Oxidation of primary alcohols to carboxylic acids

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

Oxidation of primary alcohols to carboxylic acids

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. A listing of the most common oxidants is the following:

Contents

[edit] Potassium permanganate

Main article: 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 tiols. 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 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
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 till the oxidation is complete.

[edit] Jones oxidation

Main article: 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 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.
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.

[edit] PDC in DMF (Corey and Schmidt)

Main article: pyridinium dichromate

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.

[edit] Heyns oxidation

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[edit] Ruthenium tetroxide

Main article: Ruthenium tetroxide
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[edit] TEMPO-Mediated oxidations

Main article: TEMPO
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[edit] Two-step oxidation of alcohols to acids via isolated aldehydes

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[edit] References

  1. ^ Fournier, H.M. Compt. Rend. Chim. 1907, 331.
  2. ^ Fournier, H.M. Bull. Soc. Chim. Fr. 1909, 920.
  3. ^ Ciufolini, M.A.; Swaminathan, S. Tetrahedron Lett. 1989, 30, 3027[1]
  4. ^ Heilbron, I.; Jones, E.R.H.; Sondheimer, F. J. Chem. Soc. 1947, 1586.
  5. ^ Heilbron, I.; Jones, E.R.H. J. Chem. Soc. 1949, 604.
  6. ^ Holland, B.C.; Gilman, N.W. Synth. Commun. 1974, 604.
  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. Tetrahedron Lett. 1998, 39, 5323.
  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. J. Org. Chem. 1999, 64, 9658.
  10. ^ Crimmins, M.T.; and DeBaillie, A.C., J. Am. Chem. Soc., 2006, 128, 4936
  11. ^ Corey, E.J.; Schmidt, G. Tetrahedron Lett. 1979, 20, 399.