Intramolecular Hydrogen Bonding and Intermolecular Dimerization in the Crystal Structures of Imidazole-4,5-dicarboxylic Acid Derivatives

Diamide and amide-ester derivatives of imidazole-4,5-dicarboxylic acid form reliable hydrogen-bonding
motifs in the solid state. The crystal structures of symmetrically substituted and dissymmetrically substituted
diamides as well as amide-ester combinations were analyzed in order to identify the intermolecular hydrogen-bonding
patterns. An intramolecular seven-membered hydrogen-bonded conformation forms in all derivatives where the
possibility existed due to the functionality present. The motifs observed for the diamides include intermolecular
NH···O and NH···N hydrogen-bonded dimers, with the exceptions to these motifs occurring in compounds having
benzylamine substituents. The amines with a higher classification (i.e., 3° > 2° > 1°) in the dissymmetrically
substituted diamides are the intramolecular hydrogen bond donors in the solid state, consistent with the capacity
of the alkyl group to stabilize developing carbocation character resulting from bond polarization. The amide-ester
derivatives also form an intramolecular hydrogen bond and an intermolecular motif based on NH···N and two different
C2−H···O hydrogen bonds. A pyrrole amide-ester derivative forms an intramolecular NH···O hydrogen bond in the
solid state and an intermolecular NH···O hydrogen-bonded chain. With the exception of the benzylamine-substituted
diamides, the intermolecular hydrogen-bonded motifs appear reliable for these imidazole-4,5-dicarboxylic acid
derivatives and will be useful in the design of analogues for specific applications.

咪唑-4,5-二羧酸(imidazole-4,5-dicarboxylic acid)的二酰胺与酰胺-酯衍生物在固态下可形成稳定的氢键基序。为明确分子间氢键作用模式，研究人员对对称取代与不对称取代的二酰胺以及酰胺-酯组合的晶体结构开展了分析。所有具备对应官能团可能性的衍生物中，均会形成分子内七元环氢键构象。二酰胺类衍生物观测到的氢键基序包括分子间NH···O与NH···N氢键二聚体，此类基序的例外情况出现在带有苄胺取代基的化合物中。在不对称取代的二酰胺中，胺类取代度越高（即三级胺＞二级胺＞一级胺），其在固态下作为分子内氢键供体的特性越显著，这与烷基稳定键极化过程中产生的碳正离子特性的能力相一致。酰胺-酯衍生物同样可形成分子内氢键，以及基于NH···N与两种不同C2−H···O氢键的分子间氢键基序。一类吡咯酰胺-酯衍生物在固态下可形成分子内NH···O氢键，并形成分子间NH···O氢键链状结构。除苄胺取代的二酰胺外，此类咪唑-4,5-二羧酸衍生物的分子间氢键基序具备可靠的可预测性，可用于面向特定应用的类似物设计。