1,2,3,4-tetramethoxybenzene

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

Procedure: Syper, L. et al., Tetrahedron 36:123 (1980). To a solution of 1,2,3,4-tetramethoxybenzene 12 (4.0 g, 20.2 mmol) and TMEDA (6 mL, 38.0 mmol) in hexanes (44 mL) and THF (80 mL) at 0° C. under Ar, n-BuLi in hexane (1.6 M, 25.6 mmol) was added dropwise over a 10 min period and the reaction stirred for 30 min at 0° C. under Ar. Subsequent to dropwise addition of CH3I (20 mL, 160 mmol) over an 8 min period, the reaction was stirred for 3 h at 0° C. under Ar and then quenched by addition of aqueous NH4Cl and ether (20 mL). The organic layer was sequentially washed with concentrated NH4OH, water, and brine. Drying and concentration of the organic layer was followed by purification of the residue by flash chromatography (hexanes, hexanes/EtOAc, 19:1, v/v) to afford 13 as a clear oil (3.6 g, 83%). 1H NMR (CDCl3): δ6.45 (s, 1 H), 3.93 (s, 3 H), 3.87 (s, 3 H), 3.82 (s, 3 H), 3.79 (s, 3 H), 2.23 (s, 3 H). 13C NMR (CDCl3): δ149.0, 146.9, 145.3, 140.7, 125.7, 108.2, 61.0, 60.9, 60.5, 55.9, 15.7. the reaction was stirred for 3 h at 0° C. under Ar quenched by addition of aqueous NH4Cl and ether (20 mL) The organic layer was sequentially washed with concentrated NH4OH, water, and brine Drying concentration of the organic layer was followed by purification of the residue by flash chromatography (hexanes, hexanes/EtOAc, 19:1

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

Procedure: Syper, L. et al., Tetrahedron 36:123 (1980). To a solution of 1,2,3,4-tetramethoxybenzene 12 (4.0 g, 20.2 mmol) and TMEDA (6 mL, 38.0 mmol) in hexanes (44 mL) and THF (80 mL) at 0° C. under Ar, n-BuLi in hexane (1.6 M, 25.6 mmol) was added dropwise over a 10 min period and the reaction stirred for 30 min at 0° C. under Ar. Subsequent to dropwise addition of CH3I (20 mL, 160 mmol) over an 8 min period, the reaction was stirred for 3 h at 0° C. under Ar and then quenched by addition of aqueous NH4Cl and ether (20 mL). The organic layer was sequentially washed with concentrated NH4OH, water, and brine. Drying and concentration of the organic layer was followed by purification of the residue by flash chromatography (hexanes, hexanes/EtOAc, 19:1, v/v) to afford 13 as a clear oil (3.6 g, 83%). 1H NMR (CDCl3): δ6.45 (s, 1 H), 3.93 (s, 3 H), 3.87 (s, 3 H), 3.82 (s, 3 H), 3.79 (s, 3 H), 2.23 (s, 3 H). 13C NMR (CDCl3): δ149.0, 146.9, 145.3, 140.7, 125.7, 108.2, 61.0, 60.9, 60.5, 55.9, 15.7. the reaction was stirred for 3 h at 0° C. under Ar quenched by addition of aqueous NH4Cl and ether (20 mL) The organic layer was sequentially washed with concentrated NH4OH, water, and brine Drying concentration of the organic layer was followed by purification of the residue by flash chromatography (hexanes, hexanes/EtOAc, 19:1

