(2-chlorophenyl)methyl thiocyanate

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:

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To diisopropylamine (15.3 mL, 109 mmol) in toluene (500 mL), at 0-5° C., under nitrogen, was added drop wise over ˜½ hour 1.6M″ BuLi/THF (68.5 mL, 109 mmol). The reaction mixture was stirred for a further 15 minutes before the drop wise addition of 2-pyridylacetonitrile (5.55 mL, 49.6 mmol) over 1 hour. 2-Chlorobenzylthiocyanate (20.0 g, 109 mmol), described in the literature by Schlesinger J. Am. Chem. Soc. 1954, 76, 585, was then added in solution in toluene (100 mL) over a period of 1 hour. The reaction mixture was stirred for an additional 2 hours. Water was added and the layers were separated. The organic phase was extracted twice with 200 mL 2N NaOH. The combined aqueous phases were cooled down to 0° C and acidified to ˜pH 1. The precipitate obtained was filtered and dried to give the title compound as a pale tan solid (4.50 g, 63% yield). δH (DMSO-d6) 6.79 (1H, t), 7.09 (1H, d), 7.73 (1H, t), 7.79 (1H, dd), 12.95 (1H, br s). the layers were separated The organic phase was extracted twice with 200 mL 2N NaOH The precipitate obtained was filtered dried

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To diisopropylamine (15.3 mL, 109 mmol) in toluene (500 mL), at 0-5° C., under nitrogen, was added drop wise over ˜½ hour 1.6M″ BuLi/THF (68.5 mL, 109 mmol). The reaction mixture was stirred for a further 15 minutes before the drop wise addition of 2-pyridylacetonitrile (5.55 mL, 49.6 mmol) over 1 hour. 2-Chlorobenzylthiocyanate (20.0 g, 109 mmol), described in the literature by Schlesinger J. Am. Chem. Soc. 1954, 76, 585, was then added in solution in toluene (100 mL) over a period of 1 hour. The reaction mixture was stirred for an additional 2 hours. Water was added and the layers were separated. The organic phase was extracted twice with 200 mL 2N NaOH. The combined aqueous phases were cooled down to 0° C and acidified to ˜pH 1. The precipitate obtained was filtered and dried to give the title compound as a pale tan solid (4.50 g, 63% yield). δH (DMSO-d6) 6.79 (1H, t), 7.09 (1H, d), 7.73 (1H, t), 7.79 (1H, dd), 12.95 (1H, br s). the layers were separated The organic phase was extracted twice with 200 mL 2N NaOH The precipitate obtained was filtered dried

反応条件: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a flame dried 5L 3-neck flask equipped with a mechamical overhead stirrer under nitrogen was added diisopropylamine (78.60 mL, 0.56 mol, 2.2 eq) and 2 L of benzene. After cooling to 0-5° C., 1.6 M n-BuLi (351.0 mL, 0.56 mol, 2.2 eq) was added dropwise via addition funnel while keeping the temperature at 0-5° C. The LDA was stirred for 45 min. at 0-5° C. 3-Bromophenylacetonitrile (50.0 g, 0.26 mol, 1.0 eq) dissolved in 200 mL of benzene was added dropwise via addition funnel keeping the temperature at 0-5° C. The mixture was stirred an additional 15 min at this temperature. 2-Chlorobenzylthiocyanate (J. Am. Chem. Soc., 1954, 76, 585) (103.0 g, 0.56 mol, 2.2 eq) dissolved in 200 mL benzene was added dropwise via addition funnel keeping the temperature at 0-5° C. During the addition, a precipitate formed. The reaction was allowed to warm to room temperature and the mixture stirred overnight. The reaction was quenched by adding water and 200 mL 10% NaOH. The layers were separated, and the benzene layer extracted with 10% NaOH (3×1 L). The basic layers were collected and acidified with conc. HCl to pH 1-2. A precipitate formed. Methylene chloride was added to dissolve the precipitate. The layers were separated and the aqueous layer reextracted with methylene chloride (2×). The methylene chloride layers were collected, dried (MgSO4) and the solvent removed in vacuo to yield 65.32 g of 2-(3-bromophenyl)malononitrile as a yellow solid. Recrystallization from methylcyclohexane yielded two crops: crop 1, 42.86 g of orange crystals, m.p. 99.5-101.5° C.; crop 2, 2.18 g of orange crystals, m.p. 97.0-99.0° C. Combined yield 79.9%. 1H-NMR (CDCl3) δ: 7.67 (s, 1H); 7.63 (d, 1H, J=7 Hz); 7.47 (d, 1H, J=7 Hz); 7.39 (t, 1H, J=7 Hz); 5.08 (s, 1H). To a flame dried 5L 3-neck flask equipped with a mechamical overhead stirrer under nitrogen at 0-5° C was added dropwise via addition funnel at 0-5° C was added dropwise via addition funnel at 0-5° C During the addition a precipitate formed to warm to room temperature the mixture stirred overnight The reaction was quenched by adding water and 200 mL 10% NaOH The layers were separated the benzene layer extracted with 10% NaOH (3×1 L) The basic layers were collected A precipitate formed to dissolve the precipitate The layers were separated The methylene chloride layers were collected dried (MgSO4) the solvent removed in vacuo

