Alcohol oxidation

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Alcohol oxidation is a collection of oxidation reactions in organic chemistry that convert alcohols to aldehydes, ketones, carboxylic acids, and esters. The reaction mainly applies to primary and secondary alcohols. Secondary alcohols form ketones, while primary alcohols form aldehydes or carboxylic acids. [1]

Contents

A variety of oxidants can be used.

Stages in the oxidation of primary alcohols to carboxylic acids via aldehydes and aldehyde hydrates Alcohol to aldehyde to acid.png
Stages in the oxidation of primary alcohols to carboxylic acids via aldehydes and aldehyde hydrates

Almost all industrial scale oxidations use oxygen or air as the oxidant. [2]

Through a variety of mechanisms, the removal of a hydride equivalent converts a primary or secondary alcohol to an aldehyde or ketone, respectively. The oxidation of primary alcohols to carboxylic acids normally proceeds via the corresponding aldehyde, which is transformed via an aldehyde hydrate (gem-diol, R-CH(OH)2) by reaction with water. Thus, the oxidation of a primary alcohol at the aldehyde level without further oxidation to the carboxylic acid is possible by performing the reaction in absence of water, so that no aldehyde hydrate can be formed.

Oxidation of alcohols to aldehydes and ketones Alcohol to aldehyde or ketone (cropped).png
Oxidation of alcohols to aldehydes and ketones

To aldehydes and ketones

In industry

The largest operations involve methanol and ethanol to formaldehyde and acetaldehyde, which are produced on million ton scale annually. Both processes use O2 as the oxidant. Methanol oxidation employs a molybdenum oxide-based catalyst. Other large scale aldehydes and ketones are produced by autoxidation or hydrocarbons: benzaldehyde from toluene, acrolein from propylene, acetone from cumene, cyclohexanone from cyclohexanol. [2]

Laboratory

In teaching laboratories and small scale operations, many reagents have been developed for the oxidation secondary alcohols to ketones and primary alcohols to aldehydes. Allylic and benzylic alcohols are especially prone to oxidation. Aldehydes are susceptible to over oxidation to carboxylic acids.

Chromium(VI) reagents

Alcohol oxidation to carbonyls.svg

Chromium(VI) reagents are commonly used for these oxidations. One family of Cr(VI) reagents employs the complex CrO3(pyridine)2. [3]

  • Sarett's reagent: a solution of CrO3(pyridine)2 in pyridine. It was popularized for selective oxidation of primary and secondary alcohols to carbonyl compounds.
  • Collins reagent is a solution of the same CrO3(pyridine)2 but in dichloromethane. The Ratcliffe variant of Collins reagent relates to details of the preparation of this solution, i.e., the addition of chromium trioxide to a solution of pyridine in methylene chloride. [4]

A second family of Cr(VI) reagents are salts, featuring the pyridinium cation (C5H5NH+).

These salts are less reactive, more easily handled, and more selective than Collins reagent in oxidations of alcohols.

The above reagents represent improvements over the older Jones reagent, a solution of chromium trioxide in aqueous sulfuric acid.

The Dess–Martin periodinane is a mild oxidant for the conversion of alcohols to aldehydes or ketones. [5] The reaction is performed under standard conditions, at room temperature, most often in dichloromethane. The reaction takes between half an hour and two hours to complete. The product is then separated from the spent periodinane. [6] Many iodosyl-based oxidants have been developed, e.g. IBX.

Swern oxidation

Swern oxidation uses oxalyl chloride, dimethylsulfoxide, and an organic base, such as triethylamine.

Swern Oxidation Scheme.png

The by-products are dimethyl sulfide (Me2S), carbon monoxide (CO), carbon dioxide (CO2) and – when triethylamine is used as base – triethylammonium chloride (C6H15NHCl).

The related N-tert-Butylbenzenesulfinimidoyl chloride combines both the sulfur(IV), the base, and the activating Lewis acid in one molecule.

Oppenauer oxidation

Oppenauer.png

This seldom-used method interconverts alcohols and carbonyls.

Niche methods

Ley oxidation uses NMO as the stoichiometric oxidant with tetrapropylammonium perruthenate as a catalyst.

Fétizon oxidation, also a seldom-used method, uses silver carbonate supported on Celite. This reagent operates through single electron oxidation by the silver cations.

