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

Authors

  • A. H. Halstyan State Enterprise “Lugansk State Medical University”, Rubizhne, Ukraine, Ukraine
  • A. S. Bushuiev State Enterprise “Lugansk State Medical University”, Rubizhne, Ukraine, Ukraine

DOI:

https://doi.org/10.14739/2409-2932.2021.2.230051

Keywords:

oxidation, 4-nitroethylbenzene, 4-nitroacetophenone, acetic acid, kinetics, ozone

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.

Author Biographies

A. H. Halstyan, State Enterprise “Lugansk State Medical University”, Rubizhne, Ukraine

PhD, DSc, Professor of the Department of Industrial Pharmacy

A. S. Bushuiev, State Enterprise “Lugansk State Medical University”, Rubizhne, Ukraine

PhD, Associate Professor, Head of the Department of Industrial Pharmacy

References

Maiofis, L. S. (1958). Tekhnologiya khimiko-farmatsevticheskikh preparatov [Technology of chemical and pharmaceutical preparations]. Leningrad: Medgiz. [in Russian].

Panarin, E. F., & Shul'tsev A. L. (2014). Sposob polucheniya para-nitroaczetofenona [Method of obtaining 4-nitroacetophenone]. Russian Federation Patent 2518894 RU. [in Russian]. http://www.freepatent.ru/patents/2518894

Galstyan, G. A., Tyupalo, N. F., & Galstyan, A. G. (2009). Zhidkofaznoe kataliticheskoe okislenie aromaticheskikh soedinenii ozonom [Liquid-phase catalytic oxidation of aromatic compounds by ozone]. Lugansk: VNU. [in Russian].

Pan, H., Li, S., Shu, M., Ye, Y., Cui, Q., & Zhixiang, Z. (2018). p-Xylene catalytic oxidation to terephthalic acid by ozone. ScienceAsia, 44(3), 212-217. https://doi.org/10.2306/scienceasia1513-1874.2018.44.212

Ku, Y., Ji, Y. S., & Chen, H. W. (2008). Ozonation of o-cresol in aqueous solutions using a rotating packed-bed reactor. Water environment research, 80(1), 41-46. https://doi.org/10.2175/106143007x220905

Hwang, K. C., Sagadevan, A., & Kundu, P. (2019). The sustainable room temperature conversion of p-xylene to terephthalic acid using ozone and UV irradiation. Green Chem, 22, 6082-6088. https://doi.org/10.1039/c9gc02095k

Razumovskyi, S. D., Halstian, H. A., & Tiupalo M. F. (2000). Ozon ta yoho reaktsii z alifatychnymy spolukamy [Ozone and its reactions with aliphatic compounds]. Luhansk: SUDU. [in Ukrainian].

Romanovskii, B. V. (2006). Osnovy khimicheskoi kinetiki [Fundamentals of chemical kinetics]. Moscow: Ekzamen. [in Russian].

Galstyan, A., Galstyan, G., & Timoshyna, L. (2018). Research of the process of liquid phase selective oxidation of 4-aminotoluene with ozone. Chemistry and Chemical Technology, 12(3), 341-345. https://doi.org/10.23939/chcht12.03.341

Bailey, P. S. (1982). Ozonation in organic chemistry. Vol. 2. Nonolefinic Compounds. N.-Y.: Academic Press.

Emanuel', N. M., Denisov, E. T., & Maizus, Z. K. (1965). Tsepnye reaktsii okisleniya uglevodov v zhidkoi faze [Chain reactions of oxidation of carbohydrates in the liquid phase]. Moscow: Nauka. [in Russian].

Bushuiev, A. S., Halstian, A. H., & Kotova, V. V. (2020). Ridynnofazne okysnennia 2-khlortoluenu ozonom do 2-khlorbenzoinoi kysloty – napivproduktu dlia vyrobnytstva natrii dyklofenaku [Liquid-phase oxidation of 2-chlorotoluene with ozone to 2-chlorobenzoic acid – an intermediate for diclofenac sodium production]. Current issues in pharmacy and medicine: science and practice, 13(3), 324-329. https://doi.org/10.14739/2409-2932.2020.3.216168

Published

2021-06-01

How to Cite

1.
Halstyan AH, Bushuiev AS. Investigation of catalytic oxidation of 4-nitroethylbenzene by ozone to 4-nitroacetophenone – an intermediate in the synthesis of antibiotics. Current issues in pharmacy and medicine: science and practice [Internet]. 2021Jun.1 [cited 2024Nov.23];14(2):157-61. Available from: http://pharmed.zsmu.edu.ua/article/view/230051

Issue

Section

Original research