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

Procedure: 2-hydroxy-3,4,5-trimethoxybenzoic acid (1.14 g, 0.005 mol) and 1,2,3,4-tetramethoxybenzene (0.99 g, 0.005 mol) and 25 ml of a 9% solution of P2O5 in methanesulfonic acid were shaken in a 50 ml cylindrical glass tube with a Teflon-lined screw-cap at room temperature for 54 hours. The dark orange mixture was then poured onto crushed ice (150 ml). After melting, the product was extracted with methylene chloride (3×40 ml). After removal of the solvent, the residue was chromatographed on silica gel (30 g) with CH2Cl2. Of the three fractions obtained (the eluent was monitored by thin-layer chromatography), the middle one was uniform and left pure 2-hydroxy-3,4,5,2',3',4',5'-heptamethoxybenzophenone (0.51 g, 25%) as a yellow oil upon evaporation of the solvent. This was dissolved in 100 ml 75% alcohol whereafter 5 ml of 10N NaOH were added and the mixture was heated to boiling in a beaker for three hours; the volume was kept at 100 ml by occasional addition of water. The mixture was then transferred to a 250 ml round bottom flask and refluxed for another 17 hours. After cooling, suction filtration yielded 0.36 g of 2,3,4,5,6,7-hexamethoxyxanthone as a white product (small needles, matted, 77%). In a deprotection procedure, similar to the one described above for pentamethoxyxanthone, 0.42 g of the hexamethoxyxanthone produced 0.296 g of hexahydroxyxanthone (91%) as a pale yellow powder. It was found advantageous to circumvent the need for centrifugation by stirring the methylene chloride-water mixture (from the quenching of the BBr3 -solution) in a wide-mouthed container for several hours, leading to the evaporation of the methylene chloride; the mixture is then easily filterable. lined screw-cap at room temperature for 54 hours The dark orange mixture was then poured the product was extracted with methylene chloride (3×40 ml) After removal of the solvent the residue was chromatographed on silica gel (30 g) with CH2Cl2 Of the three fractions obtained (the eluent upon evaporation of the solvent This was dissolved in 100 ml 75% alcohol whereafter 5 ml of 10N NaOH were added the mixture was heated the volume was kept at 100 ml by occasional addition of water The mixture was then transferred to a 250 ml round bottom flask refluxed for another 17 hours After cooling suction filtration

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

Procedure: Following the procedure by Syper et al.,19 N-methylformanilide (1.0 mL, 8.1 mmol) was added to a flame dried 10 mL round bottom flask under argon and a drying tube. POCl3 (1.0 mL, 11 mmol) was added at room temperature and the Argon line was removed. After 5 minutes 18 (1.067 g, 5.38 mmol) was dissolved in CH2Cl2 (2.0 mL) and added at room temperature. The reaction was stirred at room temperature under a drying tube for 48 hrs and monitored by 1H NMR. When complete the reaction was diluted with EtOAc, washed with saturated brine, dried over MgSO4, filtered, and condensed. The resulting product was separated from remaining N-methylformanilide using flash chromatography (1:4 Et2O:hexanes) to provide 19 (1.141 g, 5.04 mmol, 94%) as a colorless oil. was added to a flame dried 10 mL round bottom flask under argon the Argon line was removed added at room temperature washed with saturated brine dried over MgSO4 filtered condensed The resulting product was separated

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

Procedure: Following the procedure by Tremblay et al.,17 17 (3.851 g, 20.9 mmol) was dissolved in dry acetone (90.0 ml), and K2CO3 (9.36 g, 67.7 mmol) was added followed by MeI (9.0 mL, 144 mmol). The reaction was heated under reflux for 26 h and monitored by TLC (1:9 EtOAc:hexanes) for completion. When complete the reaction was cooled to room temperature and filtered. The acetone was removed under reduced pressure and the residue was taken up in CH2Cl2 (50 mL). The suspension was filtered, dried over MgSO4, filtered again, and condensed. The crude product can be purified by flash chromatography (1:4 EtOAc:hexanes), however, recrystallization from Et2O/hexanes was sufficient to provide pure 18 (3.405 g, 17.2 mmol, 82%) as white needles. The reaction was heated under reflux for 26 h filtered The acetone was removed under reduced pressure The suspension was filtered dried over MgSO4 filtered again condensed The crude product can be purified by flash chromatography (1:4 EtOAc:hexanes) however, recrystallization from Et2O/hexanes

