Ozonolysis reaction

Certain other systems containing adjacent functional groups that are capable of formation of a cyclic intermediate are also cleaved by periodate. Diketones are cleaved to carboxylic acids, and it has been proposed that a reactive cyclic inter- 

Lead tetraacetate is an alternative to periodate for glycol cleavage. It is particularly useful for glycols that have low solubility in the aqueous media used for periodate reactions. A cyclic mechanism is indicated by the same kind of stereochemistry-reactivity relationships discussed for periodate. Unlike periodate, however, glycols that cannot form cyclic intermediates are eventually oxidized. For 

while a cyclic transition state appears to provide the lowest energy pathway for this oxidative cleavage, other mechanisms are possible. 

Carboxylic acids are oxidized by lead tetraacetate. Decarboxylation occurs, and the product may be an alkene, alkane, acetate ester, or, under modified conditions, an alkyl halide. A free-radical mechanism operates, and the product composition 

Crieger, E. Hoger, G. Huber, P. Kruck, F. Markischeffel, and H. Schellenberger, Justus Liebigs Ann, Chem. 599,81 956). 

Both the periodate cleavage and lead tetraacetate oxidation can be applied synthetically to the generation of medium-sized rings when the glycol is at the junction of two rings. 

SECTION 10.4. SELECTIVE OXIDATIVE CLEAVAGES AT OTHER FUNCTIONAL GROUPS 

Alkanes are formed when the intermediate radical abstracts hydrogen from solvent faster than it is oxidized to the carbonium ion. This reductive process is 

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Most ozonolysis reaction products are postulated to form by the reaction of the 1,3-zwitterion with the extmded carbonyl compound in a 1,3-dipolar cycloaddition reaction to produce stable 1,2,4-trioxanes (ozonides) (17) as shown with itself (dimerization) to form cycHc diperoxides (4) or with protic solvents, such as alcohols, carboxyUc acids, etc, to form a-substituted alkyl hydroperoxides. The latter can form other peroxidic products, depending on reactants, reaction conditions, and solvent. 

Alkenes with at least one vinjdic hydrogen undergo oxidative cleavage when treated with ozone, yielding aldehydes (Section 7.9). If the ozonolysis reaction is carried out on a cyclic alkene, a dicarbonyl compound results. 

The molozonide was unstable and would either rearrange into the isozonide or form polymers. While Staudinger s theory explained the formation of the major products, some of the by-products could not be accounted for. The greatest step toward complete elucidation of the ozonolysis reaction was made by Criegee (Ref 3) In the 1950s. From a study of ozonolysis in various solvents and the constitution of the products, Criegee proposed these reactions ... 

The observed ozonolysis reaction products could now be explained by the reaction of the zwitterion (5) with itself and other reactive compds present in the reaction mixt (Ref 4)... 

Phenanthrene Diozonide.C14H102O3. Harries and Weiss in 1905 reported that the ozonolysis of phenanthrene in chlf soln produced a crystn, expl diozonide (Refs 2 4). Subsequently, very detailed studies of the ozonolysis reaction of phenanthrene by three different groups of investigators failed to confirm the existence... 

Scheme 12.19 illustrates some cases in which ozonolysis reactions have been used in the course of syntheses. Entries 1 to 4 are examples of use of ozonolysis to introduce carbonyl groups under reductive workup. Entries 5 and 6 involve oxidative workup and give dicarboxylic acid products. The reaction in Entry 7 is an example of direct generation of a methyl ester by methoxide trapping. 

Fliszar, S., and J. Renard. Quantitative investigation of the ozonolysis reaction. XIV. A simple carbonium ion stabilization approach to the ozone cleavage of un-symmetrical olefins. Can. J. Chem. 48 3002-3018, 1970. 

M.J. Pelletier, M.L. FabiUi and B. Moon, On-line analysis of a continnons-flow ozonolysis reaction nsing Raman spectroscopy, A/jpZ. Spectrosc., 61, 1107-1115 (2007). 

