Catalytic conversions in water. Part 5: Carbonylation of 1-(4-isobutylphenyl)ethanol to ibuprofen catalysed by water-soluble palladium–phosphine complexes in a two-phase system

1-(4-Isobutylphenyl)ethanol (IBPE) was carbonylated to 2-(4-isobutylphenyl)propionic acid (ibuprofen) in an aqueous/organic two phase system using the water-soluble Pd(tppts)₃ catalyst tppts = P(C₆H₄-m-SO₃Na)₃] in the presence of p-CH₃C₆H₄SO₃H at 363 K, 15 MPa CO pressure and a palladium concentration of 150 ppm without addition of organic solvents. Under these conditions the conversion of IBPE was 83% and the selectivity to ibuprofen 82% with no decomposition of the Pd(tppts)₃ catalyst. Both the activity and selectivity were strongly influenced by the tppts/Pd molar ratio and the nature of the added Brønsted acid. Maximum efficiency was observed for P/Pd = 10. Acids of weakly or non-coordinating anions, such as p-CH₃C₆H₄SO₃H, CF₃COOH or HPF₆ afforded carbonylation. No catalytic activity was observed in the presence of acids of strongly coordinating anions, such as HI. The water-soluble Pd/dppps catalyst dppps = Ar_2-nPh_nP-(CH₂)₃-PPh_n′Ar_2-n′; Ar = C₆H₄-m-SO₃Na; n = nń = 0: 86% and n = 0, nń = 1: 14%] exhibited low catalytic activity and the major product obtained was the linear isomer of ibuprofen, 3-(4-isobutylphenyl)propionic acid (3-IPPA) with selectivities up to 78%. Replacement of tppts by a ligand containing less ?SO₃Na groups such as monosulphonated triphenylphosphine (tppms) gives rise to a dramatic drop in the catalytic activity and selectivity to ibuprofen. No catalytic activity was observed using palladium catalysts modified with 2-pyridyldiphenylphosphine (PyPPh₂) and tris(2-pyridyl)phosphine (PPy₃) which are both water soluble in their protonated form. A catalytic cycle is proposed to explain the observed results. ©1997 SCI