One-pot synthesis of N-substituted pantolactams from pantolactone

Rac-N-substituted pantolactams (5) are readily obtained in medium to good yields by reaction of rac-pantolactone (1) with primary amines under acid catalysis, whether at 250°C in a pressure reactor or under microwave irradiation. It appears that the amine can react with pantolactone at the carbonyl carbon atom to give a hydroxyamide (3) in a reversible way and at the methylene carbon atom to give a γ-amino acid (4). The last one on dehydration would give the corresponding pantolactam (5).