Control of catalytic debenzylation and dehalogenation reactions during liquid-phase reduction by H 2

Abstract

Heterogeneous catalysis, which is being used more frequently in the fine chemicals industry, does not always provide the desired selectivity because various functional groups become labile to reduction by hydrogen on a noble metal under similar reaction conditions. To study the selectivity of debenzylation versus dechlorination in an aromatic compound, the kinetics of the reduction of 4-chloro-N,N-dibenzylaniline on supported Pd catalysts in a buffered solvent under hydrogen reduction conditions were investigated. The turnover frequency on a Pd/C catalyst was 2–40 times higher than that on Pd dispersed on SiO 2, TiO 2, and Al 2O 3. The effects of hydrogen pressure, organic substrate concentration, temperature, solvent, and catalyst support on the selectivity were not great at a pH of 5.4, whereas the effect of acid or base modifiers was very significant. Only dechlorination reactions occurred under basic conditions, and the use of an acid confirmed a preferential promotion of debenzylation reactions; consequently, as the pH decreased from 12 to 0.1, the selectivity for dechlorination decreased from essentially 100% to almost 0. Using a triethylamine/acetic acid buffer system to control pH, it was determined that the inflection point in selectivity corresponds to a pH value equal to the p K a of the benzyl-protected amine (4.5 in this case). Consequently, one important finding is that the dechlorination reaction can occur at high rates even under acidic conditions, as long as the pH of the reaction mixture is greater than the p K a of the protected amine. Furthermore, generation of an acidic product like HCl during a dechlorination reaction can decrease the system pH and markedly alter selectivity unless a buffer is present. For reactions carried out at a pH of 5.4, the initial rate of organic substrate consumption was modeled by a classical Langmuir–Hinshelwood sequence, with the assumption of two types of active sites, one site to adsorb H atoms and the other to adsorb the organic substrate, yielding a slightly better fit to the data. The Weisz–Prater criterion was applied to verify the absence of mass transfer effects.