Next Article in Journal
Depolymerization of Heparin Benzyl Ester in a Flow System
Previous Article in Journal
Cyclodextrin-Based Host–Guest Supramolecular Nanofibrous Composite for Biomedical Applications
 
 
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Proceeding Paper

Fe-Catalyzed Synthesis of 2-Benzoxazolone—An Important Fragment of Biologically Active Compounds †

by
Zemfira G. Urazbaeva
1,2,*,
Alfiya R. Bayguzina
1,2 and
Ilfir R. Ramazanov
1,2
1
Institute of Petrochemistry and Catalysis, Russian Academy of Sciences, 141 Prospekt Oktyabrya, Ufa 450075, Russia
2
Faculty of Technology, Ufa State Petroleum Technological University, 1 Kosmonavtov Str., Ufa 450062, Russia
*
Author to whom correspondence should be addressed.
Presented at the 26th International Electronic Conference on Synthetic Organic Chemistry, 15–30 November 2022; Available online: https://sciforum.net/event/ecsoc-26.
Chem. Proc. 2022, 12(1), 63; https://doi.org/10.3390/ecsoc-26-13564
Published: 14 November 2022

Abstract

:
2-Benzoxazolone, as well as its derivatives, are valuable structural fragments of a number of important biologically active substances. 2-Benzoxazolone derivatives are promising as antitumor, antimicrobial, antiretroviral, anticonvulsant, tranquilizing, and insecticidal agents. 2-Benzoxazolone is usually produced by the condensation of o-aminophenol with urea, phosgene, and other carbonic acid derivatives. There are also methods for the synthesis of 2-benzoxazolone from salicylamide with trichloroisocyanuric acid as a chlorinating agent, from hydroxybenzoic acid using ammonium azide and the Vilsmeier complex. The disadvantages of these methods are the high cost of the initial reagents, the need to use aggressive and toxic reagents (phosgene, ammonium azide), and the complexity of the hardware design for the reactors. We have developed the highly efficient oxidative cyclocarbonylation of 2-aminophenol to oxazolidin-2-one using FeCl3*6H2O and Fe(acac)3 as catalysts under relatively mild conditions (100–120 °C) in the presence of CCl4 and water. We assume that in situ-formed carbon dioxide is involved in a cyclization reaction with o-aminophenol to form the target 2-benzoxazole. The reaction takes 2–10 h to give 2-benzoxazolone a high yield.

1. Introduction

2-Benzoxazolone, as well as its derivatives, are valuable structural fragments of a number of important biologically active substances. 2-Benzoxazolone derivatives are promising as antitumor [1], antimicrobial [2], antiretroviral [3], anticonvulsant [4], tranquilizing [5], and insecticidal [6] agents. 2-Benzoxazolone is usually produced by the condensation of o-aminophenol with urea [7], phosgene [8], and other carbonic acid derivatives. There are also methods for the synthesis of 2-benzoxazolone from salicylamide with trichloroisocyanuric acid as a chlorinating agent [9], from hydroxybenzoic acid using ammonium azide, and the Vilsmeier complex [10]. The disadvantages of these methods are the high cost of the initial reagents, the need to use aggressive and toxic reagents (phosgene, ammonium azide), and the complexity of the hardware design for the reactors.

2. Results and Discussion

We have developed the highly efficient oxidative cyclocarbonylation of 2-aminophenol to 2-benzoxazolone 1 using FeCl3*6H2O and Fe(acac)3 as catalysts under relatively mild conditions (100–120 °C) in the presence of CCl4 and water. The reaction was studied under various conditions, including the molar ratio of catalyst and reagents: [o-aminophenol]:[CCl4l:[H2O]:[FeCl3*6H2O] = [50–200]:[400–7800]:[0–800]:[1–10], 100–120 °C, 0.25–10 h. A number of solvents were also tested: propanol, ethanol, 1-butanol, benzyl alcohol, ethyl acetate, toluene, and acetonitrile. The yield of 2-benzoxazolone was 75% in acetonitrile using the following conditions: [o-aminophenol]:[CCl4l:[H2O]:[FeCl3*6H2O] = 50:400:800:1, 120 °C, 2 h (Scheme 1). The reaction was carried out in a micro-autoclave (ampoule with stirring). Carrying out the reaction in an open system using microwave irradiation made it possible to reduce the reaction time to 30 min; however, the yield of 2-benzoxazolone did not exceed 40%. The structure of 2-benzoxazolone was established by 1H, 13C NMR spectroscopy, infrared spectroscopy, and GC-MS, as well as a comparison with the literature data [11]:
We assume that carbon dioxide and hydrogen chloride are formed in situ under the reaction conditions, similarly to [12]. Then, CO2 reacts to o-aminophenol to give the target benzoxazolone (Scheme 2).
The formation of carbon dioxide was confirmed by GC-MS. According to the weather observatory on Mauna Loa in May 2022, the maximum concentration of CO2 in the atmosphere was 0.042% (420.99 ppm) [13]. In the sample we analyzed, there was 12.5 times more carbon dioxide than in the atmosphere (Figure 1).
It should be noted that the introduction of Et3N into the reaction reduces the yield of 2-benzoxazole by 25%. Et3N “binds” to the HCl formed during the reaction, so we do not exclude the role of acid catalysis.

