Search Results (4)

Commercially available and air- and moisture-stable rhodium complex [Rh(OH)(cod)]₂ (2) was utilized in the synthesis of [RhX(cod)(NHC)] (3). The presence of an OH group in complex 2 serves as an internal base, facilitating the deprotonation of the C–H bond of the azolium ring in the hydroxyamide-substituted benzimidazolium salt 1. This reaction between 1 and 2 proceeded in THF at room temperature without temperature control, affording the desired NHC/Rh complex 3 in excellent yield. The characterization of complex 3 was accomplished through NMR and HRMS analyses, revealing its existence as a diastereomeric mixture of two NHC/Rh complexes. Furthermore, its catalytic performance was briefly evaluated in the reaction between 2-naphthaldehyde (5) and phenylboronic acid (6). Full article

Crystal engineering of multi-component molecular crystals, cocrystals, is a subject of growing interest, thanks in part to the potential utility of pharmaceutical cocrystals as drug substances with improved properties. Whereas molecular cocrystals (MCCs) are quite well studied from a design perspective, ionic cocrystals (ICCs) remain relatively underexplored despite there being several recently FDA-approved drug products based upon ICCs. Successful cocrystal design strategies typically depend on strong and directional noncovalent interactions between coformers, as exemplified by hydrogen bonds. Understanding of the hierarchy of such interactions is key to successful outcomes in cocrystal design. We herein address the crystal engineering of ICCs comprising azole functional groups, particularly imidazoles and triazoles, which are commonly encountered in biologically active molecules. Specifically, azoles were studied for their propensity to serve as coformers with strong organic (trifluoroacetic acid and p-toluenesulfonic acid) and inorganic (hydrochloric acid, hydrobromic acid and nitric acid) acids to gain insight into the hierarchy of NH⁺···N (azolium-azole) supramolecular heterosynthons. Accordingly, we combined data mining of the Cambridge Structural Database (CSD) with the structural characterization of 16 new ICCs (11 imidazoles, 4 triazoles, one imidazole-triazole). Analysis of the new ICCs and 66 relevant hits archived in the CSD revealed that supramolecular synthons between identical azole rings (A⁺B⁻A) are much more commonly encountered, 71, than supramolecular synthons between different azole rings (A⁺B⁻C), 11. The average NH⁺···N distance found in the new ICCs reported herein is 2.697(3) Å and binding energy calculations suggested that hydrogen bond strengths range from 31–46 kJ mol⁻¹. The azolium-triazole ICC (A⁺B⁻C) was obtained via mechanochemistry and differed from the other ICCs studied as there was no NH⁺···N hydrogen bonding. That the CNC angles in imidazoles and 1,2,4-triazoles are sensitive to protonation, the cationic forms having larger (approximately 4.4 degrees) values than comparable neutral rings, was used as a parameter to distinguish between protonated and neutral azole rings. Our results indicate that ICCs based upon azolium-azole supramolecular heterosynthons are viable targets, which has implications for the development of new azole drug substances with improved properties. Full article

Organocatalysis by N-heterocyclic carbenes is normally initiated by the deprotonation of precursor azolium ions to form active nucleophilic species. Substituent effects on deprotonation have an impact on catalytic efficiency and provide insight into general catalytic mechanisms by commonly used azolium systems. Using an NMR kinetic method for the analysis of C(3)-H/D exchange, we determined log k_ex–pD profiles for three ortho-substituted N-aryl triazolium salts, which enables a detailed analysis of ortho-substituent effects on deprotonation. This includes N-5-methoxypyrid-2-yl triazolium salt 7 and di-ortho-methoxy and di-ortho-isopropoxyphenyl triazolium salts 8 and 9, and we acquired additional kinetic data to supplement our previously published analysis of N-pyrid-2-yl triazolium salt 6. For 2-pyridyl triazoliums 6 and 7, novel acid catalysis of C(3)-H/D exchange is observed under acidic conditions. These kinetic data were supplemented by DFT analyses of the conformational preferences of 6 upon N-protonation. A C(3) deprotonation mechanism involving intramolecular general base deprotonation by the pyridyl nitrogen of the N(1)-deuterated dicationic triazolium salt is most consistent with the data. We also report k_DO values (protofugalities) for deuteroxide-catalyzed exchange for 6–9. The protofugalities for 8 and 9 are the lowest values to date in the N-aryl triazolium series. Full article

In the last twenty years, N-heterocyclic carbenes (NHCs) have acquired considerable popularity as ligands for transition metals, organocatalysts and in metal-free polymer synthesis. NHCs are generally derived from azolium based salts NHCH⁺X⁻ by deprotonation or reduction (chemical or electrochemical) of NHCH⁺. The extensive knowledge of the physicochemical properties of NHCH⁺/NHC system could help to select the conditions (scaffold of NHC, nature of the counter-ion X⁻, solvent, etc.) to enhance the catalytic power of NHC in a synthesis. The electrochemical behavior of NHCH⁺/NHC system, in the absence and in the presence of solvent, was extensively discussed. The cathodic reduction of NHCH⁺ to NHC and the anodic oxidation of NHC, and the related effect of the scaffold, solvent, and electrodic material were emphasized. The electrochemical investigations allow acquiring further knowledge as regards the stability of NHC, the acidic and nucleophilic properties of NHCH⁺/NHC system, the reactivity of NHC versus carbon dioxide and the effect of the hydrogen bond on the catalytic efficiency of NHC. The question of the spontaneous or induced formation of NHC from particular ionic liquids was reconsidered via voltammetric analysis. The results suggested by the classical and the electrochemical methodologies were compared and discussed. Full article