3-bromo-2,2-bis(bromomethyl)propan-1-ol

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

実験手順: The compounds which constitute one of the starting reagents according to the present invention, consist of dibromoneopentyl glycol 2-bromomethyl-2-hydroxymethylpropane-1,3-diol, 2-bromomethyl-2-hydroxymethyl-1,3-dibromopropane, or mixtures thereof. As known, commercial DBNPG is obtained by the bromination of pentaerythritols. Depending on the method of operation, the product may be a relatively pure DBNPG or mixtures of 2-bromomethyl-2-hydroxymethylpropane-1,3-diol, 2,2-bis(bromomethyl)propane-1,3-diol, and 2-bromomethyl-2-hydroxymethyl-1,3-dibromopropane, wherein an average of 1.7 to 2.5 of the hydroxyls per molecule have been replaced by bromine. This represents a mixture of 2-bromomethyl-2-hydroxymethylpropane-1,3-diol,2,2-bis(bromomethyl)propane-1,3-diol and 2-bromomethyl-2-hydroxymethyl-1,3-dibromopropane whose concentration ranges vary from 5% 2-bromomethyl-2-hydroxymethylpropane-1,3-diol, 80% 2,2-bis(bromomethyl)propane-1,3-diol and 15% 2-bromomethyl-2-hydroxymethyl -1,3-dibromopane to 15% 2-bromomethyl-2-hydroxymethylpropane-1,3-diol, 80% 2,2-bis(bromomethyl)propane-1,3-diol, and 5% 2-bromomethyl-2-hydroxymethyl-1,3-dibromopropane. The residual hydroxyl groups of this mixture of compounds can also be readily hydroxymethylated. Therefore instead of utilizing pure DBNPG, the latter can be successfully replaced by the less expensive mixtures.

反応条件: temp:22.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Sodium hydride (1.67 g, 42 mmol) was added carefully to 3-bromo-2,2-bis(bromomethyl)propanol (9.75 g, 30 mmol) and allyl bromide (12.9 ml, 150 mmol) in dry and degassed DMF (40 ml) under nitrogen at 0° C. The temperature was then increased to room temperature (22° C.) and the reaction mixture was stirred for another 3 h. The reaction mixture was then carefully added to an aqueous saturated NH4Cl (50 ml). The H2O-phase was then extracted with diethyl ether (2×50 ml) and the combined organic phases were washed with H2O (5×50 ml) and then brine (50 ml). The organic phase was dried with Na2SO4 followed by filtration. The volatile materials were removed at reduced pressure to give a pale yellow oil (9.7 g). Column chromatography on silica (heptane:EtOAc 9:1) gave 6.6 g (62%) of the product as a clear oil. 1H-NMR (CDCl3); 5.93 (m, 1H), 5.28 (m, 2H), 4.05 (d, 2H), 3.58 (s, 6H), 3.52 (s, 2H). in dry degassed DMF (40 ml) under nitrogen at 0° C The reaction mixture was then carefully added to an aqueous saturated NH4Cl (50 ml) The H2O-phase was then extracted with diethyl ether (2×50 ml) the combined organic phases were washed with H2O (5×50 ml) The organic phase was dried with Na2SO4 followed by filtration The volatile materials were removed at reduced pressure

反応条件: temp:22.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Sodium hydride (1.67 g, 42 mmol) was added carefully to 3-bromo-2,2-bis(bromomethyl)propanol (9.75 g, 30 mmol) and allyl bromide (12.9 ml, 150 mmol) in dry and degassed DMF (40 ml) under nitrogen at 0° C. The temperature was then increased to room temperature (22° C.) and the reaction mixture was stirred for another 3 h. The reaction mixture was then carefully added to an aqueous saturated NH4Cl (50 ml). The H2O-phase was then extracted with diethyl ether (2×50 ml) and the combined organic phases were washed with H2O (5×50 ml) and then brine (50 ml). The organic phase was dried with Na2SO4 followed by filtration. The volatile materials were removed at reduced pressure to give a pale yellow oil (9.7 g). Column chromatography on silica (heptane:EtOAc 9:1) gave 6.6 g (62%) of the product as a clear oil. 1H-NMR (CDCl3); 5.93 (m, 1H), 5.28 (m, 2H), 4.05 (d, 2H), 3.58 (s, 6H), 3.52 (s, 2H). in dry degassed DMF (40 ml) under nitrogen at 0° C The reaction mixture was then carefully added to an aqueous saturated NH4Cl (50 ml) The H2O-phase was then extracted with diethyl ether (2×50 ml) the combined organic phases were washed with H2O (5×50 ml) The organic phase was dried with Na2SO4 followed by filtration The volatile materials were removed at reduced pressure

