Oxidative synthesis of benzo[1,4]oxazines from α-branched primary amines and ortho-benzoquinones

Abstract

The efficient oxidative construction of benzo [1,4]oxazines from simple α-branched amines and ortho-benzoquinones is reported. The procedure pivots on a triethylamine and iodine mediated oxidative ring closure from the ketimine intermediate formed upon their condensation. This reaction was shown to tolerate a variety of α-branched benzylamines and downstream derivatization to substituted benzomorpholine structures was also demonstrated.

Condensation-Based Methods for the C–H Bond Functionalization of Amines

“…This strategy was later extended by the same group to the synthesis of 1,4-benzoxazines. 68 Here, imine intermediates are converted into enamines under basic conditions, followed by the oxidation with iodine to provide -iodo imines. Finally, displacement of the iodide by the ortho-hydroxy group provides 1,4-benzoxazines.…”

A new heteropentacyclic system via coupling sterically crowded o-benzoquinone with o-phenylenediamines

“…The reactions of highly electrophilic and redox-active o-quinones with amines, which are vitally important in biomolecular chemistry as rational ways for selective biofunctionalization, 1 cross-linking transformations [2][3][4] and modeling enzymatic processes, 5,6 have been extensively employed for the syntheses of various five-membered, six-membered [7][8][9] and polycyclic 10,11 N,O-heterocyclic systems and o-aminophenols. 12 The detailed mechanisms and outcomes of these reactions, particularly those performed under oxidative conditions, are extremely sensitive to the structural peculiarities of the involved compounds and the reaction conditions.…”

“…12 The detailed mechanisms and outcomes of these reactions, particularly those performed under oxidative conditions, are extremely sensitive to the structural peculiarities of the involved compounds and the reaction conditions. 3,8,13 A representative example of the complexity of the mechanisms of quinone-amine reactions was given by the detailed study of the reaction between 4-methyl catechol ( precursor of the corresponding o-quinone) and propylamine performed under aerobic, oxidative and acidic conditions. 3 Using LC-MS techniques, it was found that more than 60 products, the majority of which were derived via the initial steps of 1,6-conjugate addition, Schiff base condensation and aroxyl phenol coup-ling, were formed within 6 min.…”

Facile Approach to the N,O,S-Heteropentacycles via Condensation of Sterically Crowded 3H-Phenoxazin-3-one with ortho-amino-, hydroxy- and mercaptoanilines

“…Reactivity of 3Hphenoxazin-3-ones is primarily determined by the properties of its p-quinone imine moiety. Therefore, these compounds can react with nucleophiles, in particular with amines, via one of the three pathways: Schiff base formation (attack at C(3) center), Michael type addition (at C(4)) or nucleophilic substitution (SNH) at C(2) center [13][14][15].…”