[3,5-bis(hydroxymethyl)phenyl]methanol

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

Procedure: A 3-liter, round-bottom flask equipped with an overhead stirrer, an addition funnel and a reflux condenser was charged with lithium aluminum hydride (49.7 grams, 1.31 mol) and anhydrous THF (500 ml) under nitrogen atmosphere. The resulting suspension was slowly heated to reflux and a solution of trimethyl-1,3,5-benzenetricarboxylate (100.0 grams, 0.40 mol) in anhydrous THF (1.0 liter) was added dropwise thereto while maintaining a gentle reflux (3 hours). The resulting gray suspension was stirred under reflux for additional 7 hours and then cooled in an external ice-water bath. The excess lithium aluminum hydride was hydrolyzed by dropwise addition of water (50 ml, 45 minutes), then 15% NaOH (50 ml, slow stream), and finally more water (150 ml, slow stream). The resulting suspension was stirred at ambient temperature for 14 hours. The solids were filtered off and the filtrate was concentrated under high vacuum to obtain a colorless oil which slowly solidified to afford 1,3,5-tris(hydroxylmethyl)benzene (62.3 grams, 94%) as a white solid. The 1H NMR and 13C NMR spectra were consistent with the assigned structure. A 3-liter, round-bottom flask equipped with an overhead stirrer, an addition funnel and a reflux condenser The resulting suspension was slowly heated to reflux while maintaining a gentle reflux (3 hours) under reflux for additional 7 hours cooled in an external ice-water bath The resulting suspension was stirred at ambient temperature for 14 hours The solids were filtered off the filtrate was concentrated under high vacuum to obtain a colorless oil which

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

Procedure: A 3-liter, round-bottom flask equipped with an overhead stirrer, an addition funnel and a reflux condenser was charged with lithium aluminum hydride (49.7 grams, 1.31 mol) and anhydrous THF (500 ml) under nitrogen atmosphere. The resulting suspension was slowly heated to reflux and a solution of trimethyl-1,3,5-benzenetricarboxylate (100.0 grams, 0.40 mol) in anhydrous THF (1.0 liter) was added dropwise thereto while maintaining a gentle reflux (3 hours). The resulting gray suspension was stirred under reflux for additional 7 hours and then cooled in an external ice-water bath. The excess lithium aluminum hydride was hydrolyzed by dropwise addition of water (50 ml, 45 minutes), then 15% NaOH (50 ml, slow stream), and finally more water (150 ml, slow stream). The resulting suspension was stirred at ambient temperature for 14 hours. The solids were filtered off and the filtrate was concentrated under high vacuum to obtain a colorless oil which slowly solidified to afford 1,3,5-tris(hydroxylmethyl)benzene (62.3 grams, 94%) as a white solid. The 1H NMR and 13C NMR spectra were consistent with the assigned structure. A 3-liter, round-bottom flask equipped with an overhead stirrer, an addition funnel and a reflux condenser The resulting suspension was slowly heated to reflux while maintaining a gentle reflux (3 hours) under reflux for additional 7 hours cooled in an external ice-water bath The resulting suspension was stirred at ambient temperature for 14 hours The solids were filtered off the filtrate was concentrated under high vacuum to obtain a colorless oil which

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

Procedure: A 3-liter, round-bottom flask equipped with an overhead stirrer, an addition funnel and a reflux condenser was charged with lithium aluminum hydride (49.7 grams, 1.31 mol) and anhydrous THF (500 ml) under nitrogen atmosphere. The resulting suspension was slowly heated to reflux and a solution of trimethyl-1,3,5-benzenetricarboxylate (100.0 grams, 0.40 mol) in anhydrous THF (1.0 liter) was added dropwise thereto while maintaining a gentle reflux (3 hours). The resulting gray suspension was stirred under reflux for additional 7 hours and then cooled in an external ice-water bath. The excess lithium aluminum hydride was hydrolyzed by dropwise addition of water (50 ml, 45 minutes), then 15% NaOH (50 ml, slow stream), and finally more water (150 ml, slow stream). The resulting suspension was stirred at ambient temperature for 14 hours. The solids were filtered off and the filtrate was concentrated under high vacuum to obtain a colorless oil which slowly solidified to afford 1,3,5-tris(hydroxylmethyl)benzene (62.3 grams, 94%) as a white solid. The 1H NMR and 13C NMR spectra were consistent with the assigned structure. A 3-liter, round-bottom flask equipped with an overhead stirrer, an addition funnel and a reflux condenser The resulting suspension was slowly heated to reflux while maintaining a gentle reflux (3 hours) under reflux for additional 7 hours cooled in an external ice-water bath The resulting suspension was stirred at ambient temperature for 14 hours The solids were filtered off the filtrate was concentrated under high vacuum to obtain a colorless oil which

