SYNTHESIS: To a solution of 27.6 g protocatechualdehyde
(3,4-dihydroxybenzaldehyde) in 250 mL acetone there was added 57 g
finely powdered anhydrous K2CO3 and 43 g 1,2-dibromoethane. The
mixture was held at reflux for 16 h, and then the acetone removed by
evaporation. The remaining tar-like goo was distributed between equal
volumes of H2O and CH2Cl2, and the phases separated by centrifugation.
The organic phase was washed with 2x50 mL 5% NaOH, and the solvent
removed under vacuum. The residue (22.0 g with the smell of the
starting halide) was distilled to give a fraction that boiled at 110
°C at 0.25 mm/Hg to yield 3,4-ethylenedioxybenzaldehyde
(1,4-benzodioxane-6-carboxaldehyde) as a white oil weighing 6.88 g.
This spontaneously crystallized to give white solids that melted at
50-51 °C.
A solution of 6.64 g 3,4-ethylenedioxybenzaldehyde in 40 mL
nitroethane was treated with 0.26 g anhydrous ammonium acetate and
held at reflux for 3 days. TLC analysis showed that there was much
aldehyde remaining unreacted, so an additional 0.7 g ammonium acetate
was added, and the mixture held at reflux for an additional 6 h. The
excess nitroethane was removed under vacuum. The residue was
dissolved in 30 mL hot MeOH which, with patience and slow cooling,
finally deposited a heavy yellow-gold powder. This product
1-(3,4-ethylenedioxyphenyl)-2-nitro-propene melted at 95-96 °C and
weighed 6.03 g when air dried to constant weight. Recrystallization
from either MeOH or EtOAc gave the product as a yellow solid, but
without any improvement in mp.
A solution of 4.0 g of 1-(3,4-ethylenedioxyphenyl)-2-nitropropene was
made in 30 mL warm acetic acid. This was added to a suspension of 16
g elemental electrolytic iron in 75 mL acetic acid. The mixture was
heated on the steam bath, and an exothermic reaction set in at about
70 °C. Heating was continued and the reaction allowed to proceed
until the mass was a thick gray color and a dirty scum had been formed
on the surface. After about 2 h, the entire mix was poured into 2 L
H2O and filtered free of a little residual unreacted iron which was
washed with CH2Cl2. The filtrate and washes were extracted with 3x100
mL CH2Cl2 and the pooled organic extracts washed with 2x50 mL 5% NaOH.
Removal of the solvent gave 3.38 g of an amber oil which was
distilled. The product 1-(3,4-ethylenedioxyphenyl)-2-propanone
distilled as a white oil, at 105-110 °C at 0.2 mm/Hg. It weighed 2.74
g.
To 2.0 g. of 1 inch squares of light-weight aluminum foil there was
added a solution of 50 mg mercuric chloride in 70 mL water. After
standing at room temperature for 30 min, the H2O was drained away, and
the amalgamated aluminum washed twice with H2O, and shaken as dry as
possible. There was then added, promptly and in immediate sequence, a
solution of 3 g methylamine hydrochloride in 3 mL H2O, 9 mL IPA, 7.25
mL 25% NaOH, 2.70 g of 1-(3,4-ethylenedioxyphenyl)-2-propanone, and 18
mL IPA. The mixture was heated on the steam bath until an exothermic
reaction set in, and then it was continuously swirled as the reaction
proceeded. When the aluminum was consumed, there was a colorless gray
sludge, and this was filtered and washed with 2x10 mL MeOH. The
combined mother liquors and washes were stripped of solvent under
vacuum. The two phase residue was suspended in 400 mL H2O containing
sufficient H2SO4 to make the resulting water solution acidic to pH
paper. This was washed with 3x50 mL CH2Cl2, made basic with 25% NaOH,
and the product extracted with 3x50 mL CH2Cl2. The resulting 3.01 g
slightly amber residue oil was distilled at 110-120 °C at 0.25 mm/Hg
to give 2.53 g of a white oil, which did not appear to absorb carbon
dioxide. This was dissolved in 12 mL IPA, neutralized with 1 mL
concentrated HCl and diluted with anhydrous Et2O to the point of
initial turbidity. There separated white crystals of
3,4-ethylenedioxy-N-methylamphetamine hydrochloride (MDMC) which
weighed, when air dried to constant weight, 2.53 g.
DOSAGE: 200 or more mg.
DURATION: 3 - 5 h.
QUALITATIVE COMMENTS: (with 150 mg) A flood of paresthesia at the 30
minute point, and then nothing. There was the development of a plus
one-and-a half effect over the next hour with the tendency to drift
into a dozing state with hypnogogic imagery. There were colored
letters in the periphery of my visual field. There was no appetite
loss nor was there any blood pressure rise. And no eye jiggle or
teeth clenching. I was out of the experience in 4 to 5 hours. A
repeat of this level a few days later gave a bare possible threshold
with no other effects.
(with 200 mg) There was something unmistakable at 45 minutes, with
hints of nystagmus. Possibly MDMA-like, with no indicators of
anything psychedelic. Subtle return to baseline, and there were no
after-effects.
(with 250 mg) Alert at 40 minutes, and to a clear ++ at an hour.
Slight something in the eye muscles. Dropping thirty minutes later,
and baseline at three hours.
(with 250 mg) I am at a bare threshold at best.
EXTENSIONS AND COMMENTARY: What a strange and completely
unsatisfactory compound! In the original run-up from low levels to
increasing higher levels, there never was a dosage that was a minus,
that had no effect. At every level, something was thought to be
there, usually at a level of a single plus or thereabouts. But with
different people, different responses. There is no way of guessing
what an active level might be, or how consistent that level might be
between different people, or for that matter what the responses are
that might be expected at that level.
This was yet one more effort to find an MDMA-like substitute by the
miniscule manipulation of the MDMA molecule. Perhaps a small
molecular change might leave the particular magic of the MDMA action
alone, but eliminate the serotonin neuron problem in test animals.
Maybe the serotonin neuron change is essential for MDMA to have the
action it has. Who can tell?
The original name that this compound got, during the several
explorations of MDMA analogues, was based on the nickname for MDMA
which was Adam. HAD'EM was mentioned with the hydroxy compound, MADAM
with the 6-methyl homologue, and FLADAM with the 6-fluoro analogue.
This compound got the sobriquet MACADAM from that horrible black gooey
mess generated at the aldehyde stage. This was shortened to RCS and
eventually the RCS was added to the MDMA parent name. Thus, MDMC. It
doesn't really make sense; EDMA is more reasonable. But then there is
no reason why MDMC should make sense.
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