Fetizon's reagent mechanism.jpg

Another method is the oxoammonium-catalyzed oxidation.

Additionally, sodium hypochlorite (or household bleach) in acetone has been reported for efficient conversion of secondary alcohols in the presence of primary alcohols (Stevens oxidation). [7]

Soluble transition metal complexes catalyze the oxidation of alcohols by presence of dioxygen or another terminal oxidant. [8]

Oxidation of diols

Oxidative cleavage of carbon-carbon bond in 1,2-diols Oxidative breakage of 1,2-diol (cropped).png
Oxidative cleavage of carbon-carbon bond in 1,2-diols

The largest scale oxidation of 1,2-diols gives glyoxal from ethylene glycol. The conversion uses air or sometimes nitric acid. [2]

In the laboratory, vicinal diols suffer oxidative breakage at a carbon-carbon bond with some oxidants such as sodium periodate (NaIO4), (diacetoxyiodo)benzene (PhI(OAc)2) [9] or lead tetraacetate (Pb(OAc)4), resulting in generation of two carbonyl groups. The reaction is also known as glycol cleavage.

To carboxylic acids

Alcohol to acid (cropped).png

In industry

The oxidation of primary alcohols to carboxylic acids can be carried out using a variety of reagents, but O2/air and nitric acid dominate as the oxidants on a commercial scale. Large scale oxidations of this type are used for the conversion of cyclohexanol alone or as a mixture with cyclohexanone to adipic acid. Similarly cyclododecanol is converted to the 12-carbon dicarboxylic acid. 3,5,5-Trimethylcyclohexanol is similarly oxidized to trimethyladipic acid. [2]

Many specialty reagents have been developed for laboratory scale oxidations of alcohols to carboxylic acids.

Potassium permanganate

Potassium permanganate (KMnO4) oxidizes primary alcohols to carboxylic acids very efficiently. This reaction, which was first described in detail by Fournier, [10] [11] is typically carried out by adding KMnO4 to a solution or suspension of the alcohol in an alkaline aqueous solution. For the reaction to proceed efficiently, the alcohol must be at least partially dissolved in the aqueous solution. This can be facilitated by the addition of an organic co-solvent such as dioxane, pyridine, acetone or t-BuOH. KMnO4 reacts with many functional groups, such as secondary alcohols, 1,2-diols, aldehydes, alkenes, oximes, sulfides and thiols, and carbon-carbon double bonds. Thus, selectivity is an issue.

Ciufolini and Swaminathan oxidized a primary alcohol to carboxylic acid with KMnO4 in aqueous NaOH during the obtention of a rare amino acid derivative needed for the preparation of antibiotics isolated from Actinomadura luzonensis, a microorganism found in a soil sample collected in Luzon island in the Philippines Oxidation with KMnO4.png
Ciufolini and Swaminathan oxidized a primary alcohol to carboxylic acid with KMnO4 in aqueous NaOH during the obtention of a rare amino acid derivative needed for the preparation of antibiotics isolated from Actinomadura luzonensis, a microorganism found in a soil sample collected in Luzon island in the Philippines

Jones oxidation

The so-called Jones reagent, prepared from chromium trioxide (CrO3) and aqueous sulfuric acid, oxidizes alcohols to a carboxylic acid. The protocol frequently affords substantial amounts of esters. [13] Problems are the toxicity and environmental unfriendliness of the reagent. Catalytic variant, involving treatment with excess of periodic acid (H5IO6) have been described. [14]

Crimmins and DeBaillie Zhao`s oxidation.png
Crimmins and DeBaillie

Two-step oxidation of alcohols to acids via isolated aldehydes

As a lot of the aforementioned conditions for the oxidations of primary alcohols to acids are harsh and not compatible with common protection groups, organic chemists often use a two-step procedure for the oxidation to acids. The alcohol is oxidized to an aldehyde using one of the many procedures above. This sequence is often used in natural product synthesis as in their synthesis of platencin. [16]

Niche methods and reagents

Ruthenium tetroxide is an aggressive, seldom-used agent that allows mild reaction conditions.

Heyns oxidation. [17]

The use of chlorites as terminal oxidants in conjunction with both hypochlorites and TEMPO gives carboxylic acids without chlorination side products. [18] The reaction is usually carried out in two steps in the same pot: partial oxidation is effected with TEMPO and hypochlorite, then chlorite is added to complete the oxidation. Only primary alcohol oxidation is observed. In conjunction with Sharpless dihydroxylation, this method can be used to generate enantiopure α-hydroxy acids. [19]

The Pinnick oxidation uses sodium chlorite. [20]

Related Research Articles

<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 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.

