Understanding the efficacy of N,N-dimethylformamide and oxalyl chloride combination as chemoselective O-formylating agent: An unified experimental and theoretical study

ABSTRACT

We have developed a simple but efficient synthetic protocol for the O-formylation of a wide range of aromatic hydroxyl/phenolic substrates using an N,N-dimethylformamide (DMF) and oxalyl chloride [(COCl)₂] combination in dichloromethane (DCM) as solvent at ambient temperature. The DMF/(COCl)₂ combination was found to be highly chemoselective for the aromatic/phenolic hydroxyl group over aliphatic hydroxyl or aromatic amine/thiol groups. This chemoselectivity of DMF/(COCl)₂ combination towards O-formylation of aromatic alcohols was explained on the basis of outcomes of both experimental and density functional theory–based theoretical studies.

GRAPHICAL ABSTRACT

KEYWORDS:

• Aromatic alcohols
• chemoselective O-formylation
• N,N-dimethylformamide
• oxalyl chloride