SYNTHESIS: A suspension of 17.4 g electrolytic elemental iron in 100 g
glacial acetic acid was heated on the steam-bath until there were the
first signs of bubbling and reaction, about 60 °C. There was then
added, in small portions, a suspension of 9.2 g
1-(2-methoxy-4,5-methylenedioxyphenyl)-2-nitropropene (see under
MMDA-2 for its preparation) in 40 g warm glacial acetic acid. The
reaction was extremely exothermic. After the color had lightened as
much as possible, there was added an additional quantity of iron
sufficient to completely discharge the residual yellow color.
Mechanical stirring was maintained as the reaction mixture was allowed
to return to room temperature. All was poured into 800 mL H2O, and
the insolubles were removed by filtration. These were washed
alternately with H2O and with CH2Cl2, the combined filtrate and washes
were separated, and the aqueous phase extracted with 3x100 mL CH2Cl2.
All organics were combined, washed with 2x75 mL 5% NaOH (which removed
most of the color) and the solvent removed under vacuum. The 8.7 g
residue was distilled at 90-105 °C at 0.2 mm/Hg to give 6.7 g of
2-methoxy-4,5-methylenedioxyphenylacetone as a pale yellow oil.
To a magnetically stirred solution of 30 g methylamine hydrochloride
in 150 mL warm MeOH, there was added 6.5 g
2-methoxy-4,5-methylenedioxyphenylacetone followed by 3.0 g sodium
cyano-borohydride. Concentrated HCl was added as was required to keep
the mixture at a pH of about 6. When the reaction was complete, it
was added to 1 L H2O and made strongly basic with 25% NaOH. This was
extracted with 3x100 mL CH2Cl2, and the pooled extracts were, in turn,
extracted with 2x100 mL dilute H2SO4. This aqueous phase was washed
with CH2Cl2, made basic with NaOH, and extracted with 3x100 mL CH2Cl2.
Removal of the solvent from these pooled extracts under vacuum gave
8.7 g of an amber oil. This was distilled at 110-125 °C at 0.25 mm/Hg
to give 5.1 g of a colorless oil. This was dissolved in 30 mL IPA,
neutralized with about 3 mL concentrated HCl, and diluted with 60 mL
anhydrous Et2O. The clear solution slowly deposited white crystals
which were removed by filtration and air dried to give 4.2 g
2-methoxy-N-methyl-4,5-methylenedioxyamphetamine hydrochloride
(METHYL-MMDA-2) with a mp of 168-169 °C. Anal. (C12H18ClNO3) C,H.
DOSAGE: greater than 70 mg.
DURATION: unknown.
QUALITATIVE COMMENTS: (with 70 mg) Maybe a threshold--pleasant but
not possible to characterize it.
EXTENSIONS AND COMMENTARY: With the effective dosage of the
unmethylated homologue being the range of 25 to 50 milligrams, this
N-methyl compound is, as with the other N-methylated materials
discussed here, again of reduced activity. The highest dose yet
reported was 70 milligrams, and there is no way of estimating what
miight be an active level nor, once there, what the quality of the
effects might be.
This is the only MMDA analogue that has been explored as an N-methyl
derivative. A more highly substituted analogue has also been made,
the N-methyl derivative of DMMDA. Isoapiole (see its preparation
under DMMDA) was oxidized with formic acid and hydrogen peroxide to
the ketone (2,5-dimethoxy-3,4-methylenedioxyphenylacetone, a solid
with a mp of 75-76 °C from methanol) which was reductively aminated
with methylamine and amalgamated aluminum to give
2,5-dimethoxy-N-methyl-3,4-methylenedioxyamphetamine hydrobromide
monohydrate (METHYL-DMMDA, or DMMDMA) as a white crystalline solid
with a mp of 91-92 °C. The hydrochloride salt was a hygroscopic
solid. Anal. (C13H22BrNO5) C,H. The above ketone has also been used
in the synthesis of another methylated DMMDA, on the beta-carbon.
This is described under DMMDA itself. DMMDMA has not yet been
launched into an evaluation program, and I wouldn't be surprised if
the needed dosage might be up there somewhere over 100 milligrams. I
feel quite sure that the answers may be known in the near future.
There is a surprisingly large number of inconspicuous chemical
explorers out there all over the world, doing their synthetic thing in
their private laboratories. They are truly the astronauts of inner
space.
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