Ozonolysis molozonide

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 ozonolysis of olefins may be analyzed as a sequence of two 1,3-dipolar cycloadditions initial electrophilic attack by ozone 18 to form the first intermediate, which decomposes into a carbonyl compound and a carbonyl oxide 14 followed by nucleophilic 1,3-dipolar addition of the carbonyl ylide 14 to the ketone, yielding the molozonide. 

The mechanism proposed by Criegee for the ozonolysis of alkenes <1975AGE745> considers an initial it-complex between the alkene and ozone which decays via a 1,3-dipolar cycloaddition into a 1,2,3-trioxolane or primary ozonide, known also as the molozonide . These compounds are unstable, even at low temperatures, and due to cycloreversion decompose into a carbonyl fragment and a CO, which may recombine by another 1,3-dipolar cycloaddition step to form the more stable 1,2,4-trioxolane ( secondary ozonide or final ozonide (see also Section 6.06.2). 

Co-ozonolysis of 1,2-dihydronaphthalene with formaldehyde, acetyl cyanide (pyruvonitrile), benzoyl cyanide, or acetaldehyde afforded an ozonide attached to a benzaldehyde group 89 and none of the isomeric ozonide with a propionaldehyde group. This indicates the preference for scission of the molozonide so as to favor conjugation between the aromatic ring and the aldehyde group rather than with the carbonyl oxide group. Subsequent co-ozonolysis of products 89 with vinyl acetate produced diozonides 90, as shown in Scheme 26 and Table 11. 

Trioxolanes (molozonides) 232 are highly unstable species but because of their involvement in ozonolysis they have been the subject of many MO calculations. There is general agreement that the envelope conformation with 0(2) out of plane is the most stable. For the 4-halo derivatives 232 (R = F, Cl) the yy/z-conformation is calculated to be the most stable ( 2kcalmol-1) due to electrostatic repulsion and an anomeric effect <2002JPCA4745, CHEC-III(6.05.4.2)150>. 

Generation of oxygen-18 labeled ozonides followed by location of the isotopic label using reductive techniques has served to substantiate a new mechanism of ozonolysis which was proposed to account for the dependence of ozonide cis/trans ratios on olefin geometry. The new mechanism requires fragmentation of the molozonide to produce some aldehyde and zwitterion but further requires that ozonide may also be formed by the reaction of molozonide and aldehyde. 

The labeling experiments, therefore, provide strong support for the mechanism we proposed to account for the dependence of ozonide cis/trans ratios on olefin geometry 14). In this particular case, under conditions of added aldehyde, approximately 70-75% of the ozonide (5ab) was, by all indications, formed through the molozonide-aldehyde reaction. However, in a normal ozonolysis aldehyde is not present initially, and before the molozonide-aldehyde mechanism can become important, a sufficient quantity of aldehyde must be produced, presumably by fission of the molozonide to zwitterion and aldehyde. Under these conditions it would not be surprising to find the new mechanism somewhat less important than in the present study. Once sufficient aldehyde is obtained in the normal ozonolysis, production of zwitterion may well nearly cease since the molozonide-aldehyde reaction does not deplete aldehyde concentration, and at sufficiently high aldehyde concentrations this reaction competes well with molozonide fission. Reaction temperature should be important in this competition. 

While the oxygen-18 labeling results described here confirm the molozonide-aldehyde mechanism for the types of olefins considered, the ozonolysis reaction in general is quite complex and seems to vary widely depending especially upon the stereochemistry of the olefin. To sum up, the molozonide-aldehyde mechanism 14) considered here appears to be applicable to any important degree only to trans-disubstituted olefins, relatively unhindered cis olefins, and perhaps to unhindered terminal olefins. As pointed out, more hindered olefins seem to react by one or more different pathways, which differ most notably from the present system in the apparent absence of a molozonide intermediate (2, 8, i2,14). 

