A Stepwise, Nitrosonium-Catalyzed Aerobic Oxidation of Thiols to Disulfides and Thiosulfonates

Abstract

A selective and controllable oxidation of thiols to disulfides or thiosulfonates has been developed using molecular oxygen, trifluoroacetic acid, and catalytic NaNO₃. Both aromatic and aliphatic thiols afford high yields. Sequential oxidation from thiols to disulfides and then to thiosulfonates was observed, with the second step governed by the acid concentration and substrate steric and electronic effects. Acid and oxygen cooperatively enable in situ generation and turnover of the active nitrosonium species.

Introduction

Thiosulfonates, also named as sulfonothioates or the S-esters of thiosulfonic acid, are a special class of disulfides, in which one of the sulfur atoms bears two-oxygen atoms (R–SO₂–S–R′). Thiosulfonates are increasingly found in natural products and have been recognized for their biological activities, agricultural applications and therapeutic potential (Figure ). , Recently, thiosulfonates have emerged as powerful and convenient reagents for introducing sulfur-containing functional groups. − Therefore, the development of efficient methods for their synthesis has attracted considerable attention from chemists. Oxidation of thiols or disulfides with various oxidants, including chlorine, N-bromosuccinimide (NBS), ceric ammonium nitrate (CAN), activated hydrogen peroxide (H₂O₂), potassium peroxymonosulfate (OXONE), m-chloroperbenzoic acid (mCPBA), Selectfluor, hypervalent iodines, HNO₃/Al­(H₂PO₄)₃ and dinitrogen tetroxide (N₂O₄), has been applied to prepare thiosulfonates. Thiosulfonates have also been prepared through self-coupling reactions of sulfinamides, sulfonyl hydrazides, and sodium sulfinates and via reductive coupling reactions of sulfonyl chlorides. Various cross-coupling reactions, such as those involving sodium thiosulfonates with alkyl halides, or sulfonic, sulfinic acids and sulfur dioxide (and their derivatives) with diverse sulfur-containing partners, − have been developed for the synthesis of unsymmetrical thiosulfonates. Although numerous synthetic strategies have been developed for thiosulfonates, methods that align well with the principles of green chemistryparticularly those demonstrating high atom economy (AE), reaction mass efficiency (RME), and low process mass intensity (PMI)are still in demand. , In this regard, employing nontoxic molecular oxygen, the greenest and most economical oxidant, is especially appealing. Representative examples of thiosulfonate synthesis using oxygen or air are shown in Scheme . ,,, Early studies employing oxygen as the oxidant or photoassisted conditions generally afforded thiosulfonates in low yields. , The subsequent introduction of catalysts such as Cu­(I), Fe­(III), and polyoxomolybdates significantly improved reaction efficiency. Nevertheless, alkyl thiosulfonates are typically obtained in lower yields than their aryl counterparts, highlighting the need for further enhancement of the reactivity of aliphatic thiols and for milder, more sustainable reaction conditions, such as low temperatures and metal-free protocols. In this context, a nitrosonium (NO⁺)-catalyzed strategy offers a promising alternative, and our recent advances in this area are described herein.

1.

Selected examples of pharmaceutically important thiosulfonates.

1. Syntheses of Thiosulfonates under Oxygen.

Results and Discussion

We began our investigation by treating thiophenol (1a, 1.0 mmol) with trifluoroacetic acid (TFA, 2.0 mmol) and various nitrosonium (NO⁺) precursors, including nitrosonium tetrafluoroborate (NOBF₄), tert-butyl nitrite (t-C₄H₉-ONO), sodium nitrite (NaNO₂), sodium nitrate (NaNO₃) and nitric acid (HNO₃), in dichloromethane under an oxygen atmosphere (entries 1–5, Table ). After 1–2 h at room temperature, all reactions afforded S-phenyl benzenesulfonothioate (2a) in excellent yields (90% to quantitative). In contrast, thiosulfonate 2a was not formed when either TFA or the NO⁺ source was omitted or when the reaction was conducted under a nitrogen atmosphere (entries 6–8). Under air, the reaction was slow, yielding 1,2-diphenyl disulfide (3a) after 16 h (entry 9). When nitronium tetrafluoroborate (NO₂BF₄) was useda precursor to NO₂ ⁺ and expected to generate NO⁺ via equilibrium with TFA the yield of 2a was slightly lower (79%, entry 10) after 2 h. Considering the reagent cost, operational convenience, and need to monitor or isolate reaction intermediates (e.g., disulfides; vide infra), sodium nitrate was selected as the preferred precursor for in situ generation of NO⁺. The reaction required 2 equiv or more of TFA as the formation of 2a was suppressed with 1.5 equiv of TFA, but the yield of 2a did not go higher with 2.5 equiv of the acid (entries 11 and 12). Other organic acids, such as acetic and trichloroacetic acids, did not give the product (entries 13 and 14). A small amount of 2a was formed with p-toluenesulfonic acid, but 83% of thiosulfonate was obtained with methanesulfonic acid (entries 15 and 16, respectively). Among the inorganic acids screened (entries 17–21), only hydroiodic acid (HI) provided 2a in a reasonable yield (68%). We believe that the pK _a values of the acids (see Table S1) play an important role; however, competing side reactions, such as further oxidation of thiols to sulfonic acids, may also contribute to the low efficiency observed. Regarding the usage of solvents, we found that this reaction was compatible with toluene (entry 22). In 1,2-dichloroethane, thiophenol was quantitatively converted to disulfide 3a within 1 h but produced a complex mixture after 3 h; similarly, the reaction in chloroform led to a decomposition mixture after 3 h (entries 23 and 24). This reaction did not proceed in acetonitrile, dimethyl sulfoxide, N,N-dimethylformamide, alcohols and ethers (see Table S2 for the complete list). We concluded that the optimal conditions for this transformation are NaNO₃ (0.1 mmol) and TFA (2.0 mmol) in dichloromethane at room temperature for 1 h. A gram-scale reaction of 1a to 2a was also achieved in 92% yield (shown in parentheses, entry 4).

1. Optimization of Thiosulfonate Formation .

entry	NO+ source (0.1 equiv)	acid (equiv)	solvent	time (h)	yield (%)
1	NOBF4	TFA (2.0)	CH2Cl2	1	90
2	t-C4H9-ONO	TFA (2.0)	CH2Cl2	1	94
3	NaNO2	TFA (2.0)	CH2Cl2	1	97
4	NaNO3	TFA (2.0)	CH2Cl2	2	99 (92)
5	HNO3	TFA (2.0)	CH2Cl2	1	99
6	–	TFA (2.0)	CH2Cl2	16	0
7	NaNO3	–	CH2Cl2	16	0
8	NaNO3	TFA (2.0)	CH2Cl2	2	0
9	NaNO3	TFA (2.0)	CH2Cl2	16	98
10	NO2BF4	TFA (2.0)	CH2Cl2	2	79
11	NaNO3	TFA (1.5)	CH2Cl2	16	0
12	NaNO3	TFA (2.5)	CH2Cl2	2	84
13	NaNO3	CH3CO2H (2.0)	CH2Cl2	24	0
14	NaNO3	CCl3CO2H (2.0)	CH2Cl2	24	0
15	NaNO3	p-TsOH (2.0)	CH2Cl2	24	24
16	NaNO3	CH3SO3H (2.0)	CH2Cl2	3	83
17	NaNO3	HCl(aq) (2.0)	CH2Cl2	24	0
18	NaNO3	HBr(aq) (2.0)	CH2Cl2	16	–
19	NaNO3	HI(aq) (2.0)	CH2Cl2	16	68
20	NaNO3	H2SO4 (2.0)	CH2Cl2	3	0
21	–	HNO3 (2.0)	CH2Cl2	1	20
22	NaNO3	TFA (2.0)	toluene	3	87
23	NaNO3	TFA (2.0)	(CH2Cl)2	1	98
24	NaNO3	TFA (2.0)	CHCl3	3	–

^aA source of nitrosonium ion (0.1 mmol) was added to a solution of 1a (110.2 mg, 1.0 mmol), TFA (153.1 μL, 2.0 mmol) and a solvent (1.0 mL) at 25 °C. The reaction mixture was stirred at 25 °C under an atmosphere of oxygen (balloon) for the time indicated, and then water (5 mL) was added. The products were obtained after extractions (5 mL CH₂Cl₂ × 3), dried over Na₂SO₄, filtered through a Celite pad and concentrated.

