| 88% |
With sodium tetrahydroborate; In methanol; diethyl ether; water; |
Step 1a: Synthesis of 2,3-Dimethoxy-5-methylhydroquinoneTo a stirred solution of NaBH4 (1.04 g, 27.5 mmol) in water (30 mL), a solution of commercial 2,3-dimethoxy-5-methylbenzoquinone (1.00 g, 5.50 mmol) in diethyl ether (15 mL) and methanol (8 mL) was added dropwise. Afterward, the reaction mixture was extracted with diethyl ether and washed with brine. The combined organic layers were dried over sodium sulphate and concentrated to dryness to give the product as a pale yellow solid (950 mg, 88%).TLC: R/= 0.20 petroleum ether:EtOAc 90:10 v/v. Spectroscopic data were as reported in the literature by Daquino, C. et al, J. Org. Chem. 2008, 75, 9270 |
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EXAMPLE 1Preparation of Grignard Reagent of 2,3 Dimethoxy-5-bromo-6-methyl 1,4 dimethoxyethoxy methyl ether Compound of Formula IIb2,3-Dimethoxy 5-methyl-1,4-benzoquinone of formula 2, (2.5 g) was dissolved in 7.5 ml of methylene dichloride and treated with sodium hydrosulphite (3.56 g) in an alkaline solution at 10-20 C. After 2 hours the reaction mixture was treated with conc. HCl (3.4 ml) to acidic pH. The reaction mixture was extracted with methylene dichloride and washed with water. The organic solvent was concentrated and poured in hexane. The precipitated solid was filtered to obtain 2.25 g of 2,3-dimethoxy-5-methyl-1,4-hydroquinone compound of formula 4. The solid was taken in methylene dichloride and treated with bromine (1.96 g) at 10 to 20 C. The reaction was quenched in water after 2 hours and extracted in methylene dichloride. The methylene dichloride was evaporated. The concentrated mass was added to hexane to precipitate out the solid of 2,3-dimethoxy-5-bromo-6-methyl-1,4-hydroquinone (3.06 g). The bromo compound was dissolved in toluene and treated with 1.024 g sodium hydride (60% suspension) in toluene at 0 to -5 C. Methoxyethoxy methyl chloride (3.17 g) was added at 5 to 10 C. The temperature was slowly raised to room temperature and the reaction was continued for 2 hrs. The reaction was quenched with methanol, followed by water and the toluene layer separated. The organic layer was distilled under vacuum to obtain 4.65 g of 2,3-dimethoxy-5-bromo-6-methyl-1,4-hydroquinone dimethoxyethoxy methyl ether compound of the formula 14a. The compound of formula 14a (4.65 g) was reacted with Magnesium (0.301 g) in tetrahydrofuran, in presence of a pinch of iodine at ambient temperature to form the Grignard reagent of 2,3 dimethoxy-5-bromo-6-methyl 1,4 dimethoxyethoxy methyl ether compound of formula IIb; EXAMPLE 2Preparation of Grignard Reagent of 2,3 Dimethoxy-5-bromo-6-methyl 1,4 dimethoxyethoxy methyl ether Compound of Formula IIb 2,3 dimethoxy 5-methyl 1,4 benzoquinone compound of formula 2 (2.5 g) was dissolved in 7.5 ml of methylene dichloride and treated with sodium hydrosulphite (3.56 g) in alkaline solution at 10-20 C. After 2 hours the reaction mixture was treated with conc. HCl 3.4 ml to acidic pH. The reaction mixture was extracted with methylene dichloride and washed with water. The organic solvent was concentrated and poured in hexane (10 ml). The precipitated solid was filtered to obtain 2.25 g of 2,3 dimethoxy 5 methyl 1,4 hydroquinone compound of formula 4. The solid was taken in methylene dichloride 15 ml and treated with bromine (1.96 g) at 10-20 C. The reaction was quenched in water after 2 hours and extracted in methylene dichloride. The methylene dichloride was evaporated. The concentrated mass was added to hexane to precipitate out the solid of 2,3 dimethoxy-5 bromo-6-methyl 1,4 hydroquinone (3.06 g). The bromo compound was dissolved in methanol and treated with sodium methoxide (1.5 g) at 5-10 C. Methoxyethoxy methyl chloride (3.17 g) was added at 5 C.