Process for preparing aryl-substituted aliphatic carboxylic acids and their esters using cyclic phosphine catalysts

A process for preparing ibuprofen or the alkyl esters thereof which comprises carboxylating 4-isobutylstyrene with carbon monoxide in an anhydrous acidic medium containing tetrahydrofuran as a solvent and about 3-24 mols of anhydrous methanol or ethanol per mol of said 4-isobutylstyrene at a temperature in the range of about 25.degree.-120.degree. C. and a carbon monoxide pressure in the range of about 0-1,000 psig in the presence of (a) a mixture of a palladium(II) compound and a copper (II) compound and (b) a ligand of the formula:

• ##STR10## where R' is the same or different than R" and are individually alkyl or aryl, said aryl, either substituted or unsubstituted and Ar' is phenyl, naphthyl, substituted phenyl or substituted naphthyl and n is an integer from 3 to 6, and in the presence of an amount of hydrogen chloride such as to provide an amount up to about 10 mols of hydrogen chloride per mol of 4-isobutylstyrene.

A process for preparing ibuprofen or the alkyl esters thereof which comprises carboxylating 4-isobutylstyrene with carbon monoxide in a neutral or acidic medium containing tetrahydrofuran as a solvent and about 2-24 mols of water or an aliphatic alcohol per mol of said isobutylstyrene and no added acid at a temperature in the range of about 25.degree.-100.degree. C. and a carbon monoxide pressure in the range of about 0-1,000 psig, in the presence of (a) a mixture of palladium(II) inorganic salt and a copper(II) inorganic salt, and (b) a ligand of the formula:

• ##STR11## where R' is the same or different than R" and are individually alkyl or aryl, said aryl, either substituted or unsubstituted and Ar' is phenyl, naphthyl, substituted phenyl or substituted naphthyl and n is an integer from 3 to 6, and in the presence of an amount of hydrogen chloride such as to provide an amount up to about 10 mols of hydrogen chloride per mol of 4-isobutylstyrene.

A process for preparing ibuprofen ester which comprises carboxylating 4-isobutylstyrene with carbon monoxide in an anhydrous neutral or acidic medium containing about 2-20 mols of a source of alkoxide ions per mol of said olefinic compound at a temperature from about 25.degree. to about 200.degree. C. and a carbon monoxide pressure from about 0 to about 3000 psig in the presence of (a) a palladium(II) compound or (b) a mixture of a palladium(II) compound and a copper(II) compound and a ligand of the formula:

• ##STR12## where R' is the same or different than R" and are individually alkyl or aryl, said aryl, either substituted or unsubstituted and Ar' is phenyl, naphthyl, substituted phenyl or substituted naphthyl and n is an integer from 3 to 6, and in the presence of an amount of hydrogen chloride such as to provide an amount up to about 10 mols of hydrogen chloride per mol of 4-isobutylstyrene.