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Oxidation of Primary Alcohols to Carboxylic Acids

The inclusion of an article in this document does not give any indication of safety or operability. Anyone wishing to use any reaction or reagent must consult and follow their internal chemical safety and hazard procedures and local laws regarding handling chemicals

⃰ Exact position depends on nature of co-oxidant

⃰ ⃰ Scale-up may be hazardous without appropriate control

General Overview

Carboxylic acids are very widely used synthons in the synthesis of pharmaceuticals and fine chemicals. One route to prepare these compounds is by the oxidation of primary alcohols. Often, aldehydes are intermediates (or indeed the target of choice), and many reagents employed for aldehyde synthesis will over-oxidize aldehydes to carboxylic acids at the right stoichiometry.

Many classical reagents for the CH2OH to CO2H transformation, like SeO2 and Pd(OAc)4, have thankfully been mostly phased out, but some heavy metal reagents based on Cr (VI) and Mn (VII) are still used, or at least taught, as reagents for this oxidation. Much greener alternatives are now available using metal catalysts and green co-oxidants, including NaOCl, air(O2) and H2O2, as well as organocatalytic transformations using TEMPO and related nitroxyl radical catalysts. A number of biocatalytic routes to oxidize alcohols to acids are being developed. Generally, these biological systems use two enzymes – an alcohol oxidase and an aldehyde oxidase – or laccase enzymes as part of a catalytic cycle with TEMPO/O2.

 

General Reviews

Caron, S.; Dugger, R. W.; Ruggeri, S. G.; Ragan, J. A.; Ripin, D. H. B. Large-Scale Oxidations in the Pharmaceutical Industry. Chem. Rev. 2006, 106 (7), 2943–2989.

Hollmann, F.; Arends, I. W. C. E.; Buehler, K.; Schallmey, A.; Bühler, B. Enzyme-Mediated Oxidations for the Chemist. Green Chem. 2011,13, 226-265.

Tojo, G.; Fernández, M. Oxidation of Primary Alcohols to Carboxylic Acids: A Guide to Current Common Practice; Basic Reactions in Organic Synthesis; Springer: New York, 2007; pp 1-78.

Organic Chemistry Portal. www.organic-chemistry.org/synthesis/C2O/carboxylicacids/oxidationsalcohols.shtm (accessed Sept. 2017).

Guo, Z.; Liu, B.; Zhang, Q.; Deng, W.; Wang, Y.; Yang, Y. Recent Advances in Heterogeneous Selective Oxidation Catalysis for Sustainable Chemistry. Chem. Soc.  Rev.  2014, 43 (10), 3480-3524.