2013 Volume 61 Issue 4 Pages 460-463
The oxidation of dithioacetals with 16 eq of 30% hydrogen peroxide in the presence of 10 mol% niobium(V) chloride at room temperature provides bissulfonylmethylenes in high yields.
The bissulfonylmethylene compounds (1) can act as active methylene compounds, therefore, they are important building blocks in organic synthesis.1–4) Moreover, some of them (sulfonal, trional, and tetronal) are classical sedative-hypnotics5) (Fig. 1).
One of the representative methods for preparing 1 is the oxidation of dithioacetals (2, bissulfinylmethylenes) using potassium permanganate (KMnO4),6) peracids (RCO3H),7,8) or dimethyldioxorane (DMDO)9) (Chart 1). These reactions have some drawbacks, such as producing large amounts of waste (for KMnO4), low chemoselectivity (for KMnO4 and RCO3H), using explosive reagents (for RCO3H), and the need to prepare the reagent by troublesome methods prior to the reaction (DMDO).
We have been working on the oxidations of organosulfur compounds using hydrogen peroxide as the oxidant, and reported that the reaction of sulfides with 30% hydrogen peroxide in the presence of catalytic amounts of Nb(V),10) Ta(V),10,11) or niobium carbide (NbC)12) in methanol provided the corresponding sulfones in high yields (Chart 2).
We also found that the reaction of 2 with 30% hydrogen peroxide catalyzed by Nb(V)-NaI or Ta(V)-NaI in ethyl acetate effectively afforded the corresponding carbonyl compounds13,14) (Chart 3). The use of iodide ion (I−) as the catalyst is essential to obtain the carbonyl compounds. Actually, the reaction of a dithioacetal with 30% hydrogen peroxide in the presence of only a catalytic amount of tantalum(V) chloride (without NaI) in aqueous acetonitrile did not proceed at all within 20 h.
During the further study of the reaction of 2 with 30% hydrogen peroxide catalyzed by Nb(V), Ta(V), or NbC, we found that 1 can be efficiently prepared from the reaction of 2 with 30% hydrogen peroxide in the presence of a catalytic amount of niobium(V) chloride in methanol (Chart 4).
As we noted in the introduction, we found that methanol is the good solvent for the synthesis of sulfones from the oxidation of sulfides with 30% hydrogen peroxide catalyzed by Nb(V),10) Ta(V),10,11) or NbC.12) Therefore, the reactions of 2-methyl-2-(2-naphthyl)-1,3-dithiane (2a) with 16 eq of 30% hydrogen peroxide in methanol were examined in the presence of 0.1 eq of niobium or tantalum compounds (Table 1).
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|---|---|---|---|---|
| Run | Catalyst | Time | 1H-NMR ratio (%) | |
| 1a | 3a | |||
| 1 | Nb(OEt)5 | 1 h 30 min | >99 | Trace |
| 2 | Ta(OE)5 | 2 h 40 min | >99 | Trace |
| 3 | NbCl5 | 2 h | 93 | 7 |
| 4 | TaCl5 | 19 h | >99 | Trace |
| 5 | NbC | 25 h | 98 | 2 |
| 6 | TaC | 94 h 40 min | >99 | Trace |
| 7 | — | 192 h | Complex mixture | |
The desired compound (1a) was obtained in all cases accompanied by small amounts of the ketone (3a) (runs 1–6). Conversely, in the absence of catalysts, the reaction proceeded very slow and afforded complex mixtures (run 7). Among the catalysts, niobium(V) ethoxide (run 1) and niobium(V) chloride (run 3) exhibited a strong catalytic activity. Niobium(V) chloride was chosen as the catalyst for the hydrogen peroxide oxidation of 2, and further reaction conditions were examined, because it is less expensive than niobium(V) ethoxide.
The oxidations of 2a with 30% hydrogen peroxide using niobium(V) chloride as a catalyst were examined in several solvents in order to evaluate the solvents effect. In solvents other than methanol, the reactions proceeded more slowly and afforded 1a in lower yields and accompanied by notable amounts of 3a (Table 2).
