1.2- Dioxetanes, as intermediates

Instead of the fully accepted concerted mechanism via an ene reaction, a mechanism with perepoxides and dioxetanes as intermediates for hydroperoxides and carbonyl products, respectively, was proposed [21] (equation 6). 

Dioxetanes as intermediates in reactions of 1,2-diphenylcyclopropenes and -cyclobutenes with singlet O2 81 H( 15) 1643. 

The first detailed investigation of the reaction kinetics was reported in 1984 (68). The reaction of bis(pentachlorophenyl) oxalate [1173-75-7] (PCPO) and hydrogen peroxide cataly2ed by sodium saUcylate in chlorobenzene produced chemiluminescence from diphenylamine (DPA) as a simple time—intensity profile from which a chemiluminescence decay rate constant could be determined. These studies demonstrated a first-order dependence for both PCPO and hydrogen peroxide and a zero-order dependence on the fluorescer in accord with an earher study (9). Furthermore, the chemiluminescence quantum efficiencies Qc) are dependent on the ease of oxidation of the fluorescer, an unstable, short-hved intermediate (r = 0.5 /is) serves as the chemical activator, and such a short-hved species "is not consistent with attempts to identify a relatively stable dioxetane as the intermediate" (68). 

Carotene cleavage enzymes — Two pathways have been described for P-carotene conversion to vitamin A (central and eccentric cleavage pathways) and reviewed recently. The major pathway is the central cleavage catalyzed by a cytosolic enzyme, p-carotene 15,15-oxygenase (BCO EC 1.13.1.21 or EC 1.14.99.36), which cleaves p-carotene at its central double bond (15,15 ) to form retinal. Two enzymatic mechanisms have been proposed (1) a dioxygenase reaction (EC 1.13.11.21) that requires O2 and yields a dioxetane as an intermediate and (2) a monooxygenase reaction (EC 1.14.99.36) that requires two oxygen atoms from two different sources (O2 and H2O) and yields an epoxide as an intermediate. ... 

The dioxetane derivative 79 may be formed as intermediate in the brilliant chemiluminescence reaction between 10,10 -dimethyl-9,9 -bi-acridylidene and excited-singlet oxygen 125>. Chemiluminescence also occurs when potassium cyanide is added to lucigenin solutions in the... 

As mentioned earlier (see p. 122) the previously postulated dioxetane intermediate in firefly bioluminescence has been challenged as no 180 is in-corporated in the carbon dioxide released during oxidation of firefly luciferin with 18C>2. In view of the crucial significance of the 180. experiments De Luca and Dempsey 202> rigorously examined the reliability of their tracer method. They conclude from their experiments that all available evidence is in favour of a linear, not a cyclic peroxide intermediate — in contrast to Cypridina bioluminescence where at least part of the reaction proceeds via a cyclic peroxide (dioxetane) as concluded from the incorporation of 180 into the carbon dioxide evolved 202,203). However, the dioxetane intermediate is not absolutely excluded as there is the possibility of a non-chemiluminescent hydrolytic cleavage of the four-membered ring 204>. 

A promising unprecedented application of the chiral enecarbamates Ic in asymmetric synthesis is based on the ship-in-the-bottle strategy, which entails the oxidation of these substrates in zeolite supercages . In this novel concept, presumably dioxetanes intervene as intermediates, as illustrated for the oxidation of the chiral enecarbamate Ic in the NaY zeolite (Scheme 6). By starting with a 50 50 mixture of the diastereomeric enecarbamates (45, 3 R)-lc and (45, 3 5 )-lc, absorbed by the NaY zeolite, its oxidation furnishes the enantiomerically enriched (ee ca 50%) S -methyldesoxybenzoin, whereas the (4R,3 R)-lc and (4R,3 S)-lc diastereomeric mixture affords preferentially (ee ca 47%) the R enantiomer however, racemic methylbenzoin is obtained when the chirality center at the C-4 position in the oxazolidinone is removed. Evidently, appreciable asymmetric induction is mediated by the optically active oxazolidinone auxiliary. 

The 1,2-dioxetane postulated as intermediate was never isolated . However, indirect evidence of a 1,2-dioxetane as a reaction intermediate was obtained by chemiluminescence resulting from the reaction of 10,10 -dimethyl-9,9 -biacridene (40) with singlet... 

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. 

Although 1,2-dioxetanes are excluded as intermediates in the formation of allylic hydroperoxides, they may be formed as primary products in the reaction of singlet oxygen with alkenes not possessing allylic hydrogen 360 363 366 368-370 374... 