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a flame dried 5L 3-neck flask equipped with a mechamical overhead stirrer under nitrogen was added diisopropylamine (78.60 mL, 0.56 mol, 2.2 eq) and 2 L of benzene. After cooling to 0-5° C., 1.6 M n-BuLi (351.0 mL, 0.56 mol, 2.2 eq) was added dropwise via addition funnel while keeping the temperature at 0-5° C. The LDA was stirred for 45 min. at 0-5° C. 3-Bromophenylacetonitrile (50.0 g, 0.26 mol, 1.0 eq) dissolved in 200 mL of benzene was added dropwise via addition funnel keeping the temperature at 0-5° C. The mixture was stirred an additional 15 min at this temperature. 2-Chlorobenzylthiocyanate (J. Am. Chem. Soc., 1954, 76, 585) (103.0 g, 0.56 mol, 2.2 eq) dissolved in 200 mL benzene was added dropwise via addition funnel keeping the temperature at 0-5° C. During the addition, a precipitate formed. The reaction was allowed to warm to room temperature and the mixture stirred overnight. The reaction was quenched by adding water and 200 mL 10% NaOH. The layers were separated, and the benzene layer extracted with 10% NaOH (3×1 L). The basic layers were collected and acidified with conc. HCl to pH 1-2. A precipitate formed. Methylene chloride was added to dissolve the precipitate. The layers were separated and the aqueous layer reextracted with methylene chloride (2×). The methylene chloride layers were collected, dried (MgSO4) and the solvent removed in vacuo to yield 65.32 g of 2-(3-bromophenyl)malononitrile as a yellow solid. Recrystallization from methylcyclohexane yielded two crops: crop 1, 42.86 g of orange crystals, m.p. 99.5-101.5° C.; crop 2, 2.18 g of orange crystals, m.p. 97.0-99.0° C. Combined yield 79.9%. 1H-NMR (CDCl3) δ: 7.67 (s, 1H); 7.63 (d, 1H, J=7 Hz); 7.47 (d, 1H, J=7 Hz); 7.39 (t, 1H, J=7 Hz); 5.08 (s, 1H). To a flame dried 5L 3-neck flask equipped with a mechamical overhead stirrer under nitrogen at 0-5° C was added dropwise via addition funnel at 0-5° C was added dropwise via addition funnel at 0-5° C During the addition a precipitate formed to warm to room temperature the mixture stirred overnight The reaction was quenched by adding water and 200 mL 10% NaOH The layers were separated the benzene layer extracted with 10% NaOH (3×1 L) The basic layers were collected A precipitate formed to dissolve the precipitate The layers were separated The methylene chloride layers were collected dried (MgSO4) the solvent removed in vacuo

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: With stirring and cooling, 0.3 mol of 1-naphthylaceto-nitrile and then, dropwise, 0.6 mol of 2-chlorobenzyl thiocyanate are added to a solution of 0.65 mol of lithium diisopropylamide in benzene. After one hour, the reaction mixture is introduced into 1 l of 0.3 molar NaOH, and the mixture is allowed to stand for a while and then the two phases which are formed are separated. The aqueous solution is neutralized by adding hydrochloric acid and allowed to stand overnight. The precipitated product is filtered off with suction, dried and purified by recrystallization from ethanol. cooling the two phases which are formed are separated by adding hydrochloric acid to stand overnight The precipitated product is filtered off with suction dried purified by recrystallization from ethanol

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To diisopropylamine (15.3 mL, 109 mmol) in toluene (500 mL), at 0-5° C., under nitrogen, was added drop wise over ˜½ hour 1.6M″ BuLi/THF (68.5 mL, 109 mmol). The reaction mixture was stirred for a further 15 minutes before the drop wise addition of 2-pyridylacetonitrile (5.55 mL, 49.6 mmol) over 1 hour. 2-Chlorobenzylthiocyanate (20.0 g, 109 mmol), described in the literature by Schlesinger J. Am. Chem. Soc. 1954, 76, 585, was then added in solution in toluene (100 mL) over a period of 1 hour. The reaction mixture was stirred for an additional 2 hours. Water was added and the layers were separated. The organic phase was extracted twice with 200 mL 2N NaOH. The combined aqueous phases were cooled down to 0° C and acidified to ˜pH 1. The precipitate obtained was filtered and dried to give the title compound as a pale tan solid (4.50 g, 63% yield). δH (DMSO-d6) 6.79 (1H, t), 7.09 (1H, d), 7.73 (1H, t), 7.79 (1H, dd), 12.95 (1H, br s). the layers were separated The organic phase was extracted twice with 200 mL 2N NaOH The precipitate obtained was filtered dried