Lactamomethylation of alkylphenols: Synthesis and quantum-chemical study of the reaction pathway

Six novel lactamomethyl derivatives of 2,5-dimethylphenol and 2,3,5-trimethylphenol were prepared with moderate yields by the reaction of corresponding phenols with 1-(hydroxymethyl)lactams in the presence of an acid catalyst. In all cases, the substitution occurred at position 4 to the phenolic hydroxyl group. The structures of all synthesized compounds were confirmed by FT-IR, H-1 and C-13 NMR, 2D NMR and elemental analysis. The selectivity and possible pathways of the lactamomethylation reaction were studied by quantum-chemical methods. In silico calculations showed that the substitution at para-position to the hydroxyl group of the corresponding phenols was more preferable due to the higher stability of forming intermediates. (C) 2021 The Authors. Published by Elsevier B.V. on behalf of King Saud University.