2-Chloro-6-Methylphenyl Isothiocyanate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 2-chloro-6-methylphenyl-isothiocyanate (18.3 g), N-methyl aminooxy acetic acid hydrochloride (15.5 g), triethylamine (30 g) and chloroform (300 mL) was heated at reflux for one hour, stirred at ambient temperature for one hour, then evaporated to dryness. The residue was dissolved in ethyl acetate (500 mL) and washed with 2N HCl (2×300 mL) then with water (300 mL). The organic phase was dried over anhydrous magnesium sulfate and evaporated to dryness affording (28 g) of [[[[(2-Chloro-6-ethylphenyl)amino]thioxomethyl]methylamino]oxy]acetic acid as a semi solid. 1H-NMR (DMSO-d6; 300 Mhz) δ12.8 (br s, 1H), 10.04 (s, 1H), 7.38-7.20 (m, 3H), 4.61 (s, 2H), 3.58 (s, 3H), and 2.20 ppm (s, 3H). The acid (26.8 g) was dissolved in benzene (300 mL). Phosphorus pentachloride (18 g) was added in portions. The mixture was heated at reflux for one half hour then evaporated to dryness. The residue was dissolved in ethyl acetate (500 mL) and washed with sodium bicarbonate saturated solution (2×300 mL) then with water (300 mL). The organic phase was dried over anhydrous magnesium sulfate and evaporated to dryness. Crystallization from ethanol afforded the title compound (10.5 g) as a solid, m.p. 176-178° C. Mass spectrum (ESl, [M+H]+) m/z 271/273. 1H-NMR (CDCl3; 400 MHz) δ7.37 (d, 1H), 7.29 (t, 1H), 7.22 (d, 1H), 4.86 (ABq, 2H), 3.76 (s, 3H), and 2.21 ppm (s, 3H). was heated at reflux for one hour evaporated to dryness The residue was dissolved in ethyl acetate (500 mL) washed with 2N HCl (2×300 mL) The organic phase was dried over anhydrous magnesium sulfate evaporated to dryness

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was prepared by the procedure described in Example 11 using 6.5 g of 2-chloro-6-methylphenyl-isothiocyanate, 8.5 g of N-butyl glycine, 10.0 g of triethyl amine, and 150 mL of methylene chloride. Purification was achieved by flash chromatography on silica gel (methylene chloride). Crystallization from ethanol afforded the title compound (3.85 g) as a light pink solid, m.p. 97°-100° C. Anal. Calcd. for. C14H17Cl N2O S : C, 56.65; H, 5.77; N, 9.44. Found: C, 56.45; H, 5.67; N, 9.33. Mass spectrum (+FAB, [M+H]+) m/z 297. The title compound was prepared by the procedure Purification Crystallization from ethanol

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of the crude N-ethyl glycine (9.2 g), 2-chloro-6-methylphenyl-isothiocyanate (9.1 g), triethylamine (10.1 g), and methylene chloride (150 mL) was heated at reflux for 3.5 hours. The solvent was evaporated to dryness. Purification was achieved by flash chromatography on silica gel (methylene chloride). Crystallization from ethanol afforded the title compound (5.4 g) as a creamy solid, m.p. 124°-126° C. Anal. Calcd. for. C12H13Cl N2 O S: C, 53.63; H, 4.87; N, 10.42. Found: C, 53.43; H, 4.79; N, 10.28. Mass spectrum (EI, M.+) m/z 268/270. was heated at reflux for 3.5 hours The solvent was evaporated to dryness Purification Crystallization from ethanol

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: was obtained in a similar manner to the method specified in Example 6a) by reacting a mixture prepared from 0.74 g (=1.01 ml) of N-ethyl-N,N-diisopropylamine in 40 ml of THF, 0.8 g of 3,4-diaminothiophene dihydrobromide and 0.473 g of 2-chloro-6-methylphenyl isothiocyanate. was obtained in a similar manner to the method

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was prepared by the procedure described in Example 54 using 6.5 g of 2-chloro-6-methylphenyl-isothiocyanate, 8.5 g of N-butyl glycine, 10.0 g of triethyl amine, and 150 mL of methylene chloride. Purification was achieved by flash chromatography on silica gel (methylene chloride). Crystallization from ethanol afforded the title compound (3.85 g) as a light pink solid, m.p. 97°-100° C. Anal. Calcd. for. C14H17Cl N2O S: C, 56.65; H, 5.77; N, 9.44. Found: C, 56.45; H, 5.67; N, 9.33. Mass spectrum (+FAB, [M+H]+) m/z 297. The title compound was prepared by the procedure Purification Crystallization from ethanol

