Project description:The total synthesis and structure determination of cis- and trans-flocoumafen was described. The key synthetic steps involve Knoevenagel condensation with p-methoxybenzaldehyde, in situ decarboxylation and intramolecular ring cyclization to construct the tetralone skeleton. Stereospecific reduction of the O-alkylated ketone 13 afforded good yield of precusor alcohol 5. Final coupling of alcohol 5 with 4-hydroxy-coumarin yielded flocoumafen (1). Separation and structure determination of cis- and trans-flocoumafen through 2D NMR analyses-assisted computer simulation techniques for the evaluation of anticoagulant activities are reported for the first time. This method is useful for generating the core tetralone skeleton of 4-hydroxycoumarin derivatives and provides a generalized access to various warfarin type anticoagulants.
Project description:4H-Pyrans (4H-Pys) and 1,4-dihydropyridines (1,4-DHPs) are important classes of heterocyclic scaffolds in medicinal chemistry. Herein, an indium(III)-catalyzed one-pot domino reaction for the synthesis of highly functionalized 4H-Pys, and a model of 1,4-DHP is reported. This alternative approach to the challenging Hantzsch 4-component reaction enables the synthesis of fused-tricyclic heterocycles, and the mechanistic studies underline the importance of an intercepted-Knoevenagel adduct to achieve higher chemoselectivity towards these types of unsymmetrical heterocycles.
Project description:The mechanochemical Knoevenagel condensation of malononitrile with p-nitrobenzaldehyde was studied in situ using a tandem approach. X-ray diffraction and Raman spectroscopy were combined to yield time-resolved information on the milling process. Under solvent-free conditions, the reaction leads to a quantitative conversion to p-nitrobenzylidenemalononitrile within 50 minutes. The in situ data indicate that the process is fast and proceeds under a direct conversion. After stopping the milling process, the reaction continues until complete conversion. The continuous and the stopped milling process both result in crystalline products suitable for single crystal X-ray diffraction.
Project description:The sequential three-component reaction between o-hydroxybenzaldehydes, N-(cyanomethyl)pyridinium salts and a nucleophile towards substituted chromenoimidazopyridines under oxidative conditions has been developed. The employment of Mn(OAc)3·2H2O or KMnO4 as stoichiometric oxidants allowed the use of a wide range of nucleophiles, such as nitromethane, (aza)indoles, pyrroles, phenols, pyrazole, indazole and diethyl malonate. The formation of the target compounds presumably proceeds through a domino Knoevenagel/cyclization/Michael addition/oxidative cyclization reaction sequence.
Project description:The transformation of a base-catalyzed, mechano-assisted Knoevenagel condensation of mono-fluorinated benzaldehyde derivatives (p-, m-, o-benzaldehyde) with malonodinitrile was investigated in situ and in real time. Upon milling, the para-substituted product was found to crystallize initially into two different polymorphic forms, depending on the quantity of catalyst used. For low catalyst concentrations, a mechanically metastable phase (monoclinic) was initially formed, converting to the mechanically stable phase (triclinic) upon further grinding. Instead, higher catalyst concentrations crystallize directly as the triclinic product. Inclusion of catalyst in the final product, as evidenced by mass spectrometric analysis, suggests this complex polymorphic pathway may be due to seeding effects. Multivariate analysis for the in situ Raman spectra supports this complex formation pathway, and offers a new approach to monitoring multi-phase reactions during ball milling.
Project description:A variety of highly functionalized indole-based [n.3.3]propellane derivatives is described. The synthesis of the propellane derivatives involves a Weiss-Cook condensation, a Fischer indole cyclization, and a ring-closing metathesis as key steps.
Project description:For the first time, an aza-Heck cyclization that allows the preparation of indoline scaffolds is described. Using N-hydroxy anilines as electrophiles, which can be easily accessed from the corresponding nitroarenes, this method provides indolines bearing pendant functionality and complex ring topologies. Synthesis of challenging indolines, such as those bearing fully substituted carbon atoms at C2, is also possible using this method.
Project description:The preparation of novel organic-inorganic hybrid mesoporous organosilica containing pyridinedicarboxamide functional groups uniformly distributed inside the nanostructured pore walls has been addressed. The mesoporosity and uniformity of the synthesized nanomaterials were characterized by different techniques such as nitrogen adsorption/desorption measurements and powder X-ray diffraction (PXRD). Additionally, the presence of the pyridinedicarboxamide in the pore walls of the nanomaterials was assessed by Fourier-transform infrared spectroscopy (FT-IR), as well as 29Si and 13C solid-state cross-polarization and magic angle spinning nuclear magnetic resonance (CP/MAS-NMR). The Knoevenagel condensation of aldehydes with active methylene compounds was carried out over the pyridinedicarboxamide functionalized mesoporous organosilica, which has been proven to be an efficient heterogeneous basic catalyst in the presence of ethanol as solvent. The catalytic activity of the investigated materials was investigated in the Knoevenagel condensation between malononitrile and several benzaldehyde derivatives exhibiting a high conversion (>90%) and excellent selectivity toward the final condensation products under very mild reaction conditions. Furthermore, the catalyst stability is noteworthy as it could be recycled and reused at least twelve times without any significant change in the performance.
Project description:In the present study, a novel catalytic route for the Knoevenagel condensation reaction has been developed by Pickering interfacial catalysis using magnesium oxide (MgO) as both an emulsion stabilizer and a base catalyst. MgO was prepared by the precipitation method using sodium hydroxide or ammonium hydroxide as the precipitating agent and calcined at different temperatures. The calcined samples were characterized by XRD, SEM, TEM, AFM, BET, and DLS techniques. The catalytic application of the emulsions stabilized by MgO was investigated for the Knoevenagel condensation reaction of benzaldehyde and its derivatives with malononitrile. All of the reactions were carried out at an ambient temperature (30 °C) under static conditions without stirring. Both the emulsion-stabilizing ability and the catalytic activity of MgO were found to be affected by the method of preparation, calcination temperature, and the nature of the oil phase. It was observed that the method of preparation varied the texture and morphology of MgO and thus the stability and droplet size of the emulsion formed. This was further reflected in the catalytic activity. The highest yield (87%) of the condensation product was obtained with MgO prepared by precipitation using a strong base (NaOH) and further calcined at 400 °C. The developed catalytic system offers several green chemistry advantages such as reusable solid-base catalyst and use of a single material as both emulsion stabilizer and catalyst. Room-temperature reaction under static conditions is an additional advantage of the developed catalytic system.
Project description:The rapid development of on-surface synthesis provides a unique approach toward the formation of carbon-based nanostructures with designed properties. Herein, we present the on-surface formation of CN-substituted phenylene vinylene chains on the Au(111) surface, thermally induced by annealing the substrate stepwise at temperatures between 220 °C and 240 °C. The reaction is investigated by scanning tunneling microscopy and density functional theory. Supported by the calculated reaction pathway, we assign the observed chain formation to a Knoevenagel condensation between an aldehyde and a methylene nitrile substituent.