Microwave-Enhanced On-Water Amination of 2-Mercaptobenzoxazoles To Prepare 2-Aminobenzoxazoles

Abstract

In this work, we developed a catalyst-free amination of 2-mercaptobenzoxazoles on water under microwave irradiation. The product, 2-aminobenzoxazoles, was successfully produced via direct amination with various amines in moderate to high yields. The formal synthesis of Suvorexant, a medication for the treatment of insomnia, was accomplished using a developed amination process. The reaction was completed in an hour at 100–150 °C in a microwave reactor without the use of external catalyst or additive. Key benefits of this process include an on-water reaction, short reaction time, being scalable and catalyst-free, and use of 2-mercaptobenzoxazoles as an inexpensive starting material having low environmental impact in its preparation.

2-Mercaptobenzoxazoles: a class of carbonic anhydrase inhibitors with a novel binding mode to the enzyme active site

“…1) constitute a very interesting compound family due to their applications not only in organic synthesis, but also in the biomedical field as antibacterial, antiviral, anti-inflammatory, analgesic and anthelmintic agents. [13][14][15][16][17] Moreover, interesting studies have shown that the complexes of 2-mercaptobenzoxazoles with various transition metals possess a cytotoxic activity against cancer cells. 18…”

Recent Advances and Prospects in the Amination of Benzoxazoles

“…A catalyst-free protocol was reported to synthesise 2-aminobenzoxazole, through the amination of 2mercaptabenzoxazole. [61] The reaction was carried out under microwave irradiation at 100-150 °C for 1 h. On-water amination procedure made this approach eco-friendly and costeffective. Various substituted amines and benzoxazoles provided moderate to good yields of the required products.…”

Recent Advances and Prospects of Organic Reactions “On Water”

“…A microwave enhanced catalyst‐free amination of 2‐mercaptobenzoxazoles 1 on water was developed by Wacharasindhu and co‐workers (Scheme ) . Addition of amine 2 to 1 generates adduct 5 as an intermediate.…”