Ketone from ozonide

The oxidative workup used to produce acids from ozonides such as 349 uses reagents such as hydrogen peroxide, peroxy acids, silver oxide, chromic acid or permanganate. The conversion of cyclohexene to adipic acid by treatment with (1) O3 and (2) H2O2 is a simple example of a typical oxidative workup. When the ozonide is disubstituted (two carbon groups on the initial carbon of the alkene), the product is a ketone and... 

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]. 

Gas-phase products from the reactions of ozone with the monoterpenes (-)-p-pinene and (+)-sabinene included the ketones formed by oxidative fission of the exocyclic C=C bonds as well as ozonides from the addition of ozone to this bond (Griesbaum et al. 1998). 

The zwitterion (59) is thereby prevented from reacting with the ketone (58) to form the ozonide in the normal way, and both (58) and (60) may now be isolated and identified. In preparative ozonolysis it is important to decompose the ozonide (57a) by a suitable reductive process, as otherwise H202 is produced (on decomposition of the ozonide with H20, for example) which can further oxidise sensitive carbonyl compounds, e.g. aldehydes— carboxylic acids. 

An alternative procedure for decomposing ozonides from di- or trisubstituted alkenes is to treat them with methanol (CH3OH). The use of this reagent results in the formation of an aldehyde or ketone and a carboxylic acid ... 

On stirring at room temperature ozonides of terminal alkenes (prepared in dichloromethane at — 70 °C) with a polymer-supported tertiary amine obtained from chloromethylated poly(styrene/divinylbenzene) and piperidine, followed by filtration and concentration under reduced pressure, the products (aldehydes or ketones) can be obtained easily in almost pure form in high yields <2003T493>. However, yields are low for cycloalkenes because apparently they form monomeric and polymeric ozonides. 

For reducing ozonides or sterically hindered peroxides, magnesium and methanol proved to be a better and mild reducing agent <2004JOC2851>. Thus, the bicylic ozonide prepared from 1-phenylcyclopentene, which is prone to base-mediated cleavage, was cleanly reduced by Mg/MeOH to the keto-acid with the ketonic methyl ester as a by-product, whereas reduction with zinc and acetic acid affords mainly the keto-aldehyde with the keto-acid as a by-product (Equation 7). 

When a twofold molar excess of an aldehyde, ketone, ketonitrile, or vinyl acetate (the latter provides formaldehyde oxide +CH2-0-0 ) is co-ozonolyzed with various cycloalkene derivatives, three main products are obtained (1) an ozonide 83 with an aldehydic group tethered via an -carbon chain (2) a bicyclic tetraoxepane compound 84 formed from the above dipolar chain and the added carbonyl derivative and (3) a diozonide 85 resulted from the formaldehyde oxide and the aldehydic compound 83. Structures and yields of these products are presented in Scheme 25 and Table 9. 

Treatment of 2-butyne with ozone leads to unstable primary ozonides that cleave to cr-oxo-carbonyl oxides these could be trapped in the presence of aldehydes or ketones affording cross- -oxo-l, 2,4-trioxolanes. Subsequent cycloadditions between such cr-oxo-ozonides and cyclohexanone oxide, generated in situ from O-methylcyclohex-anone oxime (which affords methyl nitrite as a side-product), yield cr-diozonides 101 (Scheme 30) <1997J(P1)1601>. 

Another source of potential antimalarial compounds has been the isolation of stable ozonides 67, produced via the ozonolytic cleavage of the bicyclic ketones 68 (Scheme 11.19).66 Variation of the groups R within 68 allows for formation of a wide range of stable ozonides 67 as exemplified by R = n-heptyl that has a melting point of 75°C to 76°C. The ozonolysis can be carried out in dichloromethane at -5°C to 0°C, and the ozonides 67 usually crystallize directly from the reaction mixture. 

On an industrial scale, the traditional method for cleavage of carbon-carbon double bonds is ozonolysis, used for the manufacture of azelaic acid and nonanoic acids from oleic acid, and of butane tetracarboxylic acid from tetrahydrophthalic anhydride. The process is effectively a quantitative and mild process.178 However, it is capital and energy intensive. The intermediate ozonide is worked up either reductively or oxidatively to produce the aldehyde, ketone or carboxylic acid. Hydrogen peroxide is the common oxidizing agent used in the second step.179-181 Oxygen can also be used either alone182 or in combination with zeolites.183 Reviews on ozonolysis are available and the reader is directed to reference 184 for further information. 

The determination of the active oxygen in ozonides with sodium iodide in glacial acetic acid gives reliable values only in the case of ketozonides. The reaction products are ketones.96 Iodometric peroxide determination in the case of aldozonides gives less than 60% of the theoretical value 112 carboxylic acids are formed as well as aldehydes. The reduction with iodide ions probably suffers competition from the reaction shown in Eq. (7). 

Aldehydes result from the decomposition of certain ozonides. The technique is similar to that used for the preparation of ketones (method 182). High yields are obtained by catalytic hydrogenation of the ozonides. This step coupled with Grignard and dehydration reactions has been used as a procedure for the degradation of an aldehyde to its next lower homolog, viz.,... 

---