Potential forensic markers from synthetic pathways to 1-phenyl-2-propanone from uncontrolled and controlled substances

Abstract

2-Phenylpropionaldehyde (a controlled substance; known as hydratropic aldehyde) was converted to 1-phenyl-2-propanone, using acid sources, with both a very high acidity and low oxidising strength. Key side products, acetophenone and 1,4-dimethyl-2-phenylnaphthalene, were identified as potential marker compounds. These results allowed 2-phenylpropionaldehyde to be identified as a pre-precursor to methamphetamine. Application of a previously reported rearrangement of hydratropic aldehyde, and formation of semicarbazone derivatives, established that acetophenone had been erroneously reported in the older literature as 1-phenyl-2-propanone. Density functional theory calculations at the B3LYP/6-31G(d,p) and ωB97X-D/6–31++G(d,p) level of theory indicated that a proposed superelectrophile rearrangement mechanism of 2-phenylpropionaldehyde to 1-phenyl-2-propanone (involving double protonation of the 2-phenylpropionaldehyde) was more energetically favourable than an analogous mechanism involving singly protonated species, rationalising the requirement for very high acidities to achieve the rearrangement. Ethyl methylphenylglycidate (an uncontrolled substance) was identified as a potential pre-precursor to methamphetamine through conversion to 2-phenylpropionaldehyde and its subsequent rearrangement to 1-phenyl-2-propanone and key side product acetophenone. Notably, the key side products acetophenone and 1,4-dimethyl-2-phenylnaphthalene should serve as forensic markers for profiling and may indicate the 2-phenylpropionaldehyde and ethyl methylphenylglycidate rearrangement pathways when screening seized clandestine samples of 1-phenyl-2-propanone and methamphetamine.