^b 1a (1.0 g, 9.1 mmol), NaNO₃ (77.2 mg, 0.91 mmol) and TFA (1.4 mL) was applied to yield 2a (1.04 g, 4.15 mmol, 92%).

^cStarting material 1a recovered.

^dUnder nitrogen atmosphere.

^eUnder air.

^fDiphenyl disulfide.

^gDecomposed.

After having the optimized reaction conditions in hand, the scope of this thiosulfonate formation was examined using various thiols (Table ). In addition to thiophenol (1a), aryl thiols with alkyl substituents at para-, meta- and ortho-positions were all converted to the corresponding thiosulfonates (2b–2f) in excellent yields (entries 1–5). The reaction of thiol 1e was not influenced by the sterically hindered 2,4,6-trimethylphenyl group at the sulfur atom (entry 4). para-Substituents on thiophenol, ranging from electron-donating (σ_para = −0.14, OMe) and electron-neutral (σ_para = 0, NHAc) to electron-withdrawing (σ_para = 0.15, 0.24, 0.26, 0.31, 0.47 for fluoro-, chloro-, bromo-, acetate and acetyl group, respectively), have little effect on the reaction (2g–2m, entries 6–12). 2-Naphthylthiol was converted to 2-naphthyl thiosulfonate 2n with a 74% yield (entry 13). For thiols with sulfur bonded to an sp³ carbon, or alkyl thiols, a higher loading of TFA (4 equiv) was required to afford the corresponding thiosulfonates (2o–2w, entries 14–22). We were glad to find that all primary thiols reacted smoothly to give near-quantitative yields (98–99%, 2o–2u), except for volatile n-propyl thiol, which furnished 2p in 81% yield. Secondary thiols, such as isopropyl and cyclohexyl thiols, also provided the corresponding thiosulfonates 2v and 2w in slightly lower yields (96% and 98%, respectively; entries 21 and 22). In contrast, tertiary tert-butyl thiol (1x) exclusively formed disulfide 3x (entry 23), indicating that disulfide formation precedes oxidation to thiosulfonates and that steric hindrance of the tert-butyl group inhibits this subsequent oxidation step. On the basis of this observation, a series of disulfides 3 were selectively prepared by reducing the TFA loading (1–2 equivalence) and shortening the reaction time (Table ). These include 1,2-diphenyldisulfide (3a) and its derivatives bearing either electron-donating or electron-withdrawing substituents, such as 4-methyl (3b), 4-methoxy (3g), 4-fluoro (3i), and 4-nitro (3y) groups (entries 2–5). Using 3 equiv of TFA converted alkyl thiols, such as 1-dodecanethiol (1t), to 1,2-didodecyldisulfide (3t, entry 6). Notably, electron-deficient thiols, including 4-nitrobenzenethiol and pyridine-2-thiol, afforded exclusively the corresponding disulfides 3y and 3z (entries 5 and 7). These results indicate that electron-deficient aryl substituents, as well as steric hindranceas observed for tert-butyl thiolmay disfavor further oxidation of disulfides to thiosulfonates. In addition, we observed that glutathione (GSH, 4) underwent clean oxidation to its disulfide form, GSSG (5), a well-established biomarker of oxidative stress, under this condition (eq ).

2. Formation of Thiosulfonates .

entry	R	product (% yield)
1	4-CH3-C6H4	2b (98)
2	3-CH3-C6H4	2c (75)
3	2,6-(CH3)2-C6H3	2d (83)
4	2,4,6-(CH3)3-C6H2	2e (88)
5	4-t-Bu-C6H4	2f (94)
6	4-OMe-C6H4	2g (93)
7	4-AcHN-C6H4	2h (74)
8	4-F-C6H4	2i (98)
9	4-Cl-C6H4	2j (94)
10	4-Br-C6H4	2k (82)
11	4-CO2CH3-C6H4	2l (94)
12	4-Ac-C6H4	2m (81)
13	2-naphthyl	2n (74)
14	2-phenylethyl	2o (99)
15	n-propyl	2p (81)
16	n-butyl	2q (98)
17	n-hexyl	2r (98)
18	n-octyl	2s (98)
19	n-dodecyl	2t (98)
20	isobutyl	2u (98)
21	isopropyl	2v (96)
22	cyclohexyl	2w (98)
23	tert-butyl	(t-BuS)2, 3x (94)

^aSodium nitrate (0.10 mmol) was added to a solution of thiol (1.0 mmol), dichloromethane (1.0 mL), and trifluoroacetic acid (153.1 μL, 2.0 mmol). The reaction mixture was stirred at rt for 1 h under an oxygen atmosphere (balloon).

^bTFA (306.0 μL, 4.0 mmol).

3. Formation of Disulfides.

entry	R	condition	Product (% yield)
1	phenyl	TFA (2.0 equiv), 25 °C, 30 min	3a (98)
2	4-Me-C6H4	TFA (1.0 equiv), 25 °C, 1 h	3b (97)
3	4-OMe-C6H4	TFA (1.0 equiv), 25 °C, 3 h	3g (98)
4	4–F-C6H4	TFA (1.0 equiv), 25 °C, 3 h	3i (98)
5	4-NO2-C6H4	TFA (2.0 equiv), 25 °C, 3 h	3y (98)
6	n-dodecyl	TFA (3.0 equiv), 25 °C, 3 h	3t (98)
7	2-pyridinyl	TFA (4.0 equiv), 25 °C, 16 h	3z (95)

1

The stepwise oxidation of thiol 1 to disulfide 3 and then to thiosulfonate 2 was further confirmed by monitoring the reaction of 4-methylbenzenethiol (1b) with ¹H NMR, in which the methyl signals of the three species were clearly resolved in the range of 2.1 ∼ 2.4 ppm (Figure ). After the addition of sodium nitrate to the reaction mixture, 1b was rapidly consumed, achieving complete conversion within 40 min to form disulfide 3b, followed by the gradual conversion of 3b into thiosulfonate 2b over the next 30 min. Indeed, treating disulfide 3a under the nitrosonium-catalyzed aerobic oxidation condition also afforded thiosulfonate 2a in 96% yield (see the Experimental Section). We also observed that this reaction was inhibited by 2,6-di-tert-butyl-4-methylphenol (BHT) and 2,2,6,6-tetramethyl-1-piperidinyloxyl (TEMPO).

2.

Stacked ¹H NMR spectra (300 MHz, CDCl₃) recorded during the oxidative conversion of 1b.