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was prepared by the procedure described in Example 19 using 9.2 g of N-ethyl glycine, 9.1 g of 2-chloro-6-methylphenyl-isothiocyanate, 10.1 g of triethylamine, and 150 mL of methylene chloride. Purification was achieved by flash chromatography on silica gel (methylene chloride). Crystallization from ethanol afforded the title compound (5.4 g) as a creamy solid, m.p. 124°-126° C. Anal. Calcd. for. C12H13Cl N2O S: C, 53.63; H, 4.87; N, 10.42. Found: C, 53.43; H, 4.79; N, 10.28. Mass spectrum (El, M.+) m/z 268/270. The title compound was prepared by the procedure Purification Crystallization from ethanol

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was prepared by the procedure described in Example 1 using 9.2 g of 2-chloro-6-methylphenyl-isothiocyanate, 7.68 g of sarcosine ethyl ester hydrochloride, 12 g of triethyl amine, and 200 mL of chloroform. Crystallization from ethanol afforded the title compound (7.1 g) as an orange solid (7.1 g), m.p. 142°-145° C. Anal. Calcd. for. C11H11N2O S: C, 51.87; H, 4.35; N,11.00. Found: C, 51.96; H, 4.26; N, 10.97. Mass spectrum (El, M.+) m/z 254. The title compound was prepared by the procedure Crystallization from ethanol

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 2-chloro-6-methylphenyl-isothiocyanate (18.3 g), N-methyl aminooxy acetic acid hydrochloride (15.5 g), triethylamine (30 g) and chloroform (300 mL) was heated at reflux for one hour, stirred at ambient temperature for one hour, then evaporated to dryness. The residue was dissolved in ethyl acetate (500 mL) and washed with 2N HCl (2×300 mL) then with water (300 mL). The organic phase was dried over anhydrous magnesium sulfate and evaporated to dryness affording (28 g) of [[[[(2-Chloro-6-ethylphenyl)amino]thioxomethyl]methylamino]oxy]acetic acid as a semi solid. 1H-NMR (DMSO-d6; 300 Mhz) δ12.8 (br s, 1H), 10.04 (s, 1H), 7.38-7.20 (m, 3H), 4.61 (s, 2H), 3.58 (s, 3H), and 2.20 ppm (s, 3H). The acid (26.8 g) was dissolved in benzene (300 mL). Phosphorus pentachloride (18 g) was added in portions. The mixture was heated at reflux for one half hour then evaporated to dryness. The residue was dissolved in ethyl acetate (500 mL) and washed with sodium bicarbonate saturated solution (2×300 mL) then with water (300 mL). The organic phase was dried over anhydrous magnesium sulfate and evaporated to dryness. Crystallization from ethanol afforded the title compound (10.5 g) as a solid, m.p. 176-178° C. Mass spectrum (ESl, [M+H]+) m/z 271/273. 1H-NMR (CDCl3; 400 MHz) δ7.37 (d, 1H), 7.29 (t, 1H), 7.22 (d, 1H), 4.86 (ABq, 2H), 3.76 (s, 3H), and 2.21 ppm (s, 3H). was heated at reflux for one hour evaporated to dryness The residue was dissolved in ethyl acetate (500 mL) washed with 2N HCl (2×300 mL) The organic phase was dried over anhydrous magnesium sulfate evaporated to dryness

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was prepared by the procedure described in Example 11 using 6.5 g of 2-chloro-6-methylphenyl-isothiocyanate, 8.5 g of N-butyl glycine, 10.0 g of triethyl amine, and 150 mL of methylene chloride. Purification was achieved by flash chromatography on silica gel (methylene chloride). Crystallization from ethanol afforded the title compound (3.85 g) as a light pink solid, m.p. 97°-100° C. Anal. Calcd. for. C14H17Cl N2O S : C, 56.65; H, 5.77; N, 9.44. Found: C, 56.45; H, 5.67; N, 9.33. Mass spectrum (+FAB, [M+H]+) m/z 297. The title compound was prepared by the procedure Purification Crystallization from ethanol