Nitriles Separated by Reaction and Extraction

Although mixtures of carboxylic acids or mixtures of amines are each fit for separations based on extractions at controlled pHs, most functional groups are not so easy to isolate from each other. Kilomentor thinks a good deal about how to simplify separating molecules with the same functional group in slightly different structural environments.  Although it has not been demonstrated in the literature yet, two different molecules each with a nitrile functionality but differing in the steric environments around them can likely be separated by selective reaction followed by a simple acid-base extraction.

Nitriles are known to react smoothly with azide in a 3+2 cycloaddition to give 1,2,3,4 tetrazoles. This is a ‘click chemistry’ reaction . Cycloadditions are typically quite sensitive to steric environment. Thus, although these reactions are generally fast, it is likely that conditions can easily optimized to get good selectivity between cyanide groups in different molecules using an insufficient amount of azide.  The result will leave a nitrile in one substrate untouched and the nitrile in the other substrate converted essentially completely to tetrazole.  The beauty of this is that these tetrazoles have the acidity of carboxylic acids and can be extracted into water with alkali. Thus the tetrazole derivative removes the reactive nitrile substrate from the organic phase leaving the unreactive nitrile substrate clean for a simple recovery.

Two references that I could locate concerning the kinetics of the reaction of nitriles with azide are: Khimiya Geterotsiklicheskikh Soedinenii (1992) (9) 1214-17, which is in Russian [C.A. 11; 8945a, 8948a]; and Inorganica Chimica Acta (1985). 102(2), 157-62 that does the condensation with the nitrile coordinated in a Co(III)complex.

The synthesis of tetrazoles from nitriles and azide has been studied intensively because of its relevance to the preparation of the sartan family of drugs. Relevant patents are US5744612, US6040454, WO2005014602, WO2007054965 and CN1718574