One-Pot Silylation-Amination Synthesis of 3‑N‑Substituted Benzo[d]isothiazole 1,1-Dioxides

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Synthetic Chemistry

Background:

• Saccharin-based scaffolds are gaining attention in medicinal chemistry.
• They show potential as hypoxia-inducible factor-2 modulators.
• Existing synthesis methods involve chlorination-amination, which has drawbacks.

Purpose of the Study:

• To develop an alternative, efficient synthesis for 3-N-substituted benzo-[d]-isothiazole 1,1-dioxides.
• To establish a one-pot silylation-amination protocol.
• To provide a greener alternative to chlorination-based methods.

Main Methods:

• A one-pot silylation-amination reaction was employed.
• Hexamethyldisilazane was used as the silylating agent.
• The reaction was performed under solvent-free conditions.

Main Results:

• The protocol successfully synthesized 3-N-substituted benzo-[d]-isothiazole 1,1-dioxides.
• Yields ranged from moderate to excellent (31-99%).
• The method demonstrated broad substrate scope and operational simplicity.

Conclusions:

• The developed silylation-amination route is a viable and efficient alternative for synthesizing saccharin derivatives.
• This method offers advantages over traditional chlorination approaches.
• The protocol is suitable for medicinal chemistry applications requiring these scaffolds.