Samarium oxide as efficient and non-endangered metal for synthesis of sulfones from sulfides: an elemental sustainability concept

Oxidation of sulfide to sulfone is a fundamental process to produce many important pharmaceutical compounds. Formerly, efficient methods have been reported for the synthesis of sulfones from sulfides. Yet some limitations were identified, such as the unbalance use of metal catalysts and expensive oxidizing agent, low reaction yields and production of by-products. In this current research, oxidation of sulfides to sulfones is described in the presence of samarium oxide (Sm2O3) along with hydrogen peroxide. The SEM image showed the crystalline morphology of the Sm2O3 as a cubic single phase (ICSD 98-001-2948) with a size distribution between 120 and 300 nm. In the recyclability experiment, Sm2O3 catalyst can be reutilized for five successive cycles and afforded the desired end-products in great yields (97–95%). This current work is vital, as the usage of non-endangered metals in organic transformation is geared towards achieving the elemental sustainability concept.


Introduction
In organic chemistry, oxidation is a significant and essential reaction [1].Oxidation of sulfides is one of the most prominent methods in the synthesis of a wide range of useful chemical, such as pharmaceuticals [2], agrochemicals [3], chiral auxiliaries [4] and so on.Owing to the unique electronic and biological properties of the sulfonyl functional group, this versatile intermediate functional group is embedded in many functional or advanced materials [5], including eletriptan [6], bicalutamide [7], mesotrione [8], N, N-diethyl-3-mesitylsulfonyl-1H-1,2,4-triazole-1carboxamide [9].Due to the increased demand in sulfones and their derivatives, alternative methods to synthesize sulfones have been dedicated to acquire a sustainable and efficient oxidation process.However, most of the oxidation methods still utilize nitric acid, potassium manganate (VII), and manganese (IV) oxide as oxidizing agents.Classical chemical synthesis methods for the oxidation of sulfides to sulfones usually possess limitations such as the use of precious metal catalysts, low products yield, and production of waste by-product.
On the contrary, hydrogen peroxide (H 2 O 2 ) has been regarded as a potential oxidant that is considered as low cost, high efficiency, high oxygen content and environ- mentally friendly [10].This alternative synthesis method also requires the supplementation of a sustainable catalyst to prevent the usage of hazardous reagent [11] and production of toxic by-products [12], in line with the principles of green chemistry.For years, many literature on the oxidation of sulfones from sulfides were generated based on the use of various endangered metals, such as selenium [13], caesium [14], tungstate [3], vanadium [2] and so on.In addition, some literature also revealed the overexploitation of certain metals for industrial mass usage that will eventually lead to the depletion of these metals in the coming century and may lead to another serious problem known as resource deficits.These endangered elements can be replaced by a sustainable catalyst in the organic transformation synthesis of sulfones from sulfides.There have been various studies that reported on the use of titanium [15], lutetium [16], praseodymium [17], dysprosium [18] and other sustainable elements in organic syntheses to conserve natural resources and prevent resource deficits [19].
In this study, an alternative method for the oxidation process of sulfides to sulfones with the use of samarium oxide (Sm 2 O 3 ) as catalyst and H 2 O 2 as green oxidant, respectively (Figure 1) was described.Samarium is one of the elements that belongs to lanthanide rare-earth metals that has been previously employed as Lewis acid catalyst in organic transformations [20] due to its high conductivity and great catalytic activity.Sm 2 O 3 shows outstanding performance as they consist of high surface areas, effective mass transport, high sensitivity, high selectivity, reduced overpotential, and high electrocatalytic performance.Furthermore, Sm 2 O 3 is considered as a green and sustainable catalyst and non-endangered metal in most organic transformations [21].

Material and instruments
All chemical solvents and reagents, including methyl acetate, samarium oxide, sulfide, chloroform-d (CDCl 3 ) 99.8 atom % D, hydrogen peroxide (30%) and dimethyl sulfoxide-d 6 (DMSO-d6) 99.96 atom % D were bought from Sigma-Aldrich (Malaysia) and were employed in this work without purification unless stated.Bruker Nuclear Magnetic Resonance (NMR) spectrometer, Varian Inova 400 Megahertz (MHz) was used to perform the proton ( 1 H) and carbon-13 ( 13 C) analysis.In the NMR spectra, all chemical shifts (δ) and coupling constants (J) were noted in parts per million (ppm) and Hertz (Hz), respectively.The gas chromatography-mass spectrometry (GC-MS) QP2010SE (Shimadzu) was employed to determine the molecular mass and the data were expressed as mass/charge ratio (m/z).
Thin layer chromatography (TLC) was performed using silica gel coated polyester backed sheets.The mass spectra were obtained using column C18 (4.6 mm × 250 mm) combined with the detection power of mass spectrometry was resulted from the Hewlett-Packard 5989A spectrometer coupling with Hewlett-Packard 5890 gas chromatography.The surface morphology of the samarium oxide was studied by using scanning electron microscopy (SEM) and was studied using X-ray diffraction (XRD, Rigaku Miniflex).The samples coated with gold were determined using an energy dispersive X-ray spectroscopy (EDS) detector with X-ray mapping capability to check the elements content of the samples.

