Nucleophilic aromatic substitution amines, base catalysis

In the nucleophilic addition reactions of amines to substituted aromatic aldehydes where acid catalysis is required, the use of EAN seems to be convenient. The EAN can take part in an acid-base equilibrium with the aromatic aldehydes substituted by electron-withdrawing groups. The imine products from the selected aldehydes could be obtained, confirming the dual behaviour of EAN as Brbnsted acid and potential nucleophile in these type of processes (Fig. 13.7). 

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... 

While the major use for palladium catalysis is to make carbon-carbon bonds, which are difficult to make using conventional reactions, the success of this approach has recently led to its application to forming carbon-heteroatom bonds as well. The Overall result is a nucleophilic substitution at a vinylic or aromatic centre, which would not normally be possible. A range of aromatic amines can be prepared direcdy from the corresponding bromides, iodides, or triflates and the required amine in the presence of palladium(O) and a strong alkoxide base. Similarly, lithium thiolates couple with vinylic triflates to give vinyl sulfides provided lithium chloride is present. 

---