Ozonolysis

Last updated
Ozonolysis
Reaction type Organic redox reaction
Identifiers
Organic Chemistry Portal ozonolysis-criegee-mechanism

In organic chemistry, ozonolysis is an organic reaction where the unsaturated bonds are cleaved with ozone (O3). Multiple carbon–carbon bond are replaced by carbonyl (C=O) groups, such as aldehydes, ketones, and carboxylic acids. The reaction is predominantly applied to alkenes, but alkynes and azo compounds are also susceptible to cleavage. The outcome of the reaction depends on the type of multiple bond being oxidized and the work-up conditions. [1]

Contents

Detailed procedures have been reported. [2] [3] [4]

Ozonolysis of alkenes

Alkene Ozonolysis
Reaction type Organic redox reaction
Reaction
Alkene
+
O3
+
Typically reducing agents
↓
Cleavage products
Identifiers
Organic Chemistry Portal ozonolysis-criegee-mechanism
RSC ontology ID RXNO:0000344

Alkenes can be oxidized with ozone to form alcohols, aldehydes or ketones, or carboxylic acids. In a typical procedure, ozone is bubbled through a solution of the alkene in methanol at −78 °C until the solution takes on a characteristic blue color, which is due to unreacted ozone. Industry however recommends temperatures near -20 °C. [5] This color change indicates complete consumption of the alkene. Alternatively, various other reagents can be used as indicators of this endpoint by detecting the presence of ozone. If ozonolysis is performed by introducing a stream of ozone-enriched oxygen through the reaction mixture, the effluent gas can be directed through a potassium iodide solution. When the solution has stopped absorbing ozone, the excess ozone oxidizes the iodide to iodine, which can easily be observed by its violet color. [6] For closer control of the reaction itself, an indicator such as Sudan Red III can be added to the reaction mixture. Ozone reacts with this indicator more slowly than with the intended ozonolysis target. The ozonolysis of the indicator, which causes a noticeable color change, only occurs once the desired target has been consumed. If the substrate has two alkenes that react with ozone at different rates, one can choose an indicator whose own oxidation rate is intermediate between them, and therefore stop the reaction when only the most susceptible alkene in the substrate has reacted. [7] Otherwise, the presence of unreacted ozone in solution (seeing its blue color) or in the bubbles (via iodide detection) only indicates when all alkenes have reacted.

After completing the addition, a reagent is then added to convert the intermediate ozonide to a carbonyl derivative. Reductive work-up conditions are far more commonly used than oxidative conditions.

The use of triphenylphosphine, thiourea, zinc dust, or dimethyl sulfide produces aldehydes or ketones. While the use of sodium borohydride produces alcohols. (R group can also be hydrogens)

Ozonolysis Scheme 2 examples.svg

The use of hydrogen peroxide can produce carboxylic acids.

Ozonolysis Scheme, H2O2.svg

Amine N-oxides produce aldehydes directly. [8] Other functional groups, such as benzyl ethers, can also be oxidized by ozone. It has been proposed that small amounts of acid may be generated during the reaction from oxidation of the solvent, so pyridine is sometimes used to buffer the reaction. Dichloromethane is often used as a 1:1 cosolvent to facilitate timely cleavage of the ozonide. Azelaic acid and pelargonic acids are produced from ozonolysis of oleic acid on an industrial scale.

An example is the ozonolysis of eugenol converting the terminal alkene to an aldehyde: [9]

EugenolOzonolysis.png

By controlling the reaction/workup conditions, unsymmetrical products can be generated from symmetrical alkenes: [10]

Reaction mechanism

Carbonyl oxide (Criegee zwitterion) Carbonyl oxide (Criegee zwitterion).svg
Carbonyl oxide (Criegee zwitterion)

In the generally accepted mechanism proposed by Rudolf Criegee in 1953, [11] [12] [13] the alkene and ozone form an intermediate molozonide in a 1,3-dipolar cycloaddition. Next, the molozonide reverts to its corresponding carbonyl oxide (also called the Criegee intermediate or Criegee zwitterion) and aldehyde or ketone (3) in a retro-1,3-dipolar cycloaddition. The oxide and aldehyde or ketone react again in a 1,3-dipolar cycloaddition, producing a relatively stable ozonide intermediate, known as a trioxolane (4).

