[4,5-二氯-2-(羟甲基)苯基]甲醇

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A 1.24 g portion of 4,5-dichlorophthalic acid is dissolved in 40 mL anhydrous tetahydrofuran and the solution is cooled to 0° C. To this solution is slowly added 4 mL of borane-methyl sulfide. The reaction flask is first warmed to room temperature, then heated to reflux for 12 hours. The product mixture is cooled to 0° C., then slowly quenched with 50 mL methyl alcohol. Following removal of the solvent, the residue is partitioned between 40 mL water, and 100 mL 1:1 ethyl acetate tetrahydrofuran. The organic layer is washed with 30 mL brine, then dried over magnesium sulfate. Purification by silica gel chromatography (2:1 ethyl acetate/hexane) affords 1.01 g of the desired product as a white solid, m.p. 128°-136° C. The reaction flask is first warmed to room temperature heated to reflux for 12 hours The product mixture is cooled to 0° C. slowly quenched with 50 mL methyl alcohol removal of the solvent the residue is partitioned between 40 mL water, and 100 mL 1:1 ethyl acetate tetrahydrofuran The organic layer is washed with 30 mL brine dried over magnesium sulfate Purification by silica gel chromatography (2:1 ethyl acetate/hexane)

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A 1.24 g portion of 4,5-dichlorophthalic acid is dissolved in 40 mL anhydrous tetahydrofuran and the solution is cooled to 0° C. To this solution is slowly added 4 mL of borane-methyl sulfide. The reaction flask is first warmed to room temperature, then heated to reflux for 12 hours. The product mixture is cooled to 0° C., then slowly quenched with 50 mL methyl alcohol. Following removal of the solvent, the residue is partitioned between 40 mL water, and 100 mL 1:1 ethyl acetate tetrahydrofuran. The organic layer is washed with 30 mL brine, then dried over magnesium sulfate. Purification by silica gel chromatography (2:1 ethyl acetate/hexane) affords 1.01 g of the desired product as a white solid, m.p. 128°-136° C. The reaction flask is first warmed to room temperature heated to reflux for 12 hours The product mixture is cooled to 0° C. slowly quenched with 50 mL methyl alcohol removal of the solvent the residue is partitioned between 40 mL water, and 100 mL 1:1 ethyl acetate tetrahydrofuran The organic layer is washed with 30 mL brine dried over magnesium sulfate Purification by silica gel chromatography (2:1 ethyl acetate/hexane)

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A 1.24 g portion of 4,5-dichlorophthalic acid is dissolved in 40 mL anhydrous tetahydrofuran and the solution is cooled to 0° C. To this solution is slowly added 4 mL of borane-methyl sulfide. The reaction flask is first warmed to room temperature, then heated to reflux for 12 hours. The product mixture is cooled to 0° C., then slowly quenched with 50 mL methyl alcohol. Following removal of the solvent, the residue is partitioned between 40 mL water, and 100 mL 1:1 ethyl acetate tetrahydrofuran. The organic layer is washed with 30 mL brine, then dried over magnesium sulfate. Purification by silica gel chromatography (2:1 ethyl acetate/hexane) affords 1.01 g of the desired product as a white solid, m.p. 128°-136° C. The reaction flask is first warmed to room temperature heated to reflux for 12 hours The product mixture is cooled to 0° C. slowly quenched with 50 mL methyl alcohol removal of the solvent the residue is partitioned between 40 mL water, and 100 mL 1:1 ethyl acetate tetrahydrofuran The organic layer is washed with 30 mL brine dried over magnesium sulfate Purification by silica gel chromatography (2:1 ethyl acetate/hexane)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of dimethyl 4,5-dichlorophthalate A5 (98.86 g, 375.78 mmol) in tetrahydrofuran (150 mL) is added dropwise over 1 h to a mechanically stirred suspension of LAH (20.8 g, 548.1 mmol) in tetrahydrofuran (1.5 L). During the addition, the reaction is cooled in an ice-water bath. When the addition is completed, the reaction is stirred overnight at RT. The excess LAH is decomposed by cautious addition of water (20 mL), 10% aqueous NaOH (40 mL) and water (20 mL). The solids are removed by filtration through a celite pad and washed with tetrahydrofuran. The combined filtrate and wash is concentrated in vacuo on a rotary evaporator to afford crude 251 as white solid that is purified by crystallization from acetone (150 mL)-heptane (150 mL). The crystals are collected by filtration, washed with heptane and dried to give 4,5-dichloro-1,2-bis(hydroxymethyl)benzene (37.2 g). The combined filtrate and wash afforded a second crop of 251 (18.8 g, 24.1%). [L. A. Levy, Synth. Commun., 13, 639-648 (1983); O. Farooq, Synthesis, 1035-1036 (1994)] During the addition the reaction is cooled in an ice-water bath When the addition The solids are removed by filtration through a celite pad washed with tetrahydrofuran The combined filtrate and wash is concentrated in vacuo on a rotary evaporator

