Electrochemical Synthesis of Dibenzothiophene S,S-Dioxides from Biaryl Sulfonyl Hydrazides

Abstract

The electrochemical synthesis of dibenzothiophene S,S-dioxides was achieved by the anodic oxidation of biaryl sulfonyl hydrazides. The use of Bu₄NOTf as the electrolyte in HFIP/CH₃NO₂ (15 : 1) is essential. Several biaryl sulfonyl hydrazides followed by dibenzothiophene S,S-dioxides under mild electrochemical conditions. Control experiments and density functional theory calculations suggested that the electrooxidation of biaryl sulfonyl hydrazides would generate sulfonyl radicals or sulfonyl cations which were converted to dibenzothiophene S,S-dioxides.

Dibenzothiophene S,S-dioxides and its derivatives are widely used in the fields of material science^1,2 and pharmaceuticals.³ They are also used as important precursors for the syntheses of heterocyclic compounds.⁴ In particular, dibenzothiophene S,S-dioxides has been focused on organic light-emitting materials⁵ owing to their strong electron acceptor properties and their highly fluorescence efficiency. Since dibenzothiophene S,S-dioxides are important structures, several methods for their synthesis have been reported. A simple method for the synthesis of dibenzothiophene S,S-dioxides is the oxidation of dibenzothiophene (Scheme 1a).^1,5 Although oxidation is one of the most conventional synthetic methods of dibenzothiophene S,S-dioxides, stoichiometric amounts of chemical oxidants are required. Transition-metal-catalyzed reactions are also useful for the synthesis of dibenzothiophene S,S-dioxide derivatives. For instance, Laha and co-worker reported the Pd-catalyzed intramolecular oxidative C–C bond formation of biaryl sulfones (Scheme 1b).⁶ Jiang and co-workers reported a Cu-catalyzed SO₂/I exchange reaction of diaryliodonium(III) salts (Scheme 1c).⁷ Although these reactions are straightforward ways of constructing benzothiophene S,S-dioxides, they require the use of toxic or precious metals under harsh conditions. C–S bond formation is a powerful tool for the construction of sulfonyl group-containing organic compounds (Scheme 1d). Zhang and co-workers reported a Friedel–Crafts-type sulfonylation reaction using sulfonyl azides as sulfonyl donors (Scheme 1d).⁸ Despite the simple set-up, HN₃ would be generated which is acutely toxic and intensively explosive. Therefore, a transition metal- and oxidant-free and safety method for synthesizing dibenzothiophene S,S-dioxide is in high demand.

Scheme 1.

Conventional syntheses of dibenzothiophene S,S-dioxides and electrochemical synthesis of dibenzothiophene S,S-dioxides (This work).

Electrochemical synthesis helps fulfill these demands, as electricity is a powerful oxidant for performing the desired reactions.⁹ In particular, electrochemical C–X bond formation, such as C–O^10,11 and C–S,^12,13 has been in the spotlight for the synthesis of heterocyclic compounds. Recently, sulfonyl hydrazides have been used in electrochemical synthesis as sulfonyl radical precursor.¹⁴ For instance, Zhang and co-workers reported the electrochemical synthesis of benzothiophene S,S-dioxide derivatives via intermolecular C–S and C–C bond formation by the reaction of sulfonyl hydrazide with internal alkynes.¹⁵ However, to the best of our knowledge, there are no reports on the electrochemical synthesis of dibenzothiophene S,S-dioxide motifs and the intramolecular cyclization reaction by the oxidation of sulfonyl hydrazides. Herein, we report the electrochemical synthesis of dibenzothiophene S,S-dioxides from biaryl sulfonyl hydrazides via the generation of a sulfonyl radical or cation species via a denitrogenative reaction and dehydrogenative C–S bond formation (Scheme 1e).

