Ozonides fragmentation

Ozonation ofAlkenes. The most common ozone reaction involves the cleavage of olefinic carbon—carbon double bonds. Electrophilic attack by ozone on carbon—carbon double bonds is concerted and stereospecific (54). The modified three-step Criegee mechanism involves a 1,3-dipolar cycloaddition of ozone to an olefinic double bond via a transitory TT-complex (3) to form an initial unstable ozonide, a 1,2,3-trioxolane or molozonide (4), where R is hydrogen or alkyl. The molozonide rearranges via a 1,3-cycloreversion to a carbonyl fragment (5) and a peroxidic dipolar ion or zwitterion (6). 

The dipolar ion can react in several ways according to the solvent and the stmcture of the olefin. In inert solvents, if the carbonyl compound is highly reactive (eg, an aldehyde), the dipolar ion can be added to the carbonyl fragment to give the normal ozonide or 1,2,4-trioxolane (7) for example, 1,1-and 1,2-dialkylethylenes react in this manner. Tri- or tetraalkyl-substituted olefins produce a smaH, if any, yield of an ozonide when the ozonolysis is... 

Low -molecular-weight ozonides are explosive and are theretore not isolated. Instead, the ozonide is immediately treated with a reducing agent such as zinc metal in acetic acid to convert it to carbonyl compounds. The net result of the ozonolysis/reduction sequence is that the C=C bond is cleaved and oxygen becomes doubly bonded to each of the original alkene carbons. If an alkene with a letrasubstituted double bond is ozonized, two ketone fragments result if an alkene with a trisubstituted double bond is ozonized, one ketone and one aldehyde result and so on. 

Due to the retractive forces in stretched mbber, the aldehyde and zwitterion fragments are separated at the molecular-relaxation rate. Therefore, the ozonides and peroxides form at sites remote from the initial cleavage, and underlying mbber chains are exposed to ozone. These unstable ozonides and polymeric peroxides cleave to a variety of oxygenated products, such as acids, esters, ketones, and aldehydes, and also expose new mbber chains to the effects of ozone. The net result is that when mbber chains are cleaved, they retract in the direction of the stress and expose underlying unsaturation. Continuation of this process results in the formation of the characteristic ozone cracks. It should be noted that in the case of butadiene mbbers a small amount of cross-linking occurs during ozonation. This is considered to be due to the reaction between the biradical of the carbonyl oxide and the double bonds of the butadiene mbber [47]. 

Several procedures that intercept the intermediates have been developed. When ozonolysis is done in alcoholic solvents, the carbonyl oxide fragmentation product can be trapped as an a-hydroperoxy ether.202 Recombination to the ozonide is then prevented, and the carbonyl compound formed in the fragmentation step can also be... 

The suggested fragments from (54a) are a carbonyl compound (58) and a peroxy zwitterion (59), the latter then effecting a 1,3-dipolar addition on the former to yield the ozonide (57a). Alternative reactions of the zwitterion (59), including its polymerisation, lead to the formation of the abnormal products that are sometimes observed in addition to the ozonide, If ozonolysis is carried out in MeOH as solvent then (59) is trapped , as it is formed, by its conversion into the relatively stable a-hydroperoxy ether (60) ... 

The rearrangement is thought to go through dissociation of the initial ozonide into reactive fragments that recombine to give the ozonide. 

It has been shown that abstraction of an a or p hydrogen from the ozonide also can occur. In fact, a-hydrogen abstraction can occur up to 2.5 times faster than Criegee fragmentation [36], As an example, the proposed mechanism for the reaction of ds-2-butene with ozone is shown in Figure 4. 

For analysis of dienes and polyenes via oxidations one has to distinguish between the formation of an oxidized product of the target molecule (epoxide, peroxide, ozonide etc.) and the oxidative fragmentation of the molecule as in the case of ozonolysis30. Both... 

The use of both ozonation and ozonolysis is reviewed32. Ozonation leads to ozonide and ozonolysis leads to oxidized fragments, showing the use of both oxidative (AgN03) or reductive [(CH3)2S or PI13P] methods to produce the FAME (fatty acids methyl esters) that by subsequent GC analysis enabled determination of the position of the double bonds in the original molecule (equations 2-4). 

The reaction gave only the rearrangement products 333 and 334, and the side product 335, as expected from the reactivity of alkylidenecyclopropane derivatives (Scheme 49). Compound 333 might arise from the 0-0 bond cleavage followed by the rearrangement of a cyclopropyloxy cation to an oxoethyl cation (Scheme 49, path a). Spiro-hexanone 334 could arise from a different fragmentation of ozonide C-O bond and further cyclopropyloxy-cyclobutanone rearrangement (Scheme 49, path b). Oxirane 335 can eventually derive from the same path b or from other side processes [13b]. 

The reaction of alkenes with ozone constitutes an important method of cleaving carbon-carbon double bonds.138 Application of low-temperature spectroscopic techniques has provided information about the rather unstable species that are intermediates in the ozonolysis process. These studies, along with isotope labeling results, have provided an understanding of the reaction mechanism.139 The two key intermediates in ozonolysis are the 1,2,3-trioxolane, or initial ozonide, and the 1,2,4-trioxolane, or ozonide. The first step of the reaction is a cycloaddition to give the 1,2,3-trioxolane. This is followed by a fragmentation and recombination to give the isomeric 1,2,4-trioxolane. The first step is a... 

In the ozonolysis of allylic compounds, varying amounts of products are formed that are due to cleavage of both the C=C double bond and the adjacent C—C single bond. These are the so called abnormal or anomolous products which arise from a fragmentation of the intermediate ozonide (59) (Scheme 10) <81TL1447>. 

Most of the examples given here involve fairly strong acid catalysts to effect fragmentations. Many ozonides are stable to mild acids, so that if a molecule contains other functionality, chemoselective reactions are possible. Reactions of compounds containing both an aldehyde and ozonide group (88) have been studied. The aldehyde could be protected as an acetal using ethylene glycol with... 

SCHEME 21. Fragmentation pattern of the ozonide of an unsaturated glycerophosphochohne hpid in electrospray MS 0 2 r r r... 

In any event, in the solvent cage in which they are formed in the liquid phase, or for higher molecular weight alkenes condensed on surfaces, the two fragments formed by decomposition of the primary ozonide are held in close proximity and recombine to form a secondary ozonide ... 

Ah initio calculations suggest that in ozonolysis, as the two fragments formed by dissociation of the primary ozonide start to move apart, a strong electrostatic attraction builds up between newly formed dipoles.157 The torque created causes a flip of one relative to the other, with formation of a dipolar complex which converts to the secondary ozonide. Thus, the authors suggest that the carbonyl oxide and carbonyl are never actually separated to a van der Waals distance. This argument goes some way to explaining some observed experimental stereoselectivities. 

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