Alcohols with ozonides

It can thus be seen that zwitterions IV and V would be stabilized by the interaction of the alcohol with them, and the ozonide would have no opportunity to form and decompose abnormally. Whether zwitterions IV and V are formed in equal amounts depends upon the groups which are attached to the double bond and the carbon atom to which the ozone molecule initially adds. The final products, VI and VII, may be considered as hemiperacetals or hemiperketals and could be isolated only under special conditions. However, they can be easily decomposed with either sulfurous acid or sodium bisulfite and the ketones or aldehydes formed determined quantitatively as their 2,4-dinitrophenylhydrazones. 

The reaction of methyllithium with ozonide (5ab) was extremely rapid and exothermic, and although methane was evolved, the reaction appears to proceed principally by displacement on the oxygen-oxygen bond by methide to yield isopropyl alcohol (9), 3-methyl-2-butanol (10), and methyl alcohol. The source of the methane is unknown at present. However, the entire reaction is being investigated. 

A few other special procedures are quoted elsewhere in this book Methods for preparing ozonides (pp. 406—409) and for formation of mercury(II)-acetate adducts of unsaturated lipids (p. 402) procedures for esterifying fatty acids with diazomethane (p. 175) and for acetylation of alcohols with acetic anhydride (p. 175). The procedures described for preparing trifluoroacetates or trimethylsilyl ethers can be applied to aliphatic alcohols. 

Commercially, pure ozonides generally are not isolated or handled because of the explosive nature of lower molecular weight species. Ozonides can be hydrolyzed or reduced (eg, by Zn/CH COOH) to aldehydes and/or ketones. Hydrolysis of the cycHc bisperoxide (8) gives similar products. Catalytic (Pt/excess H2) or hydride (eg, LiAlH reduction of (7) provides alcohols. Oxidation (O2, H2O2, peracids) leads to ketones and/or carboxyUc acids. Ozonides also can be catalyticaHy converted to amines by NH and H2. Reaction with an alcohol and anhydrous HCl gives carboxyUc esters. 

Most ozonolysis reaction products are postulated to form by the reaction of the 1,3-zwitterion with the extmded carbonyl compound in a 1,3-dipolar cycloaddition reaction to produce stable 1,2,4-trioxanes (ozonides) (17) as shown with itself (dimerization) to form cycHc diperoxides (4) or with protic solvents, such as alcohols, carboxyUc acids, etc, to form a-substituted alkyl hydroperoxides. The latter can form other peroxidic products, depending on reactants, reaction conditions, and solvent. 

The hydroperoxide (POOH) concentration was determined iodometri-cally after decomposition of the ozonides with excess of alcoholic sodium hydroxide. 

There are many ways to categorize the oxidation of double bonds as they undergo a myriad of oxidative transformations leading to many product types including epoxides, ketones, diols, endoperoxides, ozonides, allylic alcohols and many others. Rather than review the oxidation of dienes by substrate type or product obtained, we have chosen to classify the oxidation reactions of dienes and polyenes by the oxidation reagent or system used, since each have a common reactivity profile. Thus, similar reactions with each specific oxidant can be carried out on a variety of substrates and can be easily compared. 

When ozonolysis is done in alcoholic solvents, the carbonyl oxide fragmentation product can be trapped as an a-hydroperoxy ether.146 Recombination to the ozonide is then prevented, and the carbonyl compound formed in the fragmentation step can also be isolated. If the reaction mixture is treated with dimethyl sulfide, the hydroperoxide is reduced and the second carbonyl compound is also formed in good yield.147 This procedure prevents oxidation of the aldehyde by the peroxidic compounds present at the conclusion of ozonolysis. 

Ozonolysis of alkenes in participating solvents such as alcohols often leads to trapping of intermediates. Most commonly, an alcohol will react with the carbonyl oxide zwitterion, generated from cycloreversion of the primary ozonide (Section 4.16.8.2), to give an alkoxy hydroperoxide. The secondary ozonide (1,2,4-trioxolane) is usually more stable to nucleophilic attack from alcohols. 

Formation of the diozonide (120) as a mixture of meso- and ( + )-isomers was achieved by ozonolysis of the corresponding diene on polyethylene (Section 4.16.9.2). This compound underwent an unusual reaction with benzyl alcohol in the presence of NaHCOj, leading to the formation of a 3-benzyloxy-l,2,4-trioxolane (121) (Scheme 32) <89TLl5ii>. It was suggested that the C—C bond linking the two ozonide rings is cleaved giving rise to an intermediate carbocation. 

A 1989 report describes preparation of 3-alkoxy-l,2,4-trioxolanes (122) by reaction of the corresponding 3-acetoxy derivative (123) with an alcohol under basic conditions (Equation (22)) <89TLi5ii>. Apart from the unusual related reaction of diozonide (120) in Section 4.16.6.2, this sort of nucleophilic substitution at an ozonide is rare. 

Trioxolanes are key intermediates in the ozonolysis of alkenes (Section 4.16.8.2). This reaction is of considerable importance in synthetic chemistry where ozonide intermediates are often reduced (to aldehydes or alcohols) or oxidized (to carboxylic acids) in situ. Advantage has been taken of the stability of certain derivatives to investigate selective chemical reactions. An example of selective reduction is shown in Scheme 47 <91TL6454> with other uses of the 1,2,4-trioxolane ring as a masked aldehyde or ester referred to in Section 4.16.5.2.1. 

Substrates suitable for oxidative conversion into carbonyl compounds are alkenes, primary or secondary alcohols, and benzyl halides. Polystyrene-bound alkenes have been converted into aldehydes (with the loss of one carbon atom) by ozonolysis followed by reductive cleavage of the intermediate ozonide (Entry 1, Table 12.3). 

---