Effect of Neighboring Groups on the Methylolation of Acid Amides

Abstract

Methylolation of acid amides containing various electron-releasing and electron-withdrawing substituents has been carried out with formaldehyde in the presence of sodium hydroxide at pH 10 and at 55°C. The methylolation relative rates and extents of these acid amides have been studied. The results indicate that a number of factors, such as inductive effect, hyperconjugation, stereochemistry, and solvation, govern the rate and extent of methylolation. It was observed that methylol derivatives of acid amides with electron-withdrawing substituents tend to polymerize during methylolation. Methylolation of acid amides containing electron-releasing substituents proceeds better in the presence of triethylamine as compared to sodium hydroxide.