Dispersion In Plug Flow Tube Reactors Used for Pharmaceutical Intermediates

Flow tube reactors are gaining widespread use in process development groups at Eli Lilly.  Characterizing axial dispersion is important to evaluate reactor design and is used to predict conversion and product distribution along the length of the reactor.  Lilly has utilized tube reactors for continuous asymmetric hydrogenations, hydroformylations, thermal rearrangements, thermal couplings, cyclizations, azide chemistries, direct hydroxylation, cyclopropanation, and oxidation reactions.  Dispersion in both coiled tube reactors and pipes in series geometries were investigated. The volume of the reactors ranged from 70 ml to 7 L. The residence time distribution was used to determine the dispersion of each reactor. To determine the RTD a step change in a solution of 40/60% THF/Toluene to 40/60% THF/m-Xylene was implemented. The concentration of m-Xylene in the reactor effluent was monitored by an in line Raman probe positioned at the outlet of the reactor. From the F curve the dispersion coefficient was calculated. The reactors investigated in the study were designed for low axial dispersion and resulted in dispersion numbers on the order of 0.001.