Bromonitromethane (pictured) is a useful reagent in organic synthesis, e.g., for the preparation of nitrocyclopropanes or α-functionalized terminal nitroalkanes. Jeffrey N. Johnston, Vanderbilt University, Nashville, TN, USA, and colleagues found that bromonitromethane has become more expensive and less easily accessible from commercial suppliers, with prices ranging from USD 0.48/mmol to over USD 6.00/mmol. Nitromethane, in contrast, was available for less than USD 0.01/mmol.
The team has developed a robust procedure for the preparation of bromonitromethane from nitromethane at the decagram scale (up to 56 g), ensuring an affordable supply of the reagent. To achieve this, the researchers optimized the reaction of nitromethane with NaOH in water, followed by the addition of elemental bromine.
The team found that the addition of sodium bromide in substoichiometric quantities improved the protocol’s consistency, which they attribute to the formation of sodium tribromide from Br2 and NaBr. They also observed that a rapid addition of the entire amount of bromine (as opposed to dropwise addition) led to high selectivity for the monobrominated product. Lower temperatures down to –5 °C also improved the selectivity for the monobrominated product over a dibrominated product.
According to the researchers, the optimized reaction yields a product with sufficient purity for most applications, avoiding a need for further purification by distillation. They caution that safe operating procedures are important and that the isolation of desolvated nitronate intermediates should be avoided.
- Resolving Bromonitromethane Sourcing by Synthesis: Preparation at the Decagram Scale,
Madelaine P. Thorpe, Abigail N. Smith, Michael S. Crocker, Jeffrey N. Johnston,
J. Org. Chem. 2022.
https://doi.org/10.1021/acs.joc.2c00405
