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

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 rho value (1.86), implying that electron-withdrawing substituents enhance the reaction rate by an initial deprotonation step. However, C-alkylated imines [Ph2C=NCH(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(N=CHCN)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 C-13- and N-15-labelled N-(1-phenylethylidene)cyanomethylamines [PhC(=NCH2-(CN)-C-13)CH3 and PhC(=(NCH2CN)-N-15)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.