Ring-opening reactivity basicity 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. 

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. 

H2)2 Usually the b"asicity of a heteroc lic compound is affected in the expected order by the inductive effects, conjugation, steric effects, and ring size ( ). The order of basicities is the only estimation of the monomer nucleophilicities, and it reflects fairly well the overall reactivity observed in ring-opening cationic polymerization. 

A simple reaction to see if either of these effects is apparent is the hydrolysis of the P-lactam antibiotics. The alkaline hydrolysis of benzylpeni-cillin opens the P-lactam ring to give benzylpenicilloate [30]. With respect to hydroxide ion, benzylpenicillin shows a reactivity similar to that of ethyl acetate. The p/L -value of the protonated amine in the thiazolidine derivative [30] is 5.2 and because of this weakly basic nitrogen the leaving group ability of the amine is expected to be improved. Therefore, in order to assess any special reactivity of the P-lactam antibiotics, the dependence of the rate of hydrolysis of simple amides and P-lactams upon substituents must be known. 

---