,2].
———
 Corresponding authors.
E-mail addresses: bingyu@zzu.edu.cn(B. Yu), heln@nankai.edu.cn (L. He)

Fig. 1. Marketed drugs containing a sulfoxide or a sulfone.
The previous studies by our group [3,4] and Jiang’s group [5] have shown that the employment of appropriate solvents or catalytic
conditions allows the precisely controlled selective oxidation of sulfides to the corresponding sulfoxides or sulfones. Despite these
important achievements, however, volatile solvents (e.g., ethanol, acetonitrile) or external catalysts (e.g., UO2(OAc)2·2H2O, H3PO4)
were still required to realize the switchable synthesis. Therefore, the development of catalyst-free oxidative procedure with green
oxidant (ideally molecular oxygen) and sustainable solvents for the controllable oxidation of sulfides is highly desirable.
Considering that the reaction of polyether and molecular oxygen could generate the corresponding peroxide intermediates [6], it
should be possible to apply an appropriate polyether as solvent and initiator to trigger the selective oxidation using molecular oxygen as
oxidant. Very recently, the research group of Professor Wei-Min He [7] in Hunan University of Science and Engineering realized such a
concept for the selective oxidation of sulfides to sulfoxides or sulfones in the presence of atmosphere pressure of molecular oxygen. In
this work, a simple and catalyst-free solvent-controllable procedure was disclosed by using the inexpensive and easily available high-
boiling-point ether as solvent. For example, when bis(2-butoxyethyl)ether (BBE) was applied as solvent, the oxidation of aromatic
sulfides 1 under oxygen balloon at 100 oC for 20 h gave the corresponding sulfones 2 as products. On the other hand, when
poly(ethylene glycol)dimethyl ether (pegdme) (average molecular weight ~250) was employed as reaction media, the same reaction
o
under 90 C for 16 h provided the corresponding sulfoxides 3 as products in good yields (Scheme 1, a and b). This solvent-controlled
reaction showed broad substrate scope and excellent functional group compatibility. Overall, 38 examples of sulfones 2 and 35
examples of sulfoxides 3 were successfully synthesized. Notably, the sulfone- and sulfoxide-containing bioactive molecules including
pesticides and pharmaceuticals could be prepared through this selective oxidation procedure. For instance, the sulfone-containing
artificial pharmaceuticals (e.g., Etoricoxib, Mesotrione, Zolimidine, and Rofecoxib) and sulfoxide-containing drug Sulindac were
successfully prepared via the selective oxidation of precursors in good yields (Scheme 1, c). Furthermore, the large-scale synthesis
suggested that this eco-friendly protocol is potentially practical.

Scheme 1. Controllable synthesis of sulfoxides or sulfones.
The investigation of reaction mechanism revealed that the singlet oxygen should be generated from the interaction of polyether and
molecular oxygen. Moreover, the reaction could be inhibited by radical scavengers, suggesting the oxidation proceeds via a radical
pathway. Both the both singlet oxygen and the peroxyl radical were confirmed by the electron paramagnetic resonance (EPR)
experiments. In addition, the 18O-labelled experiment demonstrated that the oxygen atoms of sulfoxides and sulfones are originally from
the molecular oxygen. Based on those investigations, two possible reaction pathways were proposed for the oxidation. The singlet
oxygen (1O2) or peroxide radical (polyether-OO) were probably generated in the presence of polyether by heating. As shown in
Scheme 2, the addition of the singlet oxygen to the sulfide 1 generates the intermediate A, which interacts with another 1 to form
sulfoxide 3 (path a). Alternatively, the peroxide radical could oxidize the sulfide 1 via a single electron transfer to produce the radical
cation intermediate B, which was converted into the persulfoxide radical C by reacting with oxygen. Then the intermediate C reacts
with another 1 to afford sulfoxide 3 (path b). Furthermore, the sulfoxide 3 could be oxidized into the sulfone 2 through the similar
process.
Scheme 2. Proposed reaction pathway.
In conclusion, the He’s group have developed a solvent-controlled selective oxidation of sulfides into sulfoxides or sulfones under
molecular oxygen. Such findings provide a deeper insight into the polyether-initiated aerobic selective oxidation reaction. The
application of the high-boiling-point polyether as an initiator and green media can eliminate the need of large quantities of additives and
volatile solvents. These results will open new avenues in the field of green oxidative transformations due to the impressive simplicity
and selectivity.
Declaration of interests
☒ The authors declare that they have no known competing financial interests or personal relationships that
could have appeared to influence the work reported in this paper.
References
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