The synthesis of alkyl aryl nitriles from N-(1-arylalkylidene)cyanomethylamines. Part 2. Mechanism

Abstract

The mechanism of the rearrangement of N-(1-arylalkylidene)cyanomethylamines ArC(NCH2CN)R 1 to the corresponding nitriles ArCH(CN)R 2 (in DMF, at 150 °C, with K2CO3) is described. Reaction 1 → 2 was investigated for different types of imine 1, and it was found that with a leaving group other than CN− the reaction does not proceed to yield the nitrile, whereas imines such as PhC(NCH2CN)H, prepared starting from aldehydes rather than ketones, yield the expected phenylacetonitrile even at temperatures as low as 120 °C. Evidence for the mechanism comes from a study of the reactivity of the postulated intermediates: 2-cyano-3-phenylaziridine 4c, and 2,2-diphenyl-2H-azirine 5b. The route involving aziridine 4c is ruled out, since this compound does not react at all under the investigated conditions. The 2H-azirine 5b instead, yields the corresponding diphenylacetonitrile in DMF with K2CO3, at 150 °C. The transformation seems to involve an initial deprotonation, followed by an intramolecular ring closure–CN elimination step, which yields the 2H-azirine. The azirine then isomerizes to the nitrile. Additional evidence for the intermediacy of the 2H-azirine, based on 1H NMR monitoring of the reaction 1 → 2, is described. Finally, the results of a simple isotope exchange experiment provide a rationale for the previously observed scrambling of labels, and further confirm the proposed mechanism.