Studies On The Aromatic Nucleophilic Substitution Reactions Of Halogenobenzene And Their Reaction Mechanisms

Being important synthetic methods in organic chemistry, aromatic substitution reactions of halogenobenzenes are widely used for the preparation of a great number of building blocks in organic synthesis. Their reaction mechanisms are complex and interesting, attracting more and more attention from chemists. In this paper, the application of aromatic substitution reactions and their reaction mechanisms were reviewed. Also, we launched an investigation on the aromatic nucleophilic substitution reaction of a series of halogenobenzenes with four different nucleophiles (ethyl 2-cyanoacetate, ethyl acetoacetate, ethyl 2-methylacetoacetate and N-methylpiperazine).Firstly, a series of activated halogenobenzene were prepared through some general methods; then ethyl acetoacetate and N-methylpiperazine were selected as the nucleophiles and 4-chloro-3-nitrobenzonitrile as the substrate, the reaction conditions (temperatures, solvents, bases used as catalysts) were optimized through the model reaction.Under the optimal reaction condition, the activated holgenobenzenes reacted with the selected nucleophiles. The effects of activated groups and leaving groups on the reaction were investigated and the nucleophilicities of the nucleophiles were compared. The enol-substituted product of ethyl 2-methylacetoacetate was obtained and a novel method to prepare aryloxy-substitutedα,β-unsaturated esters was discovered.The reaction mechanisms of the four nucleophilic sbustitution reactions were investigated preliminarily. It was found that all these reactions were in accord with the characters of Meisenheimer Complex mechanism. A great emphasis was placed on the reaction of ethyl 2-cyanoacetate with halogenobenzenes, the result indicated that it complied with both the Meisenheimer addition-elimination mechanism and the free radical feature. Based on the reaction facts, another Radical- Meisenheimer Complex pathway(S_RMAr) was proposed.At the same time, we got a series of new substituted compounds and some of them were characterized by 1H- NMR spectra.