Ozonolysis of alkene

Ozone (O3), the triatomic form of oxygen, is a polar molecule (p, = 0.5 D) that can be represented as a hybrid of its two most stable Lewis structures. 

It is a powerful electrophile and reacts with alkenes to cleave the double bond, forming an ozonide. Ozonides undergo hydrolysis in water, giving carbonyl compounds. 

Because hydrogen peroxide is a product of ozonide hydrolysis and has the potential to oxidize the products, the second half of this two-stage ozonolysis sequence is carried out in the presence of a reducing agent, usually zinc or dimethyl sulfide. 

1-Methylcyclopentene gives a single compound (C6H12O2) on ozonolysis. What is it  

Ozonolysis has both synthetic and analytical applications in organic chemistry. In synthesis, ozonolysis of alkenes provides a method for the preparation of aldehydes and ketones. When the objective is analytical, the products of ozonolysis are isolated and identified, thereby allowing the structure of the alkene to be deduced. In one such example, an alkene having the molecular formula CgHig was obtained from a chemical reaction and gave acetone and 2,2-dimethylpropanal as the products. 

Ozone is a powerful electrophile and undergoes a remarkable reaction with alkenes in which both the cr and tt components of the carbon-carbon double bond are cleaved to give a product referred to as an ozonide. 

Ozonides undergo hydrolysis in water, giving carbonyl compounds. 

Two aldehydes, two ketones, or one aldehyde and one ketone may be formed. Let s recall the classes of carbonyl compounds from Table 2.2. Aldehydes have at least one hydrogen substituent on the carbonyl group ketones have two carbon substituents—alkyl groups, for example—on the carbonyl. Carboxylic acids have a hydroxyl substituent attached to the carbonyl group. 

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

Ozonolysis followed by reductive workup gives a mixture of aldehydes and ketones whose structures depend on the groups bonded to the sp -hybridized carbon atoms. Thus, as a synthetic method, the process is limited by the requirement of having the appropriate aUcene. This reaction also wastes part of the starting material because usually only one of the cleavage products is desired and the two carbonyl compounds must be separated. Nevertheless, the method proves useful in specific cases, such as the oxidative cleavage of a-pinene. In this case, the methanal byproduct is a gas that escapes from solution and does not contaminate the bicyclic ketone product. 

TABLE 6.4 Relative Rates of Epoxidation of Some Representative Alkenes with Peroxyacetic Acid  

Alkene Structural formula Relative rate of epoxidation  

Alkene epoxidation is believed to be concerted, occurring by way of a single bimo-lecular elementary step, as shown in Mechanism 6.9. 

Hexane does not react with purple KMn04 (left) cyclohexene (right) reacts, producing a brown-black precipitate of MnOa. 

The net result of this reaction is to break the double bond of the alkene and to form two carbon-oxygen double bonds (carbonyl groups), one at each carbon of the original double bond. The overall process is called ozonolysis. 

Ozonolysis can be used to locate the position of a double bond. For example, ozonolysis of 1-butene gives two different aldehydes, whereas 2-butene gives a single aldehyde. 

Ozonolysis is the oxidation of alkenes with ozone to give carbonyl compounds. 

Using ozonolysis, one can easily tell which butene isomer is which. By working backward from the structures of ozonolysis products, one can deduce the structure of an unknown alkene. 

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Ozonolysis has both synthetic and analytical applications m organic chemistry In synthesis ozonolysis of alkenes provides a method for the preparation of aldehydes and ketones... 

I Ozonolysis of alkenes yields ketones if one of the unsaturated carbon atoms is disubstituted (Section 7.9). 

Ozonolysis of alkene 446 in the presence of acetaldehyde afforded diketone 448 through the intermediacy of 447. Ring expansion through Beckmann rearrangement took place when bis-oxime 449 was mesylated and warmed in aqueous tetrahydrofuran (THF). The bis-lactam so formed gave piperidinediol 450 on reduction with lithium aluminium hydride, and this compound was transformed into ( )-sparteine by treatment with triphenylphosphine, CCI4, and triethylamine (Scheme 105) <20050BC1557>. 

With advances in technology, theoretical methods have gained importance as a powerful tool. 1,2,4-Trioxolanes have attracted the most interest, undoubtedly because of their pivotal role in the mechanism of the ozonolysis of alkenes. Apart from 1,2,4-trithiolane (2) nothing has been reported for the other five-membered rings (3)-(6) or their derivatives. 

Acid-catalyzed dimerization and oligomerization of 1,2,4-trioxolanes will be covered in Section 4.16.5.2.1. In general, ozonides are not prone to spontaneous polymerization. Polymeric products can be obtained from the ozonolysis of alkenes but most likely arise from reaction of the primary ozonide. Bicyclic 1,2,4-trioxolanes such as 2,5-dimethylfuran endoperoxide can dimerize on warming in CCI4 (Section 4.16.5.1.1). 1,2,4-Trithiolane tends to polymerize at room temperature especially if left open to air, whilst more highly substituted ring systems are stable. 

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. 

The ozonolysis of alkenes has been comprehensively covered in several excellent reviews (see Section 4.16.1) and will therefore not be discussed in detail here. It is pertinent, given the importance of 1,2,4-trioxolane synthesis, to highlight the key points of the ozonolysis reaction mechanism and several other developments. 

Ozonolysis of alkenes on solid supports, notably polyethylene <85JA5309>, has greatly increased the scope of the reaction in the preparation of 1,2,4-trioxolanes. Competing reactions of intermediates are avoided and the mild conditions often allow isolation of relatively unstable or previously unobtainable 1,2,4-trioxolanes. 

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. 

Schindler and coworkers verified the formation of hydroxyl radicals kinetically and further RRKM calculations by Cremer and coworkers placed the overall concept on a more quantitative basis by verifying the measured amount of OH radical. An extensive series of calculations on substituted alkenes placed this overall decomposition mechanism and the involvement of carbonyl oxides in the ozonolysis of alkenes on a firm theoretical basis. The prodnction of OH radicals in solution phase was also snggested on the basis of a series of DFT calculations . Interestingly, both experiment and theory support a concerted [4 4- 2] cycloaddition for the ozone-acetylene reaction rather than a nonconcerted reaction involving biradical intermediates . 

Gutbrod, R., R. N. Schindler, E. Kraka, and D. Cremer, "Formation of OH Radicals in the Gas Phase Ozonolysis of Alkenes The Unexpected Role of Carbonyl Oxides, Chem. Phys. Lett., 252, 221-229 (1996). 

Ozonolysis of alkenes (end of Section 6.4) and cleavage of glycols (Section 14.11) afford carbonyl compounds. These reactions, once used for structure determinations, have been superseded by spectral methods. 

Aldehydes and ketones are obtained by ozonolysis of alkenes (see Section 5.7.6) and hydration of alkynes (see Section 5.3.1). 

Carbon monoxide has been used to scavenge OH fonned from the ozonolysis of alkenes. The CO2 tints generated was detected by FTIR spectroscopy and the "OH yields for individual reactions were calculated.239 The significance of the OH-induced intramolecular transformation of glutathione thiyl radicals to a-aminoalkyl radicals has been discussed with respect to its biological implications.240 The kinetics and mechanism of the process indicated that it could be a significant pathway for the selfremoval of glutathione thiyl radicals in vivo. 

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