Preparation of N-Aryl Amides by Epimerization-Free Umpolung Amide Synthesis.

Amide synthesis is one of the most widely practiced chemical reactions, owing to its use in drug development and peptide synthesis. Despite the importance of these applications, the attendant effort to eliminate waste associated with these protocols has met with limited success, and pernicious α-epimerization is most often minimized but not eliminated when targeting challenging amides (e.g., N-aryl amides). This effort has focused on what is essentially a single paradigm in amide formation wherein an electrophilic acyl donor reacts with a nucleophilic amine. Umpolung amide synthesis (UmAS) emerged from α-halo nitroalkane reactions with amines and has since been developed into a method for the synthesis of enantiopure amides using entirely catalytic, enantioselective synthesis. However, its inability to forge N-aryl amides has been a longstanding problem, one limiting its application more broadly in drug development where α-chiral N-aryl amides are increasingly common. We report here the reaction of α-fluoronitroalkanes and N-aryl hydroxyl amines for the direct synthesis of N-aryl amides using a simple Brønsted base as the promoter. No other activating agents are required, and experiments guided by mechanistic hypotheses outline a mechanism based on the UmAS paradigm and confirm that the N-aryl amide, not the N-aryl hydroxamic acid, is the direct product. Ultimately, select chiral α-amino-N-aryl amides were prepared with complete conservation of enantioenrichment, in contrast to a parallel demonstration of their ability to epimerize using the conventional amide synthesis alternative.

Bio-grafted silica to make an asphalt road a sink for reactive environmental pollutants.

Asphalt-surfaced areas such as roads have been reported as major non-combustion sources of reactive organic compounds in urban areas. Emission of latter compounds from asphalt is exacerbated due to exposure to sunlight and high temperature, contributing to negative human and environmental health outcomes. Furthermore, loss of asphalt components over time is linked to bitumen's aging that reduces service life of roads. Here, we introduce a designed bio-grafted-silica nano-filler derived from wood pellet as a sink for latter volatile compounds in an asphalt mixture. Molecular modeling calculations showed the remarkable adsorptive activity of the bio-grafted silica for trapping select asphalt volatiles, especially for the sulfur-containing aromatics and the oxygen-containing aromatics. Laboratory experiment revealed that the bitumen modified with bio-grafted silica exhibited up to 23% lower signs of aging. Thermogravimetric analysis proved that the modified bitumen exhibited a 16% reduction in mass loss compared to neat bitumen. Dynamic vapor sorption analysis also showed bio-grafted silica adsorbed higher amounts of a candidate volatile than pristine silica. The study outcomes highlights the advantages of a bio-derived modifier in asphalt to address concerns associated with the loss of hazardous compounds.

Resolving Bromonitromethane Sourcing by Synthesis: Preparation at the Decagram Scale.

The accessibility of bromonitromethane has declined in recent years, limiting its viability as a reagent for chemical synthesis. The reinvestigation and optimization of a variety of preparations, and the development of safe operating principles, are described. The reproducible protocol described here leverages the effectiveness of hydroxide for nitromethane bromination while respecting its incompatibility with the product it forms. This careful balance was achieved at scales up to 56 g, resulting in a reproducible procedure that provides straightforward, sustainable, and affordable access to this critical reagent.

Direct Observation and Analysis of the Halo-Amino-Nitro Alkane Functional Group.

Conventional amide synthesis is a mainstay in discipline-spanning applications, and it is a reaction type that historically developed as a singular paradigm when considering the carbon-nitrogen bond-forming step. Umpolung amide synthesis (UmAS) exploits the unique properties of an α-halo nitroalkane in its reaction with an amine to produce an amide. The "umpolung" moniker reflects its paradigm-breaking C-N bond formation on the basis of evidence that the nucleophilic nitronate carbon and electrophilic nitrogen engage to form a tetrahedral intermediate (TI) that is an unprecedented functional group, a 1,1,1-halo-amino-nitro alkane (HANA). Studies probing HANA transience have failed to capture this (presumably) highly reactive intermediate. We report here the direct observation of a HANA, its conversion thermally to an amide functionality, and quantitative analysis of this process using computational techniques. These findings validate the HANA as a functional group common to UmAS and diverted UmAS, opening the door to its targeted use and creative manipulation.

MDSIMAID: automatic parameter optimization in fast electrostatic algorithms.

MDSIMAID is a recommender system that optimizes parallel Particle Mesh Ewald (PME) and both sequential and parallel multigrid (MG) summation fast electrostatic solvers. MDSIMAID optimizes the running time or parallel scalability of these methods within a given error tolerance. MDSIMAID performs a run time constrained search on the parameter space of each method starting from semiempirical performance models. Recommended parameters are presented to the user. MDSIMAID's optimization of MG leads to configurations that are up to 14 times faster or 17 times more accurate than published recommendations. Optimization of PME can improve its parallel scalability, making it run twice as fast in parallel in our tests. MDSIMAID and its Python source code are accessible through a Web portal located at http://mdsimaid.cse.nd.edu.