Ozonides, formation reduction

Dichloroaluminium hydride in ether or sodium borohydride in TEA can lead to formation of ethers from ozonides by reductive cleavage of the two C—O bonds of the peroxide bridge (Equation (19)) <85JOC275>. 

The catalytic properties of Co in the hydrocarbon oxidation have been the subject of intensive investigations [107], It has been established that during the cumene-AcOH ozonolysis in 1 1 (v v) in the presence of Co(AcO)2 the oxidation reaction is accelerated (Fig. 17).In contrast to the noncatalysed process in the catalyzed by transition metal salts the ozonolysis is characterized by 1) absence of ozonides formation that is indicative of the absence of ozone interaction with the phenyl ring and 2) the main product is DMPC, the accumulation rate of which proportional to the concentration of Co after the 10 min. The initial rates of CHP formation do not vary with the changes in Co + but after the 15 min the rates increase with [Co ]. It can be seen from Table 9 that if we assume the ozonolysis of pure cumene as a reference then the addition of AcOH results in autoretardation of the oxidation rate and to reduction of the products yield. The ratio [IP]/[03 reaches value of 6.9. 

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. 

Ozonolysis of alkenes in the presence of amine A-oxides resulted in reductive ozonolysis, i.e, the direct formation of aldehydes in high yields, avoiding the generation and isolation of ozonides or other peroxide products. Use of DMSO and tertiary amines improved the yield of aldehydes but some amount of ozonides remained. This... 

An older paper <1971MI873> reported that ozonolysis of alkenes in the presence of tertiary amines resulted in the formation of aldehydes. A recent reinvestigation <20060L3199> has shown that amine oxides were responsible for this reductive ozonolysis . Indeed, pretreatment of the tertiary amines with ozone, giving rise to amine oxides, accounted for this phenomenon. A preparative method emerged, by treating the alkene (e.g., 1-decene) at 0 °C with a solution of 2% 03/02 in dichloromethane (2 equiv of ozone relative to the alkene) in the presence of an excess (about threefold molar excess) of A-methylmorpholine A-oxide, pyridine A-oxide, or l,4-diazabicyclo[2.2.2]octane A-oxide (DABCO A-oxide). Yields of aldehydes (nonanal in the above example) were 80-96%, and the excess of amine oxide ensured the absence of residual ozonide (Scheme 21). 

When the O-methyloxime of acetone was co-ozonided with diacetyl, the known stereoisomers of the ct-diozonide (the achiral meso and the racemic) were obtained. A similar result was obtained when the O-methyloxime of cyclohexanone was co-ozonided with diacetyl. Reduction with Ph3P afforded the expected products plus acetic anhydride, whose formation may be explained by the formation of a diradical or the corresponding dioxirane 82 that rearranged to an anhydride (Scheme 24) <1997T5463>. 

Greenwood91,92 demonstrated the formation of primary ozonides in the reaction of some reaction with liquid ozone gave products that formed glycols on mild reduction with isopropylmagnesium bromide. On the other hand, primary ozonides have not been detected with certainty in the case of cis-olefins.88 91 The reaction of cis-3-hexene,93 eis-2-butene, cis-2-pentene, and ethylene92 with ozone at —112° in pentane led to extremely explosive substances, which could be primary ozonides. In the... 

The first step, a 1,3-dipolar addition, results in the formation of a primary ozonide (1 equation 6). This intermediate then opens to give a carbonyl and a zwitterion that can recombine to give the more stable normal ozonide (2 equation 7). Reduction of (2), without isolation, by lithium aluminum hydride, diborane or sodium borohydride dten gives either primary or secondary alcohols, depending on the nature of starting alkene (equation 8). 

