Investigation of catalytic oxidation of 4-nitroethylbenzene by ozone to 4-nitroacetophenone – an intermediate in the synthesis of antibiotics

Abstract

4-Nitroacetophenone is an important intermediate for the manufacture of broad-spectrum antibiotics, in particular chloramphenicol. Existing methods of ketone synthesis are imperfect. The disadvantage of the simplest of them (the oxidation of 4-nitroethylbenzene by oxygen at atmospheric pressure and temperature of 135 °C, in the presence of manganese oxide) is the low yield and the need for the process in a heterogeneous environment. Therefore, the development of affordable and inexpensive ways to obtain 4-nitroacetophenone is an actual task.

The aim of the work is to investigate the products and kinetics of the reaction of catalytic oxidation of 4-nitroethylbenzene by ozone in acetic acid and to develop a new low-temperature synthesis of 4-nitroacetophenone.

Materials and methods. The experiments were used 4-nitroethylbenzene, 4-nitroacetophenone and 1-(4-nitrophenyl)ethanol by company Acros organics qualification “puriss.”; manganese (II) acetate qualification “puriss.”; as a solvent – glacial acetic acid by company Sigma qualification “puriss.”.

A spectrophotometric method was used to continuously monitor the current concentration of ozone in the gas phase. A Teflon flow cell with quartz windows was installed in the measuring chamber of the SF-46 LOMO spectrophotometer, which allowed the measurement of the optical density of the gas flow in the UV region. The concentration of ozone at the inlet and outlet of the reactor was determined by recording the results on the potentiometer KSP-4 in the form of an ozonogram when passing ozone-containing gas through a cuvette at a wavelength of a monochromatic light source 254–256 nm. The quantitative content of the reaction mixture was performed using gas-liquid chromatography, calculations of the concentration of components were performed by the method of internal standard.

Results. The products and kinetics of the reaction of ozone with 4-nitro-ethylbenzene in the presence of a catalyst – manganese (II) acetate were studied. It was found that at a temperature of 20 °C the oxidation process proceeds mainly along the side chain, while the yield of 4-nitroacetophenone reaches 98.5 %, also the system identified trace amounts of 1-(4-nitrophenyl)ethanol. This fact is explained by the fact that ozone under catalysis conditions preferably reacts not with the substrate, but with Mn (II) with the formation of the active form of Mn (IV) which, in turn, is reduced by reaction with 4-nitroethylbenzene, and thus initiates oxidation of the substrate. on the side chain.

Conclusions. Catalytic oxidation of 4-nitroethylbenzene by ozone in acetic acid solution proceeds mainly along the side chain to form 4-nitroacetophenone with a yield of 98.5 %. The optimum reaction temperature is 20–30 °C, as its increase deepens the oxidation process and the ketone begins to be converted into 4-nitrobenzoic acid.