1.2- Dioxetan-3-one

Dioxetan-3-ones spectroscopy, 7, 455 synthesis, 7, 469, 476 thermal reactions, 7, 459... 

The bioluminescence observed in glowworms and fireflies is due to the decomposition of 1,2-dioxetan-3-ones [12]. 

Dioxetan-ones appear to be intermediates in the chemiluminescent reaction of singlet oxygen with ketenes, in the presence of fluorescers 81> ... 

Excitation appears to be general for this reaction but yields of excited products vary substantially with the substituent R. The highest yield reported is from tetramethyl-l,2-dioxetane [35856-82-7] (TMD) where the yield of triplet acetone is 50% of total acetone formed (18,19). Probably only one carbonyl of the two produced can be excited by the thermal decomposition, and TMD provides 100% of the possible yield of triplet acetone. Singlet excited acetone is also formed, but at the low yield of 0.1—0.3% (17—21). Other tetraaLkyldioxetanes behave similarly to TMD (22). 

Subsequent studies (63,64) suggested that the nature of the chemical activation process was a one-electron oxidation of the fluorescer by (27) followed by decomposition of the dioxetanedione radical anion to a carbon dioxide radical anion. Back electron transfer to the radical cation of the fluorescer produced the excited state which emitted the luminescence characteristic of the fluorescent state of the emitter. The chemical activation mechanism was patterned after the CIEEL mechanism proposed for dioxetanones and dioxetanes discussed earher (65). Additional support for the CIEEL mechanism, was furnished by demonstration (66) that a linear correlation existed between the singlet excitation energy of the fluorescer and the chemiluminescence intensity which had been shown earher with dimethyl dioxetanone (67). 

The conversion of small rings to smaller ones, without loss, is not common. 3-Chloroazetidine isomerizes reversibly to 2-chloromethylaziridine (Section 5.09.2.2.5). Flash vacuum pyrolysis can convert isoxazoles to azirines (Section 5.04.4.3). More common is the isomerization of medium-sized, i.e. five- or six-membered rings, e.g. certain succinimides (Scheme 23) (81JOC27) to azetidinediones, or bicyclic 1,2-dioxetanes to bis-oxiranes (Section 5.05.4.3.2). 

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. 

If a four-membered ring peroxide (1.2-dioxetane) is involved in a reaction, its concerted bond cleavage into two carbonyl moieties should yield one of these in its excited electronic state on the basis of the orbital symmetry conservation rules of R. B. Woodward and R. Hoffmann ... 

A closer examination by ex situ analysis using NMR or gas chromatography illustrates that intrazeolite reaction mixtures can get complex. For example photooxygenation of 1-pentene leads to three major carbonyl products plus a mixture of saturated aldehydes (valeraldehyde, propionaldehyde, butyraldehyde, acetaldehyde)38 (Fig. 33). Ethyl vinyl ketone and 2-pentenal arise from addition of the hydroperoxy radical to the two different ends of the allylic radical (Fig. 33). The ketone, /i-3-penten-2-one, is formed by intrazeolite isomerization of 1-pentene followed by CT mediated photooxygenation of the 2-pentene isomer. Dioxetane cleavage, epoxide rearrangement, or presumably even Floch cleavage130,131 of the allylic hydroperoxides can lead to the mixture of saturated aldehydes. 

The reaction mechanism for the aerobic oxidation of the pz to seco-pz can be attributed to a formal 2 + 2 cycloaddition of singlet oxygen to one of the pyrrole rings, followed by cleavage (retro 2 + 2) of the dioxetane intermediate to produce the corresponding seco-pz (160). This mechanism is shown in Scheme 29 for an unsymmetrical bis(dimethylamino)pz. Further photophysical studies show that the full reaction mechanism of the photoperoxidation involves attack on the reactant by singlet oxygen that has been sensitized by the triplet state of the product, 159. As a consequence, the kinetics of the process is shown to be autocatalytic where the reactant is removed at a rate that increases with the amount of product formed. 

Unquestionably, the advantage of the present methodology is that the intermediary dioxetane serves as a vehicle to place the chiral inductor (the oxazolidinone auxiliary) and the racemic substrate to be resolved (the methyldesoxybenzoin) in one and the same zeolite supercage. These represent optimal conditions for efficacious asymmetric induction, a novel application of chiral dioxetanes which merits further elaboration. 

In parallel with the ab initio calculations, also semiempirical smdies on the thermolysis of 1,2-dioxetane were performed. Most computations have been conducted by the PM3 method because it is the best semiempirical method for describing lone electron pairs on adjacent atoms . As an illustration, only the PM3 method reveals that in the dioxetane molecule the 0-0 bond is longer and weaker compared with the C—C one, as manifested by the computed values of bond lengths [rf(0—O) = 1.600 > d(C—C) = 1.522 A] and bond orders [n(0—O) = 0.973 < w(C—C) = 0.989] . In contrast, the AMI and MNDO semiempirical methods exhibit the opposite trends, i.e. AMI gives d 0—0) = 1.334 A, d(C-C) = 1.539 A, n(O-O) = 0.995 and n(C-C) = 0.976, whereas MNDO furnishes d(0-0) = 1.316 A, d(C-C) = 1.558 A, n(O-O) = 0.996 and n(C-C) = 0.9622 f-8. Nevertheless, despite the quantitative differences in the computed bond lengths, bond orders and bond angles, both the AMI and PM3 methods disclosed qualitatively similar reaction trajectories . 

