E is for Ecstasy by Nicholas Saunders

Appendix 4: Bibliography

Anon: Verfahren zur Darstellung von Alkyloxyaryl-, Dialkyloxyaryl- und Alkylendioxyarylaminopropanen bzw. deren am Stickstoff monoalkylierten Derivaten. German Patent, 274,350; Filed December 24, 1912, issued May 16, 1914. Assigned to E. Merck in Darmstadt.

A chemical process is described for the conversion of several allyl- and propenyl-aromatic compounds to the corresponding beta-or alpha-bromopropanes. These, in turn, react with ammonia or primary amines to produce the corresponding primary or secondary propylamines. Specifically, safrole was reacted with aqueous HBr, and the impure reaction product reacted with alcoholic methylamine to produce MDMA in an unstated yield. Also described and characterized are MDA and DMA, as well as the corresponding 1-phenyl-1-aminopropanes. No pharmacology is mentioned.

Anon: Formyl Derivatives of Secondary Bases. German Patent 334,555, assigned to E. Merck. 1920. CA 17:1804a (1923).

A chemical conversion of MDMA to its formyl derivative, and the properties of the latter, are described. No pharmacology is mentioned.

Biniecki, S. and Krajewski, E. Preparation of DL-1-(3,4-Methylenedioxy)-2-(methylamino)propane and DL-1-(3,4-dimethoxyphenyl)- 2-(methylamino)propane. Acta Polon. Pharm. 17 421-425 (1960). CA 55:14350e (1961).

A chemical procedure is given for the conversion of safrole to the beta-bromopropane with HBr, and its subsequent conversion with alcoholic methylamine to MDMA. 4-Allylveratrole was similarly converted to 3,4-dimethoxy-N-methyl- amphetamine.

Bohn, M., Bohn, G. and Blaschke, G. Synthesis Markers in Illegally Manufactured 3,4-Methylenedioxyamphetamine and 3,4-Methylenedioxymethamphetamine. Int. J. Legal Med. 106 19-23 (1993).

Some twelve impurities have been described and identified in samples of illicitly prepared MDMA and MDA. Their role as markers for the synthetic routes used, or for connercting different lots of the drugs, is discussed.

Braun, U., Shulgin, A.T. and Braun, G. Centrally Active N- Substituted Analogs of 3,4-Methylenedioxyphenylisopropylamine (3,4-Methylenedioxyamphetamine), J. Pharm. Sci. 69 192-195 (1980).

Twenty two homologues and analogs of MDA were synthesized and their physical properties presented. Twelve of them were assayed in man as psychotomimetic agents. Three of them were found to be active: MDMA with a human potency of between 100 and 160 mg orally; MDE somewhat less potent with a dosage requirement of 140-200 mg orally; and MDOH, which was similar to MDMA in potency. Some animal pharmacology is reviewed, and a comparison between MDMA and MDA (toxicology, CNS pharmacology, and human effectiveness) is tabulated.

Cerveny, L., Kozel, J. and Marhoul, A. Synthesis of Heliotropin. Perfumer and Flavorist 14 13-18 (1989).

Piperonal is a most desirable precursor to piperony methyl ketone (PMK) which can, in turn, be converted directly to either MDA or MDMA. This is a synthetic procedure for the preparation of piperonal (heliotropin) from the precursor catechol (pyrocatechol).

Fujisawa, T. and Deguchi, Y. Concerning the Commercial Utilization of Safrole. J. Pharm. Soc. Japan 74 975 (1954). CA 49:10958i (1955).

The conversion of safrole to piperonylacetone is described, using formic acid and hydrogen peroxide, in acetone. The yield is satisfactory, and this is probably the most direct and efficient conversion of a natural product to an immediate precursor to MDMA.

Hashimoto, K., Hirai, K. and Goromaru, T. Synthesis of Racemic, S(+)- and R(-)-N-[methyl-3H] 3,4-Methylenedioxymethamphetamine. J. Labelled Cpds. and Radiopharmaceut. 28 465-469 (1990).

Tritium-labelled MDMA was synthesized from MDA by reaction with radioactive methyl iodide in a 60% yield. The optical isomers were separated on a chiral HPLC column.

Janesko, J.L. and Dal Cason, T.A. Seizure of a Clandestine Laboratory: The N-Alkyl MDA Analogs. Paper presented at the 39th Annual Meeting of the American Academy of Forensic Sciences, San Diego, CA Feb. 16-21 (1987). See Microgram 20 52 (1987).

Several clandestine laboratories have been seized, revealing the illicit preparation of not only MDMA, but the N-ethyl (MDE), the N-propyl (MDPR), the N-isopropyl (MDIP) and the N,N-dimethyl (MDDM) homologues. These were all synthesized by the NaCNBH3 reduction method from the appropriate amine salt and piperonylacetone. Also, the N-ethyl-N-methyl, and the N,N-diethyl homologues were found, prepared by catalytic hydrogenation.

Nakai, M. and Enomiya, T. Process for Producing Phenylacetones. U.S. Patent #4,638,094, dated January 20, 1987.

A high yield procedure is described, for the conversion of an allylbenzene to the corresponding phenylacetone. Specifically, the MDMA precursor 3,4-methylenedioxyphenylacetone is prepared in a 95% yield from safrole and butyl nitrite, in the presence of palladium bromide.

Nichols, D.E. Synthesis of 3,4-Methylenedioxymethamphetamine Hydrochloride. FDA Master File on MDMA. 1986.

A detailed synthesis of MDMA from piperonylacetone is presented, including all the spectroscopic and physical detail, bibliographies and CVs as required to define a drug product for medical needs.

Shulgin, A.T. and Jacob III, P. Potential Misrepresentation of 3,4-Methylenedioxyamphetamine (MDA). A Toxicological Warning. J. Anal. Tox. 6 71-75 (1982).

The commercial availability and overt misrepresentation of 3,4-methylenedioxybenzylacetone as 3,4-methylenedioxyphenylacetone might well suggest that an unsuspecting attempt to synthesize MDMA may yield a new and unexplored base, 1-(3,4-methylenedioxyphenyl)-3-(methylamino)butane. This compound was synthesized, and characterized in comparison to MDMA. The analogous relationship between MDA and its comparable homologue, 1-(3,4-methylenedioxyphenyl)-3-aminobutane, was also explored.

Yourspigs, U.P. The Complete Book of Ecstasy. Synthesis Books, Birmingham, Alabama. 1992.

This is an underground press book describing, quite adequately, the equipment and the synthetic prosesses needed for the synthesis of MDMA, starting with safrole or Oil of Sassafras. The preparation of MDEA (EVE) is also offered.