General procedure for synthesis of sulfone
The sulfide (1 mmol) was transferred to a round bottom flask containing aqueous hydrogen peroxide 30% wt/v (3 mL) and Sm 2 O 3 (10 mmol).The mixture was stirred and heated for 3 h at 80°C.Thin layer chromatography (TLC) was employed to monitor the progression of the oxidation reaction.After the completion of the reaction, the aqueous layer containing Sm 2 O 3 was then extracted with ethyl acetate (3 × 5 mL).The organic layer was separated, combined, and concentrated under reduced pressure to gain the crude products.The targeted products were purified by precipitation technique.Sm 2 O 3 was recycled for the subsequent processes with the exact reaction condition.The desired products were confirmed with the GC-MS, 1 H-and 13 C-NMR analyses.

Results and discussion
In this experiment, the Sm 2 O 3 catalyst was subjected to the XRD and SEM analyses, and the results of characterization were shown in Figure S1.The SEM image showed the crystalline morphology of the Sm 2 O 3 to be indexed as cubic single phase (ICSD 98-001-2948) (Figure S1) with a size distribution between 120 and 300 nm.
Generally, all the reactions were executed under mild conditions.Reaction optimization was performed with sulfide (1 mmol) as the starting material dissolved in 3 mL of hydrogen peroxide 30% along with Sm 2 O 3 (10 mmol) in a 50 mL round bottom flask.Then, the mixture was stirred and heated at 60°C.TLC analysis was used to monitor the progress of desired product formation.The production of diphenyl sulfone was obtained at 62% yield after 1 h (Table 1, Entry 2).The amount of the H 2 O 2 employed amplifies the production of diphenyl sulfone.The synthesized diphenyl sulfone was afforded a good yield (85% yield) when 3 mL of H 2 O 2 was utilized as a green oxidant (Table 1, Entry 4).Furthermore, the longer the reaction time, the higher the yield of diphenyl sulfone obtained (89% yield) as the reaction time increased from 2 to 3 h (Table 1, Entry 5).Additionally, an excellent yield of diphenyl sulfone (97% yield) was also obtained when a higher reaction temperature was used (Table 1, Entry 8).At this stage, about   12).From the gained data, the optimized reaction condition was confirmed (Table 1, Entry 8).This optimized reaction condition was determined to be adequate to oxidize sulfides into sulfones with great reaction yields.The optimized reaction condition was applied to synthesize various sulfone derivatives (2a-j) by using different sulfides as starting material.Results showed that phenyl sulfide replaced by electron-withdrawing and donating groups (1b-j), afforded different kinds of sulfones as the desired end-products in excellent yields (Table 2, entries 2-10).Moreover, the sulfones were obtained by precipitation method without further purification by column chromatography.All the oxidation of sulfides involved in this study have afforded the respective sulfones (2a-j) with great yields (97-62%) (Table 2, Entries 1-10).In this experiment, no hazardous reagents and solvents were utilized.The generated sulfones were confirmed using the 1 H and 13 C-NMR and GC-MS analyses.Likewise, all the data of the characterized sulfones were compared to previous literature [22].
Sm 2 O 3 catalyst can be recovered at the end of the reaction and the catalytic performances of the reused Sm 2 O 3 were investigated.From the recyclability experiment, the Sm 2 O 3 catalyst could be used again for five consecutive cycles with no obvious loss of catalytic performances and afforded the desired end-products in great yields (97-95%).(Figure S2).Due to its appealing merits in the synthesis of sulfones in this study, the Sm 2 O 3 catalyst could be a potential catalyst for application at an industrial scale, and it may meet the criteria of green chemistry [23].
The outcome of this research was compared to past procedures on the formation of diphenyl sulfone (Table 3).In most cases, endangered-metal catalysts, hazardous reagents and complicated protocol were employed in the synthesis of sulfones from sulfides.
On the contrary, this current method encourages the utilization of non-endangered metal and promotes sustainable and greener organic transformation, by eliminating the usage of dangerous chemicals in the oxidation process.

Conclusion
An alternative method for the synthesis of sulfone from sulfide in the presence of the Sm 2 O 3 catalyst is unravelled.Application of the Sm 2 O 3 in the oxidation process had contributed to a safer and more feasible chemical reaction by minimizing dangerous chemicals in the oxidation process, low cost, and the targeted products were afforded with great yields (62-97%).The SEM image showed the crystalline morphology of the Sm 2 O 3 as a cubic single phase, Sm 2 O 3 had shown excellent catalytic performance, even after five successive usages in the recyclability test (97-62% product yields).The current study is important as the proposed green protocol minimizes the usage of dangerous reagents, contributes to balanced utilization of elements in the periodic table and minimizes the application of metals that are vulnerable in organic transformations, while striving for industrial advancement.

Figure 1 .
Figure 1.Synthetic route for the synthesis of sulfone from sulfide using samarium oxide and hydrogen peroxide.

Table 1 .
Optimization study of diphenyl sulfone synthesis from sulfide.

Table 2 .
Oxidation of sulfide to sulfone using Sm 2 O 3 as catalyst at 80°C.Sm 2 O 3 was utilized in the oxidation process of sulfide tp sulfone (Table 1, Entry 8).On the contrary, a control experiment carried out without Sm 2 O 3 by using the same starting materials and reaction condition resulted in only 27% yield of diphenyl sulfone (Table 1, Entry 11).At room temperature (rt), only 8% yield of diphenyl sulfone was afforded (Table 1, Entry

Table 3 .
Overview of past and current procedures for the synthesis of diphenyl sulfone and their yields