Oxirene reactivity

Due to their strain and putative electronic destabilization, such three-membered heterocycles possessing a cyclic array of 47r-electrons offer a considerable challenge to synthesis. Such molecules are expected to be both unimolecularly and bimolecularly reactive, if they exist at all as energy minima. Since no isolable tellurirenes have been reported, only some reactions of selenirenes are described in this section. Selenirene and its kindred systems, oxirene, azirine, and thiirene, are of interest because of their theoretical significance as prototypes of antiaromatic species. 

With carbon-carbon triple bonds, oxygen insertion yields an oxirene which opens by heterolytic C — O bond cleavage to form a highly reactive intermediate which binds covalently to the enzyme. In the case of 17a-ethynyl steroids, the reaction can also result in an extension of ring D (Fig. 31.12). 

There is no doubt that matrix isolation experiments have provided many examples of great interest in this and other areas where reactive intermediates are produced, a-Diazoketones were discussed in an earlier section since the singlet state reaction undergoes the well-known photo-Wolff process. Other studies on these compounds in matrices at 77 K have shown that the diazoketones 571 and 572 undergo equilibration via an oxirene intermediate. Again this is an example of intramolecular trapping . Others have also observed the formation of oxirenes and the existence of a keto-carbene/oxirene equilibrium in a variety of systems, such as the diazoquinone 573. ... 

Occasionally, xenobiotics undergo metabolic activation to produce reactive intermediates, where these intermediates rearrange to form an unpredictable metabolite. For example, the metabolic activation of DPC 963 in rat formed a highly reactive oxirene intermediate (Chen et al., 2002). This intermediate rapidly rearranged to form an unstable cyclobutenyl ketone through possible intermediates a or b (Fig. 12.13). This reactive intermediate was prone to nucleophilic attack and in this case reacted with glutathione via a 1,4 Michael addition that resulted in two isomeric GSH adducts M3 and M4. The H NMR spectrum provided evidence in support of the M3 and M4 structures. First, both the aromatic hydrogens were still present in the metabolite. Second, the... 

Calculations comparing the benzooxirenes 20-24 (Fig. 3.17) revealed an interesting pattern of reactivity [91]. The rationale behind this study was that higher benzooxirenes, derived from naphthalene, anthracene, etc., can have the oxirene ring fused on linearly or angularly, as shown here for naphthalene the tendency to maintain the maximum amount of benzenoid character should make the linear systems have dimethyleneoxirane, rather than oxirene, character, while the converse should be the case for the angularly fused molecules ... 

Fig. 3.17 The reactivity of a series of benzooxirenes was studied by semiempirical, ab initio and DFT methods [91], The numbers over the arrows are the activation energies (kJ mol ) for conversion to the oxo carbenes, calculated by a DFT method. 21-24 are drawn with a resonance form that maximizes the number of benzenoid rings this forces the formal oxirene rings to be formally dimethyleneoxirane moieties in the linear 21 and 23, and oxirene moieties in the angular 22 and 24. Comparing the linear with the angular molecules, former have much higher calculated barriers to rearrangement...

The C10 ion oxidation of 2-hydroxy-l-(4-sulfonato-l-naphthylazo) naphthalene-3,6-disulfonate (amaranth dye, Am) was first order in Am and the oxidant under varied pH conditions. The species HOCl was more reactive than C10 ion. The oxidation products were 3,4-dihydroxy naphthalene-2,7-disulfonic sodium salt, dichloro-1,4-naphthoquione, and naphtha(2,3)oxirene-2, 3-dione. The oxidation of 1,3,7-trimethylxanthine (caffeine) by C10 ion in aqueous medium at pH 8.2 was first order in the substrate and the oxidant. ... 

As a result of the wide applicability of a-diazoketones, much effort has been apphed to understanding the mechanistic pathways available to this class of compounds. Several possible intermediates (e.g., a-carbonylcarbenes, oxirenes, and excited-state species) have played a central role in the proposed mechanisms of the Wolff rearrangement. This chapter examines both experimental and theoretical work that has furthered our understanding of the mechanisms underlying the complex reactivities of these systems. 

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