Intra- and intermolecular thermal transformations of 2-acyl- and 2-alkoxycarbonyl-N-phthalimidoaziridines

Abstract

Heating 2-acyl-and 2-alkoxycarbonyl-N-phthalimidoaziridines leads to substituted oxazoles in 45-65% yield. Only esters of oxazolecarboxylic acids are formed when the aziridine contains acyl and alkoxy groups. The thermolysis of the same aziridines in the presence of N-phenylmaleimide and the dimethyl ester of acetylenedicarboxylic acid gives both oxazoles and the products of 1,3-dipolar cycloaddition from aziridines with two substituents at the carbon atoms but only oxazoles from trisubstituted aziridines.The thermally or photochemically induced dissociation of the C−C bond in the strained aziridine ring leads to 1,3-dipoles, which have been termed azomethinylids [1]. The addition of these species at multiple bonds of dipolarophiles yields various five-membered nitrogen heterocycles [2]. The generation of azomethinylids upon heating derivatives of N-phthalimidoaziridine and subsequent 1,3-dipolar cycloaddition have been demonstrated experimentally [3][4][5]. On the other hand, heating N-phthalimidoaziridines having acyl [6] or alkoxycarbonyl substituents [7] at the carbon atoms of the aziridine ring in the absence of dipolarophiles leads to oxazoles, which may be attributed to a 1,5-electrocyclization of the intermediate acylazomethinylids accompanied by loss of the phthalimide group.Thus, two types of thermal transformations are possible for acyl and alkoxycarbonyl derivatives of N-phthalimidoaziridine: 1) 1,3-dipolar cycloaddition and 2) rearrangement to give oxazoles. These reactions may compete and their preparative value will depend on which pathway predominates. In the present work, we studied both the intra-and intermolecular thermal transformations of 2-acyl-and 2-alkoxy-N-phthalimidoaziridines.We selected aziridines 1a-f for this study. The corresponding oxazole has already been obtained in 60% yield upon heating aziridine 1a [6]. However, the reaction of this aziridine with dipolarophiles has not been investigated. Aziridines 1b,c were selected in light of the possibility of obtaining not readily available spirofused heterocyclic structures as the result of 1,3-dipolar cycloaddition. We considered the possibility of _______ * Dedicated to Leonid Isaakovich Belen'kii on the occasion of his eightieth birthday.

Azirinium ylides from α-diazoketones and 2H-azirines on the route to 2H-1,4-oxazines: three-membered ring opening vs 1,5-cyclization

“…Several examples of the 1,5-cyclization of azomethine ylides bearing an α-keto group into oxazole derivatives were reported [ 27 – 29 ]. As also known, the azomethine ylide derived from N -benzylideneanisidine and diazoacetylacetone under Rh 2 (OAc) 4 -catalysis undergoes 1,3-cyclization to an aziridine derivative in high yield, rather than 1,5-cyclization [ 22 ].…”

Room Temperature Copper(II)-Catalyzed Oxidative Cyclization of Enamides to 2,5-Disubstituted Oxazoles via Vinylic C–H Functionalization

“…: 82 °C). 42 1 H NMR (400 MHz, CDCl 3 ) δ: 8.09 (d, J = 7.6 Hz, 2H), 7.49-7.44 (ovrlp, 5H), 7.35 (t, J = 7.2 Hz, 2H), 7.27 (t, J = 7.2 Hz, 1H), 7.13 (t, J = 7.6 Hz, 2H), 6.90 (d, J = 16.4 Hz, 1H). 13 C NMR (100 MHz, CDCl 3 ) δ: 161.1, 150.4, 136.4, 130.5, 129.5, 128.9, 128.3, 127.4, 126.62, 126.57, 126.4, 113.1.…”

Intramolecular thermal transformations of N-phthalimidoaziridines: 1,3-dipolar cyclo-addition and rearrangements*

“…5-Methoxyoxazole 16, which may be seen as the product of the 1,5-electrocyclization of the intermediate azomethine ylide with subsequent loss of a phthalimide molecule and formation of the aromatic oxazole system (see our previous works [10,11]) was isolated from the reaction mixture in addition to phthalimide and 2-benzyloxybenzaldehyde. This is the first report of the preparation of 5-methoxyoxazole 16 but due to the instability of this compound at room temperature, we were able to record only its 1 H NMR spectrum displaying a singlet at _______ *The yields of imines 13a and 14a were calculated using the 1 H NMR spectrum of the reaction mixture relative to isolated product 12, while the yields of imines 13b and 14b were calculated from the 1 H NMR spectrum of their mixture.…”