Differentiation of o-, m-, and p-fluoro-α-pyrrolidinopropiophenones by Triton B-mediated one-pot reaction

• DOI: 10.1016/j.forsciint.2019.06.005
• Publication Date: 2019-06-30T13:24:18Z
• Authors: Takaya Murakami; Yoshiaki Iwamuro; Reiko Ishimaru; Satoshi Chinaka; Hiroshi Hasegawa; Rahul D. Kavthe; Naoki Asao
• Keywords: Pyrrolidine; Structural isomer; Enamine; Cathinone

Positional isomer differentiation is crucial for the analysis of forensic drugs. Presently, it is difficult to distinguish among ortho, meta, and para positional isomers of ring-fluorinated synthetic cathinones, a major class of new psychoactive substances (NPSs), because they exhibit similar chromatographic properties and mass spectral patterns. We describe herein that the ring-fluorinated synthetic cathinone positional isomers, viz. o-, m-, and p-fluoro-α-pyrrolidinopropiophenones (o-, m-, and p-FPPPs), can be discriminated by their benzyltrimethylammonium hydroxide (Triton B)-mediated one-pot reaction with methanol at ambient temperature, followed by chromatographic and mass spectral analyses of the corresponding products. For p-FPPP, fluorine was nucleophilically substituted by the methoxy group to afford p-methoxy-α-pyrrolidinopropiophenone, while o- and m-FPPPs afforded the corresponding FPPP-enamine-pyrrolidine adducts, which allowed the above positional isomers to be unambiguously differentiated by comparing the reaction product chromatograms and mass spectra. The adopted approach, which does not require excess heating or use of metallic catalysts and features the advantages of simplicity and convenience, is expected to contribute toward practical NPS identification.