DMMDA

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] It is possible that the hallucinogenic effects of DMMDA result from action as a 5-HT_2A serotonin receptor agonist or partial agonist in the brain.

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. 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.[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]

Precursors in the synthesis of DMMDA and analogs

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 aluminum hydride under an inert atmosphere (e.g. helium).[1] Finally, the freebase DMMDA converted into its hydrochloride salt.[1]

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] 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.[6]

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  Alexander Shulgin's synthesis of DMMDA.