In summary, although the computed structural details of the reaction profile depend on the method used for calculations, the general salient mechanistic conclusion is that the dioxetane thermolysis starts with the 0—0 bond rupture to generate the 0C(H2)—C(H2)0 triplet diradical, which is followed by C—C bond cleavage to afford the final ketone products one of them is formed preferentially in its triplet excited state. Since even simple 1,2-dioxetanes still present a computational challenge to resolve the controversial thermolysis mechanism, the theoretical elucidation of complex dioxetanes constitutes to date a formidable task. 

The unimolecular decomposition of 1,2-dioxetanes and 1,2-dioxetanones (a-peroxylac-tones) is the simplest and most exhaustively studied example of a thermal reaction that leads to the formation, in this case in a single elementary step, of the electronically excited state of one of the product molecules. The mechanism of this transformation was studied intensively in the 1970s and early 1980s and several hundreds of 1,2-dioxetane derivatives and some 1,2-dioxetanones were synthesized and their activation parameters and CL quantum yields determined. Thermal decomposition of these cyclic peroxides leads mainly to the formation of triplet-excited carbonyl products in up to 30% yields. However, formation of singlet excited products occurs in significantly lower yields (below... 

In view of the above exposed facts, to date there is no direct experimental evidence of the intermediary 1,4-dioxy biradical in the decomposition of 1,2-dioxetanes. Therefore, it appears that the asynchronous (biradicaloid or biradical-like) concerted mechanism (merged mechanism) is the one consistent with aU the experimental and theoretical data currently available. 

Legg and Hercules have shown that the reaction of superoxide with lucigenin results in chemiluminescence. A similar conclusion was reached by Fridovich and coworkers, who observed chemiluminescence upon the addition of lucigenin to the xanthine-xanthine oxidase system, which is known to produce 02 . In order to emit chemiluminescence, lucigenin must first be reduced by one electron to produce the radical cation 43 (Scheme 30). This species reacts with superoxide ion, producing the intermediate 1,2-dioxetane, whose decomposition is responsible for luminescence. ... 

Catherall and coworkers studied the reaction kinetics of bis(pentachlorophenyl) oxalate and H2O2 catalyzed by salicylate in the presence of DBA and verified that the delayed addition of DPA did not alter the reaction kinetics. The authors also conducted several kinetic smdies on the peroxyoxalate system and proposed the participation of 4-hydroxy-4-(pentachlorophenoxy)-l,2-dioxetan-3-one (48, R=Cl5C60) as the HEI in the reaction ... 

Chokshi and coworkers reported the first attempt to obtain more direct evidence of the HEI structure. Using the reaction of hydrogen peroxide and bis(2,6-difluorophenyl) oxalate in acetonitrile/water (3 1), monitored by F NMR, the authors observed a peak (different from those of the reagent or the released 2,6-difluorophenol) assigned putatively to a 2,6-difluorophenyl-containing peracid (53), whose intensity decreased in the presence of the activator. Considering that peracid derivatives like 50 were later excluded as possible HEIs °, another HEI structure accountable for the observed NMR peak could be 4-hydroxy-4-(2,6-difluorophenoxy)-l,2-dioxetan-3-one, a derivative of 48. 

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. 

A similar photooxidation pathway was found for Mg(ll)TPP. It reacted readily with molecular oxygen to give the corresponding 15,16-dihydrobiliverdin, similar to the one shown for Mg(II)OEP in Scheme 1. Further studies have proposed that the photooxygenation of metallo-me o-tetrasubstituted porphyrins proceeds via a one-molecule mechanism involving only one oxygen molecule. Most likely, the first intermediates formed upon photooxygenation are short-lived peroxides. Such compounds are very unstable and a possible dioxetane structure is shown in formula 31. 

For a-peroxylactones (l,2-dioxetan-3-ones) which are usually quite unstable, the IR band at 1875 cm 1 is the best indicator of the ring s presence (72JA2894, 77JA5836, 5768). PES and MS studies on dioxetanes have also been reported (77AHC(21)437). 

The most remarkable property of both dioxetanes and dioxetanones is their ability to chemiluminesce when heated to their decomposition point. In general this behavior can be summarized as in Scheme 15 (79MI51502). Both 1,2-dioxetanes and l,2-dioxetan-3-ones (a -peroxylactones) give more triplet than singlet ketones (< x = 2 25 00 (77AHC(21)437))... 

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