1.2- Dioxetanes characterization

In contrast, the radical cation of the tetracychc system is significantly distorted The parent system has D2d symmetry and a b2 HOMO, whereas the radical cation is distorted toward 2 equiv structures of Cav symmetry ( E), with a two-center three-electron N-N bond (3 +). The ESR data (an = 0.709 mT, 4N ah = 0.768 mT, 8H, N—C—N ah = 0.414 mT, 8H, N—C—support the rapid interconversion of the two structures. The structure of 3 " is one of many doubly or multiply bridged diaza compounds forming three-electron N—N bonds (e.g., 4 " ). Many additional examples involving three-electron S—S or I I bonds are also known. Dioxetane radical cations (e.g., 5 ), characterized by ESR spectroscopy as intermediates in oxygenations (cf.. Section 5), contain analogous three-electron 0—0 bonds. 

Kinetically stabilized azetes also show a high tendency for cycloaddition with a variety of other reagents. Cycloaddition of (47) with triplet oxygen produced a fully characterized dioxetan adduct (48), which decomposed at 25°C into t-butyl cyanide and the a-dione fragment (88AG(E)272). 

Among radical cations of n-donors we mention briefly those of 1,4-diazabicy-clo[2.2.2]-octane (99) and of the tricyclic tetraaza compound (100). For the bicyclic system a perfect correspondence has been reported between the AEs of the radical ion and the AIs of its precursor [276], The radical cation of the tetracyclic system, on the other hand, is significantly distorted. While the parent system has D2d symmetry and a b2 HOMO, the radical cation is distorted towards two equivalent structures of C2y symmetry (2E), with a two-center three-electron N — N bond [281, 282]. The dioxetane radical cations (101), invoked as intermediates in oxygenations via oxygen capture (Scheme 6), and characterized by ESR spectroscopy [8] contain analogous three-electron O—O bonds. 

Only experimental information obtained over the last decade has been incorporated within this section and the reader is directed to the previous version of this chapter <1996CHEC-II(1B)1041> for information prior to 1996. Over the last decade, there have only been reports on the characterization of 1,2-dioxetanes 1 and 2-dioxetanones 2 (a-peroxy lactones) consequently, this section contains no information for structures of type 3-9. 

Mass spectrometry remains of limited use for the characterization of dioxetanes however, numerous relatively stable 1,2-dioxetanes have been prepared over the last decade allowing not only for the detection of their parent ions but also allowing for high-resolution mass spectrometry (HRMS) measurements to be taken. See references associated with structures depicted in Figure 1 or Table 1. 

Dioxetanes have been the sole subject of several specialized reviews in recent years (Bartlett and Landis, 1979 Horn et al., 1978-79 Adam, 1977 T. Wilson, 1976 Turro et al., 1974a Mumford, 1975). These articles cover with depth which is not possible here such topics as (1) preparation, (2) physical and spectroscopic characterization, (3) experimental techniques, especially for the study of chemiluminescence, (4) mechanisms of decomposition and chemiexcitation, (5) ground state transformations, and (6) reactions involving dioxetanes as postulated intermediates. The interested reader is referred to these articles for details on these specialized topics, and for some interesting historical perspectives. 

In the past few years two rather distinct classes of chemiluminescent dioxetanes have become evident. Alkyl, alkoxy, and simple aryl substituted dioxetanes, which includes the earliest dioxetanes prepared, are characterized... 

Further evidence for ground-state complexation as the cause of the special catalysis was obtained by a spectroscopic study in a model system. Such complexes are typically characterized by a shift of the maximum of the porphyrin Soret absorption band relative to that of the non-complexed porphyrin. In the presence of a high concentration of tetramethy 1-1,2-dioxetane, used as a model for the co-ordinating ability of [21], the absorption maximum of ZnTPP was determined to be shifted by 1.2 nm. 

The enamine is unique in that it also has a photosensitizer (the dihydro-fullerene chromophore) in the same molecule, and brief exposure to air and room light leads to cleavage of the enamine double bond, producing the ketoamide shown below. The well-known photooxidative cleavage of enamines proceeds via an intermediate 1,2-dioxetane [119,120]. Although many 1,2-dioxetanes are relatively stable, those from enamines are not, and cleave to ketone and amide fragments, below — 40 °C in most cases. The ketoamide was characterized by FAB ms (m/e = 863), IR, and and CNMR (carbonyls at 170 ppm for the amide and 204 ppm for the ketone and overall C, symmetry for the fullerene carbons). 

If so, one may expect products to result from chemical bond formation between the cation-radical-anion-radical pair, which are both paramagnetic and of opposite charge. In the latter route, there is a precedent for the formation of dioxetane intermediates of stable olefin cation radicals [51], as in the characterization by Nelsen and coworkers of a dioxetane cation radical from adamantylidene cation radical [52]. If a dioxetane is formed, either in neutral form or as a cation radical, the Ti02 surface can function in an additional role, that is, as a Lewis acid catalyst, to induce decomposition of the dioxetane. Since no chemiluminescence could be observed in these reactions, apparently Lewis acid catalysis provides a nonradiative route for cleavage of this high-energy intermediate. That Ti02 can indeed function in this way can be demonstrated by independent synthesis of the dioxetane derived from 1,1-diphenylethylene, which does indeed decompose to benzophenone when it is stirred in the dark on titanium dioxide. 

Serendipity, insight, and keen observation power were the ingredients of success in the preparation, isolation, and characterization of the first stable 1,2-dioxetane, namely, the trimethyl derivative (2) obtained in the base-catalyzed dehydrobromi-nation of 3-bromo-2-hydroperoxy-2-methylbutane (Eq. 5). Since then, well over a hundred 1,2-dioxetanes have been documented in the organic literature, most as transient intermediates and a good number (Table 1) as stable, isolable substances. 

Whenever feasible, a combustion analysis is an essential method of characterization because it establishes the elemental composition. All precautions should be exercised in view of the explosive nature of 1,2-dioxetanes. 

As already pointed out on several occasions, the unique property of dioxetanes is to generate electronically excited states on thermolysis, which then manifest themselves by light emission (Eq. 28). The total yield of excited states (Eq. 33), that is, the sum of the singlet excitation yield (0 ), triplet excitation yield (0 ), and the spin-state selectivity (Eq. 34), that is, the ratio of the triplet and singlet excitation yields, are excitation parameters that characterize a particular dioxetane. 

To characterize the MOA of the novel TNAP inhibitor series we selected compound 9v for additional studies. By performing detailed kinetic studies, we demonstrated that 9v is competitive with respect to both substrates, the water-soluble 1,2-dioxetane reagent disodium 2-chloro-5-(5 -chloro-4-methoxyspiro[l,2-dioxetane-3,20-tricyclo[3.3.1.13,7]decan]-4-yl)-phenol-l-(dihydrogen phosphate) (CDP-star) and DBA (Fig. 6). This is the first time that a competitive MOA has been established for an inhibitor of TNAP. 

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