Using modern analytical methods, a number of transient intermediates and byproducts could be verified [19, 20]. The first step in the mechanism of ozonolysis is the 1,3-dipolar cycloaddition of the dipole ozone to the double bond of OA. A 1,2,3-trioxolane is formed, the unstable primary ozonide or molozonide. The primary ozonide collapses in a 1,3 dipolar cycloreversion to a carbonyl compound and a carbonyl oxide, the so-called Criegee zwitterion. Since OA is substituted with two diverse groups at the double bond, two different opportunities exist for the formation of carbonyl compound and carbonyl oxide. Again, a 1,3-dipolar cycloaddition of these intermediates leads to three different pairs of 1,2,4-trioxolane derivatives (cisltram), the secondary ozonides, which are more stable than the primary ones. Their oxidative cleavage results in AA and PA. 

The Criegee mechanism for the ozonolysis of alkenes (Figure 11.73) can be analyzed in terms of a series of three 1,3-dipolar cycloadditions. The addition of ozone to an alkene leads first to a 1,2,3-trioxacyclopentane structure known variously as an initial ozonide, primary ozonide, or molozonide,... 

Ozonolysis is now more extensively employed for both analytical and preparative purposes. Reaction occurs via the molozonide which breaks down to aldehyde and the Criegee zwitterion. The latter then reacts with aldehyde to give ozonide or with solvent to give alkoxyhydroperoxide (alcohol) or acyloxyhydroperoxide (carboxylic acid). All of these subsequently break down to the same ozonolysis products. 

Mechanism of Ozonolysis (Criegee mechanism) The initial step of the reaction involves a 1,3-dipolar cycloaddition of ozone to the alkene leading to the formation of the primary ozonide (molozonide or 1,2,3-trioxolane), which decomposes to give a carbonyl oxide and a carbonyl compound. The carbonyl oxides are similar to ozone in being 1,3-dipolar compounds and undergo 1,3-dipolar cycloaddition to the carbonyl compound with the reverse regio-chemistry, leading to a relatively stable secondary ozonide (1,2,4-trioxolane) (Scheme 5.47). 

The first step of the ozonolysis mechanism is the initial electrophilic addition of ozone to the C=C double bond to form the molozonide intermediate. Its instability leads to a further reaction, producing a carbonyl and carbonyl oxide molecule (Scheme 2.10, II). The carbonyl and carbonyl oxide rearrange to create the stable ozonide intermediate (Scheme 2.10, III). A reductive workup is then undertaken to convert the ozonide specie into carbonyl products (Scheme 2.10,1) [19]. 

A dioxetan intermediate (123) has been isolated from the ozonolysis of ethylidenecyclohexane in pinacolone and appears to be formed via reduction of the molozonide (124) by solvent. On heating, (123) gave cyclohexanone and acetaldehyde, which are the normal ozonolysis products. 

The process called ozonolysis involves the reaction of ozone with an alkene to give a five-membered ring containing three oxygen atoms adjacent to one another, as shown in Figure 10.50. Such a ring is called a primary ozonide or a molozonide. 

Certain aldehydes and ketones, when used as solvents, intercept and reduce a labile intermediate in the ozonolysis of olefins. The intermediate, which can be considered the progenitor of many other ozonolysis products, is formulated as the Staudinger molozonide, e.g. (577), and its reduction generates the corresponding dioxetan (578) with a Baeyer-Villiger oxidation of the aldehyde or ketone solvent. The dioxetan intermediate, normally cleaved to the carbonyl components, has now been isolated and characterized by using pinacolone as a solvent. Low-temperature infrared studies of simple alkene-ozone reactions have been made. ... 

The mechanism of ozonolysis proceeds through initial electrophilic addition of ozone to the double bond, a transformation that yields the so-called molozonide. In this reaction, as in several others already presented, six electrons move in concerted fashion in a cyclic transition state. The molozonide is unstable and breaks apart into a carbonyl fragment and a carbonyl oxide fragment through another cychc six-electron rearrangement. Recombination of the two fragments as shown yields the ozonide. 

Mechanism of Ozonolysis Step 1. Molozonide formation and cleavage... 

Ozonolysis occurs in several steps. First, an unstable intermediate, called a molozonide, forms by a cyclic concerted addition of the terminal oxygen atoms of ozone to the 7i bond of the alkene. This step requires a total of three electron pair shifts, as shown below. 

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