We chose [1,1′-biphenyl]-2-sulfonohydrazide (1a) as model compound and subjected it to electrochemical cyclization under several conditions (Table 1). The electrolysis was first conducted under a constant current of 15 mA in an undivided cell equipped with a carbon rod (C) anode and a Pt plate (Pt) cathode, using Bu₄NOTf (0.2 M) as the supporting electrolyte in 1,1,1,3,3,3-hexafluoropropan-2-ol (HFIP)/CH₃NO₂ (15 : 1). After 4.0 F mol⁻¹ of constant current was passed, the desired dibenzo[b,d]thiophene 5,5-dioxide (2a) was obtained in 48 % yield as a major product (entry 1). Unfortunately, sultone 3a was obtained in 17 % yield, and 4a, which would be obtained by-nucleophilic attack of the HFIP anion, was also obtained in 23 % yield as a by-product. 3a would be formed when sulfonyl radicals are quenched by oxygen, and the resulting sulfonate undergoes anodic oxidation.¹¹ Moreover, the formation of 4a suggests that sulfonyl cation intermediates would be generated during electrolysis.^8,16 We next examined the effect of the electrolyte. Other electrolytes examined so far were ineffective (entries 2–5). In particular, the use of Bu₄NBF₄ or Bu₄NPF₆ resulted in the generation of [1,1′-biphenyl]-2-sulfonyl fluoride (entry 3: 30 % yield, and entry 4: 34 % yield), which also suggests the generation of the sulfonyl cation intermediates.¹⁷ The reactions were significantly affected by the solvent (entries 6–12 and Tables S1 and S2 in Section 1 in the Supporting Information). In HFIP without CH₃NO₂, the yield of 2a decreased slightly (41 %, entry 6). In CH₃NO₂ without HFIP, 2a was not obtained (entry 7). When we examined the ratio of HFIP/CH₃NO₂, the yield of 2a decreased as the ratio of CH₃NO₂ increased (Table S1). Using ⁱPrOH or 2,2,2-trifluoroethanol (TFE) instead of HFIP was ineffective (entries 8 and 9). When we used several other solvents (e.g. DMSO, EtOAc, toluene) instead of CH₃NO₂, the yield of 2a decreased (entries 10–12, and Table S2 in the Section 1 of the Supporting Information). We considered that the co-solvent of HFIP/CH₃NO₂ would stabilize the electrogenerated radical intermediates.¹⁸

Table 1. Effects of electrolytes and solvents.^[a]

Next, we examined electrochemical parameters of the reactions (Table 2). With 3.0 F mol⁻¹ of electricity, only 57 % of 1a was converted, and 2a was obtained in 30 % yield (entry 1). In contrast, with 5.0 F mol⁻¹ of electricity, almost all of 1a was converted, but the yield of 2a decreased (entry 3 vs. entry 2). These results suggest that 2a might have been absorbed on the carbon anode and decomposed by over-oxidation. As the current was decreased to 2.5, 5, or 10 mA, the yield of 2a decreased (entries 4–6). When the current was increased to 20 mA, the yield of 2a increased. Lower yields of 2a were obtained when the carbon rod was replaced by reticulated vitreous carbon (RVC), glassy carbon (GC), or a Pt plate. Passing of electricity was necessary for the reaction, and the reaction did not proceed without electrolysis (entry 11). Overall, we identified the optimized conditions, involving Bu₄NOTf (0.2 M) in a mixed solvent of HFIP/CH₃NO₂ (15 : 1) with 4.0 F mol⁻¹ of constant current electricity (15 mA).

Table 2. Electrochemical oxidation of 1a under several conditions.^[a]

Under the optimized conditions, we next examined the electrochemical synthesis of several benzothiophene S,S-dioxides (Scheme 2). First, we carried out the reaction of substrates bearing several Ar². From 4′-methyl-[1,1′-biphenyl]-2-sulfonohydrazide (1b) and 4′-(trifluoromethyl)-[1,1′-biphenyl]-2-sulfonohydrazide (1c), the desired dibenzothiophene S,S-dioxides (2b and 2c) were obtained in 32 % and 24 % yields, respectively. The reaction of 2-(naphthalen-2-yl)benzenesulfonohydrazide (1d) afforded 2d in 21 % yield. Benzothiophene S,S-dioxide fused with benzothiophene (2e) was also obtained in a similar manner (50 % yield by the 7.5 mA of constant current electrolysis, performed with 3.0 F mol⁻¹ of electricity). These results suggest that biaryl sulfonyl hydrazides bearing electron-donating groups proceeded more efficiently, probably because of the high nucleophilicity of the Ar² ring.

Scheme 2.

Electrochemical syntheses of dibenzothiophene S,S-dioxides under the optimized conditions.^[a] The structure of 2d was confirmed by the x-ray analysis (CCDC 2289413). For the details, see Section 2 in the Supporting Informations.

Next, we examined the Ar¹ ring. The reaction of 1b′, bearing a methyl group, gave the corresponding dibenzothiophene S,S-dioxide 2b′ in low yield (7 %). In contrast, 1f bearing a fluoro group afforded 2f in 47 % yield. This is probably because the use of an Ar¹ ring substituted with an electron-withdrawing group makes the radical or cationic intermediates more electrophilic and promotes the reaction more efficiently. Unfortunately, 2-phenylbenzo[b]thiophene-3-sulfonohydrazide 2e′ was not obtained from 1e′.

