The synthesis of alkyl aryl nitriles from N-(1-arylalkylidene)cyanomethyl amines: some mechanistic conclusions

Abstract

A mechanistic investigation of the rearrangement of N-(1-arylalkylidene)cyanomethylamines [1, ArC(NCH₂CN)R; R = alkyl, aryl] to alkyl aryl nitriles [2, ArCH(R)CN] in refluxing DMF in the presence of a base is reported.

Under these conditions, p-phenyl substituted N-(1-arylethylidene)cyanomethylamines (Ar = p-BrC₆H₄, p-ClC₆H₄, p-CH₃C₆H₄ and p-CH₃OC₆H₄; R = CH₃) follow the Hammett linear free-energy relationship, with a large positive ρ value (1.86), implying that electron-withdrawing substituents enhance the reaction rate by an initial deprotonation step. However, C-alkylated imines [Ph₂CNCH(R′)CN; R′ = Me, n-Bu] do not yield the corresponding nitriles [Ph₂C(R′)CN], indicating the need for both methylene protons in order for the reaction to begin.

Different mechanistic pathways are then discussed. A base-catalysed imine double bond isomerisation, considered plausible, is excluded, since N-alkylformimidoyl cyanides [ArCH(NCHCN)R] interconvert quantitatively to imines 1 prior to the formation of nitriles 2. The photochemical activation of the reaction is also ruled out. The results of isotope labelling experiments, using ¹³C- and ¹⁵N-labelled N-(1-phenylethylidene)cyanomethylamines [PhC(NCH₂¹³CN)CH₃ and PhC(¹⁵NCH₂CN)CH₃] are consistent with a mechanism based upon an intramolecular nucleophilic substitution reaction, since the cyano groups of the products 2 appear to come in preference from the methylene-iminic fragment (NCH₂–) of the reagents.

The mechanism is proposed to proceed via an intermediate three-membered nitrogen heterocycle, generated by a nucleophilic intramolecular attack, which eliminates cyanide to afford the product nitrile.