Preparation of MDP2P from safrole using a novel catalyst

by Rhodium

Introduction

Preparation of the catalyst [1]

A suspension of tungstic acid (2.50g, 10 mmol) in 7 ml of 30% aqueous H2O2 was stirred and heated to 60°C until a colorless solution was obtained. To this solution, filtered and cooled to room temperature, was added 40% w/v H3PO4 (0.62ml, ca 2.5 mmol), and the whole was diluted to 30 ml with water. To the resultant soluton, 2.09g of methyltrioctylammonium chloride (97% pure, equivalent to 2.027g, 5 mmol) in DCM (40 ml) was added dropwise with stirring over about 2 min. Stirring was continued for an additional 15 min. The organic phase was then separated, dried over Na2SO4, filtered, and gently evaporated on a rotary evaporator under reduced pressure at 40-50°C (bath temp) to give 3.70 g (98.4%, based on the quaternary ammonium salt charged) of an almost colorless syrup.

Oxidation of safrole to MDP2P [2,3]

In a 100ml three-necked, round-bottomed flask equipped with mechanical stirrer, thermometer and a reflux condenser, a vigorously stirred mixture of the above catalyst (0.7g, 0.31 mmol), safrole (13.24g, 80mmol), benzene (35 ml) and 40% w/v H2O2 (5.10ml, 60 mmol) was heated to 60°C and kept at this temperature for 60 min (External cooling is needed!). The mixture was cooled to room temp, the organic phase was separated and diluted with 30 ml Et2O. In order to remove the catalyst, the organic solution was first stirred with a solution of Na2CO3 (0.75g) and Na2SO3 (0.75g) in water (10 ml) for a few minutes, then separated, dried over Na2SO4 and passed through a short column (2.5 cm diam) of silica gel (50g), and ~300ml anhydrous Et2O was passed through the column to ensure complete elution of the products. The solvent was evaporated and the residue dissolved in 18 ml of tetraglyme and treated with anhydrous LiI (0.130g, 0.97 mmol) at 130°C for 5h. After cooling, the products were distilled under vacuum, recovering 5.17 grams safrole (saved for the next run) and collecting 6.25 grams of MDP2P.

References

[1] C. Venturello, J. Org. Chem. 53, 1553-1557 (1988)
[2] C. Venturello, US Pat 4,731,482
[3] C. Venturello, Synthesis, 1229-1231 (1992)