Ortho-Quinone Methide Driven Synthesis of New O,N- or N,N-Heterocycles

István Szatmári, Khadija Belasri, Matthias Heydenreich, Andreas Koch, Erich Kleinpeter, Ferenc Fülöp

Research output: Contribution to journalArticle

Abstract

To synthesize functionalized Mannich bases that can serve two different types of ortho-quinone methide (o-QM) intermediates, 2-naphthol and 6-hydroxyquinoline were reacted with salicylic aldehyde in the presence of morpholine. The Mannich bases that can form o-QM and aza-o-QM were also synthesized by mixing 2-naphthol, 2-nitrobenzaldehyde, and morpholine followed by reduction of the nitro group. The highly functionalized aminonaphthol derivatives were then tested in [4+2] cycloaddition with different cyclic imines. The reaction proved to be both regio- and diastereoselective. In all cases, only one reaction product was obtained. Detailed structural analyses of the new polyheterocycles as well as conformational studies including DFT modelling were performed. The relative stability of o-QMs/aza-o-QM were also calculated, and the regioselectivity of the reactions could be explained only when the cycloaddition started from aminodiol 4. It was summarized that starting from diaminonaphthol 25, the regioselectivity of the reaction is driven by the higher nucleophilicity of the amino group compared with the hydroxy group. 12H-benzo[a]xanthen-12-one (11), formed via o-QM formation, was isolated as a side product. The proton NMR spectrum of 11 proved to be very unique from NMR point of view. The reason for the extreme low-field position of proton H-1 could be accounted for by theoretical calculation of structure and spatial magnetic properties of the compound in combination of ring current effects of the aromatic moieties and steric compression within the heavily hindered H(1)-C(1)-C(12b)-C(12a)-C(12)=O structural fragment.

Original languageEnglish
Pages (from-to)961-971
Number of pages11
JournalChemistryOpen
Volume8
Issue number7
DOIs
Publication statusPublished - Jul 2019

Keywords

  • DFT calculations
  • NMR spectroscopy
  • conformational analysis
  • cycloaddition
  • modified Mannich reaction
  • ortho-quinone methide (o-QMs)

ASJC Scopus subject areas

  • Chemistry(all)

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