Biphasic Synthesis of 2-Phenylpropionic Acid and Ester by Interfacial Carbonylation of α-Methylbenzyl Bromide

Abstract

An interfacial synthesis technique has been successfully extended to the carbonylation of α-methylbenzyl bromide in an organic−aqueous sodium hydroxide mixture at 35−60 °C and 1 atm using surface-active palladium−(4-dimethylaminophenyl)diphenylphosphine complex as the catalyst and dodecyl sodium sulfate as the emulsifier. Depending on the reaction conditions, 2-phenylpropionate in the form of sodium salt and an ester was obtained in 0−83% yield, along with varying amounts of side products that included α-methylbenzyl alcohol, 2,3-diphenylbutane, di(α-methylbenzyl)ether, and an asymmetric ether derived from the substrate and an alcoholic medium. When 2-methyl-1-butanol or 2-ethyl-1-hexanol was used as the organic phase, 2-phenylpropionate ester and sodium salt were obtained in 40−83% yield, with a maximum yield obtained at an optimal aqueous base concentration of about 5 M. At a lower aqueous base concentration, more of α-methylbenzyl alcohol was formed, whereas at a higher aqueous base concentration, more of 2,3-diphenylbutane and asymmetric ether were formed. When toluene was used as the organic phase, 2-phenylpropionate salt was obtained in less than 13% yield, and the major side product was α-methylbenzyl alcohol at a low aqueous base concentration and 2,3-diphenylbutane at a high aqueous base concentration. In all cases, the formation of 2,3-diphenylbutane was accompanied by a stoichiometric formation of carbonate. The latter implicates the involvement of an oxidative intermediatetentatively identified as hypobromous acidthat could deactivate the catalyst complex through ligand degradation. Along with the carbonylation reaction, carbon monoxide also underwent a slow, base-induced hydrolysis reaction to form formic acid. With 2-ethyl-1-hexanol as the organic phase, the carbonylation of α-methylbenzyl bromide showed an apparent temperature-dependent activation energy, a first-order dependence each on the substrate, catalyst, and ligand concentrations up to the catalyst concentration of 0.0020 M and a ligand:catalyst ratio of 3:1, and a variable-order dependence on the carbon monoxide pressure that switched from first to zeroth order as the carbon monoxide pressure was increased above 450 mmHg. A reaction mechanism is proposed which yields model rate and yield expressions in accord with the experimental findings. Results of control experiments with α,α-dibromotoluene in a toluene−aqueous sodium hydroxide mixture indicate that replacement of the α-methyl group in α-methylbenzyl bromide by a second bromo group suppressed the formation of substituted benzyl alcohol and coupled product. They suggest that the broad product distribution in the carbonylation of α-methylbenzyl bromide relative to the carbonylation of benzyl chloride and α,α-dibromotoluene is attributable to the electron-releasing α-methyl group making the substrate susceptible to hydrolysis and coupling reactions.