3-Aminooxetanes: versatile 1,3-amphoteric molecules for intermolecular annulation reactions

Despite the versatility of amphoteric molecules, stable and easily accessible ones are still limitedly known.

Spontaneous proton transfer in a series of amphoteric molecules under hydrostatic pressure

Hydrostatic pressure has induced intermolecular proton transfer in the crystals of a series of amphoteric molecules, which results in significant color changes.

Efficient access to unprotected primary amines by iron-catalyzed aminochlorination of alkenes

Primary amines are essential constituents of biologically active molecules and versatile intermediates in the synthesis of drugs and agrochemicals. However, their preparation from easily accessible alkenes remains challenging. Here, we report a general strategy to access primary amines from alkenes through an operationally simple iron-catalyzed aminochlorination reaction. A stable hydroxylamine derivative and benign sodium chloride act as the respective nitrogen and chlorine sources. The reaction proceeds at room temperature under air; tolerates a large scope of aliphatic and conjugated alkenes, including densely functionalized substrates; and provides excellent anti-Markovnikov regioselectivity with respect to the amino group. The reactivity of the 2-chloroalkylamine products, an understudied class of amphoteric molecules, enables facile access to linear or branched aliphatic amines, aziridines, aminonitriles, azido amines, and homoallylic amines.

Log D Analysis Using Dynamic Approach

ABSTRACTLog D is one of the important parameters used in Lipinski’s rule to assess the druggability of a molecule in pharmaceutical formulations. It represents the logarithm (log10) of the distribution coefficient (D) of a molecule. The distribution coefficient is defined as the ratio of the concentration of the sum of ionized and unionized species of a molecule distributed between a hydrophobic organic phase and an aqueous buffer phase. Since the pH affects the ionic state of a molecule, log D value (which is dependent on the concentrations of the ionized species) also becomes dependent on pH. In this work, the conventional algebraic method is compared with a more generalized ‘dynamic’ approach to model the distribution coefficient of amphoteric, diamino-monoprotic molecule and monoprotic acid in the presence of salt or co-solvent. Recently reported experimental log D data of amphoteric molecules such as nalidixic acid, mebendazole, benazepril and telmisartan, were analyzed using both these approaches to show their equivalence.GRAPHICAL ABSTRACT