Synthesis and antimicrobial activity of 5-nitrofurfural heteryl hydrazones

An Improved Method for the Synthesis of Dissymmetric N,N‘-Disubstituted Imidazole-4,5-dicarboxamides

“…A subsequent pyrazine ring-opening reaction with a different amine provides the dissymmetric I45DC ( 6 ) in as high as 87% isolated yield. The maximum overall yield reported for this five-step synthesis is 19.2%. 6a,11e Dissymmetric I45DCs have been synthesized from analogues of 5 in 34−87% yield for this step alone 1 …”

“…In addition to the previously described syntheses of I45DCs in the literature, ,, examples of mixed acid-amide or ester-amide functional group combinations substituted at the 4- and 5-positions of the imidazole ring have been reported. 6a, We report herein an improved synthesis of the dissymmetrically disubstituted I45DCs undertaken as part of a research effort to further explore the structure and function of these compounds. Symmetrically disubstituted I45DCs are naturally dissymmetric both by the tautomeric form of the imidazole ring as well as by the consequence of an intramolecular hydrogen bonded conformation that forms preferentially in these compounds. ,11e, However, for the purposes of this paper, the term dissymmetric refers to the relative identity of the two carboxamide substitutents.…”

“…We have previously reported the use of symmetric N,N‘-disubstituted imidazole-4,5-dicarboxamides (I45DCs) in a study on heterocyclic HIV-1 protease inhibitors, finding modest inhibitory activity with this class of compounds . The I45DCs are also known to affect memory, to protect embryos from teratogens, and as structural components of antibiotics . Intramolecular hydrogen bonded conformations of I45DCs are structurally similar to purine bases, and select I45DCs are known to influence respiration as well as bind to adenosine receptors .…”

“…The literature route to dissymmetric I45DCs utilizes imidazole-4,5-dicarboxylic acid ( 1 ) as the starting material to create the pyrazine diacid dichloride ( 2 ) in 89% yield by refluxing with SOCl 2 in benzene with catalytic DMF (Scheme ) 6a. Addition of water hydrolyzes the two acid chlorides to give 3 in 97% yield.…”

“…The preparation of 2 was slightly altered in this work as compared with the literature method,6a including modified reagent quantitites and the total time of the reflux. The reactivity of 2 and its relative insolubility in CDCl 3 made routine characterization difficult, as 1 H NMR analysis in DMSO- d 6 results in partial hydrolysis due to the trace water present in the DMSO- d 6 .…”