Oxadiazoles Boulton-Katritzky rearrangement

A theoretical study of degenerate Boulton-Katritzky rearrangements concerning the anions of the 3-hydroxyimi-nomethyl-l,2,5-oxadiazole has been carried out by using semi-empirical modified neglect of diatomic overlap (MNDO) and ab initio Hartree-Fock procedures. Different transition structures and reactive pathways were obtained in the two cases. Semi-empirical treatment shows asymmetrical transition states and nonconcerted processes via symmetrical intermediates. By contrast, ab initio procedures describe concerted and synchronous processes involving symmetrically located transition states <1998JMT(452)67>. 

A theoretical study of degenerate Boulton-Katritzky rearrangements concerning the anions of 3-formylamino-l,2,4-oxadiazole and 3-hydroxy-iminomethyl-1,2,5-oxadiazole has been carried out7 The treatment has shown the participation of asymmetric transition states and non-concerted processes via symmetrical intermediates. A detailed ab initio and density functional study of the Boulton-Katritzky rearrangement of 4-nitrobenzofuroxan has indicated a one-step mechanism for the process. 

Furazans are formed via the Boulton-Katritzky rearrangement of the oximes of several classes of 3-acyl-l-oxa-2-azoles, including 1,2,4-oxadiazoles, isoxazoles, and furazans. These reactions have been intensively investigated over many years, and the literature comprehensively reviewed <81 AHC(29)i4i, 90KGS1443> the latter survey deals specifically with the exploitation of such rearrangements for furazan synthesis. 

One of the most studied heterocyclic rearrangement in the series of five-membered heterocydes is the Boulton—Katritzky rearrangement (BKR) of 1,2,4-oxadiazoles. This type of ring transformation can occur under a variety of conditions and with different types of participating side-chains, as shown in Scheme 6. Novel mechanistic studies have recently been carried out, including studies in micellar environments (2012JCIS67, 2014EJ07006). 

Figure 3 Examples of heterocyclic products from Boulton-Katritzky rearrangement of 1,2,4-oxadiazoles.

Although a wide variety of heterocycle/side-chain combinations can be used in the Boulton-Katritzky rearrangement, among these, the most commonly used heterocycle has been the 1,2,4-oxadiazole. This is due to the relative ease with which it is synthesized as well as the fact that it has a very low index of aromaticity. Its heightened chemical reactivity has made it an important target for medicinal and materials chemists and the subject of multiple reviews in the last several years. ... 

In efforts toward the synthesis of fluorinated heterocycles, Buscemi and CO-workers treated 1,2,4-oxadiazole 14 with hydrazine in DMF to produce 15 in moderate yield. The isolation of 16 as a byproduct was rationalized as forming via the Boulton-Katritzky rearrangement. Carbons A and B of the starting oxadiazole are both electrophilic when nucleophilic attack of the hydrazine happens at A, the ring enlargement process to give 15 occurs. However, reaction at carbon B, produces a C-N-N side chain, which readily participates in a Boulton-Katritzky rearrangement to produce 16. When smaller fluorous chains were used, attack at carbon A was the... 

Based on the extensive utility of the Boulton-Katritzky rearrangement when employing the aforementioned 1,2,4- and 1,2,5-oxadiazole moieties, the application of analogous moieties such as 1,2,4-thiadiazoles has been investigated. Vivona and co-workers developed a general method for the... 

The 1H, 13C, and 15N NMR chemical shifts of the (Z)-phenylhydrazones of 5-alkyl-and 5-aryl-3-benzoyl-l,2,4-oxadiazoles have provided information on the ground-state electronic distribution.27 The effects of the substituents on the chemical shifts of N(4) and C(5) correlate with kinetic results of the rearrangement of 1,2,4-oxadiazoles to 1,2,3-triazoles (Boulton-Katritzky reaction) support the importance of the leaving group. 

The paper of Frenna, Spinelli et al. contained data on the kinetics of the rearrangement of 3-benzoyl-5-phenyl-l,2,4-oxadiazole 129 into the corresponding 2-aryltriazoles 130 (Boulton-Katritzky reaction) [114]. 

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