The Vilsmeier-Haack reaction of isoxazolin-5-ones. Synthesis and reactivity of 2-(dialkylamino)-1,3-oxazin-6-ones

Synthesis, biological evaluation, and molecular modelling studies of potent human neutrophil elastase (HNE) inhibitors

“…A mixture of the appropriate intermediate ( 1a 41 ) (0.57 mmol), K 2 CO 3 (1.14 mmol), and 1-(chloromethyl)-3-methylbenzene (0.86 mmol) in 2 ml of anhydrous acetonitrile was stirred at reflux for 2 h. After cooling, the mixture was concentrated in vacuo , diluted with ice-cold water (10 ml), and extracted with ethyl acetate (3 × 15 ml). The organic phase was dried over sodium sulphate and the solvent was evaporated in vacuo to afford the final compound 2 , which was purified by column chromatography using cyclohexane/ethyl acetate 2:1 as eluent.…”

Reaction of 2‐Alkoxy‐4,5‐diphenyl‐1,3‐oxazin‐6‐one with different alcohols and elucidation of the products

“…For further confirmation of the structure 4a , carbamate acid 3a was prepared by route b. A method for cleavage of some oxazinone derivatives was reported previously [10]. Hydrolysis of compound 1a with dilute sodium hydroxide solution at room temperature (r.t.) followed by HCl gave acid 3a that subsequently was converted to carbamate ester 4a by diazomethane.…”

“…According to Beccalli and Marchesini report about chemical reactivity of the 2‐(dialkylamino)‐1,3‐oxazin‐6‐ones [10], a thermal equilibrium between ketene intermediate a and b in the cleavage of compound 1b could be postulated (Scheme 5).…”

Structures of eight 2-dialkylamino-6H-1,3-oxazin-6-ones

“…The thermal or catalytic alcoholysis rate of these compounds increases with the length of the C(4)-C(5) double bond; for example, the thermal reaction with methanol takes about 2 h to complete for (1), (2), (3), (7), 20h for (6) and about 2 days for (4) and (5) (Beccalli & Marchesini, 1987;. This increasing reaction rate is probably connected with the increasing importance of electronic structures (according to the following scheme) that can favour both nucleophilic and electrophilic attack to the ring.…”

“…A series of 2-dialkylamino-6H-1,3-oxazin-6-ones was synthetized by Beccalli & Marchesini (1987) via a Vilsmeier-Haack reaction on isoxazolin-5-ones. The reactivities of these molecules vary greatly as a function of the substituents at the heterocycle.…”