Diamines intramolecular catalysis

The reduced reaction order and the higher rate constants with diamines was explained in terms of intramolecular catalysis involving an intermediate like 57. 

For the intramolecular catalysis in the aminolysis of N-acetyl-imidazole by diamines [68, 69] the catalytic group is in the same molecule as the nucleophile, and the problem of distinguishing between nucleophilic and general base catalysis does not arise. The rate law for the aminolysis of N-acetylimidazole by monoamines has both terms of first and of second order in amine, but in the aminolysis by ethylene diamine the term which is first order in amine is relatively more important. The rate constant for this reaction is 186 times greater than that for a monoamine of comparable basicity and a similar rate enhancement is found for the reaction with 1,3-diaminopropane. Rather smaller rate enhancements are found with 1,4-diaminobutane and 1,5-diaminopentane (see Table 4). Intramolecular catalysis is also found in the aminolysis of methyl formate... 

In some situations intramolecular catalysis via a five-membered cyclic transition state appears to be possible. Thus Page and Jencks in their investigation of the reactions of N-acetylimidazole with diamines obtained maximum rate enhancements with 1,2-diamino-ethane and 1,3-triaminopropane, corresponding to five- and six-membered cyclic transition states if no solvent molecule is involved in the proton transfer [69] (see p. 359). The effective molarities for these reactions are small (ca 1m). This may arise because the transition states of the intramolecularly catalysed reactions have an unfavourable strain energy or because this transition state is loose and is... 

Another type of bifunctional catalysis has been noted with a,cn-diamines in which one of the amino groups is primary and the other tertiary. These substituted diamines are from several times to as much as 100 times more reactive toward imine formation than similar monofunctional amines. This is attributed to a catalytic intramolecular proton transfer. 

Diamines of varying structure show rate enhancements of 20-200 fold, compared to monofunctional aliphatic amines, in nucleophilic reactions with N-acetylimidazole (Page and Jencks, 1972). These were attributed to intramolecular general base catalysis of proton removal from the attacking nitrogen, viz.. 

An example of a proton-transfer reaction occurring by the stepwise trapping mechanism (Ch. 7, Section 2.1) is the general base-catalysed aminolysis of benzyl-penicillin. Amines react with penicillin to form an unstable tetrahedral intermediate which may be trapped by a diffusion-controlled encounter with a strong base as shown in Eqn. 8. Diamines also undergo this reaction but at a much faster rate than monoamines of the same basicity which is attributed to intramolecular general base catalysis i.e. the second amino group acts as a proton acceptor (V). However, the effect of intramolecularity itself is small and the effective concentration (Ch. 1)... 

The attractive combination of transition metals and iodobenzene diacetate as strong oxidant allowed the subsequent development of additional diamination reactions. For example, in the presence of a conventional ttiphenylphosphino-gold(l)chloride complex, intramolecular diamination using ureas as nitrogen sources proceeds within a gold(l/lll) cycle with results that are comparable to the mentioned paUadium(II/IV) catalysis [99]. However, as the initial step consists of an anti-aminoauration, this reaction provides the opposite stereochemistry with respect to the overall product configuration. 

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-... 

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