Journal of Chromatographic Science, Vol. 34, January 1996 Analysis of 1 -(3-Methoxy-4,5-Methylenedioxyphenyl)-2- Propanamine (MMDA) Derivatives Synthesized from Nutmeg Oil and 3-Methoxy-4,5-Methylenedioxybenzaldehyde C. Randall Clark* and Jack DeRuiter Department of Pharmacal Sciences, School of Pharmacy, Auburn University, Auburn, Alabama 36849 Abstract Myristicin, a natural product found in nutmeg oil and nutmeg extract, contains the carbon skeleton for a series of drugs of abuse related to the 3,4-methylenedioxyamphetamines (MDAs). Myristicin, 1-(3-methoxy-4,5-methylenedioxyphenyl)-2-propene, was identified as the major component of commercially available nutmeg oil and in the organic extract of nutmeg powder. The starting materials, intermediates, and products in the synthesis of the drug of abuse N-methyl-1-(3-methoxy-4,5-methylenedioxyphenyl)-2-propanamine (MMDMA) from myristicin were characterized by gas chromato- graphic-mass spectrometric analysis. MMDMA and several primary amine derivatives including 1-(3-methoxy-4,5-methylene- dioxyphenyl)-2-ethanamine, -propanamine, and -butanamine were also prepared from the commercially available aldehyde, 3-methoxy- 4,5-methylenedioxybenzaldehyde. Each of these amine derivatives has a distinct mass spectrum characterized by amine-dominated fragmentation. All four amines in this study were resolved by reversed-phase liquid chromatography using an acidic aqueous mobile phase. Relative retention in this system was determined by differences in the hydrophobic surface area of the four amines. Introduction A number of phenalkylamines (Chart 1) including the am- phetamines (amphetamine and methamphetamine) and 3,4- methylenedioxyamphetamines (MDA, MDMA) remain popular drugs of abuse in the United States and abroad (1). These com- pounds are synthesized in clandestine laboratories by a variety of methods using commercially available synthetic precursors. For example, methamphetamine is commonly prepared by hydrogenolysis reactions using the ephedrines or pseu- doephedrines or by reductive amination of 1-phenyl-2- propanone (P-2-P) (2,3). Similarly, 3,4-methylenedioxymeth- amphetamine is typically synthesized by reductive amination of l-(3,4-methylenedioxyphenyl)-2-propanone (MDP-2-P) (4). The synthetic route by which illicit samples of these compounds are produced can frequently be determined by complete charac- terization and analysis of the sample (2–4). Based on these synthetic strategies, the availability of the precursors and related substances has been controlled by the Drug Enforcement Administration under the Chemical Diver- sion and Trafficking Act in March of 1989 (5). The restricted availability of these key precursors has prompted clandestine laboratory operators to seek alternative approaches for the syn- thesis of amphetamines and MDA-type compounds and to ex- plore the synthesis of new, structurally related compounds or so- called designer drugs for which precursor chemicals are available. For example, an alternate method reported for the syn- thesis of MDMA uses the natural product safrole (6), which is commercially available or can be obtained by extraction or dis- tillation of the sassafras plant, which is native to the United States. Safrole may be used to synthesize the ketone MDP-2-P or may be brominated with hydrobromic acid to yield l-(3,4- methylenedioxyphenyl)-2-bromopropane, which can be con- verted to MDMA by direct displacement with methylamine. This same synthetic approach could be used with the primary com- ponent of nutmeg oil, myristicin, to yield l-(3-methoxy-4,5- methylenedioxyphenyl)-2-propanamine derivatives such as the N-methyl analogue MMDMA and the primary amine MMDA. These compounds are the m-methoxy analogues of MDMA and * Author to whom correspondence should be addressed. Chart 1. Synthetic drugs of abuse: amphetamine, methamphetamine, MDA, MDMA, MMDA, and MMDMA. 34 Reproduction (photocopying) of editorial content of this journal is prohibited without publisher's permission. F. Taylor Noggle Alabama Department of Forensic Sciences, Wire Road, Auburn, Alabama 36830