A Study On Aminomethylation Of Aromatic Compounds

Aminomethylation, especially Mannich aminomethylation, is one of the most important kinds of organic reactions. Mannich reaction can be used to synthesize lots of important compounds such as pharmaceutical intermediates and fine organic chemicals which have been applied in medicine, coatings, spices, organic fertilizer, pesticides, polymer materials and other industries. In addition, some compounds that are difficult to synthesize by general methods can be obtained by Mannich reaction.In this paper, we studied one-pot amidomethylation of aromatic compounds with low-cost polyformaldehyde, acetamide or 2-chloroacetamide as amidomethylation reagent and acid as catalyst. This reaction also belongs to Mannich reaction. Generally, in Mannich reaction aldehydes, ketones or aromatic compounds containing active hydrogens as acid components and secondary amines as alkaline components were utilized. However, in this paper, we chose passivated aromatic compounds and heterocyclic compounds as well as active hydrogens-containing aromatic compounds as acid components and primary amide for alkaline components. Transformation of secondary amine into primary amide is a very significant change that not only prevents consecutive aminomethylation of primary amine but also provides a one-step methord for the direct synthesis of amidomethyl aromatic compounds. These amidomethyl aromatic compounds are very stable and easy to store. Under acidic or alkaline conditions, they can be hydrolyzed into primary aminomethyl aromatic compounds. Thus it is helpful for the preservation of primary aminomethyl aromatic compounds.By investigating of various factors that influence reaction yield, the best conditions of amidomethylation of some aromatic compounds were found. Mea-nwhile, by amidomethylation and hydrolysis, a route of the preparation of pri-mary aminomethyl aromatic compound was established. This method has many advantages such as simple operation, cheap raw materials, mild reaction condition and simple post-processing. Some compounds were synthetized as follows: N-(2-methyl-5-nitrobenzyl)acetamide, N-(2,5-dimethylbenzyl)acetamide, 2,5-diacet- amidomethyl-1,4-dimethylbenzene, N-(2,4-dimethylbenzyl)acetamide, 4,6-diaceta- midomethyl-1,3-dimethylbenzene, N-(3,4-dimethylbenzyl)acetamide, N-(2,5-difluor- obenzyl)acetamide, N-(4-methylbenzyl)acetamide, N-(4-chlorobenzyl)acetamide, N- (2-chloro-5-(trifluoromethyl)benzyl)acetamide, 5-(acetamidomethyl)-2-chlorobenzoic acid, 4,4'-(dichloroacetamidomethyl)biphenyl, 4-acetamidomethylbiphenyl,α- acetamidomethylnaphthalene, 2-acetamidomethylthiophene.In addition, hydrolysis of acetamidomethyl aromatics was studied. 2-Methyl-5-nitrobenzylamine hydrochloride, 4,4'-(diaminomethyl)biphenyl hydro- chloride, 2,5-dimethylbenzylamino hydrochloride, 2,5-difluorobenzylamino hydro- chloride and 2,5-diaminomethyl-1,4-dimethylbenzene hydrochloride were successfully prepared.The structures of all the synthesized compounds were confirmed by 1H NMR, 13C NMR and other means. All characterization results of these compounds are consistent with the reported data or theoretical consequences. Among them, N-(2-chloro-5-(trifluoromethyl)benzyl)acetamide, N-(2,5-difluorobenzyl)acetamide are new compounds that have not been reported in any other literature.