Zerewitinoff Determination

Abstract

The quantitative determination of active hydrogens in a chemical substance by means of adding methylmagnesium iodide in pentyl ether to the solution of substrate and quantitatively measuring the volume of gaseous methane evolved is generally known as the Zerewitinoff determination. In addition, Zerewitinoff extended this method to determine the active hydrogens of compounds with hydroxyl, amino, imino, and amido groups. It has been reported that methylmagnesium chloride is less reactive than corresponding bromide and iodide and is unstable when kept standing for a long time. The molecules that react with methylmagnesium iodide fall into two groups. Furthermore, the Zerewitinoff determination has also some limitations. It yields incorrect data for certain types of molecules and has problems with the picrotoxin series of compounds. Such inaccuracy of the Zerewitinoff determination may be partially caused by temperature and solvent effects. This method has been widely applied in early stages for the structural analysis for organic compounds.