Oxidation of primary alcohols to carboxylic acids


Oxidation of primary alcohols to carboxylic acids

The oxidation of primary alcohols to carboxylic acids is an important oxidation reaction in organic chemistry.

When a primary alcohol is converted to a carboxylic acid, the terminal carbon atom increases its oxidation state by four. Oxidants able to perform this operation in complex organic molecules, featuring other oxidation-sensitive functional groups, must possess substantial selectivity. The most common oxidants are potassium permanganate (KMnO4), Jones reagent, PDC in DMF, Heyns oxidation, ruthenium tetroxide (RuO4) and TEMPO.

Oxidation of primary alcohols to carboxylic acids

Contents

Potassium permanganate

Potassium permanganate (KMnO4) is a very strong oxidant able to react with many functional groups, such as secondary alcohols, 1,2-diols, aldehydes, alkenes, oximes, sulfides and thiols. Under controlled conditions, KMnO4 oxidizes very efficiently primary alcohols to carboxylic acids. This reaction, which was first described in detail by Fournier,[1][2] is typically carried out by adding KMnO4 to a solution or suspension of the alcohol in an alkaline aqueous solution. The resulting mixture is stirred till the oxidation is complete. 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 will readily react with a carbon - carbon double bond before oxidizing a primary alcohol.

Normally, these oxidations are performed under strong alkaline conditions using a ca. 1N NaOH or KOH solution, because this promotes a greater oxidation speed and selectivity. In substrates sensitive to strong base, the reaction can be carried out at a lower pH – or even under acidic conditions — at the cost of a greatly decreased reaction velocity.

Ciufolini and Swaminathan [3] 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

KMnO4 is decomposed in water, resulting in formation of manganese dioxide (MnO2) and gaseous oxygen. This decomposition is catalyzed by acid, base and MnO2. As the extent of this decomposition is difficult to estimate during the oxidation of primary alcohols, the quantity of KMnO4 must be adjusted during the oxidation by adding it sequentially until the oxidation is complete.

Jones oxidation

The so-called Jones reagent is prepared by dissolving chromium trioxide (CrO3) in aqueous sulfuric acid, which results in formation of a reddish solution containing chromic acid (H2CrO4) and oligomers thereof. Addition of Jones reagent to a solution of a primary alcohol in acetone — as first described by Jones — [4][5] results in oxidation of the alcohol to a carboxylic acid. This classical protocol, involving a direct addition, is used very often regardless of the fact that it frequently leads to the formation of substantial amounts of esters — possessing the structure R-CO-O-CH2-R — derived from oxidative dimerization of primary alcohols. Holland and Gilman[6] proved that this side reaction can be greatly suppressed by following the inverse addition protocol whereby a solution of the primary alcohol in acetone is slowly added to Jones reagent under conditions as dilute as practical.

Jones reagent interacts with secondary alcohols resulting in oxidation to ketones.[7] Treatment of compounds, containing both primary and secondary alcohols, with Jones reagent leads to formation of ketoacids.

Problems encountered with the use of large quantities of chromium trioxide, which is toxic and dangerous for the environment, prompted the development by Zhao [8] of a catalytic procedure, involving treatment with excess of periodic acid (H5IO6) in presence of about 1.2 mol% of CrO3. Zhao's procedure for the use of catalytic CrO3 is very well-suited for reactions on a large scale.[9]

Crimmins and DeBaillie[10] employed Zhao’s oxidation of primary alcohols to acids, using catalytic CrO3 and excess H5IO6, in one step of the synthesis of Bistramide A1, an antitumor compound isolated from the marine ascidian Lissoclinum bistratum with potential for the treatment of nonsmall cell pulmonary carcinoma.

PDC in DMF (Corey and Schmidt)

Pyridinium dichromate (PDC) is a bright-orange solid with the formulae (C5H5NH)2Cr2O7 that is very often used for the oxidation of primary and secondary alcohols to aldehydes and ketones respectively. On the other hand, in 1979, Corey and Schmidt reported [11] that reaction of saturated primary alcohols with PDC, using dimethylformamide (Me2NCHO, DMF) as solvent, results in oxidation to carboxylic acids rather than aldehydes. Interestingly, no oxidation to carboxylic acids occurs on allylic and benzylic primary alcohols. The procedure of Corey and Schmidt for the oxidation of saturated primary alcohols to carboxylic acids is run under essentially neutral conditions.

Heyns oxidation

In the heyns oxidation the oxidizing reagent is a combination of oxygen and platinum.