The reaction mechanism of ozonolysis. Ozonolysis mechanism.svg
The reaction mechanism of ozonolysis.

Evidence for this mechanism is found in isotopic labeling. When 17O-labelled benzaldehyde reacts with carbonyl oxides, the label ends up exclusively in the ether linkage of the ozonide. [14] There is still dispute over whether the molozonide collapses via a concerted or radical process; this may also exhibit a substrate dependence.

History

Christian Friedrich Schönbein, who discovered ozone in 1840, also did the first ozonolysis: in 1845, he reported that ethylene reacts with ozone – after the reaction, neither the smell of ozone nor the smell of ethylene was perceivable. [15] The ozonolysis of alkenes is sometimes referred to as "Harries ozonolysis", because some attribute this reaction to Carl Dietrich Harries. [16] Before the advent of modern spectroscopic techniques, the ozonolysis was an important method for determining the structure of organic molecules. Chemists would ozonize an unknown alkene to yield smaller and more readily identifiable fragments.

Ozonolysis of alkynes

Ozonolysis of alkynes generally gives an acid anhydride or diketone product, [17] not complete fragmentation as for alkenes. A reducing agent is not needed for these reactions. The mechanism is unknown. [18] If the reaction is performed in the presence of water, the anhydride hydrolyzes to give two carboxylic acids.

Ozonolysis-alkyne.png

Other substrates

Although rarely examined, azo compounds (N=N) are susceptible to ozonolysis. Nitrosamines (N−N=O) are produced. [19]

Applications

The main use of ozonolysis is for the conversion of unsaturated fatty acids to value-added derivatives. Ozonolysis of oleic acid is an important route to azelaic acid. The coproduct is nonanoic acid: [20]

CH3(CH2)7CH=CH(CH2)7CO2H} + 4 O3 → HO2C(CH2)7CO2H} + CH3(CH2)7CO2H

Erucic acid is a precursor to brassylic acid, a C13-dicarboxylic acid that is used to make specialty polyamides and polyesters. The conversion entails ozonolysis, which selectively cleaves the C=C bond in erucic acid: [21]

CH3(CH2)7CH=CH(CH2)11CO2H + O3 + 0.5 O2 → CH3(CH2)7CO2H + HO2C(CH2)11CO2H

A number of drugs and their intermediates have been produced by ozonolysis. [22] The use of ozone in the pharmaceutical industry is difficult to discern owing to confidentiality considerations. [5]

Ozonolysis as an analytical method

Ozone cracking in natural rubber tubing Ozone cracks in tube1.jpg
Ozone cracking in natural rubber tubing

Ozonolysis has been used to characterize the structure of some polyolefins. Early experiments showed that the repeat unit in natural rubber was shown to be isoprene.

Occurrence

Ozonolysis can be a serious problem, known as ozone cracking where traces of the gas in an atmosphere degrade elastomers, such as natural rubber, polybutadiene, styrene-butadiene, and nitrile rubber. Ozonolysis produces surface ketone groups that can cause further gradual degradation via Norrish reactions if the polymer is exposed to light. To minimize this problem, many polyolefin-based products are treated with antiozonants.

Ozone cracking is a form of stress corrosion cracking where active chemical species attack products of a susceptible material. The rubber product must be under tension for crack growth to occur. Ozone cracking was once commonly seen in the sidewalls of tires, where it could expand to cause a dangerous blowout, but is now rare owing to the use of modern antiozonants. Other means of prevention include replacing susceptible rubbers with resistant elastomers such as polychloroprene, EPDM or Viton.

