Experimental and DFT Studies on Competitive Heterocyclic Rearrangements. Part 2: 1 A One-Atom Side-Chain versus the Classic Three-Atom Side-Chain (Boulton−Katritzky) Ring Rearrangement of 3-Acylamino-1,2,4-oxadiazoles ‡
Dipartimento di Chimica Organica E. Paterno, Università degli Studi di Palermo, Viale delle Scienze, Parco d'Orleans II, Edificio 17, I-90128 Palermo, Italy. The Journal of Organic Chemistry
(Impact Factor: 4.72).
10/2007; 72(20):7656-66. DOI: 10.1021/jo701306t
The experimental investigation of the base-catalyzed rearrangements of 3-acylamino-1,2,4-oxadiazoles evidenced a new reaction pathway which competes with the well-known ring-degenerate Boulton-Katritzky rearrangement (BKR). The new reaction consists of a one-atom side-chain rearrangement that is base-activated, occurs at a higher temperature than the BKR, and irreversibly leads to the corresponding 2-acylamino-1,3,4-oxadiazoles. An extensive DFT study is reported to elucidate the proposed reaction mechanism and to compare the three possible inherent routes: (i) the reversible three-atom side-chain ring-degenerate BKR, (ii) the ring contraction-ring expansion route (RCRE), and (iii) the one-atom side-chain rearrangement. The results of the computational investigation point out that the latter route is kinetically preferred over the RCRE and can be considered as the ground-state analogue of a previously proposed C(3)-N(2) migration-nucleophilic attack-cyclization (MNAC) photochemically activated pathway. The MNAC consists of the formation of a diazirine intermediate, involving the exocyclic nitrogen, that eventually evolves into a carbodiimide intermediate (migration); the latter undergoes a single intramolecular nucleophilic attack-cyclization step leading to the final 2-acylamino-1,3,4-oxadiazole.
Available from: Vincenzo Frenna
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ABSTRACT: By studying the rearrangement in dioxane/water of a series of (Z)-arylhydrazones of 5-amino-3-benzoyl-1,2,4-oxadiazole (1a-k) into the relevant (2-aryl-5-phenyl-2H-1,2,3-triazol-4-yl)ureas (2a-k) in a wide range of pS + (an operational scale of proton concentration in the mixed solvent used; dioxane/water, 1:1, v:v), the occurrence of three different reaction pathways (specific-acid-catalyzed, uncatalyzed, and general-base-catalyzed) for the relevant S N i process has been recently enlightened. The significantly different substituent effects on the three pathways cause some crossovers in the log k A,R versus pS + plots. Both the pS + value at which the crossover occurs and the width of the uncatalyzed pathway appear in turn substituent-dependent. Thus, thanks to the wide and complete range of substituents examined, the data obtained have been treated by using free-energy relationships. Interestingly enough, these results also furnish valuable information concerning the effects of "small" variations in chemical structures able to produce "large" reactivity variations in some way recalling what can occur in biological systems.
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ABSTRACT: 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.
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