3,5-Disubstituted trioxolanes

Ozonides having one or two substituents at the trioxolane ring—in the latter case symmetrically or unsymmetrically—were prepared from the corresponding olefins by ozonization in pentane, usually at —78°C. The 3,5-disubstituted trioxolanes were separated into cis- and transisomers by crystallization or by column chromatography. 

Fragmentation Products. All ozonides except for the tetrasubstituted ones are cleaved quantitatively by many solvents. While symmetrically disubstituted ozonides give one mole of acid and one mole of aldehyde as products, and trisubstituted ozonides yield one mole acid and one mole of a ketone, in the case of monosubstituted or unsymmetrically 3,5-disubstituted trioxolanes, two kinds of acids and two kinds of aldehydes are possible. The fragmentation products in these cases were treated with diazomethane, and the mixture of the methyl esters was analyzed by gas chromatography. The results are shown in Table VI. In all of these examples, the reactions go predominantly in one direction. When R and R are more similar, however, both kinds of reaction products would be expected in more nearly equal amounts. 

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. 

Ozonolysis of cyclic olefins in the presence of carbonyl compounds gives the corresponding cross-ozonides.1329 In the ozonation of 1,2,4,5-tetramethyl-1,4-cyclohexadiene, oxidative dehydrogenation (formation of 1,2,4,5-tetramethylben-zene) was found to compete with oxidative cleavage because of steric hindrance.1330 Secondary ozonides (the 76 1,2,4-trioxolanes) are formed in high yields in the gas-phase, low-temperature ozonation of terminal and disubstituted alkenes.1331... 

The transformation of tetrasubstituted ethylenes into 1,2,4-trioxolanes may also be achieved if the ozonolysis is carried out in the presence of a foreign carbonyl compound as described in Section 4.33.3.4. With formaldehyde as added carbonyl compound, 3,3-disubstituted derivatives are obtained, whereas in the presence of excess ketone (e.g. by using the latter as solvent), the ozonolysis gives rise to tetrasubstituted 1,2,4-trioxolanes which are difficult to prepare by other methods. Reactions (163) -> (164) and (165) -> (166) provide two examples of this versatile 1,2,4-trioxolane synthesis. Unlike the parent system (2), alkyl- and/or aryl-substituted 1,2,4-trioxolanes generally are stable, non-explosive compounds. Mixtures of crossed ozonides (cf. Section 4.33.3.1.1) or of cis and trans isomers can be separated by thin layer, column or gas chromatography. The cis isomers of symmetrical 3,5-disubstituted 1,2,4-trioxolanes are meso forms, whereas the corresponding trans isomers represent racemates which in some cases have been resolved into their optical... 

Some trisubstituted ozonides could be obtained only by the method of Murray, Story, and Loan (1)—namely, the ozonization of disubstituted olefins in ketones as solvents. Ozonization of tetraphenylethylene in acetone, methyl ethyl ketone, or benzophenone gave the hitherto unknown trioxolanes with four hydrocarbon residues (2). Table I shows some examples. 

The effects contributed by alkyl groups to the relative rate constants, kreh for the reaction of ozone with cis- and trans-1,2-disubstituted ethylenes are adequately described by Taft s equation = k °reX -f pSo-, where So- is the sum of Taft s polar substituent constants. The positive p values (3.75 for trans- and 2.60 for cis-l,2-disubstituted ethylenes) indicate that for these olefins the rate-determining step is a nucleophilic process. The results are interpreted by assuming that the electrophilic attack of ozone on the carbon-carbon double bond can result either in a 1,3-dipolar cycloaddition (in which case the over-all process appears to be electrophilic) or in the reversible formation of a complex (for which the ring closure to give the 1,2,3-trioxolane is the nucleophilic rate-determining step). 

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