The original synthesis involves first the condensation ofmethylethylketone with two equivalents ofcyanoacetamide. The product can be rationalized by assuming first aldol condensation of ketone and active methylene compound followed by dehydration to give 3.Conjugate addition of a second molecule ofcyanoacetamide would afford 4. Addition of one of the amide amines to the nitrile would then afford the iminonitrile 5. The observed product 6 can be rationalized by assuming loss of thecarboxamide under strongly basic conditions. Decarboxylative hydrolysis of 6 then leads to bemegride 7.
Bemegride was the drug which suspectedserial killerJohn Bodkin Adams who, as ageneral practitioner, failed to prescribe correctly to his patientGertrude Hullett. Hullett took an overdose of barbiturates on 19 July 1956, but Adams only gave her a single 10cc dose of bemegride three days later on the 22nd, despite having acquired 100cc for her treatment. Hullett died the next day on 23 July 1956. Adams was charged but never tried for her murder.[4]
^abThole FB, Thorpe JF (1911). "LIII.—The formation and reactions of iminocompounds. Part XV. The production of imino-derivatives of piperidine leading to the formation of the ββ-disubstituted glutaric acids".Journal of the Chemical Society, Transactions.99:422–448.doi:10.1039/CT9119900422.