-10 C., the temperature raised to room temperature and maintained for 8 hrs. The reaction was quenched in water and extracted in diisopropyl ether. The organic layer was distilled under vacuum to obtain 4.75 g of 2,3 Dimethoxy-5-bromo-6-methyl 1,4 di methoxyethoxy methyl ether compound of the formula 14a. The compound was reacted with magnesium (0.34 g) in tetrahydrofuran, in presence of a pinch of iodine at ambient temperature to form the Grignard reagent of 2,3 dimethoxy-5-bromo-6-methyl 1,4 dimethoxyethoxy methyl ether of the formula IIb.; EXAMPLE 3Preparation of Grignard Reagent of 2,3,4,5 tetramethoxy-6-methyl-bromobenzene Compound of Formula IIc 2,3dimethoxy-5-methyl 1,4 benzoquinone compound of formula 2, 2.5 g was dissolved in 7.5 ml of methylene dichloride and treated with sodium hydrosulphite (3.56 g) in alkaline solution at 10-20 C. After 2 hours the reaction mixture was treated with conc. HCl (3.4 ml) to acidic pH. The reaction mixture was extracted with methylene dichloride and washed with water. The organic solvent was concentrated and poured in hexane. The precipitated solid was filtered to obtain 2.25 g. of 2,3 dimethoxy 5 methyl 1,4 hydroquinone compound of formula 4. The solid was taken in alkaline solution and dimethyl sulphate (5.75 g) was added at 40-50 C. The reaction mixture was quenched after 4 hours in water and extracted in methylene dichloride. The solvent was evaporated and the crude obtained was distilled under vacuum at 80 C. at 0.5-1.0 mm Hg to obtain 2.33 g of 2,3,4,5-tetramethoxy toluene. The compound was taken in methylene dichloride (15 ml) and treated with bromine (1.75 g) at 10-20 C. The reaction was quenched in water after 2 hours and extracted in methylene dichloride. The methylene dichloride was evaporated. The concentrated mass was added to hexane to precipitate out the solid of 2,3,4,5-tetramethoxy-6-methyl bromobenzene (3.03 g) of formula 14b. The compound of formula 14b was reacted wit... |
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With potassium borohydride; In methanol; at 0℃; for 0.166667h; |
To a solution of coenzyme Q0 1 (4.00 g, 21.7 mmol) in methanol (30 mL) at 0 C was dropwise added a solution of KBH4 (5.85 g, 108.5 mmol) in methanol (30 mL). After 10 min, the reaction was quenched by the addition of EtOAc and then 5% aqueous HCl[38] and [39] (see Scheme 4). The mixture was extracted with EtOAc (3×50 mL) and the organic layer was washed successively with water and brine, dried (MgSO4), and evaporated at reduced pressure. The crude hydroquinone (4.20 g) was dissolved in EtOH (20 mL) and to this solution at room temperature was added a solution of NaOH (2.20 g in 6 mL H2O) and dimethyl sulfate (5.30 mL, 56.0 mmol) with cooling in a ice water bath in six portions simultaneously. After 45 min, 5% aqueous HCl was added and the mixture was extracted with EtOAc (3×50 mL). The organic layer was washed successively with water and brine, dried (MgSO4), and evaporated to give 5a (74%) as a light yellow liquid.40 1H NMR (500.0 MHz, CDCl3, 298 K): 3.99 (s, 12H, 4× -OCH3), 2.25 (s, 3H, -CH3), 6.45(s, 1H, ArH) ppm. |
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