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Specific Solvent Issues with Oxidation of Primary Alcohols to Carboxylic Acids

Historically, many oxidations were run in chlorinated solvents like dichloromethane (DCM), 1,2-dichloroethane, and CHCl3. The use of DCM was prevalent in early TEMPO-catalyzed oxidations, but recent publications have shown that other more environmentally friendly solvents can be successfully used in TEMPO oxidations.

Greener solvents for TEMPO/PIPO use (methyl or isopropyl acetate often give better results than DCM: Janssen, M. H. A.; Castellana, J. F. C.; Jackman, H.; Dunn, P. J.; Sheldon, R. A. Towards Greener Solvents for the Bleach Oxidation of Alcohols Catalyzed by Stable N-oxy Radicals. Green Chem. 2011, 13 (4), 905-912.

Many of the emerging greener catalytic oxidations using metal catalysts and green oxidants like air/O2/H2O2 need careful consideration when run in flammable organic solvents since highly flammable or explosive mixtures can be generated. A recent publication describes limiting O2 concentrations for a range of solvents.

Osterberg, P. M.; Niemeier, J. K.; Welch, C. J.; Hawkins, J. M.; Martinelli, J. R.; Johnson, T. E.; Root, T. W.; Stahl, S. S. Experimental Limiting Oxygen Concentrations for Nine Organic Solvents at Temperatures and Pressures Relevant to Aerobic Oxidations in the Pharmaceutical Industry. Org. Process Res. Dev. 2015. 19 (11), 1537-1543.

Many oxidations of CH2OH- CO2H proceed via the aldehyde, and in most cases, it is the hydrated aldehyde (CH(OH)2 that undergoes oxidation to the carboxylic acid product. Thus, working in water or high water content solvents can be advantageous, and several catalytic oxidation catalysts have been designed to work in aqueous systems.

Ten Brink, G.; Arends, I. W. C. E.; Sheldon, R. A. Green, Catalytic Oxidation of Alcohols in Water. Science. 2000, 287 (5458), 1636–1639.