The Peaceful Pill eHandbook Stages in Barbiturate Synthesis
There are three basic steps in the synthesis of a barbiturate Peaceful Pill:
• Step 1: Attaching the first sidechain to the di-ethyl malonate • Step 2: Attaching the second sidechain to the product of step 1
• Step 3: Condensing the di-substituted malonate with urea to form the required barbiturate
Looking at these steps in more detail
Step 1 In the case of the target barbiturates, Nembutal or Amytal, the first sidechain to be attached to the di-ethyl malonate is an ethyl halide, usually ethyl bromide is used. To form the mono-sustituted malonic ester, ethyl bromide is heated with the di-ethyl malonate in the presence of the required catalyst - the base, sodium ethoxide.
The catalyst may be purchased or made as part of the process. To make the required ethoxide add 5.7g of metallic sodium that has been cleaned by passing through a press - see ‘Betty cooks with Sodium’ - and 125ml of very dry alcohol.
Into this mixture of dry alcohol and sodium ethoxide add 38ml of di-ethyl malonate and 26g of bromoethane. Heat is applied and the mixture stirred using a magnetic stirrer. In an open system a reflux condenser must be fitted and a calcium chloride guard tube used to ensure no contamination by atmospheric moisture.