Cyclohexene ozonolysis

The cycloalkenes ozonolysis in the presence of methyl pymvate results in tri-substituted ozonides formation. The latter contain three reaction centers (peroxides, proton on the ozonides cycle and methoxy-carbonyl group) accessible for various functionalization. The cyclohexene ozonolysis in the presence of methylpyrovate gives ozonide whose treatment with PPhj or EtjN yields CHO(CHj) CHO and CHO(CH3),COOMe (after esterification), respectively. This method proved to be very convenient and practical way for the synthesis of linear compounds containing various ter-... 

Environmental Aspects. Airborne particulate matter (187) and aerosol (188) samples from around the world have been found to contain a variety of organic monocarboxyhc and dicarboxyhc acids, including adipic acid. Traces of the acid found ia southern California air were related both to automobile exhaust emission (189) and, iadirecfly, to cyclohexene as a secondary aerosol precursor (via ozonolysis) (190). Dibasic acids (eg, succinic acid) have been found even ia such unlikely sources as the Murchison meteorite (191). PubHc health standards for adipic acid contamination of reservoir waters were evaluated with respect to toxicity, odor, taste, transparency, foam, and other criteria (192). BiodegradabiUty of adipic acid solutions was also evaluated with respect to BOD/theoretical oxygen demand ratio, rate, lag time, and other factors (193). 

A sequence of an ozonolysis-PK reaction has been used to convert functionalized cyclohexenes to pyrroles (for example 49 and 50) that are important precursors to natural tetrapyrroles, hemes, and porphyrins ... 

The most common procedure is ozonolysis at -78 °C (P.S. Bailey, 1978) in methanol or methylene chloride in the presence of dimethyl sulfide or pyridine, which reduce the intermediate ozonides to aldehydes. Unsubstituted cydohexene derivatives give 1,6-dialdehydes, enol ethers or esters yield carboxylic acid derivatives. Oxygen-substituted C—C bonds in cyclohexene derivatives, which may also be obtained by Birch reduction of alkoxyarenes (see p. 103f.), are often more rapidly oxidized than non-substituted bonds (E.J. Corey, 1968 D G. Stork, 1968 A,B). Catechol derivatives may also be directly cleaved to afford conjugated hexa-dienedioic acid derivatives (R.B. Woodward, 1963). Highly regioselective cleavage of the more electron-rich double bond is achieved in the ozonization of dienes (W. KnOll, 1975). 

If norbornene is added to a mixture of WCl6/Me4Sn/cyclohexene (1/2.4/5) in toluene at 25 °C, 5% of the cyclohexene is consumed and incorporated into the polymer of nor-bomene, as shown by the presence of 7.5% 1,6-hexanediol in the products obtained by ozonolysis of this polymer followed by reduction with UAIH4. If the copolymer is allowed to stand overnight in the presence of the catalyst at 25 °C the cyclohexene units are split out, with 99% recovery of the original cyclohexene. 

Two examples of preparative ozonolysis are given (Expt 5.79). In the first cyclohexene is subjected to ozonolysis in ethyl acetate to provide a convenient synthesis of the a, co-dicarbonyl compound, adipaldehyde. In the second, the... 

This represents a particular case of the co-ozonolysis reaction when the intermediate carbonyl oxide can be trapped giving rise to other 1,2,4-trioxolanes having a remote functionality. Scheme 38 shows the ozonolysis of cyclohexene... 

This last example makes it clear that we shall normally have to make the cyclohexenes we need for oxidative cleavage and one of the best routes to such compounds is the Diels-Alder reaction (Chapter 17). A generalised example would be ozonolysis of the alkene 21, the adduct of butadiene and the enone 20. The product 22 has a 1,6-relationship between the two carboxylic acids. Since Diels-Alder adducts have a carbonyl group outside the ring (the ketone in 21) the cleavage products 22 also have 1,5- and 1-4-diCO relationships and would be a matter for personal judgement which of these should be disconnected instead if you choose that alternative strategy. 

