Metal-Free Synthesis of Polysubstituted Triazoloquinoxalines Using Alkynols as the Key Building Blocks

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Heterocyclic Chemistry

Background:

• Quinoxaline derivatives are important scaffolds in medicinal chemistry.
• Efficient synthesis of substituted triazoloquinoxalines remains a challenge.

Purpose of the Study:

• To develop a novel, mild, and metal-free synthetic route to substituted (dihydro)triazoloquinoxalines.
• To explore the preparation of related fused heterocycles like benzotriazolodiazepines and benzotriazolodiazocines.

Main Methods:

• Conversion of o-phenylenediamines to N-Ts/Ns derivatives.
• Mitsunobu alkylation with propargyl alcohols.
• One-pot azidation followed by Huisgen cycloaddition.
• Arylsulfonyl group cleavage for final product formation.

Main Results:

• Successfully synthesized Ts/Ns-dihydrotriazoloquinoxalines via a multi-step sequence.
• Prepared diversely substituted (dihydro)triazoloquinoxalines by modifying the N5 position.
• Extended the methodology to synthesize benzotriazolodiazepines and benzotriazolodiazocines.

Conclusions:

• The developed protocol offers a versatile and efficient pathway to complex fused nitrogen heterocycles.
• The method operates under mild, metal-free conditions, utilizing accessible starting materials.
• This approach facilitates the synthesis of novel compounds for potential applications.