thiirane

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2,6-dimethylpyridine (19.2 mL, 0.165 mol) and methanesulfonic acid (3.27 mL, 0.050 mol) was stirred for 15 min, treated with ethylene sulfide, (4.17 mL, 0.070 mol) and stirred at 100° C. for 42 h under a nitrogen atmosphere. After cooling to 25° C., the reaction mixture was diluted with ether (45 mL) and water (30 mL). The two layers were separated and the organic layer was extracted with water (2×5 mL). The aqueous layers were combined, filtered through a Celite pad, washed with ether (2×15 mL), pumped to remove the traces of organic solvents and poured on top of a column (3.0×12 cm) of μ-bondapak C-18. Elution with 3% acetonitrile 97% water mixture gave after lyophylization of the appropriate fractions 2.5 g of the impure title compound as a syrup. It was repurified by hplc (μ-bondapak C-18) to give 0.90 g (7%) of the title compound. ir (film) νmax : 2520 (SH), 1640 and 1625 (pyridinium), 1585, 1490, 1200 cm-1 (sulfonate), 1Hmr (DMSO-d6 +D2O) δ: 2.36 (3H, s, CH3SO3-), 4.62 (2H, m, CH2N+), 7.74 (2H, m, Pm of pyridinium), 8.24 (1H, m, Hp of pyridinium), uv (H2O) max : 272 (4080)mμ. stirred at 100° C. for 42 h under a nitrogen atmosphere The two layers were separated the organic layer was extracted with water (2×5 mL) filtered through a Celite pad washed with ether (2×15 mL) to remove the traces of organic solvents poured on top of a column (3.0×12 cm) of μ-bondapak C-18 Elution with 3% acetonitrile 97% water mixture

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3-methylthiopyridine1 (2.00 g, 0.016 mol) in 10 mL of ether was added 15 mL of 1 N HCl and the mixture was well shaken. The aqueous phase was separated, washed with 10 mL of ether and then evaporated. The residual hydrochloride was then dried in vacuo (P2O5) to give a white solid. To this solid hydrochloride was added 3-methylthiopyridine (1.88 g, 0.015 mol) and ethylene sulfide (0.89 mL, 0.015 mol) and the resulting mixture was heated (oil bath) at 55°-65° C. under N2 for 15 h. This gave a slightly turbid oil which was taken up in 125 mL of H2O and washed with CH2Cl2. The aqueous solution was concentrated to about 25 mL and then a few drops of acetonitrile were added to make the mixture homogenous. The resulting aqueous solution was applied to a C18 reverse-phase column. Elution with H2O and subsequent evaporation of the relevant fractions afforded the product (2.66 g 80%) as a pale yellow, viscous oil. ir (film) νmax : 2410 (br, --SH) cm-1 ; 1Hnmr (d6 -DMSO+D2O) δ: 8.88-7.88 (m, 4H, aromatic), 4.70 (t, J=6.5 Hz, 2H, N--CH2), 3.08 (skewed t, J=6.5 Hz, 2H, S--CH2), 2.64 (s, 3H, S-Me). The aqueous phase was separated washed with 10 mL of ether evaporated The residual hydrochloride was then dried in vacuo (P2O5) to give a white solid the resulting mixture was heated (oil bath) at 55°-65° C. under N2 for 15 h This gave a slightly turbid oil which washed with CH2Cl2 The aqueous solution was concentrated to about 25 mL a few drops of acetonitrile were added Elution with H2O and subsequent evaporation of the relevant fractions afforded the product (2.66 g 80%) as a pale yellow, viscous oil