The reaction mechanism is depicted in Scheme . Nitrosonium ion reacts with thiol 1 to form the corresponding S-nitrosothiol 6, which subsequently reacts with another equivalent of thiol to afford disulfide 3. Nitrosonium ions are regenerated from nitroxyl (azanone, HNO) by molecular oxygen under acidic conditions. Complete consumption of the thiol and accumulation of the disulfide were observed (Figure ), enabling the isolation of disulfide 3 as shown in Table . Further oxidation of the disulfide to thiosulfonate is proposed to proceed via NO⁺-mediated, stepwise oxygenation, forming thiosulfinate 7, disulfoxide 8, and subsequent rearrangement to thiosulfonate 2. , Alternatively, direct oxidation of thiosulfinate 7 to the corresponding thiosulfonate has also been proposed. , Consistent with our previous observations in NO⁺-mediated sulfide oxidation, no H₂O₂ was detected in the reaction medium using starch-iodide test (Figure S1), supporting a distinct NO⁺-driven oxygenation pathway. Previous oxidation methods relied on stoichiometric amounts of nitrogen oxides, such as N₂O₄; , in contrast, the presence of TFA and molecular oxygen enables nitrosonium recycling, thereby facilitating efficient thiol conversion.

2. Reaction Mechanism for the Formation of (a) Disulfide and (b) Thiosulfonates.

Conclusion

In summary, we have developed a practical and efficient method for the selective oxidation of thiols. The reaction is catalyzed by NO⁺, generated in situ from NaNO₃ in the presence of trifluoroacetic acid, and proceeds cooperatively with molecular oxygen at room temperature. Compared with previously reported aerobic thiol oxidations, this metal-free and mild system enables a stepwise, controllable conversion of thiols to disulfides or thiosulfonates with particularly high efficiency for aliphatic thiols.

Experimental Section

General Information

Reagents, such as NaNO₂, NaNO₃, NOBF₄, NO₂BF₄, tert-butyl nitrite, sulfuric acid, TFA, and acetic acid, were purchased from commercial sources (ACS grade) and used without further purification. Thin-layer chromatography (TLC) was conducted using precoated silica gel 60 F₂₅₄ plates containing a fluorescent indicator; spots were examined under UV light or revealed by KMnO₄ solution. Purification by chromatography was conducted using silica gel (230–400 mesh). The ¹H and ¹³C NMR spectra were recorded in a CDCl₃ or D₂O solution by using a Bruker Avance 500 and 300 NMR spectrometer. Chemical shifts for ¹H and ¹³C NMR spectra are reported in δ units (parts per million) with reference to residual solvent peaks. High-resolution mass spectrometry (HRMS) data were recorded on a JMS-700 quadrupole mass spectrometer. Caution! Trifluoroacetic acid, a GHS Category 1 corrosive chemical; dichloromethane, a serious eye and skin irritant; and toxic chemicals, including many foul-smelling thiols, pose significant safety hazards. All reactions involving these reagents should be conducted in a well-ventilated fume hood with the appropriate personal protective equipment.

S-Phenyl Benzenesulfonothioate (2a)

Sodium nitrate (8.5 mg, 0.10 mmol) was added to a solution of thiophenol (1a, 110.2 mg, 1.0 mmol) and trifluoroacetic acid (153 μL, 228.0 mg, 2.0 mmol) in dichloromethane (1.0 mL) at 25 °C. The resulting reaction mixture was stirred at 25 °C for 1 h under an oxygen atmosphere (O₂ balloon). After completion, the mixture was filtered through a pad of Celite and eluted with dichloromethane (10 mL). The filtrate was added with water (10 mL) and extracted with dichloromethane (3 × 5 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (SiO₂, EtOAc/hexanes, 1:9, R _f 0.52) to give compound 2a (123.3 mg, 0.49 mmol, 98%) as a colorless solid. Mp 40.0–42.0 °C; ¹H NMR (300 MHz, CDCl₃) δ 7.59–7.53 (m, 3H), 7.48–7.45 (m, 1H), 7.44–7.37 (m, 2H), 7.34–7.28 (m, 4H); ¹³C­{¹H} NMR (75 MHz, CDCl₃) δ 142.8, 136.6, 133.8, 131.5, 129.5, 128.9, 127.8, 127.5. The spectroscopic data were consistent with the reported values. Compound 2a was also prepared from diphenyldisulfide 3a (218.4 mg, 1.0 mmol), sodium nitrate (8.5 mg, 0.10 mmol), and TFA (153 μL, 2.0 mmol) using the same procedure to give 2a in 96% yield (239.6 mg, 0.96 mmol). The reactions were completely inhibited with BHT and TEMPO (0.3 mmol), and only 1a was observed in the TLC analysis.

S-(p-Tolyl) 4-Methylbenzenesulfonothioate (2b)

Sodium nitrate (8.5 mg, 0.10 mmol) was added to a solution of 4-methylbenzenethiol (1b, 124.2 mg, 1.0 mmol) and trifluoroacetic acid (153 μL, 228.0 mg, 2.0 mmol) in dichloromethane (1.0 mL) at 25 °C. The resulting reaction mixture was stirred at 25 °C for 1 h under an oxygen atmosphere (O₂ balloon). After completion, the mixture was filtered through a pad of Celite and eluted with dichloromethane (10 mL). The filtrate was added with water (10 mL) and extracted with dichloromethane (3 × 5 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (SiO₂, EtOAc/hexanes, 1:9, R _f 0.56) to give compound 2b (135.1 mg, 0.49 mmol, 98%) as a colorless solid. Mp 74.0–76.0 °C; ¹H NMR (300 MHz, CDCl₃) δ 7.44 (d, J = 8.1 Hz, 2H), 7.24–7.19 (m, 4H), 7.13 (d, J = 8.1 Hz, 2H), 2.41 (s, 3H), 2.37 (s, 3H); ¹³C­{¹H} NMR (75 MHz, CDCl₃) δ 144.7, 142.1, 140.3, 136.4, 130.2, 129.4, 127.5, 124.4, 21.6, 21.4. The spectroscopic data were consistent with the reported values.

S-(m-Tolyl) 3-Methylbenzenesulfonothioate (2c)

Sodium nitrate (8.5 mg, 0.10 mmol) was added to a solution of 3-methylbenzenethiol (1b, 124.2 mg, 1.0 mmol) and trifluoroacetic acid (153 μL, 228.0 mg, 2.0 mmol) in dichloromethane (1.0 mL) at 25 °C. The resulting reaction mixture was stirred at 25 °C for 1 h under an oxygen atmosphere (O₂ balloon). After completion, the mixture was filtered through a pad of Celite and eluted with dichloromethane (10 mL). The filtrate was added with water (10 mL) and extracted with dichloromethane (3 × 5 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (SiO₂, EtOAc/hexanes, 1:9, R _f 0.55) to give compound 2c (104.2 mg, 0.37 mmol, 75%) as a colorless liquid. ¹H NMR (300 MHz, CDCl₃) δ 7.42–7.37 (m, 3H), 7.35–7.27 (m, 2H), 7.24–22 (m, 1H), 7.18–7.16 (m, 2H), 2.37 (s, 3H), 2.32 (s, 3H); ¹³C­{¹H} NMR (75 MHz, CDCl₃) δ 142.9, 139.5, 139.1, 137.3, 134.4, 133.8, 132.3, 129.3, 128.7, 128.1, 127.7, 124.9, 21.3. The spectroscopic data were consistent with the reported values.

S-(2,6-Dimethylphenyl) 2,6-Dimethylbenzenesulfonothioate (2d)

Sodium nitrate (8.5 mg, 0.10 mmol) was added to a solution of 2,6-dimethylbenzenethiol (1d, 138.2 mg, 1.0 mmol) and trifluoroacetic acid (153 μL, 228.0 mg, 2.0 mmol) in dichloromethane (1.0 mL) at 25 °C. The resulting reaction mixture was stirred at 25 °C for 1 h under an oxygen atmosphere (O₂ balloon). After completion, the mixture was filtered through a pad of Celite and eluted with dichloromethane (10 mL). The filtrate was added with water (10 mL) and extracted with dichloromethane (3 × 5 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (SiO₂, EtOAc/hexanes, 1:9, R _f 0.58) to give compound 2d (126.7 mg, 0.41 mmol, 83%) as a colorless solid. Mp 118.0–120.0 °C; ¹H NMR (300 MHz, CDCl₃) δ 7.35–7.30 (m, 1H), 7.28–7.23 (m, 1H), 7.11–7.09 (m, 4H), 2.41 (s, 6H), 2.21 (s, 6H); ¹³C­{¹H} NMR (75 MHz, CDCl₃) δ 145.8, 142.1, 139.9, 133.0, 131.6, 131.5, 128.7, 126.6, 22.9, 21.6. The spectroscopic data were consistent with the reported values.