Chromic acid is jargon for a solution formed by the addition of sulfuric acid to aqueous solutions of dichromate. It consists at least in part of chromium trioxide.

<span class="mw-page-title-main">Pyridinium chlorochromate</span> Chemical compound

Pyridinium chlorochromate (PCC) is a yellow-orange salt with the formula [C5H5NH]+[CrO3Cl]−. It is a reagent in organic synthesis used primarily for oxidation of alcohols to form carbonyls. A variety of related compounds are known with similar reactivity. PCC offers the advantage of the selective oxidation of alcohols to aldehydes or ketones, whereas many other reagents are less selective.

<span class="mw-page-title-main">Chromium trioxide</span> Chemical compound

Chromium trioxide is an inorganic compound with the formula CrO3. It is the acidic anhydride of chromic acid, and is sometimes marketed under the same name. This compound is a dark-purple solid under anhydrous conditions and bright orange when wet. The substance dissolves in water accompanied by hydrolysis. Millions of kilograms are produced annually, mainly for electroplating. Chromium trioxide is a powerful oxidiser, a mutagen, and a carcinogen.

<span class="mw-page-title-main">Dess–Martin periodinane</span> Chemical reagent

Dess–Martin periodinane (DMP) is a chemical reagent used in the Dess–Martin oxidation, oxidizing primary alcohols to aldehydes and secondary alcohols to ketones. This periodinane has several advantages over chromium- and DMSO-based oxidants that include milder conditions, shorter reaction times, higher yields, simplified workups, high chemoselectivity, tolerance of sensitive functional groups, and a long shelf life. However, use on an industrial scale is made difficult by its cost and its potentially explosive nature. It is named after the American chemists Daniel Benjamin Dess and James Cullen Martin who developed the reagent in 1983. It is based on IBX, but due to the acetate groups attached to the central iodine atom, DMP is much more reactive than IBX and is much more soluble in organic solvents.

<span class="mw-page-title-main">Tetrapropylammonium perruthenate</span> Chemical compound

Tetrapropylammonium perruthenate (TPAP or TPAPR) is the chemical compound described by the formula N(C3H7)4RuO4. Sometimes known as the Ley–Griffith reagent, this ruthenium compound is used as a reagent in organic synthesis. This salt consists of the tetrapropylammonium cation and the perruthenate anion, RuO−4.

<span class="mw-page-title-main">2-Iodoxybenzoic acid</span> Chemical compound

2-Iodoxybenzoic acid (IBX) is an organic compound used in organic synthesis as an oxidizing agent. This periodinane is especially suited to oxidize alcohols to aldehydes. IBX is most often prepared from 2-iodobenzoic acid and a strong oxidant such as potassium bromate and sulfuric acid, or more commonly, oxone. One of the main drawbacks of IBX is its limited solubility; IBX is insoluble in many common organic solvents. IBX is an impact- and heat-sensitive explosive (>200°C). Commercial IBX is stabilized by carboxylic acids such as benzoic acid and isophthalic acid.

Ruthenium tetroxide is the inorganic compound with the formula RuO4. It is a yellow volatile solid that melts near room temperature. It has the odor of ozone. Samples are typically black due to impurities. The analogous OsO4 is more widely used and better known. It is also the anhydride of hyperruthenic acid (H2RuO5). One of the few solvents in which RuO4 forms stable solutions is CCl4.

Oppenauer oxidation, named after Rupert Viktor Oppenauer, is a gentle method for selectively oxidizing secondary alcohols to ketones.

<span class="mw-page-title-main">Sarett oxidation</span> Organic reaction

The Sarett oxidation is an organic reaction that oxidizes primary and secondary alcohols to aldehydes and ketones, respectively, using chromium trioxide and pyridine. Unlike the similar Jones oxidation, the Sarett oxidation will not further oxidize primary alcohols to their carboxylic acid form, neither will it affect carbon-carbon double bonds. Use of the original Sarett oxidation has become largely antiquated however, in favor of other modified oxidation techniques. The unadulterated reaction is still occasionally used in teaching settings and in small scale laboratory research.

