Aminolysis intermolecular catalysis

Most of this rate enhancement is a result of the greater basicity of the amino group compared with water. Very little of the rate enhancement is attributable to intramolecularity, with the catalyst being covalently linked to the nucleophile. This is evident from the effective molarity of ca 1 mol 1 for the reaction which is obtained by dividing the second-order rate constant, k, for the reaction of 1,2-diaminoethane with penicillin by the third-order rate constant, ky, for intermolecular catalysis of aminolysis by a second molecule of amine of similar basicity. The effective molarity is the concentration of catalysing amine required to give the same rate of reaction as the diamine. Similar, small effective molarities have been observed for intra-... 

The mechanism of the intramolecular general acid catalysis of the oxygen esters has not been established since the possible formation of anhydride intermediates has not been thoroughly investigated. The hydrolysis of phthalamic acid has been shown to proceed through an anhydride intermediate, detected by double labeling experiments (Bender et al., 1958a), as does the aminolysis of succinic acid. In these cases, the reaction may involve either a four-center path, symbolised by 40, or involve prior protonation followed by intermolecular attack by the carboxylate anion (41). 

Intermolecular general base catalysis 234 Intramolecular general base catalysis 241 Intramolecular general acid catalysis and the direction of nucleophilic attack 243 Uncatalysed aminolysis 244 Metal-ion catalysed aminolysis 246 Imidazole catalysed isomerisation of penicillins 248 Intramolecular aminolysis 249... 

Intermolecular general base catalysis in the aminolysis of penicillins is a major pathway for product formation (p. 234). It is not surprising therefore that intramolecular general base catalysed aminolysis has been observed (Schwartz, 1968). 

The reactions of salicylate esters in aprotic solvents are also intra-molecularly catalysed. Thus the reactions of phenyl salicylate and phenyl o-methoxybenzoate with n-butylamine in acetonitrile are both second-order in amine but phenyl salicylate reacts 132 times faster [31]. These reactions are also catalysed by triethylenediamine and the rate constant for the reaction which is first-order in n-butylamine and first-order in triethylenediamine is over one hundred times greater for phenyl salicylate than for phenyl o-methoxybenzoate. The reaction of phenyl o-methoxybenzoate, but not that of phenyl salicylate, is catalysed by n-butylamine hydrochloride, which suggests that the phenolic hydroxyl group of the latter acts as an internal acid catalysis. Since the rate-limiting step in the aminolysis of esters in acetonitrile solutions is the breakdown of tetrahedral intermediate [32], a reasonable mechanism for the reaction of phenyl salicylate is one in which breakdown of the tetrahedral intermediate is catalysed intermolecularly by a second molecule of amine and intramolecularly by the phenolic hydroxyl group as shown in 25. The reaction of... 

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