Sulfur dioxide was purchased in lecture-size bottles from the City Chemical Corporation. The gas was condensed into a precalibrated 50-ml. Erlenmeyer flask cooled in the dry ice-methanol bath used for cooling the ozonolysis reaction. 

The ozonolysis reaction, followed by reductive workup with sulfur dioxide, as described in Part A of the present procedure, illustrates a general method which has been developed for the preparation of acetals. Application of the procedure is illustrated by conversion of the following olefins in alcoholic solution to the corresponding acetals (1) l-chloro-4-(o-nitrophenyl)-2-butene to o-nitrophenylacetaldehyde dimethyl acetal in 84% yield (2) l,4-dibromo-2-butene tobromoacetaldehyde dimethyl acetal in 67% yield (3) 3-butenoic acid to malonaldehydic acid diethyl acetal ethyl ester in 61% yield (4) cyclopentadiene to malonaldehyde bis(diethyl acetal) in 48% yield and (5)... 

Cyclooctene gives dimethyl octanedioate under these conditions. Scheme 12.18 illustrates some cases in which ozonolysis reactions have been used in the course of synthesis. 

It has been suggested that the oligomers and polymers formed in the ozonolysis reactions of some alkenes arise from the reactive 1,2,3-trioxolane intermediates or their fragmentation products (cf. Section 4.15.4.1) , though relatively little is known about the mode of formation of many of these polymeric species. The tendency of simple 1,2,3-trithiolanes to polymerize has... 

The formation of 1,2,3-trioxolanes from an alkene and ozone is the first step in the ozonolysis reaction, which is widely used in synthesis to convert alkenes to aldehydes or carboxylic acids. No instances of double bond migration during ozonolysis are known (since the first step is a cyclo-... 

Trioxolanes remain the most studied ring system by microwave spectroscopy and recently, 1,2,4-trithiolane also became the subject of attention. In all cases, isotopically labelled derivatives were made which have very different rotational constants. These aid assignment of structures and also provide useful tools for looking at the mechanism of the ozonolysis reaction. Rotational constants for the parent compounds and their calculated dipole moments are given in Table 3. 

O NMR resonances for several 1,2,4-trioxolanes have been reported <91CC816> (Table 6). The ether and peroxide signals are very distinct proving the value of O NMR as an analytical tool for characterization of ozonides. It can be used to determine unequivocally whether a compound is an ozonide (peroxide 6 295-327 ppm) or tetroxane ((26), for example d = 256 ppm). This is often a competing product from the ozonolysis reaction of alkenes (Section 4.16.8.2). 

The ozonolysis of alkenes has been comprehensively covered in several excellent reviews (see Section 4.16.1) and will therefore not be discussed in detail here. It is pertinent, given the importance of 1,2,4-trioxolane synthesis, to highlight the key points of the ozonolysis reaction mechanism and several other developments. 

One of the most important features of the ozonolysis reaction of alkenes is one in which ozone adds to the C=C bond to form a primary ozonide (1,2,3-trioxolane). The Criegee mechanism suggests that this unstable intermediate decomposes into a carbonyl compound and a carbonyl oxide that recombine to form a final isomeric ozonide (1,2,4-trioxolane). Direct spectroscopic evidence for a substituted carbonyl oxide has only recently been reported by Sander and coworkers for the NMR characterization of dimesityl carbonyl oxide. Kraka and coworkers have theoretically modeled dimesityl carbonyl oxide and confirmed the structural aspects reported by Sander and coworkers on the basis of NMR data. 

Alkenes can be cleaved by ozone followed by an oxidative or reductive work-up to generate carbonyl compounds. The products obtained from an ozonolysis reaction depend on the reaction conditions. If ozonolysis is followed by the reductive work-up (Z11/H2O), the products obtained are aldehydes and/or ketones. Unsubstituted carbon atoms are oxidized to formaldehyde, mono-substituted carbon atoms to aldehydes, and di-substituted carbon atoms to ketones. 

Caution The ozonolysis reaction produces peroxidia intermediates which can present a potential explosion hasard. Accordingly, it is recommended that the following experiments be carried out in a hood and behind a safety shield. 

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