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

Procedure: 2-hydroxy-3,4,5-trimethoxybenzoic acid (1.14 g, 0.005 mol) and 1,2,3,4-tetramethoxybenzene (0.99 g, 0.005 mol) and 25 ml of a 9% solution of P2O5 in methanesulfonic acid were shaken in a 50 ml cylindrical glass tube with a Teflon-lined screw-cap at room temperature for 54 hours. The dark orange mixture was then poured onto crushed ice (150 ml). After melting, the product was extracted with methylene chloride (3×40 ml). After removal of the solvent, the residue was chromatographed on silica gel (30 g) with CH2Cl2. Of the three fractions obtained (the eluent was monitored by thin-layer chromatography), the middle one was uniform and left pure 2-hydroxy-3,4,5,2′,3′,4′, 5′-heptamethoxybenzophenone (0.51 g, 25%) as a yellow oil upon evaporation of the solvent. This was dissolved in 100 ml 75% alcohol whereafter 5 ml of 10N NaOH were added and the mixture was heated to boiling in a beaker for three hours; the volume was kept at 100 ml by occasional addition of water. The mixture was then transferred to a 250 ml round bottom flask and refluxed for another 17 hours. After cooling, suction filtration yielded 0.36 g of 2,3,4,5,6,7-hexamethoxyxanthone as a white product (small needles, matted, 77%). In a deprotection procedure, similar to the one described above for pentamethoxyxanthone, 0.42 g of the hexamethoxyxanthone produced 0.296 g of hexahydroxyxanthone (91%) as a pale yellow powder. It was found advantageous to circumvent the need for centrifugation by stirring the methylene chloride-water mixture (from the quenching of the BBr3-solution) in a wide-mouthed container for several hours, leading to the evaporation of the methylene chloride; the mixture is then easily filterable. lined screw-cap at room temperature for 54 hours The dark orange mixture was then poured the product was extracted with methylene chloride (3×40 ml) After removal of the solvent the residue was chromatographed on silica gel (30 g) with CH2Cl2 Of the three fractions obtained (the eluent upon evaporation of the solvent This was dissolved in 100 ml 75% alcohol whereafter 5 ml of 10N NaOH were added the mixture was heated the volume was kept at 100 ml by occasional addition of water The mixture was then transferred to a 250 ml round bottom flask refluxed for another 17 hours After cooling suction filtration

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

Procedure: Syper, L. et al., Tetrahedron 36:123 (1980). To a solution of 1,2,3,4-tetramethoxybenzene 12 (4.0 g, 20.2 mmol) and TMEDA (6 mL, 38.0 mmol) in hexanes (44 mL) and THF (80 mL) at 0° C. under Ar, n-BuLi in hexane (1.6 M, 25.6 mmol) was added dropwise over a 10 min period and the reaction stirred for 30 min at 0° C. under Ar. Subsequent to dropwise addition of CH3I (20 mL, 160 mmol) over an 8 min period, the reaction was stirred for 3 h at 0° C. under Ar and then quenched by addition of aqueous NH4Cl and ether (20 mL). The organic layer was sequentially washed with concentrated NH4OH, water, and brine. Drying and concentration of the organic layer was followed by purification of the residue by flash chromatography (hexanes, hexanes/EtOAc, 19:1, v/v) to afford 13 as a clear oil (3.6 g, 83%). 1H NMR (CDCl3): δ6.45 (s, 1 H), 3.93 (s, 3 H), 3.87 (s, 3 H), 3.82 (s, 3 H), 3.79 (s, 3 H), 2.23 (s, 3 H). 13C NMR (CDCl3): δ149.0, 146.9, 145.3, 140.7, 125.7, 108.2, 61.0, 60.9, 60.5, 55.9, 15.7. the reaction was stirred for 3 h at 0° C. under Ar quenched by addition of aqueous NH4Cl and ether (20 mL) The organic layer was sequentially washed with concentrated NH4OH, water, and brine Drying concentration of the organic layer was followed by purification of the residue by flash chromatography (hexanes, hexanes/EtOAc, 19:1