Impurity Profiling of ATS Synthesized From Ring-Substituted APAAN and MAPA Analogs

Designer precursors for the synthesis of amphetamine-type stimulants pose a significant challenge to law enforcement. The precursors APAAN (α-phenylacetoacetonitrile) and MAPA (methyl α-acetylphenylacetate) became popular in the previous decade and have since been restricted. Recently, a ring-substituted analog of MAPA used for the synthesis of MDMA (3,4-methylenedioxymethamphetamine) was detected, highlighting the potential for criminal misuse of substituted analogs of these designer precursors. Previous research has characterized the impurity profiles of methamphetamine synthesized from APAAN and MAPA. In this study, the impurity profiles of MDMA and PMMA (p-methoxymethamphetamine) synthesized from ring-substituted analogs of APAAN and MAPA were characterized. In addition, byproducts forming from the conversion of p-methyl and p-fluoro analogs of APAAN and MAPA into analogs of P2P were investigated. MDMA was synthesized from 3,4-methylenedioxy-substituted MAPA (methyl α-acetyl-[3,4-methylenedioxyphenyl]acetate, MAMDPA) via sodium cyanoborohydride reductive amination and hydrogenation with platinum oxide and methylamine. Four impurities originating from MAMDPA were detected in MDMA synthesized via reductive amination, all of which are 3,4-methylenedioxy analogs of the impurities detected in methamphetamine synthesized from MAPA. Synthesis of MDMA via the hydrogenation route only produced one characteristic impurity, which, due to its instability under acidic conditions, is not likely to be present in clandestine MDMA hydrochloride samples. PMMA was synthesized via sodium cyanoborohydride reductive amination of MeO-P2P produced from methoxyl-substituted APAAN (α-p-methoxyphenylacetoacetonitrile, APMPAAN). Five impurities were identified as originating from APMPAAN, two of which are proposed to be the most reliable markers for the use of APMPAAN in the synthesis of PMMA.