Synthesis, characterization, and antibacterial activity of novel bis(indolyl)methanes sourced from biorenewable furfurals using gluconic acid aqueous solution (GAAS) as a sustainable catalyst.

Bis(indolyl)methanes (BIMs) are important heterocycle-containing molecular scaffolds that show remarkable biological and pharmacological activities. This work reports the synthesis of novel BIMs using carbohydrate-derived 5-substituted-2-furaldehydes as renewable reactants. Structural diversity was introduced in the BIMs as substituents in the indole and furaldehyde moieties. Various commonly encountered biorenewable carboxylic acids were screened as catalysts for the acid-catalyzed transformation under organic solvent-free conditions. All the novel BIMs were characterized by spectroscopic techniques (FTIR, 1H-NMR, 13C-NMR) and elemental analysis. The reaction was optimized on the reaction temperature, duration, catalyst type, and catalyst loading. The gluconic acid aqueous solution (GAAS) showed the best catalytic activity for the transformation, affording satisfactory isolated yields (68-96%) of the targeted BIMs under optimized conditions. The GAAS catalyst was conveniently recovered from the reaction mixture and reused for four consecutive cycles without catastrophic loss in either mass or activity. Moreover, the antibacterial activities of the novel BIMs were studied on Gram-positive and Gram-negative bacterial strains, such as Enterococcus faecalis and Pseudomonas syringae.

Efficient Synthesis of Novel Biginelli and Hantzsch Products Sourced from Biorenewable Furfurals Using Gluconic Acid Aqueous Solution as the Green Organocatalyst.

The Biginelli reaction provides 3,4-dihydropyrimidin-2(1H)-ones (DHPMs), whereas the Hantzsch reaction leads to 1,4-dihydropyridines (DHPs) by the one-pot, multicomponent, and operationally simple transformations starting from readily available starting materials. DHPMs and DHPs are well-established heterocyclic moieties in the synthetic organic chemistry literature and have pronounced pharmacological activities. This work reports the synthesis of novel DHPMs and DHPs from carbohydrate-derived 5-substituted-2-furaldehydes by employing gluconic acid aqueous solution (GAAS) as an efficient, inexpensive, and eco-friendly catalyst. The use of urea (or thiourea) as the reagent led to DHPMs, whereas ammonium acetate produced DHPs, selectively, keeping the other two starting materials (i.e., furfurals and ethyl acetoacetate) and the reaction parameters unaltered. Using the general synthetic protocol under optimized reaction conditions (60 °C, 3-6 h, 25 mol % GAAS cat.), all the DHPM and DHP derivatives were obtained in good to excellent isolated yields.