A. V. Velikorodov, L. Sukhenko
2004
Citations
0
Influential Citations
10
Citations
Journal
Pharmaceutical Chemistry Journal
Abstract
Compounds containing isoxazoline and isoxazole nuclei are known to possess antiinflammatory, antihypertensive, bactericidal, and some other types of biological activity [1 – 3]. In this context, we have studied the antimicrobial properties of some N-arylcarbamates containing isoxazolines and isoxazole rings. Previously [4 – 6], we have reported that the reactions of allyl-N-phenylcarbamate (I), methyl-N-( p-allyloxyphenyl)carbamate (II), and propargyl-N-phenylcarbamate (III) with benzonitrile N-oxides (formed via interaction of benzaldehyde oximes with chloramine B trihydrate in boiling ethanol) yield 3-aryl-5-(N-phenylaminocarboxymethyl)-2isoxazolines (IVa – IVg), 3-aryl-5-( p-methoxycarboxamidophenyloxymethyl)-2-isoxazolines (Va – Vg), and 3-aryl-5(N-phenylaminocarboxymethyl)-2-isoxazoles (VIa – VIg), respectively. Aiming at the study of antimicrobial activity in a broad series of compounds belonging to this class, we have used the same reaction pathways to synthesize the new derivatives IVh – IVj, Vh – Vj, and VIh – VIj. In addition, we have established the possibility of obtaining isoxazolines IV using a different scheme. It was found that the cycloaddition of benzonitrile N-oxides (obtained via interaction of 2-methoxy-, 3-bromo-, and 3,4-dimethoxybenzaldehyde oximes with chloramine B) to dipolarophilic compounds I – III is a regiospecific process leading to a sufficiently high yield of the corresponding isoxazolines IVh – IVj and Vh – Vj and isoxazoles VIh – VIj. In order to establish the boundaries of applicability of this approach to the synthesis of isoxazolines IV and V, we have studied the possibility of in situ cycloaddition of the benzonitrile N-oxides to allyl alcohol. It was found that the interaction of allyl alcohol with 4-nitrobenzaldehyde N-oxides on boiling in ethanol in the presence of chloramine B leads to the formation of a 3,5-disubstituted isoxazoline VII. The regiodirectional character of the 1,3-dipolar cycloaddition reaction is confirmed by the fact that heating compound VII with phenylisocyanate yields isoxazoline identical with compound IVg.