Mechanistic Insights for Nitromethane Activation into Reactive Nitrogenating Reagents

Recently, it was found that nitromethane (CH3NO2) can be activated into a useful nitrogenating reagent for the synthesis of amide and nitrile compounds. In this work, the mechanisms of CH3NO2 activation are explored in detail by extensive DFT calculations. In aqueous triflic acid (HOTf) solution, the formal 1,3-H-shift of CH3NO2 into transient CH2=NO2H is identified as the rate-limiting step over a barrier of 29.6 kcal/mol, followed by multistep acid hydrolysis to cleave the C=N bond to form NH3OH+ (and HCOOH) as final product. In contrast, in non-aqueous acetic acid (AcOH) solution with electrophilic Tf2O and nucleophilic HCOOH additives, the C=N bond is cleaved by sequential steps of H2O elimination, electrophilic Tf2O activation, nucleophilic HCOOH addition and acetate/TfO- exchange, affording AcONH3+ as more reactive nitrogenating reagent for Beckmann-type reactions.

Automated summary

Nitromethane can be activated into a nitrogenating reagent for the synthesis of amide and nitrile compounds under different solvent conditions using different mechanisms. In aqueous conditions, acid hydrolysis leads to the formation of NH3OH+ and HCOOH as products; while in non-aqueous conditions, a multi-step nitrogenating reaction produces the more reactive nitrogenating reagent AcONH3+.