Degradative reactions, ozonolysis

The viabihty of this synthetic approach to the introduction of a carboxylic acid fimction at C2 has been demonstrated in two ways. Following lithium diphenylcuprate addition to 564, the newly introduced phenyl group is subsequently degraded by ozonolysis to provide 567. Alternatively, reaction of 564 with diethylaluminium cyanide in toluene gives 568 which is also conveniently transformed into 567... 

Ozonolysis is not used often in synthesis because it is a degradative reaction—it breaks larger molecules into smaller ones. In synthetic schemes we are usually attempting to build larger molecules from smaller ones. However, the ozonolysis reaction can provide a useful way to prepare an aldehyde or ketone if the appropriate alkene is readily available. One such example is provided by the cleavage of cyclohexene to produce the dialdehyde shown in the previous equation. 

The structure of pseudodistomin B has recently been revised as 186d, based on its degradation reaction. The new structure was confirmed by synthesis of racemic 186d [461], Revision of the structure of pseudodistomin B led to reinvestigation of pseudodistomin A. Ozonolysis of pseudodistomin A led to a revision of its structure as 186c [462]. 

The biosynthesis of erythroskyrin was investigated by Shibata et al. (1966), who established the distribution of in the molecule which was obtained by cultivation of the mold on Czapek-Dox media containing various "Relabeled substrates. The degradation reactions which were carried out on the labeled erythroskyrin are summarized in Fig. 1 (10-12). Erythroskyrin containing the label from added DL-[l-R"RC]valine was decomposed into A-methylvaline (10) by ozonolysis. The product was converted into its N-(2,4-dinitrophenyl) derivative, which was decomposed photochemically into isobutanal (11). The 2,4-dinitrophenylhydrazone derivative of the aldehyde contained no radioactivity, while the A-(2,4-dinitrophenyl)-A-methyl-valine contained 79% of the activity of the erythroskyrin. The result showed that [l-R"RC]valine was incorporated (essentially) intact into the lactam portion of erythroskyrin, with the radioactivity located mainly at C(4). 

Alicyclic hydroxamic acids undergo several specific oxidative cleavage reactions which may be of diagnostic or preparative value. In the pyrrolidine series compounds of type 66 have been oxidized with sodium hypobromite or with periodates to give y-nitroso acids (113). Ozonolysis gives the corresponding y-nitro acids. The related cyclic aldonitrone.s are also oxidized by periodate to nitroso acids, presumably via the hydroxamic acids.This periodate fission was used in the complex degradation of J -nitrones derived from aconitine. 

Reaction of 3,5-disubstituted-1,2,4-trioxolanes (89) with oxidants (usually under basic conditions) leads to carboxylic acids (Equation (14)). This reaction is often carried out as the work up procedure for alkene ozonolysis, avoiding the need to isolate the intermediate ozonide. Typical oxidants are basic hydrogen peroxide or peracids and this type of oxidative decomposition is useful for both synthetic and degradative studies. 

While die above reactions will provide carboxylic acid products, each has problems associated with it. The cleavage of olefins to carboxylic acids [reaction (7.1)] can be carried out using potassium permanganate or by ozonolysis at low temperature followed by oxidative workup with hydrogen peroxide. Neither of diese mediods is very useful since only symmetric olefins provide a single carboxylic acid product. Unsymmetrical olefins give a mixture of two acids which must be separated. Furthermore the most useful synthetic processes are those which build up structures, whereas these reactions are degradative in nature. 

The UV/ozone process destroyed about 75% of the influent anthracene within about 2 min. The degradation rate was generally steady for about the first minute of treatment but decreased somewhat thereafter, perhaps indicating the buildup of scavengers reacting with hydroxyl radicals. The UV / ozone process decelerates the chemical reaction of the ozonolysis of anthracene with molecular ozone as compared with ozone treatment alone (Trapido et al., 1995). 

Singlet-oxygen studies have being reported to such diverse areas as chemiluminescence [14], photocarcinogenity [15], ozonolysis [16], photodynamic action [17], peroxide decomposition [7], photosynthesis [14], air pollution [18], metallocatalyzed oxygenation reactions [19,20], synthetic applications [21], and polymer degradation [10]. 

Several reports of the effects of ozone in vivo are presented in Table XII. It is impossible to decide whether the effects of ozone are primary reactions or the result of a series of reactions initiated by ozone. All results can be rationalized as enzyme inhibition of one sort or another. Effects on membrane structure are harder to observe, and in one case it was reported that the malonaldehyde which would be expected on fatty acid ozonolysis was only observed after symptoms were apparent (74). Results of electron microscope examination showed that the first observable damage was in the stroma of the chloroplasts (70). One can easily argue that earlier damage could not be detected by microscopic techniques. However, recent reports that the chloroplast polyribosomes are much more susceptible to degradation by ozone are important observations which are consistent with the microscopy experiments (76). Chloroplast polysomes are also more susceptible to sulfhydryl reagents than are cytoplasmic polysomes (77). This evidence indicates that ozone itself, or a toxic product from primary oxidation, can pass through the cytoplasm and have its effect in the chloroplast. 

Ozonolysis of olefins has found little application in the preparation of ketones for synthetic purposes. Since the ozonides may be explosive, the method has been limited to the reaction of small quantities of olefins, mostly for degradation studies and location of double bonds. 

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