Cooperative Lewis Acid-1,2,3-Triazolium-Aryloxide Catalysis: Pyrazolone Addition to Nitroolefins as Entry to Diaminoamides

Pyrazolones represent an important structural motif in active pharmaceutical ingredients. Their asymmetric synthesis is thus widely studied. Still, a generally highly enantio- and diastereoselective 1,4-addition to nitroolefins providing products with adjacent stereocenters is elusive. In this article, a new polyfunctional Cu^II-1,2,3-triazolium-aryloxide catalyst is presented which enables this reaction type with high stereocontrol. DFT studies revealed that the triazolium stabilizes the transition state by hydrogen bonding between C(5)−H and the nitroolefin and verify a cooperative mode of activation. Moreover, they show that the catalyst adopts a rigid chiral cage/pore structure by intramolecular hydrogen bonding, by which stereocontrol is achieved. Control catalyst systems confirm the crucial role of the triazolium, aryloxide and Cu^II, requiring a sophisticated structural orchestration for high efficiency. The addition products were used to form pyrazolidinones by chemoselective C=N reduction. These heterocycles are shown to be valuable precursors toward β,γ’-diaminoamides by chemoselective nitro and N−N bond reductions. Morphological profiling using the Cell painting assay identified biological activities for the pyrazolidinones and suggest modulation of DNA synthesis as a potential mode of action. One product showed biological similarity to Camptothecin, a lead structure for cancer therapy.     

Numerical simulation of interfacial debonding in particulate composites considering material inhomogeneities

A comparative study in the framework of large deformations has been conducted to get insight into micro mechanical response of particulate polymeric composites. The propound model enables finite element predictions of displacement response and resulting debonding of a three-phase material subjected to incremental loading conditions. Predictions employ a unit cell of certain shape under specified loading and constraints. The proposed model involves nonlinear material properties and incorporates a strong or weak non-homogeneous interphase region. The interphase toughness is expressed in terms of the adhesion efficiency between the filler and the matrix, though contact conditions are preserved utilizing special contact elements. Interfacial nonlinear spring joint elements regulate debonding initialization, in relation to the imposed failure criterion. Numerical results are presented and discussed for axial tensile and compressive loadings for a variety of values of the imposed parameters.     

Effect of a π-donor on the radical bulk polymerization of methyl methacrylate

Bulk polymerizations of methyl methacrylate (MMA) at 60°C initiated with 2,2′-azoisobutyronitrile are influenced by the presence of an organic π-donor such as tetrathiafulvalene (TTF). Upon addition of TTF, the ratio of weight- to number-average molecular weights M̄_w/M̄_n are significantly reduced and the thermal stability of the poly(methyl methacrylate) samples is increased. Kinetic investigations indicate that TTF acts as a retarder on the polymerization mechanism.