Ring-opening reactivity nucleophilicity effects

In this section three main aspects will be considered. Firstly, the basic strengths of the principal heterocyclic systems under review and the effects of structural modification on this parameter will be discussed. For reference some pK values are collected in Table 3. Secondly, the position of protonation in these carbon-protonating systems will be considered. Thirdly, the reactivity aspects of protonation are mentioned. Protonation yields in most cases highly reactive electrophilic species. Under conditions in which both protonated and non-protonated base co-exist, polymerization frequently occurs. Further ipso protonation of substituted derivatives may induce rearrangement, and also the protonated heterocycles are found to be subject to ring-opening attack by nucleophilic reagents. 

The nature of antibody catalysis remains to be elucidated, and antibodies will not reach the efficiency of enzymes until they can emulate the conformational changes, acid/base, redox, and/or nucleophilic/electro-philic reactivities of catalytic residues along the entire reaction coordinate. It is worthy of note that Hollfelder et al recently demonstrated that serum albumins catalyze the eliminative ring-opening of a benzoisoxazole at rates that are similar to those observed with catalytic antibodies. They suggest that formal general base catalysis contributes only modestly to the efficiency of both systems, and they favor the view that the antibody catalysis may be enhanced in some cases by nonspecific medium effects. 

On one hand, they increase the reaction rate due to an electrophilic assistance for the epoxy ring opening and, on the other, lower the reactivity of the alcoxy anion owing to its solvation and the decrease of its nucleophility. Positive, neutral or even negative effects of the alcohol additives on the reaction rate are governed by the relationship between these two factors. The chain propagation reaction mechanism itself remains trimolecular. 

Reaction with Nitrogen Nucleophiles. The acid-catalyzed reaction of primary, secondary, and tertiary amines with ethyleneimine yields asymmetrically substituted ethylenediamines (71). Steric effects dominate basicity in the relative reactivity of various amines in the ring-opening reaction with ethyleneimine (72). The use of carbon dioxide as catalyst in the aminoethylation of aliphatic amines, for which a patent application has been filed (73), has two advantages. First, the corrosive salts produced when mineral acids are used as catalysts (74,75) are no longer formed, and second, the reaction proceeds with good yields under atmospheric pressure. 

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