Safety

The use of ozone in the pharmaceutical industry is limited by safety considerations. [5]

See also

Related Research Articles

<span class="mw-page-title-main">Alkene</span> Hydrocarbon compound containing one or more C=C bonds

In organic chemistry, an alkene, or olefin, is a hydrocarbon containing a carbon–carbon double bond. The double bond may be internal or in the terminal position. Terminal alkenes are also known as α-olefins.

<span class="mw-page-title-main">Carboxylic acid</span> Organic compound containing a –C(=O)OH group

In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group attached to an R-group. The general formula of a carboxylic acid is often written as R−COOH or R−CO2H, sometimes as R−C(O)OH with R referring to an organyl group, or hydrogen, or other groups. Carboxylic acids occur widely. Important examples include the amino acids and fatty acids. Deprotonation of a carboxylic acid gives a carboxylate anion.

<span class="mw-page-title-main">Ether</span> Organic compounds made of alkyl/aryl groups bound to oxygen (R–O–R)

In organic chemistry, ethers are a class of compounds that contain an ether group—an oxygen atom bonded to two organyl groups. They have the general formula R−O−R′, where R and R′ represent the organyl groups. Ethers can again be classified into two varieties: if the organyl groups are the same on both sides of the oxygen atom, then it is a simple or symmetrical ether, whereas if they are different, the ethers are called mixed or unsymmetrical ethers. A typical example of the first group is the solvent and anaesthetic diethyl ether, commonly referred to simply as "ether". Ethers are common in organic chemistry and even more prevalent in biochemistry, as they are common linkages in carbohydrates and lignin.

<span class="mw-page-title-main">Ester</span> Compound derived from an acid

In chemistry, an ester is a compound derived from an acid in which the hydrogen atom (H) of at least one acidic hydroxyl group of that acid is replaced by an organyl group. Analogues derived from oxygen replaced by other chalcogens belong to the ester category as well. According to some authors, organyl derivatives of acidic hydrogen of other acids are esters as well, but not according to the IUPAC.

<span class="mw-page-title-main">Ketone</span> Organic compounds of the form >C=O

In organic chemistry, a ketone is an organic compound with the structure R−C(=O)−R', where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group −C(=O)−. The simplest ketone is acetone, with the formula (CH3)2CO. Many ketones are of great importance in biology and in industry. Examples include many sugars (ketoses), many steroids, and the solvent acetone.

<span class="mw-page-title-main">Aldehyde</span> Organic compound containing the functional group R−CH=O

In organic chemistry, an aldehyde is an organic compound containing a functional group with the structure R−CH=O. The functional group itself can be referred to as an aldehyde but can also be classified as a formyl group. Aldehydes are a common motif in many chemicals important in technology and biology.

In organic chemistry, the Swern oxidation, named after Daniel Swern, is a chemical reaction whereby a primary or secondary alcohol is oxidized to an aldehyde or ketone using oxalyl chloride, dimethyl sulfoxide (DMSO) and an organic base, such as triethylamine. It is one of the many oxidation reactions commonly referred to as 'activated DMSO' oxidations. The reaction is known for its mild character and wide tolerance of functional groups.

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The Wittig reaction or Wittig olefination is a chemical reaction of an aldehyde or ketone with a triphenyl phosphonium ylide called a Wittig reagent. Wittig reactions are most commonly used to convert aldehydes and ketones to alkenes. Most often, the Wittig reaction is used to introduce a methylene group using methylenetriphenylphosphorane (Ph3P=CH2). Using this reagent, even a sterically hindered ketone such as camphor can be converted to its methylene derivative.

<span class="mw-page-title-main">Ozonide</span> Polyatomic ion (O3, charge –1), or cyclic compounds made from ozone and alkenes

Ozonide is the polyatomic anion O−3. Cyclic organic compounds formed by the addition of ozone to an alkene are also called ozonides.

The Baeyer–Villiger oxidation is an organic reaction that forms an ester from a ketone or a lactone from a cyclic ketone, using peroxyacids or peroxides as the oxidant. The reaction is named after Adolf von Baeyer and Victor Villiger who first reported the reaction in 1899.

