Electrophilic substitution in malonamide. Evidence for reaction via the enol tautomer

Abstract

The kinetics of the nitrosation, bromination and iodination of malonamide [MA] have been studied in water at 25 °C. Throughout, reaction was first order in [MA]. At low acidity and relatively high [I₂], reactions were fully zero-order in [I₂] and acid-catalysed. At higher acidity and lower [I₂] reaction was first-order in [I₂] and not now acid-catalysed. Similar first-order behaviour was found for bromination and nitrosation (by BrNO and ONSCN generated in situ). It was not possible by changing the reaction conditions to achieve the zero-order pattern with either bromination or nitrosation. The results are consistent with a mechanism involving reaction of the electrophile with an intermediate derived from MA which we suggest is the enol tautomer. For iodination either enolisation or reaction of the enol can be made rate-limiting. For enolisation the value of the rate constant k_e, (in Rate =k_e[MA][H⁺]) was found to be 3.3 × 10^–3 dm³ mol^–1 s^–1. The results also suggest that l₂, Br₂, BrNO and ONSCN react with the enol at or close to the encounter controlled limit, enabling a value for K_E(the equilibrium constant for enolisation) of (4 ± 2)× 10^–10 to be obtained. The methylene protons in MA are readily exchanged with D from the solvent in an acid catalysed process. The enolisation of CD₂(COND₂)₂ is slower than that of CH₂(CONH₂)₂ by a factor of 2.3 and the deuterium solvent isotope effect is close to 1. The mechanism of enolisation of MA is discussed.