The strecker reaction of benzaldehyde, amines and cyanide: some mechanistic and synthetic studies

Abstract

The Strecker reaction involves the formation of aminonitriles by the reaction of an aldehyde with an amine in the presence of cyanide ions. In this work kinetic, equilibrium and synthetic measurements have been made using benzaldehyde, or 4-nitrobenzaldehyde, as the aldehyde and benzylamine or allylamine as the amine. A side reaction involves the formation of a cyanohydrin from benzaldehyde and cyanide ion. The equilibria involved m the reaction and their pH dependence have been examined. For comparison values for the equilibrium constants for the reaction of benzaldehyde with sulfite are also reported. The syntheses and structural characterisations of N-benzylidene benzylamine, N-benzylidene allylamine and N-(4-nitro)-benzylidene benzylamine are reported. A major part of the thesis is concerned with the kinetics and equilibria involved in the reaction of N-benzylidene benzylamine and N-benzylidene allylamine with cyanide in aqueous solutions. The results are compatible with the rate-determining step involving reaction of the corresponding iminium ions with cyanide ions. The pH profile is bell-shaped with a plateau between pH = 6.5 and 8.5 defined by the pK(_a) values of the iminium ions and hydrogen cyanide. pK(_a) values of 6.14 ± 0.1 and 6.05 ± 0.1 have been calculated for N- benzylidene benzyliminium and N-benzylidene allyliminium ions respectively. Rate constants for reaction of cyanide ion with these cations are 6.70x10(^3) and 1.03x10(^4) dm(^3)mol(^-1)s(^-1) respectively. The hydrolysis reactions of imines to yield benzaldehyde have also been quantitatively investigated. The relatively low reactivity found for those iminium ions may be attributed to charge delocalisation in the aromatic ring. An important aspect of the Strecker reaction is the possibility of forming enantiomerically pure products. The asymmetric catalysis by Salen metal complexes of the reaction of the imines with trimethylsilyl cyanide in organic solvents has been investigated. Various methods for the determination of the enantiomeric excess were tested and the most reliable was found to be use of camphorsulfonic acid. The reaction carried out in the presence of a Salen V(V) complex was optimised to yield aminonitriles in a 80% e.e. at -30 C and 69% e.e. at room temperature. Trifluoroacetic anhydride (TFFA) has been reported in the literature as a reagent for reaction with aminonitriles to allow the separation of enantiomers. Here the reaction of imines with TFAA in acetonitrile and in benzene has been investigated In each solvent there are strong reactions yielding hifluoroacetylated derivatives which are thought to exist in both ionic and covalentiy-bound forms.