Amino groups ring-substituted anilines

Homologous Amines. Toluidines.—The amino derivatives of the homologues of benzene are formed by the same kind of reactions as those for preparing aniline, viz., the reduction of the homologous mono-nitro compounds. The- amino toluenes in which the amino group is substituted in the benzene ring are known as toluidines, and there are, of course, three isomeric compounds, orthoj meta and para. In the ordinary nitration of toluene the ortho and para compounds are formed. By indirect methods (p. 532) the meta-nitro toluene may also be prepared. These nitro compounds by reduction yield the corresponding toluidines. 

From the table on p. 112 it will be seen that when a ring-substituted aniline has the para position to the amino group unoccupied, mercury invariably enters that position. A similar statement holds for the ortho position to the amino group, but should these two be filled, the mercury may enter the C position, if vacant. 

Acid catalysis in nucleophilic aromatic displacements with amines has been observed only with heterocyclic substrates. Banks (86) has shown that the reaction rates of 2-chloro-4,6-diamino-s-triazene and of 2-amino-4-chloropyrimidine with aniline and with ring-substituted anilines in aqueous solution or suspension are accelerated by an increase in the hydrogen ion concentration. This catalysis is due to conversion of the substrate to its conjugate acid, since the heterocyclic nitrogen is a better activating group for the displacement reaction in the ammonium form than in the amino form. 

From limited data the generalization has been made that this method fails for the synthesis of 1-substituted dibenzofurans and for the synthesis of 4-substituted dibenzofurans unless the amino group and the potential 4-substituent are in the same ring. These generalizations are not substantiated in the synthesis of polychlorodibenzofurans. Polychloro-2-phenoxy-anilines are poorly soluble and nonbasic so that the usual method is precluded. In these cases aprotic diazotization with isopentyl nitrite in tetrachloroethylene at 80 C is the method of choice. Yields, as determined by GLC, are usually of the order of 40-50%. The yields of pure isolated... 

The free amino group strongly activates the aromatic ring towards electrophilic attack and aromatic substitution of amines often results in polysubstitution. For example, the bromination of aniline yields largely 2,4,6-tribromoaniline (Expt 6.59). 

A more detailed analysis has been performed for ring-2,6-disubstituted A-substituted anilines. In these molecules there are possibilities for interactions between a proton on the amino group and a substituent in the ortho-position. A total of 106 crystal structures have been retrieved from the CSD. Frequency histograms of bond and angle values are shown in Figure 29. 

---