A Continuous‐Flow Microreactor for Knoevenagel Condensation of Ethyl Cyanoacetate with Benzaldehyde: The Effect of Grafted Amino Groups on Catalytic Activity

Abstract

Ethyl α‐cyanocinnamate was synthesized in the Knoevenagel condensation of benzaldehyde and ethyl cyanoacetate in flow monolithic microreactor of 0.63 cm3 volume. The catalytically active core was made of silica monolith modified with various amine group precursors. Structural properties of the support, surface density of NHx groups, and catalytic activity were investigated. It was found that the poly‐ or di‐amine groups attached to the silica surface appeared to be more effective than the aminopropyl groups. Microreactors grafted with diamine functional groups, accompanied by hydrophobic methyl groups, showed the highest activity and stability. It was proved that the decisive role on the activity of catalysts was exerted by the presence of primary amines in diamine chain. The reaction conditions were optimized and it was found that almost full substrate conversion could be achieved in 6 min at 50 °C in the microreactor with low concentration of diamine groups equal to 0.33 mmol g−1.

Bifunctionalised acid-base hierarchically structured monolithic micro-/mesoreactors for continuous-flow tandem catalytic processes. A case study of cyanocinnamate synthesis

“…The conversion of BDMA was signi cantly higher (98%), which con rmed negative effect of methyl group on a course of the hydrolysis reaction. However, yield of EEC was smaller (68%) in agreement with our previous studies [29], which showed that a hydrophobic environment increases the e ciency of the condensation reaction. The negative impact of neighbouring groups is hardly visible in the Knoevenagel reaction (entry 2 vs. 9), which con rmed that there is no interaction between acid sites located on the silica surface and the amine groups attached via propyl linker.…”

“…Decomposition of functional groups was observed in the range of 180-700°C. In this process, not only organic amino groups were released, but also ethyl groups, which were attached to the silica surface during grafting as a result of the esteri cation reaction of ethanol with surface hydroxyls, as was discussed earlier [29]. The DTG curve clearly showed the well-developed peaks with maxima at 280°C and 350°C, which indicated that thermal decomposition of aminoethylaminopropyl group occurred in two steps.…”

“…The selection of the solvent in a tandem process, where the reactions follow different mechanisms, is a challenge. On the one hand, the use of non-polar solvents does not contribute to catalyst deactivation in the Knoevenagel condensation [29], and on the other one, deacetalisation requires a solvent that forms a homogeneous mixture with H 2 O. The solubility of water in non-polar solvents is negligible, therefore the substrate-solvent system had to be modi ed.…”

Continuous Flow Synthesis of 4‐methyl‐3‐oxo‐n‐phenyl‐pentanamide

“…Knoevenagel condensed continuous flow microreactor has been reported for a long time. [16] Formic acid was used as the chosen catalyst, with a total flow rate of 0.2 ml/min and a back pressure of 75PSI. The equivalents of p-benzaldehyde were sequenced (refer to Table 3).…”

“…We conducted the Knoevenagel condensation reaction. Knoevenagel condensed continuous flow microreactor has been reported for a long time [16] . Formic acid was used as the chosen catalyst, with a total flow rate of 0.2 ml/min and a back pressure of 75PSI.…”