ENTROPIC STRAIN AND CONFORMATIONAL PREFERENCE IN THE HYDROLYSIS OF SOME N-ALKYL-6-ACETYLAMINOTRIAZINEDIONES

The rate-pH profiles for hydrolysis of the title compounds 1 show four distinct regions: k(A), k(B) and k(C) for rate plateaux corresponding to cationic, neutral and anionic species, plus k(D) for attack of OH- on the anion. At the ends of the pH scale the reaction is much slower than for model amides of comparable pK(1g), due to exceptional charge dispersal in reactant and leaving group. The plateau rates k(B) and k (C) are due to hydrolysis by water, not to some kinetically equivalent process, and are much faster than model calculations would predict. T his is traced to intramolecular general base catalysis via solvent bri dges, and leads to remarkable rate enhancements in aqueous alcohols. T he considerable, and quite independent, variations in k(B), k(C) and a cid pK(a) with only alkyl substitution in the amide moiety points to a dominant effect of conformation which has been explored using a numbe r of techniques, notably octanol-water partitioning, and appears best rationalised in terms of Taft's 'steric hindrance of motions' or Tille tt's 'entropic strain'. The overall picture for the effect of pH is of successively increasing C-O bond formation in the transition state al ong the sequence k(A) --> k(B) --> k(C) but with C-N bond breaking qui te out of line and largely dependent on conformational factors. Given pK(cat) < 0, the presence of effective intramolecular general base cat alysis in k(B) is unexpected. We explain this as being due to a unique feature of 1 whereby catalyst and leaving group are part of the same conjugated structure, leading to pK(cat) --> pK(1g) as C-N bond-breaki ng proceeds. Further light on k(B) comes from the ring-N-methylated an alogue 3d, which cannot form the intramolecular hydrogen bond found el sewhere and whose otherwise similar rate-pH profile shows an anomalous 'apparent pK(4)' that can be explained as a consequence of this.