Nucleophilic substitution reactions, aliphatic steric effects

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. 

The nucleophilic substitution of the reactive chlorine atoms in hexa- and dichloride clathrochelates by a series of aliphatic amines is very sensitive to the effects of the medium (primary, the solvent employed), and the trend of the reaction is determined to a great extent by the donor properties of the amines and the steric accessibility of the nucleophilic centre. The subsequent substitution reaction course and feasible reaction products in the case of hexachloride precursors are presented in Scheme 24. The stepwise-formed clathrochelate complexes are denoted according to the degree of the substitution of chlorine atoms by amine groups ... 

To put this working hypothesis on a more quantitative basis aromatic nucleophihc substitutions with azide as a nucleophile were tested for catalytic effects with 24 and 25. The corresponding transition states are even more delocalized than their aliphatic counterparts and thus higher rate augmentations should be expected. All or part of this favourable effect, however, can be anihilated due to an unfavourable activation entropy because the formation of the large transition state may suffer from the severe steric restrictions in the cavity of the host. As a corollary it was no surprise to find that the smaller tricyclic host 24 inhibited the substitution of 39 with azide in aqueous methanol The same reaction experienced a big rate acceleration in the... 

Reactions involving amine nucleophiles have played an important part in the study of aromatic substitutions, partly because the observation of base catalysis in these reactions provides evidence for the two-step nature of the mechanism. Early work [1 ] on the reactions of aliphatic amines with l-chloro-2,4-dinitrobenzene in ethanol, where nucleophilic attack is rate limiting, showed the importance of steric effects so that, for example, wo-propylamine is roughly 10 times less reactive than n-propylamine. The general pathway for these reactions is shown in Scheme 6.10. Here, the base B may be excess of the nucleophile or added bases such as DABCO or hydroxide ions. The... 

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