3,3‐Dimethyl‐2‐Nitroso‐2,3‐Dihydrobenzo[ d ]Isothiazole‐1,1‐Dioxide

Abstract

[2619509-30-5] C9H10N2O3S (MW 226.25) InChI = 1S/C9H10N2O3S/c1-9(2)7-5-3-4-6-8(7)15(13,14)11(9)10-12/h3-6H,1-2H3 InChIKey = RTKXPAFZAUMCEE-UHFFFAOYSA-N (reagent used for transnitrosation of alkyl alcohols, amines, amides, ureas, and thiols1) Physical Data: mp 70 and 90 °C (two possible rotational isomers).1 Solubility: Soluble in THF, acetonitrile, dichloromethane, and dichloroethane.1 Form Supplied in: yellow solid. Analysis of Reagent Purity: 1H NMR (500 MHz, CDCl3) δ 7.88–7.75 (m, 2H), 7.64 (t, J = 7.7 Hz, 1H), 7.58 (d, J = 7.8 Hz, 1H), 1.99 (s, 6H); 13C NMR (125 MHz, CDCl3) δ: 135.5, 130.3, 123.5, 122.0, 65.5, 29.6. Preparative Method: the title compound was prepared according to the following synthetic route starting from commercially available saccharin. The last step of the synthetic scheme potentially yields a mixture of NO–1a and NO–1b rotational isomers depending on the reaction conditions. To a 500-mL round bottom flask with saccharin (10.1 g, 55 mmol) in 1,4-dioxane (250 mL), SOCl2 (10 mL, 138 mmol) was added dropwise. Catalytic DMF (1 mL) was added after 5 min of stirring. The round bottom flask was placed on a heating mantle with a reflux condenser and refluxed for 48 h. The clear brown solution was concentrated under vacuum using a rotary evaporator in a water bath at 80 °C to remove excess SOCl2. The beige solid, 1, was used in the next step without further purification. Long-term storage of 1 should be done under argon at 0 to −4 °C. Dry diethyl ether (100 mL) was added via cannula to a nitrogen-purged 500-mL round bottom flask containing 1 (11 g, 55 mmol). The reaction mixture was cooled to −10 °C in a dry ice/methanol bath (MeOH/H2O:10/90) and stirred for 10 min. To the cooled reaction mixture, 1.6 M methyl lithium (138 mL, 220 mmol) was added dropwise via syringe with moderate stirring. The reaction mixture was stirred for 1 h at −10 °C, then warmed to room temperature, and stirred overnight. The crude reaction was then poured into cold 5% HCl solution (150 mL) and extracted with dichloromethane (50 mL × 3). The combined organic layer was washed with a saturated NaCl solution (50 mL × 3) and dried over MgSO4. The organic layer was concentrated, absorbed onto silica, and purified with column chromatography using DCM (Rf = 0.4) as the mobile phase. The isolated product was a yellow solid with minor, colored impurities. The compound was then recrystallized with DCM to give clear crystals of DMBS (9.9 g, 80% yield). To a 500-mL round bottom flask with DMBS (10 g, 50 mmol) and pTsOH (8.6 g, 70 mmol) was added 250 mL of dichloromethane. The resulting mixture was stirred at room temperature for 10 min before cooling to 0 °C and stirred for an additional 10 min. NaNO2 (5.0 g, 72 mmol) was added slowly to the cooled mixture over the course of 5 min. The reaction was allowed to warm to room temperature and stirred overnight. The reaction mixture was filtered through a Büchner funnel to remove insoluble materials. The filtrate was then concentrated and purified with column chromatography using dichloromethane (Rf = 0.7) as the mobile phase. Product NO–1 (8.9 g, 81% yield) was isolated as a yellow solid with melting points of 70 and 90 °C. Handling, Storage, and Precautions: Nitrososulfonamides are hazardous. The decomposition of the material releases nitric oxide, which can be harmful if inhaled. Manipulations of the material should be performed in a ventilated fume hood. Long-term storage should be done using an amber-colored container at 0 to −4 °C. The last step in the synthesis of NO–1 potentially yields two different rotational isomers, NO–1a and NO–1b, that differ in the orientation of the nitroso functional group. Evidence suggests that the isomers may be interconverted thermally or via catalytic Brønsted acid.