S-Mesityl 2,4,6-Trimethylbenzenesulfonothioate (2e)

Sodium nitrate (8.5 mg, 0.10 mmol) was added to a solution of 2,4,6-trimethylbenzenethiol (1e, 152.3 mg, 1.0 mmol) and trifluoroacetic acid (153 μL, 228.0 mg, 2.0 mmol) in dichloromethane (1.0 mL) at 25 °C. The resulting reaction mixture was stirred at 25 °C for 1 h under an oxygen atmosphere (O₂ balloon). After completion, the mixture was filtered through a pad of Celite and eluted with dichloromethane (10 mL). The filtrate was added with water (10 mL) and extracted with dichloromethane (3 × 5 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (SiO₂, EtOAc/hexanes, 1:9, R _f 0.62) to give compound 2e (146.3 mg, 0.44 mmol, 88%) as a colorless solid. Mp 130.0–132.0 °C; ¹H NMR (300 MHz, CDCl₃) δ 6.90–6.88 (m, 4H), 2.35 (s, 6H), 2.30 (s, 3H), 2.27 (s, 3H), 2.15 (s, 6H); ¹³C­{¹H} NMR (75 MHz, CDCl₃) δ 145.5, 143.5, 141.9, 139.8, 139.5, 132.0, 129.6, 123.4, 22.7, 21.5, 21.3, 21.1. The spectroscopic data were consistent with the reported values.

S-(4-(tert-Butyl)­phenyl) 4-(tert-Butyl)­benzenesulfonothioate (2f)

Sodium nitrate (8.5 mg, 0.10 mmol) was added to a solution of 4-(tert-butyl)­benzenethiol (1f, 166.3 mg, 1.0 mmol) and trifluoroacetic acid (153 μL, 228.0 mg, 2.0 mmol) in dichloromethane (1.0 mL) at 25 °C. The resulting reaction mixture was stirred at 25 °C for 1 h under an oxygen atmosphere (O₂ balloon). After completion, the mixture was filtered through a pad of Celite and eluted with dichloromethane (10 mL). The filtrate was added with water (10 mL) and extracted with dichloromethane (3 × 5 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (SiO₂, EtOAc/hexanes, 1:9, R _f 0.54) to give compound 2f (169.7 mg, 0.47 mmol, 94%) as a colorless solid. Mp 145.0–147.0 °C; ¹H NMR (300 MHz, CDCl₃) δ 7.48 (d, J = 8.7 Hz, 2H), 7.40 (d, J = 8.7 Hz, 2H), 7.33 (d, J = 8.4 Hz, 2H), 7.27 (d, J = 8.4 Hz, 2H), 1.33 (s, 9H), 1.31 (s, 9H); ¹³C­{¹H} NMR (75 MHz, CDCl₃) δ 157.7, 155.1, 140.2, 136.4, 127.5, 126.5, 125.8, 124.7, 35.3, 35.0, 31.2, 31.1. The spectroscopic data were consistent with the reported values.

S-(4-Methoxyphenyl) 4-Methoxybenzenesulfonothioate (2g)

Sodium nitrate (8.5 mg, 0.10 mmol) was added to a solution of 4-methoxybenzenethiol (1g, 140.2 mg, 1.0 mmol) and trifluoroacetic acid (153 μL, 228.0 mg, 2.0 mmol) in dichloromethane (1.0 mL) at 25 °C. The resulting reaction mixture was stirred at 25 °C for 1 h under an oxygen atmosphere (O₂ balloon). After completion, the mixture was filtered through a pad of Celite and eluted with dichloromethane (10 mL). The filtrate was added with water (10 mL) and extracted with dichloromethane (3 × 5 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (SiO₂, EtOAc/hexanes, 1:9, R _f 0.42) to give compound 2g (143.4 mg, 0.46 mmol, 93%) as a colorless solid. Mp 90.0–92.0 °C; ¹H NMR (300 MHz, CDCl₃) δ 7.51 (d, J = 9.0 Hz, 2H), 7.28 (d, J = 9.0 Hz, 2H), 6.90–6.84 (m, 4H), 3.88 (s, 3H), 3.84 (s, 3H); ¹³C­{¹H} NMR (75 MHz, CDCl₃) δ 163.6, 162.3, 138.4, 134.9, 130.0, 119.0, 115.0, 113.9, 55.8, 55.6. The spectroscopic data were consistent with the reported values.

S-(4-Acetamidophenyl) 4-Acetamidobenzenesulfonothioate (2h)

Sodium nitrate (8.5 mg, 0.10 mmol) was added to a solution of N-(4-mercaptophenyl)­acetamide (1h, 167.2 mg, 1.0 mmol) and trifluoroacetic acid (153 μL, 228.0 mg, 2.0 mmol) in dichloromethane (1.0 mL) at 25 °C. The resulting reaction mixture was stirred at 25 °C for 1 h under an oxygen atmosphere (O₂ balloon). After completion, the mixture was filtered through a pad of Celite and eluted with dichloromethane (10 mL). The filtrate was added with water (10 mL) and extracted with dichloromethane (3 × 5 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (SiO₂, EtOAc/hexanes, 1:9, R _f 0.2) to give compound 2h (134.3 mg, 0.37 mmol, 74%) as a colorless solid. Mp 226.0–228.0 °C; ¹H NMR (300 MHz, DMSO-d ₆) δ 10.5 (s, 1H), 10.3 (s, 1H), 7.72 (d, J = 9.0 Hz, 2H), 7.61 (d, J = 8.7 Hz, 2H), 7.47 (d, J = 9.0 Hz, 2H), 7.23 (d, J = 8.7 Hz, 2H), 2.09 (s, 3H), 2.06 (s, 3H); ¹³C­{¹H} NMR (75 MHz, DMSO-d ₆) δ 170.0, 169.7, 144.7, 142.8, 137.6, 136.0, 129.1, 120.5, 119.9, 118.9, 40.5, 40.3, 40.0, 39.7, 39.4, 39.2, 38.9, 24.6, 24.5. The spectroscopic data were consistent with the reported values.

S-(4-Fluorophenyl) 4-Fluorobenzenesulfonothioate (2i)

Sodium nitrate (8.5 mg, 0.10 mmol) was added to a solution of 4-fluorobenzenethiol (1i, 128.2 mg, 1.0 mmol) and trifluoroacetic acid (153 μL, 228.0 mg, 2.0 mmol) in dichloromethane (1.0 mL) at 25 °C. The resulting reaction mixture was stirred at 25 °C for 1 h under an oxygen atmosphere (O₂ balloon). After completion, the mixture was filtered through a pad of Celite and eluted with dichloromethane (10 mL). The filtrate was added with water (10 mL) and extracted with dichloromethane (3 × 5 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (SiO₂, EtOAc/hexanes, 1:9, R _f 0.52) to give compound 2i (140.8 mg, 0.49 mmol, 98%) as a colorless solid. Mp 64.0–66.0 °C; ¹H NMR (300 MHz, CDCl₃) δ 7.61–7.56 (m, 2H), 7.38–7.33 (m, 2H), 7.14–7.03 (m, 4H); ¹³C­{¹H} NMR (75 MHz, CDCl₃) δ 165.7 (d, J = 256.0 Hz), 165.0 (d, J = 253.0 Hz), 139.0, 138.9, 130.6 (d, J = 10.0 Hz), 123.3, 117.1 (d, J = 22.0 Hz), 116.3 (d, J = 23.0 Hz); ¹⁹F-NMR (283 MHz, CDCl₃) δ – 102.34, 106.8. The spectroscopic data were consistent with the reported values.