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|---|---|---|---|---|
| Run | Solvent | Time | 1H-NMR ratio (%) | |
| 1a | 3a | |||
| 1 | MeOH | 2 h | 93 | 7 |
| 2 | MeCN | 5 h 15 min | 84 | 16 |
| 3 | EtOAc | 67 h | 60 | 40 |
| 4 | CH2Cl2 | 78 h | 62 | 38 |
| 5 | Toluene | 143 h | 63 | 37 |
The amount of 30% hydrogen peroxide required to prepare the bissulfonylmethylene (1a) was further examined (Table 3). The reaction rates and the isolated yields decreased in the cases of 8 and 4 eq of 30% hydrogen peroxide.
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|---|---|---|---|---|
| Run | 30% H2O2 (eq) | Time (h) | Isolated yield (%) | |
| 1a | 3a | |||
| 1 | 16 | 2 | 95 | 5 |
| 2 | 8 | 3 | 79 | 10 |
| 3 | 4 | 5 | 68 | 5 |
Several dithioacetals were treated with 30% hydrogen peroxide in the presence of 10 mol% niobium(V) chloride in methanol to produce the desired bissulfonylmethylene compounds including sulfonal (sedative-hypnotic) in high yields (Table 4).
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|---|---|---|---|
| Entry | Product | Time | Yield (%) |
| 1 | ;%0A%09%09%09newWindow.document.open();%0A%09%09%09newWindow.document.write('<img src=%22./Graphics/FT4a.png%22>');%0A%09%09%09newWindow.document.close();%0A%09%09) | 2 h | 95 |
| 2 | ;%0A%09%09%09newWindow.document.open();%0A%09%09%09newWindow.document.write('<img src=%22./Graphics/FT4b.png%22>');%0A%09%09%09newWindow.document.close();%0A%09%09) (sulfonal) | 9 h 30 min | 86 |
| 3 | ;%0A%09%09%09newWindow.document.open();%0A%09%09%09newWindow.document.write('<img src=%22./Graphics/FT4c.png%22>');%0A%09%09%09newWindow.document.close();%0A%09%09) | 3 h | 72 |
| 4 | ;%0A%09%09%09newWindow.document.open();%0A%09%09%09newWindow.document.write('<img src=%22./Graphics/FT4d.png%22>');%0A%09%09%09newWindow.document.close();%0A%09%09) | 1 h 10 min | 98 |
| 5 | ;%0A%09%09%09newWindow.document.open();%0A%09%09%09newWindow.document.write('<img src=%22./Graphics/FT4e.png%22>');%0A%09%09%09newWindow.document.close();%0A%09%09) | 2 h 15 min | 85 |
Although the reaction mechanism has not been totally clarified, the niobium(V) peroxide species might play important roles as in the cases of the niobium(V) catalyzed oxidation of sulfides with 30% hydrogen peroxide. The plausible reaction mechanism is depicted in Chart 5.
Niobium(V) chloride immediately reacts with water to form niobium(V) hydroxides. The resulting hydroxides react with hydrogen peroxide or methyl hydroperoxides (derived from the reaction of hydrogen peroxide with methanol) to produce niobium(V) peroxides. Because the niobium(V) compounds act as a Lewis acid,10,11) the methanol coordinates with the metal peroxides to produce niobium(V) peroxide complexes. These peroxide complexes oxidize dithioacetals and revert back to the niobium(V) hydroxides (or a complex with the solvent). The resulting niobium(V) hydroxides then react with peroxide to reform the niobium(V) peroxide complexes.
The bissulfonylmethylene compounds (1) can be prepared by the oxidation of thioacetals with 30% hydrogen peroxide in the presence of a catalytic amount of niobium(V) chloride in methanol.
All reagents were commercially obtained from Nacalai Tesque, Inc., Wako Pure Chemical Industries, Ltd., Kanto Chemical Co., Inc., Kishida Chemical, Co., Ltd., Tokyo Chemical Industry, Co., Ltd. and Sigma-Aldrich Corp., and used without further purification. Melting points were measured using a Yanaco micromelting point apparatus (MP-J3) and are uncorrected. The 1H- and 13C-NMR spectra were recorded by a JEOL (JNM-EX400) spectrometer as solutions in CDCl3 using tetramethylsilane (TMS) or the residual CHCl3 peak as the internal standard. The IR spectra were recorded using a Jasco IR-8300 FT-IR spectrophotometer. The mass spectra were recorded on a Shimadzu GCMS-QP1100EX spectrometer.