<span class="mw-page-title-main">Collins reagent</span> Chemical compound

Collins reagent is the complex of chromium(VI) oxide with pyridine in dichloromethane. This metal-pyridine complex, a red solid, is used to oxidize primary alcohols to the corresponding aldehydes and secondary alcohols to the corresponding ketones. This complex is a hygroscopic orange solid.

<span class="mw-page-title-main">Cornforth reagent</span> Chemical compound

The Cornforth reagent (pyridinium dichromate or PDC) is a pyridinium salt of dichromate with the chemical formula [C5H5NH]2[Cr2O7]. This compound is named after the Australian-British chemist Sir John Warcup Cornforth (b. 1917) who introduced it in 1962. The Cornforth reagent is a strong oxidizing agent which can convert primary and secondary alcohols to aldehydes and ketones respectively. In its chemical structure and functions it is closely related to other compounds made from hexavalent chromium oxide, such as pyridinium chlorochromate and Collins reagent. Because of their toxicity, these reagents are rarely used nowadays.

In organic chemistry, a homologation reaction, also known as homologization, is any chemical reaction that converts the reactant into the next member of the homologous series. A homologous series is a group of compounds that differ by a constant unit, generally a methylene group. The reactants undergo a homologation when the number of a repeated structural unit in the molecules is increased. The most common homologation reactions increase the number of methylene units in saturated chain within the molecule. For example, the reaction of aldehydes or ketones with diazomethane or methoxymethylenetriphenylphosphine to give the next homologue in the series.

The Parikh–Doering oxidation is an oxidation reaction that transforms primary and secondary alcohols into aldehydes and ketones, respectively. The procedure uses dimethyl sulfoxide (DMSO) as the oxidant and the solvent, activated by the sulfur trioxide pyridine complex (SO3•C5H5N) in the presence of triethylamine or diisopropylethylamine as base. Dichloromethane is frequently used as a cosolvent for the reaction.

<span class="mw-page-title-main">Dess–Martin oxidation</span> Chemical reaction

The Dess–Martin oxidation is an organic reaction for the oxidation of primary alcohols to aldehydes and secondary alcohols to ketones using Dess–Martin periodinane. It is named after the American chemists Daniel Benjamin Dess and James Cullen Martin who developed the periodinane reagent in 1983.

Oxidation with chromium(VI) complexes involves the conversion of alcohols to carbonyl compounds or more highly oxidized products through the action of molecular chromium(VI) oxides and salts. The principal reagents are Collins reagent, PDC, and PCC. These reagents represent improvements over inorganic chromium(VI) reagents such as Jones reagent.

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

The Jones oxidation is an organic reaction for the oxidation of primary and secondary alcohols to carboxylic acids and ketones, respectively. It is named after its discoverer, Sir Ewart Jones. The reaction was an early method for the oxidation of alcohols. Its use has subsided because milder, more selective reagents have been developed, e.g. Collins reagent.

<span class="mw-page-title-main">Collins oxidation</span>

The Collins oxidation is an organic reaction for the oxidation of primary alcohols to aldehydes. It is distinguished from other chromium oxide-based oxidations by the use of Collins reagent, a complex of chromium(VI) oxide with pyridine in dichloromethane.