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

Procedure: A 3-liter, round-bottom flask equipped with an overhead stirrer, an addition funnel and a reflux condenser was charged with lithium aluminum hydride (49.7 grams, 1.31 mol) and anhydrous THF (500 ml) under nitrogen atmosphere. The resulting suspension was slowly heated to reflux and a solution of trimethyl-1,3,5-benzenetricarboxylate (100.0 grams, 0.40 mol) in anhydrous THF (1.0 liter) was added dropwise thereto while maintaining a gentle reflux (3 hours). The resulting gray suspension was stirred under reflux for additional 7 hours and then cooled in an external ice-water bath. The excess lithium aluminum hydride was hydrolyzed by dropwise addition of water (50 ml, 45 minutes), then 15% NaOH (50 ml, slow stream), and finally more water (150 ml, slow stream). The resulting suspension was stirred at ambient temperature for 14 hours. The solids were filtered off and the filtrate was concentrated under high vacuum to obtain a colorless oil which slowly solidified to afford 1,3,5-tris(hydroxylmethyl)benzene (62.3 grams, 94%) as a white solid. The 1H NMR and 13C NMR spectra were consistent with the assigned structure. A 3-liter, round-bottom flask equipped with an overhead stirrer, an addition funnel and a reflux condenser The resulting suspension was slowly heated to reflux while maintaining a gentle reflux (3 hours) under reflux for additional 7 hours cooled in an external ice-water bath The resulting suspension was stirred at ambient temperature for 14 hours The solids were filtered off the filtrate was concentrated under high vacuum to obtain a colorless oil which

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

Procedure: A 3-liter, round-bottom flask equipped with an overhead stirrer, an addition funnel and a reflux condenser was charged with lithium aluminum hydride (49.7 grams, 1.31 mol) and anhydrous THF (500 ml) under nitrogen atmosphere. The resulting suspension was slowly heated to reflux and a solution of trimethyl-1,3,5-benzenetricarboxylate (100.0 grams, 0.40 mol) in anhydrous THF (1.0 liter) was added dropwise thereto while maintaining a gentle reflux (3 hours). The resulting gray suspension was stirred under reflux for additional 7 hours and then cooled in an external ice-water bath. The excess lithium aluminum hydride was hydrolyzed by dropwise addition of water (50 ml, 45 minutes), then 15% NaOH (50 ml, slow stream), and finally more water (150 ml, slow stream). The resulting suspension was stirred at ambient temperature for 14 hours. The solids were filtered off and the filtrate was concentrated under high vacuum to obtain a colorless oil which slowly solidified to afford 1,3,5-tris(hydroxylmethyl)benzene (62.3 grams, 94%) as a white solid. The 1H NMR and 13C NMR spectra were consistent with the assigned structure. A 3-liter, round-bottom flask equipped with an overhead stirrer, an addition funnel and a reflux condenser The resulting suspension was slowly heated to reflux while maintaining a gentle reflux (3 hours) under reflux for additional 7 hours cooled in an external ice-water bath The resulting suspension was stirred at ambient temperature for 14 hours The solids were filtered off the filtrate was concentrated under high vacuum to obtain a colorless oil which

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

Procedure: A 3-liter, round-bottom flask equipped with an overhead stirrer, an addition funnel and a reflux condenser was charged with lithium aluminum hydride (49.7 grams, 1.31 mol) and anhydrous THF (500 ml) under nitrogen atmosphere. The resulting suspension was slowly heated to reflux and a solution of trimethyl-1,3,5-benzenetricarboxylate (100.0 grams, 0.40 mol) in anhydrous THF (1.0 liter) was added dropwise thereto while maintaining a gentle reflux (3 hours). The resulting gray suspension was stirred under reflux for additional 7 hours and then cooled in an external ice-water bath. The excess lithium aluminum hydride was hydrolyzed by dropwise addition of water (50 ml, 45 minutes), then 15% NaOH (50 ml, slow stream), and finally more water (150 ml, slow stream). The resulting suspension was stirred at ambient temperature for 14 hours. The solids were filtered off and the filtrate was concentrated under high vacuum to obtain a colorless oil which slowly solidified to afford 1,3,5-tris(hydroxylmethyl)benzene (62.3 grams, 94%) as a white solid. The 1H NMR and 13C NMR spectra were consistent with the assigned structure. A 3-liter, round-bottom flask equipped with an overhead stirrer, an addition funnel and a reflux condenser The resulting suspension was slowly heated to reflux while maintaining a gentle reflux (3 hours) under reflux for additional 7 hours cooled in an external ice-water bath The resulting suspension was stirred at ambient temperature for 14 hours The solids were filtered off the filtrate was concentrated under high vacuum to obtain a colorless oil which

