High-Temperature Rearrangements of 2-Acylisoxazol-5(2H)-ones and Related Oxazoles.

Abstract

2-Acyl-3-arylisoxazol-5(2H)-ones give 2-alkyl(aryl)-4-aryloxazoles in good yields at 540°C under flash vacuum pyrolysis conditions, but at higher temperatures the expected oxazoles are accompanied by increasing amounts of isomeric 2,5-disubstituted oxazoles, as well as anilides and decomposition products of the 2,4-disubstituted oxazole. The rearrangement mechanisms have been studied by the use of 13C labelled substrates and p-substituted 3-arylisoxazolones. The 2,5-disubstituted oxazoles are considered to arise from 1H-azirines, and the anilides from the nitrone ketene isomer of the acylisoxazolone.

Switchable Synthesis of Pyrroles and Pyrazines via Rh(II)-Catalyzed Reaction of 1,2,3-Triazoles with Isoxazoles: Experimental and DFT Evidence for the 1,4-Diazahexatriene Intermediate

“…Then ethanol (18 mL) was added to the reaction mixture, and refluxing continued for 30 min. The mixture was cooled and filtered off to give isoxazolone 19 as a yellow solid (2.5 g, 89%): mp 143–146 °C (lit . 145–148 °C).…”

“…4-(4-Chlorophenyl)-1-(4-methylphenylsulfonyl)-1H-1,2,3-triazole (4d): 23 White solid (1. 26 Rh-Catalyzed Reactions of Isoxazoles 3a−m with 1-Sulfonyl-1,2,3-triazoles 4a−e. Method A. Isoxazole 3 (0.29 mmol, 1 equiv), triazole 4 (0.32 mmol, 1.1 equiv), Rh 2 (OAc) 4 (3.2 mg, 0.025 equiv), and CHCl 3 (0.5 mL) were placed into a screw cap glass tube and heated at 100 °C (oil bath temperature) under stirring for 1−6 h until full consumption of isoxazole was detected (control by TLC, hexane− Et 2 O 3:1); if necessary, an additional amount of triazole was added (total amount see below).…”

“…Methyl 3-(4-Nitrophenyl)-3-oxopropanoate (18). 25 The procedure of Clark et al 26 was modified. To a rapidly stirred solution of diisopropylamine (16.3 mL, 116 mmol) in dry tetrahydrofuran (60 mL) under argon at −80 °C was added n-butyllithium (2.5 M in hexane, 47 mL), followed after 10 min by methyl acetate (9.3 mL, 116 mmol).…”

“…The organic layer was washed intensively with 5% NaHCO 3 (300 mL), water (300 mL), and brine (300 mL), dried, and concentrated in vacuo, affording the product as a pale yellow solid (11. 3-(4-Nitrophenyl)isoxazol-5(4H)-one (19). 26 Methyl 3-(4-nitrophenyl)-3-oxopropanoate 18 (3.0 g, 13.5 mmol) and H 2 NOH•HCl (2.8 g, 40.3 mmol) were refluxed in water (15 mL) for 5 min. Then ethanol (18 mL) was added to the reaction mixture, and refluxing continued for 30 min.…”

Synthesis and Reactivity of Novel 5-Imino-1,2-oxazole

“…Development of simple methods for the synthesis of new analogs of bioactive heterocyclic compounds is of extreme importance in heterocyclic and medicinal chemistry. The yet unknown 5-imino-1,2-oxazoles (I) are analogs of 1,2-oxazol-5-ones (II) (Figure 1), a class of compounds which are useful synthetic intermediates for the preparation of heterocyclic compounds, [1][2][3][4] and has attracted considerable attention in medicinal chemistry due to their pharmacological activity, 5,6 as well as remarkable activity as anti-inflammatory agents, 5,7 and anti-cancer agents. 8,9 They are also used for the treatment of central nervous system disorder.…”