3. Conclusions

Thus, we developed a method to produce 2-benzoxazolone from o-aminophenol and carbon tetrachloride in the presence of iron-containing catalysts.

4. Experimental Part

o-Aminophenol, carbon tetrachloride (Aldrich), FeCl3*6H2O, and Fe(acac)3 (Acros) were commercial reagents. 1H and 13C NMR spectra were recorded on a Bruker Avance-II 400 Ascend instrument (400 MHz for 1H and 100 MHz for13C in CDCl3). Mass spectra were run on a Shimadzu GCMS-QP2010Plus mass spectrometer (SPB-5 capillary column, 30 m × 0.25 mm, helium as the carrier gas, temperature programming from 40 to 300 °C at 8 °C/min, the evaporation temperature of 280 °C, ion source temperature of 200 °C, and ionization energy of 70 eV). The course of the reaction and the purity of the products were monitored by gas-liquid chromatography on a Shimadzu GC-9A, GC-2014 instrument [2 m × 3 mm column, SE-30 silicone (5%) on Chromaton N-AW-HMDS as the stationary phase, with temperature programming from 50 to 270 °C at 8 °C/min, helium as the carrier gas (47 mL/min)].

4.1. Method A

The reaction was carried out in a glass ampoule (V = 10 mL) placed in a stainless-steel micro-autoclave (V = 17 mL) under controlled heating with stirring. FeCl3*6H2O, o-aminophenol, CCl4, and H2O at a molar ratio [o-aminophenol]:[CCl4l:[H2O]:[FeCl3*6H2O] = 50:400:800:1 were loaded into the ampoule. The sealed ampoule was placed in an autoclave, which was hermetically sealed. The reaction was carried out at 100–120 °C for 2–10 h. After the completion of the reaction, the ampoule was opened, the reaction mixture was neutralized with dry NaHCO3, impurities were purified by chromatography (SiO2, eluent—ethyl acetate), and the solvents were distilled off on a rotary evaporator.

4.2. Method B

The synthesis of benzoxazolone was carried out in a round bottom flask equipped with a reflux condenser in a microwave oven with a power of 600 watts at 120 °C for 30 min. The reaction proceeded under constant stirring (built-in magnetic stirrer). After the completion of the synthesis, the reaction mixture was treated similarly to Method A.

Author Contributions

Conceptualization, A.R.B. and I.R.R.; methodology, A.R.B.; software, I.R.R.; validation, I.R.R.; formal analysis, A.R.B.; investigation, A.R.B.; resources, I.R.R.; data curation, I.R.R.; writing—original draft preparation, Z.G.U.; writing—review and editing, Z.G.U.; visualization, A.R.B.; supervision, I.R.R.; project administration, A.R.B.; funding acquisition, I.R.R. All authors have read and agreed to the published version of the manuscript.

Funding

This research was funded by the Russian Science Foundation, grant number 19-73-20128. The analytical part of the study was carried out within the framework of the state assignment of the Ministry of Education and Science (No. FMRS-2022-0076).

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Acknowledgments

The results were obtained on unique equipment at the “Agidel” Collective Usage Center (Ufa Federal Research Center, Russian Academy of Sciences).

