Nitric Acid

Mechanism + Description

Probably via hydride abstraction to aldehyde, or formation of a nitrate ester, then elimination to the aldehyde. The aldehyde is then oxidized to the carboxylic acid by a number of mechanisms depending on the structure of the aldehyde, either via a nitrate ester or a radical mechanism.

General comments

Nitric acid is a very cheap and powerful oxidant but is rarely used due to the potential for over-oxidation and nitration side reactions. Other issues are very exothermic reactions and the need to deal with NO_(X) off-gasses. However, a number of primary alcohols can be oxidised to carboxylic acids with HNO₃. These oxidations need to be scaled with great care due to the exothermic nature and gas output of HNO3 reactions. Continuous processing/flow chemistry may provide a safer alternative to batch or semi-batch reactions with HNO₃.

Key references

Alcohol to carboxylic acid with HNO3: Mondanaro, K. R.; Dailey, W. P. 3-Chloro-2-(Chloromethyl)-1-Propene. Org. Synth. 1998,75, 89.

Ross, D. S. Gu, C.; Hum, G. P.; Malhotra, R. Oxidation of Benzyl Alcohols by Nitrous and Nitric Acids in Strong Sulfuric Acid Media.Int. J. Chem. Kinetics. 1986, 18 (11), 1277–1288.

Van Woezik, B. A. A. Runaway and Thermally Safe Operation of a Nitric Acid Oxidation in a Semi-Batch Reactor.Ph. D. Thesis, University of Twente, Enschede, Netherlands, 2000.

Oxidation Br(CH2)4OH to Br(CH2)3CO2H with HNO3: Degering, E. F.; Boatright, L. G. Studies on the Synthesis of Lysine. J. Am. Chem. Soc. 1950, 72 (11), 5137–5139.

Relevant Scale-Up Examples with Scheme

Org. Process Res. Dev. 2011, 15 (3), 581–584.
Experimental
425 kg scale