Reactions of N-alkylglycolurils with electrophilic reagents

The N-hydroxymethylation, N-acetylation, and N-acetoxymethylation of mono-, di-, and trialkylglycolurils by reaction with the electrophilic reagents formaldehyde and acetaldehyde have been studied. General methods have been developed for the preparation of mono-, di-, and tri-Nhydroxymethylglycolurils by treatment of differently substituted N-alkylglycolurils with formaldehyde (as hemiformal in methanol) and the synthesis of di-N- and tri-N-acetyl- or N-acetoxymethylglycolurils via the electrophilic substitution of hydrogen atoms for an acetyl group at the nitrogen or oxygen atoms in the hydroxymethyl groups of glycolurils using acetic anhydride. The regioselectivity of the reaction of the 2-t-Bu- and 2-c-C6H11-glycolurils with formaldehyde has been shown to yield a 4,6-di(hydroxymethyl) derivative. It was found that the hydroxymethylation of 2,4- and 2,6-dialkylglycolurils occurs regioselectively with a stoichiometric ratio of glycoluril to hemiformal and permits preparation of their mono- and dihydroxymethyl derivatives. The enantiomeric analysis of the obtained compounds has been carried out for the first time using HPLC on chiral phases. X-ray analysis has been carried out on the previously unreported racemic 2,6-diacetoxymethyl-4,8-dimethylglycoluril.