Α‐ and β‐Lapachone Isomerization in Acidic Media: Insights from Experimental and Implicit/Explicit Solvation Approaches. Issue 1 (13th December 2018)

• Record Type: Journal Article
• Authors: Delarmelina, Maicon; Nicoletti, Caroline D.; de Moraes, Marcela C.; Futuro, Debora O.; Bühl, Michael; de C. da Silva, Fernando; Ferreira, Vitor F.; de M. Carneiro, José W.
• Is Part Of: ChemPlusChem. Volume 84:Issue 1(2019)
• Page Start: 52
• Page End: 61
• Publication Date: 2018-12-13
• Subjects: acidic solution -- density functional calculations -- explicit solvation -- lapachol -- lapachone; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/cplu.201800485
• Languages: English
• ISSNs: 2192-6506

Abstract

Abstract: Combined experimental and mixed implicit/explicit solvation approaches were employed to gain insights into the origin of switchable regioselectivity of acid‐catalyzed lapachol cyclization and α‐/β‐lapachone isomerization. It was found that solvating species under distinct experimental conditions stabilized α‐ and β‐lapachone differently, thus altering the identity of the thermodynamic product. The energy profile for lapachol cyclization revealed that this process can occur with low free‐energy barriers (lower than 8.0 kcal mol −1 ). For α/β isomerization in a dilute medium, the computed enthalpic barriers are 15.1 kcal mol −1 (α→β) and 14.2 kcal mol −1 (β→α). These barriers are lowered in concentrated medium to 11.5 and 12.6 kcal mol −1, respectively. Experimental determination of isomers ratio was quantified by HPLC and NMR measurements. These findings provide insights into the chemical behavior of lapachol and lapachone derivatives in more complex environments. Abstract : A conundrum : Combined experimental and mixed implicit/explicit solvation approaches have been employed to gain insights into the origin of switchable regioselectivity of acid‐catalyzed lapachol cyclization and α‐/β‐lapachone isomerization. Solvating species under distinct experimental conditions stabilized α‐ and β‐lapachone differently, thus altering the identity of the thermodynamic product (see figure).