Franz Dallacker, Wolfgang Edelmann, Anton Weiner. Derivate des Methylendioxybenzols, XXIII. Ueber das Benzo[1.2-d:4.5-d’]bis[1.3]dioxol. Liebigs Ann Chem 719 (1968) 112-118
[…]
3.4-Methylenedioxyphenol (sesamol) (3a) – Applying ice-cooling, 250 mL 85% HCOOH was added to 75 mL 30% hydrogen peroxide and the resulting mixture set aside at room temperature for 1 h. Subsequently, the performic acid solution was added portionwise and with stirring to a solution of 75 g 3.4-methylenedioxybenzaldehyde (piperonal) in 750 mL 85% HCOOH, cooled at –5°C. After 16 h, the resulting mixture was poured into 5 L ice/water (ca. –10°C) and filtered 30 min later. The precipitate was dissolved in slightly warmed 2 N NaOH, chilled, acidified with dilute HCl and the resulting mixture extracted with ether. The combined organic phases were washed with water and dried over magnesium sulfate, yielding a colorless oil, bp.4 110-112°C, which solidifies rapidly giving colorless crystals, mp 65°C. Total yield: 35 g (51%).
2-Hydroxy-4.5-methylenedioxybenzaldehyde (3b) – A solution of 19.6 g N-methylformanilidine in 100 mL chlorobenzene was added drop-wise to 22.2 g POCl3 (temperature: 0°C; anhydrous reaction conditions). After 1 h, 9 g 3a was added and the temperature allowed to rise to 20°C in the course of 6 h. Subsequently, the mixture is heated for 8 h to 60-70° (bath) and poured over ice. The reaction mixture is extracted with ether and the organic phase washed with 2 N NaOH. The alkaline phase is acidified with 2 N HCl and extracted with ether once again. By distillation under reduced pressure, colorless crystals (mp 128°C, bp.1 103-104°C) are obtained. Total yield: 6.5 g (60%).
2-Methoxy-4.5-methylenedioxybenzaldehyde (3c) – Analogous to 3b, a VH-complex was prepared by adding 115 g POCl3 to 111.5 g N-methylformanilidine in 100 mL chlorobenzene. Subsequentlym a solution of 76 g 1-methoxy-3.4-methylenedioxybenzene in 150 mL chlorobenzene was added to the complex at 0-70°C, but now the mixture was filtered with suction, the precipitate washed with water and recrystallized from aqueous methanol (1:1). This yielded colorless needles, mp 111°C. Total yield: 73 g (81%).
2-Methoxy-4.5-methylenedioxyphenol (3d) – Analogous to 3a, a solution of 60 g 3c in 500 mL 85% HCOOH was added to a mixture of 165 mL 85% HCOOH and 50 g 30% hydrogen peroxide. After 16 h at 0°C, the mixture was diluted with water and filtered. The precipitate was washed with water, dissolved in 300 mL 3 N NaOH by gentle heating, the cold alkaline solution filtered and acidified. The resulting product was extracted with ether, washed with water and dried over magnesium sulfate, giving colorless needles with mp 84°C (from cyclohexane). Total yield: 51.5 g (92%).
4.5-Methylenedioxy-o-benzoquinone (1a)
a) An 8 L stainless steel funnel was charged with a slurry of 530 g potassium nitrosodisulfonate in 6 L water containing 22 g KH2PO4 and a saturated solution of 100 g 3a in acetone. Vigorous shaking causes an immediate dark red discoloration, from which the yellow o-benzoquinone 1a precipitates. The latter is isolated via filtration (Buechner), the filtrate extracted trice with 1 L CHCl3 and the combined organic phases dried over magnesium sulfate. The residue was further processed.
b) As described in a) using 16.6 g 3b and 70 g potassium nitrosodisulfonate. Yield: 10.5 g (69%).
c) Analogous to a) using 16.8 g 3d and 70 g potassium nitrosodisulfonate. The residue contains 2.5-dimethoxy-1.4-benzoquinone: yellow crystals with mp 219°C (from GAA). Total yield: 5 g (33%). 1a crystallizes from the filtrate as lemon crystals, mp 206°C. Total yield: 1.9 g (12%).