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirring solution of trimethyl 1,3,5-benzenetricarboxylate (10.45 g, 41.4 mmol) in 70 ml of anhydrous THF is added at room temperature a 10M solution of borane-methyl sulfide complex (25 ml, 248 mmol) and the solution is heated to reflux for 3 h. The mixture is then added slowly to 50 ml of MeOH and the resulting mixture is heated at 70° C. for 10 min to remove the methyl sulfide. Evaporation of solvent, washing twice with 50 ml of MeOH and evaporation of MeOH gives 1,3,5-tris(hydroxymethyl)benzene (6.96 g, 100%). 1H NMR (D2O): δ 4.52 (6H, s), 7.15 (3H, s). the solution is heated to reflux for 3 h to remove the methyl sulfide Evaporation of solvent washing twice with 50 ml of MeOH and evaporation of MeOH

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of triphenylphosphine (577 mg, 2.2 mmol) in anhydrous THF (5 mL) was added diethyl azodicarboxylate (2.2 M in toluene, 791 μL, 1.7 mmol) dropwise at 0° C. After stirred at 0° C. for 50 minutes, a solution of 1,3,5-tri(hydroxymethyl)benzene (269 mg, 1.6 mmol, prepared by reduction of trimethyl 1,3,5-benzenetricarboxylate with lithium aluminum hydride in THF, co-evaporated with dry benzene and dried on high vacuum for couple hours before use) and thioacetic acid (108 μL, 1.45 mmol) in dry THF (4 mL) was added dropwise. After 1 hour, the ice/water bath was removed and the reaction was stirred at room temperature for 15 hours. The solvents were removed by rotary evaporation in vacuo. The residue was purified by flash chromatography to give 5-acetylthiomethyl-1,3-bis(hydroxymethyl)-benzene as colorless solid (110 mg). 1H NMR (400 Hz, CDCl3): δ 7.13-6.99 (m, 3H), 4.45 (apt, J=20.4 Hz, 4H), 3.98 (apt, J=20.4 Hz, 4H), 3.73 (bs, 2H), 2.24 (apt, J=20.4 Hz, 3H); MS (ESI): m/z 249.0 (M+Na)+. After 1 hour the ice/water bath was removed the reaction was stirred at room temperature for 15 hours The solvents were removed by rotary evaporation in vacuo The residue was purified by flash chromatography

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

Procedure: 1,3,5-Tris(hydroxymethyl)benzene 15 (927 mg, 5.12 mmol) was suspended in CH2Cl2 (25 mL) and solid PCC (5.94 g, 27.6 mmol) was added. After 30 minutes of stirring, the reaction was diluted with acetone (10 mL) and was allowed to stir for 3 hr at RT. TLC (10% MeOH, 90% CH2Cl2 Rf=0.50) was used to determine if the reaction was complete. After the reaction was complete, the precipitated chromium salts were filtered off and washed with CH2Cl2. The aqueous layer was extracted 3 times in CH2Cl2 and saturated Na2CO3. The organic layers were combined and dried over anhydrous Na2SO4, filtered, and concentrated. Flash column chromatography (100% CH2Cl2 Rf=0.4) gave 16 (272 mg, 1.68 mmol, 33%). 1H NMR (CDCl3): δ 10.21 (s, 3H), 8.63 (s, 3H). to stir for 3 hr at RT the precipitated chromium salts were filtered off washed with CH2Cl2 The aqueous layer was extracted 3 times in CH2Cl2 dried over anhydrous Na2SO4 filtered concentrated

