Synthesis of Arylbenzoxazole from 2-Aminophenol and Aldehydes

In this study, an efficient method was developed for the synthesis of 2-heterosubstituted benzoxazole derivatives via a redox condensation reaction between 2-nitrophenol and isothiocyanate. The reaction was carried out in N-methylpyrrolidone (NMPone) as the solvent, using an Fe/S catalytic system in combination with the base N-methylpiperidine (NMP). It was found that the reaction only proceeded in the simultaneous presence of all three components: iron salt (FeCl₂·4H₂O), sulfur, and NMP. 

A total of 41 2-heterosubstituted benzoxazole derivatives (70ab–70ka) were successfully synthesized. 

This method is simple, does not require high-pressure conditions, and demonstrates high synthetic efficiency as well as broad applicability to substrates bearing diverse electron-donating and electron-withdrawing groups. 

Comprehensive spectroscopic data sets (including ¹H and ¹³C NMR spectra) were established to confirm the structures of all 41 synthesized compounds (70ab–70ka).

Synthesis of 2-Aminobenzoxazole from Amine, Carbon Disulfide and 2-Nitrophenol

A novel and efficient method was developed for the synthesis of 2-aminobenzoxazole derivatives via a redox condensation reaction between 2-nitrophenol, amines, and carbon disulfide, catalyzed by iron salts. The reaction was carried out in N-methylpyrrolidone (NMP) and involved the in situ formation of a dithiocarbamate intermediate from the amine and CS₂, which acted as the reducing agent for the nitro group.

A total of 24 2-aminobenzoxazole derivatives (73bc–73bz) were successfully synthesized.

Comprehensive spectral datasets, including ¹H and ¹³C NMR spectra, were established to confirm and characterize the structures of 26 2-aminobenzoxazole compounds (73bc–73bz).

Synthesis of 3-Arylquinoxalin-2-one from o-Phenylenediamine and Arylacetate

A selective and environmentally friendly oxidative condensation method was successfully applied for the synthesis of quinoxalin-2-one derivatives via an oxidative condensation reaction between o-phenylenediamine and arylacetates, using elemental sulfur as the oxidant in combination with DABCO and DMSO.

The advantages of this protocol include the use of inexpensive reagents, mild reaction conditions, and the ease of product isolation through simple techniques such as crystallization or filtration, making it a promising approach for large-scale synthesis.

A total of 26 3-arylquinoxalin-2-one derivatives (76ab–76ja) were synthesized.

Comprehensive spectroscopic data sets (including ¹H and ¹³C NMR spectra) were established to confirm and elucidate the structures of all 26 synthesized compounds.

Multicomponent reaction for synthesis of derivatives Thione

Thiones represent an important class of compounds due to their catalytic properties in organic synthesis, biological activity, potential applications in functional materials, and their role as intermediates in various synthetic transformations. In previous studies, thioureas have typically been synthesized through the condensation of amines with carbon disulfide or related compounds without changing the oxidation state. However, carbon disulfide is volatile, flammable, and toxic, making it unsuitable for large-scale synthesis. Additionally, the generation of hydrogen sulfide as a by-product poses significant safety concerns. To address these limitations, we propose a simple and environmentally friendlier method for thiourea synthesis using nitromethane and elemental sulfur—both of which are safer and more sustainable reagents.

Notably, perimidinethione (79f) was obtained in high yield and demonstrated scalability, indicating its potential as an intermediate in further synthetic applications.

A total of 10 thione derivatives (79a–79k) were successfully synthesized.

Comprehensive spectroscopic data sets, including ¹H and ¹³C NMR spectra, were established to confirm and elucidate the structures of all 10 synthesized thione compounds.

Anti-inflammatory activity survey NO 

We have successfully developed four novel methods for the synthesis of compounds bearing the 2-heterosubstituted benzazole scaffold. These methods employ mild reaction conditions and utilize inexpensive, readily available, and non-toxic starting materials. The synthetic procedures are environmentally friendly and show strong potential for large-scale production. Notably, the reactions proceed efficiently even in the presence of strong electron-withdrawing groups (e.g., –NO₂), overcoming limitations observed in previous studies, which often required complex, expensive, and toxic catalysts when using such substrates

- 1 Completed Report 

- Published articles (list): 

- 04 Articles in international journals listed in ISI, SCIE, IF>2

• Le Anh Nguyen, Thi Yen Tran, Quoc Anh Ngo, Dinh Hung Mac, Pascal Retailleau, and Thanh Binh Nguyen, Sulfur-Promoted Access to 3‑Arylquinoxalin-2-ones by Oxidative Coupling of o‑Phenylenediamines with Arylacetates, Org. Lett. 2024, 26, 6098−6102. (IF = 5.0)

• Le Anh Nguyen, Supasorn Phaenok, Duc Long Le, Thi Thu Tram Nguyen, Quoc Anh Ngo,*and Thanh Binh Nguyen, Fe/S-Catalyzed Redox Condensation of o‑Nitrophenols with Isothiocyanates to 2‑Aminobenzoxazoles, Org. Lett. 2023, 25, 5145−5150. (IF = 5.0)

• Duc Long Le,[a, b] Thi Yen Tran, Le Anh Nguyen, Quoc Anh Ngo, Dinh Hung Mac, and Thanh Binh Nguyen, Iron-Promoted Redox Access to 2-Aminobenzoxazoles from Amines, Carbon Disulfide and 2-Nitrophenols, Asian J. Org. Chem. 2024, e202400212. (IF = 2.8)

• Supasorn Phaenok, Le Anh Nguyen, Darunee Soorukram, Thi Thanh Tam Nguyen, Pascal Retailleau,[a] and Thanh Binh Nguyen, Sulfur- and Amine- Promoted Multielectron Autoredox Transformation of Nitromethane: Multicomponent Access to Thiourea Derivatives, Chem. Eur. J. 2024, 30, e202303703. (IF = 3.9)

• Articles are online and all have task codes in the acknowledgements 

• The project has contributed to training 01 PhD student