Oxidation of Dithioacetals to Bissulfonylmethylenes; General ProcedureTo a stirred solution of a dithioacetal (1 mmol) in methanol (6 mL) was added niobium(V) chloride (27 mg, 0.1 mmol) and 30% hydrogen peroxide (1.6 mL, 16.0 mmol), then the mixture was stirred at r.t. The reaction was monitored by TLC. After the dithioacetal disappeared from the TLC, sat. aq. sodium thiosulfate (20 mL) was added, and the resulting mixture was extracted with dichloromethane (20 mL×2). The extract was dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified by silica gel column chromatography (hexane–EtOAc) to afford the 1,3-bissulfonylmethylenes.
2-Methyl-2-naphthalen-2-yl-[1,3]dithiane 1,1,3,3-TetraoxideColorless crystals; mp 182–183°C. 1H-NMR (CDCl3) δ: 2.25 (3H, s), 2.31–2.42 (1H, m), 2.51–2.57 (1H, m), 3.20–3.28 (2H, m), 3.57–3.62 (1H, m), 3.76–3.84 (1H, m), 7.56–7.62 (2H, m), 7.95–7.98 (1H, m), 8.01–8.05 (3H, m), 8.40 (1H, s). 13C-NMR (CDCl3) δ: 10.71, 16.93, 46.35, 46.41, 82.38, 126.62, 127.03, 127.20, 127.45, 127.48, 127.83, 128.65, 131.25, 132.99, 133.56. IR (KBr) cm−1: 1559, 1314, 1136, 1056. MS (m/z): 324 (M+). HR-MS Calcd for C15H17O4S2 (M++H): 325.0568. Found: 325.0559.
2,2-Bis(ethanesulfonyl)propane (Sulfonal)6)Colorless crystals; mp 126–128°C (lit.6) 124–125°C). 1H-NMR (acetone-d6) δ: 1.37 (6H, t, J=7.5 Hz), 1.76 (6H, s), 3.47 (4H, q, J=7.5 Hz). 13-C-NMR (acetone-d6) δ: 4.44, 16.22, 43.91, 81.16. IR (neat) cm−1: 3425, 1633, 1304, 1107. MS (m/z): 228 (M+), 135, 95, 77, 59.
1,1-Bis(ethanesulfonyl)ethane6)Colorless crystals; mp 75–76°C (lit.6) 74–75°C). 1H-NMR (acetone-d6) δ: 1.37 (6H, t, J=7.3 Hz), 1.77 (3H, d, J=7.3 Hz), 3.37–3.52 (4H, m), 4.84 (1H, q, J=7.3 Hz). 13-C-NMR (acetone-d6) δ: 4.85, 8.21, 46.28, 73.50. IR (neat) cm−1: 1313, 1127. MS (m/z): 214 (M+), 122, 94, 66.
1,1-Bis(ethanesulfonyl)methane6)Colorless crystals; mp 101–103°C (lit.6) 100–101.5°C). 1H-NMR (acetone-d6) δ: 1.38 (6H, t, J=7.6 Hz), 3.44 (4H, q, J=7.6 Hz), 4.98 (2H, s). 13C-NMR (acetone-d6) δ: 5.31, 48.26, 66.63. IR (neat) cm−1: 3452, 1635, 1316, 1129, 1050. MS (m/z): 200 (M+), 108, 80.
Bis(benzenesulfonyl)methane6)Colorless crystals; mp 121–122°C (lit.6) 117–119°C). 1H-NMR (CDCl3) δ: 5.38 (2H, s), 7.64 (4H, t, J=7.5 Hz), 7.77 (2H, t, J=7.5 Hz), 7.96 (4H, d, t, J=7.5 Hz). 13C-NMR (acetone-d6) δ: 73.11, 128.82, 129.23, 134.50, 139.41. IR (neat) cm−1: 3616, 3235, 1642, 1328, 1152. MS (m/z): 142 (M+−2×C6H5−H), 107, 91, 77.
