Ozonolytic synthesis of 2-nitrobenzyl alcohol as an intermediate for the production of biologically active compounds

The oxidation of 2-nitrotoluene by ozone in acetic anhydride was studied, revealing that the reaction proceeds via two pathways: predominantly through the aromatic ring, leading to the formation of ozonides, aliphatic peroxidic products, and to a lesser extent, via oxidation of the methyl group to the corresponding benzoic acid. The addition of sulfuric acid to the ozone–2-nitrotoluene–acetic anhydride system does not affect the ratio of these pathways but enables the oxidation process to be halted at the stage of alcohol and aldehyde formation in the form of 2-nitrobenzyl acetate and 2-nitrobenzylidene diacetate. It was demonstrated that during ozonation of 2-nitrotoluene in the presence of manganese(II) compounds and sulfuric acid, the primary reaction pathway is the oxidation of the methyl group, predominantly yielding 2-nitrobenzyl acetate (42%). The role of the catalyst as a generator of the oxidized metal species, which initiates selective oxidation via the methyl group, was established. Furthermore, sulfuric acid not only accelerates the acylation of the aromatic alcohol and aldehyde formed during oxidation but also enhances the consumption rate of the oxidized catalyst species through reactions with the substrate, facilitating the process under mild conditions. New theoretical insights into the liquid-phase ozonation of 2-nitrotoluene in the presence of a quenching reagent were proposed. Based on these findings, principles for controlling oxidation selectivity and depth through targeted selection of reaction conditions, catalysts, and solvents were formulated. A novel method for the synthesis of 2-nitrobenzyl alcohol was developed, characterized by high selectivity, reduced harmful waste, and feasibility under mild reaction conditions. These results provide a foundation for the further practical application of ozone in methylbenzene oxidation reactions.