ALKYLATION OF DISUBSTITUTED GLYCOLURIL
Abstract
A new method is suggested herein for the synthesis of tetrasubstituted glycolurils by treatment of disubstituted glycolurils (di-tert-butylglycolurils, di-isopropylglycoluril) with alkylating agents such as methyl iodide, ethyl bromide and benzyl chloride in acetonitrile in the presence of KOH. Optimum conditions for the preparation of the target product in high yield were studied by the example of the synthesis of dibenzyl-di-tert-butylglycoluril: time 3 h and reaction temperature 75 ºС at a 1:4 M/M molar ratio of disubstituted glycoluril to benzyl chloride. Thus, the target product yield was 83 %. It was also found that benzyl chloride should be used as the alkylating agent because the product yield under the same equal conditions was higher with benzyl chloride than with benzyl bromide which in turn is more toxic and less available. By using the PASS program (Prediction of Activity Spectra for Substances), the following properties were chosen that would be responsible for antidepressant action: serotonin-release stimulation, antipsychotic and anxiolytic. Only dimethyl-di-tert-butylglycoluril and dimethyl-diisopropylglycoluril demonstrated a positive effect with a probability over 70%. These compounds structurally bear methyl groups which are likely the very groups that are responsible for biological activity, since the common anxiolytics Mebicar and Albicar comprise structurally the СН3 group as well.