DMMDA

IdentifiersCAS NumberChemSpiderUNIIChEMBLCompTox Dashboard (EPA)Chemical and physical dataFormulaC₁₂H₁₉NO₄Molar mass241.287 g·mol⁻¹3D model (JSmol)  (verify)

2,5-Dimethoxy-3,4-methylenedioxyamphetamine (DMMDA) is a psychedelic drug of the phenethylamine and amphetamine chemical classes.^[1] It was first synthesized by Alexander Shulgin and was described in his book PiHKAL.^[1] Shulgin listed the dosage as 30–75 mg and the duration as 6–8 hours.^[1] He reported DMMDA as producing LSD-like images, mydriasis, ataxia, and time dilation.^[1]

Pharmacology

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-HT_2A partial agonist.^[1]

Chemistry

Shulgin explains in his book that DMMDA has 6 isomers similar to TMA.^[1] DMMDA-2 is the only other isomer that has been synthesized as of yet. DMMDA-3 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.^[2] 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.^[2] Additionally, yet another isomer of DMMDA could be made from pseudo-dillapiole or 4,5-dimethoxy-2,3-methylenedioxyallylbenzene.^[3]

Synthesis

Shulgin describes the synthesis of DMMDA from apiole in his book PiHKAL.^[1] 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.^[1] 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.^[1] The 2-nitro-isoapiole is finally reduced to freebase DMMDA by adding it to a well-stirred and refluxing suspension of diethylether and lithium aluminium hydride under an inert atmosphere (e.g. helium).^[1] Finally, the freebase DMMDA converted into its hydrochloride salt.^[1]

• 
  Alexander Shulgin's synthesis of DMMDA.

Shulgin's synthesis of DMMDA is reasonably unsafe, since it involves the use of tetranitromethane, which is toxic, carcinogenic and prone to detonating.^[4] 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.^[5] The Peracid oxidation can be accomplished by combining hydrogen peroxide with formic acid to create a peracid. The hydrolysis is usually acid-catalyzed with sulphuric acid because sulphuric acid will also result in the intermediary isoapiole monoformyl glycol being dehydrated to DMMDP2P. Then the DMMDP2P can then be subjected to a reductive amination with a source of nitrogen, such as ammonium chloride, and a reducing agent, such as sodium cyanoborohydride or an amalgam of mercury and aluminium, to yield freebase DMMDA.^[6]

References