S-(4-Chlorophenyl) 4-chlorobenzenesulfonothioate (2j)

Sodium nitrate (8.5 mg, 0.10 mmol) was added to a solution of 4-chlorobenzenethiol (1j, 144.6 mg, 1.0 mmol) and trifluoroacetic acid (153 μL, 228.0 mg, 2.0 mmol) in dichloromethane (1.0 mL) at 25 °C. The resulting reaction mixture was stirred at 25 °C for 1 h under an oxygen atmosphere (O₂ balloon). After completion, the mixture was filtered through a pad of Celite and eluted with dichloromethane (10 mL). The filtrate was added with water (10 mL) and extracted with dichloromethane (3 × 5 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (SiO₂, EtOAc/hexanes, 1:9, R _f 0.49) to give compound 2j (149.8 mg, 0.47 mmol, 94%) as a colorless solid. Mp 130.0–132.0 °C; ¹H NMR (300 MHz, CDCl₃) δ 7.51 (d, J = 8.7 Hz, 2H), 7.42 (d, J = 8.7 Hz, 2H), 7.35–7.28 (m, 4H); ¹³C­{¹H} NMR (75 MHz, CDCl₃) δ 141.4, 140.7, 138.6, 137.8, 130.0, 129.4, 129.0, 126.1. The spectroscopic data were consistent with the reported values.

S-(4-Bromophenyl) 4-bromobenzenesulfonothioate (2k)

Sodium nitrate (8.5 mg, 0.10 mmol) was added to a solution of 4-bromobenzenethiol (1k, 189.1 mg, 1.0 mmol) and trifluoroacetic acid (153 μL, 228.0 mg, 2.0 mmol) in dichloromethane (1.0 mL) at 25 °C. The resulting reaction mixture was stirred at 25 °C for 1 h under an oxygen atmosphere (O₂ balloon). After completion, the mixture was filtered through a pad of Celite and eluted with dichloromethane (10 mL). The filtrate was added with water (10 mL) and extracted with dichloromethane (3 × 5 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (SiO₂, EtOAc/hexanes, 1:9, R _f 0.51) to give compound 2k (168.5 mg, 0.41 mmol, 82%) as a colorless solid. Mp 148.0–150.0 °C; ¹H NMR (300 MHz, CDCl₃) δ 7.60 (d, J = 8.4 Hz, 2H), 7.51 (d, J = 8.4 Hz, 2H), 7.44 (d, J = 8.7 Hz, 2H), 7.24 (d, J = 8.1 Hz, 2H); ¹³C­{¹H} NMR (75 MHz, CDCl₃) δ 142.0, 138.0, 133.1, 132.4, 129.3, 129.1, 127.2, 126.7. The spectroscopic data were consistent with the reported values.

Methyl 4-(((4-(Methoxy­carbonyl)­phenyl)­thio)­sulfonyl)­benzoate (2l)

Sodium nitrate (8.5 mg, 0.10 mmol) was added to a solution of methyl 4-mercaptobenzoate (1l, 166.3 mg, 1.0 mmol) and trifluoroacetic acid (153 μL, 228.0 mg, 2.0 mmol) in dichloromethane (1.0 mL) at 25 °C. The resulting reaction mixture was stirred at 25 °C for 1 h under an oxygen atmosphere (O₂ balloon). After completion, the mixture was filtered through a pad of Celite and eluted with dichloromethane (10 mL). The filtrate was added with water (10 mL) and extracted with dichloromethane (3 × 5 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (SiO₂, EtOAc/hexanes, 1:9, R _f 0.54) to give compound 2l (169.7 mg, 0.47 mmol, 94%) as a colorless solid. Mp 142.0–144.0 °C; ¹H NMR (300 MHz, CDCl₃) δ 8.07 (d, J = 8.4 Hz, 2H), 7.98 (d, J = 8.4 Hz, 2H), 7.61 (d, J = 8.7 Hz, 2H), 7.43 (d, J = 8.4 Hz, 2H), 3.94 (s, 3H), 3.93 (s, 3H); ¹³C­{¹H} NMR (75 MHz, CDCl₃) δ 166.0, 165.3, 146.4, 136.4, 134.9, 133.0, 132.5, 130.6, 127.6, 52.9, 52.7. The spectroscopic data were consistent with the reported values.

S-(4-Acetylphenyl) 4-Acetylbenzenesulfonothioate (2m)

Sodium nitrate (8.5 mg, 0.10 mmol) was added to a solution of 1-(4-mercaptophenyl)­ethan-1-one (1m, 76.2 mg, 0.50 mmol) and trifluoroacetic acid (76 μL, 114.0 mg, 1.0 mmol) in dichloromethane (1.0 mL) at 25 °C. The resulting reaction mixture was stirred at 25 °C for 1 h under an oxygen atmosphere (O₂ balloon). After completion, the mixture was filtered through a pad of Celite and eluted with dichloromethane (10 mL). The filtrate was added with water (10 mL) and extracted with dichloromethane (3 × 5 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (SiO₂, EtOAc/hexanes, 1:9, R _f 0.45) to give compound 2m (67.4 mg, 0.20 mmol, 81%) as a colorless solid. Mp 126.0–128.0 °C; ¹H NMR (300 MHz, CDCl₃) δ 7.99 (d, J = 8.4 Hz, 2H), 7.91 (d, J = 8.1 Hz, 2H), 7.67 (d, J = 8.4 Hz, 2H), 7.49 (d, J = 8.1 Hz, 2H), 2.64 (s, 3H), 2.62 (s, 3H); ¹³C­{¹H} NMR (75 MHz, CDCl₃) δ 197.2, 196.6, 146.5, 140.9, 139.2, 136.6, 132.6, 129.3, 129.0, 127.9, 27.1, 26.9. The spectroscopic data were consistent with the reported values.

S-(Naphthalen-2-yl) Naphthalene-2-sulfonothioate (2n)

Sodium nitrate (8.5 mg, 0.10 mmol) was added to a solution of naphthalene-2-thiol (1n, 160.2 mg, 1.0 mmol) and trifluoroacetic acid (153 μL, 228.0 mg, 2.0 mmol) in dichloromethane (1.0 mL) at 25 °C. The resulting reaction mixture was stirred at 25 °C for 1 h under an oxygen atmosphere (O₂ balloon). After completion, the mixture was filtered through a pad of Celite and eluted with dichloromethane (10 mL). The filtrate was added with water (10 mL) and extracted with dichloromethane (3 × 5 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (SiO₂, EtOAc/hexanes, 1:9, R _f 0.30) to give compound 2n (127.4 mg, 0.37 mmol, 74%) as a colorless solid. Mp 98.0–100.0 °C; ¹H NMR (300 MHz, CDCl₃) δ 7.91–7.87 (m, 2H), 7.84–7.82 (m, 2H), 7.73 (d, J = 8.4 Hz, 1H), 7.67–7.63 (m, 3H), 7.61–7.60 (m, 1H), 7.58–7.53 (m, 2H), 7.51–7.45 (m, 1H), 7.35 (dd, J = 8.4, 6.9 Hz, 1H); ¹³C­{¹H} NMR (75 MHz, CDCl₃) δ139.8, 137.8, 135.2, 134.2, 133.4, 132.0, 131.7, 129.6, 129.5, 129.4, 129.3, 129.2, 128.5, 128.4, 128.0, 127.9, 127.8, 127.0, 125.3, 122.5. The spectroscopic data were consistent with the reported values.