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Methylthiopyridine (2.75 g, 22.0 mmol) was added slowly to methanesulfonic acid* (0.65 mL, 10.5 mmol) by cooling in an ice-bath. To this solid was added ethylene sulfide* (0.66 mL, 11.0 mmol, Aldrich) and the mixture was heated at 50°-60° C. for 21 h. As reaction proceeds the solid went to solution. After cooling, the reaction mixture was dissolved in H2O (5 mL) and washed with Et2O (5×4 mL). The cloudy aqueous layer was filtered over Celite and the filtrate was purified by reverse phase silica gel column chromatography (C18 micro bondapack 10 g) eluting with H2O. Each fraction of 10 mL was collected. Fractions 2 and 3 were combined and repurified by the reverse phase column. Fraction 2 gave 1.258 g (4.48 mmol, y. 42.6%) of the title compound as a viscous oil: 1Hmr (DMSO-d6, CFT-20) δ: 2.32 (3H, s, MeSO3⃝), 2.72 (3H, s, --SMe), 2.68 (1H, m, SH), 2.9-3.2 (3H, m, --CH2S--), 4.59 (2H, t, J=6.4 Hz, --CH2N⊕), 7.97 (2H, "d", J=7.2 Hz, aromatic-Hs) and 8.72 ppm (2H, "d", J=7.2 Hz, aromatic-Hs); ir (neat) νmax : 1630, 1200 (br, --SO3⃝), 785 and 770 cm-1. by cooling in an ice-bath the mixture was heated at 50°-60° C. for 21 h As reaction After cooling washed with Et2O (5×4 mL) The cloudy aqueous layer was filtered over Celite the filtrate was purified by reverse phase silica gel column chromatography (C18 micro bondapack 10 g) eluting with H2O Each fraction of 10 mL was collected repurified by the reverse phase column

Conditions: temp:23.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of p-toluenesulfonic acid (1.72 g, 0.01 mol) in benzene (6.5 mL) was added 4-picoline (1.17 mL, 0.012 mL). The resulting mixture was stirred under a nitrogen atmosphere at 23° C. for 30 min, treated with ethylenesulfide (0.65 mL, 0.011 mol) and stirred at 75° for 24 h. More ethylenesulfide (0.65 mL, 0.011 mol) was added and the stirring was continued at 75° C. for 24 h more. The reaction mixture was cooled to 23° C. and diluted with water (5 mL) and ether (8 mL). The aqueous layer was separated and washed with ether (3×8 mL). The traces of organic solvents were removed under vacuum and the compound was chromatographed on μ-bondapack C-18 with water as eluting solvent to give 2.94 g (90%) of the title compound as a colorless syrup; ir (film) θmax : 2510 (SH) 1640 (pyridinium), 1595, 1582, 1475, 1200 (sulfonate), 1031, 1010, 818 cm-1, 1Hmr (DMSO, d6) δ: 2.29 (3H, s, CH3 on pyridinium), 2.61 (s, CH3Ph), 2.4-2.8 (4H, SH, CH3Ph), 3.03 (2H, m[addition of D2O gave a t, J=6.4 Hz, at 3.04]CH2S), 4.68 (2H, t, J=6.4 Hz, CH2N+), 7.11, 7.49 (4H, 2d, J=7.9 Hz, Phenyl), 8.00 (2H, d, J=6.5 Hz, Bm of pyridinium), 8.89 (2H, d, J=6.5 Hz, Ho of pyridinium), uv (H2O) λmax : 256 (ε4315), 222 (ε17045)mμ. stirred at 75° for 24 h the stirring was continued at 75° C. for 24 h The reaction mixture was cooled to 23° C. The aqueous layer was separated washed with ether (3×8 mL) were removed under vacuum the compound was chromatographed on μ-bondapack C-18 with water as eluting solvent

