Synthesis of 5-hetaryluracil derivatives via 1,3-dipolar cycloaddition reaction

Abstract

1,3-Dipolar cycloaddition is a convenient method for construction of various heterocyclic systems. We applied this method for the synthesis 5-hetaryluracil derivatives where substituted uracils played the role of 1,3-dipoles or dipolarophiles. Treatment of the nitrile oxide derived from 5-formyluracil and substituted alkenes gave the appropriate 5-(4,5-dihydroisoxazol-3-yl)pyrimidine-2,4(1H,3H)-diones, which by oxidation with Nbromosuccinimide were transformed into appropriate 5-(isoxazol-3-yl)uracils. When 5-cyanouracil was used as a dipolarophile in the reaction with nitrile oxides, generated from aromatic aldoximes, several 5-(1,2,4-oxadiazol-5-yl)uracils were obtained. An alternative reaction of 5-formyluracil with an excess of nitriles in the presence of cerium ammonium nitrate as an oxidant gave 1,2,4-oxadiazol-3-yl derivatives in moderate yields.

Nitrile Oxide, Alkenes, Dipolar Cycloaddition, Isomerization and Metathesis Involved in the Syntheses of 2-Isoxazolines

“…The same year, Jakubiec and coworkers described the synthesis of 3,5-disubstituted 2-isoxazolines equipped with uracyl motif in position 3. They performed regioselective 1,3-DP cycloaddition of uracyl-motif-containing nitrile oxide to dipolarophiles of the RCH=CH 2 type—see Scheme 122 below [ 130 ].…”

“… Syntheses of 2-isoxazolines possessing uracyl motif in position 3 [ 130 ]. R 1 , R 2 , R 3 = Me, Me, CN; CH 2 CH 2 COOMe, H, CN; Me, Me, OEt; and others; a = NCS, CHCl 3 , rt, 2 h; b = NEt 3 , CHCl 3 , rt, 24 h; up to 65% yield.…”