Methyl iodide → 2-Isopropylanisole

Participants

Reaction Steps

A 22 L three-necked round bottom flask equipped with mechanical stirring was charged with KOH (1154 g, 20.56 moles), tetrabutylammonium hydrogen sulfate (140 g, 0.411 mole), and deionized water (5.6 L). The mixture was cooled to a temperature of approximately 20° C. to 25° C. Methylene chloride (5.6 L) was added to the flask, then 2-isopropylphenol (590 g, 4.33 moles). The mixture was stirred for 0.5 h before iodomethane (741 g, 5.22 moles) was added. The stirring was continued at room temperature until the reaction was observed to be complete by HPLC, typically after approximately 5 h. Stirring was discontinued and the reaction mixture was allowed to settle into aqueous and organic layers, which were then separated. Triethylamine (185 mL, 1.33 moles) was added to the organic phase with stirring for at least 15 min. Solvent was then removed by vacuum distillation to afford a white solid. Cyclohexane (41) was added to the white solid, which was filtered and washed with further cyclohexane to remove the reaction product as a solvate. The cyclohexane solution was washed with aqueous HCl (2N), then half-saturated aqueous NaCl, and finally saturated aqueous NaCl. The cyclohexane was removed by vacuum distillation to afford 1-isopropyl-2-methoxybenzene as a light yellow oil of medium viscosity (612 g, 94% yield).

Provenance & Evidence