|CompTox Dashboard (EPA)|
|Chemical and physical data|
|Molar mass||241.287 g·mol−1|
|3D model (JSmol)|
2,5-Dimethoxy-3,4-methylenedioxyamphetamine (DMMDA) is a psychedelic drug of the phenethylamine and amphetamine chemical classes. It was first synthesized by Alexander Shulgin and was described in his book PiHKAL. Shulgin listed the dosage as 30–75 mg and the duration as 6–8 hours. He reported DMMDA as producing LSD-like images, mydriasis, ataxia, and time dilation.
The mechanism behind DMMDA's hallucinogenic effects has not been specifically established, however Shulgin describes that a 75 milligram dose of DMMDA is equivalent to a 75–100 microgram dose of LSD. LSD is a known 5-HT2A partial agonist. It is possible that the hallucinogenic effects of DMMDA result from action as a 5-HT2A serotonin receptor agonist or partial agonist in the brain.
Shulgin explains in his book that DMMDA has 6 isomers similar to TMA. DMMDA-2 is the only other isomer that has been synthesized as of yet. A new isomer of DMMDA could be made from exalatacin (1-allyl-2,6-dimethoxy-3,4-methylenedioxybenzene). Exalatacin can be found in the essential oil of both Crowea exalata and Crowea angustifolia var. angustifolia. In other words, exalatacin is an isomer of both apiole and dillapiole, which can be used to make DMMDA and DMMDA-2 respectively. Exalatacin is almost identical to apiole and dillapiole, but differs from them in its positioning of its methoxy groups, which are in the 2 and 6 positions. Additionally, yet another isomer of DMMDA could be made from pseudo-dillapiole or 4,5-dimethoxy-2,3-methylenedioxyallylbenzene.
Shulgin describes the synthesis of DMMDA from apiole in his book PiHKAL. Apiole is subjected to an isomerization reaction to yield isoapiole by adding to solution of ethanolic potassium hydroxide and holding the solution at a steam bath. The isoapiole is then nitrated to 2-nitro-isoapiole or 1-(2,3-dimethoxy-3,4-methylenedioxyphenyl)-2-nitropropene by adding it to a stirred solution of acetone and pyridine at ice-bath temperatures and treating the solution with tetranitromethane. The pyridine acts as a catalyst in this reaction. The 2-nitro-isoapiole is finally reduced to freebase DMMDA by adding it to a well-stirred and refluxing suspension of diethylether and lithium aluminum hydride under an inert atmosphere (e.g. helium). Finally, the freebase DMMDA converted into its hydrochloride salt.
Shulgin's synthesis of DMMDA is reasonably unsafe, since it involves the use of tetranitromethane, which is toxic, carcinogenic and prone to detonating. DMMDA can be made from apiole via other safer methods. Among other methods, DMMDA can be synthesize from apiole via the intermediate chemical 2,5-dimethoxy-3,4-methylenedioxyphenylpropan-2-one or DMMDP2P in the same manner as MDA is made from safrole. DMMDP2P can be made from apiole via a Wacker oxidation with benzoquinone. DMMDP2P can be alternatively made by subjecting apiole to an isomerisation reaction to yield isoapiole followed by a Peracid oxidation and finally a hydrolytic dehydration. Then the DMMDP2P can then be subjected to a reductive amination with ammonium chloride with sodium cyanoborohydride acting as a reducing agent to yield freebase DMMDA.