Introduction to Phenethylamine Drug Chemistry

This page is a chapter in 'Book Clandestine Drug Chemistry'

The Phenethylamine class of chemicals includes some of the most popular products of clandestine drug labs around the world. These include MDMA, Methamphetamine, 2C-B, and a variety of “research chemicals”. This class of chemicals was giving center stage in the great Dr. Alexander Shulgin’s book PIHKAL: A Chemical Love Story[/b] (PIHKAL stands for “Phenethylamines I have Known And Loved”) . The Phenethylamine class of drugs spans a wide variety of structurally similar chemicals with the base structure Phenethylamine. These powerful drugs possess a wide range of effects, from the stimulants amphetamine and methamphetamine, the hallucinogenic 2C-X chemicals such as 2C-B and 2C-I, and the empathogenic MDX chemicals which include MDMA, MDA, and MDE.
The synthesis of the bulk of these drugs is rather straight forward with the simple requirement of availability of a direct precursor and laboratory equipment. For example, 2C-B is extremely easy to synthesize from the chemical 2,5-dimethyoxyphenethylamine, requiring only a reaction with elemental bromine in an open flask. The chemicals MDA, MDMA, amphetamine, and methamphetamine are all easily synthesized through the reaction of MDP2P with either ammonia or methylamine for the former two and P2P with the same for the later two. These reactions are easily carried out once the precursors are obtained.
In addition to the general synthesis of methamphetamine from P2P, methamphetamine and methcathinone may also be easily prepared from ephedrine or pseudoephedrine. The former of these is one of the most popular syntheses throughout the world, utilizing a variety of reagents. One such route utilizes the action of hydriodic acid or elemental iodine and a phosphorous source such as red phosphorous or hypophosphorous acid (known by a variety of names when red phosphorous is used, such as “Push Pull” or “LWR” usually dependant on the vessel used), while another uses anhydrous ammonia and sodium or lithium metal (known as the “Birch reduction”).
Barring the availability of a direct precursor, some of these drugs still lend themselves well to synthesis from farther removed precursors. In general, many such routes proceed via the Henry reaction and require a benzaldehyde and nitromethane or nitroethane to produce Phenethylamines and Amphetamines, respectively. For example, The 2C-X chemicals may be synthesized from 2,5-dimethoxybenzaldehyde and nitromethane while methamphetamine may be synthesized from benzaldehyde and nitroethane. In addition, the MDX chemicals may be synthesized through a variety of other routes from chemicals such safrole, piperonal, or many other naturally occurring compounds containing the MD (methylenedioxy) moiety.
In some instances total synthesis of the drug is desired, and while this is possible for all of the Phenethylamines, most total synthesis requires more skill than the average clandestine chemist may possess. The one exception is the drug methamphetamine, which is easily produced from such basic chemicals as benzene and acetone. With the decreasing availability of pseudoephedrine and ephedrine these methods are becoming more popular.
A variety of other chemicals, some well known like mescaline and some not so well known like DOM, also fall under the Phenethylamine umbrella. The synthesis of these drugs, as well as the previously mentioned “popular” chemicals, can be found here in our drug chemistry information pages, as well as a variety of articles pertaining to the synthesis and extraction of the necessary precursor chemical to carry out a large number of the synthesis.

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