<span class="mw-page-title-main">Dakin oxidation</span> Organic redox reaction that converts hydroxyphenyl aldehydes or ketones into benzenediols

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<span class="mw-page-title-main">Criegee intermediate</span>

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Selenoxide elimination is a method for the chemical synthesis of alkenes from selenoxides. It is most commonly used to synthesize α,β-unsaturated carbonyl compounds from the corresponding saturated analogues. It is mechanistically related to the Cope reaction.

Alcohol oxidation is a collection of oxidation reactions in organic chemistry that convert alcohols to aldehydes, ketones, carboxylic acids, and esters where the carbon carries a higher oxidation state. The reaction mainly applies to primary and secondary alcohols. Secondary alcohols form ketones, while primary alcohols form aldehydes or carboxylic acids.

<span class="mw-page-title-main">Jones oxidation</span> Oxidation of alcohol

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α,β-Unsaturated carbonyl compound Functional group of organic compounds

α,β-Unsaturated carbonyl compounds are organic compounds with the general structure (O=CR)−Cα=Cβ-R. Such compounds include enones and enals, but also carboxylic acids and the corresponding esters and amides. In these compounds, the carbonyl group is conjugated with an alkene. Unlike the case for carbonyls without a flanking alkene group, α,β-unsaturated carbonyl compounds are susceptible to attack by nucleophiles at the β-carbon. This pattern of reactivity is called vinylogous. Examples of unsaturated carbonyls are acrolein (propenal), mesityl oxide, acrylic acid, and maleic acid. Unsaturated carbonyls can be prepared in the laboratory in an aldol reaction and in the Perkin reaction.

The Griesbaum coozonolysis is a name reaction in organic chemistry that allows for the preparation of tetrasubstituted ozonides (1,2,4-trioxolanes) by the reaction of O-methyl oximes with a carbonyl compound in the presence of ozone. Contrary to their usual roles as intermediates in ozonolysis and other oxidative alkene cleavage reactions, 1,2,4-trioxolanes are relatively stable compounds and are isolable.

