Ozonation reductive hydrolysis

It seemed desirable to point out the connection between these two phenomena— namely, autoxidation and production of ozonides, which at first glance seem to have nothing whatsoever to do with each other. This connection is of practical interest, because it is useful to know that aldehydes, such as anisaldehyde or vanillin, are already present to a considerable extent in the prefabricated state— that is, before the reductive hydrolysis to which the ozonization products are finally submitted with a view to scission of the ozonides formed. 

Methyldihydrotestosterone on being subjected to bromination followed by dehydrobromination gives rise to the formation of 1,2-dehydro derivative, which upon ozonization and hydrolysis yields an aldehyde-acid (1). The resulting acid (1) on reduction produces the corresponding hydroxy-acid (11) which when lactonized produces the desired compound, oxandrolone. 

Scheme 6.11. A proposed pathway (after Criegee) for the ozonolysis (reaction with ozone followed by reductive hydrolysis) of alkenes. so that two equivalents of aldehyde, or two equivalents of ketone, or one equivalent of each, depending upon the substitution pattern of the alkene, results. (See Criegee, R. Angew. Chem. Int. Edit, 1975,87,745.)...

Although in some cases the ozonide can be isolated, these compounds are generally fragile and decompose explosively. Usually, the ozonides are reductively decomposed immediately after formation with zinc (Zn) in acetic add (ethanoic acid, CH3CO2H) or dimethyl sulfide [( 113)28] to give two equivalents of aldehyde, two equivalents of ketone, or one equivalent of each (depending upon the structure of the alkene). The overall process of ozonization coupled with reductive hydrolysis is known as ozonolysis. 

Finally, in this vein, oxidation by ozone (O3) followed by reductive hydrolysis (ozonolysis) (Equation 6.76) can be effected on aromatic compounds and, while it occurs less readily than with alkenes, produces results that suggest that the Kekul6 structures are real. 

Aldehydes are easily oxidized to carboxylic acids under conditions of ozonide hydroly SIS When one wishes to isolate the aldehyde itself a reducing agent such as zinc is included during the hydrolysis step Zinc reduces the ozonide and reacts with any oxi dants present (excess ozone and hydrogen peroxide) to prevent them from oxidizing any aldehyde formed An alternative more modem technique follows ozone treatment of the alkene m methanol with reduction by dimethyl sulfide (CH3SCH3)... 

Alkenes are reduced by addition of H2 in the presence of a catalyst such as platinum or palladium to yield alkanes, a process called catalytic hydrogenation. Alkenes are also oxidized by reaction with a peroxyacid to give epoxides, which can be converted into lTans-l,2-diols by acid-catalyzed epoxide hydrolysis. The corresponding cis-l,2-diols can be made directly from alkenes by hydroxylation with 0s04. Alkenes can also be cleaved to produce carbonyl compounds by reaction with ozone, followed by reduction with zinc metal. 

These substances, like most compounds with peroxide (O—O) bonds, may explode violently and unpredictably. Therefore ozonizations must be carried out with appropriate caution. The general importance of these reactions derives not from the ozonides, which usually are not isolated, but from their subsequent products. The ozonides can be converted by hydrolysis with water and reduction, with hydrogen (palladium catalyst) or with zinc and acid, to carbonyl compounds that can be isolated and identified. For example, 2-butene... 

The enol acetate 77 of 3,4-dihydro-7-methoxy-5-methyl-l-(2l/)-naphthalenone was converted to the acid 78 by ozonolysis and hydrolysis and this by a Wittig reaction with a-methoxyethyltriphenyl-phosphonium chloride gave 79. Compound 79 was converted into 80 by a series of reactions, five in number, which in turn was converted into 81 by reaction with potassium in -butanol. The methyl ester of compound 81, one isomer of which was recognized as that having the correct stereo structure, was converted to 82 by heating with acetic anhydride and 10-camphorsulfonic acid. Subsequent steps involved ozonization, reaction with V,iV -carbonyldiimidazole, lactam formation, reaction with pyridinium bromide perbromide, reaction with sodium hydride, and a further series in which (+ )-oxodendrobine (83) was ultimately obtained. Reduction of the latter to ( )-dendrobine... 

T he reaction of ozone with olefins usually results in cleavage of the double bond and the formation of aldehydes, ketones, and/or carboxylic acids, depending upon the reaction conditions and the structures involved. For aldehydes, the intermediate ozonides are ordinarily treated with a mild reducing agent—for example, hydrogen or zinc—or subjected to neutral hydrolysis. Yields in excess of 70% are exceptional for the reduction methods, while hydrolysis gives considerably lower yields. 

An interesting conversion of an erythrinan (9) into a -erythroidine derivative (12) has been reported (Scheme 1). Birch reduction of (9) followed by hydrolysis gave a good yield of the conjugated enone (10), which upon successive treatment with benzaldehyde, ozone, hydrogen peroxide, and diazomethane provided the... 

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