SYNTHESIS: A solution of 10.0 g 3-methoxy-4-ethoxybenzaldehyde in 150
mL nitromethane was treated with 1.7 g anhydrous ammonium acetate, and
heated on the steam bath for 1 h. The excess nitromethane was removed
under vacuum, yielding a loose, yellow crystalline mass that was
filtered and modestly washed with cold MeOH. The 8.0 g of damp yellow
crystals thus obtained were dissolved in 50 mL of vigorously boiling
CH3CN, decanted from a small amount of insolubles (probably ammonium
acetate residues) and cooled in an ice bath. The crystals so obtained
were removed by filtration, washed with 2x5 mL cold CH3CN, and air
dried to constant weight. The yield of
4-ethoxy-3-methoxy-beta-nitrostyrene was 6.3 g of beautiful yellow
crystals.
A solution of 2.3 g LAH in 70 mL anhydrous THF was cooled, under He to
0 °C with an external ice bath. With good stirring there was added
2.3 mL 100% H2SO4 dropwise, to minimize charring. This was followed
by the addition of 6.2 g 3-ethoxy-4-methoxy-beta-nitrostyrene in
anhydrous THF. After a few min further stirring, the temperature was
brought up to a gentle reflux on the steam bath, and then all was
cooled again to 0 °C. The excess hydride was destroyed by the
cautious addition of IPA followed by sufficent 10% NaOH to give a
white granular character to the oxides, and to assure that the
reaction mixture was basic. The reaction mixture was filtered and the
filter cake well washed with THF. The filtrate and washes were
combined and stripped of solvent under vacuum. The residue was
dissolved in dilute H2SO4. This was washed with 2x75 mL CH2Cl2, which
removed the residual yellow color. The remaining aqueous phase was
made basic with NaOH, and extracted with 3x75 mL CH2Cl2. These
extracts were combined and the solvent removed under vacuum. The
residue was distilled at 108-115 °C at 0.4 mm/Hg to give 4.2 g of a
mobile, colorless liquid. This was dissolved in 12 mL IPA,
neutralized with 60 drops concentrated HCl, and diluted with 100 mL
anhydrous Et2O. There was deposited a fine white crystalline product
which, after removal by filtration, ether washing, and air drying,
yielded 3.8 g of 3-methoxy-4-ethoxyphenethylamine hydrochloride
(MEPEA).
DOSAGE: 300 mg or greater.
DURATION: short.
QUALITATIVE COMMENTS: (with 120 mg) I am at perhaps a +1, a very
slight effect of lightness, without any body awareness at all. And
then in another hour, I was completely baseline again.
(with 300 mg) Whatever changes took place were complete at the end of
an hour. The effects were very quiet, very pleasant, and very light.
There was nothing psychedelic here, but rather a gentle lifting of
spirits. No sensory enhancement or other expected changes.
EXTENSIONS AND COMMENTARY: This is one of the very few phenethylamines
with only two substituents that shows even a hint of central activity.
And there is an interesting story attached. I got a call out of
absolutely nowhere, from a Stanislov Wistupkin, that he had discovered
a number of new psychedelic drugs which he would like to share with
me. Two of them were simple phenethylamines, one with an ethoxy group
at the 4-position, and one with an allyloxy group there. Both, he
said, were mood elevators active between 100 and 300 milligrams. One
of them was this material, here called MEPEA, and the other one was
3-methoxy-4-allyloxyphenethylamine, or MAPEA. When I did meet him in
person, he gave me a most remarkable publication which had been
authored some ten years earlier, by a person named Leminger, now dead.
It was all in Czech, but quite unmistakably, right there on the third
page, were the structures of MEPEA and MAPEA, and the statement that
they were active at between 100 and 300 milligrams. I have not yet
made the allyloxy compound, but I feel that it too might be a gentle
mood elevator similar to the ethoxy.
A most appealing extension of these materials would be the amphetamine
derivatives, things with a 3-methoxy group, and something small and
terse on the 4-position. The immediate analogies of MEPEA and MAPEA
would be 3-methoxy-4-ethoxy- (and 3-methoxy-4-allyloxy)-amphetamine.
And equally interesting would be the 4-hydroxy analogue. This would
be an easily made compound from vanillin, one of our most enjoyable
spices in the kitchen cabinet, and it would be directly related to the
essential oils, eugenol and isoeugenol. This amphetamine compound has
already been synthesized, but it is still unexplored in man.
Some years ago a report appeared in the forensic literature of Italy,
of the seizure of a small semitransparent capsule containing 141
milligrams of a white powder that was stated to be a new
hallucinogenic drug. This was shown to contain an analogue of DOM,
3-methoxy-4-methylamphetamine, or MMA. The Italian authorities made
no mention of the net weight contained in each dosage unit, but it has
been found that the active level of MMA in man is in the area of 40-60
milligrams. The compound can apparently be quite dysphoric, and long
lived.
In the Czechoslovakian publication that presented MEPEA and MAPEA.
there were descriptions of escaline (E), proscaline (P), and the
allyloxy analogue (AL). These are all active in man, and have been
entered elsewhere. This is the only published material dealing with
psychedelic drugs I have ever been able to find, from the laboratory
of Otakar Leminger. What sort of man was this chemist? He worked for
years in industry, and only at the time of his retirement did he
publish this little gem. He lived at Usti, directly north of Praha,
on the Labe river (which is called by the better known name, the Elbe,
as soon as it enters Germany). Might there be other treasures that he
had discovered, and never published? Was young Wistupkin a student of
his? Are there unrecognized notes of Otakar Leminger sitting in some
farm house attic in Northern Czechoslovakia? I extend my heartfelt
salute to an almost unknown explorer in the psychedelic drug area.
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