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Turanl, S.; Uslu, A.G.; Ödemi, A. Synthesis of Novel Potential ROCK Inhibitors and Their Antimigratory Effects. Org. Commun. 2020, 13, 165–174. [Google Scholar] [CrossRef]
  2. Zheng, Z.; Parsons, J.B.; Tangallapally, R.; Zhang, W.; Rock, C.O.; Lee, R.E. Discovery of Novel Bacterial Elongation Condensing Enzyme Inhibitors by Virtual Screening. Bioorg. Med. Chem. Lett. 2014, 24, 2585–2588. [Google Scholar] [CrossRef] [PubMed]
  3. Safakish, M.; Hajimahdi, Z.; Zabihollahi, R.; Aghasadeghi, M.R.; Vahabpour, R.; Zarghi, A. Design, Synthesis, and Docking Studies of New 2-Benzoxazolinone Derivatives as Anti-HIV-1 Agents. Med. Chem. Res. 2017, 26, 2718–2726. [Google Scholar] [CrossRef]
  4. Bywater, B.W.G.; Coleman, W.R.; Kamm, O.; Merritt, H.H.; Merritt, H. Synthetic Anticonvulsants and Pharmacology. Prelim. Anticonvuls. 1945, 27, 4–6. [Google Scholar]
  5. Ceccarelli, S.M.; Jaeschke, G.; Buettelmann, B.; Huwyler, J.; Kolczewski, S.; Peters, J.U.; Prinssen, E.; Porter, R.; Spooren, W.; Vieira, E. Rational Design, Synthesis, and Structure-Activity Relationship of Benzoxazolones: New Potent Mglu5 Receptor Antagonists Based on the Fenobam Structure. Bioorg. Med. Chem. Lett. 2007, 17, 1302–1306. [Google Scholar] [CrossRef] [PubMed]
  6. Maag, D.; Dalvit, C.; Thevenet, D.; Köhler, A.; Wouters, F.C.; Vassao, D.G.; Gershenzon, J.; Wolfender, J.L.; Turlings, T.C.J.; Erb, M.; et al. 3-β-d-Glucopyranosyl-6-Methoxy-2-Benzoxazolinone (MBOA-N-Glc) Is an Insect Detoxification Product of Maize 1,4-Benzoxazin-3-Ones. Phytochemistry 2014, 102, 97–105. [Google Scholar] [CrossRef] [PubMed]
  7. Pena-Lopez, M.; Neumann, H.; Beller, M. (Enantio)Selective Hydrogen Autotransfer: Ruthenium-Catalyzed Synthesis of Oxazolidin-2-Ones from Urea and Diols. Angew. Chem. Int. Ed. 2016, 55, 7826–7830. [Google Scholar] [CrossRef] [PubMed]
  8. Vo, L.; Ciula, J.; Gooding, O.W. Chemical Development on the Chiral Auxiliary (S)-4-(Phenylmethyl)-2-Oxazolidinone Utilizing Automated Synthesis and DoE. Org. Process Res. Dev. 2003, 7, 514–520. [Google Scholar] [CrossRef]
  9. Gambacorta, G.; Baxendale, I.R. Continuous-Flow Hofmann Rearrangement Using Trichloroisocyanuric Acid for the Preparation of 2-Benzoxazolinone. Org. Process Res. Dev. 2022, 26, 422–430. [Google Scholar] [CrossRef]
  10. Sridhar, R.; Perumal, P.T. A Novel Method for the Synthesis of 2 (3 H)-Benzimidazolones, 2 (3 H)-Benzoxazolone, and 2 (3 H)-Benzothiazolone via In Situ Generated Ortho Substituted Benzoic Acid Azides: Application of Ammonium Azide and Vilsmeier Complex for Acid Azide Generation. Synth. Commun. 2004, 34, 735–742. [Google Scholar] [CrossRef]
  11. Prasanthi, A.V.G.; Begum, S.; Srivastava, H.K.; Tiwari, S.K.; Singh, R. Iron-Catalyzed Arene C-H Amidation Using Functionalized Hydroxyl Amines at Room Temperature. ACS Catal. 2018, 8, 8369–8375. [Google Scholar] [CrossRef]
  12. Khusnutdinov, R.I.; Bayguzina, A.R.; Asylbaeva, R.S.; Aminov, R.I.; Dzhemilev, U.M. Synthesis of N-arylsubstituted pyrrolidines and piperidines by reaction of anilines with α,ω-diols catalyzed by FeCl3.6H2O in carbon tetrachloride. ARKIVOC 2014, 341, 350. [Google Scholar]
  13. National Oceanic and Atmospheric Administration. Carbon Dioxide Now More Than 50% Higher Than Pre-Industrial Levels. Available online: https://www.noaa.gov/ (accessed on 15 September 2022).
Scheme 1. The preparation of 2-benzoxazolone 1.
Scheme 1. The preparation of 2-benzoxazolone 1.
Chemproc 12 00063 sch001
Scheme 2. Mechanism of 2-benzoxazolone 1 synthesis.
Scheme 2. Mechanism of 2-benzoxazolone 1 synthesis.
Chemproc 12 00063 sch002
Figure 1. Data from the mass spectrum of the gas phase of the reaction mixture.
Figure 1. Data from the mass spectrum of the gas phase of the reaction mixture.
Chemproc 12 00063 g001
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Urazbaeva, Z.G.; Bayguzina, A.R.; Ramazanov, I.R. Fe-Catalyzed Synthesis of 2-Benzoxazolone—An Important Fragment of Biologically Active Compounds. Chem. Proc. 2022, 12, 63. https://doi.org/10.3390/ecsoc-26-13564

AMA Style

Urazbaeva ZG, Bayguzina AR, Ramazanov IR. Fe-Catalyzed Synthesis of 2-Benzoxazolone—An Important Fragment of Biologically Active Compounds. Chemistry Proceedings. 2022; 12(1):63. https://doi.org/10.3390/ecsoc-26-13564

Chicago/Turabian Style

Urazbaeva, Zemfira G., Alfiya R. Bayguzina, and Ilfir R. Ramazanov. 2022. "Fe-Catalyzed Synthesis of 2-Benzoxazolone—An Important Fragment of Biologically Active Compounds" Chemistry Proceedings 12, no. 1: 63. https://doi.org/10.3390/ecsoc-26-13564

Article Metrics

Back to TopTop