Wall-catalyzed and homogeneous gas-phase reactions for the gas-phase oxidation of 1,3-butadiene are studied using the Multiple Automated Reactor System (MARS) described in part 1 of this series of papers to assess reaction inertness for a typical parallel catalytic reactor system. The heterogeneous catalyzed version of 1,3-butadiene oxidation represents an alternate C-4 hydrocarbon-based route for the manufacture of a tetrahydrofuran (THF) monomer. Polyether glycol polymers derived from THF are used to manufacture various commercial materials where elastic or flexible impact-resistant properties are desirable. Experiments were performed using parallel banks of the MARS U-tube and straight-through-tube reactor designs in both empty tube and packed-bed modes. Empty tube mode data using typical heterogeneous catalyst reaction conditions showed the presence of significant reactant conversion to combustion products for both reactor designs. The U-tube design generated different reactant conversion results when compared to the straight-through-tube design. These differences were attributed to the interaction between system design features and reaction conditions, such as the reactor tube geometry, the product transfer line design, and the contact times in various heated zones. Various materials of construction and catalyst bed retaining materials were also evaluated for inertness using the packed-bed mode. When a butadiene-rich feed gas was used, the O-2 conversion was generally higher in the presence of various metals versus glass according to type 316 stainless steel > Ti > glass wool > glass beads. The results suggest that caution must be exercised when catalyst performance data are measured using parallel gas-phase reactor systems, especially for substrates with functional groups that may react in the gas phase and in the presence of various materials of construction. Each reactor unit in the parallel bank should be evaluated for reaction inertness before a catalyst development campaign is initiated to avoid incorrect conclusions on catalyst ranking and generation of biased data that contain false measures of catalyst performance.