Development and Scale Up of a Route to Cyclohexylhydrazine Dimethanesulfonate

A mild, high-yielding synthesis of cyclohexylhydrazine dimethanesulfonate has been developed that is suitable for further scale up. The process consists of three chemical steps: condensation of cyclohexanone with tert-butyl carbazate, reduction of the hydrazone carboxylate to a hydrazine carboxylate with borane−THF, and hydrolysis, decarboxylation, and derivatization with methanesulfonic acid. From studies using a reaction calorimeter, it was determined that the last stage of the process occurs in two discrete steps, requiring 2 equiv of methanesulfonic acid. The first equivalent of acid is consumed by N-protonation. Deprotection of the Boc group occurs with the second equivalent of acid, as evident by the gas evolution. The heat of reaction for the acid addition was determined to be 57.7 kJ/kg and represents an adiabatic temperature rise of 27.4 °C.