Biphasic Synthesis of 2-Phenylpropionic Acid and Ester by Interfacial Carbonylation of -Methylbenzyl Bromide Academic Article uri icon

abstract

  • An interfacial synthesis technique has been successfully extended to the carbonylation of -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 -methylbenzyl alcohol, 2,3-diphenylbutane, di(-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 -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 -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 intermediate - tentatively identified as hypobromous acid - that 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 -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 ,-dibromotoluene in a toluene-aqueous sodium hydroxide mixture indicate that replacement of the -methyl group in -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 -methylbenzyl bromide relative to the carbonylation of benzyl chloride and ,-dibromotoluene is attributable to the electron-releasing -methyl group making the substrate susceptible to hydrolysis and coupling reactions. 1998 American Chemical Society and Royal Society of Chemistry.

published proceedings

  • Organic Process Research & Development

author list (cited authors)

  • Norman, C., Wilhite, B. A., Pham, D., Lim, P. K., & Brown, P. A.

citation count

  • 2

complete list of authors

  • Norman, Carnley||Wilhite, Benjamin A||Pham, Duc||Lim, Phooi K||Brown, Philip A

publication date

  • November 1998