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred solution of borane tetrahydrofuran complex (45 mL of 1.5 M solution in tetrahydrofuran/diethyl ether) cooled to 0° C. under nitrogen was added a solution of 4,5-dichlorophthalic acid (5.013 g; 21.1 mmol) in tetrahydrofuran (35 mL) dropwise over a 20 minute period. At the end of the addition, the mixture was allowed to stir for 2.5 h at 0° C. The mixture was quenched by slow addition of methanol until gas evolution ceased. The mixture was allowed to stir at room temperature for 30 minutes and the solvent removed in vacuo. The residue was taken up into ethyl acetate, washed with saturated sodium bicarbonate solution followed by brine solution. The organic extract was dried (sodium sulfate), filtered and concentrated in vacuo to give 4.41 g (100%) of 4,5-dichloro-1,2-di-hydroxymethyl benzene as a white solid: ES-LRMS calcd for C8H7C12O2 (M+−1) 205, found 205. At the end of the addition The mixture was quenched by slow addition of methanol until gas evolution to stir at room temperature for 30 minutes the solvent removed in vacuo washed with saturated sodium bicarbonate solution The organic extract was dried (sodium sulfate) filtered concentrated in vacuo

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A 1.24 g portion of 4,5-dichlorophthalic acid is dissolved in 40 mL anhydrous tetahydrofuran and the solution is cooled to 0° C. To this solution is slowly added 4 mL of borane-methyl sulfide. The reaction flask is first warmed to room temperature, then heated to reflux for 12 hours. The product mixture is cooled to 0° C., then slowly quenched with 50 mL methyl alcohol. Following removal of the solvent, the residue is partitioned between 40 mL water, and 100 mL 1:1 ethyl acetate tetrahydrofuran. The organic layer is washed with 30 mL brine, then dried over magnesium sulfate. Purification by silica gel chromatography (2:1 ethyl acetate/hexane) affords 1.01 g of the desired product as a white solid, m.p. 128°-136° C. MS(Hi res): m/z Calcd for C8H8Cl2O2 205.9901 Found 205.9872 The reaction flask is first warmed to room temperature heated to reflux for 12 hours The product mixture is cooled to 0° C. slowly quenched with 50 mL methyl alcohol removal of the solvent the residue is partitioned between 40 mL water, and 100 mL 1:1 ethyl acetate tetrahydrofuran The organic layer is washed with 30 mL brine dried over magnesium sulfate Purification by silica gel chromatography (2:1 ethyl acetate/hexane)

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A 1.24 g portion of 4,5-dichlorophthalic acid is dissolved in 40 mL anhydrous tetahydrofuran and the solution is cooled to 0° C. To this solution is slowly added 4 mL of borane-methyl sulfide. The reaction flask is first warmed to room temperature, then heated to reflux for 12 hours. The product mixture is cooled to 0° C., then slowly quenched with 50 mL methyl alcohol. Following removal of the solvent, the residue is partitioned between 40 mL water, and 100 mL 1:1 ethyl acetate tetrahydrofuran. The organic layer is washed with 30 mL brine, then dried over magnesium sulfate. Purification by silica gel chromatography (2:1 ethyl acetate/hexane) affords 1.01 g of the desired product as a white solid, m.p. 128°-136° C. MS(Hi res): m/z Calcd for C8H8Cl2O2 205.9901 Found 205.9872 The reaction flask is first warmed to room temperature heated to reflux for 12 hours The product mixture is cooled to 0° C. slowly quenched with 50 mL methyl alcohol removal of the solvent the residue is partitioned between 40 mL water, and 100 mL 1:1 ethyl acetate tetrahydrofuran The organic layer is washed with 30 mL brine dried over magnesium sulfate Purification by silica gel chromatography (2:1 ethyl acetate/hexane)

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A 1.24 g portion of 4,5-dichlorophthalic acid is dissolved in 40 mL anhydrous tetahydrofuran and the solution is cooled to 0° C. To this solution is slowly added 4 mL of borane-methyl sulfide. The reaction flask is first warmed to room temperature, then heated to reflux for 12 hours. The product mixture is cooled to 0° C., then slowly quenched with 50 mL methyl alcohol. Following removal of the solvent, the residue is partitioned between 40 mL water, and 100 mL 1:1 ethyl acetate tetrahydrofuran. The organic layer is washed with 30 mL brine, then dried over magnesium sulfate. Purification by silica gel chromatography (2:1 ethyl acetate/hexane) affords 1.01 g of the desired product as a white solid, m.p. 128°-136° C. The reaction flask is first warmed to room temperature heated to reflux for 12 hours The product mixture is cooled to 0° C. slowly quenched with 50 mL methyl alcohol removal of the solvent the residue is partitioned between 40 mL water, and 100 mL 1:1 ethyl acetate tetrahydrofuran The organic layer is washed with 30 mL brine dried over magnesium sulfate Purification by silica gel chromatography (2:1 ethyl acetate/hexane)

