## Discussion
### Catalysis in Batch and in Flow
Given the better performance and apparently lower deactivation rate in the run with **R1**, all the subsequent experiments made use of mixtures of MeOH and THF. The flow-rate in these experiments was kept fixed at \(\oplus\) = 0.6 mL h\({}^{-1}\) and, instead of placing the reactors inside the glove-bag, sodium l-ascorbate (1 mol%) was added to the reactant stream as a more practical measure to prevent catalyst oxidation by adventitious oxygen. The reuse of **R1** and **R2** under the said conditions showed that both devices were still active and could promote the CuAAC reaction of benzylazide with propargyl alcohol and 1-hexylne, respectively. Nevertheless, the conversions determined by GC-MS were lower than in the previous runs and ultimately translated into moderate isolated yields (49% and 39%, respectively) of the corresponding triazole products (Table 3, entries 2 and 4). Further trials with the fresh reactors **R3**, **R4**, and **R5** aimed to explore the substrate scope (Table 3, entries 5-14). In general, the best results (83%-97% isolated yields) were recorded with polar alkynes, i.e., those provided with an alcohol or amine functional group in proximity of the acetylene unit. On the contrary, under the adopted conditions, 1,7-octadiyne afforded a mixture of mono- and bis-triazole products in a low overall yield (Table 3, entry 10). Even though a more detailed study will be required for clarifying this aspect, these results appear to conform to the conclusion drawn for the batch experiments, about the much reduced reactivity of the purely hydrocarbon substrates under the CuAAC conditions of this work (see Table 1, entries 13-16). In the case of phenylacetylene, the precipitation of the corresponding triazole product from the MeOH/THF (4:1) reaction medium was an additional issue (Table 3, entry 7). However, when the run was repeated in a THF-enriched mixture, a nearly quantitative yield of the expected triazole product could be easily obtained (Table 3, entry 8). Irrespective of the exact composition of the solvent mixture, the continuous-flow CuAAC reaction between dipropyaglamine (**5**) and benzylazide gave the bis-triazole product **6** in a high isolated yield (Table 3, entries 11 and 13). However, when the reactor **R5** was employed again, in an extended run with the same reactants, **6** and its mono-triazole analogue were only obtained in a moderate overall yield (Table 3, entry 14). In order to shed some light on these latter findings, selected samples of crude triazole products were evaporated to dryness and assayed by ICP-OES for their copper content. Not unexpectedly, a significantly larger amount of metal was found in the bis-triazole derivative **6** (853 and 257 ppm,  
Figure 4: Set flow-rate \(\phi\) (continuous line) and conversion values at the outlet of PCFRs **R1** (_circles_) and **R2** (_crosses_) as a function of the time on stream; the filled triangle marks a daily break in the experiment’s course (for the conditions, see Table 3, entries 1 and 3). Table 3, entries 13 and 14) than in the other (mono-triazole) crudes (138-175 ppm, Table 3, entries 4, 5, and 9). On this basis, it seems reasonable to conclude that the sudden drop in the catalytic activity of **R5**, noted above, must be related to the possibility for the chelating derivative **6** to effectively compete with the supported TBTA units for Cu(I) complexation. In turn, this resulted in extensive leaching of the active centers in the initial run and, therefore, to a much faster deactivation of the catalytic material than in the CuAAC runs, leading to mono-triazole derivatives. Concerning the latter, it is worth noting that the \(\leq\)175 ppm in the dry crude corresponds to \(<\)5% of the copper initially loaded in the flow device.