Ozonolysis as used below is the oxidation process involving addition of ozone to an alkene to form an ozonide intermediate which eventually leads to the final product. Beyond the initial reaction of ozone to form ozonides and other subsequent intermediates, it is important to recall that the reaction can be carried out under reductive and oxidative conditions. In a general sense, early use of ozonolysis in the oxidation of dienes and polyenes was as an aid for structural determination wherein partial oxidation was avoided. In further work both oxidative and reductive conditions have been applied . The use of such methods will be reviewed elsewhere in this book. Based on this analytical use it was often assumed that partial ozonolysis could only be carried out in conjugated dienes such as 1,3-cyclohexadiene, where the formation of the first ozonide inhibited reaction at the second double bond. Indeed, much of the more recent work in the ozonolysis of dienes has been on conjugated dienes such as 2,3-di-r-butyl-l,3-butadiene, 2,3-diphenyl-l,3-butadiene, cyclopentadiene and others. Polyethylene could be used as a support to allow ozonolysis for substrates that ordinarily failed, such as 2,3,4,5-tetramethyl-2,4-hexadiene, and allowed in addition isolation of the ozonide. Oxidation of nonconjugated substrates, such as 1,4-cyclohexadiene and 1,5,9-cyclododecatriene, gave only low yields of unsaturated dicarboxylic acids. In a recent specific example... 

The constitution of the ozonide was proved by analysis and by reduction to acetone and methyl pyruvate. The formation of this new ozonide can be explained by... 

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. 

Methyldihydrocodeine [xxn] on heating with thionyl chloride is dehydrated to 6-methyldesoxycodeine-C [xxm] phosphorus penta-chloride effects chlorination in position 1 in addition to dehydration. 6-methyldesoxycodeine-C is non-phenolic and gives no formaldehyde on ozonolysis the ozonide on treatment with iodine and alkali yields iodoform, indicating formation of a methyl ketone. Catalytic reduction of [xxm] gives 6-methyltetrahydrodesoxycodeine [xxiv] [16]. 

Tertiary amines. Using a secondary amine to decompose an ozonide derived from 1-alkene effects its alkylation. The amine initiates an eliminative fragmentation of the ozonide to generate an aldehyde and dialkylammonium formate. Schiff base formation from the aldehyde and another molecule of the amine is then followed by reduction by the formate ion. 

As discussed in Section 3.7.B, ozone adds to an alkene to generate a 1,2,3-trioxolane. Addition of ozone to 1-pentene, for example, generated 425. Rearrangement of this initially formed cycloadduct is facile, even at temperatures as low as -78°C, and results in cleavage of the carbon-carbon bond in 425, with formation of a 1,2,4-trioxolane (426). This product is usually called an ozonide and can be either oxidized or reduced to give the carbonyl compounds characteristic of the oxidative or reductive cleavage reactions. 

The structure of the ozonide from the reaction of the allylic alcohol 13 with ozone is shown below. This is the normal product from ozonolysis. Notice that there is no oxidant (such as H2O2) or reductant (such as Mc2S) in the formation of the keto-acid 14. The formation of the product 14 can be explained by fragmentation of the ozonide (see below), which occurs in a similar way to that described for the ozonolysis of a,p-unsaturated carbonyl compounds given in Scheme 5.105. See R. L. Cargill and B. W. Wright, / Org. Chem., 40 (1975), 120. 

Mechanistically, the first step mimics the quench with EtsN proceeding through deprotonation of the intermediate ozonide (eq 51). The second equivalent of the amine then forms the enamine intermediate observed if the reaction is not kept at the reflux point. The enamine intermediate undergoes a modified Wal-lach reduction with piperidinium formate that is generated during the initial deprotonation step of the reaction to give the target amine. 

Ozone is a god target reagent for microreactor applications since it is toxic, difficult to handle and very reactive. A silicon-etched 16-channel (600 (tm x 300 pm x 22.7 mm) microreactor covered with Plexiglas was used for oxidation of 1-decene into nonanal with quantitative conversion and selectivity [20]. This reaction proceeds in fact through the formation of the very reactive intermediate ozonide, which formally results from [3 + 2] addition of O3 to the C=C bond. A consecutive reduction step with P(OEt)3-EtOAc is required to yield the aldehyde. The reaction time is as short as 0.32 s. From the published data, a daily production of ca. 1600 g of nonanal per day may be obtained, which is well suited for preparation in fine chemistry. 

The main reaction products upon oxidative decomposition of the ozonide of (-) tetrahydrohumulone are 3-methylbutanoic acid and 4-methylpentanoic acid. Reductive decomposition furnishes in addition 5,5-dimethyltetrahydrofuran-2-one and the optically active 2-hydroxy-5-methylhexanoic acid with unknown optical purity. The reaction sequence for the formation of the hydroxycarboxylic acid is given in Fig. 7. 

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