S-Phenethyl 2-Phenylethane-1-sulfonothioate (2o)

Sodium nitrate (8.5 mg, 0.10 mmol) was added to a solution of 2-phenylethane-1-thiol (1o, 138.2 mg, 1.0 mmol) and trifluoroacetic acid (153 μL, 228.0 mg, 2.0 mmol) in dichloromethane (1.0 mL) at 25 °C. The resulting reaction mixture was stirred at 25 °C for 1 h under an oxygen atmosphere (O₂ balloon). After completion, the mixture was filtered through a pad of Celite and eluted with dichloromethane (10 mL). The filtrate was added with water (10 mL) and extracted with dichloromethane (3 × 5 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (SiO₂, EtOAc/hexanes, 1:9, R _f 0.32) to give compound 2o (151.4 mg, 0.49 mmol, 99%) as a colorless solid. Mp 42.0–44.0 °C; ¹H NMR (300 MHz, CDCl₃) δ 7.42–7.33 (m, 5H), 7.30–7.28 (m, 3H), 7.24–7.22 (m, 2H), 3.50–3.43 (m, 4H), 3.24–3.18 (m, 2H), 3.11 (t, J = 6.0 Hz, 2H); ¹³C­{¹H} NMR (75 MHz, CDCl₃) δ 138.5, 136.9, 128.8, 128.7, 128.5, 127.1, 127.0 63.4, 37.6, 36.0, 29.5. The spectroscopic data were consistent with the reported values.

S-Propyl Propane-1-sulfonothioate (2p)

Sodium nitrate (8.5 mg, 0.10 mmol) was added to a solution of propane-1-thiol (1p, 76.2 mg, 1.0 mmol) and trifluoroacetic acid (306 μL, 456.0 mg, 4.0 mmol) in dichloromethane (1.0 mL) at 25 °C. The resulting reaction mixture was stirred at 25 °C for 1 h under an oxygen atmosphere (O₂ balloon). After completion, the mixture was filtered through a pad of Celite and eluted with dichloromethane (10 mL). The filtrate was added with water (10 mL) and extracted with dichloromethane (3 × 5 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (SiO₂, EtOAc/hexanes, 1:9, R _f 0.76) to give compound 2p (73.6 mg, 0.40 mmol, 81%) as a colorless liquid. ¹H NMR (300 MHz, CDCl₃) δ 3.31–3.25 (m, 2H), 3.11 (t, J = 7.2 Hz, 2H), 2.02–1.89 (m, 2H), 1.82–1.74 (m, 2H), 1.11–1.01 (m, 6H); ¹³C­{¹H} NMR (75 MHz, CDCl₃) δ 64.5, 38.3, 23.3, 17.5, 13.3, 12.8. The spectroscopic data were consistent with the reported values.

S-Butyl Butane-1-sulfonothioate (2q)

Sodium nitrate (8.5 mg, 0.10 mmol) was added to a solution of butane-1-thiol (1q, 90.2 mg, 1.0 mmol) and trifluoroacetic acid (306 μL, 456.0 mg, 4.0 mmol) in dichloromethane (1.0 mL) at 25 °C. The resulting reaction mixture was stirred at 25 °C for 1 h under an oxygen atmosphere (O₂ balloon). After completion, the mixture was filtered through a pad of Celite and eluted with dichloromethane (10 mL). The filtrate was added with water (10 mL) and extracted with dichloromethane (3 × 5 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (SiO₂, EtOAc/hexanes, 1:9, R _f 0.66) to give compound 2q (103.7 mg, 0.49 mmol, 98%) as a colorless liquid. ¹H NMR (300 MHz, CDCl₃) δ 3.30–3.25 (m, 2H), 3.13–3.08 (m, 2H), 1.91–1.80 (m, 2H), 1.74–1.65 (m, 2H), 1.52–1.35 (m, 4H), 0.96–0.88 (m, 6H); ¹³C­{¹H} NMR (75 MHz, CDCl₃) δ 62.4, 36.0, 31.7, 25.5, 21.8, 21.3, 13.6, 13.5. The spectroscopic data were consistent with the reported values.

S-Hexyl Hexane-1-sulfonothioate (2r)

Sodium nitrate (8.5 mg, 0.10 mmol) was added to a solution of hexane-1-thiol (1r, 118.2 mg, 1.0 mmol) and trifluoroacetic acid (306 μL, 456.0 mg, 4.0 mmol) in dichloromethane (1.0 mL) at 25 °C. The resulting reaction mixture was stirred at 25 °C for 1 h under an oxygen atmosphere (O₂ balloon). After completion, the mixture was filtered through a pad of Celite and eluted with dichloromethane (10 mL). The filtrate was added with water (10 mL) and extracted with dichloromethane (3 × 5 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (SiO₂, EtOAc/hexanes, 1:9, R _f 0.66) to give compound 2r (130.4 mg, 0.49 mmol, 98%) as a colorless liquid. ¹H NMR (300 MHz, CDCl₃) δ 3.25 (t, J = 7.8 Hz, 2H), 3.08 (t, J = 7.5 Hz, 2H), 1.90–1.80 (m, 2H), 1.74–1.64 (m, 2H), 1.42–1.32 (m, 4H), 1.32–1.23 (m, 8H), 0.87–0.83 (m, 6H); ¹³C­{¹H} NMR (75 MHz, CDCl₃) δ 62.6, 36.2, 31.2, 31.1, 29.6, 28.2, 27.6, 23.5, 22.4, 22.3₄, 22.2₇, 13.9. The spectroscopic data were consistent with the reported values.

S-Octyl Octane-1-sulfonothioate (2s)

Sodium nitrate (8.5 mg, 0.10 mmol) was added to a solution of octane-1-thiol (1s, 146.3 mg, 1.0 mmol) and trifluoroacetic acid (306 μL, 456.0 mg, 4.0 mmol) in dichloromethane (1.0 mL) at 25 °C. The resulting reaction mixture was stirred at 25 °C for 1 h under an oxygen atmosphere (O₂ balloon). After completion, the mixture was filtered through a pad of Celite and eluted with dichloromethane (10 mL). The filtrate was added with water (10 mL) and extracted with dichloromethane (3 × 5 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (SiO₂, EtOAc/hexanes, 1:9, R _f 0.71) to give compound 2s (159.3 mg, 0.49 mmol, 98%) as a colorless liquid. ¹H NMR (300 MHz, CDCl₃) δ 3.27 (t, J = 7.8 Hz, 2H), 3.11 (t, J = 7.5 Hz, 2H), 1.94–1.84 (m, 2H), 1.77–1.67 (m, 2H), 1.41–1.39 (m, 4H), 1.26 (s, br, 16H), 0.89–0.84 (m, 6H); ¹³C­{¹H} NMR (75 MHz, CDCl₃) δ 62.8, 36.4, 31.8, 29.7, 29.2, 29.1, 29.0, 28.7, 28.1, 23.6, 22.7, 14.2. The spectroscopic data were consistent with the reported values.

