Hofmann N-alkylation of aniline derivatives with alcohols using ferric perchlorate immobilized on SiO2 as a catalyst through Box-Behnken experimental design

An efficient method for the N-alkylation of poorly nucleophilic amines using ferric perchlorate immobilized on SiO2 as a catalyst is described. Fe(ClO4)(3) was prepared from mixing iron(III) hydroxide and perchloric acid and adsorbed on silica gel. The catalyst was characterized using various techniques. The supported ferric perchlorate (Fe(ClO4)(3)/SiO2) revealed high efficiency and selectivity for N-alkylation of aromatic amines with alcohols to provide alkylated amines. Various secondary amines were synthesized from primary amines and alcohols in good to excellent yields, with water as the only by-product. The optimization of the reaction conditions was investigated using the response surface method, and involving the Box-Behnken design matrix. The conditions for optimal reaction yield and time were: amount of catalyst = 0.34 mmol, temperature = 60 degrees C and molar ratio of amine to alcohol = 1.2. The catalyst was recovered and reused for five cycles without a considerable decrease in catalytic activity. The stability of the recycled catalyst was investigated. The proposed method has numerous advantages including procedure simplicity, short reaction times, low cost, good to excellent yields, reusability of the catalyst and mild and environmentally benign conditions.