Catalyst-Free Synthesis of Functionalized 4-Substituted-4H-Benzo[d][1,3]oxazines via Intramolecular Cyclization of ortho-Amide-N-tosylhydrazones

Abstract

Functionalized 4-aryl-4H-benzo­[d]­[1,3]­oxazines are synthesized under transition-metal-free conditions using ortho-amide-N-tosylhydrazones. This synthetic method uses readily available N-tosylhydrazones as the diazo compound precursors and involves an intramolecular ring closure reaction mediated by a protic polar additive (iPrOH). A wide range of functionalized oxazines are obtained by this straightforward method in good to excellent yields. Furthermore, the viability of our strategy is illustrated by the gram-scale elaboration of a bromo-substituted 4H-benzo­[d]­[1,3]­oxazine and its post-functionalization by palladium-catalyzed cross-couplings.

Leveraging in situ N-tosylhydrazones as diazo surrogates for efficient access to pyrazolo-[1,5-c]quinazolinone derivatives

“…Compound 2r was then subjected to various post-functionalization reactions. A Suzuki–Miyaura cross-coupling was performed with (3-methoxyphenyl)boronic acid, K 3 PO 4 as the base and PdCl 2 (PPh 3 ) 2 as the catalyst in DME/H 2 O/EtOH 31 to afford 3 in 83% yield (Scheme 4, eqn (2)).…”

“…Given our sustained interest in studying the reactivity of N -tosylhydrazones (NTHs), 25–32 we formulated plans to investigate reactions involving these reactive species for the construction of N-heterocyclic moieties, specifically the pyrazolo-[1,5- c ]quinazolinone scaffold. Within this framework, we conceived an original strategy for pyrazolo-[1,5- c ]quinazolinone synthesis through intramolecular cycloaddition (Scheme 1g).…”

Direct Regioselective Reductive Allylation of Imines: Application to Synthesis of Oxazines with Halogenated Reagent

“…Compared to the well-developed oxazoline ligands, oxazine ligands with a six member ring have been found to exhibit specific catalytic activities in the transition metal catalysis . In addition, oxazines are prevalent scaffolds in pharmaceuticals and biologically active molecules, such as 1,3-disubstituted-1 H -naphtho­[1,2- e ]­[1,3]­oxazines (Antimicrobal activity) and Etifoxine (anxiolytic and anticonvulsant drug) (Figure A) . Although it is very sensitive to acid, numerous synthetic approaches toward that core have been developed .…”