MDMA is known as a semisynthetic drug. To make MDMA involves a natural precursor known as safrole, an oil found in sassafras plants. This article will walk you through the process to understand how MDMA is made.
In the illicit manufacturing of MDMA, safrole or its isomer isosafrole is used to create a ketone intermediate called MDP2P, which is then reductively aminated to create MDMA. Many of the chemicals used to make MDMA are closely watched by the DEA. In addition, common synthesis routes involve hazardous chemicals such as formaldehyde, ammonium chloride, and mercury.
Who First Manufactured MDMA?
German chemist Anton Köllisch, an employee at Merck Pharmaceuticals, first synthesized MDMA in 1912. At the time, Merck was systematically developing new medications to stop bleeding. MDMA, originally called “methylsafrylaminc,” was discovered as an intermediate step in the synthesis of a drug named methylhydrastinine. Originally, Merck synthesized MDMA by adding hydrobromic acid to safrole and then subsequently reacting the brominated product (bromosafrole) with methylamine. MDMA was thus merely a precursor and didn’t arouse much interest initially. Merck patented it in 1914, but pharmacological studies on it began only in 1927.
For several decades MDMA fell into obscurity, but its toxicity was briefly studied by the U.S. Army in the 1950s alongside other phenethylamines like mescaline. The first scientific paper published on MDMA appeared in 1960, when two Polish chemists reported a synthesis route. Later, Alexander Shulgin synthesized MDMA in 1965 and embarked on a series of self-experimentations. His positive experiences led him to popularize the drug within the psychotherapeutic community. By the 1970s, underground labs were manufacturing it, partly as a legal alternative to close relative MDA, that was scheduled in 1970. MDMA gained popularity in the 1980s, particularly within the rave scene. This eventually led to its federal scheduling in 1985.
Chemical Structure Explained
MDMA, or 3,4-Methylenedioxymethamphetamine, is a semisynthetic entactogen with stimulating and euphoric properties. Similar to mescaline and 2C-B, it belongs to the family of substituted phenethylamines. All substituted phenethylamine drugs build upon the parent compound phenethylamine, which consists of a phenyl ring bound to an amino group (NH2) through a 2-carbon ethyl chain. In the case of MDMA, the aromatic ring is substituted with a methylenedioxy group (O-CH2-O), an addition that confers its unique pharmacological properties.
MDMA is structurally related to the amphetamine class of drugs, which includes methamphetamine and its homolog MDA (3,4-methylenedioxymethamphetamine). Like methamphetamine, MDMA exists in two enantiomeric forms (R and S). MDMA is found on the street as the racemic mixture (both R and S enantiomers). However, the S enantiomer is the more potent of the two.
Like MDA, chemists synthesize MDMA starting with the carefully watched and regulated precursor safrole. It is a natural product derived from the oil of the sassafras tree but also found in other essential oils. It is a member of the methylenedioxybenzene group of compounds. This means its structure closely resembles MDMA with the exception of the double bond at the ethyl chain, which is oxidized to produce MDP2P.
MDP2P, or 3,4-methylenedioxyphenyl-2-propanone, is an intermediate compound created in the synthesis of MDMA. It is also known as PMK or piperonyl methyl ketone. It is typically made by the oxidation of safrole or its isomer isosafrole, but can also be prepared from piperonal, a widely used industrial chemical. Since MDP2P is on the DEA watch list similar to safrole, it has more recently been produced from a less-controlled precursor known as PMK glycidate. When refluxed with hydrochloric acid, PMK glycidate readily breaks down into MDP2P. This is then reductively aminated to form racemic MDMA.
How to Make MDMA: Key Procedures Explained
The synthesis overviewed below, known as the Brightstar synthesis, involves the oxidation of safrole into a ketone (MDP2P), followed by reductive amination with methylamine and aluminum-mercury amalgam to yield MDMA.
Isolate Safrole Oil
Safrole, the key starting ingredient for MDMA production, is extracted from safrole-rich essential oils. These essential oils include sassafras oil and brown camphor oil, which contain up to 94% safrole.
The oil is distilled under a vacuum to isolate safrole from other phenylpropenes and terpenoids found in sassafras. Sassafras oils are List 1 chemicals, closely watched and not easily obtained in the United States in large quantities.
Convert Safrole to MDP2P
The next step involves a catalytic oxidation method known as the Wacker oxidation.
In this reaction, benzoquinone acts as an oxidizer, adding oxygen across the double bond on the ethyl chain of the phenethylamine backbone. The addition of palladium chloride (PdCl2) then catalyzes the reaction.
The end result, after 8 hours of constant stirring, is the ketone MDP2P. The MDP2P is extracted with an organic solvent and purified by vacuum distillation, resulting in a light yellow colored oil that is stable only at low temperatures.
Reductively Aminate MDP2P to MDMA
Next, MDP2P is reductively aminated to MDMA oil in a dissolving metal reduction process known as the mercury-aluminum amalgam. First, methylamine is prepared from formaldehyde and ammonium chloride, then converted into a freebase form with sodium hydroxide. The mercury-aluminum amalgam is created by dissolving mercury chloride in methanol, then adding this solution to a flask of aluminum foil squares.
Once the amalgam starts to bubble, the methylamine freebase and MDP2P solution are added, and the solution is allowed to reflux for several hours. The MDP2P undergoes a condensation reaction with methylamine, forming an imine that is reduced by the aluminum amalgam to MDMA.
After the reaction is complete, sodium hydroxide is added to turn the amalgam solution into a filterable consistency, and then MDMA freebase (an oil) is collected via an acid-base extraction.
Crystallize the MDMA Oil
This step is done in anhydrous (no water) conditions.
Once the solvent is vacuum distilled away, the MDMA freebase is dissolved in dry isopropyl alcohol.
Then, hydrochloric acid is added drop-wise until the solution turns acidic, at which point MDMA hydrochloride crystals form in the reaction flask under vacuum distillation.
The crystals are filtered with a coffee filter, heated, acetone-washed, and finally dried to produce the final off-white-colored MDMA hydrochloride crystals. The pure MDMA powder can be further processed with other ingredients and compressed into tablets that range in purity.
Disclaimer: MDMA is potentially categorized as an illegal drug. Reality Sandwich is not encouraging the use or making of this drug where it is prohibited. However, we believe that providing information is imperative for the safety of those who choose to explore this substance. This guide is intended to give educational content and should in no way be viewed as medical recommendations.
RS Contributing Author: Dylan Beard
Dylan Beard is a freelance science writer and editor based in the beautiful Pacific Northwest. After finishing his physics degree and dabbling in neuroscience research at UC Santa Barbara in 2017, he returned to his first love: writing. As a long-term fan of the human brain, he loves exploring the latest research on psychedelics, nootropics, psychology, consciousness, meditation, and more. When not writing, you can probably find him on hiking trails around Oregon and Washington or listening to podcasts. Feel free to follow him on Insta @dylancb88.