Permanganate oxidation of 3-methyl-4-nitro-5-styrilisoxazole: a correction

An anomalous hydration/dehydration sequence for the mild generation of a nitrile oxide

“…22 Upon heating in DMF at 100 °C in the absence of nucleophile, isoxazolone 5a was found to remain intact, but bubbles were formed in the reaction mixture after activated carbon was 25 added. From this mixture, bis(N-methylcarbamoyl)-1,2,5-oxadiazole-2-oxide (furoxan) (6) could be isolated in 40% yield (based on 5a), indicating the in situ generation of carbamoylnitrile oxide (2d, R 1 = Me, R 2 = H) from nitroisoxazolone 5a and the concurrent elimination of carbon 30 dioxide.…”

“…1 With the growing demand for environmentfriendly synthesis protocols, there has been increased focus on 1,3-dipolar cycloaddition reactions in aqueous media. 2 Nitrile oxide, one of the most popular classes of 1,3-dipoles, affords isoxazoles, 2-isoxazolines, and 1,2,4-oxadiazoles upon 25 treatment with alkynes, alkenes, and nitriles, respectively. [1][2][3][4] While there are numerous reports on nitrile oxides, most of them are related to aryl-or alkyl-substituted nitrile oxides.…”

“…20c Since even anionic isoxazolone 4a is deprotonated by 5 pyrrolidine, the ring proton of N-methylisoxazolone 5a should be sufficiently acidic for easy deprotonation by water. 2,3-Dimethylnitroisoxazolone 5b, 25 which has no ring protons, remains intact under the same conditions to be recovered, although the steric effect of the additional methyl group in this 10 compound must be taken into consideration. On the basis of these observations, we propose a plausible mechanism for the generation of nitrile oxide 2d, as shown in Scheme 5.…”

“…27 In our reaction, the cummulene carbon of ketenimine 13 is attacked by water to afford α-hydroxy-β-nitroenamine 14 (route a), which in turn undergoes a tautomeric rearrangement to form nitroacetamide 9 by tautomerism. Another reaction path (route b), 25 which involves the intramolecular attack of carboxylate on the cummulene carbon to give β-lactone 15, can also be considered.…”

“…Relative energies (kcal/mol) for the formation of 2d' from 17' via transition state 19 with simultaneous decarboxylation and dehydration. 25 Nitroacetates can be used as the precursors of nitrile oxide 1, which has an ester function; however, dehydrating agents and severe conditions need to be employed for this conversion. 6-9 Indeed, nitroacetamide 9, the tautomer of 30 hydroxynitroenamine 14, is not converted to nitrile oxide 2d upon treatment with an acetonitrile/water (3/1, v/v) mixture alone.…”