Experimental and DFT studies on competitive heterocyclic rearrangements. 3. A cascade isoxazole-1,2,4-oxadiazole-oxazole rearrangement.
The thermal rearrangements of 3-acylamino-5-methylisoxazoles 1 have been investigated under basic and neutral conditions and interpreted with the support of computational data. The density functional theory (DFT) study on the competitive routes available for the base-catalyzed thermal rearrangement of isoxazoles 1 showed that the Boulton-Katritzky (BK) rearrangement, producing the less stable 3-acetonyl-1,2,4-oxadiazoles 5, is a much more favored process than either the migration-nucleophilic attack-cyclization (MNAC) or the ring contraction-ring expansion (RCRE). In turn, an increase in reaction temperature will promote the MNAC of oxadiazoles 5, producing the more stable 2-acylaminooxazoles 8. The thermal rearrangement of 3-acylaminoisoxazoles 1 into oxazoles 8 can therefore be interpreted in terms of a cascade BK-MNAC rearrangement involving 3-acetonyl-1,2,4-oxadiazoles 5 as ancillary intermediates.
Pace
Andrea
A
Dipartimento di Chimica Organica E. Paterno, Universita degli Studi di Palermo, Viale delle Scienze, Parco d'Orleans II, Edificio 17, I-90128 Palermo, Italy. pace@unipa.it
Pierro
Paola
P
Buscemi
Silvestre
S
Vivona
Nicolò
N
Barone
Giampaolo
G
D003198:Computer Simulation; D003500:Cyclization; D008956:Models, Chemical; D015394:Molecular Structure; D010080:Oxazoles / Q000138:chemical synthesis / Q000737:chemistry*; D013237:Stereoisomerism; D013696:Temperature
D010080:Oxazoles