References

  1. ↑ Smith, Michael B.; March, Jerry (2007), Advanced Organic Chemistry: Reactions, Mechanisms, and Structure (6th ed.), New York: Wiley-Interscience, p. 1036, ISBN   978-0-471-72091-1
  2. ↑ Bailey, P. S.; Erickson, R. E. (1973). "Diphenaldehyde". Organic Syntheses ; Collected Volumes, vol. 5, p. 489.
  3. ↑ Tietze, L. F.; Bratz, M. (1998). "Dialkyl Mesoxalates by Ozonolysis of Dialkyl Benzalmalonates". Organic Syntheses ; Collected Volumes, vol. 9, p. 314.
  4. ↑ Harwood, Laurence M.; Moody, Christopher J. (1989). Experimental Organic Chemistry: Principles and Practice (Illustrated ed.). Wiley-Blackwell. pp.  55–57. ISBN   978-0632020171.
  5. 1 2 3 Van Ornum, Scott G.; Champeau, Robin M.; Pariza, Richard (2006). "Ozonolysis Applications in Drug Synthesis". Chemical Reviews. 106 (7): 2990–3001. doi:10.1021/cr040682z. PMID   16836306.
  6. ↑ Ikan, Raphael (1991). Natural Products: A Laboratory Guide (2nd ed.). San Diego, CA: Academic Press. p. 35. ISBN   0123705517.
  7. ↑ Veysoglu, Tarik; Mitscher, Lester A.; Swayze, John K. (1980). "A Convenient Method for the Control of Selective Ozonizations of Olefins". Synthesis. 1980 (10): 807–810. doi:10.1055/s-1980-29214.
  8. ↑ Schwartz, Chris; Raible, J.; Mott, K.; Dussault, P. H. (2006). "Fragmentation of Carbonyl Oxides by N-Oxides: An Improved Approach to Alkene Ozonolysis". Org. Lett. 8 (15): 3199–3201. doi:10.1021/ol061001k. PMID   16836365.
  9. ↑ Branan, Bruce M.; Butcher, Joshua T.; Olsen, Lawrence R. (2007). "Using Ozone in Organic Chemistry Lab: The Ozonolysis of Eugenol". J. Chem. Educ. 84 (12): 1979. Bibcode:2007JChEd..84.1979B. doi:10.1021/ed084p1979.
  10. ↑ Claus, Ronald E.; Schreiber, Stuart L. (1986). "Ozonolytic Cleavage of Cyclohexene to Terminally Differentiated Products". Organic Syntheses. 64: 150. doi:10.15227/orgsyn.064.0150.
  11. ↑ Criegee, R. (1975). "Mechanism of Ozonolysis". Angew. Chem. Int. Ed. Engl. 14 (11): 745–752. doi:10.1002/anie.197507451.
  12. ↑ "Ozonolysis mechanism". Organic Chemistry Portal.
  13. ↑ Li, Jie Jack (2006). "Criegee mechanism of ozonolysis". Name Reactions. Springer. pp. 173–174. doi:10.1007/3-540-30031-7_77. ISBN   978-3-540-30030-4.
  14. ↑ Geletneky, C.; Berger, S. (1998). "The Mechanism of Ozonolysis Revisited by 17O-NMR Spectroscopy". Eur. J. Org. Chem. 1998 (8): 1625–1627. doi:10.1002/(SICI)1099-0690(199808)1998:8<1625::AID-EJOC1625>3.0.CO;2-L.
  15. ↑ Christian Friedrich Schönbein (1847). "Ueber das Verhalten des Ozons zum oelbildenden Gas". Bericht über die Verhandlungen der Naturforschenden Gesellschaft in Basel (in German). 7: 7–9.
  16. ↑ Mordecai B. Rubin (2003). "The History of Ozone Part III, C. D. Harries and the Introduction of Ozone into Organic Chemistry". Helv. Chim. Acta . 86 (4): 930–940. doi: 10.1002/hlca.200390111 .
  17. ↑ Bailey, P. S. (1982). "Chapter 2". Ozonation in Organic Chemistry. Vol. 2. New York, NY: Academic Press. ISBN   0-12-073102-9.
  18. ↑ Cremer, D.; Crehuet, R.; Anglada, J. (2001). "The Ozonolysis of Acetylene – A Quantum Chemical Investigation". J. Am. Chem. Soc. 123 (25): 6127–6141. doi:10.1021/ja010166f. PMID   11414847.
  19. ↑ Enders, Dieter; Kipphardt, Helmut; Fey, Peter. "Asymmetric Syntheses using the SAMP-/RAMP-Hydrozone Method: (S)-(+)-4-Methyl-3-heptanone". Organic Syntheses . 65: 183. doi:10.15227/orgsyn.065.0183 ; Collected Volumes, vol. 8, p. 403.
  20. ↑ Cornils, Boy; Lappe, Peter (2000). "Dicarboxylic Acids, Aliphatic". Ullmann's Encyclopedia of Industrial Chemistry. doi:10.1002/14356007.a08_523. ISBN   978-3-527-30673-2.
  21. ↑ Anneken, David J.; Both, Sabine; Christoph, Ralf; Fieg, Georg; Steinberner, Udo; Westfechtel, Alfred (2006). "Fatty Acids". Ullmann's Encyclopedia of Industrial Chemistry. doi:10.1002/14356007.a10_245.pub2. ISBN   3527306730.
  22. ↑ Caron, Stéphane; Dugger, Robert W.; Ruggeri, Sally Gut; Ragan, John A.; Ripin, David H. Brown (2006). "Large-Scale Oxidations in the Pharmaceutical Industry". Chemical Reviews. 106 (7): 2943–2989. doi:10.1021/cr040679f. PMID   16836305.
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