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

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.

Synthesis and Conformational Analysis of Naphthoxazine-Fused Phenanthrene Derivatives

“…In analogy to previous investigations [25] and to the results of the structural analyses of 14-16 (vide supra), reactions starting from 21, in all cases, yielded trans isomers 24a, 26a, and 28a. Their NMR spectra are akin to the corresponding spectra of the compounds without an OH group at position 2′ (14)(15)(16) and to compounds having a naphthalene moiety instead of phenanthrene [25].…”

“…The reactive moiety thus formed can be stabilized by reactions with different dienophiles [14,21,22] or it can participate in [4 + 2] cycloadditions with cyclic imines to form new heterocycles [18,23,24]. Very recently the transformation of functionalised 1-aminobenzyl-2-naphthols via [4 + 2] cycloaddition has been examined [25]. It was found that the regio-and diastereoselectivity of the cycloaddition depend on the functional group of the phenyl substituent.…”

Catalyst‐Free Synthesis of Thioethers through C−N Bond Cleavage of Aminonaphthol/Aminophenol Derivatives

“…Hence, readily available aminonaphthol/aminophenol (Betti base) derivatives were chosen as the substrate to investigate the sequential C−N bond cleavage and C−S bond forming reactions. It was presumed that the use of aminonaphthol/aminophenol derivatives as the substrate would result in the formation of the in situ generated ortho ‐quinone methide intermediates [28,29] which on subsequent reaction with thiol would produce the desired thioether derivatives. Hence, both aminonaphthol and aminophenol derivatives 1 a – 1 d were chosen as a model substrates to screen the reaction conditions.…”

Brønsted Acid Promoted Facile Synthesis of Benzoacridines from Aromatic Aldehydes and N‐Phenyl Naphthylamines

“…In view of the significance of these valuable compounds, many efforts have been made in the construction of benzoacridine derivatives. However, most of the early synthesis methods require highly functionalized precursors or multi‐step procedures [11–16] . The general methods for the synthesis of benzoacridines can mainly be classified into three categories.…”