1.2-Dihydroxy-4.5-methylenedioxybenzene (2a)
a) A solution of 15.2 g 1a in 35 mL acetone and 300 mL water was warmed up to 70°C (bath). For 10 min, a vigorous beam of SO2 was introduced into the mixture. The latter was allowed to reach ambient temperature, extracted twice with 200 mL ether and the organic phases washed with a saturated NaHCO3 solution and water. Drying and removal of the mixture yielded 12.5 g (81%) of product.
b) The crude 1a obtained as described in a) was suspended in water and joined by 3 L ether in a 5 L stainless steel funnel. After addition of saturated aqueous Na2S2O4, decoloration is noted when the mixture is shaken. Extraction with ether and drying over magnesium sulfate yields colorless crystals, mp 159°C (from cyclohexane). Total yield: 74.3 g (66%, relative to 2a).
1.2-Dimethoxy-4.5-methylenedioxybenzene (3e) – A mixture of 15.5 g 2a, 125 mL anhydrous acetone, 26 g DMS and 28 g anhydrous potassium carbonate is stirred and heated to reflux for 12 h. Subsequently, the mixture is diluted with water and extracted with ether. Washing the combined ether extracts with water and drying the organic phase over magnesium sulfate yield colorless crystals, mp 111°C (from cyclohexan or ligroin). Total yield: 13.3 g (73%).
1.3-Dioxolo[4.5-g][1.4]benzodioxan (4a) – A mixture of 16 g 2a, 40 g 1.2-dibromoethane, 40 g anhydrous potassium carbonate and 300 mL anhydrous acetone are stirred at 125° (bath). After 42 h, the mixture is reduced in volume, diluted with water and extracted trice with 200 mL ether. The combined ether phases were washed with diluted aqueous NaOH and water, and subsequently dried over magnesium sulfate, giving colorless crystals, mp 89°C (from cyclohexane). Total yield: 4.35 g (23%).
Benzo[1.2-d:4.5-d’]bis[1.3]dioxol (5a) – 74.3 g 2a in 250 mL DMF is mixed with 76 g potassium carbonate and 72.5 CH2BrCl, and the mixture stirred 42 h at 100°C (bath). The mixture is chilled and the precipitate filtered, washed with a little DMF and poured into 3 L ether. The latter is combined with 1 L water, decanted from resinous material and the ether phase washed twice with 1 L water, once with 0.5 N NaOH and anew with water. Drying the ether phase over magnesium sulfate and removal of the solvent yields 20.1 g (25%) of colorless crystals (recrystallized from cyclohexane), mp 141°C.
3-Methoxy-4.5-methylenedioxy-o-benzoquinone (1b) – Synthesis analogous to 1a, using 16.8 g 2-methoxy-3.4-methylenedioxyphenol (mp 61.5°C). Deep red crystals, mp 160°C (from ethanol). Total yield: 15.9 g (69%).
1.2-Dihydroxy-3-methoxy-4.5-methylenedioxybenzene (2b) – Synthesis analogous to 2a from 18.2 g 1b. Colorless needles, mp 130° (ligroin). Total yield: 12 g (65%).
1.2.3-Trimethoxy-4.5-methylenedioxybenzene – A mixture of 9.2 g 2b, 14.2 g MeI, 13.8 g potassium carbonate and 250 mL acetone is heated at 50°C for 10 h, and the resulting mixture reduced in volume and diluted with water. The mixture is subsequently extracted with ether and washed with 1 N NaOH and water. This yields a colorless oil, bp.2 113°C, which solidifies after standing for several hours. Colorless crystals, mp 46°C. Total yield: 8 g (76%).
