Novel two-dimensional molecular space with regular pyridine groups layered pyridine-4-amidepropylsilica (PAPS) and pyridine-4-amidephenylsilica (PAPhS) were successfully synthesized through grafting pyridine groups ill the layer structure of two-dimensional molecular space with regular ammonium groups layered aminopropylsilica (ATMS-DS) and layered aminophenylsilica (APhTMS-DS). The two-dimensional structures were kept after grafting reaction of pyridine groups in PAPS and PAPhS. The catalytic potentials of two-dimensional Molecular space with regular ammonium and pyridine groups were investigated. The catalytic capability of APhTMS-DS, PAPS, and PAPhS was confirmed through Knoevenagel condensation reactions. Knoevenagel condensation of aromatic aldehydes with malononitrile was not observed in the presence of ATMS-DS. Otherwise, the lower yield of Knoevenagel condensation of higher active 2-chlorobenzaldehyde with malononitrile in the presence of APhTMS-DS, PAPS, and PARS indicated the potential of the two-dimensional molecular space with regular catalyst molecules oil influencing catalysis processes utilizing the chemical and geometrical limits.