Conditions: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of 2-methylpyridinium methanesulfonate in 2-methylpyridine prepared by the addition of methanesulfonic acid (0.65 mL, 0.010 mol) to cold 2-methylpyridine (2.17 mL, 0.022 mol) was added ethylene sulfide (0.655 mL, 0.011 mol). The reaction mixture was stirred under a nitrogen atmosphere at 55° C. for 21 h, cooled to 23° C. and diluted with water (5 mL). The aqueous solution was washed with ether (6×4 mL) pumped to remove traces of organic solvents and poured on top of a column (2.5×10.0 cm) of μ-bondapak C-18. The column was eluted with water and lyophilization of the appropriate fractions gave 2.13 g (85%) of the title compound, ir (film) νmax : 2520 (SH), 1623 (pyridinium) 1574, 1512, 1485, 1412, 1195 (sulfonate), 1038 cm-1, 1Hmr (DMSO-d6 +D2O) δ: 2.37 (3H, s, CH3SO3-), 2.83 (3H, s, CH3 on pyridinium), 3.09 (2H, J=6.9 Hz, CH2S), 4.71 (2H, t, J=6.9 Hz, CH2N+), 7.93 (2H, m, Hm of pyridinium), 8.44 (1H, m, Hp of pyridinium), 8.89 (1H, m, Ho of pyridinium), uv (H2O) λmax : 266 (ε3550) m μ. cooled to 23° C. The aqueous solution was washed with ether (6×4 mL) to remove traces of organic solvents poured on top of a column (2.5×10.0 cm) of μ-bondapak C-18 The column was eluted with water and lyophilization of the appropriate fractions

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-pyridinemethanol (1.635 g, 0.015 mol) in 10 mL of CH2Cl2, at 0° C. under N2, was added dropwise trifluoromethanesulfonic acid (1.327 mL, 0.015 mol). A yellow-brown oil rapidly separated out. An additional equivalent of 4-pyridine-methanol (1.635 g, 0.015 mol) was added to this mixture and the solvent was removed under reduced pressure to give an oil. To this oil was added ethylene sulfide (0.891 mL, 0.015 mol) and the resulting homogeneous mixture was heated (oil bath) at about 60° C. for 3 h. The reaction mixture was then taken up in 15 mL of H2O and the aqueous solution was washed with CH2Cl2 (5×5 mL). After removing residual organic solvent in vacuo the aqueous solution was applied to a C18 reverse-phase column. Elution with H2O and subsequent evaporation of the relevant fractions afforded an oilwhich was further dried in vacuo over P2O5 to give the product (4.64 g, 97% as a colourless oil. ir (film) νmax : 3455 (s, OH), 2565, (w, SH) cm-1 ; 1Hnmr (d6 -acetone) δ: 9.07, 8.18 (ABq, J=6.8 Hz, 4H, aromatic), 5.03 (s, 2H, CH2OH), 4.96 (t, J=6.5 Hz, 2H, N--CH2), 4.09 (br s, 1H, --OH), 3.5-3.1 (m, 2H, S--CH2), 2.25 (brs, 1H, --SH). A yellow-brown oil rapidly separated out the solvent was removed under reduced pressure to give an oil the aqueous solution was washed with CH2Cl2 (5×5 mL) After removing residual organic solvent in vacuo the aqueous solution Elution with H2O and subsequent evaporation of the relevant fractions afforded an oilwhich was further dried in vacuo over P2O5 to give the product (4.64 g, 97% as a colourless oil

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To precooled (ice bath) N-methylthiomorpholine* (5.00 g, 42.7 mmol) was added methanesulfonic acid (1.47 mL, 20.5 mmol) and ethylene sulfide (1.30 mL, 21.4 mmol). The mixture was heated at 65° C. for 24 h and diluted with water (25 mL). The aqueous solution was washed with diethyl ether (3×25 mL), pumped under vacuum and poured over a silica gel reverse phase column; the title compound being eluted with water. The appropriate fractions were combined and evaporated to afford the thiol as an oil (4.80 g, yield 86%); ir (film) νmax : 2550 cm-1 (w, SH); 1Hmr (DMSO d6)δ: 3.25-2.95 (6H, m, CH2N⊕), 3,32 (3H, s, CH3N⊕), 3.20-2.65 (7H, m, CH2S, SH) and 2.32 ppm (3H, s, CH3SO3). The aqueous solution was washed with diethyl ether (3×25 mL) poured over a silica gel reverse phase column the title compound being eluted with water evaporated