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

実験手順: To a solution of 3-bromo-2,2-bis(bromomethyl)propanol (127) (3.25 g, 10 mmol) and potassium hydroxide (1.12 g, 20 mmol, in 10 mL water) in EtOH (20 mL) were added toluene-4-sulfonamide (3.76 g, 22 mmol). The reaction mixture was refluxed for 2 h, evaporated to remove EtOH then diluted with EAOAc (20 mL), washed with H2O (20 mL). The organic layer was washed with brine (20 mL), dried over Na2SO4, and filtered, evaporated to give the product to give 6-(toluene-4-sulfonyl)-2-oxa-6-aza-spiro[3.3]heptane (128) (1.6 g, 6.3 mmol, yield: 63%). The reaction mixture was refluxed for 2 h evaporated to remove EtOH then diluted with EAOAc (20 mL) washed with H2O (20 mL) The organic layer was washed with brine (20 mL) dried over Na2SO4 filtered evaporated to give the product

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

実験手順: To a solution of KOH (4.98 g, 0.089 mol) and 4-methylbenzenesulfonamide (5.7 g, 0.033 mol) in 90 ml of ethanol, 3-bromo-2,2-bis(bromomethyl)propan-1-ol (9 g, 0.0277 mol) was added at room temperature and the reaction mixture was heated to reflux for 45 h. The solvent was removed by evaporation, 75 ml of 1 M KOH were added and the white suspension was left to stir for another 2 h at room temperature. The mixture was filtered and the white filter cake was rinsed with water until the washing water was neutral. The filter cake was dried under high vacuum to give 4.87 g 6-toluene-4-sulfonyl-2-oxa-6-azaspiro[3.3]heptane (69%) as a white solid. 1H NMR (300 MHz, CDCl3) δ 7.70-7.68 (m, 2H), 7.36-7.34 (m, 2H), 4.58 (s, 4H), 3.90 (s, 4H), 2.45 (s, 3H). the reaction mixture was heated to reflux for 45 h The solvent was removed by evaporation, 75 ml of 1 M KOH were added the white suspension was left The mixture was filtered the white filter cake was rinsed with water until the washing water The filter cake was dried under high vacuum

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

実験手順: The compounds which constitute one of the starting reagents according to the present invention, consist of dibromoneopentyl glycol 2-bromomethyl-2-hydroxymethylpropane-1,3-diol, 2-bromomethyl-2-hydroxymethyl-1,3-dibromopropane, or mixtures thereof. As known, commercial DBNPG is obtained by the bromination of pentaerythritols. Depending on the method of operation, the product may be a relatively pure DBNPG or mixtures of 2-bromomethyl-2-hydroxymethylpropane-1,3-diol, 2,2-bis(bromomethyl)propane-1,3-diol, and 2-bromomethyl-2-hydroxymethyl-1,3-dibromopropane, wherein an average of 1.7 to 2.5 of the hydroxyls per molecule have been replaced by bromine. This represents a mixture of 2-bromomethyl-2-hydroxymethylpropane-1,3-diol,2,2-bis(bromomethyl)propane-1,3-diol and 2-bromomethyl-2-hydroxymethyl-1,3-dibromopropane whose concentration ranges vary from 5% 2-bromomethyl-2-hydroxymethylpropane-1,3-diol, 80% 2,2-bis(bromomethyl)propane-1,3-diol and 15% 2-bromomethyl-2-hydroxymethyl -1,3-dibromopane to 15% 2-bromomethyl-2-hydroxymethylpropane-1,3-diol, 80% 2,2-bis(bromomethyl)propane-1,3-diol, and 5% 2-bromomethyl-2-hydroxymethyl-1,3-dibromopropane. The residual hydroxyl groups of this mixture of compounds can also be readily hydroxymethylated. Therefore instead of utilizing pure DBNPG, the latter can be successfully replaced by the less expensive mixtures.

反応条件: temp:22.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Sodium hydride (1.67 g, 42 mmol) was added carefully to 3-bromo-2,2-bis(bromomethyl)propanol (9.75 g, 30 mmol) and allyl bromide (12.9 ml, 150 mmol) in dry and degassed DMF (40 ml) under nitrogen at 0° C. The temperature was then increased to room temperature (22° C.) and the reaction mixture was stirred for another 3 h. The reaction mixture was then carefully added to an aqueous saturated NH4Cl (50 ml). The H2O-phase was then extracted with diethyl ether (2×50 ml) and the combined organic phases were washed with H2O (5×50 ml) and then brine (50 ml). The organic phase was dried with Na2SO4 followed by filtration. The volatile materials were removed at reduced pressure to give a pale yellow oil (9.7 g). Column chromatography on silica (heptane:EtOAc 9:1) gave 6.6 g (62%) of the product as a clear oil. 1H-NMR (CDCl3); 5.93 (m, 1H), 5.28 (m, 2H), 4.05 (d, 2H), 3.58 (s, 6H), 3.52 (s, 2H). in dry degassed DMF (40 ml) under nitrogen at 0° C The reaction mixture was then carefully added to an aqueous saturated NH4Cl (50 ml) The H2O-phase was then extracted with diethyl ether (2×50 ml) the combined organic phases were washed with H2O (5×50 ml) The organic phase was dried with Na2SO4 followed by filtration The volatile materials were removed at reduced pressure