Novel Thermal and Microwave-Assisted Facile Route to Naphthalen-2(1H)-ones via an Oxidative Alkoxylation-Ring-Opening Protocol

Abstract

Several novel 1,1-disubstituted-8-hydroxynaphthalen-2(1H)-ones have been efficiently synthesized via a two-step sequence from 2-hydroxy-1-naphthaldehyde oxime. The methodology involves oxidative ring closure and alkoxylation to 3a-alkoxynaphtho[1,8-de][1,2]oxazin-4(3aH)-ones, followed by thermal ring-opening. Both thermal and microwave irradiation conditions were used. A novel one-pot reaction of oxime to 8-isopropoxynaphthalene-1,7-diol using microwave irradiation is also reported.

Intramolecular cyclization of β-nitroso-o-quinone methides. A theoretical endoscopy of a potentially useful innate ‘reclusive’ reaction

“…In our earlier reports, they have been proposed as transiently generated during the oxidation of o-hydroxyaryl acyloximes. [42][43][44][45] A theoretical insight into the salient features of the structure of 3 and 4 (all its isomers) and the reflection upon M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT 4 their reactivity profile has been recently reported. 46 Many useful heterocylic structures have been and can be prepared from these intermediates, fused 1,2-oxazoles 9 or 10 and 1,2-oxazines 12 among them (Scheme 1).…”

“…Furthermore, ring opening of these heterocycles, asymmetric reduction in particular, provides access to optically active structures, core components in a variety of medicines. 48 Indeed, facile ring cleavage of 1,2-oxazine 12 43,44 or 1,2-oxazole 9 49 lead to chemically and biologically useful outcomes, for instance ring hydroxylation 43,44 or diaryl amines as perspective metal ion chelating ligands. It is, thus, the documented significance of 1 (or 2) and the potential of their nitroso analogues 3 (or 4) as key intermediates or that of 9 and 12 in (bio)organic synthesis and biology, outlined above, along with some intriguing experimental data, 44,45 that sparked the present theoretical insight into the pathways of their innate intramolecular reactivity profile.…”

“…Experimental findings on the cyclization of 3 or 4, oxidatively generated from the oximes 5 or 6, have been quite intriguing, with regard to the varying reaction outcomes. [43][44][45] Accordingly, 3b,c and 4a-d give the corresponding 9 and 10, respectively (Scheme 1, path (iv) ) while 3a is quite tempermental, furnishing mainly hydrolysis and polymerization products. 42,43 The latter is a hardly surprising result, taking note of (a) the propensity of 3a to rapid re-aromatization and (b) the C-3 unsubstituted reactive position of 9, as soon as it is formed, giving rise to other, alternative to cyclization, competing reactions.…”

“…In that case, however, benzo-fusion (a) confers stabilization and (b) offers alternative peri-cyclization routes (Scheme 1, paths (v) and (vi) ). 43,44,46 Lead (IV) acetate (LTA) oxidation of oximes 5 or 6 produces both 12 and 14 78 while the use of phenyliododiacetate (PIDA) as oxidant, under similar conditions, directs the reaction selectively to 12. [43][44][45]79 Worth noting is that the reaction proceeds equally well in solvents of varying polarity, e.g.…”

“…The reaction is so fast that takes precedence over any other that could compete through the presence of a nucleophile. 44 The term "reclusive" is, therefore, coined to identify its uniqueness.…”