5-Methoxy-1.3-dioxolo[4.5-g][1.4]benzodioxane (4b)] – A mixture containing 25 g 2b, 40 g 1.2-dibromoethane, 60 g potassium carbonate and 200 mL acetone was heated for 25 h at 130°C (bath). The mixture was reduced in volume, diluted with water and extracted with ether. The extract was washed with 1 N NaOH and water, yielding colorless crystals, mp 66° (from cyclohexane). Total yield: 17.5 g (61%).
4-Methoxy-benzo[1.2-d:5.4-d’]bis[1.3]dioxol (5b) – In analogy to 5a, 18.5 g 2b gave colorless crude and fine needles, mp 83°C, after 36 h at 120°C (bath). Total yield: 8.8 g (45%).
2.5-Dimethoxy-3-hydroxy-p-benzoquinone – Prepared in analogy to 1a from 1.8 g 2.5-dimethoxy-3.4-methylenedioxyphenol (mp 85.5°C), 24 g potassium nitrosodisulfonate and 13.6 g KH2PO4 in acetone/water with addition of 0.01 g 4.5-methylenedioxy-o-benzoquinone (1a). This yields violet red crystals, mp 207°C. Total yield: 0.9 g (53%).
3-Allyl-4.5-methylenedioxy-o-benzoquinone (1c) – Analogous to 1a from 9 g 2-allyl-3.4-methylenedioxyphenol. Orange crystals, mp 104° (from ligroin). Total yield: 5.6 g (58%).
1.2-Dihydroxy-3-allyl-4.5-methylenedioxybenzene (2c) – The crude quinone 1c was dissolved in ether and mixed with a cold saturated aqueous NaS2O4 solution. The mixture decolorizes and is washed with water. The ether phase is dried over magnesium sulfate and the solvent in vacuo removed. The residue is subjected to methylenation as soon as possible due to instability of the intermediary product.
4-Allyl-benzo-[1.2-d:4.5-d’]bis[1.3]dioxol (5c) and dimere 6 – A mixture of 19.4 g crude 2c, 19.4 g CH2BrCl, 27.6 g potassium carbonate and 250 mL acetone is heated (150°C, bath) and stirred for 56 h. The mixture is reduced in volume at 100°C and the residue extracted with ether. The organic phase is washed with 1 N NaOH and water. The residue is crystallized from acetone at –5°C.
6 – The precipitate is filtered (with suction) and washed with little acetone. This yields a colorless substance, mp 152°C. Total yield: 2.9 g (21%).
5c - The filtrate obtained from 6 is reduced in volume and the oily residue subjected to distillation under reduced pressure. A colorless oil, bp.2 108-112°C, is obtained. It crystallizes from n-hexane (colorless needles, mp 53.5°C). Total yield: 3 g (44%).
8-Formyl-5-methoxy-1.3-benzodioxolo[4.5-g][1.4]benzodioxane (4d) – Analogous to 3b from 15.3 g POCl3 and 13.5 g N-methylformanilidine dissolved in 200 mL o-dichlorobenzene, and 16 g 4b in 40 mL o-dichlorobenzene at 0-50°C. For this procedure, the precipitate is washed with water and dried over magnesium sulfate, yielding yellow crystals, mp 160°C (from ethanol). Total yield: 12.5 g (68%).
Thiosemicarbazone: from GAA with addition of decolorizing C, colorless crystals decomposing at 233°C.
1-Formyl-4-methoxy-benzo[1.2d:4.5-d’]bis[1.3]dioxol (5d) – Analogous to 3b using 8 g POCl3 and 16 g DMF with 8 g 5b at 0-100°C. Isolation of the product as described for 4d yields colorless crystals, mp 164°C (from GAA). Total yield: 4.4 g (48%).
Thiosemicarbazone: colorless crystals, decomposition at 242°C (from GAA).