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

Procedure: Trimethyl-1,3,5-benzenetricarboxylate 14 (1.98 g, 7.83 mmol) in dry THF (30 mL) was added through a pressure-equalized addition funnel into a stirring suspension of LiAlH4 (0.95 g, 24.9 mmol) in dry THF (65 mL) at 0° C. under an argon atmosphere. The mixture was allowed to warm to rt and stirred for 4 hours. 1H NMR (CDCl3) was used to monitor the reaction. After determining a large amount of starting material remained, additional LiAlH4 (0.50 g, 13.1 mmol) was added to the reaction mixture and the reaction was allowed to proceed at RT for an additional 4 hours. 1H NMR (CDCl3) was used to determine if reaction was complete. After the reaction was complete, MeOH (25 mL) was used to quench the reaction. The suspension was filtered using Celite and the Celite was washed with MeOH (100 mL). The filtrate was concentrated under reduced pressure. The residue was stirred in THF (30 mL), KHSO4 (3.53 g, 26 mmol) and Celite (1.53 g, 25.4 mmol) for 30 minutes. The suspension was filtered and washed with MeOH (50 mL). Solvents were removed under reduced pressure. The resulting solid was dissolved in hot ethyl acetate and filtered. The solid that remained at the filter was collected, dried and to yield triol 15 (0.954 g, 5.68 mmol, 73%). 1H NMR (DMSO): δ 7.22 (s, 3H), 5.17 (br s, 3H), 4.48 (s, 6H). the reaction to proceed at RT for an additional 4 hours to determine if reaction to quench the reaction The suspension was filtered the Celite was washed with MeOH (100 mL) The filtrate was concentrated under reduced pressure The residue was stirred in THF (30 mL) The suspension was filtered washed with MeOH (50 mL) Solvents were removed under reduced pressure The resulting solid was dissolved in hot ethyl acetate filtered was collected dried

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

Procedure: A solution of trimethyl 1,3,5-benzenetricarboxylate (8.83 g, 0.035 M; Aldrich) in THF (125 mL) is added dropwise over a period of 45 minutes to a stirred mixture of lithium aluminum hydride (3.98 g, 0.105 M) and dry THF (150 mL) under a nitrogen atmosphere. The initial phase of the addition results in vigorous reaction and consequently the addition is very slow at first. As the ester solution is added, an orange mass forms when the drops came in contact with the LiAlH4 mixture. A yellowish-green mixture results and is stirred at room temperature. The excess LiAlH4 is quenched carefully by the addition of ethyl acetate and the resulting mixture is acidified with aqueous 2N HCl solution until the pH is <3 and aluminum salts have dissolved. The layers are separated and the aqueous layer is extracted 3 times with additional ethyl acetate and then with methylene chloride. The organic extract layers are dried (sodium sulfate), filtered, and concentrated under reduced pressure to give a white solid (2.98 g, 51%). Recrystallization from acetonitrile-methylene chloride gives the title compound as white crystals (1.13 g) which appear to be hygroscopic when collected by suction filtration. The crystals are dried several days over P2O5 in a vacuum desiccator after which they have amp of 76.5°-78° C. results in vigorous reaction consequently the addition A yellowish-green mixture results The excess LiAlH4 is quenched carefully by the addition of ethyl acetate have dissolved The layers are separated the aqueous layer is extracted 3 times with additional ethyl acetate The organic extract layers are dried (sodium sulfate) filtered concentrated under reduced pressure

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

Procedure: A 3-liter, round-bottom flask equipped with an overhead stirrer, an addition funnel and a reflux condenser was charged with lithium aluminum hydride (49.7 grams, 1.31 mol) and anhydrous THF (500 ml) under nitrogen atmosphere. The resulting suspension was slowly heated to reflux and a solution of trimethyl-1,3,5-benzenetricarboxylate (100.0 grams, 0.40 mol) in anhydrous THF (1.0 liter) was added dropwise thereto while maintaining a gentle reflux (3 hours). The resulting gray suspension was stirred under reflux for additional 7 hours and then cooled in an external ice-water bath. The excess lithium aluminum hydride was hydrolyzed by dropwise addition of water (50 ml, 45 minutes), then 15% NaOH (50 ml, slow stream), and finally more water (150 ml, slow stream). The resulting suspension was stirred at ambient temperature for 14 hours. The solids were filtered off and the filtrate was concentrated under high vacuum to obtain a colorless oil which slowly solidified to afford 1,3,5-tris(hydroxylmethyl)benzene (62.3 grams, 94%) as a white solid. The 1H NMR and 13C NMR spectra were consistent with the assigned structure. A 3-liter, round-bottom flask equipped with an overhead stirrer, an addition funnel and a reflux condenser The resulting suspension was slowly heated to reflux while maintaining a gentle reflux (3 hours) under reflux for additional 7 hours cooled in an external ice-water bath The resulting suspension was stirred at ambient temperature for 14 hours The solids were filtered off the filtrate was concentrated under high vacuum to obtain a colorless oil which