Application of combinatorial catalysis for the direct amination of benzene to aniline

Abstract High-throughput synthesis and screening methods have been developed for the direct amination of benzene to aniline using solid cataloreactants as oxidants. The discovery libraries consisted of hundreds of samples in the primary screen, and arrays of 24 catalysts in the secondary screen. Catalysts were prepared in multi-well batch reactors and screened in parallel for catalytic activity using modified TLC detection as a primary screen and fast serial GC detection as a secondary screen. Around 25,000 samples were screened in about a year. Promising hits identified in the high-throughput screens were successfully scaled up and optimized in conventional autoclaves. Novel cataloreactant systems consisting primarily of a noble metal and a reducible metal oxide have been discovered. Rh, Ir, Pd, and Ru were found to be suitable noble metal dopants. Ni and Co oxides were the only active and selective oxidants identified. Ni is the most active oxidant but requires a Mn dopant as a stabilizer to improve the regenerability, whereas Co is stable even at high regeneration temperatures. The best performing cataloreactants contain Rh or Ir as noble metals, NiO as an oxidant, and ZrO 2 or K–TiO 2 as carrier. An optimized cataloreactant, Rh/Ni–Mn/K–TiO 2 achieved stable 10% benzene conversion and >95% selectivity to aniline at 300 °C and 300 bar. Significantly, the cataloxidant can be regenerated repeatedly without a substantial loss of performance by reoxidation in air. Any noble metal oxides formed during regeneration are effectively reduced in situ during the next amination reaction.