{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T04:48:22Z","timestamp":1785905302664,"version":"3.56.0"},"reference-count":21,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Six 9-thienyl-10-aryl-substituted 3,3,6,6-tetramethyl-decahydroacridine-1,8-diones (5a\u2013f) 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\u201375%, corresponding to calculated overall two-step yields of 58.2\u201368.6% after accounting for the isolated enaminone-preparation yields. These overall yields remained higher than those of the one-pot procedure (40\u201347%), 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\u2013c were isolated in 13\u201315% yields and showed diagnostic spectral changes relative to 5a\u2013f, including loss of the C-9 methine resonance and appearance of a strongly deshielded aromatic proton at 9.17\u20139.21 ppm. Within the limitations of an operational preparative comparison, the product distribution is consistent with a sequence-control interpretation in which preformation of the \u03b2-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.<\/jats:p>","DOI":"10.3390\/molecules31152680","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T15:02:01Z","timestamp":1785510121000},"page":"2680","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sequence-Controlled Synthesis of Heteroaryl-Substituted Decahydroacridine-1,8-diones: Comparative Evaluation of Preformed Enaminone and Multicomponent Routes"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1140-1996","authenticated-orcid":false,"given":"G\u00f6khan","family":"\u00d6zokan","sequence":"first","affiliation":[{"name":"Department of Chemistry, Faculty of Science, Yildiz Technical University, Davutpasa Campus, Istanbul 34220, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"o3743","DOI":"10.1107\/S1600536805032903","article-title":"9-(4-Chlorophenyl)-3,3,6,6-tetramethyl-1,8-dioxo-1,2,3,4,5,6,7,8,9,10-decahydroacridine-10-acetic acid","volume":"61","author":"Tu","year":"2005","journal-title":"Acta Crystallogr. Sect. E"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"o1870","DOI":"10.1107\/S1600536804023621","article-title":"9-(4-Hydroxy-3-methoxyphenyl)-3,3,6,6,10-pentamethyl-1,2,3,4,5,6,7,8,9,10-decahydroacridine-1,8-dione","volume":"60","author":"Tu","year":"2004","journal-title":"Acta Crystallogr. Sect. E"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"o2328","DOI":"10.1107\/S1600536804028612","article-title":"10-Cyclopropyl-9-(4-hydroxy-3-methoxyphenyl)-3,3,6,6-tetramethyl-1,2,3,4,5,6,7,8,9,10-decahydroacridine-1,8-dione","volume":"60","author":"Tu","year":"2004","journal-title":"Acta Crystallogr. Sect. E"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"o383","DOI":"10.1107\/S1600536801005189","article-title":"9-(4-Chlorophenyl)-3,3,6,6-tetramethyl-1,2,3,4,5,6,7,8,9,10-decahydroacridine-1,8-dione","volume":"57","author":"Tu","year":"2001","journal-title":"Acta Crystallogr. Sect. E"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"o1326","DOI":"10.1107\/S1600536806007951","article-title":"9-(3,4-Dichlorophenyl)-3,3,6,6-tetramethyl-1,2,3,4,5,6,7,8,9,10-decahydroacridine-1,8-dione","volume":"62","author":"Rong","year":"2006","journal-title":"Acta Crystallogr. Sect. E"},{"key":"ref_6","first-page":"821","article-title":"10-(4-Fluorophenyl)-substituted hexahydroacridine-1,8-diones","volume":"57","author":"Pandi","year":"2001","journal-title":"Acta Crystallogr. Sect. C"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"o1330","DOI":"10.1107\/S160053680201958X","article-title":"10-[2-(4-Hydroxyphenyl)ethyl]-3,3,6,6,9-pentamethylhexahydroacridine-1,8-dione","volume":"58","author":"Seshadri","year":"2002","journal-title":"Acta Crystallogr. Sect. E"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"o696","DOI":"10.1107\/S1600536803007530","article-title":"10-[2-(4-Acetylpiperazin-1-yl)ethyl]-9-(4-chlorophenyl)-3,3,6,6-tetramethylhexahydroacridine-1,8-dione","volume":"59","author":"Seshadri","year":"2003","journal-title":"Acta Crystallogr. Sect. E"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"o1139","DOI":"10.1107\/S1600536803015125","article-title":"9-(4-Chlorophenyl)-3,3,6,6-tetramethyl-10-(4-methylphenyl)-decahydroacridine-1,8-dione","volume":"59","author":"Wang","year":"2003","journal-title":"Acta