Experimental and DFT studies on competitive heterocyclic rearrangements. Part 2: a one-atom side-chain versus the classic three-atom side-chain (Boulton-Katritzky) ring rearrangement of 3-acylamino-1,2,4-oxadiazoles.
ABSTRACT 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.
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ABSTRACT: A novel base-induced rearrangement of isoxazoles into imidazole derivatives is reported. In the isoxazole series, this represents the first example of a three-atom side-chain rearrangement involving a CNC sequence. The reactions are carried out under nitrogen and produced 2-aryl-4(5)-phenacyl-5(4)-phenyl-imidazoles in high yields. In the presence of oxygen, a cascade rearrangement-oxidation reaction sequence was observed and imidazole derivatives bearing an oxidized side-chain were isolated.Organic & Biomolecular Chemistry 11/2010; 9(2):491-6. · 3.57 Impact Factor
Article: The new era of 1,2,4-oxadiazoles.[Show abstract] [Hide abstract]
ABSTRACT: The synthesis, the chemical and photochemical reactivity, and the use of 1,2,4-oxadiazoles in materials and as bioactive compounds have been reviewed. The material in this survey includes some historical background, general features, state-of-the-art applications together with a critical discussion about current limitations and suggestions for future developments.Organic & Biomolecular Chemistry 11/2009; 7(21):4337-48. · 3.57 Impact Factor