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a dry 500 mL three-necked flask equipped with a thermometer and a dropping funnel, was added a solution of dry CH2Cl2 (60 mL) and oxalyl chloride (2.7 mL, 34.35 mmol) under Ar. The stirred solution was cooled to −78° C. and a solution of DMSO (4.24 mL, 59.67 mmol) in CH2Cl2 (10 mL) was added dropwise. The solution was stirred for 3-5 min. and 4,5-dichlorobenzene-1,2-dimethanol (2.0 g, 9.71 mmol) dissolved in CH2Cl2-DMSO mixture (25 mL) was added dropwise. The reaction was allowed to continue for 0.5 h and then triethylamine (24 mL, 0.18 mol) was slowly added at −78° C. the reaction mixture was allowed to stir for 10 min. and then slowly warmed to RT. Ice-cold water (50 mL) was added to the reaction mixture and the aqueous layer extracted with CH2Cl2 (2×50 mL) and then dried over CaCl2. Removal of solvent gave the yellow solids of 4,5-dichlorobenzene-1,2-dicarbaldehyde in 78% yield (1.53 g). 1H NMR (500 MHz, CDCl3): δ 10.46 (s, 2H), 8.05 (s, 2H). 13C NMR (125.68 MHz, CDCl3): δ 189.92, 139.07, 135.32, 133.08. To a dry 500 mL three-necked flask equipped with a thermometer and a dropping funnel was added dropwise to continue for 0.5 h to stir for 10 min. slowly warmed to RT the aqueous layer extracted with CH2Cl2 (2×50 mL) dried over CaCl2 Removal of solvent

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a slurry of LiAlH4 (1.61 g, 42.54 mmol) in dry THF (75 mL) cooled to −78° C., a solution of dimethyl 4,5-dichlorobenzene-1,2-dicarboxylic acid (5.0 g, 21.27 mmol) in dry THF (25 mL) was added dropwise over a period of 1 h. After slow warming of the system to RT over a period of 2 h the mixture was heated at reflux overnight. The heterogeneous mixture was then cooled to 0° C. and sodium hydroxide solution (15%, 100 mL) cooled to 0° C. was very slowly added. This was followed by addition of ice-cold water (100 mL), and the reaction mixture was diluted with diethyl ether (200 mL) and the organic layer was separated, dried over MgSO4. Removal of solvents gave a white solid which was passed through a pad of silica gel to afford pure product in 88% yield (3.85 g). 1H NMR (500 MHz, CDCl3): δ 7.60 (s, 2H), 4.65 (s, 4H), 4.50 (bs, 2H). was heated at reflux overnight The heterogeneous mixture was then cooled to 0° C. was very slowly added the organic layer was separated dried over MgSO4 Removal of solvents gave a white solid which to afford pure product in 88% yield (3.85 g)

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A 1.24 g portion of 4,5-dichlorophthalic acid is dissolved in 40 mL anhydrous tetahydrofuran and the solution is cooled to 0° C. To this solution is slowly added 4 mL of borane-methyl sulfide. The reaction flask is first warmed to room temperature, then heated to reflux for 12 hours. The product mixture is cooled to 0° C., then slowly quenched with 50 mL methyl alcohol. Following removal of the solvent, the residue is partitioned between 40 mL water, and 100 mL 1:1 ethyl acetate tetrahydrofuran. The organic layer is washed with 30 mL brine, then dried over magnesium sulfate. Purification by silica gel chromatography (2:1 ethyl acetate/hexane) affords 1.01 g of the desired product as a white solid, m.p. 128°-136° C. The reaction flask is first warmed to room temperature heated to reflux for 12 hours The product mixture is cooled to 0° C. slowly quenched with 50 mL methyl alcohol removal of the solvent the residue is partitioned between 40 mL water, and 100 mL 1:1 ethyl acetate tetrahydrofuran The organic layer is washed with 30 mL brine dried over magnesium sulfate Purification by silica gel chromatography (2:1 ethyl acetate/hexane)

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A 1.24 g portion of 4,5-dichlorophthalic acid is dissolved in 40 mL anhydrous tetahydrofuran and the solution is cooled to 0° C. To this solution is slowly added 4 mL of borane-methyl sulfide. The reaction flask is first warmed to room temperature, then heated to reflux for 12 hours. The product mixture is cooled to 0° C., then slowly quenched with 50 mL methyl alcohol. Following removal of the solvent, the residue is partitioned between 40 mL water, and 100 mL 1:1 ethyl acetate tetrahydrofuran. The organic layer is washed with 30 mL brine, then dried over magnesium sulfate. Purification by silica gel chromatography (2:1 ethyl acetate/hexane) affords 1.01 g of the desired product as a white solid, m.p. 128°-136° C. The reaction flask is first warmed to room temperature heated to reflux for 12 hours The product mixture is cooled to 0° C. slowly quenched with 50 mL methyl alcohol removal of the solvent the residue is partitioned between 40 mL water, and 100 mL 1:1 ethyl acetate tetrahydrofuran The organic layer is washed with 30 mL brine dried over magnesium sulfate Purification by silica gel chromatography (2:1 ethyl acetate/hexane)