Esters, active catalysis, aminolysis

LM Siemens, FW Rottnek, LS Trzupek. Selective catalysis of ester aminolysis. An approach to peptide active esters, (phenylthiomethyl esters). J Org Chem 55, 3507,... 

An interesting example of intra-polymeric catalysis is provided by the effect of polymer side chains on the aminolysis of polymer-bound nitrophenyl ester [41a], as illustrated in Fig. 10. Thus, apparent reactivity of the polymer-bound carbonyl groups is substantially increased by changing the polymer side chains from phenyl to methoxycarbonyl, and to dimethylamide. This type of intra-polymeric catalysis (shown schematically by species 9 in Fig. 11) assumes special significance in crosslinked polymers and solid phase synthesis. An important implication of this catalytic effect for polymer synthesis is that when an activated polymer intermediate (8) is not sufficiently reactive towards a given nucleophile, polymer reactivity can be enhanced by partial aminolysis with dimethyl-amine [25]. 

A series of quantitative data for solvent effect on the aminolysis of nitrophenyl esters attached to polyacrylamides have also been reported [41b]. These data are in broad agreement with the above-mentioned observations. However, the apparent solvent effects in chemical transformation of polymers must be interpreted in terms of a dual function, i.e. polymer solvation and solvent catalysis . For example, DMSO is a poor solvent for copol3 AOTq)-styrene), but a good solvent for polymers carrying amide residues. It should also be noted that alcohols and water are not usually suitable as solvent for chemical transformation of activated esters, because they may them lves enter the reaction as nucleophiles. 

As a variation on the theme, instead of a zinc(II)-salophen unit, receptor 9 features a 2-pyridone unit, that is a known bifunctional catalyst for the rate limiting breakdown of the tetrahedral intermediate involved in the aminolysis of active esters in aprotic solvents. Turnover catalysis was indeed observed when the reaction between propylamine and PNPCC (Equation 8.5) was carried out in CH2CI2/CH3CN 99 1 in the presence of receptor 9. It was estimated that the reaction inside 9 is ca. 6000 times faster than the reaction in the bulk solvent. 

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