Control experiments were conducted to explore the mechanism of the electrochemical cyclization reaction. We first examined the electrochemical reaction of 1a in the presence of 2,2,6,6-tetramethyl-1-piperidinyloxyl (TEMPO) (Scheme 3). 2a was not obtained, and the TEMPO adduct product was detected by ESI-HRMS. This strongly suggests that sulfonyl radicals were generated in the reaction system. We next performed cyclic voltammetry (Fig. 1). The onset of the oxidation peaks of 1a and 2a were observed at 0.62 and 1.82 V (vs. Fc/Fc⁺). These results indicate that the electrooxidation of 1a occurs more easily than that of 2a.

Scheme 3.

Control experiment (Radical trap experiment).

Figure 1.

Cyclic voltammogram of [1,1′-biphenyl]-2-sulfonohydrazide (1a) and dibenzo[b,d]thiophene 5,5-dioxide (2a). Experiments were performed in CH₃CN with Bu₄NPF₆ as an electrolyte (0.1 M).

Based on mechanistic studies, a plausible reaction mechanism is illustrated in Fig. 2. First, the anodic oxidation of 1a would generate sulfonyl radical A via denitrogenation. Indeed, gas generation was observed on the anode. After the generation of sulfonyl radical A, there would be two possible pathways: radical cyclization (path a) and the S_EAr mechanism (path b). In path a, the intermolecular cyclization of A forms radical intermediate B. Further anodic oxidation of B would generate cationic intermediate D. Another possibility is that sulfonyl radical A would be oxidized to sulfonyl cation C, and the subsequent intramolecular electrophilic substitution reaction of its benzene ring to sulfonyl cation would generate intermediate D (path b). Subsequent deprotonation of D would afford the desired compound 2a. On the cathode, hydrogen would be generated via the reduction of HFIP. Actually, gas generation on the cathode was observed.

Figure 2.

Plausible mechanism.

We also performed preliminary density functional theory (DFT) calculations to gain further insight of the reaction mechanism of this cyclization reaction (for the detail of the DFT calculations, see Section 3 in the Supporting Information^19–34). The activation energy from A to B is 18.2 kcal mol⁻¹ and that of C to D is 2.9 kcal mol⁻¹, implying that both radical cyclization and electrophilic substitution would proceed even at room temperature. The calculated data agree well with the experimental results.

In summary, we developed a method for the synthesis of dibenzothiophene S,S-dioxides via electrochemical denitrogenative and dehydrogenative intramolecular cyclization. The reaction would proceed via radical or cationic pathways, and several dibenzothiophene S,S-dioxides were obtained under mild conditions. Studies on the scope and applications of this strategy using sulfonyl hydrazides via intramolecular cyclizations are ongoing in our laboratory.

Data Availability Statement

The data that support the findings of this study are openly available under the terms of the designated Creative Commons License in J-STAGE Data at https://doi.org/10.50892/data.electrochemistry.24129933.

• 1) The electrochemical synthesis of dibenzothiophene S,S-dioxides was achieved by the anodic oxidation of biaryl sulfonyl hydrazides. The use of Bu₄NOTf as the electrolyte in HFIP/CH₃NO₂ (15 : 1) is essential. Several biaryl sulfonyl hydrazides followed by dibenzothiophene S,S-dioxides under mild electrochemical conditions. Control experiments and density functional theory calculations suggested that the electrooxidation of biaryl sulfonyl hydrazides would generate sulfonyl radicals or sulfonyl cations which were converted to dibenzothiophene S,S-dioxides.

CRediT Authorship Contribution Statement

Yasuyuki Okumura: Investigation (Lead), Visualization (Lead), Writing – original draft (Lead)

Eisuke Sato: Supervision (Supporting), Writing – review & editing (Supporting)

Koichi Mitsudo: Funding acquisition (Lead), Project administration (Lead), Supervision (Lead)

Seiji Suga: Funding acquisition (Equal), Project administration (Equal), Supervision (Equal), Writing – review & editing (Equal)

Conflict of Interest

The authors declare no conflict of interest in the manuscript.

Funding

Japan Society for the Promotion of Science: 22H02122

Japan Society for the Promotion of Science: 22K05115

Japan Society for the Promotion of Science: 21H05214

Japan Society for the Promotion of Science: 23K17917

Footnotes

E. Sato, K. Mitsudo, and S. Suga: ECSJ Active Members

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