S-Dodecyl Dodecane-1-sulfonothioate (2t)

Sodium nitrate (8.5 mg, 0.10 mmol) was added to a solution of dodecane-1-thiol (1t, 202.4 mg, 1.0 mmol) and trifluoroacetic acid (306 μL, 456.0 mg, 4.0 mmol) in dichloromethane (1.0 mL) at 25 °C. The resulting reaction mixture was stirred at 25 °C for 1 h under an oxygen atmosphere (O₂ balloon). After completion, the mixture was filtered through a pad of Celite and eluted with dichloromethane (10 mL). The filtrate was added with water (10 mL) and extracted with dichloromethane (3 × 5 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (SiO₂, EtOAc/hexanes, 1:9, R _f 0.74) to give compound 2t (216.1 mg, 0.49 mmol, 98%) as a colorless liquid. ¹H NMR (300 MHz, CDCl₃) δ 3.28 (t, J = 7.8 Hz, 2H), 3.12 (t, J = 7.5 Hz, 2H), 1.95–1.84 (m, 2H), 1.77–1.68 (m, 2H), 1.42–1.40 (m, 3H), 1.25 (s, br, 33H), 0.89–0.85 (m, 6H); ¹³C­{¹H} NMR (75 MHz, CDCl₃) δ 62.8, 36.4, 32.0, 29.7, 29.6, 29.53, 29.46, 29.4, 29.2, 29.1, 28.7, 28.1, 23.6, 22.8, 14.2. The spectroscopic data were consistent with the reported values.

S-Isobutyl 2-Methylpropane-1-sulfonothioate (2u)

Sodium nitrate (8.5 mg, 0.10 mmol) was added to a solution of 2-methylpropane-1-thiol (1u, 90.2 mg, 1.0 mmol) and trifluoroacetic acid (306 μL, 456.0 mg, 4.0 mmol) in dichloromethane (1.0 mL) at 25 °C. The resulting reaction mixture was stirred at 25 °C for 1 h under an oxygen atmosphere (O₂ balloon). After completion, the mixture was filtered through a pad of Celite and eluted with dichloromethane (10 mL). The filtrate was added with water (10 mL) and extracted with dichloromethane (3 × 5 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (SiO₂, EtOAc/hexanes, 1:9, R _f 0.66) to give compound 2u (102.9 mg, 0.49 mmol, 98%) as a colorless liquid. ¹H NMR (300 MHz, CDCl₃) δ 3.20 (d, J = 6.4 Hz, 2H), 3.01 (d, J = 6.9 Hz, 2H), 2.45–2.31 (m, 1H), 2.22–1.91 (m, 1H), 1.10 (d, J = 6.9 Hz, 6H), 1.01 (d, J = 6.6 Hz, 6H); ¹³C­{¹H} NMR (75 MHz, CDCl₃) δ 70.5, 44.6, 28.9, 25.2, 22.5, 21.7. The spectroscopic data were consistent with the reported values.

S-Isopropyl Propane-2-sulfonothioate (2v)

Sodium nitrate (8.5 mg, 0.10 mmol) was added to a solution of 2-propanethiol (1v, 76.2 mg, 1.0 mmol) and trifluoroacetic acid (306 μL, 456.0 mg, 4.0 mmol) in dichloromethane (1.0 mL) at 25 °C. The resulting reaction mixture was stirred at 25 °C for 1 h under an oxygen atmosphere (O₂ balloon). After completion, the mixture was filtered through a pad of Celite and eluted with dichloromethane (10 mL). The filtrate was added with water (10 mL) and extracted with dichloromethane (3 × 5 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (SiO₂, EtOAc/hexanes, 1:9, R _f 0.54) to give compound 2v (87.5 mg, 0.48 mmol, 96%) as a colorless liquid. ¹H NMR (300 MHz, CDCl₃) δ 3.67–3.53 (m, 1H), 3.37–3.24 (m, 1H), 1.41–1.38 (m, 12H); ¹³C­{¹H} NMR (75 MHz, CDCl₃) δ 63.5, 43.0, 24.3, 16.3. The spectroscopic data were consistent with the reported values.

S-Cyclohexyl Cyclohexane­sulfonothioate (2w)

Sodium nitrate (8.5 mg, 0.10 mmol) was added to a solution of cyclohexanethiol (1w, 116.2 mg, 1.0 mmol) and trifluoroacetic acid (306 μL, 456.0 mg, 4.0 mmol) in dichloromethane (1.0 mL) at 25 °C. The resulting reaction mixture was stirred at 25 °C for 1 h under an oxygen atmosphere (O₂ balloon). After completion, the mixture was filtered through a pad of Celite and eluted with dichloromethane (10 mL). The filtrate was added with water (10 mL) and extracted with dichloromethane (3 × 5 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (SiO₂, EtOAc/hexanes, 1:9, R _f 0.42) to give compound 2w (129.7 mg, 0.49 mmol, 98%) as a colorless liquid. ¹H NMR (300 MHz, CDCl₃) δ 3.45–3.37 (m, 1H), 3.07–2.97 (m, 1H), 1.95–1.84 (m, 2H), 2.25 (d, J = 11.7 Hz, 2H), 2.07–2.03 (m, 2H), 1.69–1.66 (m, 3H), 1.61–1.45 (m, 5H), 1.41–1.33 (m, 2H), 1.29–1.13 (m, 4H); ¹³C­{¹H} NMR (75 MHz, CDCl₃) δ 71.4, 50.4, 34.2, 26.2, 25.9, 25.2, 25.13, 25.06. The spectroscopic data were consistent with the reported values.

1,2-Diphenyldisulfane (3a)

Sodium nitrate (8.5 mg, 0.10 mmol) was added to a solution of thiophenol (1a, 110.2 mg, 1.0 mmol) and trifluoroacetic acid (153 μL, 228.0 mg, 2.0 mmol) in dichloromethane (1.0 mL) at 25 °C. The resulting reaction mixture was stirred at 25 °C for 30 min under an oxygen atmosphere (O₂ balloon). After completion, the mixture was filtered through a pad of Celite and eluted with dichloromethane (10 mL). The filtrate was added with water (10 mL) and extracted with dichloromethane (3 × 5 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (SiO₂, EtOAc/hexanes, 1:9, R _f 0.64) to give compound 3a (107.0 mg, 0.49 mmol, 98%) as a colorless solid. Mp 58.0–60.0 °C; ¹H NMR (300 MHz, CDCl₃) δ 7.58–7.56 (m, 4H), 7.41–7.34 (m, 4H), 7.31–7.28 (m, 2H); ¹³C­{¹H} NMR (75 MHz, CDCl₃) δ137.1, 129.2, 127.6, 127.3. The spectroscopic data were consistent with the reported values.

1,2-Di-p-tolyldisulfane (3b)

Sodium nitrate (8.5 mg, 0.10 mmol) was added to a solution of 4-methylbenzenethiol (1b, 124.2 mg, 1.0 mmol) and trifluoroacetic acid (76 μL, 114.0 mg, 1.0 mmol) in dichloromethane (1.0 mL) at 25 °C. The resulting reaction mixture was stirred at 25 °C for 1 h under an oxygen atmosphere (O₂ balloon). After completion, the mixture was filtered through a pad of Celite and eluted with dichloromethane (10 mL). The filtrate was added with water (10 mL) and extracted with dichloromethane (3 × 5 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (SiO₂, hexanes, R _f 0.78) to give compound 3b (119.4 mg, 0.49 mmol, 97%) as a colorless solid. Mp 46.0–48.0 °C; ¹H NMR (300 MHz, CDCl₃) δ 7.46 (d, J = 8.1 Hz, 4H), 7.16 (d, J = 7.8 Hz, 4H); ¹³C­{¹H} NMR (75 MHz, CDCl₃) δ 137.5, 134.0, 129.9, 128.6, 21.1. The spectroscopic data were consistent with the reported values.