Crystallogr. Sect. E"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"o1446","DOI":"10.1107\/S1600536803019378","article-title":"3,3,6,6-Tetramethyl-9-(3,4-methylenedioxyphenyl)-decahydroacridine-1,8-dione","volume":"59","author":"Li","year":"2003","journal-title":"Acta Crystallogr. Sect. E"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1039\/a701401e","article-title":"Synthesis and laser properties of 9-alkyl-3,3,6,6-tetramethyl-decahydroacridine-1,8-dione derivatives","volume":"27","author":"Murugan","year":"1998","journal-title":"J. Chem. Soc. Perkin Trans. 2"},{"key":"ref_12","unstructured":"Martin, J.A., Sherborne, B.S., and Taylor, G.M. (1999). Acridine Derivatives. (5,969,139), U.S. Patent."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2210","DOI":"10.1002\/slct.202004536","article-title":"Acridine-1,8-diones: Synthesis and biological applications","volume":"6","author":"Sahiba","year":"2021","journal-title":"ChemistrySelect"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Alam, M.M., Mubarak, A.T., Assiri, M.A., Ahmed, S.M., and Fouda, A.M. (2019). A facile and efficient synthesis of 1,8-dioxodecahydroacridine derivatives catalyzed by a cobalt-alanine metal complex under aqueous ethanol conditions. BMC Chem., 13.","DOI":"10.1186\/s13065-019-0545-3"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1002\/ajoc.202100286","article-title":"Multicomponent dehydrogenative synthesis of acridine-1,8-diones catalyzed by Ru-doped hydrotalcite","volume":"10","author":"Sardar","year":"2021","journal-title":"Asian J. Org. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2633","DOI":"10.1039\/D3RA07629F","article-title":"Accelerated synthesis of 1,8-dioxo-octahydroxanthene and 1,8-dioxo-decahydroacridine derivatives using dendritic mesoporous nanosilica functionalized by hexamethylenetetramine","volume":"14","author":"Sabri","year":"2024","journal-title":"RSC Adv."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"20696","DOI":"10.1038\/s41598-024-71898-y","article-title":"Synthesis and characterization of bentonite-based NiO nanoparticles as a bifunctional heterogeneous catalyst for efficient synthesis of 1,8-dioxo-decahydroacridines","volume":"14","author":"Faryabi","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1039\/D4NA00264D","article-title":"A supramolecular magnetic and multifunctional Titriplex V-grafted chitosan organocatalyst for the synthesis of acridine-1,8-diones and 2-amino-3-cyano-4H-pyran derivatives","volume":"7","author":"Hassanzadeh","year":"2025","journal-title":"Nanoscale Adv."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3283","DOI":"10.1007\/s10311-021-01223-w","article-title":"Green synthesis of xanthene- and acridine-based heterocycles of pharmaceutical importance: A review","volume":"19","author":"Burange","year":"2021","journal-title":"Environ. Chem. Lett."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4187","DOI":"10.1055\/s-2006-950365","article-title":"An improved and benign synthesis of 9,10-diarylacridine-1,8-dione and indenoquinoline derivatives from 3-anilino-5,5-dimethylcyclohex-2-enones, benzaldehydes, and 1,3-dicarbonyl compounds in an ionic liquid medium","volume":"2006","author":"Wang","year":"2006","journal-title":"Synthesis"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1947","DOI":"10.1021\/jm00066a003","article-title":"Synthesis and anticonvulsant activity of enaminones. 2. Further structure-activity correlations","volume":"36","author":"Scott","year":"1993","journal-title":"J. Med. Chem."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/15\/2680\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T04:16:45Z","timestamp":1785903405000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/15\/2680"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,31]]},"references-count":21,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["molecules31152680"],"URL":"https:\/\/doi.org\/10.3390\/molecules31152680","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,31]]}}}