Optimizing selective partial hydrogenations of 4-nitroacetophenone via parallel reaction screening

The hydrogenation of 4-nitroacetophenone was optimized for selective reduct ion to the corresponding aniline-ketone (97%), aniline-alcohol (95%), and a niline-methylene (99%) as a case study demonstrating the optimization of th e selective reduction of a polyfunctional substrate using a parallel pressu re reactor. The catalyst, catalyst loading, pressure, temperature, and meth anesulfonic acid stoichiometry were varied, first in an initial coarse scre en (catalyst and acid stoichiometry), and then in a full factorial screen f or selected catalysts. Facile profiling of hydrogen uptake in each reaction aided setting reaction time and parameter ranges for the full factorial an alysis, allowed for quickly spotting under- and overreduction, aided predic ting robust reaction endpoints, and provided data for analyzing kinetic beh avior.