Denitrogenative Radical Transacetylation of Amines Using Acetohydrazide in Water at Room Temperature

Area of Science:

• Organic Chemistry
• Green Chemistry

Background:

• Traditional N-acetylation methods often employ harsh reagents like acetic anhydride or acetyl chloride.
• Existing strategies may involve expensive or sensitive enzyme catalysts.
• There is a need for milder, more sustainable acetylation protocols.

Purpose of the Study:

• To develop a nonconventional oxidative denitrogenative radical transacetylation method.
• To utilize acetohydrazide as a novel and sustainable source of acetyl radicals.
• To achieve chemoselective N-acetylation of primary and secondary aryl/heteroaryl amines under mild conditions.

Main Methods:

• Employing acetohydrazide as the acetyl radical precursor.
• Utilizing tert-butyl hydroperoxide (TBHP) and tert-butyl ammonium iodide (TBAI) as environmentally friendly reagents.
• Conducting the reaction under mild, transition-metal-free conditions in water.

Main Results:

• Achieved efficient and selective N-acetylation of a wide range of amines.
• Demonstrated the in situ generation of acetyl radicals via control experiments with radical scavengers.
• Successfully applied the protocol to the synthesis and late-stage functionalization of pharmaceutical compounds and drug intermediates.

Conclusions:

• The developed method provides a sustainable and scalable approach for amine N-acetylation.
• This protocol expands the available synthetic tools for amine functionalization.
• The method holds promise for industrial applications in drug discovery and development.