Synthesis of β-tetralones on a large scale


Several of these tetralones are not stable and thus need to be isolated cold and often as a bisulfite adduct which are then converted to the corresponding tetralone before being used in the next step. The conversion of phenylacetic acid chlorides to 2- tetralones with ethylene under Friedel-Crafts conditions is well known in the literature. The typical process involves adding ethylene gas to a mixture of phenylacetyl chloride and AlCl3 at -20 to 0 °C which usually gives the Tetralone as an oily semi-solid in less than 50% yield. After considerable study, the temperature and the dispersion rate at which ethylene was added was found to be the key to producing crystalline tetralones with acceptable purity. In order to prevent polyethylene formation, the stoichiometry of ethylene is also very critical to the process. After additional development and extensive optimization, we have been able to scale up the synthesis of various β-tetralones to 100 kg scale with excellent reproducilibilty in terms of yield (> 70 %) and purity (95 %-98 %).