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METHOD FOR PRODUCING IBUPROFEN BY HIGH PRESSURE CARBONYLATION OF 1-(4'-ISOBUTYLPHENYL)ETHANOL
METHOD FOR PRODUCING IBUPROFEN BY HIGH PRESSURE CARBONYLATION OF 1-(4'-ISOBUTYLPHENYL)ETHANOL
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机译：1-（4'-异丁烯基）乙醇的高压羰基化生产布洛芬的方法
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摘要
ABSTRACT OF THE DISCLOSUREA method is provided for the preparation ofibuprofen by carbonylating 1-(4'-isobutylphenyl)ethanol(IBPE) with carbon monoxide in an acidic aqueous medium,e.g. containing at least 10% of water based on the weightof IBPE initially added, at a temperature of at least about10°C and a carbon monoxide pressure of at least about 500psig, and in the presence of (1) a catalyst consistingessentially of a palladium compound in which the palladiumhas a valence of zero to 2 and is complexed with at leastone monodentate phosphine ligand miscible with the organicphase of the reaction medium, the phosphorus/palladium moleratio in said palladium compound and ligand being at leastabout 2:1 when the palladium/IBPE mole ratio is below about1:10,000; (2) dissociated hydrogen ions from an acid whichis substantially completely ionizable in dilute aqueoussolution such that the mole ratio of hydrogen ions to IBPEadded to the reaction zone is at least about 0.15, and themole ratio of hydrogen ions to water is at least about0.026; and (3) dissociated halide ions such that the moleratio of halide ions to IBPE added to the reaction zone isat least about 0.15. Advantageously, a hydrogen halide isthe source of hydrogen ions and halide ions. Thecarbonylation is preferably integrated with a method ofproducing IBPE from isobutylbenzene wherein the lattercompound is subjected to Friedel-Crafts reaction with anacetylating agent to produce 4'-isobutylacetophenone, whichis then reduced with hydrogen in the presence of ahydrogenation catalyst, or with a reducing agent containingavailable hydrogen, to obtain IBPE.
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