The di-substituted barbiturates of particular interest are amylobarbital (Amytal) and pentobarbital (Nembutal). The process of adding side-arms (di-substitution) needs to be undertaken before the condensation of the malonate and urea.
In Amytal, the two alkyl side arms are (a) ethyl, introduced as ethyl-bromide and (b) 3-methylbutyl, introduced as 1-bromo- 3-methylbutane. In Nembutal, the two alkyl side-arms are (a) ethyl, introduced as ethyl-bromide and (b) 1-methylbutyl, produced from 2-bromopentane. In both substitution reactions the malonate is heated, either in a closed pressure system (autoclave) or under reflux first with one and then the second alkyl bromide. In both reactions sodium ethoxide is used as the catalyst.
The final step in the production of sodium pentobarbital or sodium amylobarbital is heating of the resultant di-substituted malonate with dry urea in an autoclave or under reflux for another 12 hours. This is again done in the presence of dry alcohol and sodium. Excess alcohol is removed by distillation and the residue - predominantly sodium pentobarbital, or sodium amylobarbital - is dissolved in water to form the Peaceful Pill.
In all of the di-substitution reactions and in the condensation with urea, it is essential that there be absolutely no water present. Care must be taken to ensure no atmospheric moisture reaches the autoclave or reactor vessel. All substances used must be dry. In particular, the alcohol used in the production of the sodium ethoxide needs to be as dry as possible (super dry).