Ephedrine remains a key precursor in the production of methamphetamine. A novel ephedrine-based route to methamphetamine involved the nitrosation of propiophenone to α-isonitrosopropiophenone, followed by catalytic hydrogenation to phenylpropanolamine (± − norephedrine). Cyclization-methylation of phenylpropanolamine to 3,4-dimethyl-5-phenyl-2-oxazolidinone using dimethyl carbonate, followed by basic hydrolysis or catalytic hydrogenolysis formed ephedrine or methamphetamine, respectively.

An investigation into the stable isotope fractionation during the synthesis of methamphetamine from propiophenone, NaNO2 and dimethyl carbonate was performed using isotope ratio mass spectrometry. A negative isotopic shift was observed for δ15N upon nitrosation of propiophenone to α-isonitrosopropiophenone, and a negative isotopic shift for δ2H during catalytic hydrogenation of α-isonitrosopropiophenone to phenylpropanolamine. Minimal change in δ13C was observed throughout the reaction until the methylation step with dimethyl carbonate, where a negative isotopic shift was observed.

The δ13C values for the methamphetamine presented in a similar range to methamphetamine reported in previous work where the norephedrine/norpseudoephedrine was prepared via different starting materials (benzaldehyde and nitroethane), confirming that similar δ13C values will result from fractionation during methylation with dimethyl carbonate regardless of the origin of the norephedrine/norpseudoephedrine. Chiral analysis confirmed methamphetamine to be racemic.