Ruthenium tetroxide

TEMPO-Mediated oxidations

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 primary alcohol is oxidized to an aldehyde using one of the many existing procedures (e.g. IBX oxidation, Dess-Martin-Periodinane). The aldehyde can then be subjected to the conditions of the Pinnick oxidation using sodium chlorite.[12] This sequence is often used in natural product synthesis, Nicolaou et al. applied it in their synthesis of Platencin.[13]


References

  1. ^ Fournier, H.M. (1907). Compt. Rend. Chim.: 331. 
  2. ^ Fournier, H.M. (1909). Bull. Soc. Chim. Fr.: 920. 
  3. ^ 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. 
  4. ^ Heilbron, I.; Jones, E.R.H.; Sondheimer, F. (1947). "315. Researches on acetylenic compounds. Part XIV. A study of the reactions of the readily available ethynyl-ethylenic alcohol, pent-2-en-4-yn-1-ol". J. Chem. Soc.: 1586. doi:10.1039/jr9470001586. 
  5. ^ Heilbron, I.; Jones, E.R.H. (1949). "129. Researches on acetylenic compounds. Part XV. The oxidation of primary acetylenic carbinols and glycols". J. Chem. Soc.: 604. doi:10.1039/jr9490000604. 
  6. ^ Holland, B.C.; Gilman, N.W. (1974). "An Improved Procedure for the Oxidation of Alkynols to Alkynoic Acids". Synth. Commun. 4 (4): 203. doi:10.1080/00397917408062073. 
  7. ^ See Oxidation of Alcohols to Aldehydes and Ketones.
  8. ^ Zhao, M.; Li, J.; Song, Z.; Desmond, R.; Tschaen, D.M.; Grabowski, E.J.J.; Reider, P.J. (1998). "A novel chromium trioxide catalyzed oxidation of primary alcohols to the carboxylic acids". Tetrahedron Lett. 39 (30): 5323. doi:10.1016/S0040-4039(98)00987-3. 
  9. ^ 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. 
  10. ^ Crimmins, M.T.; and 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2546575. 
  11. ^ Corey, E.J.; Schmidt, G. (1979). "Useful procedures for the oxidation of alcohols involving pyridinium dichromate in approtic media". Tetrahedron Lett. 20 (52): 399. doi:10.1016/S0040-4039(01)93515-4. 
  12. ^ Bal B.S., Childers, Jr. W.E., Pinnick H.W. (1981). "Oxidation of α,β-unsaturated aldehydes" (abstract). Tetrahedron 37 (11): 2091. doi:10.1016/S0040-4020(01)97963-3. 
  13. ^ Nicolaou K.C., Scott Tria G., Edmonds D. J. (2008). "Total Synthesis of Platencin". Angew. Chem. 120 (9): 1804. doi:10.1002/ange.200800066. 

Further reading

  • 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. 

Wikimedia Foundation. 2010.

Look at other dictionaries:

  • Oxidation of secondary alcohols to ketones — The oxidation of secondary alcohols to ketones is an important oxidation reaction in organic chemistry. When a secondary alcohol is oxidised, it is converted to a ketone. The hydrogen from the hydroxyl group is lost along with the hydrogen bonded …   Wikipedia

  • Primary alcohol — A primary alcohol is an alcohol which has the hydroxyl radical connected to a primary carbon. It can also be defined as a molecule containing a “–CH2OH” group.cite web |url=http://cancerweb.ncl.ac.uk/cgi bin/omd?primary+alcohol |title=Definition …   Wikipedia

  • carboxylic acid — Chem. any organic acid containing one or more carboxyl groups. [1900 05; CARBOXYL + IC] * * * Any organic compound with the general chemical formula ―COOH in which a carbon (C) atom is bonded to an oxygen (O) atom by a double bond to make a… …   Universalium

  • Carboxylic acid — Structure of a carboxylic acid Carboxylate ion …   Wikipedia

  • Alcohol oxidation — Mechanism of oxidation of primary alcohols to carboxylic acids via aldehydes and aldehyde hydrates Alcohol oxidation is an important organic reaction. Primary alcohols (R CH2 OH) can be oxidized either to aldehydes (R CHO) or to carboxylic acids… …   Wikipedia

  • Oxoammonium-catalyzed oxidation — reactions involve the conversion of organic substrates to more highly oxidized materials through the action of an N oxoammonium species. Nitroxides may also be used in catalytic amounts in the presence of a stoichiometric amount of a terminal… …   Wikipedia

  • Oppenauer oxidation — Oppenauer oxidation, named after Rupert Viktor Oppenauer,[1] is a gentle method for selectively oxidizing secondary alcohols to ketones. The reaction is the opposite of Meerwein Ponndorf Verley reduction. The alcohol is oxidized with aluminium… …   Wikipedia

  • Jones oxidation — The Jones oxidation is a chemical reaction described as the chromic acid oxidation of primary and secondary alcohols to carboxylic acids and ketones, respectively. [cite journal | author = Bowden, K.; Heilbron, I. M.; Jones, E. R. H | journal = J …   Wikipedia

  • Alcohol — This article is about the generic chemistry term. For the kind of alcohol found in alcoholic beverages, see Ethanol. For beverages containing alcohol, see Alcoholic beverage. For other uses, see Alcohol (disambiguation) …   Wikipedia

  • TEMPO — Chembox new Name = TEMPO OtherNames = 2,2,6,6 Tetramethyl piperidin 1 oxyl ImageFile = TEMPO.png Section1 = Chembox Identifiers CASNo = 2564 83 2 RTECS = TN8991900 Section2 = Chembox Properties Formula = C9H18NO MolarMass = 156.25 g/mol MeltingPt …   Wikipedia