Alkanoylation of quinazoline by nucleophilic aromatic substitution: Combined experimental and computational study. Issue 3 (18th January 2018)

• Record Type: Journal Article
• Authors: Suzuki, Yumiko; Iwata, Naoto; Dobashi, Kohei; Takashima, Ryo; Arulmozhiraja, Sundaram; Ishitsubo, Erika; Matsuo, Naoya; Tokiwa, Hiroaki
• Is Part Of: Tetrahedron. Volume 74:Issue 3(2018)
• Page Start: 392
• Page End: 400
• Publication Date: 2018-01-18
• Subjects: Nitrogen heterocycles -- Breslow intermediate -- Alkanoylation -- Natural bond orbital -- CC bond formation; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tet.2017.11.071
• Languages: English
• ISSNs: 0040-4020

Abstract

Abstract: A combined experimental and computational study on the key intermediates of NHC-catalyzed acylation reaction, Breslow intermediates (BIs), has been conducted in order to achieve a direct nucleophilic alkanoylation of N -heterocycles. Various BI precursors are alternatively prepared and used in the reaction with 4-chloroquinazoline. The present study reveals that the intermediates having benzimidazole moiety serve as acylating agents for the introduction of straight-chain alkanoyl groups. Natural bond orbital analysis indicates that the reactivity of intermediates partly correlates to the occupancy of the π C-C bonds of the hydroxyl enamine moieties. The putative rate-determining step of the acylation reaction has been theoretically investigated. Several new 4-alkanoylquinazolines are synthesized using the BI precursors. Graphical abstract: