n-Bu₄NI/K₂S₂O₈-MEDIATED C-N COUPLING BETWEEN ALDEHYDES AND AMIDES

Area of Science:

• Organic Chemistry
• Synthetic Chemistry

Background:

• C-N coupling reactions are fundamental in organic synthesis.
• Developing efficient and selective methods for C-N bond formation remains a key challenge.

Purpose of the Study:

• To report a novel n-butylammonium iodide (n-Bu4NI) and potassium persulfate (K2S2O8) mediated C-N coupling reaction.
• To investigate the influence of electronic effects on aromatic aldehyde substrates in this coupling.
• To explore the application of this methodology in the synthesis of quinazolin-4(3H)-ones.

Main Methods:

• Utilizing n-butylammonium iodide (n-Bu4NI) and potassium persulfate (K2S2O8) as catalytic and oxidative systems.
• Employing aldehydes and amides as substrates for C-N coupling.
• Conducting density functional theory (DFT) calculations to elucidate reaction mechanisms.
• Performing experimental validation of the proposed mechanisms and reaction outcomes.

Main Results:

• Achieved selective transformylation from aldehydes to amides when aromatic aldehydes possess ortho or para electron-donating groups.
• Observed dominance of cross-dehydrogenative coupling in the absence of such electron-donating groups.
• Provided evidence for a single electron transfer mechanism involving an acyl radical intermediate.
• Successfully synthesized four quinazolin-4(3H)-one derivatives via oxidative cyclization in 65-99% yields.

Conclusions:

• The developed n-Bu4NI/K2S2O8 system offers a versatile approach for C-N coupling with tunable selectivity based on substrate electronics.
• The reaction proceeds via a single electron transfer mechanism, confirmed by DFT calculations and experimental data.
• This methodology provides an efficient route to valuable quinazolin-4(3H)-one scaffolds.