SYNTHESIS: To a well stirred solution of 14.8 g hydroxylamine
hydrochloride in 120 mL MeOH there was added 3.6 g of
3,4-methylenedioxyphenylacetone (see under MDMA for its preparation)
followed by 1.0 g sodium cyanoborohydride. The oxime, prepared from
the ketone and hydroxylamine in MeOH with pyridine, may be substituted
for these two components. Concentrated HCl was added over the course
of a couple of days, to keep the pH near neutrality. When the
reaction was complete, it was added to H2O, made strongly acidic with
HCl, and washed with 3x100 mL CH2Cl2. The aqueous phase was made
basic with 25% NaOH, and reextracted with 3x100 mL of CH2Cl2. The
extracts were pooled, and the solvent removed under vacuum to give 1.7
g of an oily residue which, with pumping under a hard vacuum for a few
minutes, changed to a white solid. This can be Kugelrohred if the
vacuum is sufficiently good to keep the temperature during the
distillation below 100 °C. The extremely viscous distillate formed
crystals immediately upon wetting with IPA. It was dissolved in 20 mL
of warm IPA and neutralized with concentrated HCl, with the titration
end-point being red rather than orange on universal pH paper. Modest
addition of Et2O allowed the formation of
3,4-methylenedioxy-N-hydroxyamphetamine hydrochloride (MDOH) as white
crystals, which weighed 1.4 g when air dried. If the temperature of
distillation exceeded 100 °C, there was extensive decomposition during
distillation, with the formation of 3,4-methylenedioxyamphetamine
(MDA) and the oxime of the ketone. Under these circumstances, the
only base isolated was MDA. The surest isolation procedure was to
obtain MDOH as the free base, as a crystalline solid which could be
recrystallized from 5 volumes of boiling IPA. The free base had a mp
of 94-95 °C (and should not be confused with the oxime of
3,4-methylenedioxyphenylacetone which has a mp of 86-88 °C since the
mixed mp is depressed, mp 56-62 °C, or with the free base of MDA which
is an oil). Anal. (C10H13NO3) N. The hydrochloride salt had a mp of
149-150 °C (and should not be confused with the hydrochloride of MDA
which has a mp of 185-186 °C since the mixed mp is depressed, mp
128-138 °C). Anal. (C10H14ClNO3) N. Acetic anhydride can serve as a
useful tool for distinguishing these materials. MDA gives an N-acetyl
derivative with an mp of 92-93 °C. MDOH gives an N,O-diacetyl
derivative with a mp of 72-74 °C. Methylenedioxyphenylacetone oxime
gives an O-acetyl derivative that is an oil.
DOSAGE: 100 - 160 mg.
DURATION: 3 - 6 h.
QUALITATIVE COMMENTS: (with 100 mg) I felt hampered the first hour by
some internal barrier, which prevented total enjoyment. However, this
began to break through in a wonderful way just before the supplement
was offered. Since I felt I was beginning to move through the
barrier, I declined the supplement, particularly since I was anxious
to compare the after-effects with my first experience. I had found
the first time very remarkable, but felt unusually tired for several
days following. I feel it is important to know whether this is a
specific drug-induced effect, or the result of psychological
phenomena. The experience continued in a rich, meaningful way. There
was a marvelous inner glow, the warmth from all the other participants
was wonderful to feel, nature was most beautiful. There were no
dramatic breakthroughs, or rushes of insight or energy, but just a
wonderful contemplative space where things gently unfolded as you put
your attention on them.
(with 100 mg) The material came on fairly rapidly. In about 30
minutes, I was intensely intoxicated, and more deeply than with MDMA.
It was a glorious feeling, and beauty was everywhere enhanced. With
eyes closed it felt marvelous, and it was appealing to pursue the
inner experience. I did notice an internal dryness which was
characteristic of MDMA, and I had similar difficulty in urinating, but
not as intense as with MDMA.
(with 120 mg) The colors of the market-place, of all the fresh foods,
constituted a beautiful mosaic. Nothing practical, simply a real
treasure to be used with individual intention and enjoyment.
Everything was seen with new eyes, new meanings, faces, figures, the
colors of the rainbow subconsciously individually applied. A
'soul-scape'. The following day very exhausted, tired, back-pain.
EXTENSIONS AND COMMENTARY: The first time that MDOH was synthesized,
it had inadvertently and unknowingly been converted to MDA. And the
search for proper dosage and characterization of effects of this
product was, of course, the rediscovery of the dosage and the effects
of MDA. It is one of the world's most remarkable coincidences that
after the second synthesis of MDOH, when MDOH had really and truly
been actually prepared, the brand new search for proper dosage and
characterization of effects revealed that they were almost identical
to the earlier observations for (the inadvertently produced) MDA.
This reminds me of my speculations in the discussion of both FLEA and
the HOT compound where they also showed paired molecular structures
with their prototypes that differ only by a single oxygen atom.
Again, might there be some metabolic interconversion within the body?
The immediate thought would be that the oxygen atom (the hydroxy
group) might be metabolically removed, and the effects of either drug
are due to the action of MDA. But the opposite direction is in many
ways more appealing, the in vivo conversion of MDA to MDOH. Why more
appealing? For one thing, oxidative changes are much more common in
the body than reductive changes. For another, the conversion of
amphetamine to N-hydroxyamphetamine is an intermediate in the
conversion of amphetamine to phenylacetone, a known metabolic process
in several animal species. And that intermediate,
N-hydroxyamphetamine, is a material that gives the famous cytochrome
P-450 complex that has fascinated biochemists studying the so-called
NADPH-dependent metabolism.
I would put my money on the likelihood of MDA going to MDOH if it
should turn out that the two drugs interconvert in the body. And in
that case, it would be MDOH, or another metabolite on down the line
that is common to both MDA and MDOH, that is the factor intrinsic to
the intoxication that is produced. Human metabolic studies are
needed, and they have not yet been done.
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