This approach was applied later to synthesize substituted 2-benzopyrylium salts 4 (85LA2116) via 1,5-diketones 3, and a few dioxetanes 2 were isolated as intermediates on using singlet oxygen photochemically (74JA4339). 

Dioxetanes have been also proposed [44] as intermediates. However, the pathway through dioxetanes has been found to give only carbonyl cleavage products rather than rearrange to allylic hydroperoxides [45],... 

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. 

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. 

Several years ago it was noted that the behavior of dioxetanes substituted with large resonance groups (for example the dioxetanes postulated as intermediates in many bioluminescent reactions) is quite distinct from that of alkyl-, alkoxy-, or simple aryl-substituted dioxetanes (T. Wilson, 1976). The decomposition products of these dioxetanes are often highly fluorescent, possessing lowest excited ttti states, the yields of excited singlet states are often remarkably high, and the dioxetane stability is apparently low. It was suggested at that time that an alternative mechanism, perhaps a truly concerted mechanism, was operative. 

Itoh S, Nameda N. Molecular orbital calculations for dioxetane as a part of the intermediate of firefly luciferin. Kagoshima Daigaku Kenkyu Houkoku 1996 38 257-60. 

CHEMILUMINESCENCE INVOLVING THE PHOSPHORUS CHEMISTRY. PHOSPHA-l,2-DIOXETANES AS THE MOST LIKELY HIGH-ENERGY INTERMEDIATES IN AUTOXIDATION OF PHOSPHONATE CARBANION... 

Motoyoshiya J, Isono Y, Hayashi S, Kanzaki Y, Hayashi S, Chemiluminescent oxidation of phosphonates Phospha-l,2-dioxetanes as possible intermediates. Tetrahedron Lett 1994 35 5875-78. 

Motoyoshiya J, Ikeda T, Tsuboi S, Kusaura T, Takeuchi Y, Hayashi S, Yoshioka S, Takaguchi Y, Aoyama H. Chemiluminescence in autoxidation of phosphonate carbanions. Phospha-l,2-dioxetanes as the most likely high-energy intermediates. J Org Chem 2003 68 5950-5. 

The reactivity toward singlet oxygen [238,454] should be taken into consideration if triplet states are involved (either as intermediate or as sensitizer) on irradiation of air- or oxygen-saturated solutions. Benzaldehyde, hydroperoxides, and dioxetanes have been found as products from the reaction of stilbenes with reactive oxygen species [464,465]. A rearrangement reaction has been reported for nitrostilbenes formation of a-oximinoketones, typical for / -nitrostyrenes, which may be accompanied by cleavage products [466],... 

Several accounts of syntheses of the sulphur-containing cyclophanes (489)—(494) have been produced, the n.m.r. spectra of (493) and (494) indicating that unhindered rotational movement is possible in the bridges of both. Consideration of other related conformational points is promised for the future. Tetrathio-1,2-dioxetans (495) are postulated as intermediates... 

A number of chemiluminescent reactions may proceed through unstable dioxetane intermediates (12,43). For example, the classical chemiluminescent reactions of lophine [484-47-9] (18), lucigenin [2315-97-7] (20), and transannular peroxide decomposition. Classical chemiluminescence from lophine (18), where R = CgH, is derived from its reaction with oxygen in aqueous alkaline dimethyl sulfoxide or by reaction with hydrogen peroxide and a cooxidant such as sodium hypochlorite or potassium ferricyanide (44). The hydroperoxide (19) has been isolated and independentiy emits light in basic ethanol (45). 

One is the concerted decomposition of a dioxetanone structure that is proposed for the chemiluminescence and bioluminescence of both firefly luciferin (Hopkins et al., 1967 McCapra et al., 1968 Shimomura et al., 1977) and Cypridina luciferin (McCapra and Chang, 1967 Shimomura and Johnson, 1971). The other is the linear decomposition mechanism that has been proposed for the bioluminescence reaction of fireflies by DeLuca and Dempsey (1970), but not substantiated. In the case of the Oplopborus bioluminescence, investigation of the reaction pathway by 180-labeling experiments has shown that one O atom of the product CO2 derives from molecular oxygen, indicating that the dioxetanone pathway takes place in this bioluminescence system as well (Shimomura et al., 1978). It appears that the involvement of a dioxetane intermediate is quite widespread in bioluminescence. 

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