The ozonolysis of cyclohexene to 1,6-dioxygenated compounds is shown in Figure 17.28. Other cycloalkenes similarly afford other l,y-dioxygenated cleavage products. With the three methods for workup (Figure 17.27), this ozonolysis provides access to 1,6-hexanediol, 1,6-hexanedial, or to 1,6-hexanedicarboxylic acid. Each of these compounds contains two functional groups of the same kind. 

Ozonolysis is not used often in synthesis because it is a degradative reaction—it breaks larger molecules into smaller ones. In synthetic schemes we are usually attempting to build larger molecules from smaller ones. However, the ozonolysis reaction can provide a useful way to prepare an aldehyde or ketone if the appropriate alkene is readily available. One such example is provided by the cleavage of cyclohexene to produce the dialdehyde shown in the previous equation. 

Ozonolysis of cyclohexenes is particularly useful as it gives 1,6-dicarbonyl compounds that are Otherwise difficult to make. In the simplest case we get hexane 1,6-dioic acid (adipic acid) a monomer for nylon manufacture. 

Hemiacetals are formed from hydroxy aldehydes " or ketones which are usually first in a protected form and are deblocked prior to cyclization. Ozonolysis of cyclohexene derivative 5 and reductive workup, followed by hydrolysis of the acid chloride formed in situ and borane reduction of the carboxylic acid, leads to the six-membered hemiacetal 6. a precursor for fluo-rinated sugars that are potentially versatile as molecular probes in the elucidation of biochemical processes. ... 

The literature of this reaction to 1940 has been adequately reviewed. The emphasis up to that time was placed on obtaining higher yields of carbonyl compounds by hydrolysis of the ozonides. Several methods have been described for the oxidative cleavage of ozonides to acids. These procedures may prove valuable in the synthesis of certain acids. By adding the ozonide of 1-tridecene to an alkaline silver oxide suspension at 95°, a 94% yield of lauric acid is obtained. Decomposition of ozonides with 30% hydrogen peroxide is described for the preparation of 5-methyl-hexanoic acid (67%) from 6-methyl-l-heptene and of adipic acid (60%) from cyclohexene. A study of solvents for ozonolysis has been made. ... 

The utility of the asymmetric fumarate/butadiene addition in synthesis is highlighted by the conversion of the (f ./ )-cyclohexene (313a) (derived from (+)-( 5)-menthol) to enantiomerically pure (-)-bilobalide (317) (Scheme 78). This conversion involves particularly the annulation of a cyclopentenone ring to (313a) at the acylated centers which govern the topicity of the acylation (313a) - (314) and internal Michael reaction (314) (315). Ozonolysis of the cyclohexene moiety sets the stage for the formation... 

The oxidation of alkenes and cycloalkenes and their halogen derivatives with at least one hydrogen or halogen atom at the double bond leads to carboxylic acids. Ozonolysis usually requires the oxidative decomposition of the ozonide. The oxygen content of the ozonide is not sufficient for the formation of two molecules of acids or one dicarboxylic acid. The nonoxidative decomposition of cyclohexene ozonide gives an aldehyde-acid or its derivatives [1108]. It comes, therefore, as a surprise that carboxylic acids are claimed as products of the decomposition of ozonides by hydrogenation over the Lindlar catalyst [55] (equation 108). 

Cleavage products of cycloalkenes and cydoalkynes also reveal the cyclic structure. Ozonolysis of cyclohexene, for example, does not break the molecule into two aldehydes of lower carbon number, but simply into a single six-carbon compound containing two aldehyde groups. 

Cyclohexene will undergo an ozonolysis reaction to yield adipic acid upon oxidative workup. Cyclohexene is produced from cyclohexanol by a dehydration (elimination) reaction. The synthesis of adipic acid from cyclohexanol is... 

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