Conventional vs. Microwave- or Mechanically-Assisted Synthesis of Dihomooxacalix[4]arene Phthalimides: NMR, X-ray and Photophysical Analysis

• Main Authors: Alexandre S. Miranda, Paula M. Marcos, José R. Ascenso, M. Paula Robalo, Vasco D. B. Bonifácio, Mário N. Berberan-Santos, Neal Hickey, Silvano Geremia
• Format: Article
• Language: English
• Published: MDPI AG 2021-03-01
• Series: Molecules
• Subjects: dihomooxacalix[4]arenes; phthalimide derivatives; conventional synthesis; microwave irradiation; ball milling; NMR spectroscopy
• Online Access: https://www.mdpi.com/1420-3049/26/6/1503

Direct <i>O</i>-alkylation of <i>p-tert</i>-butyldihomooxacalix[⁴]arene (<b>1</b>) with <i>N</i>-(bromopropyl)- or <i>N</i>-(bromoethyl)phthalimides and K₂CO₃ in acetonitrile was conducted under conventional heating (reflux) and using microwave irradiation and ball milling methodologies. The reactions afforded mono- and mainly distal di-substituted derivatives in the cone conformation, in a total of eight compounds. They were isolated by column chromatography, and their conformations and the substitution patterns were established by NMR spectroscopy (¹H, ¹³C, COSY and NOESY experiments). The X-ray structures of four dihomooxacalix[⁴]arene phthalimide derivatives (<b>2a</b>, <b>3a</b>, <b>3b</b> and <b>5a</b>) are reported, as well as their photophysical properties. The microwave (MW)-assisted alkylations drastically reduced the reaction times (from days to less than 45 min) and produced higher yields of both 1,3-di-substituted phthalimides (<b>3a</b> and <b>6a)</b> with higher selectivity. Ball milling did not reveal to be a good method for this kind of reaction.