Abstract

Six 9-thienyl-10-aryl-substituted 3,3,6,6-tetramethyl-decahydroacridine-1,8-diones (5a–f) were prepared by two acid-mediated routes that used the same solvent, temperature, and reaction time. In the sequential route, preformed 5,5-dimethyl-3-(arylamino)cyclohex-2-enones were reacted with a heteroaryl aldehyde and dimedone; in the corresponding one-pot route, the arylamine, heteroaryl aldehyde, and two equivalents of dimedone were combined directly. The isolated yields of the product-forming second stage were 71–75%, corresponding to calculated overall two-step yields of 58.2–68.6% after accounting for the isolated enaminone-preparation yields. These overall yields remained higher than those of the one-pot procedure (40–47%), although the sequential protocol required an additional reaction, isolation, catalyst charge, and solvent-intensive operation. Structural assignments were based on the available IR, 1H NMR, 13C NMR, and EI-MS data. Tetrahydroacridinone by-products 6a–c were isolated in 13–15% yields and showed diagnostic spectral changes relative to 5a–f, including loss of the C-9 methine resonance and appearance of a strongly deshielded aromatic proton at 9.17–9.21 ppm. Within the limitations of an operational preparative comparison, the product distribution is consistent with a sequence-control interpretation in which preformation of the β-enaminone favors the 1:1:2 aldehyde/amine/dimedone product, whereas simultaneous component activation permits competing Knoevenagel, xanthene-forming, and aromatization pathways. This study provides a practical synthesis of thienyl-substituted decahydroacridine-1,8-diones and a mechanistically cautious explanation for the reduced selectivity of the one-pot process.

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