References

  1. ↑ Burton, George et al. (2000). Salters Advanced Chemistry: Chemical (2nd ed.). Heinemann. ISBN   0-435-63120-9
  2. 1 2 3 4 Teles, J. Henrique; Hermans, Ive; Franz, Gerhard; Sheldon, Roger A. (2015). "Oxidation". Ullmann's Encyclopedia of Industrial Chemistry. pp. 1–103. doi:10.1002/14356007.a18_261.pub2. ISBN   978-3-527-30385-4.
  3. ↑ "Chromium-based Reagents". Oxidation of Alcohols to Aldehydes and Ketones. Basic Reactions in Organic Synthesis. 2006. pp. 1–95. doi:10.1007/0-387-25725-X_1. ISBN   0-387-23607-4.
  4. ↑ J. C. Collins, W.W. Hess (1972). "Aldehydes from Primary Alcohols by Oxidation with Chromium Trioxide: Heptanal". Organic Syntheses. 52: 5. doi:10.15227/orgsyn.052.0005.
  5. ↑ Dess, D. B.; Martin, J. C. J. Am. Chem. Soc. 1991, 113, 7277–87.
  6. ↑ J. S. Yadav, et al. "Recyclable 2nd generation ionic liquids as green solvents for the oxidation of alcohols with hypervalent iodine reagents", Tetrahedron, 2004, 60, 2131–35
  7. ↑ Stevens R, Chapman KT, Weller HN (1980). "Convenient and inexpensive procedure for oxidation of secondary alcohols to ketones". Journal of Organic Chemistry. 45 (10): 2030–2032. doi:10.1021/jo01298a066.
  8. ↑ Parmeggiani, Camilla; Cardona, Francesca (2012-01-03). "Transition metal based catalysts in the aerobic oxidation of alcohols". Green Chemistry. 14 (3): 547–564. doi:10.1039/C2GC16344F. ISSN   1463-9270.
  9. ↑ Nicolaou KC, Adsool VA, Hale CR (April 2010). "An expedient procedure for the oxidative cleavage of olefinic bonds with PhI(OAc)2, NMO, and catalytic OsO4". Organic Letters. 12 (7): 1552–5. doi:10.1021/ol100290a. PMC   2848477 . PMID   20192259.
  10. ↑ Fournier, H.M. (1907). "Transformation des alcools primaires saturès en acides monobasiques correspondants". C. R. Acad. Sci. : 331.
  11. ↑ Fournier, H.M. (20 July 1909). "Sur la préparation des acides gras et de leurs anhydres". Bull. Soc. Chim. Fr. : 920.
  12. ↑ Ciufolini, M.A.; Swaminathan, S. (1989). "Synthesis of a model depsipeptide segment of Luzopeptins (BBM 928), potent antitumor and antiretroviral antibiotics". Tetrahedron Lett. 30 (23): 3027. doi:10.1016/S0040-4039(00)99393-6.
  13. ↑ "Chromium-based Reagents". Oxidation of Alcohols to Aldehydes and Ketones. Basic Reactions in Organic Synthesis. 2006. pp. 1–95. doi:10.1007/0-387-25725-X_1. ISBN   0-387-23607-4.
  14. ↑ Song, Z.J.; Zhao, M.; Desmond, R.; Devine, P.; Tschaen, D.M.; Tillyer, R.; Frey, L.; Heid, R.; Xu, F.; Foster, B.; Li, J.; Reamer, R.; Volante, R.; Grabowski, E.J.J.; Dolling, U.H.; Reider, P.J. (1999). "Practical Asymmetric Synthesis of an Endothelin Receptor Antagonist". J. Org. Chem. 64 (26): 9658. doi:10.1021/jo991292t.
  15. ↑ Crimmins, M.T. & DeBaillie, A.C. (2006). "Enantioselective Total Synthesis of Bistramide A". J. Am. Chem. Soc. 128 (15): 4936–7. doi:10.1021/ja057686l. PMC   2546575 . PMID   16608311.
  16. ↑ Nicolaou K.C.; Scott Tria G.; Edmonds D. J. (2008). "Total Synthesis of Platencin". Angew. Chem. 120 (9): 1804. doi:10.1002/ange.200800066.
  17. ↑ Marcos Fernández; Gabriel Tojo (2006). Oxidation of Primary Alcohols to Carboxylic Acids: A Guide to Current Common Practice (Basic Reactions in Organic Synthesis). Berlin: Springer. ISBN   0-387-35431-X.
  18. ↑ Song, Z. J.; Zhao, M.; Desmond, R.; Devine, P.; Tschaen, D. M.; Tillyer, R.; Frey, L.; Heid, R.; Xu, F.; Foster, B.; Li, J.; Reamer, R.; Volante, R.; Grabowski, E. J. J.; Dolling, U. H.; Reider, P. J.; Okada, S.; Kato, Y.; Mano, E. J. Org. Chem.1999, 64, 9658.
  19. ↑ Sharpless, K. B.; Amberg, W.; Bennani, Y. L.; Crispino, G. A.; Hartung, J.; Jeong, K. S.; Kwong, H. L.; Morikawa, K.; Wang, Z. M.; Xu, D.; Zhang, X. L. J. Org. Chem.1992, 57, 2768.
  20. ↑ Bal B.S.; Childers, Jr. W.E.; Pinnick H.W. (1981). "Oxidation of α,β-unsaturated aldehydes". Tetrahedron (abstract). 37 (11): 2091. doi:10.1016/S0040-4020(01)97963-3.
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