1,2-Bis­(4-methoxyphenyl)­disulfane (3g)

Sodium nitrate (8.5 mg, 0.10 mmol) was added to a solution of 4-methoxybenzenethiol (1g, 140.2 mg, 1.0 mmol) and trifluoroacetic acid (76 μL, 114.0 mg, 1.0 mmol) in dichloromethane (1.0 mL) at 25 °C. The resulting reaction mixture was stirred at 25 °C for 3 h under an oxygen atmosphere (O₂ balloon). After completion, the mixture was filtered through a pad of Celite and eluted with dichloromethane (10 mL). The filtrate was added with water (10 mL) and extracted with dichloromethane (3 × 5 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (SiO₂, EtOAc/hexanes, 1:9, R _f 0.48) to give compound 3g (136.6 mg, 0.49 mmol, 98%) as a colorless solid. Mp 42.0–44.0 °C; ¹H NMR (300 MHz, CDCl₃) δ 7.27 (d, J = 8.7 Hz, 4H), 6.81 (d, J = 9.0 Hz, 4H), 3.78 (s, 6H); ¹³C­{¹H} NMR (75 MHz, CDCl₃) δ 158.6, 132.5, 119.9, 114.8, 55.4. The spectroscopic data were consistent with the reported values.

1,2-Bis­(4-fluorophenyl)­disulfane (3i)

Sodium nitrate (8.5 mg, 0.10 mmol) was added to a solution of 4-fluorobenzenethiol (1i, 128.2 mg, 1.0 mmol) and trifluoroacetic acid (76 μL, 114.0 mg, 1.0 mmol) in dichloromethane (1.0 mL) at 25 °C. The resulting reaction mixture was stirred at 25 °C for 3 h under an oxygen atmosphere (O₂ balloon). After completion, the mixture was filtered through a pad of Celite and eluted with dichloromethane (10 mL). The filtrate was added with water (10 mL) and extracted with dichloromethane (3 × 5 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (SiO₂, EtOAc/hexanes, 1:9, R _f 0.58) to give compound 3i (124.7 mg, 0.49 mmol, 98%) as a colorless liquid. ¹H NMR (500 MHz, CDCl₃) δ 7.46 (dd, J = 8.5, 5.0 Hz, 4H), 7.02 (t, J = 8.5 Hz 4H); ¹³C­{¹H} NMR (126 MHz, CDCl₃) δ 162.7 (d, J = 248.2 Hz), 132.3, 131.4 (d, J = 8.8 Hz), 116.4 (d, J = 22.7 Hz); ¹⁹F-NMR (470 MHz, CDCl₃) δ −113.3. The spectroscopic data were consistent with the reported values.

1,2-Bis­(4-nitrophenyl)­disulfane (3y)

Sodium nitrate (8.5 mg, 0.10 mmol) was added to a solution of 4-nitrobenzenethiol (1y, 155.2 mg, 1.0 mmol) and trifluoroacetic acid (76 μL, 114.0 mg, 1.0 mmol) in dichloromethane (1.0 mL) at 25 °C. The resulting reaction mixture was stirred at 25 °C for 3 h under an oxygen atmosphere (O₂ balloon). After completion, the mixture was filtered through a pad of Celite and eluted with dichloromethane (10 mL). The filtrate was added with water (10 mL) and extracted with dichloromethane (3 × 5 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (SiO₂, EtOAc/hexanes, 1:9, R _f 0.42) to give compound 3i (152.9 mg, 0.49 mmol, 98%) as a colorless solid. Mp 182.0–184.0 °C; ¹H NMR (300 MHz, CDCl₃) δ 8.19 (d, J = 9.0 Hz, 4H), 7.61 (d, J = 9.0 Hz, 4H); ¹³C­{¹H} NMR (75 MHz, CDCl₃) δ 147.0, 144.2, 126.5, 124.6. The spectroscopic data were consistent with the reported values.

1,2-Didodecyldisulfane (3t)

Sodium nitrate (8.5 mg, 0.10 mmol) was added to a solution of 1-dodecanethiol (1t, 202.4 mg, 1.0 mmol) and trifluoroacetic acid (230 μL, 342.0 mg, 3.0 mmol) in dichloromethane (1.0 mL) at 25 °C. The resulting reaction mixture was stirred at 25 °C for 3 h under an oxygen atmosphere (O₂ balloon). After completion, the mixture was filtered through a pad of Celite and eluted with dichloromethane (10 mL). The filtrate was added with water (10 mL) and extracted with dichloromethane (3 × 5 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (SiO₂, hexanes, R _f 0.9) to give compound 3t (199.4 mg, 0.49 mmol, 98%) as a colorless liquid. ¹H NMR (300 MHz, CDCl₃) δ 2.69–2.64 (m, 2H), 2.55–2.47 (m, 1H), 1.71–1.55 (m, 4H), 1.39–1.26 (m, 37H), 0.90–0.85 (m, 6H); ¹³C­{¹H} NMR (75 MHz, CDCl₃) δ 39.3, 34.2, 32.1, 29.8, 29.7, 29.5, 29.4, 29.2, 28.7, 24.8, 22.8, 14.2. The spectroscopic data were consistent with the reported values.

1,2-Di­(pyridin-2-yl)­disulfane (3z)

Sodium nitrate (8.5 mg, 0.10 mmol) was added to a solution of pyridine-2-thiol (1z, 111.2 mg, 1.0 mmol) and trifluoroacetic acid (306 μL, 456.0 mg, 4.0 mmol) in dichloromethane (1.0 mL) at 25 °C. The resulting reaction mixture was stirred at 25 °C for 16 h under an oxygen atmosphere (O₂ balloon). After completion, the mixture was filtered through a pad of Celite and eluted with dichloromethane (10 mL). The filtrate was added with water (10 mL) and extracted with dichloromethane (3 × 5 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (SiO₂, EtOAc/hexanes, 1:1, R _f 0.33) to give compound 3z (104.6 mg, 0.47 mmol, 95%) as a colorless liquid. ¹H NMR (300 MHz, CDCl₃) δ 8.38–8.37 (m, 2H), 7.53–7.51 (m, 4H), 7.05–7.00 (m, 2H); ¹³C­{¹H} NMR (75 MHz, CDCl₃) δ 158.7, 149.4, 137.4, 121.1, 119.6. The spectroscopic data were consistent with the reported values.

Oxidized Glutathione (GSSG, 5)

Sodium nitrate (8.5 mg, 0.10 mmol) was added to a solution of glutathione (4, 307.3 mg, 1.0 mmol) and trifluoroacetic acid (460 μL, 684 mg, 6.0 mmol) in dichloromethane (1.0 mL) at 25 °C. The resulting reaction mixture was stirred at 25 °C for 1 h under an oxygen atmosphere (O₂ balloon), and the solvent was removed under reduced pressure. The residue was washed with ethyl acetate (3 × 5 mL) and hexanes (3 × 5 mL) and concentrated to yield 5 (301.8 mg, 0.493 mmol, 98%) as a colorless solid. Mp 174.0–176.0 °C; ¹H NMR (300 MHz, D₂O) δ 4.63–4.59 (m, 2H), 3.99–3.94 (m, 3H), 3.88 (s, br, 4H), 3.17–3.09 (m, 2H), 2.89–2.81 (m, 1H), 2.52–2.46 (m, 4H), 2.20–2.06 (m, 4H); ¹³C­{¹H} NMR (75 MHz, D₂O) δ174.2, 172.7, 172.4, 171.3, 52.5, 52.1, 41.1, 38.6, 30.8, 25.3; HRMS (ESI) m/z calcd for [M + Na]⁺ (C₂₀H₃₂N₆O₁₂S₂Na) 635.1411, found 635.1405; The spectroscopic data were consistent with the reported values.

The data underlying this study are available in the published article and its .

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.joc.6c00062.

• Oxidation of thiol 1a conducted in various solvents, pK _a values of the acids used in this work, figures of starch-iodide test, and copies of ¹H and ¹³C­{¹H} NMR spectra for all synthesized compounds (PDF)

• FAIR data, including the primary NMR FID files, for compounds 2a–2w, 3a–3b, 3g, 3i, 3t, 3x–3z and 5 (ZIP)

The authors declare no competing financial interest.